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PHYSICS in NUCLEAR MEDICINE
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PHYSICS
in NUCLEAR
MEDICINE
FOURTH EDITION

Simon R. Cherry, PhD


Professor, Departments of Biomedical Engineering and Radiology
Director, Center for Molecular and Genomic Imaging
University of California—Davis
Davis, California

James A. Sorenson, PhD


Emeritus Professor of Medical Physics
Department of Medical Physics
University of Wisconsin—Madison
Madison, Wisconsin

Michael E. Phelps, PhD


Norton Simon Professor
Chief, Division of Nuclear Medicine
Chair, Department of Molecular and Medical Pharmacology
Director, Crump Institute for Molecular Imaging
David Geffen School of Medicine
University of California—Los Angeles
Los Angeles, California
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

Physics in Nuclear Medicine ISBN: 978-1-4160-5198-5

Copyright © 2012, 2003, 1987, 1980 by Saunders, an imprint of Elsevier Inc.

No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage
and retrieval system, without permission in writing from the publisher. Details on how
to seek permission, further information about the Publisher’s permissions policies and our
arrangements with organizations such as the Copyright Clearance Center and the Copyright
Licensing Agency, can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by the
Publisher (other than as may be noted herein).

Notice
Knowledge and best practice in this field are constantly changing. As new research and
experience broaden our understanding, changes in research methods, professional practices,
or medical treatment may become necessary or appropriate. Readers are advised to check
the most current information provided (i) on procedures featured or (ii) by the manufacturer
of each product to be administered, to verify the recommended dose or formula, the
method and duration of administration, and contraindications. It is the responsibility of
practitioners, relying on their own experience and knowledge of their patients, to make
diagnoses, to determine dosages and the best treatment for each individual patient, and
to take all appropriate safety precautions. To the fullest extent of the law, neither the
Publisher nor the authors assume any liability for any injury and/or damage to persons
or property as a matter of products arising out of or related to any use of the material
contained in this book.

Library of Congress Cataloging-in-Publication Data

Cherry, Simon R.
Physics in nuclear medicine / Simon R. Cherry, James A. Sorenson, Michael E. Phelps.
—4th ed.
â•…â•…â•… p. ; cm.
â•… Includes bibliographical references and index.
â•… ISBN 978-1-4160-5198-5 (hardback : alk. paper)
╅ 1.╇ Medical physics.╅ 2.╇ Nuclear medicine.╅ I.╇ Sorenson, James A., 1938-╅ II.╇ Phelps,
Michael E.╅ III.╇ Title.
╅ [DNLM:╅ 1.╇ Health Physics.╅ 2.╇ Nuclear Medicine. WN 110]
â•… R895.S58 2012
â•… 610.1′53—dc23
2011021330

Senior Content Strategist: Don Scholz


Content Development Specialist: Lisa Barnes
Publishing Services Manager: Anne Altepeter
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Working together to grow
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Last digit is the print number:â•… 9â•… 8â•… 7â•… 6â•… 5â•… 4â•… 3â•… 2â•… 1
Preface

Physics and instrumentation affect all of the subspecialty areas of nuclear


medicine. Because of their fundamental importance, they usually are taught
as a separate course in nuclear medicine training programs. This book is
intended for use in such programs by physicians, technologists, and scientists
who desire to become specialists in nuclear medicine and molecular imaging,
as well as a reference source for physicians, scientists, and engineers in related
fields.
Although there have been substantial and remarkable changes in nuclear
medicine, the goal of this book remains the same as it was for the first edition
in 1980: to provide an introductory text for such courses, covering the physics
and instrumentation of nuclear medicine in sufficient depth to be of permanent
value to the trainee or student, but not at such depth as to be of interest only
to the physics or instrumentation specialist. The fourth edition includes many
recent advances, particularly in single-photon emission computed tomography
(SPECT) and positron emission tomography (PET) imaging. As well, a new
chapter is included on hybrid imaging techniques that combine the exceptional
functional and physiologic imaging capabilities of SPECT and PET with the
anatomically detailed techniques of computed tomography (CT) and magnetic
resonance imaging (MRI). An introduction to CT scanning is also included in
the new chapter.
The fourth edition also marks the first use of color. We hope that this not
only adds cosmetic appeal but also improves the clarity of our illustrations.
The organization of this text proceeds from basic principles to more practi-
cal aspects. After an introduction to nuclear medicine (Chapter 1), we provide
a review of atomic and nuclear physics (Chapter 2) and basic principles of
radioactivity and radioactive decay (Chapters 3 and 4). Radionuclide produc-
tion methods are discussed in Chapter 5, followed by radiation interactions
in Chapter 6. Basic principles of radiation detectors (Chapter 7), radiation-
counting electronics (Chapter 8), and statistics (Chapter 9) are provided next.
Following the first nine chapters, we move on to detailed discussions of
nuclear medicine systems and applications. Pulse-height spectrometry, which
plays an important role in many nuclear medicine procedures, is described in
Chapter 10, followed by general problems in nuclear radiation counting in
Chapter 11. Chapter 12 is devoted to specific types of nuclear radiation-
counting instruments, for both in vivo and in vitro measurements.
Chapters 13 through 20 cover topics in radionuclide imaging, beginning
with a description of the principles and performance characteristics of gamma
cameras (Chapters 13 and 14), which are still the workhorse of many nuclear
medicine laboratories. We then discuss general concepts of image quality in
nuclear medicine (Chapter 15), followed by an introduction to the basic con-
cepts of reconstruction tomography (Chapter 16).
The instrumentation for and practical implementation of reconstruction
tomography are discussed for SPECT in Chapter 17 and for PET in Chapter
18. Hybrid imaging systems, as well as the basic principles of CT scanning,
are covered in Chapter 19. Chapter 20 provides a summary of digital image
processing techniques, which are important for all systems and applications.
The imaging section of this text focuses primarily on instruments and tech-
niques that now enjoy or appear to have the potential for achieving clinical
v
vi Preface

acceptance. However, nuclear medicine imaging has become increasingly


important in the research environment. Therefore we have included some
systems that are used for small-animal or other research purposes in these
chapters.
We then move on to basic concepts and some applications of tracer kinetic
modeling (Chapter 21). Tracer kinetic modeling and its applications embody
two of the most important strengths of nuclear medicine techniques: the ability
to perform studies with minute (tracer) quantities of labeled molecules and
the ability to extract quantitative biologic data from these studies. We describe
the main assumptions and mathematical models used and present several
examples of the application of these models for calculating physiologic, meta-
bolic, and biochemical parameters
The final two chapters address radiation dose and safety issues. Internal
radiation dosimetry is presented in Chapter 22, and the final chapter presents
an introduction to the problems of radiation safety and health physics (Chapter
23). We did not deal with more general problems in radiation biology, believing
this topic to be of sufficient importance to warrant its own special treatment,
as has been done already in several excellent books on the subject.
Additional reading for more detailed infor�mation is suggested at the end of
each chapter. We also have included sample problems with solutions to illus-
trate certain quantitative relationships and to demonstrate standard calcula-
tions that are required in the practice of nuclear medicine. Systeme
Internationale (SI) units are used throughout the text; however, traditional
units still appear in a few places in the book, because these units remain in
use in day-to-day practice in many laboratories. Appendix A provides a
summary of conversion factors between SI and traditional units.
Appendixes B, C, and D present tables of basic properties of elements and
radionuclides, and of attenuation properties of some materials of basic rele-
vance to nuclear medicine. Appendix E provides a summary of radiation dose
estimates for a number of nuclear medicine procedures. Although much of this
information now is available on the Internet, we believe that users of this text
will find it useful to have a summary of the indicated quantities and param-
eters conveniently available.
Appendixes F and G provide more detailed discussions of Fourier trans-
forms and convolutions, both of which are essential components of modern
nuclear medicine imaging, especially reconstruction tomography. This is the
only part of the book that makes extensive use of calculus.
The fourth edition includes extensive revisions, and we are grateful to our
many colleagues and friends who have assisted us with information, data, and
figures. Particular gratitude is extended to Hendrik Pretorius, Donald Yapp,
Jarek Glodo, Paul Kinahan, David Townsend, Richard Carson, Stephen
Mather, and Freek Beekman. We also wish to thank readers who reported
errors and inconsistencies in the third edition and brought these to our atten-
tion. In particular, we recognize the contributions of Andrew Goertzen, Tim
Turkington, Mark Madsen, Ing-Tsung Hsiao, Jyh Cheng Chen, Scott Metzler,
Andrew Maidment, Lionel Zuckier, Jerrold Bushberg, Zongjian Cao, Marvin
Friedman, and Fred Fahey. This feedback from our readers is critical in ensur-
ing the highest level of accuracy in the text. Naturally, any mistakes that
remain in this new edition are entirely our responsibility.
We are grateful to Susie Helton (editorial assistance), and Robert Burnett
and Simon Dvorak (graphics), at the University of California–Davis for their
dedication to this project. We also appreciate the patience and efforts of the
editorial staff at Elsevier, especially Lisa Barnes, Cindy Thoms, and Don
Scholz. Finally, we thank our many colleagues who have used this book over
the years and who have provided constructive feedback and suggestions for
improvements that have helped to shape each new edition.

Simon R. Cherry, James A. Sorenson, and Michael E. Phelps


Contents

CHAPTER 1 What Is Nuclear Medicine?â•… 1


. FUNDAMENTAL CONCEPTSâ•… 1
A
B. THE POWER OF NUCLEAR MEDICINEâ•… 1
C. HISTORICAL OVERVIEWâ•… 2
D. CURRENT PRACTICE OF NUCLEAR MEDICINEâ•… 4
E. THE ROLE OF PHYSICS IN NUCLEAR MEDICINEâ•… 6

CHAPTER 2 Basic Atomic and Nuclear Physicsâ•… 7


A. QUANTITIES AND UNITSâ•… 7
1.╇ Types of Quantities and Units╅ 7
2.╇ Mass and Energy Units╅ 7
B. RADIATIONâ•… 8
C. ATOMSâ•… 9
1.╇ Composition and Structure╅ 9
2.╇ Electron Binding Energies and Energy Levels╅ 9
3.╇ Atomic Emissions╅ 10
D. THE NUCLEUSâ•… 13
1.╇ Composition╅ 13
2.╇ Terminology and Notation╅ 13
3.╇ Nuclear Families╅ 14
4.╇ Forces and Energy Levels within the Nucleus╅ 14
5.╇ Nuclear Emissions╅ 15
6.╇ Nuclear Binding Energy╅ 15
7.╇ Characteristics of Stable Nuclei╅ 16

CHAPTER 3 Modes of Radioactive Decayâ•… 19


. GENERAL CONCEPTSâ•… 19
A
B. CHEMISTRY AND RADIOACTIVITYâ•… 19
C. DECAY BY β− EMISSIONâ•… 20
D. DECAY BY (β−, γâ•›) EMISSIONâ•… 21
E. ISOMERIC TRANSITION AND INTERNAL CONVERSIONâ•… 22
F. ELECTRON CAPTURE AND (EC, γâ•›) DECAYâ•… 24
G. POSITRON (β+) AND (β+, γâ•›) DECAYâ•… 25
H. COMPETITIVE β+ AND EC DECAYâ•… 26
I. DECAY BY α EMISSION AND BY NUCLEAR FISSIONâ•… 26
J. DECAY MODES AND THE LINE OF STABILITYâ•… 28
K . SOURCES OF INFORMATION ON RADIONUCLIDESâ•… 28

CHAPTER 4 Decay of Radioactivityâ•… 31


A. ACTIVITYâ•… 31
1.╇ The Decay Constant╅ 31
2.╇ Definition and Units of Activity╅ 31
B. EXPONENTIAL DECAYâ•… 32
1.╇ The Decay Factor╅ 32
2.╇ Half-Life╅ 33
3.╇ Average Lifetime╅ 34

vii
viii Contents

C. METHODS FOR DETERMINING DECAY FACTORSâ•… 34


1.╇ Tables of Decay Factors╅ 34
2.╇ Pocket Calculators╅ 35
3.╇ Universal Decay Curve╅ 35
D. IMAGE-FRAME DECAY CORRECTIONSâ•… 35
E. SPECIFIC ACTIVITYâ•… 37
F. DECAY OF A MIXED RADIONUCLIDE SAMPLEâ•… 38
G. PARENT-DAUGHTER DECAYâ•… 39
1.╇ The Bateman Equations╅ 39
2.╇ Secular Equilibrium╅ 40
3.╇ Transient Equilibrium╅ 41
4.╇ No Equilibrium╅ 41

CHAPTER 5 Radionuclide and Radiopharmaceutical Productionâ•… 43


A. REACTOR-PRODUCED RADIONUCLIDESâ•… 43
1.╇ Reactor Principles╅ 43
2.╇ Fission Fragments╅ 44
3.╇ Neutron Activation╅ 45
B. ACCELERATOR-PRODUCED RADIONUCLIDESâ•… 47
1.╇ Charged-Particle Accelerators╅ 47
2.╇ Cyclotron Principles╅ 47
3.╇ Cyclotron-Produced Radionuclides╅ 49
C. RADIONUCLIDE GENERATORSâ•… 50
D. EQUATIONS FOR RADIONUCLIDE PRODUCTIONâ•… 53
1.╇ Activation Cross-Sections╅ 53
2.╇ Activation Rates╅ 54
3.╇ Buildup and Decay of Activity╅ 56
E. RADIONUCLIDES FOR NUCLEAR MEDICINEâ•… 57
1.╇ General Considerations╅ 57
2.╇ Specific Considerations╅ 57
F. RADIOPHARMACEUTICALS FOR CLINICAL APPLICATIONSâ•… 59
1.╇ General Considerations╅ 59
2.╇ Labeling Strategies╅ 59
3.╇ Technetium-99m-Labeled Radiopharmaceuticals╅ 60
4.╇ Radiopharmaceuticals Labeled with Positron Emitters╅ 60
5.╇ Radiopharmaceuticals for Therapy Applications╅ 61
6.╇ Radiopharmaceuticals in Clinical Nuclear Medicine╅ 61

CHAPTER 6 Interaction of Radiation with Matterâ•… 63


A. INTERACTIONS OF CHARGED PARTICLES WITH MATTERâ•… 63
1.╇ Charged-Particle Interaction Mechanisms╅ 63
2.╇ Collisional Versus Radiation Losses╅ 64
3.╇ Charged-Particle Tracks╅ 66
4.╇ Deposition of Energy Along a Charged-Particle Track╅ 67
5.╇ The Cerenkov Effect╅ 68
B. CHARGED-PARTICLE RANGESâ•… 70
1.╇ Alpha Particles╅ 70
2.╇ Beta Particles and Electrons╅ 71
C. PASSAGE OF HIGH-ENERGY PHOTONS THROUGH MATTERâ•… 74
1.╇ Photon Interaction Mechanisms╅ 74
2.╇ The Photoelectric Effect╅ 74
3.╇ Compton Scattering╅ 74
4.╇ Pair Production╅ 76
5.╇ Coherent (Rayleigh) Scattering╅ 77
6.╇ Deposition of Photon Energy in Matter╅ 77
D. ATTENUATION OF PHOTON BEAMSâ•… 78
1.╇ Attenuation Coefficients╅ 78
2.╇ Thick Absorbers, Narrow-Beam Geometry╅ 79
3.╇ Thick Absorbers, Broad-Beam Geometry╅ 83
4.╇ Polyenergetic Sources╅ 84
Contents ix

CHAPTER 7 Radiation Detectorsâ•… 87


A. GAS-FILLED DETECTORSâ•… 87
1.╇ Basic Principles╅ 87
2.╇ Ionization Chambers╅ 87
3.╇ Proportional Counters╅ 91
4.╇ Geiger-Müller Countersâ•… 92
B. SEMICONDUCTOR DETECTORSâ•… 96
C. SCINTILLATION DETECTORSâ•… 97
1.╇ Basic Principles╅ 97
2.╇ Photomultiplier Tubes╅ 98
3.╇ Photodiodes╅ 99
4.╇ Inorganic Scintillators╅ 100
5.╇ Considerations in Choosing an Inorganic Scintillator╅ 103
6.╇ Organic Scintillators╅ 104

CHAPTER 8 Electronic Instrumentation for Radiation Detection


Systemsâ•… 107
. PREAMPLIFIERSâ•… 107
A
B. AMPLIFIERSâ•… 110
1.╇ Amplification and Pulse-Shaping Functions╅ 110
2.╇ Resistor-Capacitor Shaping╅ 111
3.╇ Baseline Shift and Pulse Pile-Up╅ 112
C. PULSE-HEIGHT ANALYZERSâ•… 113
1.╇ Basic Functions╅ 113
2.╇ Single-Channel Analyzers╅ 113
3.╇ Timing Methods╅ 114
4.╇ Multichannel Analyzers╅ 116
D. TIME-TO-AMPLITUDE CONVERTERSâ•… 118
E. DIGITAL COUNTERS AND RATE METERSâ•… 119
1.╇ Scalers, Timers, and Counters╅ 119
2.╇ Analog Rate Meters╅ 120
F. COINCIDENCE UNITSâ•… 121
G. HIGH-VOLTAGE POWER SUPPLIESâ•… 122
H. NUCLEAR INSTRUMENT MODULESâ•… 122
I. OSCILLOSCOPESâ•… 123
1.╇ Cathode Ray Tube╅ 123
2.╇ Analog Oscilloscope╅ 124
3.╇ Digital Oscilloscope╅ 124

CHAPTER 9 Nuclear Counting Statisticsâ•… 125


. TYPES OF MEASUREMENT ERRORâ•… 125
A
B. NUCLEAR COUNTING STATISTICSâ•… 126
1.╇ The Poisson Distribution╅ 126
2.╇ The Standard Deviation╅ 128
3.╇ The Gaussian Distribution╅ 128
C. PROPAGATION OF ERRORSâ•… 128
1.╇ Sums and Differences╅ 129
2.╇ Constant Multipliers╅ 129
3.╇ Products and Ratios╅ 129
4.╇ More Complicated Combinations╅ 129
D. APPLICATIONS OF STATISTICAL ANALYSISâ•… 130
1.╇ Effects of Averaging╅ 130
2.╇ Counting Rates╅ 130
3.╇ Significance of Differences Between Counting Measurements╅ 130
4.╇ Effects of Background╅ 131
5.╇ Minimum Detectable Activity╅ 131
6.╇ Comparing Counting Systems╅ 132
7.╇ Estimating Required Counting Times╅ 132
8.╇ Optimal Division of Counting Times╅ 133
x Contents

E. STATISTICAL TESTSâ•… 133


1.╇ The χ2 Testâ•… 133
2.╇ The t-Test╅ 135
3.╇ Treatment of “Outliers”â•… 138
4.╇ Linear Regression╅ 139

CHAPTER 10 Pulse-Height Spectrometryâ•… 141


. BASIC PRINCIPLESâ•… 141
A
B. SPECTROMETRY WITH NaI(Tl)â•… 142
1.╇ The Ideal Pulse-Height Spectrum╅ 142
2.╇ The Actual Spectrum╅ 143
3.╇ Effects of Detector Size╅ 145
4.╇ Effects of Counting Rate╅ 146
5.╇ General Effects of γ-Ray Energyâ•… 147
6.╇ Energy Linearity╅ 147
7.╇ Energy Resolution╅ 148
C. SPECTROMETRY WITH OTHER DETECTORSâ•… 151
1.╇ Semiconductor Detector Spectrometers╅ 151
2.╇ Liquid Scintillation Spectrometry╅ 152
3.╇ Proportional Counter Spectrometers╅ 153

CHAPTER 11 Problems in Radiation Detection and Measurementâ•… 155


A. DETECTION EFFICIENCYâ•… 155
1.╇ Components of Detection Efficiency╅ 155
2.╇ Geometric Efficiency╅ 156
3.╇ Intrinsic Efficiency╅ 158
4.╇ Energy-Selective Counting╅ 159
5.╇ Some Complicating Factors╅ 160
6.╇ Calibration Sources╅ 164
B. PROBLEMS IN THE DETECTION AND MEASUREMENT
OF β PARTICLESâ•… 166
C. DEAD TIMEâ•… 168
1.╇ Causes of Dead Time╅ 168
2.╇ Mathematical Models╅ 168
3.╇ Window Fraction Effects╅ 170
4.╇ Dead Time Correction Methods╅ 170
D. QUALITY ASSURANCE FOR RADIATION MEASUREMENT SYSTEMSâ•… 171

CHAPTER 12 Counting Systemsâ•… 173


A. NaI(Tl) WELL COUNTERâ•… 173
╇ 1.╇ Detector Characteristics╅ 173
╇ 2.╇ Detection Efficiency╅ 174
╇ 3.╇ Sample Volume Effects╅ 175
╇ 4.╇ Assay of Absolute Activity╅ 177
╇ 5.╇ Shielding and Background╅ 177
╇ 6.╇ Energy Calibration╅ 178
╇ 7.╇ Multiple Radionuclide Source Counting╅ 178
╇ 8.╇ Dead Time╅ 179
╇ 9.╇ Automated Multiple-Sample Systems╅ 179
10.╇ Applications╅ 182
B. COUNTING WITH CONVENTIONAL NaI(Tl) DETECTORSâ•… 182
╇ 1.╇ Large Sample Volumes╅ 182
╇ 2.╇ Liquid and Gas Flow Counting╅ 182
C. LIQUID SCINTILLATION COUNTERSâ•… 182
╇ 1.╇ General Characteristics╅ 182
╇ 2.╇ Pulse-Height Spectrometry╅ 184
╇ 3.╇ Counting Vials╅ 184
╇ 4.╇ Energy and Efficiency Calibration╅ 185
╇ 5.╇ Quench Corrections╅ 185
╇ 6.╇ Sample Preparation Techniques╅ 187
Contents xi

╇ 7.╇ Cerenkov Counting╅ 188


╇ 8.╇ Liquid and Gas Flow Counting╅ 188
╇ 9.╇ Automated Multiple-Sample LS Counters╅ 188
10.╇ Applications╅ 189
D. GAS-FILLED DETECTORSâ•… 189
╇ 1.╇ Dose Calibrators╅ 189
╇ 2.╇ Gas Flow Counters╅ 190
E. SEMICONDUCTOR DETECTOR SYSTEMSâ•… 190
╇ 1.╇ System Components╅ 190
╇ 2.╇ Applications╅ 191
F. IN VIVO COUNTING SYSTEMSâ•… 192
╇ 1.╇ NaI(Tl) Probe Systems╅ 192
╇ 2.╇ Miniature γ -Ray and β Probes for Surgical Useâ•… 192
╇ 3.╇ Whole-Body Counters╅ 194

CHAPTER 13 The Gamma Camera: Basic Principlesâ•… 195


. GENERAL CONCEPTS OF RADIONUCLIDE IMAGINGâ•… 195
A
B. BASIC PRINCIPLES OF THE GAMMA CAMERAâ•… 196
1.╇ System Components╅ 196
2.╇ Detector System and Electronics╅ 197
3.╇ Collimators╅ 201
4.╇ Event Detection in a Gamma Camera╅ 204
C. TYPES OF GAMMA CAMERAS AND THEIR CLINICAL USESâ•… 206

CHAPTER 14 The Gamma Camera: Performance Characteristicsâ•… 209


A. BASIC PERFORMANCE CHARACTERISTICSâ•… 209
1.╇ Intrinsic Spatial Resolution╅ 209
2.╇ Detection Efficiency╅ 211
3.╇ Energy Resolution╅ 211
4.╇ Performance at High Counting Rates╅ 213
B. DETECTOR LIMITATIONS: NONUNIFORMITY AND NONLINEARITYâ•… 216
1.╇ Image Nonlinearity╅ 216
2.╇ Image Nonuniformity╅ 217
3.╇ Nonuniformity Correction Techniques╅ 217
4.╇ Gamma Camera Tuning╅ 219
C. DESIGN AND PERFORMANCE CHARACTERISTICS OF PARALLEL-HOLE
COLLIMATORSâ•… 220
1.╇ Basic Limitations in Collimator Performance╅ 220
2.╇ Septal Thickness╅ 220
3.╇ Geometry of Collimator Holes╅ 222
4.╇ System Resolution╅ 225
D. PERFORMANCE CHARACTERISTICS OF CONVERGING, DIVERGING,
AND PINHOLE COLLIMATORSâ•… 225
E. MEASUREMENTS OF GAMMA CAMERA PERFORMANCEâ•… 228
1.╇ Intrinsic Resolution╅ 229
2.╇ System Resolution╅ 229
3.╇ Spatial Linearity╅ 229
4.╇ Uniformity╅ 230
5.╇ Counting Rate Performance╅ 230
6.╇ Energy Resolution╅ 231
7.╇ System Sensitivity╅ 231

CHAPTER 15 Image Quality in Nuclear Medicineâ•… 233


A. BASIC METHODS FOR CHARACTERIZING AND EVALUATING
IMAGE QUALITYâ•… 233
B. SPATIAL RESOLUTIONâ•… 233
1.╇ Factors Affecting Spatial Resolution╅ 233
2.╇ Methods for Evaluating Spatial Resolution╅ 234
C. CONTRASTâ•… 239
xii Contents

D. NOISEâ•… 243
1.╇ Types of Image Noise╅ 243
2.╇ Random Noise and Contrast-to-Noise Ratio╅ 243
E. OBSERVER PERFORMANCE STUDIESâ•… 247
1.╇ Contrast-Detail Studies╅ 247
2.╇ Receiver Operating Characteristic Studies╅ 248

CHAPTER 16 Tomographic Reconstruction in Nuclear Medicineâ•… 253


. GENERAL CONCEPTS, NOTATION, AND TERMINOLOGYâ•… 254
A
B. BACKPROJECTION AND FOURIER-BASED TECHNIQUESâ•… 256
1.╇ Simple Backprojection╅ 256
2.╇ Direct Fourier Transform Reconstruction╅ 258
3.╇ Filtered Backprojection╅ 260
4.╇ Multislice Imaging╅ 262
C. IMAGE QUALITY IN FOURIER TRANSFORM AND FILTERED
BACKPROJECTION TECHNIQUESâ•… 263
1.╇ Effects of Sampling on Image Quality╅ 263
2.╇ Sampling Coverage and Consistency Requirements╅ 266
3.╇ Noise Propagation, Signal-to-Noise Ratio, and Contrast-to-Noise
Ratioâ•… 266
D. ITERATIVE RECONSTRUCTION ALGORITHMSâ•… 270
1.╇ General Concepts of Iterative Reconstruction╅ 270
2.╇ Expectation-Maximization Reconstruction╅ 272
E. RECONSTRUCTION OF FAN-BEAM, CONE-BEAM AND PINHOLE SPECT
DATA, AND 3-D PET DATAâ•… 273
1.╇ Reconstruction of Fan-Beam Data╅ 273
2.╇ Reconstruction of Cone-Beam and Pinhole Data╅ 274
3.╇ 3-D PET Reconstruction╅ 275

CHAPTER 17 Single Photon Emission Computed Tomographyâ•… 279


A. SPECT SYSTEMSâ•… 279
1.╇ Gamma Camera SPECT Systems╅ 279
2.╇ SPECT Systems for Brain Imaging╅ 280
3.╇ SPECT Systems for Cardiac Imaging╅ 281
4.╇ SPECT Systems for Small-Animal Imaging╅ 283
B. PRACTICAL IMPLEMENTATION OF SPECTâ•… 285
1.╇ Attenuation Effects and Conjugate Counting╅ 287
2.╇ Attenuation Correction╅ 293
3.╇ Transmission Scans and Attenuation Maps╅ 294
4.╇ Scatter Correction╅ 296
5.╇ Partial-Volume Effects╅ 299
C. PERFORMANCE CHARACTERISTICS OF SPECT SYSTEMSâ•… 299
1.╇ Spatial Resolution╅ 301
2.╇ Volume Sensitivity╅ 301
3.╇ Other Measurements of Performance╅ 302
4.╇ Quality Assurance in SPECT╅ 302
D. APPLICATIONS OF SPECTâ•… 303

CHAPTER 18 Positron Emission Tomographyâ•… 307


A. BASIC PRINCIPLES OF PET IMAGINGâ•… 307
1.╇ Annihilation Coincidence Detection╅ 307
2.╇ Time-of-Flight PET╅ 309
3.╇ Spatial Resolution: Detectors╅ 310
4.╇ Spatial Resolution: Positron Physics╅ 312
5.╇ Spatial Resolution: Depth-of-Interaction Effect╅ 316
6.╇ Spatial Resolution: Sampling╅ 318
7.╇ Spatial Resolution: Reconstruction Filters╅ 319
8.╇ Sensitivity╅ 319
9.╇ Event Types in Annihilation Coincidence Detection╅ 322
Contents xiii

B. PET DETECTOR AND SCANNER DESIGNSâ•… 324


1.╇ Block Detectors╅ 324
2.╇ Modified Block Detectors╅ 325
3.╇ Whole-Body PET Systems╅ 326
4.╇ Specialized PET Scanners╅ 330
5.╇ Small-Animal PET Scanners╅ 331
C. DATA ACQUISITION FOR PETâ•… 332
1.╇ Two-Dimensional Data Acquisition╅ 332
2.╇ Three-Dimensional Data Acquisition╅ 332
3.╇ Data Acquisition for Dynamic Studies and Whole-Body Scans╅ 335
D. DATA CORRECTIONS AND QUANTITATIVE ASPECTS OF PETâ•… 335
1.╇ Normalization╅ 335
2.╇ Correction for Random Coincidences╅ 336
3.╇ Correction for Scattered Radiation╅ 337
4.╇ Attenuation Correction╅ 338
5.╇ Dead Time Correction╅ 339
6.╇ Absolute Quantification of PET Images╅ 339
E. PERFORMANCE CHARACTERISTICS OF PET SYSTEMSâ•… 340
F. CLINICAL AND RESEARCH APPLICATIONS OF PETâ•… 341

CHAPTER 19 Hybrid Imaging: SPECT/CT and PET/CTâ•… 345


. MOTIVATION FOR HYBRID SYSTEMSâ•… 345
A
B. X-RAY COMPUTED TOMOGRAPHYâ•… 346
1.╇ X-ray Tube╅ 346
2.╇ X-ray Detectors╅ 347
3.╇ X-ray CT Scanner╅ 348
4.╇ CT Reconstruction╅ 348
C. SPECT/CT SYSTEMSâ•… 350
1.╇ Clinical SPECT/CT Scanners╅ 350
2.╇ Small-Animal SPECT/CT Scanners╅ 352
D. PET/CTâ•… 354
1.╇ Clinical PET/CT Scanners╅ 354
2.╇ Small-Animal PET/CT Scanners╅ 356
E. ATTENUATION AND SCATTER CORRECTION USING CTâ•… 356
1.╇ Computing Attenuation Correction Factors from CT Scans╅ 357
2.╇ Possible Sources of Artifacts for CT-Based Attenuation Correction╅ 358
3.╇ Scatter Correction╅ 360
F. HYBRID PET/MRI AND SPECT/MRIâ•… 360

CHAPTER 20 Digital Image Processing in Nuclear Medicineâ•… 363


A. DIGITAL IMAGESâ•… 364
1.╇ Basic Characteristics and Terminology╅ 364
2.╇ Spatial Resolution and Matrix Size╅ 365
3.╇ Image Display╅ 367
4.╇ Acquisition Modes╅ 367
B. DIGITAL IMAGE-PROCESSING TECHNIQUESâ•… 369
1.╇ Image Visualization╅ 369
2.╇ Regions and Volumes of Interest╅ 372
3.╇ Time-Activity Curves╅ 373
4.╇ Image Smoothing╅ 373
5.╇ Edge Detection and Segmentation╅ 373
6.╇ Co-Registration of Images╅ 375
C. PROCESSING ENVIRONMENTâ•… 376

CHAPTER 21 Tracer Kinetic Modelingâ•… 379


. BASIC CONCEPTSâ•… 379
A
B. TRACERS AND COMPARTMENTSâ•… 380
1.╇ Definition of a Tracer╅ 380
2.╇ Definition of a Compartment╅ 382
3.╇ Distribution Volume and Partition Coefficient╅ 382
xiv Contents

4.╇ Flux╅ 383


5.╇ Rate Constants╅ 384
6.╇ Steady State╅ 385
C. TRACER DELIVERY AND TRANSPORTâ•… 386
1.╇ Blood Flow, Extraction, and Clearance╅ 386
2.╇ Transport╅ 389
D. FORMULATION OF A COMPARTMENTAL MODELâ•… 390
E. EXAMPLES OF DYNAMIC IMAGING AND TRACER KINETIC
MODELSâ•… 392
1.╇ Cardiac Function and Ejection Fraction╅ 392
2.╇ Blood Flow Models╅ 392
3.╇ Blood Flow: Trapped Radiotracers╅ 393
4.╇ Blood Flow: Clearance Techniques╅ 394
5.╇ Enzyme Kinetics: Glucose Metabolism╅ 396
6.╇ Receptor Ligand Assays╅ 401
F. SUMMARYâ•… 403

CHAPTER 22 Internal Radiation Dosimetryâ•… 407


A. RADIATION DOSE AND EQUIVALENT DOSE: QUANTITIES AND
UNITSâ•… 407
B. CALCULATION OF RADIATION DOSE (MIRD METHOD)â•… 408
1.╇ Basic Procedure and Some Practical Problems╅ 408
~
2.╇ Cumulated Activity, A   409
3.╇ Equilibrium Absorbed Dose Constant, Δ  412
4.╇ Absorbed Fraction, ϕ  413
5.╇ Specific Absorbed Fraction, Φ, and the Dose Reciprocity Theoremâ•… 414
6.╇ Mean Dose per Cumulated Activity, S╅ 415
7.╇ Whole-Body Dose and Effective Dose╅ 417
8.╇ Limitations of the MIRD Method╅ 424

CHAPTER 23 Radiation Safety and Health Physicsâ•… 427


A. QUANTITIES AND UNITSâ•… 428
1.╇ Dose-Modifying Factors╅ 428
2.╇ Exposure and Air Kerma╅ 428
B. REGULATIONS PERTAINING TO THE USE OF RADIONUCLIDESâ•… 431
1.╇ Nuclear Regulatory Commission Licensing and Regulations╅ 431
2.╇ Restricted and Unrestricted Areas╅ 431
3.╇ Dose Limits╅ 431
4.╇ Concentrations for Airborne Radioactivity in Restricted Areas╅ 432
5.╇Environmental Concentrations and Concentrations for Sewage
Disposalâ•… 432
6.╇ Record-Keeping Requirements╅ 432
7.╇ Recommendations of Advisory Bodies╅ 433
C. SAFE HANDLING OF RADIOACTIVE MATERIALSâ•… 433
1.╇ The ALARA Concept╅ 433
2.╇ Reduction of Radiation Doses from External Sources╅ 434
3.╇ Reduction of Radiation Doses from Internal Sources╅ 437
4.╇ Laboratory Design╅ 438
5.╇ Procedures for Handling Spills╅ 438
D. DISPOSAL OF RADIOACTIVE WASTEâ•… 439
E. RADIATION MONITORINGâ•… 439
1.╇ Survey Meters and Laboratory Monitors╅ 439
2.╇ Personnel Dosimeters╅ 440
3.╇ Wipe Testing╅ 441

APPENDIX A Unit Conversionsâ•… 443

APPENDIX B Properties of the Naturally Occurring Elementsâ•… 445


Contents xv

APPENDIX C Decay Characteristics of Some Medically Important


Radionuclidesâ•… 449

APPENDIX D Mass Attenuation Coefficients for Water, NaI(Tl),


Bi4Ge3O12, Cd0.8Zn0.2Te, and Leadâ•… 476

APPENDIX E Effective Dose Equivalent (mSv/MBq) and Radiation


Absorbed Dose Estimates (mGy/MBq) to Adult Subjects
from Selected Internally Administered
Radiopharmaceuticalsâ•… 478

APPENDIX F The Fourier Transformâ•… 481


A.╇ THE FOURIER TRANSFORM: WHAT IT REPRESENTS╅ 481
B.╇ CALCULATING FOURIER TRANSFORMS ╅ 481
C.╇ SOME PROPERTIES OF FOURIER TRANSFORMS╅ 483
D.╇ SOME EXAMPLES OF FOURIER TRANSFORMS╅ 486

APPENDIX G Convolutionâ•… 489


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Animations, Calculators,
and Graphing Tools
(Available online at expertconsult.com.)

ANIMATIONS
1. Emission of a characteristic x ray (Figure 2-4)
2. Emission of an Auger electron (Figure 2-5)
3. Internal conversion involving K-shell electron (Figure 3-5)
4. Positron emission and annihilation (Figure 3-7)
5. Positive ion cyclotron (Figure 5-3)
6. Ionization of an atom (Figure 6-1A)
7. Bremsstrahlung production (Figure 6-1B)
8. Photoelectric effect (Figure 6-11)
9. Compton scattering (Figure 6-12)
10. Pair production (Figure 6-14)
11. Basic principles of a gas-filled chamber (Figure 7-1)
12. Basic principles of a photomultiplier tube (Figure 7-13)
13. Scintillation detector (Figure 7-16)
14. Pulse-height spectrum (Figure 8-9 and Figure 10-2)
15. Gamma camera (Figure 13-1)
16. Sinogram formation and SPECT (Figure 16-4)
17. Backprojection (Figure 16-5)

CALCULATORS
1. Decay of activity (Equations 4-7 and 4-10)
2. Image-frame decay correction (Equations 4-15 and 4-16)
3. Carrier-free specific activity (Equations 4-21 to 4-23)
4. Cyclotron particle energy (Equation 5-12)
5. Compton scatter kinematics (Equations 6-11 and 6-12)
6. Photon absorption and transmission (Equation 6-22)
7. Effective atomic number (Equations 7-2 and 7-3)
8. Propagation of errors for sums and differences (Equation 9-12)
9. Solid angle calculation for a circular detector (Equation 11-7)
10. Activity conversions (Appendix A)

GRAPHING TOOLS
1. Bateman equation (Equation 4-25)
2. Dead time models (Equations 11-16 and 11-18)
3. Resolution and sensitivity of a parallel-hole collimator (Equations 14-6
and 14-7)
4. Resolution and sensitivity of a pinhole collimator (Equations 14-15 to
14-18)

xvii
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PHYSICS in NUCLEAR MEDICINE
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chapter
1 
What Is Nuclear
Medicine?
scans, where there is not much tracer uptake
A.  FUNDAMENTAL CONCEPTS in the tissue lying above and below the bones).
For the tomographic mode of single photon
The science and clinical practice of nuclear imaging (SPECT), data are collected from
medicine involve the administration of trace many angles around the patient. This allows
amounts of compounds labeled with radioac- cross-sectional images of the distribution of
tivity (radionuclides) that are used to provide the radionuclide to be reconstructed, thus
diagnostic information in a wide range of providing the depth information missing from
disease states. Although radionuclides also planar imaging.
have some therapeutic uses, with similar Positron imaging makes use of radio�
underlying physics principles, this book nuclides that decay by positron emission. The
focuses on the diagnostic uses of radionu- emitted positron has a very short lifetime
clides in modern medicine. and, following annihilation with an electron,
In its most basic form, a nuclear medicine simultaneously produces two high-energy
study involves injecting a compound, which  photons that subsequently are detected by an
is labeled with a gamma-ray-emitting or imaging camera. Once again, tomographic
positron-emitting radionuclide, into the body. images are formed by collecting data from
The radiolabeled compound is called a radio- many angles around the patient, resulting in
pharmaceutical, or more commonly, a tracer PET images.
or radiotracer. When the radionuclide decays,
gamma rays or high-energy photons are
emitted. The energy of these gamma rays or
photons is such that a significant number can B.  THE POWER OF NUCLEAR
exit the body without being scattered or MEDICINE
attenuated. An external, position-sensitive
gamma-ray “camera” can detect the gamma The power of nuclear medicine lies in its
rays or photons and form an image of the ability to provide exquisitely sensitive mea-
distribution of the radionuclide, and hence sures of a wide range of biologic processes in
the compound (including radiolabeled prod- the body. Other medical imaging modalities
ucts of reactions of that compound) to which such as magnetic resonance imaging (MRI),
it was attached. x-ray imaging, and x-ray computed tomog�
There are two broad classes of nuclear raphy (CT) provide outstanding anatomic
medicine imaging: single photon imaging images but are limited in their ability to
[which includes single photon emission com- provide biologic information. For example,
puted tomography (SPECT)] and positron magnetic resonance methods generally have
imaging [positron emission tomography a lower limit of detection in the millimolar
(PET)]. Single photon imaging uses radionu- concentration range (≈â•›6 × 1017 molecules per
clides that decay by gamma-ray emission. A mL tissue), whereas nuclear medicine studies
planar image is obtained by taking a picture routinely detect radio�labeled substances in
of the radionuclide distribution in the patient the nanomolar (≈â•›6 × 1011 molecules per mL
from one particular angle. This results in an tissue) or picomolar (≈â•›6 × 108 molecules
image with little depth information, but which per mL tissue) range. This sensitivity advan-
can still be diagnostically useful (e.g., in bone tage, together with the ever-growing selection
1
2 Physics in Nuclear Medicine

of radiolabeled compounds, allows nuclear “inside” the human body noninvasively for the
medicine studies to be targeted to the very first time and was particularly useful for 
specific biologic processes underlying disease. the imaging of bone. X rays soon became the
Examples of the diverse biologic processes method of choice for producing “radiographs”
that can be measured by nuclear medicine because images could be obtained more quickly
techniques include tissue perfusion, glucose and with better contrast than those provided
metabolism, the somatostatin receptor status by radium or other naturally occurring radio-
of tumors, the density of dopamine receptors nuclides that were available at that time.
in the brain, and gene expression. Although the field of diagnostic x-ray imaging
Because radiation detectors can easily rapidly gained acceptance, nuclear medicine
detect very tiny amounts of radioactivity, and had to await further developments.
because radiochemists are able to label com- The biologic foundations for nuclear medi-
pounds with very high specific activity (a cine were laid down between 1910 and 1945.
large fraction of the injected molecules are In 1913, Georg de Hevesy developed the prin-
labeled with a radioactive atom), it is possible ciples of the tracer approach2 and was the
to form high-quality images even with nano- first to apply them to a biologic system in
molar or picomolar concentrations of com- 1923, studying the absorption and transloca-
pounds. Thus trace amounts of a compound, tion of radioactive lead nitrate in plants.3
typically many orders of magnitude below the The first human study employing radioactive
millimolar to micromolar concentrations that tracers was probably that of Blumgart and
generally are required for pharmacologic Weiss (1927),4 who injected an aqueous solu-
effects, can be injected and followed safely tion of radon intravenously and measured the
over time without perturbing the biologic transit time of the blood from one arm to the
system. Like CT, there is a small radiation other using a cloud chamber as the radiation
dose associated with performing nuclear med- detector. In the 1930s, with the invention of
icine studies, with specific doses to the differ- the cyclotron by Lawrence (Fig. 1-1),5 it
ent organs depending on the radionuclide, as became possible to artificially produce new
well as the spatial and temporal distribution radionuclides, thereby extending the range of
of the particular radiolabeled compound that biologic processes that could be studied. Once
is being studied. The safe dose for human again, de Hevesy was at the forefront of using
studies is established through careful dosim- these new radionuclides to study biologic pro-
etry for every new radiopharmaceutical that cesses in plants and in red blood cells. Finally,
is approved for human use. at the end of the Second World War, the
nuclear reactor facilities that were developed
as part of the Manhattan Project started to
C.  HISTORICAL OVERVIEW be used for the production of radioactive 
isotopes in quantities sufficient for medical
As with the development of any field of science  applications.
or medicine, the history of nuclear medicine The 1950s saw the development of technol-
is a complex topic, involving contributions ogy that allowed one to obtain images of the
from a large number of scientists, engineers, distribution of radionuclides in the human
and physicians. A complete overview is well body rather than just counting at a few mea-
beyond the scope of this book; however, a few surement points. Major milestones included
highlights serve to place the development of the development of the rectilinear scanner in
nuclear medicine in its appropriate historical 1951 by Benedict Cassen6 (Fig. 1-2) and the
context. Anger camera, the forerunner of all modern
The origins of nuclear medicine1 can be nuclear medicine single-photon imaging
traced back to the last years of the 19th systems, developed in 1958 by Hal Anger (Fig.
century and the discovery of radioactivity by 1-3).7 In 1951, the use of positron emitters
Henri Becquerel (1896) and of radium by and the advantageous imaging properties of
Marie Curie (1898). These developments came these radionuclides also were described by
close on the heels of the discovery of x rays in Wrenn and coworkers.8
1895 by Wilhelm Roentgen. Both x rays and Until the early 1960s, the fledgling field of
radium sources were quickly adopted for nuclear medicine primarily used 131I in the
medical applications and were used to make study and diagnosis of thyroid disorders and
shadow images in which the radiation was an assortment of other radionuclides that
transmitted through the body and onto photo- were individually suitable for only a few spe-
graphic plates. This allowed physicians to see cific organs. The use of 99mTc for imaging in
1  •  What Is Nuclear Medicine? 3

FIGURE 1-1  Ernest O. Lawrence


standing next to the cyclotron he
invented at Berkeley, California.
(From Myers WG, Wagner HN:
Nuclear medicine: How it began.
Hosp Pract 9:103-113, 1974.)

FIGURE 1-2  Left, Benedict Cassen with his rectilinear scanner (1951), a simple scintillation counter (see Chapter 7)
that scans back and forth across the patient. Right, Thyroid scans from an early rectilinear scanner following admin-
istration of 131I. The output of the scintillation counter controlled the movement of an ink pen to produce the first
nuclear medicine images. (Left, Courtesy William H. Blahd, MD; with permission of Radiology Centennial, Inc. Right,
From Cassen B, Curtis L, Reed C, Libby R: Instrumentation for 131I use in medical studies. Nucleonics 9:46-50, 1951.)
4 Physics in Nuclear Medicine

FIGURE 1-3  Left, Hal Anger with the first gamma camera in 1958. Right, 99mTc-pertechnetate brain scan of a patient
with glioma at Vanderbilt University Hospital (1971). Each image represents a different view of the head. The glioma
is indicated by an arrow in one of the views. In the 1960s, this was the only noninvasive test that could provide images
showing pathologic conditions inside the human brain. These studies played a major role in establishing nuclear medi-
cine as an integral part of the diagnostic services in hospitals. (Left, From Myers WG: The Anger scintillation camera
becomes of age. J Nucl Med 20:565-567, 1979. Right, Courtesy Dennis D. Patton, MD, University of Arizona, Tucson,
Arizona.)

1964 by Paul Harper and colleagues9 changed D.  CURRENT PRACTICE OF NUCLEAR
this and was a major turning point for the MEDICINE
development of nuclear medicine. The gamma
rays emitted by 99mTc had very good proper- Nuclear medicine is used for a wide variety of
ties for imaging. It also proved to be very diagnostic tests. There were roughly 100 dif-
flexible for labeling a wide variety of com- ferent diagnostic imaging procedures avail-
pounds that could be used to study virtually able in 2006.* These procedures use many
every organ in the body. Equally important, different radiolabeled compounds, cover all
it could be produced in a relatively long-lived the major organ systems in the body, and
generator form, allowing hospitals to have a provide many different measures of biologic
readily available supply of the radionuclide. function. Table 1-1 lists some of the more
Today, 99mTc is the most widely used radionu- common clinical procedures.
clide in nuclear medicine. As of 2008, more than 30 million nuclear 
The final important development was  medicine imaging procedures were performed 
the mathematics to reconstruct tomographic on a global basis.† There are more than 20,000
images from a set of angular views around nuclear medicine cameras capable of imaging
the patient. This revolutionized the whole gamma-ray-emitting radionuclides installed
field of medical imaging (leading to CT,  in hospitals across the world. Even many
PET, SPECT and MRI) because it replaced small hospitals have their own nuclear medi-
the two-dimensional representation of the cine clinic. There also were more than 3,000
three-dimensional radioactivity distribution, PET scanners installed in the world perform-
with a true three-dimensional representa- ing on the order of 4 million procedures
tion. This allowed the development of PET
by Phelps and colleagues10 and SPECT by *Data courtesy Society of Nuclear Medicine, Reston,
Kuhl and colleagues11 during the 1970s and Virginia.
marked the start of the modern era of †Data courtesy Siemens Molecular Imaging, Hoffman
nuclear medicine. Estates, Illinois.
1  •  What Is Nuclear Medicine? 5

TABLE 1-1â•…
SELECTED CLINICAL NUCLEAR MEDICINE PROCEDURES

Radiopharmaceutical Imaging Measurement Examples of Clinical Use


99m
Tc-MDP Planar Bone metabolism Metastatic spread of cancer,
osteomyelitis vs. cellulitis
99m
Tc-sestamibi (Cardiolite) SPECT or Myocardial perfusion Coronary artery disease
99m planar
Tc-tetrofosmin (Myoview)
201
Tl-thallous chloride
99m
Tc-MAG3 Planar Renal function Kidney disease
99m
Tc-DTPA
99m
Tc-HMPAO (Ceretec) SPECT Cerebral blood flow Neurologic disorders
99m
Tc-ECD SPECT Cerebral blood flow Neurologic disorders
123
I-sodium iodide Planar Thyroid function Thyroid disorders
131
I-sodium iodide Thyroid cancer
67
Ga-gallium citrate Planar Sequestered in tumors Tumor localization
99m
Tc-macroaggregated Planar Lung perfusion/ Pulmonary embolism
albumin and 133Xe gas ventilation
111
In-labeled white blood Planar Sites of infection Detection of inflammation
cells
18
F-fluorodeoxyglucose PET Glucose metabolism Cancer, neurological
disorders, and myocardial
diseases
82
Rb-rubidium chloride PET Myocardial perfusion Coronary artery disease
MDP, methylene diphosphonate; MAG3, mercapto-acetyl-triglycine; DTPA, diethylenetriaminepenta-acetic acid;
HMPAO, hexamethylpropyleneamine oxime; ECD, ethyl-cysteine-dimer; SPECT, single photon emission computed
tomography; PET, positron emission tomography.

annually. The short half-lives of the most commercial PET/MRI systems were being
commonly used positron-emitting radionu- delivered.
clides require an onsite accelerator or deliv- In addition to its clinical role, PET (and to
ery of PET radiopharmaceuticals from a certain extent, SPECT) continues to play a
regional radiopharmacies. To meet this need, major role in the biomedical research com-
there is now a PET radiopharmacy within 100 munity. PET has become an established and
miles of approximately 90% of the hospital powerful research tool for quantitatively and
beds in the United States. The growth of  noninvasively measuring the rates of biologic
clinical PET has been driven by the utility  processes, both in the healthy and diseased
of a metabolic tracer, 18F-fluorodeoxyglucose, state. In this research environment, the
which has widespread applications in cancer, radiolabeled compounds and clinical nuclear
heart disease, and neurologic disorders. medicine assays of the future are being devel-
One major paradigm shift that has occurred oped. In preclinical, translational and clinical
since the turn of the millennium has been research, nuclear medicine has been at the
toward multimodality instrumentation. Vir- forefront in developing new diagnostic oppor-
tually all PET scanners, and a rapidly growing tunities in the field of molecular medicine,
number of SPECT systems, are now inte- created by the merger of biology and medi-
grated with a CT scanner in combined PET/ cine. A rapid growth is now occurring in the
CT and SPECT/CT configurations. These number and diversity of PET and SPECT
systems enable the facile correlation of struc- molecular imaging tracers targeted to specific
ture (CT) and function (PET or SPECT), proteins and molecular pathways implicated
yielding better diagnostic insight in many in disease. These nuclear medicine technolo-
clinical situations. The combination of nuclear gies also have been embraced by the pharma-
medicine scanners with MRI systems also is ceutical and biotechnology industries to aid in
under inve�s�tigation, and as of 2011, first drug development and validation.
6 Physics in Nuclear Medicine

5. Lawrence EO, Livingston MS: The production of


E.  THE ROLE OF PHYSICS IN NUCLEAR high-speed light ions without the use of high volt-
MEDICINE ages. Phys Rev 40:19-30, 1932.
6. Cassen B, Curtis L, Reed C, Libby R: Instrumenta-
tion for 131I use in medical studies. Nucleonics 9:46-
Although the physics underlying nuclear 50, 1951.
medicine is not changing, the technology for 7. Anger HO: Scintillation camera. Rev Sci Instr 29:27-
33, 1958.
producing radioactive tracers and for obtain- 8. Wrenn FR, Good ML, Handler P: The use of positron-
ing images of those tracer distributions most emitting radioisotopes for the localization of brain
certainly is. We can expect to continue seeing tumors. Science 113:525-527, 1951.
major improvements in nuclear medicine 9. Harper PV, Beck R, Charleston D, Lathrop KA: Opti-
technology, which will come from combining mization of a scanning method using technetium-
99m. Nucleonics 22:50-54, 1964.
advances in detector and accelerator physics, 10. Phelps ME, Hoffman EJ, Mullani NA, Ter Pogossian
electronics, signal processing, and computer MM: Application of annihilation coincidence detec-
technology with the underlying physics of tion of transaxial reconstruction tomography. J Nucl
nuclear medicine. Methods for accurately Med 16:210-215, 1975.
11. Kuhl DE, Edwards RQ, Ricci AR, et al: The Mark IV
quantifying the concentrations of radio�labeled system for radionuclide computed tomography of the
tracers in structures of interest, measuring brain. Radiology 121:405-413, 1976.
biologic processes, and then relaying this
information to the physician in a clinically BIBLIOGRAPHY
meaningful and biologically relevant format For further details on the history of nuclear
are also an important challenge for the future. medicine, we recommend the following:
Refinement in the models used in dosimetry Myers WG, Wagner HN: Nuclear medicine: How it began.
will allow better characterization of radiation Hosp Pract 9(3):103-113, 1974.
exposure and make nuclear medicine even Nutt R: The history of positron emission tomography. Mol
Imaging Biol 4:11-26, 2002.
safer than it already is. Physics therefore con- Thomas AMK, editor: The Invisible Light: One Hundred
tinues to play an important and continuing Years of Medical Radiology, Oxford, England, 1995,
role in providing high-quality, cost-effective, Blackwell Scientific.
quantitative, reliable, and safe biologic assays Webb S: From the Watching of Shadows: The Origins of
Radiological Tomography, Bristol, England, 1990,
in living humans. Adam Hilger.
Recommended texts that cover clinical nuclear
medicine in detail are the following:
REFERENCES Ell P, Gambhir S, editors: Nuclear Medicine in Clinical
1. Mould RF: A Century of X-Rays and Radioactivity in Diagnosis and Treatment, ed 3, Edinburgh, Scotland,
Medicine, Bristol, 1993, Institute of Physics. 2004, Churchill Livingstone.
2. de Hevesy G: Radioelements as tracers in physics and Sandler MP, Coleman RE, Patton JA, et al, editors: Diag-
chemistry. Chem News 108:166, 1913. nostic Nuclear Medicine, ed 4, Baltimore, 2002, Wil-
3. de Hevesy G: The absorption and translocation of liams & Wilkins.
lead by plants: A contribution to the application of Schiepers C, editor: Diagnostic Nuclear Medicine, ed 2,
the method of radioactive indicators in the investiga- New York, 2006, Springer.
tion of the change of substance in plants. Biochem J Von Schulthess GK, editor: Molecular Anatomic Imaging:
17:439-445, 1923. PET-CT and SPECT-CT Integrated Modality Imaging,
4. Blumgart HL, Weiss S: Studies on the velocity of ed 2, Philadelphia, 2006, Lippincott, Williams and
blood flow. J Clin Invest 4:15-31, 1927. Wilkins.
chapter
2 
Basic Atomic and
Nuclear Physics

Radioactivity is a process involving events in improve scientific communication, as well as


individual atoms and nuclei. Before discuss- eliminate some of the more irrational units
ing radioactivity, therefore, it is worthwhile (e.g., feet and pounds). A useful discussion of
to review some of the basic concepts of atomic the SI system, including definitions and
and nuclear physics. values of various units, can be found in refer-
ence 1.
SI units or their metric subunits (e.g., cen-
timeters and grams) are the standard for this
A.  QUANTITIES AND UNITS
text; however, in some instances traditional
or other non-SI units are given as well (in
1.  Types of Quantities and Units parentheses). This is done because some tra-
Physical properties and processes are ditional units still are used in the day-to-day
described in terms of quantities such as time practice of nuclear medicine (e.g., units of
and energy. These quantities are measured activity and absorbed dose). In other instances,
in units such as seconds and joules. Thus SI units are unreasonably large (or small) for
a quantity describes what is measured, describing the processes of interest and spe-
whereas a unit describes how much. cially defined units are more convenient and
Physical quantities are characterized as widely used. This is particularly true for units
fundamental or derived. A base quantity is of mass and energy, as discussed in the fol-
one that “stands alone”; that is, no reference lowing section.
is made to other quantities for its definition.
Usually, base quantities and their units are 2.  Mass and Energy Units
defined with reference to standards kept at Events occurring at the atomic level, such
national or international laboratories. Time (s as radioactive decay, involve amounts of 
or sec), distance (m), and mass (kg) are exam- mass and energy that are very small when
ples of base quantities. Derived quantities are described in SI or other conventional units.
defined in terms of combinations of base Therefore they often are described in terms

of a derived quantity.
·
quantities. Energy (kgâ•› â•›m2/sec2) is an example of specially defined units that are more con-
venient for the atomic scale.
The international scientific community has The basic unit of mass is the unified atomic
agreed to adopt so-called System Interna- mass unit, abbreviated u. One u is defined as
tional (SI) units as the standard for scientific being equal to exactly 1 12 the mass of an
communication. This system is based on unbound 12C atom* at rest and in its ground
seven base quantities in metric units, with all state. The conversion from SI mass units to
other quantities and units derived by appro- unified atomic mass units is1
priate definitions from them. The four quanti-
ties of mass, length, time and electrical charge 1 u = 1.66054 × 10−27 kg (2-1)
are most relevant to nuclear medicine. The
use of specially defined quantities (e.g., “atmo-
spheres” of barometric pressure) is specifi-
cally discouraged. It is hoped that this will *Atomic notation is discussed in Section D.2.
7
8 Physics in Nuclear Medicine

The universal mass unit often is called a 2. Electromagnetic radiation, in which


Dalton (Da) when expressing the masses of energy is carried by oscillating electrical
large biomolecules. The units are equivalent and magnetic fields traveling through
(i.e., 1╯Da = 1╯u). Either unit is convenient space at the speed of light.
for expressing atomic or molecular masses, Radioactive decay processes, discussed in
because a hydrogen atom has a mass of Chapter 3, result in the emission of radiation
approximately 1╯u or 1╯Da. in both of these forms.
The basic unit of energy is the electron volt The wavelength, λ, and frequency, ν, of the
(eVâ•›). One eV is defined as the amount of oscillating fields of electromagnetic radiation
energy acquired by an electron when it is are related by:
accelerated through an electrical potential of
1╯V. Basic multiples are the kiloelectron volt λ×ν = c (2-3)
(keV╛) (1╯keV = 1000╯eV╛) and the megaelec-
tron volt (MeV╛) (1╯MeV = 1000╯keV = where c is the velocity of light.
1,000,000╯eV╛). The conversion from SI energy Most of the more familiar types of electro-
units to the electron volt is magnetic radiation (e.g., visible light and
radio waves) exhibit “wavelike” behavior in
1 eV = 1.6022 × 10−19 kg i m 2 /sec 2 (2-2) their interactions with matter (e.g., diffrac-
tion patterns and transmission and detection
Mass m and energy E are related to each of radio signals). In some cases, however, elec-
other by Einstein’s equation E = mc2, in which tromagnetic radiation behaves as discrete
c is the velocity of light (approximately 3 × “packets” of energy, called photons (also called
108╯m/sec in vacuum). According to this equa- quanta). This is particularly true for interac-
tion, 1╯u of mass is equivalent to 931.5╯MeV tions involving individual atoms. Photons
of energy. have no mass or electrical charge and also
Relationships between various units of travel at the velocity of light. These charac-
mass and energy are summarized in Appen- teristics distinguish them from the forms 
dix A. Universal mass units and electron volts of particulate radiation mentioned earlier.
are very small, yet, as we shall see, they are The energy of the photon E, in kiloelectron
quite appropriate to the atomic scale. volts, and the wavelength of its associated
electromagnetic field λ (in nanometers) are
related by
B.  RADIATION
E(keV ) = 1.24 /λ (nm) (2-4)
The term radiation refers to “energy in
transit.” In nuclear medicine, we are inter- Figure 2-1 illustrates the photon energies
ested principally in the following two specific for different regions of the electromagnetic
forms of radiation: spectrum. Note that x rays and γ rays occupy
1. Particulate radiation, consisting of the highest-energy, shortest-wavelength end
atomic or subatomic particles (electrons, of the spectrum; x-ray and γ-ray photons
protons, etc.) that carry energy in the have energies in the keV-MeV range, whereas
form of kinetic energy of mass in motion. visible light photons, for example, have

Wavelength (m)
10 1 10 –1 10 –2 10 –3 10 –4 10 –5 10 –6 10 –7 10 –8 10 –9 10 –10 10 –11 10 –12 10 –13

Radio Infrared UV Gamma rays

Microwave Vis x rays

8 9 10 11 12 13 14 15 16 17 18 19 20 21
10 10 10 10 10 10 10 10 10 10 10 10 10 10

Frequency (Hz)

FIGURE 2-1  Schematic representation of the different regions of the electromagnetic spectrum. Vis, visible light;
UV, ultraviolet light.
2  •  Basic Atomic and Nuclear Physics 9

energies of only a few electron volts. As a According to classical theory, orbiting elec-
consequence of their high energies and short trons should slowly lose energy and spiral
wavelengths, x rays and γ rays interact with into the nucleus, resulting in atomic “col-
matter quite differently from other, more lapse.” This obviously is not what happens.
familiar types of electromagnetic radiation. The simple nuclear model therefore needed
These interactions are discussed in detail in further refinement. This was provided by
Chapter 6. Niels Bohr in 1913, who presented a model
that has come to be known as the Bohr atom.
In the Bohr atom there is a set of stable elec-
C.  ATOMS
tron orbits, or “shells,” in which electrons can
exist indefinitely without loss of energy. The
1.  Composition and Structure diameters of these shells are determined by
All matter is composed of atoms. An atom is quantum numbers, which can have only
the smallest unit into which a chemical integer values (n = 1, 2, 3, …). The innermost
element can be broken down without losing shell (n = 1) is called the K shell, the next the
its chemical identity. Atoms combine to form L shell (n = 2), followed by the M shell (n = 3),
molecules and chemical compounds, which  N shell (n = 4), and so forth.
in turn combine to form larger, macroscopic Each shell actually comprises a set of
structures. orbits, called substates, which differ slightly
The existence of atoms was first postulated from one another. Each shell has 2n − 1 sub-
on philosophical grounds by Ionian scholars states, in which n is the quantum number of
in the 5th century BC. The concept was for- the shell. Thus the K shell has only one sub-
malized into scientific theory early in the 19th state; the L shell has three substates, labeled
century, owing largely to the work of the LI, LII, LIII; and so forth. Figure 2-2 is a sche-
chemist, John Dalton, and his contempo- matic representation of the K, L, M, and N
raries. The exact structure of atoms was not shells of an atom.
known, but at that time they were believed to The Bohr model of the atom was further
be indivisible. Later in the century (1869), refined with the statement of the Pauli Exclu-
Mendeleev produced the first periodic table, sion Principle in 1925. According to this prin-
an ordering of the chemical elements accord- ciple, no two orbital electrons in an atom can
ing to the weights of their atoms and arrange- move with exactly the same motion. Because
ment in a grid according to their chemical of different possible electron “spin” orienta-
properties. For a time it was believed that tions, more than one electron can exist in
completion of the periodic table would repre- each substate; however, the number of elec-
sent the final step in understanding the struc- trons that can exist in any one shell or its
ture of matter. substates is limited. For a shell with quantum
Events of the late 19th and early 20th cen- number n, the maximum number of electrons
turies, beginning with the discovery of x rays allowed is 2n2. Thus the K shell (n = 1) is
by Roentgen (1895) and radioactivity by  limited to two electrons, the L shell (n = 2) to
Becquerel (1896), revealed that atoms had a eight electrons, and so forth.
substructure of their own. In 1910, Ruther- The Bohr model is actually an over-
ford presented experimental evidence indi� simplification. According to modern theories,
cating that atoms consisted of a massive, the orbital electrons do not move in precise
compact, positively charged core, or nucleus, circular orbits but rather in imprecisely
surrounded by a diffuse cloud of relatively defined “regions of space” around the nucleus,
light, negatively charged electrons. This model sometimes actually passing through the
came to be known as the nuclear atom. The nucleus; however, the Bohr model is quite
number of positive charges in the nucleus is adequate for the purposes of this text.
called the atomic number of the nucleus (Z).
In the electrically neutral atom, the number
of orbital electrons is sufficient to balance 2.  Electron Binding Energies and
exactly the number of positive charges, Z, in Energy Levels
the nucleus. The chemical properties of an In the most stable configuration, orbital elec-
atom are determined by orbital electrons; trons occupy the innermost shells of an atom,
therefore the atomic number Z determines where they are most “tightly bound” to the
the chemical element to which the atom nucleus. For example, in carbon, which has 
belongs. A listing of chemical elements and a total of six electrons, two electrons (the
their atomic numbers is given in Appendix B. maximum number allowed) occupy the K
10 Physics in Nuclear Medicine

K shell
n=1

L shell
n=2

Nucleus

M shell
n=3

N shell
n=4
FIGURE 2-2  Schematic representation of the Bohr model of the atom; n is the quantum number of the shell. Each
shell has multiple substates, as described in the text.

shell, and the four remaining electrons are Binding energies and energy differences
found in the L shell. Electrons can be moved are sometimes displayed on an energy-level
to higher shells or completely removed from diagram. Figure 2-3 shows such a diagram for
the atom, but doing so requires an energy the K and L shells of the element iodine. The
input to overcome the forces of attraction that top line represents an electron completely
“bind” the electron to the nucleus. The energy separated from the parent atom (“unbound”
may be provided, for example, by a particle or or “free” electron). The bottom line represents
a photon striking the atom. the most tightly bound electrons, that is, the
The energy required to completely remove K shell. Above this are lines representing sub-
an electron from a given shell in an atom is states of the L shell. (The M shell and other
called the binding energy of that shell. It is outer shell lines are just above the L shell
symbolized by the notation KB for the K shell,* lines.) The distance from the K shell to the
LB for the L shell (LIB, LIIB, LIIIB for the L shell top level represents the K-shell binding
substates), and so forth. Binding energy is energy for iodine (33.2╯keV╛). To move a
greatest for the innermost shell, that is, KB > K-shell electron to the L shell requires approx-
LB > MB. Binding energy also increases with imately 33 − 5 = 28╯keV of energy.
the positive charge (atomic number Z) of the
nucleus, because a greater positive charge 3.  Atomic Emissions
exerts a greater force of attraction on an elec- When an electron is removed from one of the
tron. Therefore binding energies are greatest inner shells of an atom, an electron from an
for the heaviest elements. Values of K-shell outer shell promptly moves in to fill the
binding energies for the elements are listed vacancy and energy is released in the process.
in Appendix B. The energy released when an electron drops
The energy required to move an electron from an outer to an inner shell is exactly
from an inner to an outer shell is exactly equal to the difference in binding energies
equal to the difference in binding energies between the two shells. The energy may
between the two shells. Thus the energy appear as a photon of electromagnetic radia-
required to move an electron from the K shell tion (Fig. 2-4). Electron binding energy differ-
to the L shell in an atom is KB − LB (with slight ences have exact characteristic values for
differences for different L shell substates). different elements; therefore the photon emis-
sions are called characteristic radiation or
*Sometimes the notation Kab also is used. characteristic x rays. The notation used to
2  •  Basic Atomic and Nuclear Physics 11

“Free” electrons

4–5 keV

L shell

FIGURE 2-3  Electron energy-level diagram for


an iodine atom. Vertical axis represents the
energy required to remove orbital electrons from
different shells (binding energy). Removing an
electron from the atom, or going from an inner
(e.g., Kâ•›) to an outer (e.g., Lâ•›) shell, requires an
energy input, whereas an electron moving from

Binding energy
an outer to an inner shell results in the emission
of energy from the atom.
33.2 keV

K shell

K-shell
K vacancy

Electron
FIGURE 2-4  Emission of character-
istic x rays occurs when orbital elec- Nucleus
trons move from an outer shell to fill
an inner-shell vacancy. (Kα x-ray
emission is illustrated.)

Characteristic
x ray
12 Physics in Nuclear Medicine

identify characteristic x rays from various characteristic radiation. The process is shown
electron transitions is summarized in Table schematically in Figure 2-5. The emitted elec-
2-1. Note that some transitions are not tron is called an Auger electron.
allowed, owing to the selection rules of The kinetic energy of an Auger electron is
quantum mechanics. equal to the difference between the binding
As an alternative to characteristic x-ray energy of the shell containing the original
emission, the atom may undergo a process vacancy and the sum of the binding energies
known as the Auger (pronounced oh-zhaý) of the two shells having vacancies at the end.
effect. In the Auger effect, an electron from Thus the kinetic energy of the Auger electron
an outer shell again fills the vacancy, but  emitted in Figure 2-5 is KB − 2LB (ignoring
the energy released in the process is trans- small differences in L-substate energies).
ferred to another orbital electron. This elec- Two orbital vacancies exist after the Auger
tron then is emitted from the atom instead of effect occurs. These are filled by electrons
from the other outer shells, resulting in the
emission of additional characteristic x rays or
TABLE 2-1â•… Auger electrons.
SOME NOTATION USED FOR The number of vacancies that result in
CHARACTERISTIC X RAYS emission of characteristic x rays versus Auger
electrons is determined by probability values
Shell
that depend on the specific element and
with Shell from
Vacancy Which Filled Notation
orbital shell involved. The probability that a
vacancy will yield characteristic x rays is
K LI Not allowed called the fluorescent yield, symbolized by ωK
K LII Kα2 for the K shell, ωL for the L shell, and so forth.
K LIII Kα1 Figure 2-6 is a graph of ωK versus Z. Both
characteristic x rays and Auger electrons are
K MI Not allowed
emitted by all elements, but heavy elements
K MII Kβ3 are more likely to emit x rays (large ω),
K MIII Kβ1 whereas light elements are more likely to
emit electrons (small ω).
K NI Not allowed
The notation used to identify the shells
K NII, NIII Kβ2 involved in Auger electron emission is eabc, in
LII MIV Lβ1 which a identifies the shell with the original
LIII MIV Lα2
vacancy, b the shell from which the electron
dropped to fill the vacancy, and c the shell
LIII MV Lα1 from which the Auger electron was emitted.

L L

K K

Nucleus

Auger electron
FIGURE 2-5  Emission of an Auger electron as an alternative to x-ray emission. No x ray is emitted.
2  •  Basic Atomic and Nuclear Physics 13

1.0

0.8
Fluorescent yield, ωK

0.6

0.4

0.2

0.0
10 20 30 40 50 60 70 80 90 100
Atomic number, Z
FIGURE 2-6  Fluorescent yield, ωK, or probability that an orbital electron shell vacancy will yield characteristic x rays
rather than Auger electrons, versus atomic number Z of the atom. (Data from Hubbell JH, Trehan PN, Singh N, et╯al:
A review, bibliography, and tabulation of K, L, and higher atomic shell x-ray fluorescence yields. J Phys Chem Ref Data
23:339-364, 1994.)

Thus the electron emitted in Figure 2-5 is a Nucleons are much more massive than
KLL Auger electron, symbolized by eKLL. In electrons (by nearly a factor of 2000). Con-
the notation eKxx, the symbol x is inclusive, versely, nuclear diameters are very small in
referring to all Auger electrons produced from comparison with atomic diameters (10−13 vs.
initial K-shell vacancies. 10−8╯ cm). Thus it can be deduced that the
density of nuclear matter is very high
(∼1014╯ g/cm3) and that the rest of the atom
D.  THE NUCLEUS
(electron cloud) is mostly empty space.
1.  Composition 2.  Terminology and Notation
The atomic nucleus is composed of protons An atomic nucleus is characterized by the
and neutrons. Collectively, these particles number of neutrons and protons it contains.
are known as nucleons. The properties of The number of protons determines the atomic
nucleons and electrons are summarized in number of the atom, Z. As mentioned earlier,
Table 2-2. this also determines the number of orbital
electrons in the electrically neutral atom and
therefore the chemical element to which the
atom belongs.
TABLE 2-2â•… The total number of nucleons is the mass
BASIC PROPERTIES OF NUCLEONS AND number of the nucleus, A. The difference, A
ELECTRONS1 − Z, is the neutron number, N. The mass
number A is approximately equal to, but not
Mass the same as, the atomic weight (AWâ•›) used in
Particle Charge* u MeV chemistry. The latter is the average weight of
Proton +1 1.007276 938.272 an atom of an element in its natural abun-
dance (see Appendix B).
Neutron 0 1.008665 939.565 The notation now used to summarize
Electron −1 0.000549 0.511 atomic and nuclear composition is ZA X N , in
*One unit of charge is equivalent to 1.602 × 10−19 which X represents the chemical element to
coulombs. which the atom belongs. For example, an
14 Physics in Nuclear Medicine

atom composed of 53 protons, 78 neutrons


(and thus 131 nucleons), and 53 orbital elec- 4.  Forces and Energy Levels within  
trons represents the element iodine and is the Nucleus
symbolized by 131
53 I78 . Because all iodine atoms Nucleons within the nucleus are subject to
have atomic number 53, the “I” and the “53” two kinds of forces. Repulsive coulombic or
are redundant and the “53” can be omitted. electrical forces exist between positively
The neutron number, 78, can be inferred from charged protons. These are counteracted by
the difference, 131 − 53, so this also can very strong forces of attraction, called nuclear
be omitted. Therefore a shortened but still forces (sometimes also called exchange forces),
complete notation for this atom is 131I. An between any two nucleons. Nuclear forces are
acceptable alternative in terms of medical  effective only over very short distances, and
terminology is I-131. Obsolete forms (some- their effects are seen only when nucleons are
times found in older texts) include I131, 131I, very close together, as they are in the nucleus.
and I131. Nuclear forces hold the nucleus together
against the repulsive coulombic forces
3.  Nuclear Families between protons.
Nuclear species sometimes are grouped into Nucleons move about within the nucleus in
families having certain common characteris- a very complicated way under the influence of
tics. A nuclide is characterized by an exact these forces. One model of the nucleus, called
nuclear composition, including the mass the shell model, portrays the nucleons as
number A, atomic number Z, and arrange- moving in “orbits” about one another in a
ment of nucleons within the nucleus. To be manner similar to that of orbital electrons
classified as a nuclide, the species must have moving about the nucleus in the Bohr atom.
a “measurably long” existence, which for Only a limited number of motions are allowed,
current technology means a lifetime greater and these are determined by a set of nuclear
than about 10−12╯sec. For example, 12C, 16O, quantum numbers.
and 131I are nuclides. The most stable arrangement of nucleons
Figure 2-7 summarizes the notation used is called the ground state. Other arrange-
for identifying a particular nuclear species, ments of the nucleons fall into the following
as well as the terminology used for nuclear two categories:
families. Nuclides that have the same atomic 1. Excited states are arrangements that
number Z are called isotopes. Thus 125I, 127I, are so unstable that they have only a
and 131I are isotopes of the element iodine. transient existence before transforming
Nuclides with the same mass number A  into some other state.
are isobars (e.g., 131I, 131Xe, and 131Cs). 2. Metastable states also are unstable, but
Nuclides with the same neutron number N they have relatively long lifetimes before
are isotones (e.g., 131
53 I78, 54 Xe78 , and 55 Cs78 ). A
132 133 transforming into another state. These
mnemonic device for remembering these also are called isomeric states.
relationships is that isotopes have the same The dividing line for lifetimes between
number of protons, isotones the same number excited and metastable states is approxi-
of neutrons, and isobars the same mass mately 10−12╯sec. This is not a long time
number (A). according to everyday standards, but it is
“relatively long” by nuclear standards. (The
prefix meta derives from the Greek word for
“almost.”) Some metastable states are quite
isobars long-lived; that is, they have average life-
times of several hours. Because of this, meta-
stable states are considered to have separate
identities and are themselves classified as
A nuclides. Two nuclides that differ from one
Z
XN another in that one is a metastable state of
the other are called isomers.
In nuclear notation, excited states are
identified by an asterisk (AX*) and metastable
isotopes isotones states by the letter m (AmX or X-Am).† Thus
(Z = number of protons)
FIGURE 2-7  Notation and terminology for nuclear †The notation AXm is sometimes used in Europe (e.g.,
families. 99
Tcm).
2  •  Basic Atomic and Nuclear Physics 15

99m
Tc (or Tc-99m) represents a metastable Photons of nuclear origin are called γ rays
state of 99Tc, and 99mTc and 99Tc are isomers. (gamma rays). The energy difference between
Nuclear transitions between different the states involved in the nuclear transition
nucleon arrangements involve discrete and determines the γ-ray energy. For example, in
exact amounts of energy, as do the rearrange- Figure 2-8 a transition from the level marked
ments of orbital electrons in the Bohr atom. 0.364╯MeV to the ground state would produce
A nuclear energy-level diagram is used to a 0.364-MeV γ ray. A transition from the
identify the various excited and metastable 0.364-MeV level to the 0.080-MeV level would
states of a nuclide and the energy relation- produce a 0.284-MeV γ ray.
ships among them. Figure 2-8 shows a partial As an alternative to emitting a γ ray, the
diagram for 131Xe.* The bottom line represents nucleus may transfer the energy to an orbital
the ground state, and other lines represent electron and emit the electron instead of a
excited or metastable states. Metastable photon. This process, which is similar to the
states usually are indicated by somewhat Auger effect in x-ray emission (see Section
heavier lines. The vertical distances between C.3, earlier in this chapter), is called internal
lines are proportional to the energy differ- conversion. It is discussed in detail in Chapter
ences between levels. A transition from a 3, Section E.
lower to a higher state requires an energy
input of some sort, such as a photon or par- 6.  Nuclear Binding Energy
ticle striking the nucleus. Transitions from When the mass of an atom is compared with
higher to lower states result in the release of the sum of the masses of its individual com-
energy, which is given to emitted particles or ponents (protons, neutrons, and electrons), it
photons. always is found to be less by some amount,
Δâ•›m. This mass deficiency, expressed in energy
5.  Nuclear Emissions units, is called the binding energy EB of the
Nuclear transformations can result in the atom:
emission of particles (primarily electrons or α EB = ∆ mc2
(2-5)
particles) or photons of electromagnetic radia-
12
tion. This is discussed in detail in Chapter 3. For example, consider an atom of C. This
atom is composed of six protons, six electrons,
and six neutrons, and its mass is precisely 12╯u
0.8
(by definition of the universal mass unit u).
0.722 The sum of the masses of its components is
0.7
0.667

0.6
0.637 electrons 6 × 0.000549╯u = 0.003294╯u
protons 6 × 1.007276╯u = 6.043656╯u
Relative energy (MeV)

neutrons 6 × 1.008665╯u = 6.051990╯u


0.5
total 12.098940╯u
0.4
0.364
0.341 Thus Δâ•›m = 0.098940╯u. Because 1╯u =
0.3 931.5╯MeV, the binding energy of a 12C atom
is 0.098940 × 931.5╯MeV = 92.16╯MeV.
0.2 The binding energy is the minimum amount
0.164 (Metastable) of energy required to overcome the forces
0.1 holding the atom together to separate it com-
0.080 pletely into its individual components. Some
0.0
Ground state of this represents the binding energy of orbital
electrons, that is, the energy required to strip
FIGURE 2-8  Partial nuclear energy-level diagram for the orbital electrons away from the nucleus;
the 131Xe nucleus. The vertical axis represents energy
differences between nuclear states (or “arrangements” of however, comparison of the total binding
nucleons). Going up the scale requires energy input. energy of a 12C atom with the K-shell binding
Coming down the scale results in the emission of nuclear energy of carbon (see Appendix B) indicates
energy. Heavier lines indicate metastable states. that most of this energy is nuclear binding
energy, that is, the energy required to sepa-
*Actually, these are the excited and metastable states
rate the nucleons.
formed during radioactive decay by β− emission of 131I (see Nuclear processes that result in the release
Chapter 3, Section D, and Appendix C). of energy (e.g., γ-ray emission) always increase
16 Physics in Nuclear Medicine

the binding energy of the nucleus. Thus a A first observation is that there are favored
nucleus emitting a 1-MeV γ ray would be neutron-to-proton ratios among the naturally
found to weigh less (by the mass equivalent occurring nuclides. They are clustered around
of 1╯MeVâ•›) after the γ ray was emitted than an imaginary line called the line of stability.
before. In essence, mass is converted to energy For light elements, the line corresponds to N
in the process. ≈ Z, that is, approximately equal numbers of
protons and neutrons. For heavy elements, it
7.  Characteristics of Stable Nuclei corresponds to N ≈ 1.5╯Z, that is, approxi-
Not all combinations of protons and neutrons mately 50% more neutrons than protons. The
produce stable nuclei. Some are unstable, line of stability ends at 209Bi (Z = 83, N = 126).
even in their ground states. An unstable All heavier nuclides are unstable.
nucleus emits particles or photons to trans- In general, there is a tendency toward
form itself into a more stable nucleus. This is instability in atomic systems composed of
the process of radioactive disintegration or large numbers of identical particles confined
radioactive decay, discussed in Chapter 3. A in a small volume. This explains the instabil-
survey of the general characteristics of natu- ity of very heavy nuclei. It also explains why,
rally occurring stable nuclides provides clues for light elements, stability is favored by more
to the factors that contribute to nuclear insta- or less equal numbers of neutrons and protons
bility and thus to radioactive decay. rather than grossly unequal numbers. A mod-
Figure 2-9 is a plot of the nuclides found in erate excess of neutrons is favored among
nature, according to their neutron and proton heavier elements because neutrons provide
numbers. For example, the nuclide 126 C is rep- only exchange forces (attraction), whereas
resented by a dot at the point Z = 6, N = 6. protons provide both exchange forces and cou-
Most of the naturally occurring nuclides are lombic forces (repulsion). Exchange forces are
stable; however, 17 very long-lived but unsta- effective over very short distances and thus
ble (radioactive) nuclides that still are present affect only “close neighbors” in the nucleus,
from the creation of the elements also are whereas the repulsive coulombic forces are
shown. effective over much greater distances. Thus

160

140 Isotones
Isotopes

Is

120
ob
ar
s

100
Neutron number, N

FIGURE 2-9  Neutron number (N) versus


atomic number (â•›Zâ•›) for nuclides found in
nature. The boxed data points identify very
80 long-lived, naturally occurring unstable
(radioactive) nuclides. The remainder are
Z stable. The nuclides found in nature are clus-

N tered around an imaginary line called the line
60 of stability. N ≈ Z for light elements; N ≈ 1.5╯Z
for heavy elements.

40

20

0
0 20 40 60 80 100
Atomic number, Z
2  •  Basic Atomic and Nuclear Physics 17

an excess of neutrons is required in heavy This reflects the existence of several modes of
nuclei to overcome the long-range repulsive “isobaric” radioactive decay that permit
coulombic forces between a large number of nuclides to transform along isobaric lines
protons. until the most stable isobar is reached. This
Nuclides that are not close to the line of is discussed in detail in Chapter 3.
stability are likely to be unstable. Unstable One also notes among the stable nuclides a
nuclides lying above the line of stability are tendency to favor even numbers. For example,
said to be “proton deficient,” whereas those there are 165 stable nuclides with both even
lying below the line are “neutron deficient.” numbers of protons and even numbers of neu-
Unstable nuclides generally undergo radioac- trons. Examples are 42 He and 126 C. There are
tive decay processes that transform them into 109 “even-odd” stable nuclides, with even
nuclides lying closer to the line of stability, as numbers of protons and odd numbers of neu-
discussed in Chapter 3. trons or vice versa. Examples are 49 Be and 115 B.
Figure 2-9 demonstrates that there often However, there are only four stable “odd-odd”
are many stable isotopes of an element. Iso- nuclides: 21 H, 63 Li, 105 B, and 147 N. The stability of
topes fall on vertical lines in the diagram. For even numbers reflects the tendency of nuclei
example, there are ten stable isotopes of tin to achieve stable arrangements by the “pairing
(Sn, Z = 50)*. There may also be several stable up” of nucleons in the nucleus.
isotones. These fall along horizontal lines. In Another measure of relative nuclear stabil-
relatively few cases, however, is there more ity is nuclear binding energy, because this
than one stable isobar (isobars fall along represents the amount of energy required to
descending 45-degree lines on the graph). break the nucleus up into its separate compo-
nents. Obviously, the greater the number of
nucleons, the greater the total binding energy.
Therefore a more meaningful parameter is
*Although most element symbols are simply one- or two- the binding energy per nucleon, EBâ•›/A. Higher
letter abbreviations of their (English) names, ten symbols
derive from Latin or Greek names of metals known for values of EBâ•›/A are indicators of greater
more than 2 millennia: antimony (stibium, Sb), copper nuclear stability.
(cuprum, Cu), gold (aurum, Au), iron (ferrum, Fe), lead Figure 2-10 is a graph of EBâ•›/A versus A for
(plumbum, Pb), mercury (hydrargyrum, Hg), potassium the stable nuclides. Binding energy is great-
(kalium, K), silver (argentum, Ag), sodium (natrium, Na),
and tin (stannum, Sn). The symbol for tungsten, W, est (≈â•›8╯MeV per nucleon) for nuclides of mass
derives from the German “wolfram,” the name it was first number A ≈ 60. It decreases slowly with
given in medieval times. increasing A, indicating the tendency toward

10

8
Binding energy per nucleon,

6
EB(MeV)/A

0
0 40 80 120 160 200
Mass number, A
FIGURE 2-10  Binding energy per nucleon (EBâ•›/A) versus mass number (A) for the stable nuclides.
18 Physics in Nuclear Medicine

instability for very heavy nuclides. Finally, Recommended texts for in-depth discussions of
there are a few peaks in the curve represent- topics in atomic and nuclear physics are the
following:
ing very stable light nuclides, including 42 He ,
Evans RD: The Atomic Nucleus, New York, 1972,
6 C , and 8 O. Note that these are all even-
12 16
McGraw-Hill.
even nuclides. Jelley NA: Fundamentals of Nuclear Physics, New York,
1990, Cambridge University Press.
REFERENCES Yang F, Hamilton JH: Modern Atomic and Nuclear
1. National Institute of Standards and Technology Physics, New York, 1996, McGraw-Hill.
(NIST): Fundamental Physics Constants. Available 
at http://physics.nist.gov/cuu/Constants/index.html
[accessed July 4, 2011].

BIBLIOGRAPHY
Fundamental quantities of physics and mathematics, as
well as constants and conversion factors, can be found in
reference 1.
chapter
3 
Modes of Radioactive
Decay
Radioactive decay is a process in which an converted to photons, with a small (usually
unstable nucleus transforms into a more stable insignificant) portion given as kinetic energy
one by emitting particles, photons, or both, to the recoiling nucleus. Thus radioactive
releasing energy in the process. Atomic elec­ decay results not only in the transformation
trons may become involved in some types of of one nuclear species into another but also in
radioactive decay, but it is basically a nuclear the transformation of mass into energy.
process caused by nuclear instability. In this Each radioactive nuclide has a set of char­
chapter we discuss the general characteristics acteristic properties. These properties include
of various modes of radioactive decay and their the mode of radioactive decay and type of
general importance in nuclear medicine. emissions, the transition energy, and the
average lifetime of a nucleus of the radionu­
clide before it undergoes radioactive decay.
A.  GENERAL CONCEPTS Because these basic properties are character­
istic of the nuclide, it is common to refer to a
It is common terminology to call an unstable radioactive species, such as 131I, as a radio­
radioactive nucleus the parent and the more nuclide. The term radioisotope also is used
stable product nucleus the daughter. In many but, strictly speaking, should be used only
cases, the daughter also is radioactive and when specifically identifying a member of an
undergoes further radioactive decay. Radio­ isotopic family as radioactive; for example,
131
active decay is spontaneous in that the exact I is a radioisotope of iodine.
moment at which a given nucleus will decay
cannot be predicted, nor is it affected to any
significant extent by events occurring outside B.  CHEMISTRY AND RADIOACTIVITY
the nucleus.
Radioactive decay results in the conversion Radioactive decay is a process involving pri­
of mass into energy. If all the products of a marily the nucleus, whereas chemical reac­
particular decay event were gathered together tions involve primarily the outermost orbital
and weighed, they would be found to weigh electrons of the atom. Thus the fact that an
less than the original radioactive atom. atom has a radioactive nucleus does not affect
Usually, the energy arises from the conversion its chemical behavior and, conversely, the
of nuclear mass, but in some decay modes, chemical state of an atom does not affect its
electron mass is converted into energy as well. radioactive characteristics. For example, an
The total mass-energy conversion amount  atom of the radionuclide 131I exhibits the same
is called the transition energy, sometimes chemical behavior as an atom of 127I, the natu­
designated Q.* Most of this energy is imparted rally occurring stable nuclide, and 131I has the
as kinetic energy to emitted particles or same radioactive characteristics whether it
exists as iodide ion (â•›I−â•›) or incorporated into a

*Some texts and applications consider only nuclear mass,


rather than the mass of the entire atom (i.e., atomic modes. As well, energy originating from either source can
mass), in the definition of transition energy. As will be contribute to usable radiation or to radiation dose to the
seen, the use of atomic mass is more appropriate for the patient. For a detailed discussion of the two methods for
analysis of radioactive decay because both nuclear and defining transition energy, see Evans RD: The Atomic
nonnuclear mass are converted into energy in some decay Nucleus. New York, 1972, McGraw-Hill, pp 117-133.
19
20 Physics in Nuclear Medicine

large protein molecule as a radioactive label. The electron (e−) and the neutrino (ν) are
Independence of radioactive and chemical ejected from the nucleus and carry away the
properties is of great significance in tracer energy released in the process as kinetic
studies with radioactivity—a radioactive energy. The electron is called a β− particle.
tracer behaves in chemical and phyÂ�siologic The neutrino is a “particle” having no mass
processes exactly the same as its stable, natu­ or electrical charge.* It undergoes virtually no
rally occurring counterpart, and, further, the interactions with matter and therefore is
radioactive properties of the tracer do not essentially undetectable. Its only practical
change as it enters into chemical or physio­ consequence is that it carries away some of
logic processes. the energy released in the decay process.
There are two minor exceptions to these Decay by β− emission may be represented
generalizations. The first is that chemical in standard nuclear notation as
behavior can be affected by differences in
atomic mass. Because there are always mass β −
A
X  → Z +1
A
Y (3-2)
differences between the radioactive and the Z

stable members of an isotopic family (e.g., 131I


is heavier than 127I), there may also be chemi­ The parent radionuclide (X) and daughter
cal differences. This is called the isotope effect. product (Y) represent different chemical ele­
Note that this is a mass effect and has nothing ments because atomic number increases by
to do with the fact that one of the isotopes is one. Thus β− decay results in a transmutation
radioactive. The chemical differences are of elements. Mass number A does not change
small unless the relative mass differences are because the total number of nucleons in the
large, for example, 3H versus 1H. Although nucleus does not change. This is therefore an
the isotope effect is important in some experi­ isobaric decay mode, that is, the parent and
ments, such as measurements of chemical daughter are isobars (see Chapter 2, Section
bond strengths, it is, fortunately, of no practi­ D.3).
cal consequence in nuclear medicine. Radioactive decay processes often are rep­
A second exception is that the average life­ resented by a decay scheme diagram. Figure
times of radionuclides that decay by processes 3-1 shows such a diagram for 14C, a radionu­
involving orbital electrons (e.g., internal con­ clide that decays solely by β− emission. The
version, Section E, and electron capture, line representing 14C (the parent) is drawn
Section F) can be changed very slightly by above and to the left of the line representing
14
altering the chemical (orbital electron) state of N (the daughter). Decay is “to the right”
the atom. The differences are so small that because atomic number increases by one
they cannot be detected except in elaborate (reading Z values from left to right). The 
nuclear physics experiments and again are of vertical distance between the lines is propor­
no practical consequence in nuclear medicine. tional to the total amount of energy released,
that is, the transition energy for the decay
process (Q = 0.156╯MeV for 14C).
C.  DECAY BY β− EMISSION

Radioactive decay by β− emission is a process *Actually, in β− emission an antineutrino, ν , is emitted,


in which, essentially, a neutron in the nucleus whereas in β+ emission and EC, a neutrino, ν, is emitted.
is transformed into a proton and an electron. For simplicity, no distinction is made in this text. Also,
Schematically, the process is evidence from high-energy physics experiments suggests
that neutrinos may indeed have a very small mass, but
n → p+ + e − + ν + energy (3-1) an exact value has not yet been assigned.

14
6C

14
FIGURE 3-1  Decay scheme diagram for C, a
Q = 0.156 MeV
β− emitter. Q is the transition energy.

14
7N
3  •  Modes of Radioactive Decay 21

The energy released in β− decay is shared because they will not penetrate even rela­
between the β− particle and the neutrino. This tively thin layers of metal or other outside
sharing of energy is more or less random from protective materials that are required on
one decay to the next. Figure 3-2 shows the some types of detectors. The implications of
distribution, or spectrum, of β−-particle ener­ this are discussed in Chapter 7.
gies resulting from the decay of 14C. The The properties of various radionuclides of
maximum possible β−-particle energy (i.e., the medical interest are presented in Appendix C.
transition energy for the decay process) is Radionuclides decaying solely by β− emission
14
denoted by Eβ (0.156╯MeV for C). From the
max
listed there include 3H, 14C, and 32P.
graph it is apparent that the β− particle usually
receives something less than half of the avail­
able energy. Only rarely does the β− particle
carry away all the energy ( Eβ = Eβmax). D.  DECAY BY (β−, γâ•›) EMISSION
The average energy of the β particle is

denoted by Eβ . This varies from one radionu­ In some cases, decay by β− emission results in
clide to the next but has a characteristic  a daughter nucleus that is in an excited or
value for any given radionuclide. Typically, metastable state rather than in the ground
14
Eβ ≈ (1 / 3) Eβmax . For C, Eβ = 0.0497 MeV (0.32
state.
EβmaxIf
) an excited state is formed, the daugh­
0497 MeV (0.32 Eβmax ) . ter nucleus promptly decays to a more stable
Beta particles present special detection nuclear arrangement by the emission of a γ
and measurement problems for nuclear medi­ ray (see Chapter 2, Section D.5). This sequen­
cine applications. These arise from the fact tial decay process is called (β−, γ) decay. In
that they can penetrate only relatively small standard nuclear notation, it may be repre­
thicknesses of solid materials (see Chapter 6, sented as
Section B.2). For example, the thickness is at
most only a few millimeters in soft tissues. β− γ
Z X → Z +1 Y  → Z +A1 Y (3-3)
A A *
Therefore it is difficult to detect β− particles
originating from inside the body with a detec­
tor that is located outside the body. For this Note that γ emission does not result in a
reason, radionuclides emitting only β− parti­ transmutation of elements.
cles rarely are used when measurement in An example of (β−, γ) decay is the radio­
vivo is required. Special types of detector nuclide 133â•›Xe, which decays by β− emission to
systems also are needed to detect β particles

one of three different excited states of 133Cs.
Relative number emitted
(arbitrary units)

max
Eβ = 0.0497 MeV Eβ = 0.156 MeV

0.00 0.04 0.08 0.12 0.16 0.20


β-particle energy (MeV)
FIGURE 3-2  Energy spectrum (number emitted vs. energy) for β particles emitted by 14C. Maximum β−-particle energy
is Q, the transition energy (see Fig. 3-1). Average energy Eβ is 0.0497╯MeV, approximately (1 3) Eβmax . (Data courtesy Dr.
Jongwha Chang, Korea Atomic Energy Research Institute.)
22 Physics in Nuclear Medicine

Figure 3-3 is a decay scheme for this radionu­ characteristic value. The distribution of this
clide. The daughter nucleus decays to the energy among the β− particle, the neutrino,
ground state or to another, less energetic and the γ rays may vary from one nuclear
excited state by emitting a γ ray. If it is to decay to the next, but the sum of their ener­
another excited state, additional γ rays may gies in any decay event is always equal to the
be emitted before the ground state is finally transition energy.
reached. Thus in (β−, γ) decay more than one Because γ rays are much more penetrating
γ ray may be emitted before the daughter than β− particles, they do not present some of
nucleus reaches the ground state (e.g., β2 fol­ the measurement problems associated with
lowed by γ1 and γâ•›2 in 133â•›Xe decay). β− particles that were mentioned earlier, and
The number of nuclei decaying through the they are suitable for a wider variety of appli­
different excited states is determined by prob­ cations in nuclear medicine. Some radio­
ability values that are characteristic of the nuclides of medical interest listed in Appendix
particular radionuclide. For example, in 133â•›Xe C that undergo (β−, γ) decay include 131I, 133Xe,
decay (Fig. 3-3), 99.3% of the decay events are and 137Cs.
by β3 decay to the 0.081-MeV excited state,
followed by emission of the 0.081-MeV γ ray
or conversion electrons (Section E). Only a
very small number of the other β particles E.  ISOMERIC TRANSITION AND
and γ rays of other energies are emitted. The INTERNAL CONVERSION
data presented in Appendix C include the
relative number of emissions of different The daughter nucleus of a radioactive parent
energies for each radionuclide listed. may be formed in a “long-lived” metastable or
In contrast to β− particles, which are isomeric state, as opposed to an excited state.
emitted with a continuous distribution of The decay of the metastable or isomeric state
energies (up to Eβmax ), γ rays are emitted with by the emission of a γ ray is called an isomeric
a precise and discrete series of energy values. transition (see Chapter 2, Section D.4).
The spectrum of emitted radiation energies is Except for their average lifetimes, there are
therefore a series of discrete lines at energies no differences in decay by γ emission of meta­
that are characteristic of the radionuclide stable or excited states.
rather than a continuous distribution of ener­ An alternative to γ-ray emission is internal
gies (Fig. 3-4). In (β−, γ) decay, the transition conversion. This can occur for any excited
energy between the parent radionuclide and state, but is especially common for metastable
the ground state of the daughter has a fixed states. In this process, the nucleus decays by

133
54Xe

0.384 MeV
β1

β2

β3
γ4 γ5 γ6

0.161 MeV

γ3 γ1

Q=0.427 MeV 0.081 MeV


γ2

0
133
55Cs

FIGURE 3-3  Decay scheme diagram for 133Xe, a (β−, γâ•›) emitter. More than one γ ray may be emitted per disintegrating
nucleus. The heavy line (for β3) indicates most-probable decay mode.
3  •  Modes of Radioactive Decay 23

0.5

0.4
γ rays per disintegration

0.3
γ2 (0.081 MeV)

0.2

0.1
γ1 (0.080 MeV)

0.0
0.00 0.02 0.04 0.06 0.08 0.10
γ-ray energy (MeV)
FIGURE 3-4  Emission spectrum for 0.080- and 0.081-MeV γ rays emitted in the decay of Xe (γ1 and γ2 in Fig. 3-3;
133

higher-energy emissions omitted). Compare with Figure 3-2 for β− particles.

transferring energy to an orbital electron, have characteristic values for different radio­
which is ejected instead of the γ ray. It is as nuclides. These probabilities are expressed in
if the γ ray were “internally absorbed” by col­ terms of the ratio of conversion electrons
lision with an orbital electron (Fig. 3-5). The emitted to γ rays emitted (e/γ) and denoted by
ejected electron is called a conversion electron. α (or αK = e/γ for K-shell conversion electrons,
These electrons usually originate from one of and so on) in detailed charts and tables of
the inner shells (K or L), provided that the nuclear properties.
γ-ray energy is sufficient to overcome the Internal conversion, like β− decay, results
binding energy of that shell. The energy in the emission of electrons. The important
excess above the binding energy is imparted differences are that (1) in β− decay the elec­
to the conversion electron as kinetic energy. tron originates from the nucleus, whereas in
The orbital vacancy created by internal con­ internal conversion it originates from an elec­
version subsequently is filled by an outer- tron orbit; and (2) β− particles are emitted
shell electron, accompanied by emission of with a continuous spectrum of energies,
characteristic x rays or Auger electrons (see whereas conversion electrons have a discrete
Chapter 2, Section C.3). series of energies determined by the differ­
Whether a γ ray or a conversion electron is ences between the γ-ray energy and orbital
emitted is determined by probabilities that electron-binding energies.

Unstable nucleus
Conversion electron

FIGURE 3-5  Schematic representation of internal conversion involving a K-shell electron. An unstable nucleus trans­
fers its energy to the electron rather than emitting a γ ray. Kinetic energy of conversion electron is γ ray energy minus
electron-binding energy (Eγ − KB).
24 Physics in Nuclear Medicine

Metastable radionuclides are of great The neutrino is emitted from the nucleus and
importance in nuclear medicine. Because  carries away some of the transition energy.
of their relatively long lifetimes, it sometimes The remaining energy appears in the form of
is possible to separate them from their radio­ characteristic x rays and Auger electrons,
active parent and thus obtain a relatively which are emitted by the daughter product
“pure” source of γ rays. The separation of the when the resulting orbital electron vacancy is
metastable daughter from its radioactive filled. Usually, the electron is captured from
parent is accomplished by chemical means in orbits that are closest to the nucleus, that is,
a radionuclide “generator” (see Chapter 5, the K and L shells. The notation EC(K) is
Section C). Metastable nuclides always emit used to indicate capture of a K-shell electron,
a certain number of conversion electrons, and EC(L) an L-shell electron, and so forth.
thus they are not really “pure” γ-ray emitters. EC decay may be represented as:
Because conversion electrons are almost
EC
totally absorbed within the tissue where  A
Z X  → Z −1A Y (3-5)
they are emitted (Chapter 6, Section B.2),
they can cause substantial radiation dose  Note that like β− decay it is an isobaric
to the patient, particularly when the conver­ decay mode leading to a transmutation of
sion ratio, e/γ, is large. However, the ratio elements.
of photons to electrons emitted by metastable The characteristic x rays emitted by the
nuclides usually is greater than for (β−,γ) daughter product after EC may be suitable
emitters, and this is a definite advantage for for external measurement if they are suffi­
studies requiring detection of γ rays from ciently energetic to penetrate a few centime­
internally administered radioactivity. ters of body tissues. There is no precise energy
A metastable nuclide of medical interest cutoff point, but 25 keV is probably a reason­
listed in Appendix C is 99mTc. Technetium-99m able value, at least for shallow organs such as
is currently by far the most popular radionu­ the thyroid. For elements with Z of 50 or
clide for nuclear medicine imaging studies. more, the energy of K-x rays exceeds 25 keV.
The K-x rays of lighter elements and all L-x
rays are of lower energy and generally are not
F.  ELECTRON CAPTURE AND (EC, γâ•›) suitable for external measurements. These
DECAY lower-energy radiations introduce measure­
ment problems similar to those encountered
Electron capture (EC) decay looks like, and in with particles.
fact is sometimes called, “inverse β− decay.” EC decay results frequently in a daughter
An orbital electron is “captured” by the nucleus that is in an excited or metastable
nucleus and combines with a proton to form state. Thus γ rays (or conversion electrons)
a neutron: may also be emitted. This is called (EC, γ)
decay. Figure 3-6 shows a decay scheme for
p+ + e − → n + ν + energy (3-4) 125
I, an (EC, γ) radionuclide finding application

125
53 I

EC
125
Q = 0.177 MeV FIGURE 3-6  Decay scheme diagram for I, an
(EC, γâ•›) emitter.

0.035 MeV
γ1

125
52 Te
3  •  Modes of Radioactive Decay 25

in radioimmunoassay studies. Note that EC photons,* which leave the site of the annihila­
decay is “to the left” because EC decreases tion event in nearly exact opposite directions
the atomic number by one. Medically impor­ (180 degrees apart).
tant EC and (EC, γ) radionuclides listed in The “back-to-back” emission of annihila­
Appendix C include 57Co, 67Ga, 111In, 123I, 125I, tion photons is required for conservation of
and 201Tl. momentum for a stationary electron-positron
pair. However, because both particles actually
are moving, the annihilation photons may be
G.  POSITRON (β+) AND (β+, γâ•›) DECAY emitted in directions slightly off from the
ideal by perhaps a few tenths of a degree. The
In radioactive decay by positron emission, a effects of this on the ability to localize positron-
proton in the nucleus is transformed into a emitting radionuclides for imaging purpose
neutron and a positively charged electron. are discussed in Chapter 18, Section A.4.
The positively charged electron—or positron Energy “bookkeeping” is somewhat more
(β+)—and a neutrino are ejected from the complicated for β+ decay than for some of the
nucleus. Schematically, the process is: previously discussed decay modes. There is a
minimum transition energy requirement of
p+ → n + e + + ν + energy (3-6) 1.022╯MeV before β+ decay can occur. This
requirement may be understood by evaluat­
ing the difference between the atomic mass of
A positron is the antiparticle of an ordinary the parent and the daughter atom (including
electron. After ejection from the nucleus, it the orbital electrons). In β+ decay, a positron
loses its kinetic energy in collisions with is ejected from the nucleus, and because β+
atoms of the surrounding matter and comes decay reduces the atomic number by one, the
to rest, usually within a few millimeters of daughter atom also has an excess electron
the site of its origin in body tissues. More that it releases to reach its ground state. Thus
accurately, the positron and an electron two particles are emitted from the atom
momentarily form an “atom” called positro­ during β+ decay, and because the rest-mass
nium, which has the positron as its “nucleus” energy of an electron or a positron is 511 keV,
and a lifetime of approximately 10−10 sec. The a total transition energy of 1.022╯MeV is
positron then combines with the negative required. Note that no such requirement is
electron in an annihilation reaction, in which present for β− decay, because the daughter
their masses are converted into energy (see atom must take up an electron from the envi­
Fig. 3-7). The mass-energy equivalent of each ronment to become neutral, thereby compen­
particle is 0.511╯MeV. This energy appears in sating for the electron released during
the form of two 0.511-MeV annihilation β− decay.
In β+ decay, the excess transition energy
above 1.022╯MeV is shared between the posi­
tron (kinetic energy) and the neutrino. The
positron energy spectrum is similar to that
0.511 MeV
observed for β− particles (see Fig. 3-2). The
average β+ energy also is denoted by Eβ and
β+ again is approximately Eβ ≈ (1 / 3) Eβmax , in
which Eβmax is the transition energy minus
1.022╯MeV.
In standard notation, β+ decay is repre­
sented as
e–
β +
A
Z X  → Z −1A Y (3-7)

It is another isobaric decay mode, with a


transmutation of elements. Figure 3-8 shows

0.511 MeV
*Although the photons produced when the positron and
FIGURE 3-7  Schematic representation of mutual- an electron undergo annihilation are not of nuclear
annihilation reaction between a positron (β+) and an ordi­ origin, they sometimes are called annihilation γ rays.
nary electron. A pair of 0.511-MeV annihilation photons This terminology may be used in some instances in this
are emitted “back-to-back” at 180 degrees to each other. book.
26 Physics in Nuclear Medicine

a decay scheme for 15O, a β+ emitter of medical There also are radionuclides that can decay
interest. Decay is “to the left” because atomic by either mode. An example is 18F, the decay
number decreases by one. The vertical line scheme for which is shown in Figure 3-9. For
represents the minimum transition energy this radionuclide, 3% of the nuclei decay by
requirement for β+ decay (1.022╯MeV). The EC and 97% decay by β+ emission. Radionu­
remaining energy (1.7╯MeV) is Eβmax . With clides of medical interest that undergo com­
some radionuclides, β+ emission may leave petitive (β+, EC) decay listed in Appendix C
the daughter nucleus in an excited state, and include 11C and 18F.
thus additional γ rays may also be emitted
[(β+, γ) decay].
Positron emitters are useful in nuclear
medicine because two photons are generated I.  DECAY BY α EMISSION AND BY
per nuclear decay event. Furthermore, the NUCLEAR FISSION
precise directional relationship between the
annihilation photons permits the use of  Radionuclides that decay by α-particle emis­
novel “coincidence-counting” techniques (see sion or by nuclear fission are of relatively
Chapter 18). Medically important pure β+ little importance for direct usage as tracers in
radionuclides listed in Appendix C include 13N nuclear medicine but are described here for
and 15O. the sake of completeness. Both of these decay
modes occur primarily among very heavy ele­
ments that are of little interest as physiologic
H.  COMPETITIVE β+ AND EC DECAY tracers. As well, they are highly energetic and
tend to be associated with relatively large
Positron emission and EC have the same radiation doses (see Table 22-1).
effect on the parent nucleus. Both are isobaric In decay by α-particle emission, the nucleus
decay modes that decrease atomic number by ejects an α particle, which consists of two
one. They are alternative means for reaching neutrons and two protons (essentially a 42 He
the same endpoint (see Equations 3-5 and 3-7, nucleus). In standard notation this is repre­
and Figs. 3-6 and 3-8). Among the radioactive sented as:
nuclides, one finds that β+ decay occurs more
α
frequently among lighter elements, whereas A
Z X  → AZ−−42 Y (3-8)
EC is more frequent among heavier elements,
because in heavy elements orbital electrons The α particle is emitted with kinetic energy
tend to be closer to the nucleus and are more usually between 4 and 8╯MeV. Although quite
easily captured. energetic, α particles have very short ranges

15
8O

FIGURE 3-8  Decay scheme diagram for


Q = 2.722 MeV 15
O, a β+ emitter. Eβmax is Q, the transition
energy, minus 1.022╯MeV, the minimum
transition energy for β+ decay.

E max
β
= 1.7 MeV

15
7N
3  •  Modes of Radioactive Decay 27

18
9F

EC

FIGURE 3-9  Decay scheme diagram for 18F,


which decays by both electron capture and β+ Q = 1.655 MeV β+
emission competitively.

max
Eβ = 0.633 MeV

18
8O

in solid materials, for example, approximately  products undergo a series of decays involving
0.03 mm in body tissues. Thus they present α-particle and β−-particle emission to trans­
very difficult detection and measurement form into lighter, more stable nuclides. Figure
problems. 3-10 illustrates the “decay series” of 238U →
Decay by α-particle emission results in a 206
Pb. The radionuclide 226Ra in this series is
transmutation of elements, but it is not iso­ of some medical interest, having been used at
baric. Atomic mass is decreased by 4; there­ one time in encapsulated form for implanta­
fore this process is common among very heavy tion into tumors for radiation therapy. The
elements that must lose mass to achieve ubiquitous, naturally occurring 222Rn also is
nuclear stability. Heavy, naturally occurring produced in this series. Note that there are
radionuclides such as 238U and its daughter “branching points” in the series where either

238
α
β−
234
β−
α
230
α
Mass Number, A

226
α
FIGURE 3-10  Illustration of series 222
decay, starting from 238U and ending
with stable 206Pb. (Adapted from α
Hendee WR: Medical Radiation β− 218
α
Physics. Chicago, 1970, Year Book α
β−
Publishers Inc., p 501.) 214
β−
α α
β− β− 210
β−
α
206

81 82 83 84 85 86 87 88 89 90 91 92
Tl Pb Bi Po At Rn Fr Ra Ac Th Pa U
Atomic number, Z
28 Physics in Nuclear Medicine

α or β− emission may occur. Only every fourth of radioactive decay that occurs usually is
atomic number value appears in this series such as to move the nucleus closer to this line.
because α emission results in atomic number A radionuclide that is proton deficient (above
differences of four units. The 238U → 206Pb the line) usually decays β− emission, because
series is called the “4n + 2” series. Two others this transforms a neutron into a proton,
are 235U → 207Pb (4n + 3) and 232Th → 208Pb moving the nucleus closer to the line of stabil­
(4n). These three series are found in nature ity. A neutron-deficient radionuclide (below
because in each case the parent is a very long- the line) usually decays by EC or β+ emission,
lived radionuclide (half-lives ~ 108 to 1010╯yr) because these modes transform a proton into
and small amounts remain from the creation a neutron. Heavy nuclides frequently decay
of the elements. The fourth series, 4n + 1, is by α emission or by fission, because these are
not found naturally because all its members modes that reduce mass number.
have much shorter lifetimes and have disap­ It also is worth noting that β−, β+, and EC
peared from nature. decay all can transform an “odd-odd” nucleus
An (α, γ) radionuclide of interest in nuclear into an “even-even” nucleus. As noted in
medicine is 241Am. It is used in encapsulated Chapter 2, Section D.7 even-even nuclei are
form as a source of 60-keV γ rays for instru­ relatively stable because of pairing of alike
ment calibration and testing. particles within the nucleus. There are in fact
Nuclear fission is the spontaneous frag­ a few odd-odd nuclides lying on or near the
mentation of a very heavy nucleus into two line of stability that can decay either by β−
lighter nuclei. In the process a few (two or emission or by EC and β+ emission. An
three) fission neutrons also are ejected. The example is 40K (89% β−, 11% EC or β+). In this
distribution of nuclear mass between the example, the instability created by odd
two product nuclei varies from one decay to numbers of protons and neutrons is sufficient
the next. Typically it is split in approxi­ to cause decay in both directions away from
mately a 60â•›:â•›40 ratio. The energy released is the line of stability; however, this is the excep­
very large, often amounting to hundreds of tion rather than the rule.
MeV per nuclear fission, and is imparted 
primarily as kinetic energy to the recoiling
nuclear fragments (fission fragments) and
the ejected neutrons. Nuclear fission is the K.  SOURCES OF INFORMATION ON
source of energy from nuclear reactors. More RADIONUCLIDES
precisely, the kinetic energy of the emitted
particles is converted into heat in the sur­ There are several sources of information pro­
rounding medium, where it is used to create viding useful summaries of the properties of
steam for driving turbines and other uses. radionuclides. One is a chart of the nuclides,
The fission process is of interest in nuclear a portion of which is shown in Figure 3-11.
medicine because the fission fragment nuclei Every stable or radioactive nuclide is assigned
usually are radioactive and, if chemically a square on the diagram. Isotopes occupy
separable from the other products, can be horizontal rows and isotones occupy vertical
used as medical tracers. Also, the neutrons columns. Isobars fall along descending
are used to produce radioactive materials by 45-degree lines. Basic properties of each
neutron activation, as discussed in Chapter nuclide are listed in the boxes. Also shown in
5, Section A.3. The parent fission nuclides Figure 3-11 is a diagram indicating the trans­
themselves are of no use as tracers in nuclear formations that occur for various decay modes.
medicine. A chart of the nuclides is particularly useful
for tracing through a radioactive series.
Perhaps the most useful sources of data
for radionuclides of interest in nuclear medi­
J.  DECAY MODES AND THE LINE OF cine are the Medical Internal Radiation
STABILITY Dosimetry (MIRD) publications, compiled by
the MIRD Committee of the Society of
In Chapter 2, Section D.7, it was noted that Nuclear Medicine.1 Decay data for some of
on a graph of neutron versus proton numbers the radionuclides commonly encountered 
the stable nuclides tend to be clustered about in nuclear medicine are presented in Appen­
an imaginary line called the line of stability dix C. Also presented are basic data for
(see Fig. 2-9). Nuclides lying off the line of internal dosimetry, which will be discussed
stability generally are radioactive. The type in Chapter 22.
Radioactive Chart of the Nuclides
β− transformations (extract)

Parent

Ag94 Ag95 Ag96 Ag97 Ag98 Ag99 Ag100 Ag101 Ag102 Ag103 Ag104
β+,EC
47 Ag 0.42 s 2.0 s 5.1 s 19 s 47 s 11 s 2.1 m 2.3 m 2.0 m 3.1 s 11.1 m 7.8 m 13 m 5.7 s 66 m 33 m 69 m

Pd94 Pd95 Pd96 Pd97 Pd98 Pd99 Pd100 Pd101 Pd102 Pd103
α 46 Pd 9s 13.4 s 2.03 m 3.1 m 18 m 21.4 m 3.6 d 8.4 h 16.97 d
1.02

Rh94 Rh95 Rh96 Rh97 Rh98 Rh99 Rh100 Rh101 Rh102

45 Rh 26 s 1.2 m 1.96 m 5 m 1.5 m 9.9 m 46 m 31 m 3.5 m 8.6 m 4.7 h 16.1 d 4.7 m 20.8 h 4.34 d 3.3 y 206 d 2.9 y

Ru90 Ru91 Ru92 Ru93 Ru94 Ru95 Ru96 Ru97 Ru98 Ru99 Ru100 Ru101
44 Ru 11 s 9s 3.7 m 10.8 s 1m 52 m 1.64 h 2.89 d
5.54 1.86 12.7 12.6 17.1

Tc89 Tc90 Tc91 Tc92 Tc93 Tc94 Tc95 Tc96 Tc97 Tc98 Tc99 Tc100

43 Tc 13 s 13 s 49.2 s 8.3 s 3.3 m 3.1 m 4.2 m 43 m 2.8 h 52 m 4.9 h 61 d 20 h 52 m 4.3 d 90 d 2.6E6y 4.2E6 y 6 h 2.1E5y 15.8 s

Mo86 Mo87 Mo88 Mo89 Mo90 Mo91 Mo92 Mo93 Mo94 Mo95 Mo96 Mo97 Mo98 Mo99

3  •  Modes of Radioactive Decay


42 Mo 20 s 14 s 8.0 m 0.2 s 2.2 m 5.7 h 1.1 m 15.5 m 6.9 h 3.5E3y 65.9 h
14.84 9.25 15.92 16.68 9.55 24.13

Nb83 Nb84 Nb85 Nb86 Nb87 Nb88 Nb89 Nb90 Nb91 Nb92 Nb93 Nb94 Nb95 Nb96 Nb97 Nb98

41 Nb 4.1 s 12 s 21 s 56 s 1.5 m 3.7 m 2.6 m 7.7 m 14.4 m 2h 1.1 h 19 s 14.6 h 62 d 7E2 y 10.d 3.7E7y 6.1y 6.2 m 2.4E4y 3.6 d 35 d 23.4 h 54 s 74 m 51 m 2.8 s
100

42 44 46 48 50 52 54 56
FIGURE 3-11  Portion of a chart of the nuclides. Vertical axis = atomic number; horizontal axis = neutron number. Also listed are half-lives of radioactive nuclides
(see Chapter 4, Section B.2). Stable nuclides are indicated in bold font. Values listed for these nuclides indicate their percent natural abundance. Half-lives of
metastable states are listed on the left, where applicable.

29
REFERENCE BIBLIOGRAPHY
1. Eckerman KF, Endo A: MIRD: Radionuclide Data and A comprehensive source of radionuclide data can be
Decay Schemes, New York, 2008, Society of Nuclear found at the National Nuclear Data Center [accessed
Medicine. July 6, 2011]. Available at http://www.nndc.bnl.gov/.
chapter
4 
Decay of
Radioactivity
Radioactive decay is a spontaneous process; Some radionuclides can undergo more than
that is, there is no way to predict with cer- one type of radioactive decay (e.g., 18F: 97%
tainty the exact moment at which an unsta- β+, 3% electron capture). For such types of
ble nucleus will undergo its radioactive “branching” decay, one can define a value of λ
transformation into another, more stable for each of the possible decay modes, for
nucleus. Mathematically, radioactive decay example, λ1, λ2, λ3, and so on, where λ1 is the
is described in terms of pro�babilities and fraction decaying per unit time by decay mode
average decay rates. In this chapter we 1, λ2 by decay mode 2, and so on. The total
discuss these mathematical aspects of radio- decay constant for the radionuclide is the sum
active decay. of the branching decay constants:

A.  ACTIVITY λ = λ1 + λ 2 + λ 3 +  (4-2)

The fraction of nuclei decaying by a specific


1.  The Decay Constant decay mode is called the branching
If one has a sample containing N radioactive ratio (B.R.). For the ith decay mode, it is
atoms of a certain radionuclide, the average given by:
decay rate, Δ N/Δt, for that sample is given by:
B.R. = λ i /λ (4-3)
∆ N/∆ t = −λ N (4-1)

where λ is the decay constant for the radionu- 2.  Definition and Units of Activity
clide. The decay constant has a characteristic The quantity Δ N/Δ t, the average decay rate,
value for each radionuclide. It is the fraction is the activity of the sample. It has dimen-
of the atoms in a sample of that radionuclide sions of disintegrations per second (dps) or
undergoing radioactive decay per unit of time disintegrations per minute (dpm) and is
during a period that is so short that only a essentially a measure of “how radioactive” the
small fraction decay during that interval. sample is. The Systeme International (SI)
Alternatively, it is the probability that any unit of activity is the becquerel (Bq). A sample
individual atom will undergo decay during has an activity of 1 Bq if it is decaying at an
the same period. The units of λ are (time)−1. average rate of 1╯sec−1 (1╯dps). Thus:
Thus 0.01╯sec−1 means that, on the average,
1% of the atoms undergo radioactive decay A(Bq) = ∆ N/∆ t = λ N (4-4)
each second. In Equation 4-1 the minus sign
indicates that Δ N/Δ t is negative; that is, N is where λ is in units of sec−1. The absolute value
decreasing with time. is used to indicate that activity is a “positive”
Equation 4-1 is valid only as an estimate quantity, as compared with the change in
of the average rate of decay for a radioactive number of radioactive atoms in Equation 4-1,
sample. From one moment to the next, the which is a negative quantity. Commonly used
actual decay rate may differ from that pre- multiples of the becquerel are the kilobec-
dicted by Equation 4-1. These statistical querel (1╯kBq = 103╯sec−1), the megabecquerel
fluctuations in decay rate are described in (1╯MBq = 106╯sec−1), and the gigabecquerel
Chapter 9. (1╯GBq = 109╯sec−1).
31
32 Physics in Nuclear Medicine

The traditional unit for activity is the curie Number decaying


(Ci), which is defined as 3.7 × 1010╯dps (2.22 × during time interval
1012╯dpm). Subunits and multiples of the curie
are the millicurie (1╯mCi = 10−3 Ci), the micro- 1000
curie (1╯µCi = 10−3╯mCi = 10−6 Ci), the nano- 100
curie (1 nCi = 10−9 Ci), and the kilocurie (1╯kCi 900
= 1000 Ci). Equation 4-1 may be modified for 90
these units of activity: 800
81
A(Ci) = λ N / (3.7 × 10 )
10
(4-5) 700 73

Number of atoms
600 66
The curie was defined originally as the activity
of 1╯g of 226Ra; however, this value “changed” 500
from time to time as more accurate measure- 900 810 729 656 590
ments of the 226Ra decay rate were obtained. 400
For this reason, the 226Ra standard was aban- Number remaining
doned in favor of a fixed value of 3.7 × 1010╯dps. 300 after time interval
This is not too different from the currently
accepted value for 226Ra (3.656 × 1010╯dps/g). 200
SI units are the “official language” for
100
nuclear medicine and are used in this text;
however, because traditional units of activity 0
still are used in day-to-day practice in many 0 1 2 3 4 5
laboratories, we sometimes also indicate Decay time (sec)
activities in these units as well. Conversion FIGURE 4-1  Decay of a radioactive sample during suc-
factors between traditional and SI units are cessive 1-sec increments of time, starting with 1000
provided in Appendix A. atoms, for λ = 0.1╯sec−1. Both the number of atoms remain-
The amounts of activity used for nuclear ing and activity (decay rate) decrease with time. Note
that the values shown are approximations, because they
medicine studies typically are in the MBq-GBq do not account precisely for the changing number of
range (10s of µCi to 10s of mCi). Occasionally, atoms present during the decay intervals (see Section D).
10s of gigabecquerels (curie quantities) may
be acquired for long-term supplies. External-
beam radiation sources (e.g., 60Co therapy number of atoms decaying is 0.1 × 1000 = 100
units) use source strengths of 1000s of GBq atoms (see Equation 4-1). The activity is
[1000 GBq = 1 terraBq (TBq) = 1012 Bq]. therefore 100 Bq, and after 1╯sec there are
At the other extreme, the most sensitive  900 radioactive atoms remaining. During the
measuring systems used in nuclear medicine next second, the activity is 0.1 × 900 = 90 Bq,
can detect activities at the level of a few  and after 2╯sec, 810 radioactive atoms remain.
becquerels (nanocuries). During the next second the activity is 81 Bq,
and after 3╯sec 729 radioactive atoms remain.
Thus both the activity and the number of
B.  EXPONENTIAL DECAY
radioactive atoms remaining in the sample
are decreasing continuously with time. A
1.  The Decay Factor graph of either of these quantities is a curve
With the passage of time, the number N of that gradually approaches zero.
radioactive atoms in a sample decreases. An exact mathematical expression for N(t)
Therefore the activity A of the sample also can be derived using methods of calculus.*
decreases (see Equation 4-4). Figure 4-1 is The result is:
used to illustrate radioactive decay with the
passage of time. N (t) = N (0) e− λ t (4-6)
Suppose one starts with a sample contain-
ing N(0) = 1000 atoms* of a radionuclide
having a decay constant λ = 0.1╯sec−1. During *The derivation is as follows:
the first 1-sec time interval, the approximate dN/dt = −λN (4-6a)
dN/N = −λdt (4-6b)
*N(t) is symbolic notation for the number of atoms
present as a function of time t. N(0) is the number N at
∫ dN/N = −∫ λ dt (4-6c)
a specific time t = 0, that is, at the starting point. from which follows Equation 4-6.
4  •  Decay of Radioactivity 33

Thus N(t), the number of atoms remaining absorption of x- and λ-ray beams (see Chapter
after a time t, is equal to N(0), the number of 6, Section D) and the clearance of certain
atoms at time t = 0, multiplied by the factor tracers from organs by physiologic processes
e−λâ•›t. This factor e−λâ•›t, the fraction of radioÂ� (see Chapter 22, Section B.2).
active atoms remaining after a time t, is When the exponent in the decay factor is
called the decay factor (DF). It is a number “small,” that is, λâ•›t ≲ 0.1, the decay factor may
equal to e—the base of natural logarithms be approximated by e−λâ•›t ≈ 1 − λ t. This form
(2.718 …)—raised to the power −λ t. For given may be used as an approximation in Equations
values of λ and t, the decay factor can be 4-6 and 4-7.
determined by various methods as described
in Section C later in this chapter. Note that 2.  Half-Life
because activity A is proportional to the As indicated in the preceding section, radio�
number of atoms N (see Equation 4-4), the active decay is characterized by the disap-
decay factor also applies to activity versus pearance of a constant fraction of the activity
time: present in the sample during a given time
interval. The half-life (T1/2) of a radionuclide
A(t) = A(0) e− λ t (4-7) is the time required for it to decay to 50% of
its initial activity level. The half-life and
The decay factor e−λ t is an exponential func- decay constant of a radionuclide are related
tion of time t. Exponential decay is character- as*
ized by the disappearance of a constant
fraction of activity or number of atoms present T1 / 2 = ln 2 /λ (4-8)
per unit time interval. For example if λ =
0.1╯sec−1, the fraction is 10% per second. λ = ln 2 /T1 / 2 (4-9)
Graphs of e−λ t versus time t for λ = 0.1╯sec−1
are shown in Figure 4-2. On a linear plot, it *The relationships are derived as follows:
is a curve gradually approaching zero; on a 1 / 2 = e− λ T1 / 2 (4-8a)
semilogarithmic plot, it is a straight line. It
2 = eλ T1 / 2 (4-8b)
should be noted that there are other processes
besides radioactive decay that can be described ln 2 = λT1 / 2 (4-8c)
by exponential functions. Examples are the from which follow Equations 4-8 and 4-9.

1.0 1

0.9

0.8

0.7
Decay factor, et

0.6

0.5 0.1

0.4

0.3

0.2

0.1

0.0 0.01
0 8 16 24 32 0 8 16 24 32
A Decay time (sec) B Decay time (sec)
FIGURE 4-2  Decay factor versus time shown on linear (A) and semilogarithmic (B) plots, for radionuclide with
λ = 0.1╯secâ•›−1.
34 Physics in Nuclear Medicine

where ln 2 ≈ 0.693. Usually, tables or charts TABLE 4-1â•…


of radionuclides list the half-life of the radio- DECAY FACTORS FOR 99mTc
nuclide rather than its decay constant. Thus
it often is more convenient to write the decay Minutes
factor in terms of half-life rather than decay
constant: Hours 0 15 30 45
0 1.000 0.972 0.944 0.917
DF = e − ln 2 × t / T1 / 2 (4-10) 1 0.891 0.866 0.841 0.817
2 0.794 0.771 0.749 0.727
3.  Average Lifetime 3 0.707 0.687 0.667 0.648
The actual lifetimes of individual radioactive 4 0.630 0.612 0.595 0.578
atoms in a sample range anywhere from 
5 0.561 0.545 0.530 0.515
“very short” to “very long.” Some atoms 
decay almost immediately, whereas a few do 6 0.500 0.486 0.472 0.459
not decay for a relatively long time (see Fig. 7 0.445 0.433 0.420 0.408
4-2). The average lifetime τ of the atoms in a 8 0.397 0.385 0.375 0.364
sample has a value that is characteristic of
the nuclide and is related to the decay con- 9 0.354 0.343 0.334 0.324
stant λ by* 10 0.315 0.306 0.297 0.289

τ = 1/λ (4-11) 11 0.281 0.273 0.264 0.257


12 0.250 0.243 0.236 0.229
Combining Equations 4-9 and 4-11, one
obtains
τ = T1 / 2 / ln 2 (4-12)
at 4 pm on the same day to prepare an injec-
The average lifetime for the atoms of a radio- tion of 50╯kBq for a patient?
nuclide is therefore longer than its half-life,
by a factor 1/ ln 2 (≈1.44). The concept of Answer
average lifetime is of importance in radiation From Table 4-1 the DF for 99mTc after 8 hours
dosimetry calculations (see Chapter 22). is found to be 0.397. Therefore the concentra-
tion of activity in the vial is 0.397 × 75╯kBq/
mL = 29.8╯kBq/mL. The volume required for
C.  METHODS FOR DETERMINING 50╯kBq is 50╯kBq divided by 29.8╯kBq/mL =
1.68╯mL.
DECAY FACTORS
Tables of decay factors cover only limited
1.  Tables of Decay Factors periods; however, they can be extended by
It is essential that an individual working with employing principles based on the properties
radionuclides know how to determine decay of exponential functions, specifically eâ•›a + b =
factors. Perhaps the simplest and most e a × e b. For example, suppose that the desired
straightforward approach is to use tables of time t does not appear in the table but that it
decay factors, which are available from can be expressed as a sum of times, t = t1 + t2
vendors of radiopharmaceuticals, instrument + · · ·, that do appear in the table. Then
manufacturers, and so forth. An example of
DF(t1 + t2 + ) = DF(t1 ) × DF(t2 )  (4-13)
such a table for 99mTc is shown in Table 4-1.
Such tables are generated easily with com-
EXAMPLE 4-2
puter spreadsheet programs.
99m
What is the decay factor for Tc after 16
EXAMPLE 4-1 hours?
A vial containing 99mTc is labeled “75╯kBq/mL
at 8 am.” What volume should be withdrawn Answer
Express 16 hours as 6 hours + 10 hours. Then,
from Table 4-1, DF(16╯hr) = DF(10╯hr) ×
*The equation from which Equation 4-11 is derived is: DF(6╯hr) = 0.315 × 0.5 = 0.1575. Other combi-
∞ ∞ nations of times totaling 16 hours provide the
same result.
∫0
τ = te− λ t dt ∫0 e −λ t
dt (4-11a)
4  •  Decay of Radioactivity 35

Occasionally, radionuclides are shipped in 100 103


precalibrated quantities. A precalibrated
shipment is one for which the activity calibra-
tion is given for some future time. To deter-
mine its present activity, it is therefore
necessary to calculate the decay factor for a
time preceding the calibration time, that is, a
“negative” value of time. One can make use of 101 104
tables of decay factors by employing another
of the properties of exponential functions,

Decay factor
specifically e−x = 1/e↜x. Thus:
DF(− t) = 1/DF(t) (4-14)

EXAMPLE 4-3
102 105
A vial containing 99mTc is labeled “50╯kBq at
3 pm.” What is the activity at 8 am on the
same day?

Answer
The decay time is t = −7 hours. From Table
4-1, DF(7╯hr) = 0.445. Thus DF(−7╯hr) =
1/0.445 = 2.247. The activity at 8 am is there- 103 106
0 5 10 15
fore 2.247 × 50╯kBq = 112.4╯kBq. Number of half-lives elapsed
FIGURE 4-3  Universal decay curve.
2.  Pocket Calculators
Many pocket calculators have capabilities 
for calculating exponential functions. First 0.40. (Compare this result with the value
compute the exponent, x = ln 2 × (t/T1/2), then used in Example 4-1.)
press the appropriate keys to obtain e−x. For
precalibrated shipments, use e+â•›x.
D.  IMAGE-FRAME DECAY
3.  Universal Decay Curve CORRECTIONS
Exponential functions are straight lines on a
semilogarithmic plot (see Fig. 4-2). This useful In some applications, data are acquired
property allows one to construct a “universal during periods that are not short in compari-
decay curve” by plotting the number of half- son with the half-life of the radionuclide. An
lives elapsed on the horizontal (linear) axis example is the measurement of glucose
and the decay factor on the vertical (logarith- metabolism using deoxyglucose labeled with
mic) axis. A straight line can be drawn by fluorine-18 (see Chapter 21, Section E.5). In
connecting any two points on the curve. These such measurements, it often is necessary to
could be, for example, (t = 0, DF = 1), (t = T1/2, correct for decay that occurs during each mea-
DF = 0.5), (t = 2T1/2, DF = 0.25), and so on. The surement period while data collection is in
graph can be used for any radionuclide pro- progress. Because data are acquired in a
vided that the elapsed time is expressed in series of image frames, these sometimes are
terms of the number of radionuclide half-lives called image-frame decay corrections.
elapsed. An example of a universal decay The concept for these corrections is illus-
curve is shown in Figure 4-3. trated in Figure 4-4, showing the decay curve
for an image frame starting at time t and
EXAMPLE 4-4 ending at a time Δâ•›t later. The number of
Use the decay curve in Figure 4-3 to deter- counts acquired during the image frame is
mine the decay factor for 99mTc after 8 hours. proportional to the area ad, shown with darker
shading. The counts that would be recorded
Answer in the absence of decay are proportional to the
The half-life of 99mTc is 6 hours. Therefore the area a0, which includes both the darker and
elapsed time is 8/6 = 1.33 half-lives. From lighter shaded areas. Using the appropriate
Figure 4-3, the decay factor is approximately mathematical integrals, the effective decay
36 Physics in Nuclear Medicine

1.0

0.8

0.6
Decay factor

0.4 Area without


decay, a0

0.2 Area with


decay, ad

0.0
t tt Time

FIGURE 4-4  Basic concept for calculating the decay factor for an image frame starting at time t with duration Δ t.
The counts recorded with decay are proportional to the darker shaded area, ad. The counts that would be recorded in
the absence of decay are proportional to the total shaded area, a0. The effective decay factor is the ratio adâ•›/a0.

factor for a radionuclide with half-life T1/2 for the appropriate values for t and Δ t and for the
the indicated measurement interval is given half-life T1/2. For computational simplicity
by: and efficiency, various approximations can be
used when the parameter x in Equation 4-16
DFeff (t, ∆ t) = ad / a0 is small. For example, the following approxi-
= e− (ln 2 × t / T1 / 2 ) × [(1 − e− x ) / x] mation is accurate to within 1% when x <
= DF(t) × [(1 − e− x ) / x] (4-15) 0.25:
DFeff (t, ∆ t) ≈ DF(t) × [1 − ( x/ 2)] (4-17)
where
x = ln 2 × ∆ t/T1 / 2 where x again is defined as in Equation 4-16.
(4-16)
Another approach is to use the standard
To correct the recorded counts back to what DF (see Equation 4-10) for the midpoint of the
would have been recorded in the absence of frame:
decay, one would multiply the counts recorded
DFeff (t, ∆ t) ≈ DF [t + (∆ t/ 2)] (4-18)
during the interval (t, t + Δ t) by the inverse
of DFeff. This approximation is accurate to within 1%
The effective decay factor in Equation 4-15 for x < 0.5.
is composed of two parts. The first term is just Yet another possibility is to use the average
the standard decay factor (Equation 4-10) at of the standard decay factors for the begin-
the start of the image frame, DF(t). The second ning and end of the frame:
term is a factor that depends on the parameter
x, which in turn depends on the duration of [DF(t) + DF(t + ∆ t)]
DFeff (t, ∆ t) ≈ (4-19)
the frame, Δ t, relative to the half-life of the 2
radionuclide (Equation 4-16). This term
accounts for decay that occurs while data are This approximation is accurate to within 1%
being acquired during the image frame. Note for x < 0.35.
again that the correction in Equation 4-15
EXAMPLE 4-5
uses t = 0 as the reference point, not the start
of the individual image frame for which the What are the effective decay factor and decay
correction is being calculated. To compute the correction factor for the counts recorded 
decay occurring during the image frame itself, in an image frame starting 30╯sec and ending
only the second term should be used. 45╯sec after injection in a study performed
In a quantitative study, the data for each with 15O? Compare the results obtained
image frame would be corrected according to with Equation 4-15 and the approximation
4  •  Decay of Radioactivity 37

127
given by Equation 4-17. Assume that the data I. When stable isotopes of the radionuclide
are to be corrected to t = 0, the time of of interest are present in the sample, they are
injection. called carrier, and the sample is said to be
with carrier. A sample that does not contain
Answer stable isotopes of the element represented by
From Appendix C, the half-life of 15O is the radionuclide is called carrier-free.* Radio-
122╯sec. The decay factor at the beginning of nuclides may be produced carrier-free or with
the image frame, t = 30╯sec, is carrier, depending on the production method
(see Chapter 5).
DF(30 sec) = e− ln 2 × 30 sec / 122 sec The ratio of radioisotope activity to total
≈ e−0.170 mass of the element present is called the spe-
cific activity of the sample. Specific activity
≈ 0.843
has units of becquerels per gram, megabec-
The duration of the image frame is Δâ•›t = 15╯sec. querels per gram, and so forth. The highest
The parameter x (Equation 4-16) is given by possible specific activity of a radionuclide is
its carrier-free specific activity (CFSA). This
x = ln 2 × (∆ t/T1 / 2 ) value can be calculated in a straightforward
= ln 2 × (15 sec /122 sec) manner from the basic properties of the
radionuclide.
≈ 0.0852
Suppose a carrier-free sample contains 1╯g
Thus, decay during the image frame is given of a radionuclide AX, having a half-life T1/2
by (sec). The atomic weight of the radionuclide
is approximately equal to A, its mass number
(1 − e− x ) /x = (1 − e−0.0852 ) / 0.0852 (see Chapter 2, Section D.2). A sample con-
taining A g of the radionuclide has approxi-
≈ 0.0817 / 0.0852 mately 6.023 × 1023 atoms (Avogadro’s
≈ 0.959 number); therefore a 1-g sample has N ≈ 6.023
× 1023/A atoms. The decay rate of the sample
Taking the product of the two decay factors is Δâ•›N/Δâ•›t (dps) = λâ•›N = 0.693Nâ•›/â•›T1â•›/2. Therefore
gives the activity per gram is:

DFeff ≈ 0.843 × 0.959 A(Bq/g ) ≈ ln 2 × 6.023 × 1023 / (A × T1 / 2 )


(4-20)
≈ 0.808
Because the sample contains 1╯g of the radio�
The decay correction factor to apply to the isotope, this is also its specific activity in 
counts recorded in this frame is becquerels per gram. When the equation is 
normalized for the half-life in days (1 day =
CF ≈ 1/ 0.808 86,400╯sec), the result is

≈ 1.237 CFSA (Bq/g ) ≈ 4.8 × 1018 / (A × T1 / 2 )
(4-21)
Using the approximation given by Equation
4-17 yields where T1/2 is given in days. With appropriate
normalization, Equation 4-21 also applies for
DFeff ≈ 0.843 × [1 − (0.0852 / 2)] specific activity in kBq/mg, GBq/g, and so on.
≈ 0.843 × 0.957 In radiochemistry applications, specific
activities sometimes are specified in becquer-
≈ 0.807
els per mole of labeled compound. Because 1
which differs from the exact result obtained mole of compound contains A g of radionu-
with Equation 4-15 by only approximately clide, this quantity is
0.1%. CFSA (Bq/mole) = CFSA (Bq/g) × A (g/mole)
≈ 4.8 × 1018 /T1 / 2 (4-22)

E.  SPECIFIC ACTIVITY where T1/2 again is in days.

A radioactive sample may contain stable iso- *Because it is virtually impossible to prepare a sample
topes of the element represented by the radio- with absolutely no other atoms of the radioactive element,
nuclide of interest. For example, a given 131I the terminology without carrier sometimes is used as
sample may also contain the stable isotope well.
38 Physics in Nuclear Medicine

In traditional units, the equations for cause any “iodine reaction.” Even radioÂ�
CFSA are isotopes of highly toxic elements, such as
arsenic, have been given to patients in a carrier- 
CFSA (Ci / g) ≈ 1.3 × 108 / ( A × T1 / 2 ) free state. It is not possible to obtain carrier-
(4-23)
CFSA (Ci / mole) ≈ 1.3 × 108 /T1 / 2 free 99mTc because it cannot be separated from
its daughter product, 99Tc, a very long-lived
where T1/2 again is in days. and essentially stable isotope of technetium.
Nevertheless, the mass of technetium in most
EXAMPLE 4-6 99m
Tc preparations is very small and has no
131 99m
What are the CFSAs of I and Tc? physiologic effect when administered to a
patient.
Answer Not all production methods result in
For 131I, A = 131 and T1/2 = 8 days. Using Equa- carrier-free radionuclides. Also, in some cases
tion 4-21, carrier may be added to promote certain
chemical reactions in radiochemistry proce-
(4.8 × 1018 ) dures. When a preparation is supplied with
CFSA ( 131 I) ≈ carrier, usually the packaging material indi-
(1.31 × 102 × 8)
cates specific activity. If the radioactivity
≈ 4.6 × 1015 Bq / g exists as a label attached to some complex
molecule, such as a protein molecule, the spe-
For 99mTc, A = 99 and T1/2 = 6 hours = 0.25 days. cific activity may be expressed in terms of the
Thus, activity per unit mass of labeled substance,
such as MBqâ•›/g of protein. Methods of calcu-
(4.8 × 1018 ) lating the specific activities of radionuclides
CFSA ( 99 m Tc) ≈ produced in a non–carrier-free state are dis-
(0.99 × 102 × 0.25)
cussed in Chapter 5.
≈ 2.5 × 1017 Bq / g On rare occasions, radioactive preparations
that are not carrier-free or that are attached
In traditional units (Equation 4-23), the as labels to complex molecules may present
answers are pro�blems if the carrier or labeled molecule is
toxic or has undesired pharmacologic effects.
(1.3 × 108 ) Two examples in the past were reactor-
CFSA (131 I) ≈
(1.31 × 102 × 8) produced 42K in K+ solution (intravenous K+
injections may cause cardiac arrhythmia) and
≈ 1.24 × 105 Ci / g 131
I-labeled serum albumin (serum albumin
(1.3 × 108 ) could cause undesirably high protein levels
CFSA ( 99 m Tc) ≈ when injected into intrathecal spaces for 
(0.99 × 102 × 0.25)
cerebrospinal fluid studies). In situations such
≈ 5.3 × 106 Ci / g as these, the amount of material that can be
administered safely to a patient may be limited
by the amount of carrier or unlabeled molecule
As shown by Example 4-6, CFSAs for radio- present rather than by the amount of radio�
nuclides having half-lives of hours, days, or activity and associated radiation hazards.
even weeks are very high. Most of the radio-
nuclides used in nuclear medicine are in this
category. F.  DECAY OF A MIXED
In most instances, a high specific activity RADIONUCLIDE SAMPLE
is desirable because then a moderate amount
of activity contains only a very small mass of The equations and methods presented in Sec-
the element represented by the radioisotope tions B and C apply only to samples contain-
and can be administered to a patient without ing a single radionuclide species. When a
causing a pharmacologic response to that sample contains a mixture of unrelated species
element. This is an essential requirement of (i.e., no parent-daughter relationships), the
a “tracer study.” For example, a capsule con- total activity Aâ•›t is just the sum of the indi-
taining 0.4╯MBq (~10╯µCi) of carrier-free 131I vidual activities of the various species:
contains only approximately 10−10╯g of elemen-
tal iodine (mass = activity/specific activity), A t (t) = A1 (0) e−0.693t / T1 / 2,1 + A 2 (0) e−0.693t / T1 / 2, 2 + 
which is well below the amount necessary to (4-24)
4  •  Decay of Radioactivity 39

Total
activity

0.1
Activity (arbitrary units)

T1/2  5 days

0.01

T1/2  0.5 days

0.001
0 1 2 3 4
Time (days)
FIGURE 4-5  Activity versus time for a mixed sample of two unrelated radionuclides. The sample contains initially
(at t = 0) 0.9 units of activity with a half-life of 0.5 days and 0.1 units of activity with a half-life of 5 days.

where A1(0) is the initial activity of the first Curve stripping can be used to determine
species and T1/2,1 is its half-life, and so forth. the relative amounts of various radionu-
Figure 4-5 shows total activity versus time clides present in a mixed sample and their
for a sample containing two unrelated radio- half-lives. It is especially useful for detecting
nuclides. A characteristic of such a curve is and quantifying long-lived contaminants 
that it always eventually follows the slope of in radioactive preparations (e.g., 99Mo in
99m
the curve for the radionuclide having the Tc).
longest half-life. Once the final slope has been
established, it can be extrapolated as a straight
line on a semilogarithmic graph back to time G.  PARENT-DAUGHTER DECAY
zero. This curve can then be subtracted from
the total curve to give the net curve for the
other radionuclides present. If more than two 1.  The Bateman Equations
radionuclide species are present, the “curve- A more complicated situation occurs when 
stripping” operation can be repeated for the a sample contains radionuclides having
next-longest-lived species and so forth. parent-daughter relationships (Fig. 4-6). The

Parent Daughter Grand-daughter


T1/2  Tp T1/2  Td T1/2  Tg

FIGURE 4-6  Schematic representation of series decay. Activities of the parent (↜p), daughter (d), and grand-daughter
(↜g) are described by the Bateman equations.
40 Physics in Nuclear Medicine

equation for the activity of the parent is term in Equation 4-25, A d (0) e−λ d t, is just the
simply that for a single radionuclide species residual daughter-product activity remaining
(see Equation 4-7); however, the equation for from any that might have been present at
the activity of a daughter is complicated by time t = 0. In the rest of this discussion, it is
the fact that the daughter product is being assumed that Ad(0) = 0, and only the first term
formed (by decay of the parent) at the same in Equation 4-25 is considered.
time it is decaying. The equation is Equation 4-25 is the Bateman equation for
a parent-daughter mixture. Bateman equa-
 λd  
Ad (t) =   Ap (0) × ( e− λp t − e− λd t )  × B.R. tions for sequences of three or more radionu-
 λd − λp   clides in a sequential decay scheme are found
+ Ad (0)e − λd t in other texts.1 Equation 4-25 is analyzed for
(4-25) three general situations.†

where Ap(t) and Ad(t) are the activities of the 2.  Secular Equilibrium
parent and daughter radionuclides at time t, The first situation applies when the half-life
respectively, λp and λd are their respective of the parent, Tp, is so long that the decrease
decay constants, and B.R. is the branching of parent activity is negligible during the
ratio for decay to the daughter product of course of the observation period. An example
interest when more than one decay channel is 226Ra (Tp = 1620╯yr) → 222Rn (Td = 4.8 days).
is available (see Equation 4-3).* The second In this case, λp ≈ 0; thus Equation 4-25 can be
written
*The differential equations from which Equation 4-25 is Ad (t) ≈ Ap (0)(1 − e− λd t ) × B.R. (4-26)
derived are
Figure 4-7 illustrates the buildup of daugh-
dNp /dt = −λ p Np (4-25a) ter product activity versus time for B.R. = 1.
After one daughter-product half-life, e− λ d t = 1/ 2
dNd /dt = −λ d Nd + λ p Np (4-25b)

These equations provide

λp †A fourth (but unlikely) situation occurs when λp = λd =


Nd (t) = Np (0) × (e− λp t − e− λd t ) + Nd (0) e− λd t (4-25c)
λd − λ p λ, that is when parent and daughter have the same half-
life. In this case, it can be shown that Equation 4-25
reduces to
Multiplying Equation 4-25c by λd and substituting Ad =
λ dâ•›Nd, Aâ•›p = λ pâ•›Np, one obtains Equation 4-25. Ad (t) = Ap (0)te− λ t + Ad (0) e− λ t (4-25d)

Parent activity
1
Activity (arbitrary units)

Daughter activity

0.1
0 1 2 3 4 5 6 7 8 9 10
Number of daughter half-lives
FIGURE 4-7  Buildup of daughter activity when Td << Tp ≈ ∞, branching ratio = 1. Eventually, secular equilibrium
is achieved.
4  •  Decay of Radioactivity 41

and Ad ≈ (1/2)Ap. After two half-lives, Ad ≈ The time at which maximum daughter activ-
(3/4)Ap, and so forth. After a “very long” time, ity is available is determined using the
(~5 × Td), e− λ dt ≈ 0, and the activity of the methods of calculus* with the result
daughter equals that of the parent. When this
occurs (Ad ≈ Ap × B.R.), the parent and daugh- tmax = [1.44Tp Td / (Tp − Td )] ln(Tp /Td )
ter are said to be in secular equilibrium. (4-28)
3.  Transient Equilibrium where Tp and Td are the half-lives of the
The second situation occurs when the parent parent and daughter, respectively.
half-life is longer than the daughter half-life Figure 4-8 is similar to that for 99Mo (Tp =
but is not “infinite.” An example of this case 66╯hr) → 99mTc (Td = 6╯hr); however, the time-
is 99Mo (T1/2 = 66╯hr) → 99mTc (T1/2 = 6╯hr). activity curve for 99mTc is somewhat lower
When there is a significant decrease in parent because only a fraction (B.R. = 0.876) of the
activity during the course of the observation parent 99Mo atoms decay to 99mTc (see Fig.
period, one can no longer assume λp ≈ 0, and 5-7). The remainder bypass the 99mTc meta-
Equation 4-25 cannot be simplified. Figure stable state and decay directly to the ground
4-8 shows the buildup and decay of daughter- state of 99Tc. Thus the 99mTc activity is given
product activity for a hypothetical parent- by Equation 4-25 multiplied by 0.876 and the
daughter pair with Tp = 10Td and B.R. = 1. ratio of 99mTc↜/↜99Mo activity in transient equi-
The daughter-product activity increases and librium by Equation 4-27 multiplied by the
eventually exceeds that of the parent, reaches same factor; however, tmax remains as given by
a maximum value, and then decreases and Equation 4-28.
follows the decay of the parent. When this
stage of “parallel” decay rates has been 4.  No Equilibrium
reached—that is, parent and daughter activi- When the daughter half-life is longer than
ties are decreasing but the ratio of parent-to- the parent half-life, there is no equilibrium
daughter activities are constant—the parent between them. An example of this combina-
and daughter are said to be in transient tion is 131mTe (T1/2 = 30╯hr) → 131I (T1/2 =
equilibrium. The ratio of daughter-to-parent 8 days). Figure 4-9 shows the buildup and
activity in transient equilibrium is

A d /Ap = [Tp / (Tp − Td )] × B.R. (4-27) *Set dAd╛╛/dt = 0 and solve for tmax.

1 Parent activity
Activity (arbitrary units)

Daughter activity

0.1
0 1 2 3 4 5 6 7 8 9 10
Number of daughter half-lives
FIGURE 4-8  Buildup and decay of activity for Tp = 10 Td, branching ratio = 1. Eventually, transient equilibrium is
achieved when the parent and daughter decay curves are parallel.
42 Physics in Nuclear Medicine

Activity (arbitrary units) Parent activity

Daughter activity
0.1

0.01
0.0 0.2 0.4 0.6 0.8 1.0
Number of daughter half-lives
FIGURE 4-9  Buildup and decay of activity for Tp = 0.1 Td, branching ratio = 1. There is no equilibrium relationship
established between the parent and daughter decay curves.

decay of the daughter product activity for  daughter activity decays with its own char-
a hypothetical parent-daughter pair with Tp acteristic half-life.
= 0.1Td. It increases, reaches a maximum
(Equation 4-28 still applies for tmax), and REFERENCE
then decreases. Eventually, when the parent 1. Evans RD: The Atomic Nucleus, New York, 1972,
activity is essentially zero, the remaining McGraw-Hill, pp 477-499.
chapter
5 
Radionuclide and
Radiopharmaceutical
Production
Most of the naturally occurring radionuclides  splitting into two lighter nuclear fragments
are very long-lived (e.g., 40K, T1/2 ~ 109 years), and emitting two or three fission neutrons in
represent very heavy elements (e.g., uranium the process (see Chapter 3, Section I). Spon-
and radium) that are unimportant in meta- taneous fission of 235U is not a significant
bolic or physiologic processes, or both. Some source of neutrons or energy in of itself;
of the first applications of radioactivity for however, the fission neutrons emitted stimu-
medical tracer studies in the 1920s and 1930s late additional fission events when they
made use of natural radionuclides; however, bombard 235U and 238U nuclei. The most
because of their generally unfavorable char- important reaction is
acteristics indicated here, they have found
virtually no use in medical diagnosis since 235
U+n→ 236
U* (5-1)
that time. The radionuclides used in modern
nuclear medicine all are of the manufactured The 236U* nucleus is highly unstable and
or “artificial” variety. They are made by bom- promptly undergoes nuclear fission, releasing
barding nuclei of stable atoms with sub� additional fission neutrons. In the nuclear
nuclear particles (such as neutrons and reactor, the objective is to have the fission
protons) so as to cause nuclear reactions that neutrons emitted in each spontaneous or
convert a stable nucleus into an unstable stimulated fission event stimulate, on the
(radioactive) one. This chapter describes the average, one additional fission event. This
methods used to produce radionuclides for establishes a controlled, self-sustaining
nuclear medicine as well as some consider- nuclear chain reaction.
ations in the labeling of biologically relevant Figure 5-1 is a schematic representation of
compounds to form radiopharmaceuticals. a nuclear reactor core. “Fuel cells” containing
fissionable material (e.g., uranium) are sur-
A.  REACTOR-PRODUCED rounded by a moderator material. The purpose
of the moderator is to slow down the rather
RADIONUCLIDES
energetic fission neutrons. Slow neutrons
(also called thermal neutrons) are more effi-
1.  Reactor Principles cient initiators of additional fission events.
Nuclear reactors have for many years pro- Commonly used moderators are “heavy water”
vided large quantities of radionuclides for [containing deuterium (D2O)] and graphite.
nuclear medicine. Because of their long and Control rods are positioned to either expose
continuing importance for this application, a or shield the fuel cells from one another. The
brief description of their basic principles is control rods contain materials that are strong
presented. neutron absorbers but that do not themselves
The “core” of a nuclear reactor contains a undergo nuclear fission (e.g., cadmium or
quantity of fissionable material, typically boron). The fuel cells and control rods are
natural uranium (235U and 238U) enriched in positioned carefully so as to establish the
235
U content. Uranium-235 undergoes spon- critical conditions for a controlled chain reac-
taneous nuclear fission (T1/2 ~ 7 × 108 years), tion. If the control rods were removed (or
43
44 Physics in Nuclear Medicine

Coolant

Control
rods
Coolant out

Pneumatic line for


Moderator insertion and
removal of samples

Coolant in
Pressure
vessel

Uranium fuel Shielding

FIGURE 5-1  Schematic representation of a nuclear reactor.

incorrectly positioned), conditions would exist 2.  Fission Fragments


wherein each fission event would stimulate The fission process that takes place in a
more than one additional nuclear fission. This reactor can lead to useful quantities of medi-
could lead to a runaway reaction and to a cally important radionuclides such as 99Mo,
possible “meltdown” of the reactor core. (This the parent material in the 99mTc generator (see
sequence occurs in a very rapid time scale in Section C). As described earlier, 236U* promptly
nuclear explosives. Fortunately, the critical decays by splitting into two fragments. A
conditions of a nuclear explosion cannot be typical fission reaction (Fig. 5-2A) is
achieved in a nuclear reactor.) Insertion of
additional control rods results in excess 235
92 U+n→ 236
92 U* → 144
56 Ba + 89
36 Kr + 3n   (5-2)
absorption of neutrons and terminates the
chain reaction. This procedure is used to shut More than 100 nuclides representing 20
down the reactor. dif�ferent elements are found among the fission
Each nuclear fission event results in the pro�ducts of 236U*. The mass distribution of the
release of a substantial amount of energy fission fragments is shown in Figure 5-2B.
(200-300 MeV per fission fragment), most of It can be seen that fission of 236U* generally
which is dissipated ultimately as thermal leads to one fragment with a mass number in
energy. This energy can be used as a thermal the range of 85 to 105 and the other fragment
power source in reactors. Some radionuclides with a mass number in the range of 130 to
are produced directly in the fission process 150. It also is apparent that fission rarely
and can be subsequently extracted by chemi- results in fragments with nearly equal masses.
cal separation from the fission fragments. The fission products always have an excess
A second method for producing radio� of neutrons and hence undergo further radio-
nuclides uses the large neutron flux in the active decay by β– emission, until a stable
reactor to activate samples situated around nuclide is reached. If one of the radioactive
the reactor core. Pneumatic lines are used for intermediates has a sufficiently long half- 
the insertion and removal of samples. The life, it can be extracted from the fission prod-
method of choice largely depends on yield of ucts and used as a medical radionuclide. For
the desired radionuclide, whether suitable example,
sample materials are available for neutron − − −
β (1.5 s) β (21 s) β (15 s)
activation, the desired specific activity, and 99
39 Y   → 99
40 Zr   → 99
41 Nb   → 99
42 Mo
cost considerations. (5-3)
5  •  Radionuclide and Radiopharmaceutical Production 45

A
10

1
Yield (%)

0.1

0.01

0.001
60 80 100 120 140 160 180
B Mass number

FIGURE 5-2  A, Example of production of fission fragments produced when neutrons interact with 236
U*. B, Mass
distribution of fragments following fission of 236U*.

The half-life of 99Mo is 65.9 hours, which is interest are also produced in the fission
sufficiently long to allow it to be chemically  fragments. For example, high-specific-
separated from other fission fragments. activity 131I cannot be produced through
Molybdenum-99 plays an important role in fission because of significant contamina-
nuclear medicine as the parent radionuclide tion from 127I and 129I.)
in the 99Mo-99mTc generator (see Section C). 3. The lack of specificity of the fission
Technetium-99m is the most common radio- process is a drawback that results in a
nuclide used in clinical nuclear medicine pro- relatively low yield of the radionuclide
cedures today. Fission has also been used to of interest among a large amount of
produce 131I and 133Xe for nuclear medicine other radionuclides.
studies.
Radionuclides produced by the fission process 3.  Neutron Activation
have the following general characteristics: Neutrons carry no net electrical charge. Thus
1. Fission products always have an excess they are neither attracted nor repelled by
of neutrons, because N/Z is substantially atomic nuclei. When neutrons (e.g., from a
higher for 235U than it is for nuclei falling nuclear reactor core) strike a target, some of
in the mass range of the fission frag- the neutrons are “captured” by nuclei of the
ments, even after the fission products target atoms. A target nucleus may be con-
have expelled a few neutrons (see Fig. verted into a radioactive product nucleus as
2-9). These radionuclides therefore tend a result. Such an event is called neutron acti-
to decay by β– emission. vation. Two types of reactions commonly
2. Fission products may be carrier free (no occur.
stable isotope of the element of interest In an (n,γ) reaction a target nucleus, AZ X ,
is produced), and therefore radionu- captures a neutron and is converted into a
clides can be produced with high specific product nucleus, A +1Z X *, which is formed in an
activity by chemical separation. (Some- excited state. The product nucleus immedi-
times other isotopes of the element of ately undergoes de-excitation to its ground
46 Physics in Nuclear Medicine

state by emitting a prompt γ ray. The reaction stability (see Fig. 2-9). Therefore they
is represented schematically as tend to decay by β– emission.
2. The most common production mode is by
A
Z X (n, γ ) A +1Z X (5-4) the (n,γ) reaction, and the products of
this reaction are not carrier free because
The target and product nuclei of this reaction they are the same chemical element as
represent different isotopes of the same chem- the bombarded target material. It is pos-
ical element. sible to produce carrier-free products in
A second type of reaction is the (n,p) reac- a reactor by using the (n,p) reaction
tion. In this case, the target nucleus captures (e.g., 32P from 32S) or by activating a
a neutron and promptly ejects a proton. This short-lived intermediate product, such
reaction is represented as as 131I from 131Te using the reaction

A
Z X (n, p) Z −1A Y (5-5) 130
Te (n, γ )131 Te 
β
→ 131
I (5-6)

Note that the target and product nuclei for an 3. Even in intense neutron fluxes, only a
(n,p) reaction do not represent the same very small fraction of the target nuclei
chemical element. actually are activated, typically 1â•›:â•›106 to
In these examples, the products ( A +1Z X or 109 (see Section D). Thus an (n,γ) product
Z -1 Y ) usually are radioactive species. The may have very low specific activity
A

quantity of radioactivity that is produced by because of the overwhelming presence of


neutron activation depends on a number of a large amount of unactivated stable
factors, including the intensity of the neutron carrier (target material).
flux and the neutron energies. This is dis- There are a few examples of the produc-
cussed in detail in Section D. Production tion of electron capture (EC) decay or β+-
methods for biomedically important radionu- emitting radionuclides with a nuclear reactor,
clides produced by neutron activation are for example, 51Cr by (n,γ) activation of
50
summarized in Table 5-1. Cr. They may also be produced by using
Radionuclides produced by neutron activation more complicated production techniques. An
have the following general characteristics: example is the production of 18F (β+, T1/2 =
1. Because neutrons are added to the 110╯ min). The target material is lithium 
nucleus, the products of neutron activa- carbonate (Li2CO3). The first step is the
tion generally lie above the line of reaction

TABLE 5-1â•…
NEUTRON-ACTIVATED RADIONUCLIDES OF IMPORTANCE IN BIOLOGY AND MEDICINE

Natural Abundance
Radionuclide Decay Mode Production Reaction of Target Isotope (%)* σc(b)†
14
C β– 14
N(n,p)14C 99.6 1.81
24
Na (β–,γ ) 23
Na(n,γ )24Na 100 0.53
32
P β– 31
P(n,γ )32P 100 0.19
32
S(n,p)32P 95.0 0.1
35
S β– 35
Cl(n,p)35S 75.8 0.4
42 – 41 42
K (β ,γ ) K(n,γ ) K 6.7 1.2
51 50
Cr (EC,γ ) Cr(n,γ )51Cr 4.3 17
59 – 58 59
Fe (β ,γ ) Fe(n,γ ) Fe 0.3 1.1
75
Se (EC,γ ) 74
Se(n, γ )75Se 0.9 30
125
I (EC,γ ) 124
Xe ( n, γ ) 125
Xe 
→EC 125
I 0.1 110
β−
131
I –
(β ,γ ) 130
Te ( n, γ ) 131
Te → 131
I 33.8 0.24
*Values from Browne E, Firestone RB: Table of Radioactive Isotopes. New York, 1986, John Wiley.1

Thermal neutron capture cross-section, in barns (b) (see “Activation Cross-Sections”). Values from Wang Y: Handbook
of Radioactive Nuclides, Cleveland, Chemical Rubber Company, 1969.2
EC, Electron capture.
5  •  Radionuclide and Radiopharmaceutical Production 47

6
Li (n, γ ) 7 Li (5-7) releases a neutron. This reaction is repre-
sented as
Lithium-7 is very unstable and promptly
disintegrates: A
Z X (d, n) AZ++11 Y (5-11)

7
3 Li → 42 He + 31 H + energy (5-8) and results in a change of both the element
(atomic number) and the mass number. In
some cases, more than one neutron may be
Some of the energetic recoiling tritium nuclei promptly released from the target nucleus
(31 H) bombard stable 16O nuclei, causing the after the bombarding particle has been cap-
reaction tured. For example, a (p,2n) reaction involves
the release of two neutrons following proton
16
8 O ( 31 H, n )189 F (5-9) capture and a (d,3n) reaction involves the
release of three neutrons following deuteron
Useful quantities of 18F can be produced in capture. Some accelerators also use alpha-
this way. One problem is removal from the particles to bombard a target and produce
product (by chemical means) of the rather radionuclides. Indium-111 can be produced in
substantial quantity of radioactive tritium this way using the reaction 109Ag(α,2n)111In.
that is formed in the reaction. More satisfac- Van de Graaff accelerators, linear acceler-
tory methods for producing 18F involve the use ators, cyclotrons, and variations of cyclotrons
of charged particle accelerators, as discussed have been used to accelerate charged parti-
in Section B. cles. The cyclotron is the most widely used
form of particle accelerator for production of
medically important radionuclides.3 Many
B.  ACCELERATOR-PRODUCED larger institutions have their own compact
biomedical cyclotrons for onsite production of
RADIONUCLIDES
the shorter-lived, positron-emitting radionu-
clides. The principles and design of cyclo-
1.  Charged-Particle Accelerators trons dedicated to production of radionuclides
Charged-particle accelerators are used to for nuclear medicine are described briefly.
accelerate electrically charged particles, such
as protons, deuterons ( 21 H nuclei), and α par-
ticles ( 42 He nuclei), to very high energies. 2.  Cyclotron Principles
When directed onto a target material, these A cyclotron consists of a pair of hollow, semi�
particles may cause nuclear reactions that circular metal electrodes (called dees because
result in the formation of radionuclides in a of their shape), positioned between the poles
manner similar to neutron activation in a of a large electromagnet (Fig. 5-3). The dees
reactor. A major difference is that the parti- are separated from one another by a narrow
cles must have very high energies, typically gap. Near the center of the dees is an ion
10-20 MeV, to penetrate the repulsive coulomb source, S, (typically an electrical arc device in
forces surrounding the nucleus. a gas) that is used to generate the charged
Two types of nuclear reactions are com- particles. All these components are contained
monly used to produce radionuclides using a in a vacuum tank at ~10–3 Pa(~10–8 atm).
charged-particle accelerator. In a (p,n) reac- During operation, particles are generated
tion, the target nucleus captures a proton and in bursts by the ion source, and a high-
promptly releases a neutron. This reaction is frequency alternating current (AC) voltage
represented as generated by a high-frequency oscillator (typ-
ically 30╯kV, 25-30╯MHz) is applied across the
A
Z X (p, n) Z +1A Y (5-10) dees. The particles are injected into the gap
and immediately are accelerated toward one
This reaction can be considered the inverse of of the dees by the electrical field generated by
the (n,p) reaction that uses neutrons as the the applied AC voltage. Inside the dee there
bombarding particle and was discussed in is no electrical field, but because the particles
Section A.3. are in a magnetic field, they follow a curved,
A second common reaction is the (d,n) reac- circular path around to the opposite side of
tion in which the accelerated particle is a deu- the dee. The AC voltage frequency is such
teron (d). The target nucleus captures a that the particles arrive at the gap just as the
deuteron from the beam and immediately voltage across the dees reaches its maximum
48 Physics in Nuclear Medicine

“Dees”
Vacuum

Electrostatic
deflector Magnet

Magnet

Target “Dees”
FIGURE 5-3  Schematic representation of a positive ion cyclotron: top (left) and side (right) views. The accelerating
voltage is applied by a high-frequency oscillator to the two “dees.” S is a source of positive ions.

value (30╯kV) in the opposite direction. The in which H is the magnetic field strength in
particles are accelerated across the gap, tesla, R is the radius of the particle orbit in
gaining about 30╯keV of energy in the process, centimeters, and Z and A are the atomic
and then continue on a circular path within number (charge) and mass number of the
the opposite dee. accelerated particles, respectively. The ener-
Each time the particles cross the gap they gies that can be achieved are limited by the
gain energy, so the orbital radius continu- magnetic field strength and the dee size. In a
ously increases and the particles follow an typical biomedical cyclotron with magnetic
outwardly spiraling path. The increasing field strength of 1.5 tesla and a dee diameter
speed of the particles exactly compensates for of 76╯cm, protons (Z = 1, A = 1) and α particles
the increasing distance traveled per half (Z = 2, A = 4) can be accelerated to approxi-
orbit, and they continue to arrive back at the mately 15╯MeV and deuterons (Z = 1, A = 2)
gap exactly in phase with the AC voltage. to approximately 8╯MeV.
This condition applies so long as the charge- When the particles reach the maximum
to-mass ratio of the accelerated particles orbital radius allowed within the cyclotron
remains constant. Because of their large rela- dees, they may be directed onto a target
tivistic mass increase, even at relatively low placed directly in the orbiting beam path
energies (~100╯keV), it is not practical to (internal beam irradiation). More commonly,
accelerate electrons in a cyclotron. Protons the beam is extracted from the cyclotron and
can be accelerated to 20-30╯MeV, and heavier directed onto an external target (external-
particles can be accelerated to even higher beam radiation). Typical beam currents at the
energies (in proportion to their rest mass), target are in the range of 50-100╯µA. For
before relativistic mass changes become cyclotrons using positively charged particles
limiting.* (positive ion cyclotron), the beam is electro-
Higher particle energies can be achieved in statically deflected by a negatively charged
a variation of the cyclotron called the synchro- plate and directed to the target (Fig. 5-3).
cyclotron or synchrotron, in which the AC Unfortunately electrostatic deflectors are rel-
voltage frequency changes as the particles atively inefficient, as much as 30% of the
spiral outward and gain energy. These beam current being lost during extraction.
machines are used in high-energy nuclear This “lost” beam activates the internal parts
physics research. of the cyclotron, thus making servicing and
The energy of particles accelerated in a maintenance of the cyclotron difficult.
cyclotron is given by In a negative-ion cyclotron, negatively
charged ions (e.g. H–, a proton plus two elec-
E (MeV ) ≈ 4.8 × 10−3 ( H × R × Z)2 /A (5-12)
trons) are generated and then accelerated in
the same manner as the positive ions in a
*Even at low energies, protons, deuterons, and α parti-
positive-ion cyclotron (but in the opposite
cles gain some mass when accelerated in a cyclotron.
direction because of the different polarity).
Magnetic “field shaping” is used in the cyclotron to com- When the negatively charged ions reach the
pensate for this effect. outermost orbit within the dee electrodes,
5  •  Radionuclide and Radiopharmaceutical Production 49

they are passed through a thin (5-25╯µm) 2. Addition of positive charge to the nucleus
carbon foil, which strips off the electrons and changes its atomic number. Therefore
converts the charge on the particle from nega- cyclotron-activation products usually
tive to positive. The interaction of the mag- are carrier free.
netic beam with this positive ion bends its 3. Cyclotrons generally produce smaller
direction of motion outward and onto the quantities of radioactivity than are
target (Fig. 5-4). The negative-ion cyclotron obtained from nuclear reactors. In part
has a beam extraction efficiency close to 100% this results from generally smaller acti-
and can therefore be described as a “cold” vation cross-sections for charged parti-
machine that requires minimal levels of cles as compared with neutron irradiation
shielding. Furthermore, two beams can be (see Section D) and in part from lower
extracted simultaneously by positioning a beam intensities obtained in cyclotrons
carbon-stripping foil part way into the path of as compared with nuclear reactors.
the beam, such that only a portion of the Cyclotron products are attractive for
beam is extracted to a target. The remainder nuclear medicine imaging studies because of
of the beam is allowed to continue to orbit and the high photon/particle emission ratios that
then is extracted with a second stripping foil are obtained in β+ and EC decay. Of special
onto a different target (Fig. 5-4). This allows interest are the short-lived positron emitters
two different radionuclides to be prepared 11
C (T1/2 = 20.4╯min), 13N (T1/2 = 9.97╯min), and
simultaneously. One disadvantage of negative- 15
O (T1/2 = 2.03╯min). These radionuclides rep-
ion cyclotrons is the requirement for a much resent elements that are important constitu-
higher vacuum (typically 10–5╯Pa compared ents of all biologic substances, and they 
with 10–3╯Pa for positive ion machines) can be used to label a wide variety of biologi-
because of the unstable nature of the H– ion, cally relevant tracers. Because of their very
the most commonly used particle in negative short lifetimes, these positron-emitting radio-
ion cyclotrons. nuclides must be prepared on site with a dedi-
cated biomedical cyclotron. The high cost of
3.  Cyclotron-Produced Radionuclides owning and operating such machines has
Cyclotrons are used to produce a variety of impeded their widespread use. Nevertheless,
radionuclides for nuclear medicine, some of because of the importance of several positron
which are listed in Table 5-2. General charac- emitter–labeled radiopharmaceuticals, there
teristics of cyclotron-produced radionuclides are now many hundreds of cyclotrons world-
include the following: wide producing short-lived positron-emitting
1. Positive charge is added to the nucleus isotopes for nuclear medicine imaging studies.
in most activation processes. Therefore, A typical biomedical cyclotron is shown in
the products lie below the line of stabil- Figure 5-5.
ity (see Fig. 2-9) and tend to decay by Fluorine-18 (T1/2 = 110╯min) is another
EC or β+ emission. important positron-emitting radionuclide.

H–

Stripping Stripping
foil foil

p+
To target H– Targets
To second
stripping foil
FIGURE 5-4  Left, Schematic representation of a negative-ion cyclotron. The carbon stripping foils remove two elec-
trons from negative hydrogen (H–) ions, converting them into protons (p+) that bend in the opposite direction in the
applied magnetic field. Right, The first stripping foil intersects only part of the beam, allowing two beams to be
extracted simultaneously.
50 Physics in Nuclear Medicine

TABLE 5-2â•…
SOME CYCLOTRON-PRODUCED RADIONUCLIDES USED IN NUCLEAR MEDICINE

Decay Common Production Natural Abundance Energy Threshold


Product Mode Reaction of Target Isotope* (%) (MeV)†
11
C β+, EC 14
N(p,α)11C 99.6 3.1
10 11
B(d,n) C 19.9 0
13
N β+ 16
O(p,α)13N 99.8 5.5
12
C(d,n)13N 98.9 0.35
15
O β+ 14
N(d,n)15O 99.6 0
15 15
N(p,n) O 0.37 —
18
F β+, EC 18
O(p,n)18F 0.20 2.57
20
Ne(d,α)18F 90.5 0
67 68 67
Ga (EC,γ ) Zn(p,2n) Ga 18.8 5.96
111 109
In (EC,γ ) Ag(α,2n)111In 48.2 —
111 111
Cd(p,n) In 12.8 —
123 122
I (EC,γ ) Te(d,n)123I 2.6 —
124
Te(p,3n)123I 4.8 —
201 201
Tl (EC,γ ) Hg(d,2n)201Tl 13.2 —
*Values from Browne E, Firestone RB: Table of Radioactive Isotopes. New York, 1986, John Wiley.1

Values from Helus F, Colombetti LG: Radionuclides Production, Vols I, II. Boca Raton, 1983, CRC Press.4
EC, electron capture.

FIGURE 5-5  Photograph of a negative-ion biomedical cyclotron. Left, Cyclotron within concrete shield. Right, The
cyclotron itself. (Courtesy Siemens Molecular Imaging Inc., Knoxville, TN.)

One of its main applications is in the labeling C.  RADIONUCLIDE GENERATORS


of a glucose analog, 18F-fluorodeoxyglucose
(FDG), which provides a measure of the meta- A radionuclide generator consists of a parent-
bolic rate for glucose in the cells of the body. daughter radionuclide pair contained in an
The longer half-life of the 18F label allows apparatus that permits separation and extrac-
FDG to be produced in regional distribution tion of the daughter from the parent. The
centers and shipped to hospitals tens or even daughter product activity is replenished con-
hundreds of miles away. FDG is the most tinuously by decay of the parent and may be
widely used positron-emitting radiopharma- extracted repeatedly.
ceutical with a wide range of clinical applica- Table 5-3 lists some radionuclide gene�
tions in the heart, and brain and especially in rators of interest to nuclear medicine. They 
cancer imaging. (See Chapter 18, Section F.) are an important source of metastable
5  •  Radionuclide and Radiopharmaceutical Production 51

TABLE 5-3â•…
SOME RADIONUCLIDE GENERATORS USED Normal
Shielded saline
IN NUCLEAR MEDICINE vacuum eluent
vial
Decay
Daughter* Mode T1/2 Parent T1/2
62
Cu β ,EC
+
9.7╯min 62
Zn 9.3╯hr
68
Ga β+,EC 68╯min 68
Ge 271╯d
82
Rb β ,EC
+
1.3╯min 82
Sr 25╯d
87m 87
Sr IT 2.8╯hr Y 80╯hr
99m 99
Tc IT 6╯hr Mo 66╯hr
Alumina
113m
In IT 100╯min 113
Sn 120╯d column Lead
*Generator product. shield

EC, electron capture; IT, isomeric transition.

radionuclides. The most important generator


is the 99Mo-99mTc system, because of the wide-
spread use of 99mTc for radionuclide imaging.
Technetium-99m emits γ rays (140╯keV) that
are very favorable for use with a gamma FIGURE 5-6  Cut-away view of a 99Mo-99mTc generÂ�ator.
(Adapted from A Guide to Radiopharmaceutical Quality
camera (Chapter 13). It has a reasonable Control. Billerica, MA, 1985, Du Pont Company.)
half-life (6 hours), delivers a relatively 
low radiation dose per emitted γ ray (Chapter
22), and can be used to label a wide variety
of imaging agents. More than 1850 TBq (Equation 4-28) would be approximately 23
(50,000╯Ci) of 99Mo per week are required to hours.
meet the worldwide requirements for nuclear However, these equations do not accurately
medicine procedures. predict the amount of 99mTc actually obtained
A 99Mo-99mTc generator is shown in Figure in individual elutions, because most genera-
5-6. The parent 99Mo activity in the form of tors do not yield 100% of the available activity.
molybdate ion, MoO2- 4 is bound to an alumina Typical generator elution efficiencies are 80%
(Al2O3) column. The daughter 99mTc activity, to 90%, depending on the size and type of
produced in the form of 99 m TcO4- (pertechne- generator, volume of eluant, and so on. Fur-
tate), is not as strongly bound to alumina and thermore, the efficiency can vary from one
is eluted from the column with 5 to 25╯mL  elution to the next. In practice, efficiency vari-
of normal saline. Technetium-99m activity ations of ±10% or more can occur in successive
builds up again after an elution and maximum elutions of the same generator.5 These may be
activity is available about 24 hours later caused by chemical changes in the column,
(Equation 4-28); however, usable quantities including some that are caused by the intense
are available 3 to 6 hours later. Commercially radiation levels. Failure to keep a “dry” column
prepared generators are sterilized, well in a dry state also can substantially degrade
shielded, and largely automated in operation. elution efficiency. These issues, as well as
Typically they are used for approximately 1 other complexities of 99Mo-99mTc generators,
week and then discarded because of natural are discussed in detail in references 5 and 6.
decay of the 99Mo parent. If 90% of the 99mTc activity in a generator
Decay of the 99Mo-99mTc parent-daughter is removed during an elution, the activity
pair is an example of transient equilibrium obtained would be 10% less than predicted
(see Chapter 4, Section G.3). Equation 4-25 from Equation 4-25 and Figure 4-8. Further-
and Figure 4-8 describe the buildup and decay more, the 10% residual 99mTc activity left in
of activity for such a pair. Under idealized the generator becomes “Ad(0)” in Equation
con�ditions, and a branching ratio of 0.876, the 4-25 for the next elution interval. This activ-
ratio of 99mTc↜/↜99Mo activity in a generator in a ity provides a “jump start” for regrowth of
99m
state of transient equilibrium (see Equation Tc in the generator, thereby shortening the
4-27) would be approximately 0.96, and the time to maximum activity after an elution
time to maximum activity following an elution from that predicted by Equation 4-28.
52 Physics in Nuclear Medicine

Figure 5-7A, shows the available 99mTc for the next elution interval. Figure 5-7B,
activity, relative to parent 99Mo activity, for a shows the results of such a calculation for
generator that is eluted with 90% efficiency at elutions at 0, 24, 30, 48, and 96 hours, each
24-hour intervals, starting at t = 0 hours. done with 90% elution efficiency.
Under these conditions, the activity obtained In a practical environment, it is useful to
is approximately 77% of the parent 99Mo activ- keep records comparing generator yields to
ity in the generator at the time of elution, and those predicted from the idealized equations.
the time to maximum activity after an elution This can be helpful for identifying “low-yield”
is shortened to approximately 21 hours. generators, as well as possible problems that
If a generator is eluted at irre�gular inter- may develop in an individual generator. A
vals, the situation becomes more complicated, simplified equation that can be used to predict
because the residual 99mTc activity left in the yields for elutions performed at regular
generator varies from one elution to the next. 24-hour or other similarly “long” intervals is
In this situation, the 99mTc activity in gen�
erator can be predicted using Equation 4-25, Y1 × ( e− λ p ∆t2 − e− λd ∆t2 )
using the ideal versus actual yield to esti- Y2 = (5-13)
1 − e− (λd − λ p )∆t1 
mate the amount of residual 99mTc for Ad(0)

0.8

0.6
Activity

0.4

0.2

0
0 24 48 72 98 120
A Time (hours)

0.8

0.6
Activity

0.4

0.2

0
0 24 48 72 98 120
B Time (hours)

FIGURE 5-7  Orange lines: 99Mo activity in a generator, normalized to 1.0 at t = 0. Blue lines: 99mTc activity available
for elution, assuming 90% elution efficiency. A, Generator eluted at regular 24-hour intervals. B, Generator eluted at
irregular intervals. 99mTc activities also are expressed relative to the 99Mo activity in the generator, and assume con-
sistent 90% elution efficiency from one elution to the next.
5  •  Radionuclide and Radiopharmaceutical Production 53

Here, Y2 is the predicted yield of an elution much higher, and can be loaded into genera-
(in units of activity), Y1 is the actual yield of tors containing much smaller quantities of
the immediately preceding elution, Δ t2 is the the alumina column.
time since that elution, Δ t1 is the elution The volume of alumina required in a
99
interval between that elution and the one Mo-99mTc generator is determined essen-
immediately preceding it (i.e., prior to the tially by the amount of stable 99Mo carrier
elution yielding Y1), and λp and λd are the that is present. Therefore “fission moly” gen-
decay constants of 99Mo (~0.0105╯hr-1) and erators require much smaller volumes of
99m
Tc (~0.115╯hr-1), respectively. This equation alumina per unit of 99Mo activity. They can be
assumes that the elution efficiency is con- eluted with very small volumes of normal
stant from one elution to the next and that saline (∼5╯mL), which is useful in some
there is insignificant carryover of residual dynamic imaging studies requiring bolus
99m
Tc activity in the column at the time of the injections of very small volumes of high activ-
next elution. The latter condition is reason- ity (740╯MBq, 20╯mCi) of 99mTc.
ably satisfied for 24-hr or similarly long One problem with 99mTc generators is 99Mo
elution intervals that allow for virtually com- “breakthrough,” that is, partial elution of the
plete decay of any 99mTc left over from previ- 99
Mo parent along with 99mTc from the genera-
ous elutions. tor. From the standpoint of patient radiation
Molybdenum-99 activity is obtained by safety, the amount of 99Mo should be kept to
separation from fission fragments produced a minimum. Maximum amounts, according to
in a target containing uranium or by (n,γ) Nuclear Regulatory Commission regulations,
activation of stable molybdenum (23.8% 98Mo). are 0.15╯Bq 99Mo per kBq 99mTc (0.15╯µCi 99Mo
The former, sometimes called fission moly, per mCi 99mTc). It is possible to assay 99Mo
has significantly higher specific activity and activity in the presence of much larger 99mTc
is the production method of choice for large activity using NaI(Tl) counting systems by
quantities. The reaction by which it is pro- surrounding the sample with approximately
duced sometimes is called an (n,f ) reaction, 3╯mm of lead, which is an efficient absorber
indicating neutron irradiation causing fission. of the 140╯keV γ rays of 99mTc but relatively
The production of 99Mo is described in detail transparent to the 740-780-keV γ rays of 99Mo.
in reference 7. Thus small quantities of 99Mo can be detected
Fission moly is produced by inserting a in the presence of much larger amounts of
99m
target (typically shaped as a pin, cylinder,  Tc. Some dose calibrators are provided with
or plate) containing natural uranium, enriched a lead-lined container called a “moly shield”
with 235U, via an access port into the reactor specifically for this purpose. Other radioac-
core. The target is encapsulated in aluminum tive contaminants also are occasionally found
or stainless steel. Fission neutrons from  in 99Mo-99mTc generator eluate.
the reactor core induce fission reactions in  A second major concern is breakthrough 
the target, as shown in Equation 5-1. of aluminum ion, which interferes with label-
Molybdenum-99 is one of the more abundant ing processes and also can cause clumping 
fission products (6.1% of fission products), but of red blood cells and possible microemboli.
a wide variety of others are produced as well Maximum permissible levels are 10╯µg aluÂ�
(see Fig. 5-2B). minum per mL of 99mTc solution. Chemical
After a suitable period of irradiation (typi- test kits are available from generator manu-
cally 5-7 days), the uranium target is removed, facturers to test for the presence of alumi- 
allowed to cool, and dissolved either using an num ion.
acid or alkaline dissolution process. The 99Mo
is then extracted by chemical means. Special
care is required to assure that the many other
radioactive fission products do not contami- D.  EQUATIONS FOR RADIONUCLIDE  
nate the desired 99Mo product. As well, a large
PRODUCTION
fraction of the original 235U remains in the
solution and must be stored as long-term
radioactive waste. 1.  Activation Cross-Sections
The amount of stable molybdenum pro- The amount of activity produced when a
duced by the (n,f ) reaction is small, as com- sample is irradiated in a particle beam
pared with its concentration in a target used depends on the intensity of the particle beam,
for neutron activation of 98Mo. Therefore the the number of target nuclei in the sample,
specific activity of 99Mo in “fission moly” is and the probability that a bombarding
54 Physics in Nuclear Medicine

particle will interact with a target nucleus. symbolized by σc. Some values of σc of interest
The probability of interaction is determined for radionuclide production in nuclear medi-
by the activation cross-section. The activation cine are listed in Table 5-1.
cross-section is the effective “target area” pre-
sented by a target nucleus to a bombarding 2.  Activation Rates
particle. It has dimensions of area and is sym- Suppose a sample containing n target nuclei
bolized by σ. The Systeme International units per cm3, each having an activation cross-
for σ are m2. The traditional and more com- section σ, is irradiated in a beam having a flux
monly used unit is the barn (1 b = 10–28╯m2) density ϕ (particles/cm2 sec) (Fig. 5-9). It is
or millibarn (1╯mb = 10–3╯b = 10–31╯m2). assumed that the sample thickness Δx (cm) is
Activation cross-sections for a particular sufficiently thin that ϕ does not change much
nucleus depend on the type of bombarding as the beam passes through it. The total
particle, the particular reaction involved, and number of targets, per cm2 of beam area, is n
the energy of the bombarding particles. Δx. They present a total area n ϕ Δ x per cm2
Figure 5-8 shows the activation cross-section of beam area. The reduction of beam flux in
for the production of 18F from the 18O(p,n)18F passing through the target thickness Δ x is
reaction. Note that the cross-section is a therefore
strong function of the energy of the bombard-
∆φ/φ = n σ ∆ x (5-14)
ing proton beam, and that for the reaction
shown there is a threshold energy of 2.57╯MeV The number of particles removed from the
below which production of 18F is not possible. beam (i.e., the number of nuclei activated) per
The threshold energies for several other cm2 of beam area per second is
cyclotron-produced radionuclides are given in
∆φ = n σ φ ∆ x (5-15)
Table 5-2.
Because of their importance in radionu- Each atom of target material has mass AW/
clide production by nuclear reactors, activÂ� (6.023 × 1023) g, in which AW is its atomic
ation cross-sections for thermal neutrons weight and 6.023 × 1023 is Avogadro’s number.
have been measured in some detail. These  The total mass m of target material per cm2
are called neutron-capture cross-sections, in the beam is therefore

700

600
18O(p,n)18F

500 Threshold 2.5 MeV


Cross section (mb)

400

300

200

100

0
0 2 4 6 8 10 12 14 16
Proton energy (MeV)
FIGURE 5-8  Activation cross-section versus particle energy for the reaction 18O(p,n)18F. The energy threshold for this
reaction is ~2.5╯MeV. [From Ruth TJ, Wolf AP: Absolute cross sections for the production of 18F via the 18O(p,n)18F reac-
tion. Radiochim Acta 26:21-24, 1979.]
5  •  Radionuclide and Radiopharmaceutical Production 55

Target material
area, 1 cm2

FIGURE 5-9  Activation targets


in a particle beam.
Target nuclei
area,  cm2

Particle beam,
flux density 

x

m ≈ n × ∆ x × AW/(6.023 × 1023 ) (5-16) the target nucleus is 100% abundant in the


irradiated sample (e.g., naturally occurring
and the activation rate R per unit mass of sodium is 100% 23Na). When the target is not
target material is thus 100% abundant, then the activation rate per
gram of irradiated element is decreased by the
R ≈ ∆φ/m (5-17) percentage abundance of the isotope of inter-
est in the irradiated material.
R ≈ (6.023 10 ) × σ × φ (activations/g i sec )
× 22
EXAMPLE 5-2
AW
(5-18) Potassium 42 is produced by the reaction
41
K(n,γ)42K. Naturally occurring potassium
Equation 5-18 can be used to calculate the contains 6.8% 41K and 93.2% 39K. What is the
rate at which target nuclei are activated in a activation rate of 42K per gram of K in a
particle beam per gram of target material in reactor with thermal neutron flux density
the beam. 1013 neutrons/cm2 sec? ·
EXAMPLE 5-1 Answer
What is the activation rate per gram of sodium From Table 5-1, the neutron capture cross-
for the reaction 23Na(n,γ )24Na in a reactor section of 41K is 1.2╯b. The atomic weight of
thermal neutron flux density of 1013 neutrons/ 41
K is approximately 41. Thus (Equation 5-18)
·
cm2 sec?
R ≈ (6.023 × 1023 ) × (1.2 × 10−24 ) × 1013 / 41
Answer
From Table 5-1, the thermal neutron capture ≈ 1.76 × 1011 activations/g (41 K) i sec
cross-section for 23Na is σc = 0.53╯b. The atomic
weight of sodium is approximately 23. There- The activation rate per gram of potassium is
fore (Equation 5-18) 6.8% of this, that is,
R ≈ (6.023 × 1023 ) × (0.53 × 10−24 ) × 1013 / 23
R ≈ 0.068 × (1.76 × 1011 )
≈ 1.38 × 10 11
activations/g i sec
≈ 1.20 × 1010 activations/g (K ) i sec

Equation 5-18 and Example 5-1 describe Activation rates are less than predicted by
situations in which the isotope represented by Equation 5-18 when the target thickness is
56 Physics in Nuclear Medicine

such that there is significant attenuation of specific activity (CFSA) of 42K (the half-life of
42
particle beam intensity as it passes through K is 12.4 hours).
the target (i.e., some parts of the target are
irradiated by a weaker flux density). Also, Answer
when “thick” targets are irradiated by Applying Equation 5-20 with σ = 1.2╯b, ϕ =
charged-particle beams, the particles lose 1013, and AW ≈ 41,
energy and activation cross-sections change
as the beam penetrates the target. The equa- As = 0.6023 × 1.2 × 1013 / 41

tions for these conditions are beyond the scope = 1.76 × 1011 (Bq 42
K/g 41
K)
of this book and are discussed in reference 8.
If natural potassium is used, only 6.8% is 41K.
3.  Buildup and Decay of Activity Therefore the saturation specific activity is
When a sample is irradiated in a particle
beam, the buildup and decay of product radio- As = (1.76 × 1011 ) × 0.068
activity is exactly analogous to a special case
of parent-daughter radioactive decay dis- = 1.20 × 1010 Bq 42
K/g K
cussed in Chapter 4, Section G.2. The irradi-
ating beam acts as an inexhaustible, long-lived The CFSA of 42K (T1/2 ~ 0.5 days) is (Equation
“parent,” generating “daughter” nuclei at a 4-21)
constant rate. Thus, as shown in Figure 4-7,
the product activity starts from zero and CFSA ≈ (4.8 × 1018 ) / (41 × 0.5)

increases with irradiation time, gradually ≈ (2.3 × 1017 ) Bq 42
K/g 42
K
approaching a saturation level at which its
disintegration rate equals its production rate.
The saturation level can be determined from Example 5-3 illustrates the relatively low
Equation 5-18. The saturation disintegration specific activity that typically is obtained 
rate per gram is just equal to R, the activation by (n,γ) activation procedures in a nuclear
rate per gram, so the saturation specific activ- reactor.
ity As is A parameter that is related directly to 
the saturation activity in an activation
As (Bq/g ) = R (5-19)
problem is the production rate, A′. This is
which, when combined with Equation 5-18, the rate at which radioactivity is produced
yields during an irradiation, disregarding the
simultaneous decay of radioactivity that
As (Bq/g ) ≈ 0.6023 × σ × φ/AW (5-20)
occurs during the irradiation. It is the slope
where γ is the activation cross-section in of the production curve at time t = 0 (before
barns, ϕ is the flux in units of particles per any of the generated activity has had oppor-
·
cm2 sec, and AW is the atomic weight of the tunity to decay). The production rate can be
target material. The final equation for specific shown by methods of differential calculus to
activity, A, versus irradiation time is be equal to
A(t) (Bq/g ) = As (1 − e− λt ) (5-21)
A ′ (Bq/g i hr) = ln 2 × As (Bq/g ) /T1 / 2 (hr) (5-22)
where λ is the decay constant of the product
(compare with Equation 4-26). The specific
activity of the target reaches 50% of the satu- where T1/2 is the half-life of the product.
ration level after irradiating for one daughter Reactor production capabilities may be
product half-life, 75% after two half-lives,  defined in terms of either saturation levels or
and so on (see Fig. 4-7). No matter how long production rates. If the irradiation time t is
the irradiation, the sample-specific activity “short” in comparison with the product half-
cannot exceed the saturation level. Therefore life, one can approximate the activity pro-
it is unproductive to irradiate a target for duced from the production rate according to
longer than approximately three or four times
the product half-life. A (Bq/g ) ≈ A ′ × t (5-23)
EXAMPLE 5-3
≈ ln 2 × As × t/T1 / 2 (5-24)
What is the saturation specific activity for the
42
K production problem described in Example
5-2? Compare this with the carrier-free where t and T1/2 must be in the same units.
5  •  Radionuclide and Radiopharmaceutical Production 57

radionuclides for nuclear medicine procedures


EXAMPLE 5-4
is presented in Table 5-4.
What is the production rate of 42K for the
problem described in Example 5-2, and what 2.  Specific Considerations
specific activity would be available after an The type and energy of emissions from the
irradiation period of 3 hours? (The half-life of radionuclide determine the availability of
42
K is 12.4 hours.) useful photons or γ rays for counting or
imaging. For external detection of a radio�
Answer nuclide inside the body, photons or γ rays in
From Example 5-3, As = 1.20 × 1010 Bq 42
K/g the 50-600╯keV energy range are suitable.
K. Therefore (Equation 5-22) Very-low-energy photons and γ rays (<↜50╯keV),
or particulate radiation, have a high likeli-
A ′ = 0.693 × (1.20 × 1010 ) /12.4 hood of interacting in the body and will not

≈ 6.7 × 108 Bq 42
K/g K i hr in general escape for external detection. The
presence of such low energy or particulate
After 3 hours, which is “short” in comparison emissions increases the radiation dose to the
with the half-life of 42K, the specific activity patient. An example of this is 131I, which
of the target is (Equation 5-23) decays by (β–,γ) emitting a β– particle, fol-
lowed by γ rays at 364 (82%), 637 (6.5%), 284
A(Bq/g ) ≈ (6.7 × 108 ) × 3 (5.8%), or 80╯keV (2.6%). The γ rays are in an
appropriate range for external detection;
≈ 2.0 × 109 Bq 42
K/g K
however, the β– particle contributes addi-
tional dose as compared with radionuclides
that decay by (EC,γ).
E.  RADIONUCLIDES FOR NUCLEAR The physical half-life of the radionuclide
MEDICINE should be within the range of seconds to days
(preferably minutes to hours) for clinical
applications. If the half-life is too short, there
1.  General Considerations is insufficient time for preparation of the
In elemental form, radionuclides themselves radiopharmaceutical and injection into the
generally have a relatively small range of bio- patient. An example of this is the positron
logically interesting properties. For example, emitter 15O (T1/2 = 122╯sec). This limits
131
I as an iodide ion (I–) is useful for studying 15
O-labeled radiopharmaceuticals to simple
the uptake of elemental iodine in the thyroid compounds such as H215O and C15O. If the
or in metastatic thyroid cancer or for deliver- half-life were longer, a much wider range of
ing a concentrated radiation dose to thyroid compounds could be labeled with 15O. Other
tissues for therapeutic purposes; however, radionuclides have half-lives that are too long
elemental iodine has no other generally inter- for practical purposes. Most of the radiation
esting properties for medical usage. For this is emitted outside of the examination time,
reason, most studies in nuclear medicine which can result in a high radiation dose to
employ radiopharmaceuticals, in which the the patient in relation to the number of decays
radionuclide is attached as a label to a com- detected during the study. Long-lived radio-
pound that has useful biomedical properties. nuclides also can cause problems in terms of
For most applications, the radiopharma- storage and disposal. An example of a very
ceutical is injected into the patient, and the long-lived radionuclide that is not used in
emissions are detected using external imaging human studies because of half-life consider-
or counting systems. Certain practical require- ations is 22Na (T1/2 = 2.6╯yr).
ments must be met for a radionuclide to be a The specific activity of the radionuclide
useful label. A portion of the Chart of Nuclides largely determines the mass of a compound
was shown in Figure 3-11. A complete chart that is introduced for a given radiation dose.
contains hundreds of radionuclides that could Because nuclear medicine relies on the use of
conceivably be used for some biomedical appli- subpharmacologic tracer doses that do not
cation, either in elemental form or as a radio- perturb the biologic system under study, the
pharmaceutical label. However, the number mass should be low and the specific activity
of radionuclides actually used is much smaller high. At low specific activities, only a small
because of various practical considerations,  fraction of the molecules in the sample are
as discussed in the following section. A list� radioactive and therefore signal producing,
ing of some of the more commonly used whereas the rest of the molecules add to the
58 Physics in Nuclear Medicine

TABLE 5-4â•…
PHYSICAL PROPERTIES OF RADIONUCLIDES USED IN NUCLEAR MEDICINE STUDIES

Principal Photon Primary


Radionuclide Decay Mode Emissions Half-Life Use
11
C β+ 511╯keV 20.4╯min Imaging
13
N β+
511╯keV 9.97╯min Imaging
15
O β+ 511╯keV 2.03╯min Imaging
18
F β+
511╯keV 110╯min Imaging
32
P β– — 14.3╯d Therapy
67
Ga EC 93, 185, 300╯keV 3.26╯d Imaging
82
Rb β+ 511╯keV 1.25╯min Imaging
89
Sr β–
— 50.5╯d Therapy
99m
Tc IT 140╯keV 6.02╯hr Imaging
111
In EC 172, 247╯keV 2.83╯d Imaging
123
I EC 159╯keV 13.2╯hr Imaging
125
I EC 27-30╯keV x rays 60.1╯d In vitro
assays
131
I β– 364╯keV 8.04╯d Therapy/
imaging
153
Sm β– 41, 103╯keV 46.7╯hr Therapy
186
Re β–
137╯keV 3.8╯d Therapy
201
Tl EC 68-80╯keV x rays 3.04╯d Imaging
EC, electron capture; IT, isomeric transition.

mass of the compound being introduced, The chemical properties of the radio�nuclide
without producing signal. Theoretically, the also are an important factor. Radionuclides of
attainable specific activity of a radionuclide is elements that can easily produce useful pre-
inversely proportional to its half-life, although cursors (chemical forms that react readily to
in practice, many other factors (e.g., the abun- form a wide range of labeled products) and
dance of stable isotopes in air and glassware) that can undergo a wide range of chemical
can determine the actual specific activity of syntheses are preferred (e.g., 123I, 18F, and
11
the injected labeled compound, as described C). Radionuclides of elements that are
in Section F.1. easily incorporated into biomolecules, without
The radionuclidic purity is defined as the significantly changing their biochemical
fraction of the total radioactivity in a sample properties, also are attractive. Examples are
11
that is in the form of the desired radionuclide. C, 13N, 15O, elements that are found natu-
Radionuclidic contaminants arise in the pro- rally in many biomolecules. Metals such 
duction of radionuclides and can be signifi- as 99mTc and 67Ga also are widely used as
cant in some situations. The effect of these labels in nuclear medicine, because of the
contaminants is to increase the radiation dose desirable imaging properties of the radio�
to the patient. They may also increase detec- nuclide. To incorporate such elements into
tor dead time, and if the energy of the emis- biologically relevant molecules is challenging
sions falls within the acceptance window of but can be achieved by chelation and other
the detector system, contaminants may result techniques that seek to “hide” or shield the
in incorrect counting rate or pixel intensities metal atom from the biologically active sites
in images. Of concern in radionuclide gener� of the molecule.
ator systems is contamination with the long- Finally, the cost and complexity of pre�
lived parent radionuclide. In the case of the paring a radionuclide must be considered.
99
Mo-99mTc generator, the radionuclidic purity Sufficient quantities of radionuclide for radio-
of the 99mTc must be higher than 99.985%, as pharmaceutical labeling and subsequent
discussed in Section C. patient injection must be produced at a cost
5  •  Radionuclide and Radiopharmaceutical Production 59

(both materials and labor) consistent with  form) is also important, with desirable values
today’s health care market. of greater than 99%.
The dynamic time course of the radiopharma�
ceutical in the body must be considered. Some
radiopharmaceuticals have rapid uptake and
F.  RADIOPHARMACEUTICALS FOR clearance, whereas others circulate in blood
CLINICAL APPLICATIONS with only slow uptake into tissues of interest.
The rate of clearance of the radiopharmaceu-
As noted earlier, radionuclides almost always tical from the body is called the biologic half-
are attached as labels to compounds of  life. Together with the physical half-life of the
biomedical interest for nuclear medicine radionuclide, this determines the number of
applications. Because of the practical consid- radioactive decays that will be observed from
erations discussed in the preceding section, a particular region of tissue as a function of
the number of different radionuclides rou- time. These two factors also are important
tinely used in nuclear medicine is relatively factors in determining the radiation dose to
small, perhaps fewer than a dozen even in the subject (see Chapter 22, Section B). It is
large hospitals. On the other hand, the important that radiopharmaceuticals be
number of labeled compounds is much larger labeled with radionuclides with half-lives
and continuously growing, owing to very that are long enough to encompass the tem-
active research in radiochemistry and radio- poral characteristics of the biologic process
pharmaceutical preparation. The following being studied. For example, labeled anti�
sections summarize the properties of some bodies generally require hours to days before
radiopharmaceuticals that enjoy widespread significant uptake in a target tissue is reached
usage at this time. More detailed discussions and blood levels have dropped sufficiently for
are found in the articles and texts listed in the target to be visualized. Short-lived radio-
the Bibliography. nuclides with half-lives of minutes or less
would not be useful in this situation.
1.  General Considerations The radiopharmaceutical must not be toxic
The final specific activity of a radiopharma- at the mass levels administered. This require-
ceutical (as opposed to the radionuclide) is ment usually is straightforward in nuclear
determined by losses in specific activity that medicine studies because of the relatively
occur during the chemical synthesis of the high specific activity of most radiopharmaceu-
radiopharmaceutical. This is particularly an ticals, resulting in typical injections of micro-
issue for isotopes of elements that have high gram to nanogram quantities of material.
natural abundances. For example, the theo- Generally, milligram levels of materials are
retical maximum specific activity for 11C is 3.5 required for pharmacologic effects. Safety
× 108╯MBq/µmol (CFSA from Equation 4-22), concerns also require that all radiopharma-
whereas the specific activity of 11C-labeled ceuticals be sterile and pyrogen-free prior to
radiopharmaceuticals actually obtained in injection. Organisms can be removed by fil-
practice is approximately 105╯MBq/µmol. This tration through a sterile filter with a pore size
is largely because of the presence of stable of 0.22╯µm or better. Use of pharmaceutical-
carbon in the air (as CO2) and in the materials grade chemicals, sterile water, and sterilized
of the reaction vessels and tubing used in the equipment can minimize the risk of pyrogens.
chemical synthesis procedure. Finally, the pH of the injected solution should
Radiochemical purity is the fraction of the be appropriate.
radioactivity in the sample that is present in
the desired chemical form. Radiochemical 2.  Labeling Strategies
impurities usually stem from competing There are two distinct strategies for labeling
chemical reactions in the radiolabeling of small molecules with radionuclides. In
process or from decomposition (chemical or direct substitution, a stable atom in the mol-
radiation induced) of the sample. Radiochem- ecule is replaced with a radioactive atom of
ical impurities are problematic in that their the same element. The compound has exactly
distribution in the body is generally different, the same biologic properties as the unlabeled
thus adding a background to the image of the compound. This allows many compounds of
desired compound. The typical radiochemical biologic relevance to be labeled and studied in
purity for radiopharmaceuticals is higher vivo using radioactive isotopes of elements
than 95%. Chemical purity (the fraction of the that are widely found in nature (e.g., hydro-
sample that is present in the desired chemical gen, carbon, nitrogen, and oxygen). An
60 Physics in Nuclear Medicine

example is replacing a 12C atom in glucose


with a 11C atom to create 11C-glucose. This 3.  Technetium-99m-Labeled
radiopharmaceutical will undergo the same Radiopharmaceuticals
distribution and metabolism in the body as The 99Mo-99mTc generator produces techne-
unlabeled glucose. tium in the form of 99 m TcO4- . A number of
The second approach is to create analogs. “cold kits” are available that allow different
99m
This involves modifying the original com- Tc complexes to be produced by simply
pound. Analogs allow the use of radioactive mixing the 99 m TcO4- and the contents of the
isotopes of elements that are not so widely cold kit together. The cold kit generally con-
found in nature but that otherwise have ben- tains a reducing agent, usually stannous
eficial imaging properties (e.g., fluorine and chlor�ide, which reduces the 99mTc to lower oxi-
iodine). Analogs also allow chemists to benefi- dation states, allowing it to bind to a complex-
cially change the biologic properties of the ing agent (also known as the ligand ) to form
molecule by changing the rates of uptake, the radiopharmaceutical. Using these kits, a
clearance, or metabolism. For example, range of 99mTc-labeled radiopharmaceuticals
replacing the hydroxyl (OH) group on the that are targeted to different organ systems
second carbon in glucose with 18F results in and different biologic processes can be pre-
FDG, an analog of glucose. This has the pared quickly and conveniently in the hos�
advantage of putting a longer-lived radio� pital setting. Table 5-5 lists a few examples of
active tag onto glucose compared with 11C; 99m
Tc radiopharmaceuticals that are prepared
and even more important, FDG undergoes from kits.
only the first step in the metabolic pathway
for glucose, thus making data analysis much 4.  Radiopharmaceuticals Labeled with
more straightforward (see Chapter 21, Section Positron Emitters
E.5). FDG is now a widely used radiopharma- Positron emitters such as 11C, 13N, and 15O can
ceutical for measuring metabolic rates for be substituted for stable atoms of the same
glucose. The downside to analogs are that elements in compounds of biologic impor-
they behave differently from the native com- tance. This results in radiolabeled compounds
pound, and these differences need to be care- with exactly the same biochemical properties
fully understood if the analog is used to as the original compound. Alternatively, 18F,
provide a measure of the biologic function another positron-emitting radionuclide, can
related to the native molecule. be substituted for hydrogen to produce labeled
An alternative approach to labeling mater� analogs. Several hundreds of compounds have
ials that is possible only for larger bio� been synthesized with 11C, 13N, 15O, or 18F
molecules is to keep the radioactive label labels for imaging with positron emission
away from the bio�logically active site of the tomography. The short half-life of 11C, 13N,
molecule. Thus large molecules (e.g., antibod- and 15O requires in-house radionuclide pro-
ies, peptides, and proteins) may be labeled duction in a biomedical cyclotron and rapid
with many different radionuclides, with synthesis techniques to incorporate them into
minimal effect on their biologic properties. radiopharmaceuticals. On the other hand, the

TABLE 5-5â•…
SOME 99mTc-LABELED RADIOPHARMACEUTICALS PREPARED FROM KITS

Compound Abbreviation Stands for Applications


99m
Tc-MDP Methylene diphosphonate Bone scans
99m
Tc-DMSA 2,3-Dimercaptosuccinic acid Renal imaging
99m
Tc-DTPA Diethylenetriaminepenta acetic acid Renal function
99m
Tc-sestamibi 2-Methoxy-2-methylpropyl isonitrile Myocardial perfusion, breast
cancer
99m
Tc-HMPAO Hexamethylpropylene-amine oxime Cerebral perfusion
99m
Tc-HIDA N-(2,6-dimethylphenol-carbamoylmethyl)- Hepatic function
iminodiacetic acid
99m
Tc-ECD N,N’-1,2-ethylenediyl-bis-L-cysteine diethylester Cerebral perfusion
5  •  Radionuclide and Radiopharmaceutical Production 61

relatively longer half-life of 18F permits its determine the location of the radiopharma-
distribution within a radius of a few hundred ceutical within the body. Often, the rate of
miles from the site of production, thus obviat- change of radiopharmaceutical localization
ing the need of a cyclotron in the nuclear within a specific tissue (the rate of uptake or
medicine imaging facility. clearance) is also important and is measured
The most widely used positron-labeled by acquiring multiple images as a function of
radiopharmaceutical is the glucose analog time. The imaging systems used in nuclear
FDG. Glucose is used by cells to produce ade- medicine studies are discussed in Chapters
nosine triphosphate, the energy “currency” of 13, 14, and 17-19.
the body, and accumulation of FDG in cells is
proportional to the metabolic rate for glucose. REFERENCES
Because the energy demands of cells are 1. Browne E, Firestone RB: Table of Radioactive Isotopes,
altered in many disease states, FDG has been New York, 1986, John Wiley.
shown to be a sensitive marker for a range  2. Wang Y: Handbook of Radioactive Nuclides, Cleve-
of clinically important conditions, including land, 1969, Chemical Rubber Company.
3. Schwartz SW, Gaeble GG, Welch MJ: Accelerators 
neurodegenerative diseases, epilepsy, coro- and positron emission tomography radiopharmaceuti-
nary artery disease, and most cancers and cals. In Sandler MP, Coleman RE, Patton JA, et al,
their metastases. editors: Diagnostic Nuclear Medicine, ed 4, Philadel-
phia, 2003, Lippincott, Williams & Wilkins, pp
5.  Radiopharmaceuticals for Therapy 117-132.
Applications 4. Helus F, Colombetti LG: Radionuclides Production,
Vols I, II, Boca Raton, 1983, CRC Press.
Other radiopharmaceuticals are designed for 5. Holland ME, Deutsch E, Heineman WR: Studies 
therapy applications. These are normally on commercially available 99Mo/99mTc radionuclide
labeled with a β– emitter, and the radiophar- generators—II. Operating characteristics and behav-
ior of 99Mo/99mTc generators. Appl Radiat Isot 37:173-
maceutical is targeted against abnormal cells, 180, 1986.
commonly cancer cells. The β– emitter depos- 6. Boyd RE: Molybdenum-99: Technetium-99m genera-
its radiation only within a small radius (typi- tor. Radiochim Acta 30:123-145, 1982.
cally 0.1 to 1╯mm) and selectively kills cells 7. Medical Isotope Production Without Highly Enriched
Uranium. Washington, D.C., 2009, National Acade-
in this region through radiation damage.  mies Press.
If the radiopharmaceutical is more readily 8. Murray RL: Nuclear Energy, ed 5, Boston, 2001, But-
accumulated by cancer cells than normal terworth Heinemann.
cells, a therapeutic effect can be obtained.
BIBLIOGRAPHY
6.  Radiopharmaceuticals in Clinical
Further information on radionuclide production
Nuclear Medicine and radiopharmaceutical preparation can be
Many different radiopharmaceuticals have found in the following:
been approved for use in clinical nuclear Knapp FF, Mirzadeh S: The continuing role of radionu-
medicine studies. Each of these radio� clide generator systems for nuclear medicine. Eur J
pharmaceuticals is targeted to measuring a Nucl Med 21:1151-1165, 1994.
Lieser KH: Nuclear and Radiochemistry, ed 2, Weinheim,
specific biologic process, and therefore what Germany, 2001, Wiley VCH.
is measured depends directly on which ra� Sampson CB: Textbook of Radiopharmacy: Theory and
diopharmaceutical is administered to the Practice, ed 2, New York, 1994, Gordon & Breach.
patient. Some of the more common radio- Tewson TJ, Krohn KA: PET radiopharmaceuticals: State-
of-the-art and future prospects. Semin Nucl Med
pharmaceuticals are listed in Table 1-1 and 28:221-234, 1998.
Table 5-5. Welch MJ, Redvanly CS: Handbook of Radiopharmaceu-
Most radiopharmaceuticals are used in ticals: Radiochemistry and Applications. Chichester,
conjunction with imaging systems that can England, 2003, John Wiley & Sons.
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chapter
6 
Interaction of
Radiation with Matter
The two most important general types of radi- For these reasons, this section emphasizes 
ation emitted during radioactive decay are the interactions of electrons with matter.
charged particles, such as α particles and Except for differences in sign, the forces expe-
β particles, and electromagnetic radiation rienced by positive and negative electrons
(photons), such as γ rays and x rays. These (e.g., β+ and β− particles) are identical. There
radiations transfer their energy to matter as are minor differences between the ionizing
they pass through it. The principle mecha- interactions of these two types of particles, but
nisms for energy transfer are ionization and they are not of importance to nuclear medicine
excitation of atoms and molecules. Most of and are not discussed here. In this chapter, the
this energy ultimately is degraded into heat term electrons is meant to include both the
(atomic and molecular vibrations); however, positive and negative types. The annihilation
the ionization effect has other important con- effect, which occurs when a positive electron
sequences. For this reason, the radiations (positron) has lost all of its kinetic energy and
emitted during radioactive decay often are stopped, is discussed in Chapter 3, Section G.
called ionizing radiations. The processes by The “collisions” that occur between a
which ionizing radiations transfer their charged particle and atoms or molecules
energy to matter are fundamental to the involve electrical forces of attraction or repul-
detection of radiation, discussed in Chapter 7. sion rather than actual mechanical contact.
As well, they are important for radiation For example, a charged particle passing near
dosimetry, discussed in Chapter 22. In this an atom exerts electrical forces on the orbital
chapter, we discuss those processes in some electrons of that atom. In a close encounter,
detail. Because the mechanisms differ, they the strength of the forces may be sufficient to
are discussed separately for particulate cause an orbital electron to be separated from
versus electromagnetic radiation. the atom, thus causing ionization (Fig. 6-1A).
An ionization interaction looks like a collision
between the charged particle and an orbital
A.  INTERACTIONS OF CHARGED electron. The charged particle loses energy in
PARTICLES WITH MATTER the collision. Part of this energy is used to
overcome the binding energy of the electron
to the atom, and the remainder is given to the
1.  Charged-Particle Interaction ejected secondary electron as kinetic energy.
Mechanisms Ionization involving an inner-shell electron
High-energy charged particles, such as α par- eventually leads to the emission of character-
ticles or β particles, lose energy and slow istic x rays or Auger electrons; however, these
down as they pass through matter, as a result effects generally are very small, because most
of collisions with atoms and molecules. High- ionization interactions involve outer-shell
energy electrons, which also are charged par- electrons. The ejected electron may be suffi-
ticles, are a byproduct of these collisions. In ciently energetic to cause secondary ioniza-
addition, high-energy electrons are generated tions on its own. Such an electron is called a
when γ rays and x rays interact with matter, delta (δ) ray.
and they are emitted in internal conversion A less-close encounter between a charged
(see Chapter 3, Section E) and in the Auger particle and an atom may result in an orbital
effect (see Chapter 2, Section C.3). electron being raised to an excited state, thus
63
64 Physics in Nuclear Medicine

Incident
particle ( or )

Nucleus Nucleus
Secondary
electron

Bremsstrahlung

Nucleus

FIGURE 6-1  Interactions of charged particles with atoms. A, Interaction with an orbital electron resulting in ioniza-
tion. Less-close encounters may result in atomic excitation without ionization. B, Interaction with a nucleus, resulting
in bremsstrahlung production. [Repulsion by orbital electron (A) and attraction toward nucleus (B) indicates incident
particles are negatively charged in the examples shown.]

causing atomic or molecular excitation. These which the particle is only slightly deflected)
interactions generally result in smaller energy up to a maximum equal to the full energy of
losses than occur in ionization events. The the incident particle (events in which the par-
energy transferred to an atom in an excitation ticle is virtually stopped in the collision).
interaction is dissipated in molecular vibra- Figure 6-2 shows the energy spectrum for
tions, atomic emission of infrared, visible, bremsstrahlung photons generated in alumi-
ultraviolet radiation, and so forth. num by particles from a 90Sr-90Y source
A third type of interaction occurs when mixture ( Eβmax = 2.27 MeV) and illustrates
the charged particle actually penetrates the that most of the photons are in the lower
orbital electron cloud of an atom and interacts energy range.
with its nucleus. For a heavy charged particle
of sufficiently high energy, such as an α par-
ticle or a proton, this may result in nuclear 2.  Collisional Versus Radiation Losses
reactions of the types used for the production Energy losses incurred by a charged particle
of radionuclides (see Chapter 5); however, for in ionization and excitation events are called
both heavy charged particles and electrons, collisional losses, whereas those incurred in
a more likely result is that that particle will nuclear encounters, resulting in bremsstrah-
simply be deflected by the strong electrical lung production, are called radiation losses.
forces exerted on it by the nucleus (Fig. 6-1B). In the nuclear medicine energy range, colli-
The particle is rapidly decelerated and loses sional losses are by far the dominating factor
energy in the “collision.” The energy appears (See Fig. 6-5). Radiation losses increase with
as a photon of electromagnetic radiation, increasing particle energy and with increas-
called bremsstrahlung (German for “braking ing atomic number of the absorbing medium.
radiation”). An approximation for percentage radiation
The energy of bremsstrahlung photons can losses for β particles having maximum energy
range anywhere from nearly zero (events in Eβmax (MeV) is
6  •  Interaction of Radiation with Matter 65

10

8
Relative number of photons
7

0
0 40 80 120 160 200 240
Energy (keV)
FIGURE 6-2  Bremsstrahlung spectrum for β particles emitted by 90Sr + 90Y ( Eβmax = 2.27 MeV) mixture in aluminum.
(Adapted from Mladjenovic M: Radioisotope and Radiation Physics. New York, 1973, Academic Press, p 121.)

percentage radiation losses ≈ (ZEβmax / 3000) (7.9 × 1.7 / 3000) × 100% ≈ 0.4%
× 100%
(6-1) and in lead (Z = 82) they are

where Z is the atomic number of the absorber. (82 × 1.7 / 3000) × 100% ≈ 4.6%
This approximation is accurate to within
appro�ximately 30%. For a mixture of ele- The remaining 99.6% and 95.4%, respectively,
ments, an “effective” atomic number for are dissipated as collisional losses.
bremsstrahlung production should be used
Example 6-1 demonstrates that high-
Zeff = ∑ fi Zi2 ∑ fi Zi (6-2) energy electrons in the nuclear medicine
i energy range dissipate most of their energy
in collisional losses. Bremsstrahlung produc-
where f1,â•›f2, … are the fractions by weight of tion accounts for only a small fraction of their
the elements Z1, Z2, … in the mixture. energy. Nevertheless, bremsstrahlung can be
important in some situations, such as the
EXAMPLE 6-1 shielding of relatively large quantities of an
Calculate the percentage of radiation losses energetic β-particle emitter (e.g., hundreds of
for 32P β particles in water and in lead. MBq of 32P). The β particles themselves are
easily stopped by only a few millimeters of
Answer plastic, glass, or lead (see Section B.2);
Eβmax = 1.7 MeV for 32P. Water comprises 2 18 however, the bremsstrahlung photons they
parts hydrogen (Z = 1, AW ≈ 1) and 16 18 parts generate are much more penetrating and may
oxygen (Z = 8, AW ≈ 16); thus its effective require additional shielding around the
atomic number for bremsstrahlung produc- primary β-particle shielding. It is helpful in
tion is (Equation 6-2) such situations to use a low-Z material, such
as plastic, for the primary β-particle shield-
[(1/ 9 )(1) (8 / 9 )(8 ) ]
2 2
Zeff = = 7 .9 ing, and then to surround this with a higher-Z

[(1/ 9 )(1) + (8 / 9 )(8 )] material, such as lead, for bremsstrahlung
shielding (Fig. 6-3). This arrangement mini-
The percentage of radiation losses in water mizes bremsstrahlung production by the β
are therefore (Equation 6-1) particles in the shielding material.
66 Physics in Nuclear Medicine

When a heavy particle, such as an α par-


ticle, collides with an orbital electron, its
direction is virtually unchanged and it loses
only a small fraction of its energy (rather like
Lead a bowling ball colliding with a small lead
shot). The maximum fractional energy loss 
by a heavy particle of mass M colliding with
a light particle of mass m is approximately
4╯m/M. For an α particle colliding with
Glass or an electron, this amounts to only approxi-
plastic vial mately 0.05% [4 × (1/1840)/4 ≈ (1/2000)].
Heavy particles also undergo relatively few
bremsstrahlung-producing collisions with
nuclei. As a result, their tracks tend to be
straight lines, and they experience an almost
continuous slowing down in which they lose
small amounts of energy in a large number of
individual collisions.
By contrast, electrons can undergo large-
angle deflections in collisions with orbital
electrons and can lose a large fraction of their
-emitting radioactive solution energy in these collisions. These events 
FIGURE 6-3  Preferred arrangement for shielding ener- are more like collisions between billiard 
getic β-emitting radioactive solution. Glass or plastic balls of equal mass. Electrons also undergo
walls of a vial stop the β particles with minimum brems- occasional collisions with nuclei in which 
strahlung production, and a lead container absorbs the they are deflected through large angles 
few bremsstrahlung photons produced.
and bremsstrahlung photons are emitted. For
these reasons, electron tracks are tortuous,
and their exact shape and length are
unpredictable.
Bremsstrahlung production and radiation An additional difference between electrons
losses for α particles and other heavy charged and heavy particles is that for a given amount
particles are very small because the amount of kinetic energy, an electron travels at a
of bremsstrahlung production is inversely much faster speed. For example, a 4-MeV α
proportional to the mass of the incident particle travels at approximately 10% of the
charged particle. Alpha particles and protons speed of light, whereas a 1-MeV electron
are thousands of times heavier than electrons travels at 90% of the speed of light. As a
and therefore dissipate only a few hundredths result, an electron spends a much briefer
of 1% or less of their energy as radiation time in the vicinity of an atom than does an
losses. These particles, even at energies up to α particle of similar energy and is therefore
100 MeV, dissipate nearly all of their energy less likely to interact with the atom. Also, an
as collisional losses. electron carries only one unit of electrical
charge, versus two for α particles, and thus
3.  Charged-Particle Tracks exerts weaker forces on orbital electrons. For
A charged particle passing through matter these reasons, electrons experience less fre-
leaves a track of secondary electrons and quent interactions and lose their energy more
ionized atoms in its path. In soft tissue and slowly than α parÂ�ticles; they are much less
materials of similar density, the tracks are densely ionizing, and they travel farther
typically approximately 100╯µm wide, with before they are stopped than α particles or
occasionally longer side tracks generated by other heavy charged particles of similar
energetic δ rays. The tracks are studied in energy.
nuclear physics using film emulsions, cloud To illustrate these differences, Figure 6-4
chambers,* and other devices. shows (in greatly enlarged detail) some 
withdrawn to suddenly decrease the pressure and tem-
*A cloud chamber consists of a cylinder with a piston at perature of the vapor, droplets of condensed liquid are
one end and viewing windows at the other end and formed around ionized nuclei. Ionization tracks existing
around the sides. The cylinder contains a water-alcohol in the chamber at the time thus can be observed and
vapor mixture under pressure. When the piston is rapidly photographed through the viewing windows.
6  •  Interaction of Radiation with Matter 67

-particle track Energy loss rates and ionization densities


depend on the type of particle and its energy
 Rays and on the composition and density of the
absorbing medium. Density affects energy
loss rates because it determines the density
of atoms along the particle path. In the
High-energy nuclear medicine energy range (10 MeVâ•›),
electron tracks
energy loss rates for charged particles increase
linearly with the density of the absorbing
medium. (At higher energies, density effects
are more complicated, as discussed in the
sources cited in the references and bibliogra-
phy at the end of this chapter.)
Figure 6-5 shows collisional and radiation
Bremsstrahlung
energy loss rates for electrons in the energy
FIGURE 6-4  Representation of α particle and electron range of 0.01-10 MeV in water and in lead.
tracks in an absorber. Alpha particles leave short, Energy loss rates Δâ•›E /Δ x are expressed in
straight, densely ionized tracks, whereas electron paths
are tortuous and much longer; δ rays are energetic sec- ·
MeV/g cm–2 to normalize for density effects
ondary electrons. ∆ E /∆ x (MeV/cm)
∆ E /∆ x (MeV/g i cm −2 ) =
ρ (g/cm 3 )
possible tracks for β particles and for α par- (6-3)
ticles in water. The actual track lengths are
on the order of microns for α particles and Thus for a given density ρ the energy loss rate
fractions of a cenÂ�timeter for β particles. This in MeV/cm is given by
is discussed further in Section B.
∆ E /∆ x (MeV/cm) = [∆ E /∆ x (MeV/g i cm −2 )]

4.  Deposition of Energy Along   × ρ (g/cm 3 )


(6-4)
a Charged-Particle Track
The rate at which a charged particle loses Collisional loss rates Δâ•›Eâ•›/Δxcoll decrease
energy determines the distance it will travel with increasing electron energy, reflecting the
and the density of ionization along its track. velocity effect mentioned in Section A.3. Also,

10

Water-collisional
Energy loss rate (MeV/g·cm2)

Lead-collisional
1

0.1

Lead-radiation

Water-radiation
0.01
0.01 0.1 1 10
Electron energy (MeV)
FIGURE 6-5  Collisional (ionization, excitation) and radiation (bremsstrahlung) energy losses versus electron energy
in lead and in water. (Adapted from Johns HE, Cunningham JR: The Physics of Radiology, 3rd ed. Springfield, IL,
1971, Charles C Thomas, p 47.)
68 Physics in Nuclear Medicine

Δâ•›E/Δxcoll decreases with increasing atomic the electron shells). Ionization potentials for
number of the absorbing medium because in gases are in the range 10-15 eV. The differ-
atoms of higher atomic number, inner-shell ence between W and I is energy dissipated by
electrons are “screened” from the incident a charged particle in nonionizing excitation
electron by layers of outer-shell electrons, events. Apparently, more than half of the
making interactions with inner-shell elec- energy of a charged particle is expended in
trons less likely in these atoms. Gram for this way. Similar ratios between W and I are
gram, lighter elements are better absorbers of found in semiconductor solids, except that in
electron energy than are heavier elements. these materials the values of W and I are both
Radiation loss rates Δâ•›E /Δâ•›xâ•›rad increase approximately a factor of 10 smaller than for
with increasing electron energy and increas- gases (see Table 7-1).
ing atomic number of the absorber. This is Because W does not change appreciably
discussed in Section A.2. with particle type or energy, specific ioniza-
The total energy loss rate of a charged tion is proportional to linear energy transfer
particle, Δâ•›E /Δâ•›xâ•›total, expressed in MeV/cm, is L along a charged particle track. Figure 6-6
also called the linear stopping power (Sl). A shows specific ionization in air for electrons
closely related parameter is the linear energy as a function of their energy. The curve indi-
transfer (LET), L, which refers to energy lost cates that specific ionization increases with
that is deposited “locally” along the track. L decreasing energy down to an energy of
differs from Sl in that it does not include approximately 100 eV. This behavior reflects
radiation losses. These result in the produc- the fact that energy loss rates and L increase
tion of bremsstrahlung photons, which may as the electron slows down. Below approxi-
deposit their energy at some distance from mately 100 eV, the electron energy is inade-
the particle track. For both electrons and α quate to cause ionizations efficiently, and
particles in the nuclear medicine energy specific ionization decreases rapidly to zero.
range, however, radiation losses are small, Specific ionization values for α particles
and the two quantities Sl and L are practi- are typically 100 times greater than for elec-
cally identical. trons of the same energy because of their
The average value of the linear energy greater charge and much lower velocities.
transfer measured along a charged-particle This leads to greater rates of energy loss, as
track, L, is an important parameter in health discussed in previously in Section A.3.
physics (see Chapter 23, Section A.1.). L The fact that specific ionization increases
usually is expressed in units of keV/µm. For as a particle slows down leads to a marked
electrons in the energy range of 10╯keV to 10 increase in ionization density near the end of
MeV traveling through soft tissue, L has its track. This effect is especially pronounced
values in the range of 0.2-2╯keV/µm. Lower- for heavy particles. Figure 6-7 shows a graph
energy electrons, for example, β particles of ionization density versus distance traveled
emitted by 3H ( Eβ â•›= 5.6╯keV), have somewhat for α particles in air. The peak near the end
higher values of L. Alpha particles have of the α-particle range is called the Bragg
values of L ≈ 100╯keV/µm. ionization peak.* A similar increase in ioniza-
Specific ionization (SI) refers to the total tion density is seen at the end of an electron 
number of ion pairs produced by both primary track; however, the peak occurs when the 
and secondary ionization events per unit of electron energy has been reduced to less than
track length along a charged particle track. approximately 1╯keV, and it accounts for only
The ratio of linear energy transfer divided by a small fraction of its total energy.
specific ionization is W, the average energy
expended per ionization event: 5.  The Cerenkov Effect
An additional charged-particle interaction
W = L / SI (6-5)
deserving brief mention is the Cerenkov (pro-
This quantity has been measured and found nounced cher-en′-kof ) effect. This effect occurs
to have a relatively narrow range of values in when a charged particle travels in a medium
a variety of gases (25-45 eV per ion pair or, at a speed greater than the speed of light in
equivalently, per ionization) independent of that medium. The restriction that a particle
the type or energy of the incident particle.
The value for air is 33.7 eV per ion pair. W is *Advantage is taken of this peak in radiation therapy
not the same as the ionization potential (I ), using high-energy protons. The energy of protons is
which is the average energy required to cause adjusted so that the Bragg peak occurs within the tumor
an ionization in a material (averaged over all or other treated tissue.
6  •  Interaction of Radiation with Matter 69

10000

8000

6000
Ion pairs/mm

4000

2000

0
0.01 0.1 1 10 100 1000
Energy (keV)
FIGURE 6-6  Specific ionization for electrons versus energy in water. (Adapted from Mladjenovic M: Radioisotope and
Radiation Physics. New York, 1973, Academic Press, p 145.)

8000

Bragg ionization peak

6000
Ion pairs/mm

4000

2000

0
7 6 5 4 3 2 1 0
Distance from end of range, cm air
FIGURE 6-7  Specific ionization versus distance traveled for α particles in air. (Adapted from Mladjenovic M: Radio-
isotope and Radiation Physics. New York, 1973, Academic Press, p 111.)

cannot travel faster than the speed of light water (refractive index n = 1.33) is c′ = c/n ≈
applies to the speed of light in a vacuum  0.75╯c. Under these conditions, the particle
(c ≈ 3 × 108╯mâ•›/sec); however, a 1-MeV β par- creates an electromagnetic “shock wave” in
ticle emitted in water travels with a velocity much the same way that an airplane travel-
of v ≈ 0.8╯c, whereas the speed of light in ing faster than the speed of sound creates an
70 Physics in Nuclear Medicine

acoustic shock wave. The electromagnetic quite consistent from one particle to the
shock wave appears as a burst of visible radi- next. A transmission curve, showing percent
ation, typically bluish in color, called Ceren- transmission for α particles versus thickness
kov radiation. The Cerenkov effect can occur of absorber, remains essentially flat at 100%
for electrons with energies of a few hundred until the maximum range is reached; then it
keV; however, for heavy particles such as α falls rapidly to zero (Fig. 6-8). The mean
particles and protons, energies of several range is defined as the thickness resulting
thousands of MeV are required to meet the in 50% transmission. There is only a small
velocity requirements. amount of range fluctuation, or range strag-
The Cerenkov effect accounts for a very gling, about the mean value. Typically, range
small fraction (<â•›1%) of electron energies in straggling amounts to only approximately
the nuclear medicine energy range, but it is 1% of the mean range.
detectable in water solutions containing an For α particles emitted in radioactive decay
energetic β-particle emitter (e.g., 32P) using a (E = 4-8 MeV ), an approximation for the mean
liquid scintillation-counting apparatus. The range in air is
Cerenkov effect also is responsible for the
bluish glow that is seen in the water around R(cm) ≈ 0.325 E3 / 2 (MeV ) (6-6)
the core of an operating nuclear reactor.
EXAMPLE 6-2

Calculate the mean range in air of α particles


B.  CHARGED-PARTICLE RANGES
emitted by 241Am (Eα = 5.49 MeV ).
1.  Alpha Particles Answer
An α particle loses energy in a more or less R(cm) = 0.325 × (5.49)3 / 2
continuous slowing-down process as it
travels through matter. The particle is = 0.325 × ( 5.49 )3
deflected only slightly in its collisions with ≈ 4.2 cm
atoms and orbital electrons. As a result, the
distance traveled, or range, of an α particle
depends only on its initial energy and on its Example 6-2 illustrates that α particles have
average energy loss rate in the medium. For very short ranges. They produce densely
α particles of the same energy, the range is ionized tracks over this short range.

1.0
Source

Range
of particles detected

straggling
Relative number

0.5
Absorber

Mean range

Detector
0.0
Absorber thickness
FIGURE 6-8  Relative number of particles detected versus absorber thickness in a transmission experiment with α
particles. Range straggling is exaggerated for purposes of illustration.
6  •  Interaction of Radiation with Matter 71

Examples 6-2 and 6-4 illustrate that α par-


EXAMPLE 6-3
ticles have very short ranges in air as well as
Estimate the average value of specific  in soft tissue and other solid materials. The
ionization in air for α particles emitted by very short ranges of α particles mean that
241
Am. they constitute an almost negligible hazard
as an external radiation source. Only a few
Answer centimeters of air, a sheet of paper, or a
W = 33.7 eV/ion pair in air. Therefore the rubber glove provides adequate shielding pro-
number N of ionizations caused by an α par- tection. Even those particles that do reach
ticle of energy 5.49 MeV is the skin deliver a radiation dose only to the
most superficial layers of skin. Alpha particle
N = 5.49 × 106 eV/ 33.7 eV/ion pair emitters become a radiation hazard only

≈ 1.63 × 105 ion pairs when ingested; then, because of their densely
ionizing nature, they become very potent
Over a distance of travel of 4.2╯cm, the average radiation hazards. (See Chapter 22, Section
specific ionization is therefore A and Chapter 23, Section A.).
SI ≈ 1.63 × 105 ion pairs/ 4.2 cm
≈ 3.9 × 104 ion pairs/cm 2.  Beta Particles and Electrons

≈ 3.9 × 103 ion pairs/mm Alpha particles travel in straight lines. Thus
their path lengths (total length of path trav-
eled) and ranges (thickness of material
Compare the result in Example 6-3 with  required to stop them) are essentially equal.
the values shown in Figures 6-6 and 6-7. This does not apply to electrons, which can
Only near the very end of their ranges (E  undergo sharp deflections along their path or
1╯keV ) do electrons have specific ionizations be stopped completely in a single interaction.
comparable to the average values for α Electron ranges are quite variable from one
particles. electron to the next, even for electrons of
Alpha particle ranges in materials other exactly the same energy in the same absorb-
than air can be estimated using the ing material. Path lengths are an important
equation parameter for calculating linear energy
transfer. Ranges are important for radiation
ρ Ax  dosimetry (Chapter 22) and radiation protec-
Rx = Rair  air (6-7)
 ρx A air  tion (Chapter 23), and for determining the
limiting spatial resolution of positron imaging
where Rair is the range of the α particle in air, devices (Chapter 18). For this reason, the fol-
ρair (= 0.001293╯g/cm3) and Aâ•›air (≈14) are the lowing discussions focus on electron ranges.
density and (average) mass number of air, A transmission experiment with β parti-
and ρx and Ax are the same quantities for the cles results in a curve of the type illustrated
material of interest. This estimation is accu- in Figure 6-9. Transmission begins to decrease
rate to within approximately 15%. immediately when absorber is added because
even thin absor�bers can remove a few elec-
EXAMPLE 6-4 trons by the processes mentioned earlier.
What is the approximate mean range of α When the transmission curve is plotted on a
particles emitted by 241Am in soft tissue? semilogarithmic scale, it follows at first a
Assume that ρtissue = 1╯g/cm3. more or less straight-line decline until it
gradually merges with a long, relatively flat
Answer tail. The tail of the curve does not reflect
The elemental compositions of air and soft β-particle transmission but rather represents
tissue are similar; thus Aâ•›air ≈ Ax may be the detection of relatively penetrating brems-
assumed. From Example 6-2, Rair ≈ 4.2╯cm. strahlung photons generated by the β parti-
Therefore the approximate range in soft cles in the absorber and possibly in the source
tissue is and source holder. Extraneous instrument
and radiation background also may contrib-
Rtissue ≈ 4.2 cm × (0.001293 g/cm 3 ) / (1 g/cm 3 ) ute to the tail of the curve.
≈ 0.0054 cm The thickness of absorber corresponding to 

the intersection between the extrapolation of
≈ 54 µm
the linearly descending portion and the tail of
72 Physics in Nuclear Medicine

1
Relative number of
particles detected

Extrapolated
range
0.1

Background

0.01
Absorber thickness
FIGURE 6-9  Relative number of particles detected versus absorber thickness in an electron absorption experiment.
Compare with Figure 6-8.

the curve is called the extrapolated range Re It also is found that extrapolated ranges in
of the electrons. This is slightly less (perhaps different elements, when expressed in g/cm2,
by a few percent) than the maximum range are practically identical. There are small dif-
Rm, which is the actual maximum thickness ferences in electron energy loss rates in dif-
of absorber penetrated by the maximum ferent elements, as discussed in Section A.4,
energy β particles (Fig. 6-9); however, because but they have only a small effect on total
the difference is small and because Rm is very ranges.
difficult to measure, Re usually is specified as Figure 6-10 shows a curve for the extrapo-
the maximum β-particle range. lated range of electrons in water, in centime-
The extrapolated range for a monoener- ters, versus electron energy (or maximum
getic beam of electrons of energy E is the β-particle energy, Eβmax ). Because the density
same as that for a beam of β particles of of water is 1, this curve is numerically equal to
maximum energy Eβmax = E. In both cases, the extrapolated range in g/cm2 of water, which
range is determined by the maximum energy has the same value for all absorbers. It can be
of electrons in the beam. The shapes of the used to determine extrapolated ranges for
transmission curves for monoenergetic elec- other absorbers by dividing by the absorber
trons and for β particles are somewhat differ- density, as indicated in Equation 6-8.
ent, however. Specifically, the curve for β
EXAMPLE 6-5
particles declines more rapidly for very thin
absorbers because of rapid elimination of low- Using Figure 6-10, determine the range of
energy electrons in the β-particle energy spec- 1-MeV electrons in air (ρ = 0.001293╯g/cm3)
trum (See Fig. 3-2). and lead (ρ = 11.3╯g/cm3).
Extrapolated ranges are found to be
inversely proportional to the density ρ of the Answer
absorbing material. To normalize for density From Figure 6-10, the range of a 1-MeV elec-
effects, electron ranges usually are expressed tron in water (ρ = 1╯g/cm3) is 0.4╯cm, or 0.4╯g/
in g/cm2 of absorber. This is the weight of a cm2. Thus
1-cm2 section cut from a thickness of an
absorber equal to the range of electrons in it. Re (air) = (0.4 g/cm 2 ) / 0.001293 g/cm 3
The range in cm and in g/cm2 are related
according to ≈ 309 cm
Re (lead) = (0.4 g/cm 2 ) /11.3 g/cm 3
Re (g/cm 2 ) = Re (cm) × ρ(g/cm 3 )
(6-8)
≈ 0.035 cm
Re (cm) = Re (g/cm 2 ) /ρ(g/cm 3 )
6  •  Interaction of Radiation with Matter 73

10

Extrapolated range (cm) 1

0.1

0.01

0.001

0.0001
0.01 0.1 1 10
Energy (MeV)
FIGURE 6-10  Extrapolated range in water versus electron energy. The curve is derived from Equation 3-3 in Chapter
21 of reference 1. Curve applies to other absorbers by dividing range in water by absorber density, ρ, in g/cm3.

Example 6-5 illustrates that extrapolated It is found experimentally that the average
ranges can be several meters in air but that range for a β-particle beam is given by1
they are only a few millimeters or fractions of
a millimeter in solid materials or liquids. D1 / 2 (cm) ≈ 0.108 × [ Eβmax ]1.14 /ρ(g/cm 3 ) (6-9)
Some ranges for β particles emitted by radio-
nuclides of medical interest are summarized where Eβmax is the maximum energy of the β
in Table 6-1. particles in MeV and ρ is the density of the
The average range for electrons is the absorbing material. The average range of
thickness required to stop 50% of an electron positrons plays a significant role in imaging
beam. From Figure 6-9, it is evident that this with positron-emitting radionuclides, where
is much smaller than the extrapolated range. it places a fundamental limit on obtainable

TABLE 6-1â•…
BETA-PARTICLE RANGES FOR SOME COMMONLY USED β+ AND β− EMITTERS*

Extrapolated Range (cm) in Average Range (cm) in

Radionuclide Ebmax (MeV) Air Water Aluminum Water


3
H 0.0186 4.5 0.00059 0.00022 —
11
C 0.961 302 0.39 0.145 0.103
14
C† 0.156 21.9 0.028 0.011 0.013
13
N 1.19 395 0.51 0.189 0.132
15
O 1.723 617 0.80 0.295 0.201
18
F 0.635 176 0.23 0.084 0.064
32
P 1.70 607 0.785 0.290 0.198
82
Rb 3.35 1280 1.65 0.612 0.429
*Extrapolated and average ranges calculated from Equations 3-3 and 3-7, respectively, in Chapter 21 of reference 1.

Ranges for 35S ( Eβmax = 0.167 MeV) are nearly the same as those for 14C.
74 Physics in Nuclear Medicine

spatial resolution. This is discussed in Ejected


Chapter 18, Section A.4. Average ranges in photoelectron
water (ρ = 1) also are listed in Table 6-1. Incident
Average ranges in soft tissue are essentially photon
the same as for water.

C.  PASSAGE OF HIGH-ENERGY Nucleus


PHOTONS THROUGH MATTER

1.  Photon Interaction Mechanisms


High-energy photons (γ rays, x rays, annihila- FIGURE 6-11  Schematic representation of the photo-
tion radiation, and bremsstrahlung) transfer electric effect. The incident photon transfers its energy
their energy to matter in complex interac- to a photoelectron and disappears.
tions with atoms, nuclei, and electrons. For
practical purposes, however, these interac-
tions can be viewed as simple collisions from the atom and the photon disappears
between a photon and a target atom, nucleus, (Fig. 6-11).
or electron. These interactions do not cause Photoelectrons cannot be ejected from an
ionization directly, as do the charged-particle electron shell unless the incident photon
interactions; however, some of the photon energy exceeds the binding energy of that
interactions result in the ejection of orbital shell. ( Values of K-shell binding energies for
electrons from atoms or in the creation of the elements are listed in Appendix B.) If suf-
positive-negative electron pairs. These elec- ficient photon energy is available, the photo-
trons in turn cause ionization effects, which electron is most likely to be ejected from the
are the basis for mechanisms by which high- innermost possible shell. For example, ejec-
energy photons are detected and by which tion of a K-shell electron is four to seven times
they cause radiobiologic effects. For these more likely than ejection of an L-shell electron
reasons, high-energy photons are classified as when the energy requirement of the K shell
secondary ionizing radiation. is met, depending on the absorber element.
There are nine possible interactions The photoelectric effect creates a vacancy
between photons and matter, of which only in an orbital electron shell, which in turn
four are of significance to nuclear medicine. leads to the emission of characteristic x rays
These four interactions, and mathematical (or Auger electrons). In low-Z elements,
aspects of the passage of photon beams binding energies and characteristic x-ray
through matter, are discussed. energies are only a few keV or less. Thus
binding energy is a small factor in photo�
2.  The Photoelectric Effect electric interactions in body tissues. In heavier
The photoelectric effect is an atomic absorp- elements, however, such as iodine or lead,
tion process in which an atom absorbs totally binding energies are in the 20- to 100-keV
the energy of an incident photon. The photon range, and they may account for a significant
disappears and the energy absorbed is used fraction of the absorbed photon energy.
to eject an orbital electron from the atom. The The kinetic energy imparted to the photo-
ejected electron is called a photoelectron. It electron is deposited near the site of the 
receives kinetic energy Epe, equal to the dif- photoelectric interaction by the ionization
ference between the incident photon energy and excitation interactions of high-energy
E0 and the binding energy of the electron shell electrons described in Section A. Extrapolated
from which it was ejected. For example, if a ranges for photoelectrons of various energies
K-shell electron is ejected, the kinetic energy in soft tissue can be determined from Figure
of the photoelectron is 6-10.
Epe = E0 − K B (6-10) 3.  Compton Scattering
where KB is the K-shell binding energy for the Compton scattering is a “collision” between a
atom from which it is ejected (see Chapter 2, photon and a loosely bound outer-shell orbital
Section C.2). The photoelectric effect looks electron of an atom. In Compton scattering,
like a “collision” between a photon and an because the incident photon energy greatly
orbital electron in which the electron is ejected exceeds the binding energy of the electron to
6  •  Interaction of Radiation with Matter 75

Scattered photon The energy transferred does not depend on


of lower energy the density, atomic number, or any other
property of the absorbing material. Compton
, Scattering angle scattering is strictly a photon-electron
Incident
photon interaction.
The amount of energy transferred to the
recoil electron in Compton scattering ranges
from nearly zero for θ ≈ 0 degrees (“grazing”
Ejected collisions) up to a maximum value Eremax that
Compton occurs in 180-degree backscattering events.
recoil The minimum energy for scattered photons,
Nucleus electron
Escmin, also occurs for 180-degree backscatter-
ing events. The minimum energy of Compton-
scattered photons can be calculated from
Equation 6-11 with θ = 180 degrees (cos 180°
FIGURE 6-12  Schematic representation of Compton = –1):
scattering. The incident photon transfers part of its
energy to a Compton recoil electron and is scattered in Escmin = E0 / [1 + (2 E0 / 0.511)] (6-13)
another direction of travel (θ, scattering angle).
Thus
Eremax = E0 − Escmin
the atom, the interaction looks like a collision
between the photon and a “free” electron   1 
= E0 1 − 
(Fig. 6-12).  [1 + (2 E0 / 0.511)]  (6-14)
The photon does not disappear in Compton
scattering. Instead, it is deflected through a = E02 / ( E0 + 0.2555)
scattering angle θ. Part of its energy is trans-
ferred to the recoil electron; thus the photon The minimum energy of backscattered
loses energy in the process. The energy of the photons, Escmin, and the maximum energy
scattered photon is related to the scattering transferred to the recoil electron, Eremax , have
angle θ by considerations of energy and characteristic values that depend on E0, the
momentum conservation according to* energy of the incident photon. These energies
are of interest in pulse-height spectrometry
Esc = E0 / [1 + ( E0 / 0.511) (1 − cos θ)]   (6-11)
because they result in characteristic struc-
where E0 and Esc are the incident and scat- tures in pulse-height spectra (see Chapter 10,
tered photon energies in MeV, respectively. Section B.1).
The energy of the recoil electron, Ere, is thus Table 6-2 lists some values of Escmin and
Ere for some γ-ray and x-ray emissions from
max
Ere = E0 − Esc (6-12)
radionuclides of interest in nuclear medicine.
Note that for relatively low photon energies
*Derivations of Compton energy-angle relationships can (e.g., 125I, 27.5╯keV), the recoil electron
be found in Chapter 23 of reference 1. receives only a small fraction of the incident

TABLE 6-2â•…
SCATTERED PHOTON AND RECOIL ELECTRON ENERGIES FOR 180-DEGREE COMPTON
SCATTERING INTERACTIONS

Radionuclide Photon Energy (keV) Escmin (keV) Eremax (keV)


125
I 27.5 24.8 2.7
133
Xe 81 62 19
99m
Tc 140 91 49
131
I 364 150 214
β+ (annihilation) 511 170 341
60
Co 1330 214 1116
— ∞ 255.5 —
76 Physics in Nuclear Medicine

photon energy, even in 180-degree scattering photons would be detected in either the
events. Thus photon energy changes very forward or backward direction, with a
little in Compton scattering at low photon minimum at right angles (90 degrees) to the
energies. The smallness of this energy change direction of the incident photons. At higher
has important implications for the elimina- energies (>>╛╛╛0.5 MeV), the highest intensity
tion of Compton-scattered photons by energy- detected would be increasingly toward the
discrimination techniques (See Fig. 10-10). At forward direction (scattering angle ~0°).
higher energies the energy distribution
changes and Escmin approaches a maximum 4.  Pair Production
value of 255.5╯keV. The remaining energy, Pair production occurs when a photon inter-
which now accounts for most of the incident acts with the electric field of a charged particle.
photon energy, is transferred to the recoil Usually the interaction is with an atomic
electron in 180-degree scattering events. nucleus, but occasionally it is with an electron.
Note also that the energy of Compton- In pair production, the photon disappears and
scattered photons never is zero—that is, a its energy is used to create a positron-electron
photon cannot transfer all its energy to an pair (Fig. 6-14). Because the positron and elec-
electron in a Compton scattering event. tron both have a rest mass equivalent to 0.511
The angular distribution of Compton-scat- MeV, a minimum photon energy of 2 × 0.511
tered photons also depends on the incident MeV = 1.022 MeV must be available for pair
photon energy. Figure 6-13 shows the relative production to occur. The difference between
probability of scattering at different angles the incident photon energy E0 and the 1.022
per unit of solid angle. Solid angle is propor- MeV of energy required to create the electron
tional to the area subtended on a sphere pair is imparted as kinetic energy to the posi-
divided by the total area of the sphere (see tron ( Ee+ ) and the electron, ( Ee − )
also Fig. 11-1). Thus Figure 6-13 reflects the Ee+ + Ee− = E0 − 1.022 MeV
(6-15)
relative number of scattered photons that
would be recorded by a detector of fixed area The energy sharing between the electron and
as it was moved about at a fixed distance from positron is more or less random from one
the scattering object at different angles rela- interaction to the next, usually within the
tive to the incident beam (in the absence of 20% to 80% sharing range.
attenuation, secondary scattering, etc). At The electron and positron dissipate their
relatively low energies (10-100╯keV) the kinetic energy primarily in ionization and
highest intensity of Compton-scattered excitation interactions. When the positron

1
10 keV

100 keV
Probability of scattering

0.1
(arbitrary units)

500 keV

1 MeV

0.01

5 MeV

0.001
0 30 60 90 120 150 180
Scattering angle,  (deg)
FIGURE 6-13  Relative probability of Compton scattering (arbitrary units) per unit of solid angle versus scattering
angle θ for different incident photon energies.
6  •  Interaction of Radiation with Matter 77

Incident e
photon electron

Nucleus

e
positron Nucleus

0.511-MeV annihilation photons

FIGURE 6-14  Schematic representation of pair production. Energy of incident photon is converted into an electron
and a positron (total 1.022-MeV mass-energy equivalent) plus their kinetic energy. The positron eventually undergoes
mutual annihilation with a different electron, producing two 0.511-MeV annihilation photons.

has lost its kinetic energy and stopped, it energy to matter, it is of little practical impor-
undergoes mutual annihilation with a nearby tance in nuclear medicine.
electron, and a pair of 0.511-MeV annihila-
tion photons are emitted in opposite direc- 6.  Deposition of Photon Energy  
tions from the site of the annihilation event in Matter
(see Chapter 3, Section G). Annihilation The most important interactions in the trans-
photons usually travel for some distance fer of photon energy to matter are the photo-
before interacting again. Thus usually only electric effect, Compton scattering, and pair
the kinetic energy of the electron and positron production. The transfer of energy occurs
(Equation 6-15) is deposited at the site of the typically in a series of these interactions in
pair production event. which energy is transferred to electrons, and,
usually, secondary photons, of progressively
5.  Coherent (Rayleigh) Scattering less energy (Fig. 6-15). The products of each
Coherent or Rayleigh scattering is a type of interaction are secondary photons and high-
scattering interaction that occurs between a energy electrons (Table 6-3). The high-energy
photon and an atom as a whole. Because of
the great mass of an atom (e.g., in comparison
to the recoil electron in the Compton scatter-
ing process), very little recoil energy is
e Compton
absorbed by the atom. The photon is therefore recoil electron
deflected with essentially no loss of energy. Scattered
Coherent scattering is important only at photon
relatively low energies (<<╛50╯keV ). It can be Scattered
of signi�ficance in some precise photon trans- Incident photon
mission measurements—for example, in x-ray photon
computed tomographic scanning—because it e x ray

is a mechanism by which photons are removed Compton e
from a photon beam. Coherent scattering also recoil electron Photoelectron
is an important interaction in x-ray crystal- FIGURE 6-15  Multiple interactions of a photon passing
lography; however, because it is not an  through matter. Energy is transferred to electrons in a
effective mechanism for transferring photon sequence of photon-energy degrading interactions.
78 Physics in Nuclear Medicine

electrons ultimately are responsible for the is relatively simple; the thicker the absorber,
deposition of energy in matter. Ionization and the greater the probability that an interaction
excitation by these electrons are the mecha- will occur. The dependence on absorber com-
nisms underlying all of the photon detectors position and photon energy, however, is more
described in Chapter 7. The electrons also are complicated.
responsible for radiobiologic effects caused by Consider the photon transmission measure-
γ-ray, x-ray, or bremsstrahlung radiation. ment diagrammed in Figure 6-16. A beam of
Because of this, the average linear energy ·
photons of intensity I (photons/cm2â•› â•›sec) is
transfer of photons for radiobiologic purposes directed onto an absorber of thickness Δâ•›x.
is the same as for electrons of similar energy, Because of composition and photon energy
that is, 0.2-2╯keV/µm (see Chapter 23). effects, it will be assumed for the moment that
the absorber is composed of a single element
TABLE 6-3â•… of atomic number Z and that the beam is
PRODUCTS OF THE THREE MAJOR monoenergetic with energy E. A photon detec-
PHOTON INTERACTION PROCESSES tor records transmitted beam intensity. It is
assumed that only those photons passing
High-Energy through the absorber without interaction are
Secondary Secondary recorded. (The validity of this assumption is
Interaction Photon(s) Electron(s) discussed further in Sections D.2 and D.3.)
Photoelectric Characteristic Photoelectrons For a “thin” absorber, such that beam
x rays intensity is reduced by only a small amount
Auger electrons (10%), it is found that the fractional decrease
in beam intensity (Δâ•›I/Iâ•›) is related to absorber
Compton Scattered Recoil electron thickness Δ â•›x according to
photon
Pair Annihilation Positive- ∆ I/I ≈ −µ l × ∆ x (6-16)
production photons negative the minus sign indicating beam intensity
electron pair decreases with increasing absorber thickness.
The quantity µâ•›l is called the linear attenua-
D.  ATTENUATION OF PHOTON BEAMS tion coefficient of the absorber. It has dimen-
sions (thickness)–1 and usually is expressed in
cm–1. This quantity reflects the “absorptivity”
1.  Attenuation Coefficients of the absorbing material.
When a photon passes through a thickness of The quantity µâ•›l is found to increase lin-
absorber material, the probability that it will early with absorber density ρ. Density effects
experience an interaction depends on its are factored out by dividing µâ•›l by density ρ:
energy and on the composition and thickness
of the absorber. The dependence on thickness µ m = µ l /ρ (6-17)

Absorber

Incident Transmitted
photon beam photon beam
intensity, I intensity, (II)

Detector

x
FIGURE 6-16  Photon-beam transmission measurement.
6  •  Interaction of Radiation with Matter 79

The quantity µâ•›m has dimensions of cm2/g and 1. The photoelectric component τ decreases
is called the mass attenuation coefficient of rapidly with increasing photon energy
the absorber. It depends on the absorber and increases rapidly with increasing
atomic number Z and photon energy E. This atomic number of the absorber (τ ∝ ~
sometimes is emphasized by writing it as Z3/E3). The photoelectric effect is thus
µâ•›m(Z, E ). the dominating effect in heavy elements
It is possible to measure µâ•›m or µâ•›l in differ- at low photon energies. The photoelec-
ent absorber materials by transmission mea- tric component also increases abruptly
surements with monoenergetic photon beams. at energies corresponding to orbital
Most tables, however, are based on theoretical electron binding energies of the absorber
calculations from atomic and nuclear physics. elements. At the K-shell binding ener-
An extensive tabulation of values of µâ•›m versus gies of iodine (KB = 33.2╯keV ) and lead
photon energy for different absorber materi- (KB = 88.0╯keV ), the increase is a factor
als is found in reference 2. Some values of of 5-6. These abrupt increases are called
interest to nuclear medicine, taken from these K absorption edges. They result from
tables, are presented in Appendix D. Usually, the fact that photoelectric absorption
values of µâ•›m rather than µâ•›l are tabulated involving K-shell electrons cannot occur
because µâ•›m does not depend on the physical until the photon energy exceeds the
state (density) of the absorber. Given a value K-shell binding energy. L absorption
of µâ•›m from the tables, µâ•›l for an absorber can edges also are seen at Eâ•›~â•›13-16╯keV in
be obtained from the graph for lead. L absorption edges
in water and iodine and the K absorp-
µ l (cm −1 ) = µ m (cm 2 /g) × ρ(g/cm 3 ) (6-18)
tion edge for water also exist, but they
The mass attenuation coefficient for a occur at energies less than those shown
mixture of elements can be obtained from the in the graphs.
values for its component elements according to 2. The Compton-scatter component σ
decreases slowly with increasing photon
µ m (mix) = µ m,1 f1 + µ m,2 f2 +  (6-19)
energy E and with increasing absorber
where µm,1, µm,2 … are the mass attenuation atomic number Z. The changes are so
coefficients for elements 1, 2, …, and f1, f2, …, small that for practical purposes σ
are the fractions by weight of these elements usually is considered to be invariant
in the mixture. For example, the mass attenu- with Z and E. Compton scattering is the
ation coefficient for water (2/18 H, 16/18 O, by dominating interaction for intermediate
weight) is given by values of Z and E.
3. The pair-production component κ is zero
µ m (water) = (2 /18)µ m (H) + (16 /18)µ m (O)
for photon energies less than the thresh-
(6-20)
old energy of 1.02 MeV for this inter�
The mass attenuation coefficient µm can be action; then it increases logarithmically
broken down into components according to with increasing photon energy and with
increasing atomic number of the
µm = τ + σ + κ (6-21)
absorber (κ ∝ ~ Z log E ). Pair production
where τ is that part of µm caused by the photoÂ� is the dominating effect at higher photon
electric effect, σ is the part caused by Compton energies in absorbers of high atomic
scattering, and κ is the part caused by pair number.
proÂ�duction. Thus, for example, τ would be the Figure 6-18 shows the dominating (most
mass attenuation coefficient of an absorber in probable) interaction versus photon energy E
the absence of Compton scattering and pair and absorber atomic number Z. Note that
production. Note that µm involves both absorp- Compton scattering is the dominating inter-
tion and scattering processes. Thus µm is action for Z  20 (body tissues) over most of
properly called an attenuation coefficient the nuclear medicine energy range.
rather than an absorption coefficient.
The relative magnitudes of τ, σ, and κ vary
with atomic number Z and photon energy E. 2.  Thick Absorbers, Narrow-Beam
Figure 6-17 shows graphs of µm and its com- Geometry
ponents, τ, σ, and κ versus photon energy The transmission of a photon beam through
from 0.01-10 MeV in water, NaI(Tl), and lead. a “thick” absorber—that is, one in which 
The following points are illustrated by these the pro�bability of photon interaction is not
graphs: “small” (10%)—depends on the geometric
80 Physics in Nuclear Medicine

Water NaI(Tl)

100 100
K

Mass attenuation coefficient (cm /g)


Mass attenuation coefficient (cm /g)

10 10

2
2

1 1
m

 m
0.1 0.1



0.01 0.01

 
0.001 0.001
0.01 0.1 1 10 0.01 0.1 1 10
A Photon energy (MeV) B Photon energy (MeV)

Pb
L
100
Mass attenuation coefficient (cm /g)

K
10
2

m

0.1


0.01


0.001
0.01 0.1 1 10
C Photon energy (MeV)
FIGURE 6-17  Photoelectric (τ), Compton (σ), pair-production (κ), and total (µm) mass attenuation coefficients (square
centimeters per gram) for water (A), NaI(Tl) (B), and Pb (C ) from 0.01 to 10 MeV. K and L are absorption edges. Data
taken from reference 2. Curves for µâ•›l can be obtained by multiplying by the appropriate density values.

arrangement of the photon source, absorber, geometry. Conversely, an arrangement in which


and detector. Specifically, transmission depends many scattered photons are recorded is called
on whether scattered photons are recorded as broad-beam geometry. (They also are called
part of the transmitted beam. An arrange- good geometry and poor geometry, respec-
ment that is designed to minimize the record- tively.) Figure 6-19 shows examples of these
ing of scattered photons is called narrow-beam geometries.
6  •  Interaction of Radiation with Matter 81

100

75
Atomic number, Z Pair
production
Photoelectric
absorption
50

Compton
scattering

25

0
0.01 0.1 1 10 100
Photon energy (MeV)
FIGURE 6-18  Predominating (most probable) interaction versus photon energy for absorbers of different atomic
numbers. Curves were generated using values obtained from reference 2.

Conditions of narrow-beam geometry Under conditions of narrow-beam geome-


usually require that the beam be collimated try, the transmission of a monoenergetic
with a narrow aperture at the source so that photon beam through an absorber is described
only a narrow beam of photons is directed by an exponential equation
onto the absorber. This minimizes the prob-
ability that photons will strike neighboring I ( x) = I (0) e− µ x
l
(6-22)
objects (e.g., the walls of the room or other
parts of the measurement apparatus) and where I(x) is the beam intensity transmitted
scatter toward the detector. Matching colli- through a thickness x of absorber, I(0) is the
mation on the detector helps prevent photons intensity recorded with no absorber present,
that are multiple-scattered in the absorber and µâ•›l is the linear attenuation coefficient
from being recorded. In addition, it is desir- of the absorber at the photon energy of inter-
able to place the absorber approximately est. In contrast to charged particles, photons
halfway between the source and the do not have a definite maximum range. There
detector. is always some finite probability that a

Radiation source

Source
collimator

Absorber

Detector
collimator

Detector

Narrow-beam geometry Broad-beam geometry


FIGURE 6-19  Narrow-beam and broad-beam geometries for photon-beam attenuation measurements. Narrow-beam
geometry is designed to minimize the number of scattered photons recorded.
82 Physics in Nuclear Medicine

photon will penetrate even the thickest transmitted beam intensity by a factor of 10.
absorber [i.e., I(x) in Equation 6-22 never This quantity is given by
reaches zero].
Equation 6-22 is exactly analogous to TVT = ln 10 /µ l
(6-24)
Equation 4-6 for the decay of radioactivity, ≈ 3.32 × HVT
with the attenuation coefficient µl replacing
the decay constant λ and absorber thickness where ln 10 ≈ 2.30. Some HVTs for water and
x replacing decay time t. Analogous to the TVTs for lead are listed in Table 6-4.
concept of half-life in radio�active decay, the The quantity
thickness of an absorber that decreases
X m = 1 /µ l (6-25)
recorded beam intensity by one half is called
the half-value thickness (HVT) or half-value is called the mean free path for photons in an
layer (HVL). It is related to the linear attenu- absorber. It is the average distance traveled
ation coefficient according to by a photon in the absorber before experienc-
ing an interaction. Mean free path is related
HVT = ln 2 /µ l to HVT according to
(6-23)
µ l = ln 2 /HVT
X m = HVT/ ln 2
(6-26)
where ln 2 ≈ 0.693. Compare these equations ≈ 1.44 × HVT
with Equations 4-8 and 4-9.
Some radiation-shielding problems require Note the analogy to average lifetime, τ (Equa-
the use of relatively thick absorbers; for  tion 4-12).
this purpose it is sometimes useful to know Table 6-5 compares mean free paths for
the tenth-value thickness (TVT)—that is, photons in water against maximum ranges
the thickness of absorber that decreases for electrons in water and α particles in air as

TABLE 6-4â•…
HALF-VALUE THICKNESSES IN WATER AND TENTH-VALUE THICKNESSES IN LEAD  
(NARROW-BEAM CONDITIONS)

Photon Energy HVT in Water TVT in Lead


Radionuclide (keV) (cm) (mm)
125
I 27.5 1.7 0.06
133
Xe 81 4.3 1.0
99m
Tc 140 4.6 0.9
131
I 364 6.3 7.7
+
β (annihilation) 511 7.1 13.5
60
Co 1330 11.2 36.2
HVT, half-value thickness; TVT, tenth-value thickness.

TABLE 6-5â•…
COMPARISON OF PHOTON MEAN FREE PATHS AND MAXIMUM ELECTRON AND  
α-PARTICLE RANGES

Photon or Particle Energy Photon MFP Electron Range α-Particle Range


(MeV) (cm H2O) (cm H2O) (cm air)
0.01 0.20 0.00016 —
0.1 5.95 0.014 0.1
1 14.14 0.41 0.5
10 45.05 4.6 10.3
MFP, mean free path.
6  •  Interaction of Radiation with Matter 83

a function of their energy. Although the con-


cepts of photon mean free path and charged 3.  Thick Absorbers, Broad-Beam
particle ranges are different, the comparison Geometry
gives an indication of relative penetration of Practical problems of photon-beam attenua-
photons versus particle radiation. Over the tion in nuclear medicine usually involve
energy range 0.01-10 MeV, photons are much broad-beam conditions. Examples are the
more penetrating than electrons or α parti- shielding of radioactive materials in lead con-
cles. For this reason they sometimes are tainers and the penetration of body tissues by
called penetrating radiation. photons emitted from radioactive tracers
The quantity e−µ x [or I(x)]/I(0) in Equation
l
localized in internal organs. In both of these
6-22], the fraction of beam intensity transmit- examples, a considerable amount of scatter-
ted by an absorber, is called its transmission ing occurs in the absorber material surround-
factor. The transmission factor can be deter- ing or overlying the radiation source.
mined using the methods described for deter- The factor by which transmission is
mining decay factors in Chapter 4, Section C. increased in broad-beam conditions, relative
For example, the graph shown in Figure 4-3 to narrow-beam conditions, is called the
can be used with “decay factor” replaced by buildup factor B. Thus the transmission
“transmission factor” and “number of half- factor T for broad-beam conditions is given by
lives” replaced by “number of HVTs.”
T = Be−µ x
l (6-27)
where µâ•›l and x are the linear attenuation
EXAMPLE 6-6 coefficient and thickness, respectively, of the
Determine the transmission factor for 140-keV absorber.
photons in 10╯cm of soft tissue (water) by Buildup factors for various source-absorber-
direct calculation. detector geometries have been calculated.
Some values for water and lead for a source
Answer embedded in or surrounded by scattering and
From Table 6-4, HVT = 4.6╯cm in water at absorbing material are listed in Table 6-6.
140╯keV. Thus µâ•›l = 0.693/4.6 = 0.151╯cm–1, and Note that B depends on photon energy and on
the transmission factor is the product µâ•›lâ•›x for the absorber.
I (10) /I (0) = e−0.151×10 = e−1.51 EXAMPLE 6-8
Using a pocket calculator In Example 6-7, the transmission factor for
511-keV photons in 1╯cm of lead was found to
e = 0.221
−1.51
be 18% for narrow-beam conditions. Estimate
Thus the transmission factor for 140-keV the actual transmission for broad-beam con-
photons through 10╯cm of water is 22.1%. ditions (e.g., a vial of β+-emitting radioactive
solution in a lead container of 1-cm wall
thickness).
EXAMPLE 6-7
Estimate the transmission factor for 511-keV Answer
photons in 1╯cm of lead using graphical For 511-keV photons, HVT = 0.4╯cm (Example
methods (see Fig. 4-3). 6-7). Thus µâ•›l = 0.693/(0.4╯cm) ≈ 1.73╯cm–1, and,
for x = 1╯cm, µâ•›lâ•›x ≈ 1.73. Taking values for 0.5
Answer MeV (≈ 511╯keV) from Table 6-6 and using
From Table 6-4, the TVT of 511-keV photons linear interpolation between values for µâ•›lâ•›x =
in lead is 13.5╯mm. From Equation 6-24, HVT 1 (B = 1.24) and µâ•›lâ•›x = 2 (B = 1.39), one obtains
≈ TVT/3.32 so for 511-keV photons in lead, B = 1.24 + (0.73)(1.39 − 1.24)
HVT = 1.35╯cm/3.32 = 0.4╯cm. Thus 1╯cm = 2.5
HVTs. From Figure 4-3, the transmission = 1.35
(decay) factor for 2.5 HVTs (T1/2) is approxi- For B = 1.35, the transmission in broad-beam
mately 0.18 (18% transmission). conditions is 35% greater than calculated for
narrow-beam conditions. Thus the actual
It must be remembered that the answers transmission factor is
obtained in Examples 6-6 and 6-7 apply  T ≈ 1.35 × 0.18
only to narrow-beam conditions. Broad-beam
≈ 0.24
conditions are discussed in the following
or 24%.
section.
84 Physics in Nuclear Medicine

TABLE 6-6â•…
EXPOSURE BUILDUP FACTORS IN WATER AND IN LEAD*

µlx

Photon Energy
Material (MeV) 1 2 4 7 10 15 20
Water 0.1 4.55 11.8 41.3 137 321 938 2170
0.5 2.44 4.88 12.8 32.7 62.9 139 252
1.0 2.08 3.62 7.68 15.8 26.1 47.7 74.0
2.0 1.83 2.81 4.98 8.65 12.7 20.1 28.0
4.0 1.63 2.24 3.46 5.30 7.16 10.3 13.4
6.0 1.51 1.97 2.84 4.12 5.37 7.41 9.42
10.0 1.37 1.68 2.25 3.07 3.86 5.19 6.38
Lead 0.5 1.24 1.39 1.62 1.88 2.10 2.39 2.64
1.0 1.38 1.68 2.19 2.89 3.51 4.45 5.27
2.0 1.40 1.76 2.52 3.74 5.07 7.44 9.08
4.0 1.36 1.67 2.40 3.79 5.61 9.73 15.4
6.0 1.42 1.73 2.49 4.13 6.61 13.7 26.6
10.0 1.51 2.01 3.42 7.37 15.4 50.8 161
*Data taken from Schleien B (ed): The Health Physics and Radiological Health Handbook. Silver Spring, MD, 1992,
Scinta.3

Example 6-8 illustrates that scatter effects This issue is discussed further in Chapter 22,
can be significant in broad-beam conditions. Section B.
The thickness of lead shielding required to
achieve a given level of protection is greater
than that calculated using narrow-beam 4.  Polyenergetic Sources
equations. Many radionuclides emit photons of more
than one energy. The photon transmission
EXAMPLE 6-9 curve for such an emitter consists of a sum of
Estimate the thickness of lead shielding exponentials, one component for each of the
required to achieve an actual transmission of photon energies emitted. The transmission
18% in the problem described in Example 6-8. curve has an appearance similar to the decay
curve for a mixed radionuclide sample shown
Answer in Figure 4-5. The transmission curve drops
Because B = 1.35, it is necessary to further steeply at first as the lower-energy (“softer”)
reduce transmission by approximately 1/1.35 components of the beam are removed. Then it
≈ 0.74 to correct for scattered radiation. gradually flattens out, reflecting greater pen-
According to Figure 4-3, this would require etration by the higher-energy (“harder”) com-
approximately 0.45 HVTs, or approximately ponents of the beam. The average energy of
0.18╯cm (1 HVT = 0.4╯cm). This is only an photons remaining in the beam increases
estimate, because the HVT used applies to with increasing absorber thickness. This
narrow-beam conditions. A more exact effect is called beam hardening.
answer could be obtained by successive It is possible to detect small amounts of a
approximations. high-energy photon emitter in the presence of
large amounts of a low-energy photon emitter
Broad-beam conditions also arise in prob- by making use of the beam-hardening effect.
lems of internal radiation dosimetry—for For example, a 3-mm thickness of lead is
example, when it is desired to calculate the several TVTs for the 140-keV γ rays of 99mTc,
radiation dose to an organ delivered by a but it is only approximately 1 HVT for the
radioactive concentration in another organ. 700- to 800-keV γ rays of 99Mo. Thus a
6  •  Interaction of Radiation with Matter 85

3-mm-thick lead shield placed around a vial BIBLIOGRAPHY


containing 99mTc solution permits detection of Discussions of radiation interactions and their
small amounts of 99Mo contamination with passage through matter are found in the following:
minimal interference from the 99mTc γ rays. Johns HE, Cunningham JR: The Physics of Radiology,
(See Chapter 5, Section C). ed 4, Springfield, IL, 1983, Charles C Thomas, 
Chapter 6.
REFERENCES Lapp RE, Andrews HL: Nuclear Radiation Physics, ed 4,
Englewood Cliffs, NJ, 1972, Prentice-Hall, pp 196-203,
1. Evans RD: The Atomic Nucleus, New York, 1972, 233-247, 261-279.
McGraw-Hill, p 628. (Note: This reference contains
useful discussions of many details of radiation interac- A comprehensive tabulation of x-ray and γ-ray
tions with matter.) attenuation coefficients can be found in the
2. Berger MJ, Hubbell JH: XCOM: Photon Cross-Sections following reference.
Database, NIST Standard Reference Database 8 Hubbell JH, Seltzer SM: Tables of X-Ray Mass Attenua-
(XGAM) Available at: http://www.nist.gov/pml/data/ tion Coefficients and Mass Energy-Absorption Coeffi-
xcom/index.cfm. (Accessed August 17, 2011.). cients 1╯keV to 20 MeV for Elements Z = 1 to 92 and
3. Schleien B, editor: The Health Physics and Radiologi- 48 Additional Substances of Dosimetric Interest.
cal Health Handbook, Silver Spring, MD, 1992, Scinta, NISTIR 5632, Gaithersburg MD, 1995, US Depart-
pp 176-177. (Note: This reference also contains useful ment of Commerce. Available at: http://physics.nist.gov/
tabulations of charged-particle ranges and other PhysRefData/XrayMassCoef/cover.html (Accessed
absorption data.) August 26th, 2011.)
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chapter
7 
Radiation Detectors
When radiations from a radioactive material radiation and secondary ionization from δ
pass through matter, they interact with rays (see Chapter 6, Section A.1). The elec-
atoms and molecules and transfer energy to trons produced by ionization are attracted to
them. The transfer of energy has two effects: the positive electrode and the ionized atoms
ionization and excitation. Ionization occurs to the negative electrode, causing a momen-
when the energy transferred is sufficient to tary flow of a small amount of electrical
cause an orbital electron to be stripped away current.
from its parent atom or molecule, thus creat- Gas-filled detectors include ionization
ing an ion pair (a negatively charged electron chambers, proportional counters, and Geiger-
and a positively charged atom or molecule). Müller (GMâ•›) counters. The use of these detec-
Excitation occurs when electrons are per- tors in nuclear medicine is somewhat limited
turbed from their normal arrangement in an because their stopping power and detection
atom or molecule, thus creating an atom or efficiency for x rays and γ rays are quite low;
molecule in an excited state. Both of these however, they find some use for applications
processes are involved in the detection of in which detection efficiency is not a major
radiation events; however, ionization is the factor and for detection and measurement 
primary event, and hence the term ionizing of nonpenetrating, particle-type radiations.
radiation is used frequently when referring Some of their applications are discussed in
to the emissions from radioactive material. Chapters 12 and 23.
Radiation interactions were discussed in
detail in Chapter 6. In this chapter, we 2.  Ionization Chambers
describe the basic principles of radiation In most ionization chambers, the gas between
detectors used in nuclear medicine. the electrodes is air. The chamber may or may
not be sealed from the atmosphere. Many dif-
ferent designs have been used for the elec-
trodes in an ionization chamber, but usually
A.  GAS-FILLED DETECTORS
they consist of a wire inside of a cylinder or a
pair of concentric cylinders.
1.  Basic Principles For maximum efficiency of operation, the
Most gas-filled detectors belong to a class of voltage between the electrodes must be suf-
detectors called ionization detectors. These ficient to ensure complete collection of ions
detectors respond to radiation by means of and electrons produced by radiation within
ionization-induced electrical currents. The the chamber. If the voltage is too low, some of
basic principles are illustrated in Figure 7-1. the ions and electrons simply recombine with
A volume of gas is contained between two one another without contributing to electrical
electrodes having a voltage difference (and current flow. Figure 7-2 shows the effect of
thus an electric field) between them. The voltage difference between the electrodes on
negative electrode is called the cathode, the the electrical current recorded by an ioniza-
positive electrode the anode. The electrodes tion chamber per ionizing radiation event
are shown as parallel plates, but they may detected. Recombination occurs at low volt-
be a pair of wires, concentric cylinders, and ages (recombination region of the curve). As
so forth. Under normal circumstances, the the voltage increases there is less recombina-
gas is an insulator and no electrical current tion and the response (electrical current)
flows between the electrodes. However, radi- increases. When the voltage becomes suffi-
ation passing through the gas causes ioniza- cient to cause complete collection of all of the
tion, both direct ionization from the incident charges produced, the curve enters a plateau
87
88 Physics in Nuclear Medicine

Voltage source
 

 Anode
Current
Air or measuring
Incident device
e other
ionizing e
e gas
radiation
 e e I





 Cathode

FIGURE 7-1  Basic principles of a gas-filled detector. Electrical charge liberated by ionizing radiation is collected by
positive (anode) and negative (cathode) electrodes.

Saturation
region
Recombination
region
Amplitude of output pulse

Saturation
voltage, Vs

Applied voltage
FIGURE 7-2  Voltage response curve (charge collected vs. voltage applied to the electrodes) for a typical ionization
chamber. In usual operation, applied voltage exceeds saturation voltage Vs to ensure complete collection of liberated
charge.

called the saturation region. The voltage at ionization event in air is approximately
which the saturation region begins is called 34╯eV.* Thus a 1-MeV β particle, for example,
the saturation voltage (Vs). Typically, Vs ≈ causes approximately (106/34) ≈ 3 × 104 ioniza-
50-300╯V, depending on the design of the tions in air and releases a total amount of
chamber. Ionization chambers are operated at electrical charge of only approximately 3 ×
voltages in the saturation region. This ensures 10−15 coulombs.
a maximum response to radiation and also
that the response will be relatively insensi- *â•›The average energy expended in producing a single
tive to instabilities in the voltage applied to ionization event is symbolized by W. This is not the same
the electrodes. as the average energy required to ionize an air molecule,
The amount of electrical charge released in but is the average energy expended per ionization by the
ionizing particle, including both ionization and excitation
an ionization chamber by a single ionizing effects. This is discussed in detail in Chapter 6, Section
radiation event is very small. For example, A.4. Values of W for some detector materials are listed in
the energy expended in producing a single Table 7-1.
7  •  Radiation Detectors 89

TABLE 7-1â•…
SOME PROPERTIES OF DETECTOR
MATERIALS USED AS IONIZATION
DETECTORS

Ge(Li)
Si(Li) or Ge CdTe* Air
ρ(g/cm )3
2.33 5.32 6.06 0.001297
Z 14 32 48 & 52 ~7.6

W(eV) 3.6 2.9 4.43 33.7
CdTe, cadmium telluride; Ge, germanium; Li, lithium; Si,
silicon.
*Cadmium zinc telluride (CZT) is CdTe in which some of
the Te atoms (typically 20%) are replaced by zinc atoms.
CZT has properties similar to CdTe.

Average energy expended per electron-hole pair created
or per ionization.

FIGURE 7-3  A battery-powered radiation survey meter.


An ionization chamber is contained in the base of the
Because of the small amount of electrical unit, with the entrance window on the bottom face of the
charge or current involved, ionization cham- device (not shown). The meter indicates radiation level.
bers generally are not used to record or count The rotary switch is used to select different scale factors.
(Courtesy Ludlum Measurements, Inc., Sweetwater, TX.)
individual radiation events. Instead, the total
amount of current passing through the
chamber caused by a beam of radiation is
measured. Alternatively, the electrical charge
released in the chamber by the radiation are discussed in Chapter 23. A typical survey
beam may be collected and measured. meter can measure exposure rates down to
Small amounts of electrical current are approximately 1╯mR/hr or air kerma rates
measured using sensitive current-measuring down to approximately 10╯µGy/hr.
devices called electrometers. Two devices con- Dose calibrators are used to assay activity
sisting of ionization chambers and electrom- levels in syringes, vials, and so forth contain-
eters in nuclear medicine are survey meters ing materials that are to be administered to
and dose calibrators. A typical ionization patients. Unlike other types of ionization
chamber survey meter is shown in Figure 7-3. chambers discussed in this section, dose cali-
The survey meter is battery operated and por- brators employ sealed and pressurized cham-
table. The ionization chamber consists of an bers filled with argon gas. This eliminates the
outer cylindrical electrode (metal or graphite- effect of changing barometric pressure on
coated plastic) with a wire electrode running output readings. Dose calibrators typically
down its center. There is often a pro�tective are calibrated to read directly in units of
cap on the end of the chamber for most mea- activity (becquerels or curies), with switches
surements; however, it is removed for mea- to set the display for different radionuclides.
surement of nonpenetrating radiations such Dose calibrators are discussed in detail in
as α particles, β particles, and low-energy Chapter 12, Section D.1.
(10 keV) photons. A device that records total charge collected
Survey meters are used to monitor radiation over time is the pocket dosimeter. The basic
levels for radiation protection purposes (see principles are illustrated in Figure 7-4. The
Chapter 23, Section E). Ionization current is ionization chamber electrodes are a central
displayed on a front-panel meter. Many older charging electrode and the outside case of the
units are calibrated to read traditional units dosimeter. They are insulated electrically
of exposure rate in roentgens per hour (R/hr) from one another and form an electrical capac-
or mR/hr. Newer units are calibrated to read itor. The capacitor is first charged to a refer-
Systeme International units of air kerma in ence voltage V by connecting the charging rod
grays per hour (Gy/hr), mGy/hr, and so forth, to a separate charging unit. If the capacitance
or have a switch-selectable option for choosing between the charging electrode and the case
between the two systems of units. The defini- is C, the charge stored on the capacitor is Q =
tions and relationships between these units V × C. When the chamber is exposed to
90 Physics in Nuclear Medicine

Outside
case

C
 Charging
electrode

 Insulator

FIGURE 7-4  Schematic representation of a pocket dosimeter.

radiation, electrical charge ΔQ is collected by dosimeters are suitable for measuring radia-
the electrodes, discharging the capacitor. The tion exposures down to approximately 10╯ mR
voltage change across the capacitor is mea- (air kerma of 0.1╯ mGy) to an accuracy of
sured and is related to the amount of electrical approximately 20%.
charge collected by the ionization chamber A basic problem with ionization chambers
electrodes (ΔQ = ΔV × C). is that they are quite inefficient as detectors
Pocket dosimeters are used in nuclear for x rays and γ rays. Only a very small per-
medicine to monitor radiation levels for radi- centage (<â•›1%) of x rays or γ rays passing
ation protection purposes. A typical system is through the chamber actually interact with
shown in Figure 7-5. The ionization chamber and cause ionization of air molecules. Indeed,
is contained in a small metal or plastic cyl- most of the electrical charge released in an
inder (~1.5╯ cm diameter × 10╯ cm long) that ionization chamber by photon radiations
can be clipped to a shirt pocket or collar. comes from secondary electrons knocked loose
Electrodes recessed into one end of the from the walls of the chamber by the incident
chamber are used to connect the dosimeter radiations rather than by direct ionization of
to a separate charger unit to charge up the air molecules. The relatively low detection
capacitor to the reference voltage. Voltage on efficiency of ionization chambers is not a
the capacitor causes a fine wire within the serious limitation in the applications described
chamber to be deflected. The position of the earlier; however, it precludes their use for
wire changes as the voltage on the capacitor most other applications in nuclear medicine,
changes. The wire is observed through a such as imaging.
viewing window at one end of the chamber. Two additional problems with ionization
Its position is read against a scale that has chambers should be noted. The first is that for
been calibrated in terms of the total radia- x rays and γ rays, their response changes with
tion recorded by the chamber, usually in photon energy because photon absorption in
units of air kerma (gray) or exposure (roent- the gas volume and in the chamber walls (i.e.,
gens) (see Chapter 23, Section E). Pocket detection efficiency) and relative penetration

FIGURE 7-5  Pocket dosimeter with charging system. (Courtesy Ludlum Measurements Inc., Sweetwater, Tx.)
7  •  Radiation Detectors 91

1.2

End-cap off

1.0

Exposure rate (indicated/actual)

0.8

0.6

End-cap on
0.4

0.2

0.0
10 100 1000
Photon energy (keV)
FIGURE 7-6  Energy response curve for a typical ionization chamber survey meter with and without a removable
protective end cap.

of photons through the chamber walls are increased to a sufficiently high value, the
both energy-dependent processes. Figure 7-6 electrons liberated by radiation gain such
shows a typical energy-response curve for a high velocities and energies when accelerated
survey meter. A second problem is that in toward the positive electrode that they cause
unsealed chambers the density of the air in additional ionization in collisions with other
the chamber, and hence its absorption effi- atoms in the gas. These electrons in turn can
ciency, changes with atmospheric pressure (ρ cause further ionization and so on. This
∝ Pâ•›) and temperature (ρ ∝ 1/T ). Most cham- cascade process is called the Townsend ava-
bers are calibrated to read accurately at sea- lanche or the gas amplification of charge. The
level pressure (Pref = 1.013╯N/m2 = 760╯mm╯Hg) factor by which ionization is increased is
and average room temperature (Tref = 22°C = called the gas amplification factor. This factor
295K). For other temperatures T and pres- increases rapidly with applied voltage, as
sures P the chamber reading must be cor- shown in Figure 7-7. The gas amplification
rected (multiplied) by a temperature-pressure factor may be as high as 106, depending on
correction factor the chamber design and the applied voltage.
Detectors that operate in the ascending
CTP = ( Pref × T ) /( P × Tref ) (7-1)
portion of the curve shown in Figure 7-7 are
Temperature must be expressed on the Kelvin called proportional counters. In this region,
scale in this equation (K = °C + 273). The the ionization caused by an incident radiation
correction is significant in some cases, for event is multiplied (amplified) by the gas
example, at higher elevations (P ≈ 0.85╯N/m2 amplification factor. The total amount of
≈ 640╯mm╯Hg at 1600-meter elevation). Note charge produced is equal to the number of
that temperature-pressure corrections are not ionizations caused by the primary radiation
required with sealed chambers, such as in event (at 34╯eV/ionization in air) multiplied
most dose calibrators. A defective seal on such by the amplification factor. Thus the total
an instrument obviously could lead to errone- charge produced is proportional to the total
ous readings. amount of energy deposited in the detector by
the detected radiation event.
3.  Proportional Counters Actually, proportional counters are not
In an ionization chamber, the voltage between simply ionization chambers operated at high
the electrodes is sufficient only to collect voltages but are specially constructed cham-
those charges liberated by direct action of the bers designed to optimize the gas amplifica-
ionizing radiations. However, if the voltage is tion effect, both in terms of the amount of
92 Physics in Nuclear Medicine

Amplitude of output pulse

Ionization
chamber
region
Proportional
counter
region

Applied voltage
FIGURE 7-7  Voltage response curve for a proportional counter. With increasing applied voltage, the charge collected
increases because of the gas amplification effect.

amplification and the uniformity of this are shown in Figure 7-8. The center wire
amplification within the chamber. In particu- (anode) is maintained at a high positive
lar, proportional counters are filled with gases voltage relative to the outer cylindrical elec-
that allow easy migration of free electrons, trode (cathode). The outer electrode may be a
because this is critical for the amplification metal cylinder or a metallic film sprayed on
effect. Common fill gases are the noble gases, the inside of a glass or plastic tube. Some GM
with argon and xenon being the most popular. counters have a thin radiation entrance
The major advantage of proportional coun- window at one end of the tube. The cylinder
ters versus ionization chambers is that the of the tube is sealed and filled with a special
size of the electrical signal produced by an gas mixture, typically argon plus a quenching
individual ionizing radiation event is much gas (discussed later).
larger. They are, in fact, useful for detecting When ionization occurs in a GM counter,
and counting individual radiation events. electrons are accelerated toward the center
Furthermore, because the size of an individ- wire. Gas amplification occurs in the GM
ual current pulse is proportional to the counter as in a proportional counter. In addi-
amount of energy deposited by the radiation tion to ionizing gas molecules, the accelerat-
event in the detector, proportional counters ing electrons also can cause excitation of gas
can be used for energy-sensitive counting, molecules through collisions. These excited
such as to discriminate between radiation gas molecules quickly (~10−9╯ sec) return to
events of different energies on the basis of the ground state through the emission of
electrical pulse size (see Chapter 10). They photons at visible or ultraviolet (UV) wave-
are still inefficient detectors for higher energy lengths. If a UV photon interacts in the 
x rays and γ rays. Consequently, they find gas, or at the cathode surface by photoelec-
very limited use in nuclear medicine. Propor- tric absorption (see Chapter 6, Section C.2),
tional counters are used mostly in research this releases another electron, which can
applications for measuring nonpenetrating trigger a further electron avalanche as it
radiations such as α particles and β particles. moves toward the anode (see Fig. 7-8). In
A practical application is discussed in Chapter this way, an avalanche ionization is propa-
12, Section D.2. gated throughout the gas volume and along
the entire length of the center wire.
4.  Geiger-Müller Counters As the avalanche progresses, the electrons,
A Geiger-Müller (GM) counter is a gas-filled being relatively light, are quickly collected,
detector designed for maximum gas amplifi- but the heavy, slow-moving positive ions are
cation effect. The principles of a GM counter not. Eventually, a “hose” of slow-moving
7  •  Radiation Detectors 93

Positive ions

Primary electron
Secondary electrons

Incident
radiation
Anode

Insulator
RL Signal

Outer cylinder
Thin window (cathode) V
 

Primary electron track

Secondary electron

Electron avalanche

Ultraviolet radiation

FIGURE 7-8  Operating principles of a Geiger-Müller counter. The incoming radiation produces ion pairs by direct
ionization and through secondary fast electrons (δ rays) created in the ionization process. These ion pairs are then
multiplied by an avalanche process that in turn triggers further avalanches through the emission of ultraviolet radia-
tion. This process is terminated when a sufficient number of positive ions collect around the anode, effectively reducing
the electric field experienced by the electrons owing to charge buildup at the anode.

positive charges is formed around the center Once the avalanche has terminated in a
wire. The avalanche then terminates because GM counter, an additional problem arises.
the positive ions reduce the effective electric The positive ion cloud moves toward the outer
field around the anode wire, eventually drop- electrode. When the ion cloud is very close to
ping it below the level required for gas the outer electrode, electrons are pulled out
multiplication. from it to neutralize the positive ions. Some
The avalanche ionization in a GM tube of these electrons enter higher-energy orbits
releases a large and essentially constant of the positive ions; when they eventually
quantity of electrical charge, regardless of drop into the lower-energy orbits, UV radia-
voltage applied to the tube (Fig. 7-9) or the tion is emitted. This can cause the release of
energy of the ionizing radiation event. The more electrons from the outer wall and set off
gas amplification factor may be as high as another avalanche. Thus if no precautions are
1010. The large electrical signal is easily taken, a single ionizing radiation event can
detected with electronic circuits. Thus a GM cause the GM counter to go into a pulsating
counter, like a proportional counter, can be series of discharges.
used to detect and count individual ionizing This problem is prevented by the introduc-
radiation events. However, because the size  tion of a quenching gas into the GM counter
of the electrical signal output is constant, gas mixture. Such GM counters are called
regardless of the energy of the radiation self-quenched. Effective quenching gases have
detected, a GM counter cannot be used to three properties: First, they tend to give up
distinguish between radiation events of dif- electrons easily. When the positive ion cloud
ferent energies. is formed, molecules of the quenching gas
94 Physics in Nuclear Medicine

Geiger-Müller
region
Amplitude of output pulse

Ionization
chamber
region

Proportional
counter
region

Applied voltage
FIGURE 7-9  Voltage response curve (pulse amplitude vs. applied voltage) for a Geiger-Müller counter.

neutralize other ions by donating electrons to applied to the counter electrodes. Figure 7-10
them. The ion cloud is thus converted into shows the results of such an experiment. This
ionized molecules of quenching gas. Second, curve is called the counting curve or plateau
when the quenching gas molecules are neu- curve of the GM counter. As the high voltage
tralized by electrons entering higher energy is increased, the counting rate increases
orbits, they deenergize themselves by dissoci- rapidly as more and more of the output pulses
ating into molecular fragments rather than exceed the counter threshold. When the
by emitting UV photons. Third, the quench- voltage is sufficient that essentially all pulses
ing gas molecules are strong absorbers of UV are above the threshold and are counted, a
radiation. Thus the few UV photons that are plateau region is reached. The point at which
released during neutralization of the positive the plateau begins is called the knee of the
ion cloud are quickly absorbed before they can curve. Further increases in voltage may still
set off another avalanche. increase the amplitude of the output pulses;
Commonly used quenching gases include however, the counting rate remains constant
heavy organic vapors (e.g., alcohol) and as the radiation source is constant.*
halogen gases (e.g., Cl2). The organic vapors When the voltage is increased to a very
are more effective quenching agents but have high value, the counting rate again begins to
the disadvantage that their molecular frag- increase. This happens when the voltage is so
ments do not recombine after dissociation. high that spontaneous ionization begins to
Thus an organic quenching gas eventually is occur in the chamber. The curve then enters
used up, typically after approximately 1010 the spontaneous discharge region. GM coun-
radiations have been detected. Halogen gas ters should not be operated in the spontane-
molecules recombine after dissociation and ous discharge region because no useful
thus have an essentially unlimited lifetime in information can be obtained there. Further-
a GM counter. more, if the counter contains an organic
A certain minimum voltage is required quenching gas, it is rapidly used up by the
between the electrodes of a GM counter to spontaneous discharges, thus shortening the
sustain an avalanche ionization and to raise
the amplitude of the pulses to the threshold
of the counting system. This voltage can be
determined by exposing the GM counter to a *Actually, for most GM counters the counting rate
constant source of radiation and observing increases by 1% to 2% per 100 volts in the plateau region.
the counting rate as a function of voltage This is of no practical consequence in nuclear medicine.
7  •  Radiation Detectors 95

Spontaneous
discharge

Knee
Counting rate

Plateau

Threshold

Applied voltage
FIGURE 7-10  Counting curve (counting rate from a fixed radiation source vs. applied voltage) for a Geiger-Müller
counter. As voltage increases, pulse amplitude increases above threshold of counting system electronics. When all
events produce a signal above the threshold, a plateau is reached. At very high voltages, spontaneous discharge events
occur within the chamber. These are not caused by radiation events but by electrical breakdown in the gas.

life of the counter. The proper operating


voltage is the plateau region, about one third
the distance from the knee to the spontaneous
discharge region.
GM counters are simple, rugged, and rela-
tively inexpensive radiation detectors. Much
of the early (pre-1950s) work in nuclear medi-
cine was done with GM counters; however,
they have since been replaced for most appli-
cations by other types of detectors. The major
disadvantages of GM counters are low detec-
tion efficiency (<â•›1%) for γ rays and x rays
and an inability to distinguish between radia-
tion events of different energies on the basis
of pulse size for energy-selective counting
(because all pulses from a GM counter are the
same size).
FIGURE 7-11  Radiation survey meter with an external
GM counters are used mostly in survey Geiger-Müller (GM) “pancake” counter radiation detec-
meters for radiation protection purposes. An tor attachment. In addition to the external detector
example is shown in Figure 7-11. The detector shown, some units have built-in GM counters. (Courtesy
in this survey meter is of the pancake type. Ludlum Measurements, Inc. Sweetwater, TX.)
The entrance window at the end of the counter
tube is a thin layer of mica (0.01-mm thick)
that is sufficiently thin to permit passage of
particles and low-energy photons into the
counter. The rather fragile window is pro- for example, 0.1-mm-thick aluminum or
tected by a wire screen. GM counters designed stainless steel. Many GM counters are pro-
for counting only relatively penetrating radia- vided with removable covers on the entrance
tions, such as γ rays and high-energy β window that can be used to distinguish
particles, have thicker, sturdier windows,  between penetrating and nonpenetrating
96 Physics in Nuclear Medicine

radiations by observing the difference between In spite of their apparent advantages, semi-
counting rates with and without the cover in conductor detectors have a number of prob-
place. GM survey meters are more sensitive lems that have limited their use in nuclear
than ionization chamber survey meters, typi- medicine. The first is that both Si and Ge
cally by a factor of approximately 10. (especially Ge) conduct a significant amount
of thermally induced electrical current at
room temperature. This creates a background
B.  SEMICONDUCTOR DETECTORS “noise current” that interferes with detection
of radiation-induced currents. Therefore Si
Semiconductor detectors are essentially solid- detectors (usually) and Ge detectors (always)
state analogs of gas-filled ionization cham- must be operated at temperatures well below
bers. Because the solid detector materials room temperature.
used in semiconductor detectors are 2000 to A second problem is the presence of impuri-
5000 times more dense than gases (see Table ties even in relatively pure crystals of Si and
7-1), they have much better stopping power Ge. Impurities (atoms of other elements)
and are much more efficient detectors for x enter into and disturb the regular arrange-
rays and γ rays. ment of Si and Ge atoms in the crystal matrix.
Semiconductor detectors normally are poor These disturbances create “electron traps”
electrical conductors; however, when they are and capture electrons released in ionization
ionized by an ionizing radiation event, the events. This results in a substantial reduction
electrical charge produced can be collected by in the amount of electrical signal available
an external applied voltage, as it is with gas- and limits the thickness of a practical detec-
filled detectors. This principle could not be tor to approximately 1╯cm. Because of the
applied using a conducting material for the relatively low atomic numbers of Si and Ge,
detector (e.g., a block of metal) because such this restricts their efficiency for detection of 
a material would conduct a large amount of γ rays.
current even without ionizing events. Insula- Two approaches have been used to solve
tors (e.g., glass) are not suitable detector the impurity problem. One is to prepare very
materials either, because they do not conduct pure samples of the detector material. This
even in the presence of ionizing radiation. has been accomplished only with Ge [high-
Hence only semiconductor materials can func- purity germanium (HPGe)] and is, unfortu-
tion as “solid ionization chambers.” nately, quite expensive. Also, the size of pure
The most commonly used semiconductor crystals is limited to approximately 5╯cm in
detector materials are silicon (Si) and germa- diameter by 1╯cm thick. Detectors made of
nium (Ge). More recently, cadmium telluride HPGe are sometimes called intrinsic Ge detec-
(CdTe) or cadmium zinc telluride (CZT) have tors. A second approach is to deliberately
been used as the detector material in small introduce into the crystal matrix “compensat-
nuclear medicine counting and imaging ing” impurities that donate electrons to fill
devices. Characteristics of these semiconduc- the electron traps created by other impuri-
tor materials are listed in Table 7-1. One ion- ties. Lithium (Li) is commonly used in Si and
ization is produced per 3 to 5╯eV of radiation Ge detectors for this purpose. Detectors made
energy absorbed. By comparison, this value of “lithium-doped” materials are called
for gases (air) is approximately 34╯eV per ion- lithium-drifted detectors, or Si(Li) or Ge(Li)
ization. Thus a semiconductor detector not detectors. Unfortunately, the process of pre-
only is a more efficient absorber of radiation paring Si(Li) or Ge(Li) crystals is time con-
but produces an electrical signal that is suming and expensive. Crystal sizes are
approximately 10 times larger (per unit of limited to a few centimeters in diameter by
radiation energy absorbed) than a gas-filled approximately 1╯cm thick for Si(Li) and
detector. The signal is large enough to permit approximately 5╯cm diameter by 5╯cm thick
detection and counting of individual radiation for Ge(Li).
events. Furthermore, the size of the electrical An additional problem is that Li ions tend
signal is proportional to the amount of radia- to “condense” within the crystal matrix at
tion energy absorbed. Therefore semiconduc- room temperature, especially in Ge. There-
tor detectors can be used for energy-selective fore Si(Li) and Ge(Li) not only must be oper-
radiation counting. For reasons discussed  ated at low temperatures (to minimize
in Chapter 10, Section C.1, they are in fact thermally induced background currents) but
the preferred type of detector for this Ge(Li) detectors must and Si(Li) detectors
application. should also be stored at low temperatures.
7  •  Radiation Detectors 97

Liquid nitrogen (T = 77K or −196°C) is used evaporates and the container needs periodic
for detector cooling. Ge(Li) detectors can  refilling—typically every 2 to 3 days, deÂ�
be ruined by only an hour or so at room tem� pending on container size and insulation
perature. Si(Li) detectors can tolerate ele- characteristics.
vated temperatures, but they provide optimum CdTe and CZT (which has properties very
performance if they also are stored at liquid similar to CdTe) are more recently developed
nitrogen temperatures. semiconductor materials that overcome two of
Because of the difficulties inherent in the major disadvantages of Si and Ge: (1) they
Li-drifted detectors, HPGe has become the can be operated at room temperature without
detector material of choice for γ-ray spectros- excessive electronic noise, and (2) their high
copy applications (see Chapter 10), and most atomic number means that even relatively
manufacturers have now stopped producing thin detectors can have good stopping effi-
Ge(Li) detectors. Si(Li) finds applications in ciency for detecting γ rays. Although CdTe
low-energy x-ray and β-particle spectroscopy, and CZT are now being used in some nuclear
in which its low atomic number is not a medicine counting and imaging devices, their
disadvantage. use has generally been restricted to small
Figure 7-12 shows schematically a typical detectors, or detectors comprising multiple
semiconductor detector assembly. The detec- small elements, because of the difficulty and
tor consists of a thin, circular disc of the expense of growing large pieces of CdTe or
detector material [Si(Li), Ge(Li), or HPGe] CZT with the required purity. Additional dis-
with electrodes attached to its opposite faces cussion of their properties for pulse-height
for charge collection. One electrode is a thin spectrometry is presented in Chapter 10,
metal foil fastened to the front surface Section C.1.
(“entrance window”), whereas the other is a
wire or set of wires embedded in the opposite
surface of the crystal. Other detector shapes C.  SCINTILLATION DETECTORS
and electrode configurations also are used.
Figure 7-12 also shows in cross-section an
apparatus used to cool the crystal with liquid 1.  Basic Principles
nitrogen. A “coldfinger” extends from the liq- As indicated earlier in this chapter, radiation
uid nitrogen container (a Dewar flask) to cool from radioactive materials interacts with
the detector. Some of the preamplifier elec- matter by causing ionization or excitation of
tronic circuitry also is cooled to reduce atoms and molecules. When the ionized or
electronic noise levels. Liquid nitrogen excited products undergo recombination or
deexcitation, energy is released. Most of the
energy is dissipated as thermal energy, such
as molecular vibrations in gases or liquids or
lattice vibrations in a crystal; however, in
some materials a portion of the energy is
released as visible light.* These materials are
called scintillators, and radiation detectors
made from them are called scintillation
detectors.
Liquid The scintillator materials used for detec-
nitrogen tors in nuclear medicine are of two general
types: inorganic substances in the form of
solid crystals and organic substances dis-
solved in liquid solution. The scintillation
mechanisms are different for these two 
types and are described separately in later
“Coldfinger” sections.
Vacuum A characteristic common to all scintillators
is that the amount of light produced following
Detector
*For simplicity, the term visible light is used to describe
FIGURE 7-12  Schematic representation of a typical scintillation emission. In fact, the emissions from many
semiconductor detector assembly. “Coldfinger” is a scintillators extend into the UV portion of the spectrum
thermal conductor for cooling the detector element. as well.
98 Physics in Nuclear Medicine

the interaction of a single γ ray, β particle, or compounds are commonly used for this mate-
other ionizing radiation, is proportional to the rial. The photoemissive surface is called the
energy deposited by the incident radiation in photoca�thode, and electrons ejected from it
the scintillator. The amount of light produced are called photoelectrons. The conversion effi-
also is very small, typically a few hundred to ciency for visible light to electrons, also known
a few thousand photons for a single γ-ray as the quantum efficiency, is typically 1 to 3
interaction within the energy range of inter- photoelectrons per 10 visible light photons
est for nuclear medicine imaging (70-511╯keV╛). striking the photocathode. The dependence of
In the early days of nuclear physics, it was quantum efficiency on the wavelength of the
common to study the characteristics of par- light is shown for a conventional bialkali pho-
ticles by observing and counting, in a dark- tocathode in Figure 7-14.
ened room, the scintillations produced by A short distance from the photocathode is
these particles on a zinc sulfide scintillation a metal plate called a dynode. The dynode is
screen. The obvious limitations on counting maintained at a positive voltage (typically
speed and accuracy with this system have 200-400╯V) relative to the photocathode and
been eliminated in modern application with attracts the photoelectrons ejected from it. 
the introduction of ultrasensitive electronic A focusing grid directs the photoelectrons
light detectors called photomultiplier (PMâ•›) toward the dynode. The dynode is coated with
tubes. a material having relatively high secondary
emission characteristics. CsSb also can be
2.  Photomultiplier Tubes used for this material. A high-speed photo-
PM tubes (also called phototubes and some- electron striking the dynode surface ejects
times abbreviated PMT ) are electronic tubes several secondary electrons from it. The elec-
that produce a pulse of electrical current tron multiplication factor depends on the
when stimulated by very weak light signals, energy of the photoelectron, which in turn is
such as the scintillation produced by a γ ray determined by the voltage difference between
or β particle in a scintillation detector. Their the dynode and the photocathode.
basic principles are illustrated in Figure 7-13. Secondary electrons ejected from the first
The inside front surface of the glass dynode are attracted to a second dynode,
entrance window of the PM tube is coated which is maintained at a 50-150╯V higher
with a photoemissive substance. A photo� potential than the first dynode, and the elec-
emissive substance is one that ejects electrons tron multiplication process is repeated. This
when struck by photons of visible light. occurs through many additional dynode
Cesium antimony (CsSb) and other bialkali stages (typically 9 to 12 in all), until finally a

Photocathode Photoelectron
Glass
Dynodes envelope Vacuum
Entrance Focusing
window grid

Anode

Light
photon C R
Output
signal

High voltage
supply

FIGURE 7-13  Basic principles of a photomultiplier tube.


7  •  Radiation Detectors 99

UV
30

25
Quantum efficiency (%)

20

15

10

0
300 350 400 450 500 550 600 650 700
Wavelength (nm)
FIGURE 7-14  Quantum efficiency as a function of wavelength for a typical bialkali photocathode. The peak occurs at
approximately 400╯nm, which is well-matched to the emission wavelength of many scintillators. UV, ultraviolet light.

shower of electrons is collected at the anode. PM tubes are sealed in glass and evacu-
Typical electron multiplication factors are ×3 ated. Electrical connections to the dynodes,
to ×6 per dynode. The total electron multipli- the photocathode, and the anode are made
cation factor is very large—for example, 610 through pins in the tube. The focusing of the
(~6 × 107) for a 10-stage tube with an average electron beam from one dynode to the next
multiplication factor of 6 at each dynode. can be affected by external magnetic fields.
Thus a relatively large pulse of current is Therefore PM tubes often are wrapped in
produced when the tube is stimulated by even metal foil for magnetic shielding. “Mu-metal,”
a relatively weak light signal. Note that the an alloy composed of iron, nickel, and small
amount of current produced is proportional to amounts of copper and chromium, is com-
the intensity of the light signal incident on monly used for this purpose. PM tubes come
the photocathode and thus also to the amount in various shapes (round, square, and hexago-
of energy deposited by the radiation event in nal) and sizes (Fig. 7-15). Most of those used
the crystal. in nuclear medicine have photocathodes in
PM tubes require a high-voltage supply. the range of 1- to 7.5-cm diameter. There are
For example, as shown in Figure 7-13, if the also position-sensitive and multichannel PM
tube has 10 dynodes, with the first at +300╯V tubes available that have the ability to deter-
relative to the photocathode and the remain- mine the location of incident light on the
ing 9 dynodes and the anode at additional photocathode.
+100╯V increments, a voltage of +1300╯V is
needed. Furthermore, the voltage supply 3.  Photodiodes
must be very stable because the electron mul- In some applications, the PM tube may be
tiplication factor is very sensitive to dynode replaced by a light-sensitive semiconductor
voltage changes. Typically a 1% increase in detector, such as a Si photodiode. Note that
high voltage applied to the tube increases the in this case, the semiconductor is not being
amount of current collected at the anode by used to detect the γ rays directly but to detect
approximately 10%. This is of considerable the visible light emitted from a scintillator
importance in applications where pulse size material in which a γ ray has interacted. The
is being measured, such as in pulse-height photons from the scintillator have sufficient
spectrometry to determine γ-ray energies (see energy to cause ionization within Si, and the
Chapter 10). total charge produced is proportional to the
100 Physics in Nuclear Medicine

FIGURE 7-15  Assortment of photomultiplier tubes illustrating their wide variety of shapes and sizes. (Courtesy
Hamamatsu Corp., Bridgewater, NJ.)

number of scintillation light photons incident the gas-filled GM counter (Section A.4), and
on the photodiode. These photodiode detec- the output signal of the APD becomes very
tors have the advantage that they can be large and independent of the energy of the
made very small in area and that they are incident radiation. The gain of such devices
typically only a few millimeters thick, includ- can be as high as 107. Light-sensitive detec-
ing the packaging. They also have signifi- tors consisting of a large number of tiny 
cantly higher quantum efficiency than PM (20-50 µm) geiger-mode APDs that are incor-
tubes, with values ranging typically between porated into a single device are being devel-
60% and 80%. However, conventional Si  oped for use in scintillation detectors.
photodiodes have unity gain (compared with
106 to 107 for a PM tube), requiring very low-
noise electronics for readout. 4.  Inorganic Scintillators
A related device, the Si avalanche photo� Inorganic scintillators are crystalline solids
diode (APD) uses a very high internal electric that scintillate because of characteristics of
field such that each electron produced within their crystal structure. Individual atoms and
the device gains enough energy between colli- molecules of these substances do not scintil-
sions to create further ionization. This is anal- late. They are scintillators only in crystalline
ogous to the proportional region for gas-filled form. Table 7-2 summarizes the properties of
detectors that was discussed previously in a number of inorganic scintillators of interest
Section A.3. APD detectors can reach gains of for nuclear medicine applications.
102 to 103 but still require low-noise electronics Some inorganic crystals are scintillators in
for successful operation. The gain of these their pure state; for example, pure NaI crys-
devices also is a very strong function of bias tals are scintillators at liquid nitrogen tem-
voltage and temperature, and these parame- peratures. Most are “impurity activated,”
ters therefore must be very carefully controlled however. These are crystals containing small
for stable operation. These types of solid-state amounts of “impurity” atoms of other ele-
light detectors are used presently only in  ments. Impurity atoms in the crystal matrix
specialized nuclear medicine systems, such  cause disturbances in its normal structure.
as small animal scanners (see Chapter 17, Because they are responsible for the scin�
Section A.4, and Chapter 18, Section B.5) and tillation effect, the impurity atoms in the
dual-modality positron emission tomography– crystal matrix are sometimes called activator
magnetic resonance imaging (PET-MRI) centers. Some impurity-activated scintillators
systems (see Chapter 19, Section F). that have been used in radiation detectors
APDs also can be operated at higher bias include sodium iodide [NaI(Tl)] and cesium
voltages in geiger mode. This is analogous to iodide [CsI(Tl)]. In each case, the element in
7  •  Radiation Detectors 101

TABLE 7-2â•…
PROPERTIES OF SOME SCINTILLATOR MATERIALS USED IN NUCLEAR MEDICINE

Property NaI(Tl) BGO LSO(Ce) GSO(Ce) CsI(Tl) LuAP(Ce) LaBr3(Ce) Plastic*


3
Density (g/cm ) 3.67 7.13 7.40 6.71 4.51 8.34 5.3 1.03
Effective atomic number 50 73 66 59 54 65 46 12
Decay time (nsec) 230 300 40 60 1000 18 35 2
Photon yield (per keV) 38 8 20-30 12-15 52 12 61 10
Index of refraction 1.85 2.15 1.82 1.85 1.80 1.97 1.9 1.58
Hygroscopic Yes No No No Slightly No Yes No
Peak emission (nm) 415 480 420 430 540 365 358 Various
*Typical values—there are many different plastic scintillators available.
BGO, Bi3Ge4O12; GSO(Ce), Gd2SiO5(Ce); LSO(Ce), Lu2SiO5(Ce); LuAP(Ce), LuAlO5(Ce)

parentheses is the impurity that is added to Figure 7-16 shows the construction of a
create activator centers in the crystal. typical scintillation detector consisting of a
The most commonly used scintillator for NaI(Tl) crystal and PM tube assembly. The
detectors in nuclear medicine is NaI(Tl). Pure crystal is sealed in an aluminum or stainless-
NaI crystals are scintillators only at liquid steel jacket with a transparent glass or plastic
nitrogen temperatures. They become efficient optical window at one end to permit the exit
scintillators at room temperatures with the of scintillation light from the crystal to the
addition of small amounts of thallium. Single PM tube. A transparent optical “coupling
crystals of NaI(Tl) for radiation detectors are grease” is used between the crystal and the
“grown” from molten sodium iodide to which PM tube to minimize internal reflections at
a small amount of thallium (0.1-0.4 mole this interface. The crystal and PM tube are
percent) has been added. Crystals of rela- hermetically sealed in a light-tight jacket to
tively large size are grown in ovens under keep out moisture and extraneous light and
carefully controlled temperature conditions. for mechanical protection. The inside surface
For example, crystals for gamma cameras of the radiation entrance window and sides of
(see Chapter 13) use NaI(Tl) crystals that are the crystal are coated with a highly reflective
typically 30-50╯cm in diameter by 1-cm thick. diffuse material to maximize the light

Scintillation
Photoelectrons light
Reflector

PM Tube NaI(Tl)

 ray

First
Photocathode Interaction
dynode
Mu-metal
shield
FIGURE 7-16  Arrangement of NaI(Tl) crystal and photomultiplier (PM) tube in a typical scintillation detector
assembly.
102 Physics in Nuclear Medicine

collected by the PM tube photocathode. With 3. It is transparent to its own scintillation


efficient optical coupling, good reflective sur- emissions. Therefore there is little loss
faces, and a crystal free of cracks or other of scintillation light caused by self-
opacifying defects, approximately 30% of the absorption, even in NaI(Tl) crystals of
light emitted by the crystal actually reaches relatively large size.
the cathode of the PM tube. Some NaI(Tl) 4. It can be grown relatively inexpensively
detectors have very thin aluminum or beryl- in large plates, which is advantageous
lium foil “entrance windows” to permit detec- for imaging detectors.
tion of radiations having relatively low 5. The scintillation light is well-matched in
penetrating power, such as low-energy x rays wavelength to the peak response of the
and γ rays (E  10╯keV) and β particles; PM tube photocathode (see Fig. 7-14).
however, most NaI(Tl) detectors have thicker The emission spectrum of light from
entrance windows of aluminum or stainless NaI(Tl) is shown in Figure 7-18.
steel and are best suited for detecting higher- Some disadvantages of NaI(Tl) detectors are
energy γ rays (E  50╯keV). Figure 7-17 shows the following:
some typical integral NaI(Tl) crystal and PM 1. The NaI(Tl) crystal is quite fragile and
tube assemblies. easily fractured by mechanical or
Some reasons for the usefulness of NaI(Tl) thermal stresses (e.g., rapid tempera-
scintillation detectors include the following: ture changes). Fractures in the crystal
1. It is relatively dense (ρ = 3.67╯g/cm3) and do not necessarily destroy its usefulness
contains an element of relatively high as a detector, but they create opacifica-
atomic number (iodine, Z = 53). Therefore tions within the crystal that reduce the
it is a good absorber and a very efficient amount of scintillation light reaching
detector of penetrating radiations, such the photocathode.
as x rays and γ rays in the 50- to 250-keV 2. Sodium iodide is hygroscopic. Exposure
energy range. The predominant mode of to moisture or a humid atmosphere
interaction in this energy range is by causes a yellowish surface discoloration
photoelectric absorption. that again impairs light transmission to
2. It is a relatively efficient scintillator, the PM tube. Thus hermetic sealing is
yielding one visible light photon per required.
approximately 30╯eV of radiation energy 3. At higher γ-ray energies (â•›250╯keV),
absorbed. the predominant mechanism of interac-
tion is by Compton interaction, and
larger volumes of NaI(Tl) are required
for adequate detection efficiency.
Other types of detectors have advantages
over NaI(Tl) detectors in certain areas. For
example, gas-filled detectors are cheaper (but
have much lower detector efficiency), and
semiconductor detectors have better energy
resolution (but are expensive to use in large-
area imaging cameras). However, the overall
advantages of NaI(Tl) have made it the detec-
tor of choice for almost all routine applica-
tions in nuclear medicine involving γ-ray
detection in the 50-250-keV energy range.
At higher energies, particularly for detec-
tion of the 511-keV emissions from positron
emitters, denser scintillators generally are
preferred. Bismuth germanate (Bi4Ge3O12;
BGO) is a commonly used scintillator in PET
imaging, because of its excellent detection
efficiency at 511╯keV. Lutetium oxyortho�
silicate [Lu2SiO5(Ce); LSO] is slightly less effi-
cient at 511╯keV than BGO, but is brighter
FIGURE 7-17  NaI(Tl) crystal and photomultiplier tube
and faster and may sometimes offer advan-
assemblies. (Courtesy Crystals and Detectors Division, Saint- tages over BGO when the counting rate 
Gobain Ceramics and Plastics, Inc., Newbury, OH.) on the detector is high, when fast timing 
7  •  Radiation Detectors 103

UV

1.00

Intensity (arbitrary units) 0.80

0.60

0.40

0.20

0.00
300 350 400 450 500 550 600 650 700
Wavelength (nm)
FIGURE 7-18  The emission spectrum of NaI(Tl) scintillator at room temperature. UV, ultraviolet light. (Data courtesy
Kanai Shah and Jarek Glodo, Radiation Monitoring Devices Inc., Watertown, MA.)

information is needed, or when small scintil- The cross section for photoelectric interaction
lator elements are to be decoded in an imaging depends strongly on the atomic number of a
system (see Chapter 18, Section B). However, material (see Chapter 6, Section D.1). The
LSO is rather expensive to grow, because of cross-section for Compton interaction is lin-
its high melting point and its raw material early related to atomic number. When com-
costs. A related material, lutetium yttrium paring the ability of different scintillator
orthosilicate (LYSO—LSO in which a small materials to stop high-energy γ rays, the
fraction of the lutetium atoms are replaced effective atomic number is a useful and con-
with yttrium) has scintillation properties venient parameter. It is a way of estimating
very similar to LSO. BaF2 and CsF also have the atomic number that represents the atten-
historically been used in positron cameras uation properties of a compound or a mixture
because of their very fast decay time (which of molecules. The effective atomic number,
is important for timing of γ-ray interactions Zeff, is defined as
in coincidence detection) (see Chapter 18,
Section A.2). However, their low detection x
efficiency compared with BGO and LSO has Zeff = w1 Z1x + w2 Z2x +  wn Znx (7-2)
prevented any widespread application.
New scintillator materials continue to be where wi is a weighting factor proportional to
discovered and developed. Among the more the fractional number of electrons per gram
pro�mising recent candidates for nuclear medi- for element i and can be calculated as
cine applications are LuAP [LuAlO3(Ce)], lan-
thanum bromide [LaBr3(Ce)], and lanthanum mi Zi
chloride [LaCl3(Ce)]. wi = (7-3)
∑ i=1 mi Zi
n

5.  Considerations in Choosing an where mi represents the number of atoms of


Inorganic Scintillator element i present in the compound or mixture.
The ability of a scintillator to stop high- The power x depends on the energy of the
energy γ rays (100╯keV) is of importance, γ rays. For γ rays in the 100- to 600-keV range,
particularly in nuclear medicine imaging. x is typically taken to be between 3 and 3.5.1
104 Physics in Nuclear Medicine

handle is approximately 1/2τ. Faster scintil-


EXAMPLE 7-1
lators detectors therefore can handle higher
Calculate the effective atomic number of BGO event rates on the detector.
(Bi4Ge3O12). Compare this with the value for The efficiency of the scintillator in convert-
NaI(Tl). (Ignore the contribution of the trace ing a γ ray into visible light photons (photon
amounts of thallium.) yield) is important in determining the preci-
sion with which the energy of the interacting
Answer γ ray can be determined. This becomes rele-
There are three elements contributing to vant in many counting and imaging systems
BGO: Bi (Z = 83), Ge (Z = 32), and O (Z = 8). in which it is important to distinguish between
The denominator for the weighting factors is γ rays that have Compton scattered in the
(83 × 4) + (32 × 3) + (8 × 12) = 524. The weight- sample (and therefore lost energy; see Chapter
ing factor for Bi is (83 × 4) / 524 = 0.634, for 6, Section C.3) and those that remain unscat-
Ge is (32 × 3) / 524 = 0.183, and for O is (8 × tered. Higher photon yield also is important
12) / 524 = 0.183. These three weighting in determining the positioning accuracy in
factors add to 1, as they should. Then Zeff can many imaging systems in which it is common
be calculated as to share the limited number of scintillation
Zeff = (0.634 × 833.5 + 0.183 photons among multiple PM tubes to deter-
mine the location of an interaction (see
× 323.5 + 0.183 × 83.5 )1 / 3.5
Chapter 13 and Chapter 18, Section B).
= 73.1 The index of refraction of a scintillator plays
NaI(Tl) consists of Na (Z=11) and I (Z=53) a role in determining how efficiently scintilla-
atoms that are present in equal quantities. tion light can be coupled from a scintillator
The weighting factor for Na is 53/(53+11) = crystal into a PM tube. The index of refraction
0.828 and for I is 11/(53+11) = 0.172. There- of the glass entrance window on a PM tube is
fore Zeff for NaI(Tl) is ~1.5. Therefore for best transmission of light
from the scintillator into the PM tube with
Zeff = (0.828 × 533.5 + 0.172 × 113.5 )1 / 3.5 minimal internal reflection at the scintillator

= 50.2 crystal and PM tube interface, the scintillator
should have an index of refraction as close to
1.5 as possible. In practice, most scintillators
In addition to choosing a scintillator that of interest have indices of refraction signifi-
has sufficient stopping power for the efficient cantly higher than 1.5 and this is one reason
detection of γ rays with a particular energy, why only a fraction of the scintillation light
the other properties listed in Table 7-2 also produced actually reaches the PM tube.
influence the choice of scintillator materials Lastly, it is important that the emission
for a specific application. The decay time of spectrum of the light produced by the scintil-
the scintillator is important in two respects. lator is a good match for the quantum effi-
Firstly, it determines the precision with which ciency of the photodetector that is used to
the time of γ-ray interaction in the scintillator convert the scintillation light into an elec-
can be determined. Faster light production tronic pulse. In the case of a PM tube with 
within the scintillator (faster decay time) a standard bialkali photocathode (see Fig.
results in better timing precision. This is 7-14), it is apparent that scintillators that
important in nuclear medicine applications in have their peak light emission in the range of
which timing is important, most notably in 350-475╯nm are optimal. NaI(Tl) is an example
PET in which coincident 511╯keV annihila- of a scintillator that has an emission spec-
tion photons are detected (see Chapter 18, trum (see Fig. 7-18) that matches the quantum
Section A). Secondly, the decay time of the efficiency of PM tubes very well. The trans-
scintillator is a limiting factor in how many mission of the scintillation light through the
γ-ray interactions a detector can process per glass used in the PM tube entrance window
unit time. To unambiguously detect two inter- also must be considered. Many glasses are
actions, they should be separated by roughly efficient absorbers of UV light at wavelengths
2-3 times the decay time; otherwise events significantly shorter than ~350╯nm.
“pile up” on top of each other, leading to dead
time (see Chapter 11, Section C). As a rough 6.  Organic Scintillators
rule of thumb, if the scintillator has a decay In contrast with inorganic scintillators, 
time of τ, the maximum event rate that a the scinÂ�tillation process in organic scintilla-
detector made using that scintillator can tors is an inherent molecular property. The
7  •  Radiation Detectors 105

scintillation mechanism is one of molecular emits light. Some common primary scin-
excitation (e.g., by absorbing energy from a γ tillators include p-bis-(omethylstyryl)
ray or β particle) followed by a deexcitation benzene (abbreviated as bis-MSB) and
process in which visible light is emitted. 2,5-diphenyloxazole (also known as
These substances are scintillators whether PPO).
they are in solid, liquid, or gaseous forms. 3. The emissions of the primary solute are
Certain plastics (e.g., see Table 7-2) are not always well matched to the response
organic scintillators and have been used for characteristics of PM tubes. Therefore a
direct detection of β particles emitted from secondary solute, or waveshifter, is some-
radionuclides, particularly in compact probes times added to the solution. The function
designed for surgical use (see Chapter 12, of this material is to absorb emissions of
Section F.2). A more common application for the primary solute and reemit photons
organic scintillators, however, is to employ of longer wavelength, which are better
them in liquid form for liquid scintillation matched to the PM tube response.
(LS) counting. In these systems, the scintilla- 1,4-di-(2-5-pheny�loxazole) benzene (also
tor is dissolved in a solvent material in a glass known as POPOP) is a commonly used
or plastic vial and the radioactive sample is secondary scintillator.
added to this mixture. The vial is then placed 4. LS solutions frequently contain addi-
in a light-tight enclosure between a pair of tives to improve some aspect of their
PM tubes to detect the scintillation events performance, such as the efficiency of
(Fig. 7-19). energy transfer from the solvent to 
LS solutions consist of four components: the primary solute. Solubilizers (e.g.,
1. An organic solvent comprises most of the hyamine hydroxide) are sometimes
solution. The solvent must dissolve not added to improve the dissolution of
only the scintillator material but also added samples such as blood.
the radioÂ�active sample added to it. The The precise “cocktail” of solvent, primary
solvent actually is responsible for most and secondary solutes, and additives depends
of the direct absorption of radiation on the sample type that is being measured. A
energy from the sample. High-speed wide variety of different LS cocktails opti-
electrons generated by ionizing radia- mized for different applications are available
tion events in the solvent transfer energy commercially.
to the scintillator molecules, causing the Because of the intimate relationship
scintillation effect. Commonly used sol- between sample and detector, LS counting is
vents include di-iso-propylnapthalene the method of choice for efficient detection of
(DIN) and phenylxylylethane (PXE), particles, low-energy x rays and γ rays, and
which are replacing traditional, more other nonpenetrating radiations. It is widely
environmentally harsh solvents such as used for measurement of 3H and 14C. In
toluene and xylene. medical applications, it is used primarily for
2. The primary solute (or primary fluor) sensitive assay of radioactivity in biologic
absorbs energy from the solvent and specimens, such as blood and urine.

Liquid scintillator solution


containing dissolved
radioactive sample

Photomultiplier tube Photomultiplier tube

Scintillation
light
FIGURE 7-19  Arrangement of sample and detector for liquid scintillation counting. The sample is dissolved in a liquid
scintillator solution in a glass or plastic vial.
Although well suited for counting non- to reduce the concentration of primary
penetrating radiations in biologic samples, and secondary solutes in the final 
LS counters have numerous drawbacks as solution, thus reducing the scintillator
general-purpose radiation detectors. They are output efficiency.
inefficient detectors of penetrating radiations Quenching can be minimized in various
such as γ rays and x rays of moderate energy ways. For example, dissolved oxygen may be
because the detector solution is composed  purged by ultrasound, and hydrogen peroxide
primarily of low-density, low-Z materials. In may be added for color bleaching. However,
addition, liquid scintillators generally have there are no convenient ways to eliminate 
low light output, only about one third that of all causes of quenching; therefore a certain
NaI(Tl). This problem is worsened by the rela- amount must be accepted in all practical 
tively inefficient light coupling from the scin- LS counting. Quenching becomes a serious
tillator vial to the PM tubes as compared with problem when there are wide variations in its
NaI(Tl) integral detectors. extent from one sample to the next. This
For sample counting, special sample prepa- causes unpredictable variations in light
ration may be required to dissolve the sample.  output, for the same amount of radiation
Problems in sample preparation are discussed energy absorbed, from one sample to the next.
in Chapter 12, Section C.6. Also, the sample Quench correction methods are employed in
itself is “destroyed” when it is added to the LS counters to account for this effect (Chapter
scintillator solution. 12, Section C.5).
Finally, all LS counting suffers from the
problem of quenching. Quenching in this
context refers to any mechanism that reduces REFERENCE
the amount of light output from the sample 1. Johns HE, Cunningham JR: The Physics of Radiology,
(not to be confused with the electrical ed 4, Springfield, IL, 1983, Charles C Thomas, pp
241-243.
quenching that occurs in GM counters; see
Section A.4). There are basically three types
of LS quenching: BIBLIOGRAPHY
1. Chemical quenching is caused by sub- A comprehensive reference for many different
stances that compete with the primary radiation detectors is the following:
fluor for absorption of energy from the Knoll GF: Radiation Detection and Measurement, ed 4,
solvent but that are themselves not scin- New York, 2010, John Wiley.
tillators. Dissolved oxygen is one of the
A detailed reference for inorganic scintillator
most troublesome chemical quenchers. mechanisms, properties, growth, and applications
2. Color quenching is caused by substances is the following:
that absorb the emissions of the primary Lecoq P, Annenkov A, Getkin A, Korzhik M, Pedrini C:
or secondary solute. Blood and other Inorganic Scintillators for Detector Systems: Physical
colored materials are examples. Fogged Principles and Crystal Engineering. Berlin, 2006,
or dirty containers can also produce a Springer.
type of color quenching. A detailed general reference for scintillation
3. Dilution quenching occurs when a rela- detectors is the following:
tively large volume of sample is added Birks JB: The Theory and Practice of Scintillation Count-
to the scintillator solution. The effect is ing. London, 1967, Pergamon Press.
chapter
8 
Electronic
Instrumentation
for Radiation
Detection Systems

Most of the radiation detectors used in nuclear relatively small amplitude. In addition, most
medicine are operated in a “pulse mode”; that of the detectors listed have relatively high
is, they generate pulses of electrical charge or output impedance, that is, a high internal
current that are counted to determine the resistance to the flow of elec�trical current. In
number of radiation events detected. In addi- handling electronic signals, it is important
tion, by analyzing the amplitude of pulses that the impedance levels of successive com-
from the detector, it is possible with energy- ponents be matched to one another, or elec-
sensitive detectors, such as scintillation and tronic interferences that distort the pulse
semiconductor detectors and proportional signals may develop and system performance
counters, to determine the energy of each will be degraded.
radiation event detected. Selection of a narrow The purposes of a preamplifier (or preamp)
energy range for counting permits discrimi- are threefold: (1) to amplify, if necessary, the
nation against events other than those of the relatively small signals produced by the radi-
energy of interest, such as scattered radiation ation detector, (2) to match impedance levels
and background radiation or the multiple between the detector and subsequent compo-
emissions from a mixture of radionuclides. nents in the system, and (3) to shape the
Figure 8-1 shows in schematic form the signal pulse for optimal signal processing by
basic electronic components of a nuclear the subsequent components.
radiation-counting instrument. These compo- There are two main types of preamplifier
nents are present in systems ranging from the configurations used with radiation detectors:
most simple sample counters to complex the voltage-sensitive preamplifier and the
imaging instruments. The purpose of this charge-sensitive preamplifier. Figure 8-2
chapter is to describe the basic principles of shows a simp�lified diagram of these two con-
these components. The electronics for specific figurations. The symbol represents
systems also are described in Chapters 10, 12 the signal (pulse)-amplifying component. The
to 14, and 18. Basic principles of electricity and resistor (R) and capacitor (C) provide pulse
electronics are reviewed in the sources cited in shaping. The signal from the detector is typi-
the Bibliography at the end of this chapter. cally a sharply rising pulse of electrical
current of relatively short duration (1╯ µsec,
except for Geiger-Müller (GM) counters; see
A.  PREAMPLIFIERS Table 8-1). The voltage-sensitive preamp
amplifies any voltage that appears at its
Table 8-1 summarizes the pulse output char- input. Because radiation detectors are charge-
acteristics of detectors used in nuclear medi- producing devices, this input voltage, Vi, is
cine. Most of them produce pulse signals of given by the ratio of the charge, Q, and the
107
108 Physics in Nuclear Medicine

High voltage supply

Incident
radiation Radiation Counter /
Preamplifier Amplifier
detector digitizer

FIGURE 8-1  Schematic representation of the electronic components for a nuclear radiation counting system.

intrinsic capacitance of the detector and other detector. The resulting output voltage, given
components in the input circuit, Ci: by
Q Q
Vi = (8-1) Vo ≈ − (8-3)
Ci Cf

With energy-sensitive detectors, the amount is seen to be independent of the input capaci-
of charge, Q, and thus the amplitude tance, Ci.
of the voltage Vi are proportional to the The electrical charge leaks off the feedback
energy of the radiation event detected. The capacitor through the resistor of resistance Rf,
output voltage, Vo, in this configuration is causing the voltage on the capacitor and at the
approximately outputs of the amplifier element to decrease
exponentially with time t according to
R2
Vo ≈ − Vi (8-2)
R1 V = Vo e− t / R f Cf (8-4)

in which R1 and R2 are as shown in Figure The product Râ•›f × Cf is called the time constant
8-2. The minus sign indicates that the polar- τ of the pulse-shaping circuit. The voltage
ity of the pulse has been changed. decreases exponentially, dropping by 63% of
In semiconductor detectors, the input cap� its initial value during one time constant
acitance of the detector is sensitive to operat- interval (see Fig. 8-2C). When Râ•›f is given in
ing conditions, particularly temperature. ohms and Cf in farads, the time constant is
Therefore the proportionality between charge given in seconds. Typical preamplifier time
and the voltage seen at the preamp input may constants for nuclear medicine detectors
not be stable. The charge-sensitive preampli- (excepting those applications that require fast
fier overcomes this undesirable feature by timing signals) are 20 to 200╯ µsec.
using a feedback capacitor of capacitance Cf The amount of amplification provided by
to integrate the charge from the radiation the amplifier element of the preamplifier

TABLE 8-1â•…
TYPICAL SIGNAL OUTPUT AND PULSE DURATION OF VARIOUS RADIATION DETECTORS

Signal Pulse Duration


Detector (V) (µsec)
Sodium iodide scintillator with photomultiplier tube 10−1-1 0.23*
Lutetium oxyorthosilicate scintillator with photomultiplier 10−1-1 0.04*
tube
Liquid scintillator with photomultiplier tube 10−2-10−1 10−2*
Lutetium oxyorthosilicate scintillator with avalanche 10−5-10−4 0.04*
photodiode
Direct semiconductor detector 10−4-10−3 10−1-1
Gas proportional counter 10−3-10−2 10−1-1
Geiger-Müller counter 1-10 50-300
*Mean decay time.
8  •  Electronic Instrumentation for Radiation Detection Systems 109

R2

R1

A
Vi Ci Vo

Radiation detector
A
Rf

Cf

A
Vi Ci Vo

Radiation detector
B

63%

Preamplifier

Input Output
C
FIGURE 8-2  A, Simplified circuit diagram of a voltage-sensitive preamplifier. The output voltage is determined
by the amount of charge from the radiation detector, the input capacitance Ci, and the resistances R1 and R2. B, Sim-
plified circuit diagram of a charge-sensitive preamplifier. The output voltage is determined by the charge from the
radiation detector and the value of the feedback capacitor Cf. The symbol represents a voltage or current
amplifying element. C, Input and output pulse signals for a charge-sensitive preamplifier. τ = (Râ•›f × Cf) is the time
constant of the pulse-shaping circuit.

varies with the type of detector. With scintil- provides this amount of gain without introduc-
lation detectors that use photomultiplier (PM) ing “noise signals” and temperature-related
tubes, the PM tube already provides a consid- gain instabilities. Most of the modern high-
erable degree of amplification (106-107); thus gain preamplifiers employ field-effect transis-
relatively little additional amplification may tors, which provide the desired low-noise and
be needed. Typically, a preamplifier gain temperature-stability characteristics.
factor (ratio of output to input amplitudes) of For energy-sensitive detectors, the pream-
5-20 is used for these detectors; however, plifier must operate in a linear fashion; that
some NaI(Tl):PM tube systems employ no is, the amplitude of the signal out must be
preamplifier gain (gain factor of 1). directly proportional to the amount of charge
Detectors producing smaller signals, such delivered to it by the detector. This preserves
as semiconductor detectors, may require a the relationship between pulse amplitude and
relatively high level of preamplifier gain, energy of the radiation event detected, so that
perhaps in the range of 103-104. It is not a subsequent energy analysis may be applied to
trivial problem to design an amplifier that the pulse signals.
110 Physics in Nuclear Medicine

For the best results, the preamplifier com- The gain factor on an amplifier may range
ponent should be located as close as physi- from ×1 to ×1000. Usually it is adjustable, first
cally possible to the detector component. This by a coarse adjustment (i.e., ×2, ×4, ×8) and
maximizes the electronic signal-to-noise ratio then by a fine gain adjustment providing gain
(SNR) by amplifying the signal before addi- factors between the coarse steps. The coarse
tional noise or signal distortion can occur in gain adjustment permits amplification of
the long cable runs that frequently separate pulses over a wide range of amplitudes from
the detector from the rest of the signal- different detectors and preamplifiers to the
processing components. This is particularly maximum output capability of the amplifier.
critical for detectors with small output signals The fine gain adjustment permits precise cali-
(e.g., semiconductor detectors or scintillation bration of the relationship between amplifier
detectors used for detecting low-energy radia- output pulse amplitude (volts) and radiation
tions). It also is important for applications  energy absorbed (keV or MeV). For example,
in which energy resolution is critical (see a convenient ratio might be 10╯V of pulse
Chapter 10, Section B.7). Frequently, detec- amplitude per 1╯MeV of radiation energy
tors and preamplifiers are packaged and sold absorbed in the detector.
as single units. Pulse shaping—i.e., pulse shortening—is
an essential function of the amplifier. The
output of the preamp is a sharply rising pulse
B.  AMPLIFIERS that decays with a time constant of about
50╯ µsec, returning to baseline after approxi-
mately 500╯ µsec. Thus if a second pulse occurs
1.  Amplification and Pulse-Shaping within 500╯ µsec, it rides on the tail of the
Functions previous pulse, providing incorrect amplitude
The amplifier component of a nuclear count- information (Fig. 8-3). The system could not
ing instrument has two major functions: (1) operate at counting rates exceeding a few
to amplify the still relatively small pulses hundred events per second without introduc-
from the preamp to sufficient amplitude ing this type of amplitude distortion.
(volts) to drive auxiliary equipment (pulse- The pulse-shaping circuits of the amplifier
height analyzers, scalers, etc.), and (2) to must provide an output of cleanly separated
reshape the slow decaying pulse from the pulses, even though the output pulses from
preamp into a narrow one to avoid the problem the preamp overlap. It must do this without
of pulse pile-up at high counting rates and to distorting the information in the preamplifier
improve the electronic SNR. signal, which is, mainly, (1) pulse amplitude

Preamplifier
output
Voltage

Amplifier
output

Time
FIGURE 8-3  Sequence of pulse signals in a radiation counting system. Top, Relatively long preamplifier time constant
results in overlapping of pulse signals. Bottom, Amplifier output pulses have been shortened but without significant
loss of amplitude or timing information.
8  •  Electronic Instrumentation for Radiation Detection Systems 111

(proportional to the energy of radiation event illustrates how the CR circuit discriminates
for energy-sensitive detectors) and (2) rise against low-frequency noise signals.
time (time at which the radiation event  Figure 8-4B shows an RC, or integration
was detected). An additional function of the circuit. (Note that differentiation and integra-
pulse-shaping circuits is to discriminate tion differ only by the interchanging of the
against electronic noise signals, such as resistor R and the capacitor C.) When a
microphonic pickup and 50- to 120-Hz power sharply rising pulse is applied to this circuit,
line frequency. the output is a pulse with a shape described
The most common methods for amplifier by
pulse shaping are resistor-capacitor (RC),
gaussian, and delay-line methods. The RC Vo (t) = Vi (1 − e− t/RC ) (8-5)
technique, commonly referred to as RC
shaping, is described to illustrate the basic where Vi is the amplitude of the input pulse
principles. More detailed circuit descriptions and RC = τi is the integration time constant
are found in the sources cited in the Bibliog- of the circuit. This circuit discriminates effec-
raphy at the end of this chapter. tively against high-frequency noise, as illus-
trated in Figure 8-4B.
Figure 8-5A shows a pulse-shaping circuit
2.  Resistor-Capacitor Shaping combining differentiation and integration
Basic RC pulse-shaping circuits are shown in stages. When the time constants of the two
Figure 8-4. When a sharply rising pulse of circuits are equal (τ = τi = τd), the output is a
relatively long duration (e.g., preamplifier pulse that rises to a maximum value in a time
output pulse) is applied to a capacitor-resistor equal to 1.2τ and then decays to approxi-
(CR), or differentiation circuit (see Fig. 8-4A), mately zero in 7τ. The maximum amplitude
the output is a rapidly rising pulse that decays of the output pulse is determined by the
with a time constant τd determined by the RC amplitude of the input pulse. For scintillation
product of the circuit components (Equation and semiconductor detectors, a time constant
8-4). The amplitude of the output pulse in the range τ ~ 0.25-5.0╯ µsec usually is
depends on the amplitude of the sharply chosen. Thus the output pulse is shortened
rising portion of the input pulse and is insen- considerably relative to the pulse from the
sitive to the “tail” of any preceding pulse. preamplifier (50-500╯ µsec) and is suitable for
Note that a CR differentiation circuit also is high counting rate applications. Except for a
used for pulse shaping in the preamplifier; very small negative overshoot at the end of
however, the time constants used in the  the pulse, the output pulse from this circuit
preamplifier circuits are much longer than has only one polarity (positive in Fig. 8-5A)
those used in the amplifier. Figure 8-4A also and is called a unipolar output.

Input Cd Output
Voltage

63%
Low-frequency noise 100% Rd 100%

Time d  CdRd d
A Differentiation stage

Input Ri Output
Voltage

High-frequency noise 100% Ci 100%


63%
i  RiCi i
Time
B Integration stage
FIGURE 8-4  Basic resistor-capacitor pulse-shaping circuits. A, Differentiation provides a sharply rising output signal
that decays with time constant τd and discriminates against low-frequency noise. B, Integration circuit provides an
output pulse that rises with time constant τd and discriminates against high-frequency noise.
112 Physics in Nuclear Medicine

Input Cd Output
Ri
A

Voltage
Rd Ci

Time d  CdRd  i  RiCi 1.2


7
A Differentiation plus integration

Input Cd Ri Cd Output
A A
Voltage

Rd Ci Rd

0.7
Time d  CdRd  i  RiCi 2.2
12
B Double differentiation plus integration
FIGURE 8-5  Resistor-capacitor pulse-shaping circuits combining differentiation and integration stages. A, Differentia-
tion followed by integration. B, Differentiation-integration-differentiation circuit.

Figure 8-5B illustrates another type of Amplitude


defect
shaping, called double differential shaping.
The output pulse from this circuit has both
Voltage

positive and negative components and there-


fore is a bipolar pulse. For equal time-
constant values, the bipolar output pulse has
a shorter rise time and positive portion and 
a longer total duration than the unipolar Time
output pulse. Unipolar pulses are preferred A
for signal-to-noise characteristics and are
used where energy resolution is important.
Bipolar pulses are preferred for high count-
ing rate applications. Amplitude defect
Research-grade amplifiers generally are
Voltage

provided with adjustable pulse-shaping time


constants. A longer time constant provides
better pulse amplitude information and is
preferred in applications requiring optimal
energy resolution, for example, with semi-
conductor detectors (Chapter 10, Section Time
C.1). A shorter time constant is preferred in B
applications requiring more precise event FIGURE 8-6  A, Schematic representation of baseline
timing and higher counting rate capabilities, shift, caused by a pulse riding on the “tail” of a preceding
pulse. B, Pulse pile-up effects for two pulses occurring
such as scintillation cameras (Chapters 13 very close together in time.
and 14) and coincidence detection of positron
annihilation photons (Chapter 18).
3.  Baseline Shift and Pulse Pile-Up Inaccurate pulse amplitude and an apparent
Baseline shift and pulse pile-up are two prac- shift (decrease) in energy of the detected radi-
tical problems that occur in all amplifiers at ation event are the result (see Fig. 10-9).
high counting rates. Baseline shift is caused Special circuitry has been developed to
by the negative component that occurs at the minimize baseline shift. This is called pole
end of the amplifier output pulse. A second zero cancellation, or baseline restoration. This
pulse occurring during this component will be type of circuitry is employed in modern scin-
slightly depressed in amplitude (Fig. 8-6A). tillation cameras to provide a high counting
8  •  Electronic Instrumentation for Radiation Detection Systems 113

rate capability, particularly for cardiac of only those pulses within a certain ampli-
studies. These circuits are described in the tude range makes it possible to restrict count-
sources cited in the Bibliography at the end ing to a selected energy range and to
of this chapter. discriminate against background, scattered
At high counting rates, amplifier pulses radiation, and so forth outside the desired
can occur so close together that they fall on energy range (see Fig. 10-6).
top of each other. This is referred to as pulse A device used for this purpose is called a
pile-up (Fig. 8-6B). When this happens, two pulse-height analyzer (PHA). A PHA is used
pulses sum together and produce a single to select for counting only those pulses from
pulse with an amplitude that is not represen- the amplifier falling within selected voltage
tative of either. Pulse pile-up distorts energy amplitude intervals or “channels.” If this is
information and also contributes to counting done for only one channel at a time, the device
losses (dead time) of the detection system, is called a single-channel analyzer (SCA). A
because two pulses are counted as one device that is capable of analyzing simultane-
(Chapter 11, Section C). ously within many different intervals or chan-
Both baseline shift and pulse pile-up can nels is called a multichannel analyzer (MCA).
be decreased by decreasing the width of the Basic principles of these instruments are dis-
amplifier pulse (i.e., the time constant of the cussed in the following sections.
amplifier); however, shortening of the time
constant usually produces poorer SNR and 2.  Single-Channel Analyzers
energy resolution. It is generally true that all An SCA is used to select for counting only
the factors that provide high count rate capa- those pulses from the amplifier that fall
bilities in amplifiers also degrade energy reso- within a selected voltage amplitude range. At
lution (Chapter 10, Section B.7). this stage in the system voltage amplitude is
Generally, amplifiers with double differen- proportional to radiation energy deposited in
tiation or double delay-line bipolar outputs the detector, so it is equivalent to selecting an
are employed with NaI(Tl):PM tube detectors energy range for counting. Modern amplifiers
that must handle high counting rates. The produce output pulses with amplitudes in the
bipolar output helps to avoid baseline shift range of 0-10╯V. Therefore the voltage selec-
problems, allowing good pulse-height deter- tion provided by most SCAs is also in the 0- to
mination at high counting rates. In addition, 10-V range.
short time constants of 0.025-0.5╯ µsec are An SCA has three basic circuit components
used. The relatively poor inherent energy (Fig. 8-7): a lower-level discriminator (LLD),
resolution of NaI(Tl):PM tube detectors is  an upper-level discriminator (ULD), and an
not affected significantly by this type of ampli- anticoincidence circuit. The LLD sets a
fier, and a high counting rate capability  threshold voltage amplitude V (or energy E)
is provided. Semiconductor detectors usually for counting. The ULD sets an upper voltage
require much more sophisticated amplifiers, limit V + ΔV (or E + ΔE). The difference
with unipolar pulse shaping, longer time con- between these voltages (or energies), ΔV (or
stants (0.5-8╯ µsec), and circuits for stabilizing ΔE), is called the window width. Usually the
the baseline to maintain their exceptionally LLD and ULD voltages are selected by means
good energy resolution at high counting rates of potentiometer or other electronic controls
(Chapter 10, Section C.1). that are adjusted to select some fraction of a
10-V reference voltage.
The LLD and ULD establish voltage levels
in electronic circuits called comparators. As
C.  PULSE-HEIGHT ANALYZERS
their name implies, these circuits compare
the amplitude of an input pulse with the LLD
1.  Basic Functions and ULD voltages. They produce an output
When an energy-sensitive detector is used pulse only when these voltages are exceeded.
[e.g., NaI(Tl):PM tube or a semiconductor Pulses from the comparator circuits are then
detector], the amplitude of the voltage pulse sent to the anticoincidence circuit, which pro-
from the amplifier is proportional to the duces an output pulse when only one (LLD)
amount of energy deposited in the detector by but not both (ULD and LLD) pulses are
the detected radiation event. By examining present (see Fig. 8-7). Thus only those input
the amplitudes of amplifier output pulses, it pulses with amplitudes between V and V + ΔV
is possible to determine the energies of (i.e., within the selected energy window) cause
detected radiation events. Selective counting output pulses from the SCA.
114 Physics in Nuclear Medicine

Detector Vref
Radiation E  E

Preamp
ULD

Anti-
Amplifier Vi coincidence Scaler
Input logic circuit Output

LLD

Vref
Single-channel
analyzer

E  E (ULD)
E
E (LLD)
Voltage

Time
FIGURE 8-7  Principles of a single-channel pulse-height analyzer. Top, Electronic components that are used to gener-
ate an output pulse only when pulse amplitude falls between voltages established by lower-level discriminator (LLD)
and upper-level discriminator (ULD) circuits. These voltages are an adjustable portion of a reference voltage Vref.
Bottom, LLD and ULD voltages in effect establish an energy range (E to E + ΔE) for counting because pulse voltage
amplitude V is proportional to radiation event energy E. Only pulse signals within the ΔE bracket (solid line) are
counted.

The SCA output pulses are used to drive  On many nuclear medicine instruments,
counters, rate meters, and other circuits. The manufacturers have provided pushbuttons to
output pulses from the SCA are all of the select automatically the analyzer lower level
same amplitude and shape (typically 4-V and window voltages appropriate for com-
amplitude, 1-µsec duration). Their amplitudes monly used radionuclides. In these systems,
no longer contain information about radiation the pushbuttons insert calibrated resistance
energy, because this information has already values into the SCA circuitry in place of the
been extracted by the SCA. variable resistances shown in Figure 8-7.
Commercially made SCAs frequently have Another possibility on some instruments 
two front-panel controls: a lower-level (voltage is to remove the upper-level voltage limit
V or energy E ) control and a window (ΔV or entirely. Then all pulses with amplitudes
Δâ•›E ) control. The LLD control is also called exceeding the lower-level voltage result in
the base level on some instruments. The output pulses. An analyzer operated in this
upper-level voltage is determined by elec- mode is sometimes called a discriminator.
tronic summation of lower-level and window Many auxiliary counting circuits (e.g., scalers
voltages on these instruments. and rate meters) have a built-in discriminator
Some instruments include “percent window” at their inputs to reject low-level electronic
selections. With these instruments, the noise pulses.
window width voltage is selected as a certain
percentage of the window center voltage. (The 3.  Timing Methods
window center voltage is the lower level Accurate time placement of the radiation
voltage V plus one half of the window voltage, event is important in some nuclear medicine
ΔV/2.) For example, if one were to set the applications. For example, in the scintillation
window center at 2╯V with a 20% window, the camera (Chapter 13), accurate timing is
window width would be 0.4╯V (20% of 2╯V), required to identify the multiple phototubes
and the window would extend from 1.8 to involved in detecting individual radiation
2.2╯V. events striking the NaI(Tl) crystal (i.e., for
8  •  Electronic Instrumentation for Radiation Detection Systems 115

determining the location of each event with however, it suffers a certain amount of inac-
the position logic of the camera). Even more curacy [5 to 50╯nsec with NaI(Tl) coupled with
critical timing problems occur in coincidence a PM tube] because the timing of the output
counting of positron annihilation photons pulse depends on the amplitude of the input
(Chapter 18) and in the liquid scintillation pulse. This timing variation Δt is called timing
counter (Chapter 12, Section C). walk.
Most SCAs used in nuclear medicine More precise timing is obtained with ana-
employ leading-edge timing. With this method, lyzers employing fast timing techniques. One
as shown in Figure 8-8A, the analyzer output such method is called zero-crossover timing
pulse occurs at a fixed time TD following the (Fig. 8-8B). This method requires a bipolar
instant at which the rising portion of the input pulse to the SCA. The output pulse
input pulse triggers the LLD. This type of occurs at the time of crossover of the bipolar
timing is adequate for many applications; pulse from a positive to a negative voltage

E  E (ULD)
(1)
(2) E
E (LLD)

TD
Voltage

0 Discriminator output for (1)

t Time shift with energy

TD
0 Discriminator output for (2)
t
Time
A

E  E (ULD)
(1)
(2) E
E (LLD)

0
Voltage

0 Discriminator output for (1)

t Time shift with energy

0 Discriminator output for (2)

Time
B
FIGURE 8-8  Examples of timing methods used in pulse-height analyzers. A, With leading-edge timing, the output
pulse occurs at a fixed time TD after the leading edge of the pulse passes through the lower-level discriminator (LLD)
voltage. B, With zero-crossover timing, output pulse occurs when the bipolar input pulse passes through zero. The
latter is preferred for precise timing because there is very little time shift with different pulse amplitudes (energy).
ULD, upper-level discriminator.
116 Physics in Nuclear Medicine

value. The zero-crossover method is much less of pulse-height spectroscopy (Chapter 10).
sensitive to pulse amplitude than the leading- Multiple SCAs would be expensive, and the
edge method and can provide timing accuracy adjusting and balancing of many different
to within ± 4╯nsec with NaI(Tl):PM tube analyzer windows would be a very tedious
detectors. Other fast-timing methods include project.
peak detection and constant fraction tech- A practical solution is provided by an MCA.
niques. They are discussed in the sources Figure 8-9 demonstrates the basic principles.
cited in the Bibliography at the end of this The heart of the MCA is an analog-to-digital
chapter. converter (ADC), which measures and sorts
out the incoming pulses according to their
4.  Multichannel Analyzers amplitudes. The pulse amplitude range,
Some applications of pulse-height analysis usually 0-10╯V, is divided by the ADC into a
require simultaneous recording of events in finite number of discrete intervals, or chan-
multiple voltage or energy windows. One nels, which may range from 100 in small ana-
approach is to use many SCAs, each with its lyzers to as many as 65,536 (216) in larger
own voltage window. For example, some systems. Thus, for example, the ADC in a
imaging devices have two or three indepen- 1000-channel analyzer would divide the 0- to
dent SCAs to record simultaneously the mul- 10-V amplitude range into 1000 channels,
tiple γ-ray energies emitted by nuclides such each 10╯V/1000 = 0.01╯V wide: 0-0.01╯V cor-
as 67Ga; however, this approach is unsatisfac- responding to channel 1, 0.01-0.02╯V to
tory when tens or even thousands of different channel 2, and so forth. The ADC converts an
windows are required, as in some applications analog signal (volts of pulse amplitude),

Detector Timing/control Display

Memory

Amplifier ADC Readout device

A Multichannel pulse-height analyzer

Output pulses
from amplifier
Object
containing Detector Amplifier
99mTc

Channels 1 2 3 4 5 6 7 8 9 10 11 12

ADC
Counts channel

1 2 3 4 5 6 7 8 9 10 11 12
Channel number
Photon energy
B Memory
FIGURE 8-9  Principles of a multichannel analyzer (MCA). A, Basic components. B, Example of pulse sorting according
to amplitude for radiation events detected from an object containing 99mTc. ADC, analog-to-digital converter.
8  •  Electronic Instrumentation for Radiation Detection Systems 117

which has an essentially infinite number of


possible different values, into a digital one
(channel number), which has only a finite Input pulse from amplifier
number of integer values (see Fig. 8-9). In
addition to their use in counting systems,
ADCs are also used in the interface between
nuclear medicine imaging detectors and com-
puter systems.
Discharge of capacitor
For each analyzer channel, there is a cor-
responding storage location in the MCA
memory. The MCA memory counts and stores
the number of pulses recorded in each ana-
lyzer channel. The number of memory storage
locations available determines the number of
MCA channels. The sorting and storage of the Gate pulse
energy information from radiation detectors
with an MCA are used to record the pulse-
height spectrum (counts per channel versus
channel number, or energy), as shown in
Figure 8-9B.
MCAs also are available as boards that
Output from oscillator
plug into personal computers. The computer (clock pulses)
is used to program the settings on the MCA
(i.e., number of channels to be used and
voltage range to be selected) and also to FIGURE 8-10  Principles of analog (pulse amplitude) to
control acquisition of data from the detector digital (channel number) conversion in the Wilkinson, or
(acquisition start time and acquisition dura- ramp, converter. Input pulse is used to charge a capaci-
tion). The computer also is used to display the tor, and discharge time, which is proportional to pulse
resulting data (number of counts per MCA amplitude, is measured using a clock oscillator.
channel for the measurement period) that are
transferred from the MCA card onto the com-
puter’s hard disk. Many MCA boards are
capable of receiving data from several inputs increment by one count the memory channel
at once and can therefore be used to acquire corresponding to the number of clock pulses
and display data from several detector units counted, then clear the input circuitry and
simultaneously. prepare the MCA to accept the next input
Two types of ADCs are commonly used in pulse.
nuclear medicine for MCAs and for interfaces In the successive approximation (SA) con-
between scintillation cameras and computers. verter, digitization occurs by comparing the
In the Wilkinson, or ramp, converter (Fig. pulse amplitude with a selected sequence of
8-10), an input pulse from the radiation detec- voltage levels. The first comparison level is
tor and amplifier causes an amount of charge equal to one half of the full-scale (maximum)
to be deposited onto a capacitor at the ADC value. If the pulse amplitude is greater than
input. The amount of charge deposited this level, the first digital “bit” is set to “1”; if
depends on the pulse amplitude or energy. not, it is set to “0.” The comparison voltage
The capacitor discharges through a resistor, level then is either increased or decreased by
with a relatively long RC time constant. While one half of its initial level, (i.e., to 25% or 75%
the capacitor is discharging, a gate pulse acti- of full scale) depending on whether the pulse
vates a clock oscillator to produce a train of amplitude did or did not exceed the initial
pulses that are counted in a counting circuit. level. The comparison is repeated and the
When the capacitor has been discharged, the second digital bit is recorded as “1” or “0,”
gate pulse is terminated and the clock oscil- depending on whether the pulse amplitude is
lator is turned off. The number of clock pulses greater or smaller than the new comparison
counted is determined by the capacitor dis- voltage level. The comparisons are repeated
charge time, which in turn is determined by through several steps, each time decreasing
the initial amount of charge deposited on the the voltage increment by one half. The final
capacitor and thus depends on the amplitude set of bits provides a binary (base 2) represen-
of the input pulse. The MCA control circuits tation for the amplitude of the input pulse.
118 Physics in Nuclear Medicine

For both the ramp and SA converters, the contain MCAs that are used to examine and
output is represented as a binary number select energy windows of interest.
between 0 and 2n. The value of n determines
the number of possible digital levels into
which the input pulse amplitude can be con-
verted. For example, an 8-bit converter, for D.  TIME-TO-AMPLITUDE
which n = 8, divides the input range into 256 CONVERTERS
digital levels (28 = 256), a 10-bit converter into
1024 levels (210 = 1024), and so forth. The In certain applications it is useful to be able
larger the number of bits, the more precisely to measure the distribution of time differ-
the ADC can determine the pulse amplitude. ences between incoming pulses from a detec-
Thus an 8-bit converter can determine ampli- tor, much in the same way that an MCA
tude to a precision of one part in 256, a 10-bit measures the distribution of energies depos-
converter to one part in 1024, and so forth. ited in the radiation detector. For example,
Generally, a larger number bit is favored for we might wish to use two opposing scintilla-
precision, but the digital conversion process tion detectors to view a positron-emitting
then requires somewhat more time and the radionuclide and to measure the time differ-
digitized values for pulse amplitude require ence between the detection of two annihila-
greater amounts of computer storage space. tion photons. If the difference is “small” (â•›a
Most nuclear medicine studies can be per- few nanoseconds), they are highly likely to
formed with 8-bit converters, but 10- and arise from a single positron annihilation
12-bit converters also are used for situations event, whereas if the difference is not small,
in which precision is a prime concern (e.g., they probably reflect two independent events.
high-resolution energy spectroscopy with The time-to-amplitude converter (TAC)
semiconductor detectors; see Chapter 10, produces an output signal with a voltage pro-
Section C.1). portional to the time difference between two
A finite amount of time is required for  logic pulses supplied to the input. The logic
the digital conversion processes described pulses typically come from the output of 
earlier. For example, for a 10-bit (1024- a discriminator or SCA (see Section C.2)
channel) ramp converter with a 100-MHz (108 attached to a radiation detector and have a
cycle/sec) clock, the capacitor discharge time standard box shape with a well-defined
required for an event in the 1000th channel amplitude and duration. The concepts of a
(1000 clock pulses) is 1000 pulses ÷ 108 pulse/ TAC are illustrated in Figure 8-11. The first
sec = 10−5╯sec or 10╯ µsec. For an SA converter, logic pulse (known as the START signal ) is
time is needed for each of the voltage com- used to start the charging of a capacitor by
parisons; for example, a 10-bit SA converter a constant current source. The second logic
must perform a sequence of 10 voltage com- pulse (the STOP signal ) is used to terminate
parisons, each requiring a fraction of a micro- the charging of the capacitor. Because the
second to complete. capacitor is charged from a constant current
In addition to the conversion process, time source, the voltage across the capacitor
is required to increment the memory location, increases linearly with time and is therefore
reset the clock pulse counter on comparison proportional to the time interval between the
voltage levels, and so on. The ADC can  START and the STOP signals.
therefore be a “bottleneck” in MCAs as well  The voltage across the capacitor deter-
as in the digital conversion process for signals mines the amplitude of the output voltage
from a scintillation camera. Modern ADCs, pulse of the TAC and is therefore also pro-
however, can digitize events at rates in excess portional to the time interval between the
of 1 million counts/sec; therefore ADC speed two logic pulses. The output pulses from the
need not be a limiting factor for applications TAC can be fed to a standard MCA to produce
involving NaI(Tl) detectors, for which the a histogram of the distribution of time differ-
primary time limitation is the decay time of ences between the two logic pulses. The MCA
the individual scintillation events. is calibrated in terms of time units by sup-
Most MCAs have additional capabilities, plying the TAC with pulses with a known
such as offset or expansion of the analyzer time interval between them. Alternatively,
voltage range and time histogram capa�bilities. they can be used to set a timing threshold
These are discussed in detail in MCA operator for accepting or rejecting two detected events
manuals. Some scintillation cameras, well as being coincident (e.g., originating from the
counters, and liquid scintillation counters same nuclear decay). Following the STOP
8  •  Electronic Instrumentation for Radiation Detection Systems 119

t assemblies determines the number of decades


of scaler capacity. Thus a six-decade scaler has
six DCAs and a counting capacity from 0 to
START pulse 999,999 counts. (Usually the “1-millionth
count” resets the scaler to “0” and turns on an
overflow light). Data from each DCA are trans-
STOP pulse
ferred to the display for continuous visual
readout of the number of counts recorded
during the counting interval.
Vt As shown in Figure 8-12, the scaler gate
Voltage on can be controlled in a number of different
capacitor ways. In preset-time mode, the gate is con-
FIGURE 8-11  Principles of a time-to-amplitude con- trolled by a timer circuit (usually an oscillator-
verter (TAC). A START pulse is used to start the charging driven clock circuit) that opens the gate for a
of a capacitor by a constant current source, which is counting time selected by front-panel switches,
terminated by the STOP pulse. The voltage developed
across the capacitor is proportional to the time interval
or by a computer. The counting interval begins
between the START and STOP pulses. when a “start” button is depressed and is 
terminated automatically when the selected
counting time has elapsed. In preset-count
(PSC) mode, the counting interval ends when
signal, the TAC is reset by discharging the a preselected number of counts has been
capacitor, so it is ready for the next START recorded. PSC mode is used when one wants
signal. to achieve the same degree of statistical reli-
ability for all measurements in a series of
counting measurements (see Chapter 9).
E.  DIGITAL COUNTERS AND RATE When the PSC mode is used, a method must
be available to determine the elapsed time for
METERS
each counting measurement (e.g., a visual
display or printout of elapsed counting time)
1.  Scalers, Timers, and Counters so that counting rates for each measurement
Digital counters are used to count output can be determined (preset counts/elapsed
signals from radiation detectors after pulse- time).
height analysis of the signals. A device that
counts only pulses is called a scaler. An aux-
iliary device that controls the scaler counting Printout
time is called a timer. An instrument that
incorporates both functions in a single unit is Decimal
called a scaler-timer. These devices are often counter 106 105 104 103 102 101
referred to under the generic name of coun- assemblies
ters. The number of counts recorded and the
elapsed counting time may be displayed on a Visual readout
visual readout, or, more commonly, the output
of the scaler-timer may be interfaced to a per-
sonal computer automated data processing.
Computer-driven counters, which reside on a Signal input
Gate
board that is placed inside of the computer,
are also common.
Figure 8-12 shows schematically the basic
Manual control
elements of a scaler-timer. The input pulse
must pass through an electronic “gate” that is Preset time (PST)
opened or closed by front-panel switches or External control
pushbutton controls that select the mode of Preset count (PSC)
operation. When the gate is open, the pulses
Reset
pass through to decimal counter assemblies
(DCAs). Each DCA records from zero to nine
events. The tenth pulse resets the counter Control buttons or switch
assembly to zero and sends a pulse to the next FIGURE 8-12  Schematic representation of components
DCA in the series. The number of counter and controls for a scaler-timer.
120 Physics in Nuclear Medicine

External control of the scaler gate may be Figure 8-13 shows the basic components of
provided by an external timer or a sample- an analog rate meter. Input pulses pass
changer assembly. Manual control permits through a pulse shaper, which shapes them
the operator to start and stop the counting to a constant amplitude and width. Each
interval by depressing front-panel “start” and shaped pulse then causes a fixed amount of
“stop” buttons. In computer-controlled coun- charge, Q, to be deposited on the capacitor C.
ters, all these para�meters are controlled by The rate at which the charge discharges
keyboard entry and appropriate interface through the resistor R is determined by the
software. product R × C, which is called the rate meter
The maximum counting rate capability time constant τ.
depends on the minimum time separation Suppose that input pulses arrive at an
required between two pulses for the scaler to average rate n pulses per second. The capaci-
record them as separate events. A 20-MHz tor discharge then produces an average
scaler (2 × 107 counts/sec) can separate pulses current I through the resistor R given by
that are spaced by 50╯nsec, or 5 × 10−8╯sec I = nQ (8-6)
apart (2 × 107 counts/sec is equivalent to 1
count/5 × 10−8╯sec). Most modern scalers are By Ohm’s law, this causes an average voltage
capable of 20- to 50-MHz counting rates,
which means they can count at rates of several V = nQR (8-7)
hundred thousand counts per second with
losses of 1% or less caused by pulse overlap to appear at the input to amplifier A. If the
(see Chapter 11, Section C). Because pulse amplification factor of this amplifier is k, the
resolving times of most radiation detectors average output voltage Vo is given by
and their associated preamplifiers and ampli-
fiers are on the order of 1╯ µsec, the counting Vo = knQR (8-8)
rate limits of modern scalers are rarely of
practical concern. Thus if k, Q, and R are constant factors for a
given measurement, average output voltage
2.  Analog Rate Meters Vo is proportional to average input counting
An analog rate meter is used to determine the rate n.
average number of events (e.g., SCA output The output voltage Vo can be used to drive
pulses) occurring per unit of time. The average  a meter to read the average counting rate.
is determined continuously, rather than The calibration usually is performed by
during discrete counting intervals, as would adjusting the amplifier gain factor k. This
be the case with a scaler-timer. The output of factor is adjusted to select different full-scale
a rate meter is a continuously varying voltage ranges for the readout device, for example,
level proportional to the average rate at which 0-1000╯cpm, 0-10,000╯cpm, and so on.
pulses are received at the rate meter input. A rate meter that follows the relationship
The output voltage can be displayed on a described by Equation 8-8 is called a linear
front-panel meter or interfaced through a con- rate meter. For some applications it is desir-
tinuously sampling ADC to a personal com- able to have a logarithmic relationship:
puter. Rate meters are commonly used in
radiation monitors (see Figs. 7-3 and 7-11). Vo = k log(nQR) (8-9)

Signal Output to
Shaper A
input Meter computer
FIGURE 8-13  Schematic repre-
sentation of an analog rate
R C meter. Adjustable capacitor C
provides variable rate meter time
constant, τ.

RC
Rate meter
8  •  Electronic Instrumentation for Radiation Detection Systems 121

The logarithmic conversion usually is per-


formed by a logarithmic amplifier. Logarith- F.  COINCIDENCE UNITS
mic rate meters have the advantage of a very
wide range of counting rate measurement, Coincidence units are logic units that produce
typically 4 or 5 decades, without the need to a pulse only if two or more input pulses occur
change range settings as with a linear rate within a particular coincidence time window.
meter; however, it is more difficult to discern One method for doing this is to sum the input
small changes in counting rate with a loga- pulses and pass them through a discriminator
rithmic rate meter. that is set just below the amplitude that
The voltage relationships described by would be seen if two or more pulses occurred
Equations 8-8 and 8-9 apply to average values simultaneously. As shown in Figure 8-15, the
only. When the input pulse rate changes, the unit supplies an output pulse only when two
rate meter output voltage does not respond or more pulses overlap in time and the dis-
instantaneously but responds during a period criminator threshold is exceeded. The coinci-
determined by the rate meter time constant τ. dence timing window is the maximum time
Figure 8-14 illustrates the response charac- interval between two pulses for them to be
teristic of a linear rate meter. The relationship counted as being in coincidence. In this illus-
between indicated counting rate Ri and the tration, this is twice the width of the input
new average counting Ra , following a change pulses (2τ).
occurring at time t = 0 from a previous
average value, R0, is given by
Ri = Ra − ( Ra − R0 ) e− t / τ (8-10)
The rate meter reading (or output voltage) 
approaches its new average value exponen- Sum A+B Output
tially with time t. Typically, three to five time Input A t
constants are needed to reach a new stable t
value. Input B t t
The rate meter time constant is selected by
a front-panel switch (usually by adjusting the
capacitor value C) and may range from 100ths
of a second to 10s of seconds. Figure 8-14
shows that a rate meter actually provides a
distorted representation of counting rate Sum AB Output
Input A t
versus time (rounded edges and delayed t
response). This distortion can be minimized Input B t t
by choosing a very short time constant (Fig.
8-14 A). A long time constant has the advan- FIGURE 8-15  Principles of a coincidence unit. The
signals from the inputs are combined and passed through
tage of smoothing out statistical fluctuations a discriminator set just below the threshold required for
in counting rate, but it produces a more dis- simultaneous pulses on the two inputs. In this example,
torted representation of changes in counting the coincidence window is approximately twice the width
rates (Fig. 8-14B). of the input pulses (2τ).

Short time constant Long time constant


 
Count rate
Count rate

Time Time
A B
FIGURE 8-14  Rate meter response to a sudden change in counting rate for different rate meter time constants. A
short time constant (A) reflects the change more accurately, but a long time constant (B) provides better averaging of
statistical noise fluctuations.
122 Physics in Nuclear Medicine

Coincidence units often have up to four problems are still relatively small, because
inputs and permit selection of two-way, three- modern HV supplies are very stable for long
way, and four-way coincidences between the periods and over wide temperature ranges.
input pulses. Of most interest in nuclear med- The output current rating of the HV power
icine is the use of coincidence units to identify supply must be sufficient for the particular
the two-way coincidence events resulting detector system. Most scintillation detectors
from the detection of the annihilation photons draw about 1╯mA of current, for which the
from positron-emitting radionuclides (Chapter 0- to 10-mA rating of most commercial HV
18, Section A.1). In practice, most positron supplies is adequate. If the current load is
imaging systems record and compare the time inadvertently increased above this limit, it
for each detected event using digital elec� will affect the stability and may even damage
tronics, rather than using the analog coinci- the HV supply. Thus the current require-
dence units described previously. In this case, ments of the detector or detectors should be
the coincidence timing window is just the within the specified limits for the HV supply.
maximum time difference allowed between The current requirements need to be specified
two events for them still to be considered in at the intended operating voltage of the detec-
coincidence. Another use of coincidence units tor, because the current load drawn by the
is to minimize background in liquid scintilla- detector will increase with the applied voltage.
tion counting (Chapter 12, Section C). Most commercial HV supplies have an over-
load protection circuit that will shut off the
unit if the recommended current load is
G.  HIGH-VOLTAGE POWER SUPPLIES exceeded.
Superimposed on the DC output of the HV
The high-voltage (HV) power supply provides supply is a time-varying component, usually
the charge collection voltage for semiconduc- of relatively small amplitude, referred to as
tor, gas proportional, and GM detectors and “ripple.” The amplitude of ripple ranges from
the accelerating voltage for electron multipli- 10 to 100╯mV in most commercial units.
cation in the PM tubes used with scintillation Ripple in the HV supply can be a serious
detectors such as NaI(Tl) and liquid scintilla- problem with high-resolution semiconductor
tors. The HV power supply converts the alter- detectors, because it produces noise in the
nating current voltage provided by the line detector output and reduces the energy reso-
source into a constant or direct current (DC) lution of the detector. HV supplies used in
voltage. conjunction with high-resolution semiconduc-
Whereas variation of the HV has little tors usually have a ripple of less than 10╯mV.
effect on the output pulse amplitude with
semiconductor and GM detectors, changes in
the HV with gas proportional or scintillation H.  NUCLEAR INSTRUMENT MODULES
detectors strongly affect their output pulse
amplitude. For example, a 1% change in the Most of the counting and imaging instru-
HV on a scintillation detector PM tube can ments used in nuclear medicine are dedicated
change the output pulse amplitude by 10% or to specific and well-defined tasks. Usually,
more because the HV on the PM tube (and on they are designed as self-contained “hard-
gas proportional counters) determines the wired” units, with no capability for inter-
multiplication factor for the number of elec- changing components, such as amplifiers,
trons caused by an ionization event in those SCAs, or scalers, between different instru-
detectors (Chapter 7, Section C.2). ments. Although these integrated circuits
Instabilities in HV power supplies can generally result in an efficiently designed and
arise from a number of factors, such as tem- attractively packaged instrument, there are
perature changes, variations in line voltage, some applications, especially in research, for
and the amount of current drawn by the which interchangeability of components is
detector (commonly referred to as the output highly desirable. For example, most scalers,
load). The output can also drift over time. In timers, and rate meters can be used with any
a well-regulated HV power supply suitable for detector system, but different detectors may
scintillation detectors, drifting of the output require different amplifiers, and different
with time and temperature are more impor- types of PHAs may be desired for different
tant than the effects of line voltage and pulse-timing requirements.
current loads (unless maximum current Flexibility and interchangeability of 
ratings are exceeded); however, the former components are provided by the nuclear
8  •  Electronic Instrumentation for Radiation Detection Systems 123

instrument module (NIM). Individual NIM fits over the cathode. The electrons pass
components (such as scalers and amplifiers) through a small hole in its center. A negative
slide into slots in a master “bin” from which potential on the grid can be varied to control
they draw their operating power. They have the number of electrons that are allowed to
standard input and output signals and are pass. The first anode, or accelerating anode,
interconnectable with standard cables and is similar in shape to the grid except that its
connectors. orientation is reversed. The flat end contains
A NIM system generally is more expensive a small hole through which the electrons
than a dedicated system with the same capa- pass. It has a high positive potential that
bilities; however, it has the advantage that it attracts the electrons and accelerates them to
can be upgraded or applied to different radia- high velocities. Most of the electrons actually
tion detectors and counting problems by strike the front face of the first anode, but a
replacement of individual components rather small percentage pass through the opening
than replacing the entire unit. A wide variety and are accelerated down the CRT tube as a
of component types and performance specifi- narrow beam.
cations are available in the NIM standard. The second anode, or focusing anode,
further shapes the electron beam by focusing
it to a sharp point where it strikes the
I.  OSCILLOSCOPES phosphor-coated screen. A negative potential
on the second anode is used to both compress
The oscilloscope is an instrument that dis- and focus the beam of electrons. The diameter
plays as a function of time the amplitude of the electron beam striking the phosphor
(voltage) and frequency of signals. It is used screen is usually around 0.1╯mm.
for examining the pulses from the pulse- Deflection plates are used to move the elec-
processing units described in the previous tron beam across the screen. Electrostatic
sections of this chapter and for testing, cali- deflection employs two sets of plates mounted
brating, and repairing electronic equipment at right angles to each other. Voltages are
in nuclear medicine. applied to one pair to exert a force on the
electron beam in the vertical direction and on
1.  Cathode Ray Tube the other pair for the horizontal direction on
Analog oscilloscopes, as well as older nuclear the display screen. The amount of deflection
medicine systems (gamma cameras, liquid is proportional to the voltage applied to the
scintillation counters, well counters, and deflection plates.
MCAs) typically use a cathode ray tube (CRT) The display screen is a glass screen having
display. The CRT is an evacuated tube con- an inside surface coated with a phosphores-
taining the basic components shown in Figure cent material. The high-velocity electrons
8-16. The electron gun provides a focused striking the phosphor cause it to give off phos-
source of electrons. Most CRTs use a hot, or phorescent light. The brightness of the phos-
thermionic emission, cathode. Electrons are phorescent light depends on the intensity and
boiled off the cathode by heating it with an energy of the electron beam. The lifetime of
electric current. The control grid is a cap that the light emission from the phosphor is

Electron Focusing Deflection


source region region
Light

Electron
beam

Cathode First Vertical


anode deflection
plates
Control Second Horizontal Phosphor-
grid anode deflection coated
plates screen
FIGURE 8-16  Basic components of a cathode ray tube.
124 Physics in Nuclear Medicine

referred to as the persistence time and is typi- computer memory for further analysis and are
cally 0.5╯msec on an oscilloscope display. ideal for studying repetitive, regular pulses.
The disadvantage of using a digital oscillo-
2.  Analog Oscilloscope scope to look at the pulses from γ-ray detectors
A typical analog oscilloscope consists of a is that individual pulses generally are of a
CRT, a signal amplifier for the vertical deflec- different amplitude (reflecting differing ener-
tion plate of the CRT, and a time-sweep gen- gies deposited in the detector), and that they
erator. An amplifier is provided so that small arrive randomly in time. A digital oscilloscope
voltage inputs can be amplified and applied shows only one pulse at a time. Some digital
to the vertical deflection plate to display the oscilloscopes now have a “persistence” func-
amplitude of the input signals. The time- tion (essentially software or hardware that
sweep generator is connected to the horizon- mimics the response of a phosphorescent
tal deflection plates of the CRT to sweep the screen), which allows many pulses to be
electron beam across the screen at a constant viewed simultaneously, with appropriate
speed and repetition rate. The horizontal intensity where pulses overlap. This allows
sweep rate usually can be varied from nano- the range of pulse amplitudes and shapes to
seconds (10−9╯ sec) to seconds per centimeter be appreciated easily in a single glance and
by a calibrated selector switch on the front gives the digital oscilloscope the feel of an
panel of the oscilloscope. Thus the oscillo- older analog oscilloscope with a fairly long
scope provides a visual display of time- (10−1 to 1╯sec) persistence phosphor.
varying electrical signals.
BIBLIOGRAPHY
3.  Digital Oscilloscope
Basic nuclear electronics are discussed in the
Most modern oscilloscopes are digital, employ- following:
ing fast ADCs that digitize the amplified Knoll GF: Radiation Detection and Measurement, ed 4,
waveforms prior to display, and some form of New York, 2010, John Wiley.
microprocessor that allows pulses to be ana- Leo WR: Techniques for Nuclear and Particle Physics
lyzed and manipulated. The CRT screen is Experiments, ed 2, New York, 1994, Springer-Verlag.
typically replaced with a flat-panel liquid A comprehensive reference for electronics is:
crystal display. Digital oscilloscopes have  Horowitz P, Hill W: The Art of Electronics, ed 2, Cam-
the advantage that pulses can be stored in bridge, 1989, Cambridge University Press.
chapter
9 
Nuclear Counting
Statistics

All measurements are subject to mea�surement interpretation of data (e.g., scan reading) is
error. This includes physical meaÂ�surements, another example of systematic error, as is 
such as radiation counting measurements the use for a clinical study of two population
used in nuclear medicine procedures, as well groups having underlying differences in 
as in biologic and clinical studies, such as some important characteristic, such as differ­
evaluation of the effectiveness of an imaging ent average ages. Measurement results
technique. In this chapter, we discuss the having systematic errors are said to be
type of errors that occur, how they are ana­ inaccurate.
lyzed, and how, in some cases, they can be It is not always easy to detect the presence
minimized. of systematic error. Measurement results
affected by systematic error may be very
repeatable and not too different from the
A.  TYPES OF MEASUREMENT ERROR expected results, which may lead to a mis­
taken sense of confidence. One way to detect
Measurement errors are of three general systematic error in physical measurements is
types: blunders, systematic errors, and by the use of measurement standards, which
random errors. are known from previous mea�surements with
Blunders are errors that are adequately a properly operating system to give a certain
described by their name. Usually they measurement result. For example, radio­
produce grossly inaccurate results and their nuclide standards, containing a known quan­
occurrence is easily detected. Examples in tity of radioactivity, are used in various
radiation measurements include the use of quality assurance procedures to test for sys­
incorrect instrument settings, incorrect label­ tematic error in radiation counting systems.
ing of sample containers, and injecting the Some of these procedures are described in
wrong radiopharmaceutical into the patient. Chapter 11, Section D.
When a single value in the data seems to be Random errors are variations in results
grossly out of line with others in an experi­ from one measurement to the next, arising
ment, statistical tests are available to deter­ from physical limitations of the measurement
mine whether the suspect value may be system or from actual random variations of
discarded (see Section E.3). Apart from this the measured quantity itself. For example,
there is no way to “analyze” errors of this length measurements with an ordinary ruler
type, only to avoid them by careful work. are subject to random error because of inexact
Systematic errors produce results that repositioning of the ruler and limitations of
differ consistently from the correct result by the human eye. In clinical or animal studies,
some fixed amount. The same result may be random error may arise from differences
obtained in repeated measurements, but it is between individual subjects, for example, in
the wrong result. For example, length mea­ uptake of a radiopharmaceutical. Random
surements with a warped ruler, or activity error always is present in radiation counting
measurements with a radiation detector  measurements because the quantity that is
that was miscalibrated or had some other  being measured—namely, the rate of emis­
persistent malfunction, could contain system­ sion from the radiation source—is itself a ran­
atic errors. Observer bias in the subjective domly varying quantity.
125
126 Physics in Nuclear Medicine

Random error affects measurement repro- measurements and use the average N as an
ducibility and thus the ability to detect real estimate for the “true value.”
differences in measured data. Measurements
that are very reproducible—in that nearly  True Value ≈ N (9-1)
the same result is obtained in repeated
measurements—are said to be precise. It is N = ( N1 + N2 +  + N n ) /n
possible to minimize random error by using (9-2)
1 n
careful measurement technique, refined = ∑ Ni
n i =1
instrumentation, and so forth; however, it is
impossible to eliminate it completely. There 
is always some limit to the precision of a  where n is the number of measurements
measurement or measurement system. The taken. The notation ∑ indicates a sum that is
amount of random error present sometimes is taken over the indicated values of the param­
called the uncertainty in the measurement. eter with the subscript i.
It also is possible for a measurement to be Unfortunately, multiple measurements are
precise (small random error) but inaccurate impractical in routine practice, and one often
(large systematic error), or vice versa. For must be satisfied with only one measure­
example, length measurements with a warped ment. The question then is, how good is the
ruler may be very reproducible (precise); nev­ result of a single measurement as an esti­
ertheless, they still are inaccurate. On the mate of the true value; that is, what is the
other hand, radiation counting measurements uncertainty in this result? The answer to this
may be imprecise (because of inevitable varia­ depends on the frequency distribution of the
tions in radiation emission rates) but still measurement results. Figure 9-1 shows a
they can be accurate, at least in an average typical frequency distribution curve for radia­
sense. tion counting measurements. The solid dots
Because random errors always are present show the different possible results (i.e.,
in radiation counting and other measured number of counts recorded) versus the prob­
data, it is necessary to be able to analyze ability of getting each result. The probability
them and to obtain estimates of their magni­ is peaked at a mean value, m, which is the
tude. This is done using methods of statisti­ true value for the measurement. Thus if a
cal analysis. (For this reason, they are also large number of measurements were made
sometimes called statistical errors.) The and their results averaged, one would obtain
remainder of this chapter describes these
methods of analysis. The discussion focuses N ≈ m (9-3)
on applications involving nuclear radiation-
counting measurements; however, some of The solid dots in Figure 9-1 are described
the methods to be described also are appli­ mathematically by the Poisson distribution.
cable to a wider class of experimental data as For this distribution, the probability of getting
discussed in Section E. a certain result N when the true value is m
is given by

B.  NUCLEAR COUNTING STATISTICS P ( N ; m) = e− m m N /N ! (9-4)

where e (= 2.718 …) is the base of natural


1.  The Poisson Distribution logarithms and Nâ•›! (N factorial) is the product
Suppose that a long-lived radioactive sample of all integers up to N (i.e., 1 × 2 × 3 × · · · ×
is counted repeatedly under supposedly iden­ N). From Figure 9-1 it is apparent that
tical conditions with a properly operating the probability of getting the exact result 
counting system. Because the disintegration N = m is rather small; however, one could
rate of the radioactive sample undergoes hope that the result would at least be “close
random variations from one moment to the to” m. Note that the Poisson distribution is
next, the numbers of counts recorded in suc­ defined only for nonnegative integer values 
cessive measurements (N1, N2, N3, etc.) are of N (0, 1, 2, …).
not the same. Given that different results are The probability that a measurement result
obtained from one measurement to the next, will be “close to” m depends on the relative
one might question if a “true value” for  width, or dispersion, of the frequency distri­
the measurement actually exists. One possi­ bution curve. This is related to a parameter
ble solution is to make a large number of called the variance, σ2, of the distribution.
9  •  Nuclear Counting Statistics 127

0.14

0.12

0.10
Probability result  N

0.08

0.06

0.04 Mean
m  10

0.02

0.00
0 2 4 6 8 10 12 14 16 18 20
N
FIGURE 9-1  Poisson () and Gaussian ( – ) distributions for mean, m, and variance, σ2 = 10.

Answer
The variance is a number such that 68.3%
(~2/3) of the measurement results fall within For N1 = 100 counts, V1 = 100% / 100 = 10%
± σ (i.e., square root of the variance) of the (Equation 9-6). For N2 = 10,000 counts, V2 =
true value m. For the Poisson distribution, 100% / 10, 000 = 1%. Thus the percentage
the variance is given by uncertainty in 10,000 counts is only 1/10 the
percentage uncertainty in 100 counts.
σ2 = m (9-5)
Equation 9-6 and Example 9-1 indicate
Thus one expects to find approximately 2/3 of that large numbers of counts have smaller
the counting measurement results within the percentage uncertainties and are statistically
range ± m of the true value m. more reliable than small numbers of counts.
Given only the result of a single measure­ Other confidence intervals can be defined
ment, N, one does not know the exact value of in terms of σ or N . They are summarized
m or of σ; however, one can reasonably assume in Table 9-1. The 50% confidence interval
that N ≈ m, and thus that σ ≈ N. One can (0.675σ) is sometimes called the probable
therefore say that if the result of the measure­ error in N.
ment is N, there is a 68.3% chance that the
true value of the measurement is within the
range N ± N . This is called the “68.3% con-
fidence interval” for m; that is, one is 68.3%
TABLE 9-1â•…
confident that m is somewhere within the
CONFIDENCE LEVELS IN RADIATION
range N ± N .
COUNTING MEASUREMENTS
The range ± N is the uncertainty in N.
The percentage uncertainty in N is Confidence Level
for m (True Value)
V = ( N /N ) × 100% Range (%)
(9-6)
= 100% / N N ± 0.675σ 50
N±σ 68.3
EXAMPLE 9-1 N ± 1.64σ 90
Compare the percentage uncertainties in the  N ± 2σ 95
measurements N1 = 100 counts and N2 =
N ± 3σ 99.7
10,000 counts.
128 Physics in Nuclear Medicine

The Gaussian distribution with σ2 = m is a


2.  The Standard Deviation useful approximation for radiation counting
The variance σ2 is related to a statistical measurements when the only random error
index called the standard deviation (SD). The present is that caused by random variations
standard deviation is a number that is calcu­ in source decay rate. When additional sources
lated for a series of measurements. If n count­ of random error are present (e.g., a random
ing measurements are made, with results N1, error or uncertainty of ΔN counts caused by
N2, N3, . . . , Nn, and a mean value N for those variations in sample preparation technique,
results is found, the standard deviation is counting system variations, and so forth), the
results are described by the Gaussian distri­
bution with variance given by

n
( N i − N )2
SD = i =1 (9-7) σ 2 ≈ m + (∆N )2 (9-10)
(n − 1)
The resulting Gaussian distribution curve
The standard deviation is a measure of the would be wider than a Poisson curve with σ2
dispersion of measurement results about the = m. The confidence intervals given in Table
mean and is in fact an estimate of σ, the 9-1 may be used for the Gaussian distribution
square root of the variance. For radiation with this modified value for the variance. For
counting measurements, one therefore should example, the 68.3% confidence interval for a
obtain measurement result N would be ± N + ∆N 2
(assuming N ≈ m).
SD ≈ N (9-8)
EXAMPLE 9-2
This can be used to test whether the random A 1-mL radioactive sample is pipetted into a
error observed in a series of counting measure­ test tube for counting. The precision of the
ments is consistent with that predicted from pipette is specified as “±â•›2%,” and 5000 counts
random variations in source decay rate, or if are recorded from the sample. What is the
there are additional random errors present, uncertainty in sample counts per mL?
such as from faulty instrument performance.
This is discussed further in Section E. Answer
The uncertainty in counts arising from pipet­
ting precision is 2% × 5000 counts = 100
3.  The Gaussian Distribution counts. Therefore,
When the mean value m is “large,” the Poisson
distribution can be approximated by the σ 2 = 5000 + (100)2 ≈ 15, 000,
Gaussian distribution (also called the normal
distribution). The equation describing the and the uncertainty is 15, 000 ≈ 122 counts.
Gaussian distribution is Compare this with the uncertainty of 5000
≈ 71 counts that would be obtained without
2 / 2σ2 the pipetting uncertainty.
P ( x ; m, σ) = (1 / 2πσ 2 ) e− ( x − m) (9-9)

where m and σ2 are again the mean and vari­


ance. Equation 9-9 describes a symmetrical C.  PROPAGATION OF ERRORS
“bell-shaped” curve. As shown by Figure 9-1,
the Gaussian distribution for m = 10 and σ = The preceding section described methods for
m is very similar to the Poisson distribution estimating the random error or uncertainty in
for m = 10. For m  20, the distributions are a single counting measurement; however,
virtually indistinguishable. Two important most nuclear medicine procedures involve
differences are that the Poisson distribution multiple counting measurements, from which
is defined only for nonnegative integers, ratios, differences, and so on are used to
whereas the Gaussian distribution is defined compute the final result. In the following four
for any value of x, and that for the Poisson sections we describe equations and methods
distribution, the variance σ2 is equal to the that apply when a result is obtained from a
mean, m, whereas for the Gaussian distribu­ set of counting measurements, N1, N2, N3. . . .
tion, it can have any value. In some cases, we present first the general
9  •  Nuclear Counting Statistics 129

equation applicable for measurements of any σ (kN ) = k N (9-15)


type, M1, M2, M3, …, having individual vari­
ances, σ (M1)2, σ (M2)2, σ (M3)2, … The general The percentage uncertainty V in the product
equations can be used to compute the uncer­ kN is
tainty in the result for whatever M might
represent (e.g., a series of readings from a
V (kN ) = [σ (kN ) /kN ] × 100%
scale or a thermometer). We then apply these (9-16)
general equations to nuclear counting mea­ = 100% / N
surements. Note that in the following subsec­
tions it is assumed that random fluctuations which is the same result as Equation 9-6.
in counting measurements arise only from Thus there is no statistical advantage gained
random fluctuations in sample decay rate and or lost in multiplying the number of counts
that the individual measurements are statisti- recorded by a constant. The percentage uncer­
cally independent from one another. The latter tainty still depends on the actual number of
condition would be violated if N1 was in some counts recorded.
way correlated with N2, for example, if N1 was
the result for the first half of the counting
period for the measurement of N2. 3.  Products and Ratios
The uncertainty in the product or ratio of 
a series of measurements M1, M2, M3, … is
1.  Sums and Differences most conveniently expressed in terms of the
For either sums or differences of a series of percentage uncertainties in the individual
individual measurements, M1, M2, M3, …, results, V1, V2, V3, … The general equation is
with individual variances, σ (M1)2, σ (M2)2, given by
σ (M3)2, …, the general equation for the vari­
ance of the result is given by
V ( M1 ×÷ M2 ×÷ M3 ×÷ ) = V12 + V22 + V32 + 
(9-17)
σ ( M1 ± M2 ± M3 ± )
  (9-11)
= σ ( M1 )2 + σ ( M2 )2 + σ ( M3 )2 +  For counting measurements, this becomes

Thus, for a series of counting measurements V ( N1 ×÷ N2 ×÷ N3 ×÷ )


with individual results N1, N2, N3, …
1 1 1   (9-18)
= + + +  × 100%
σ( N1 ± N2 ± N3 ± ) = N1 + N2 + N3 +  N1 N2 N3
(9-12)
Again, this expression applies to mixed com­
and the percentage uncertainty is binations of products and ratios.

V ( N1 ± N2 ± N3 ± ) 4.  More Complicated Combinations


N1 + N2 + N3 +    (9-13) Many nuclear medicine procedures, such as
= × 100%
N1 ± N2 ± N3  thyroid uptakes and blood volume determina­
tions, use equations of the following general 
Note that these equations apply to mixed form.
combinations of sums and differences.
k( N1 − N2 )
Y= (9-19)
2.  Constant Multipliers ( N3 − N 4 )
If a measurement M having variance σM2 is The uncertainty in Y is expressed most con­
multiplied by a constant k, the general equa­ veniently in terms of its percentage uncer­
tion for the variance of the product is tainty. Using the rules given previously, one
can show that
σ (kM ) = k σM (9-14)
( N1 + N2 ) ( N3 + N 4 ) (9-20)
Substituting the appropriate quantities for VY = + × 100%
counting measurements, with M = N ( N1 − N2 ) 2
( N3 − N 4 ) 2
130 Physics in Nuclear Medicine

EXAMPLE 9-3 σ R = (1 / t) N
A patient is injected with a radionuclide. At = N / t2 (9-22)
some later time a blood sample is withdrawn
for counting in a well counter and Np = 1200 = R/t
counts are recorded. A blood sample with­
drawn prior to injection gives a blood back­ The percentage uncertainty in R is
ground of Npb = 400 counts. A standard
prepared from the injection preparation VR = (σ R /R) × 100%
(9-23)
records Ns = 2000 counts, and a “blank” = 100% / Rt
sample records an instrument background of
Nb = 200 counts. Calculate the ratio of net
patient sample counts to net standard counts, EXAMPLE 9-4
and the uncertainty in this ratio.
In a 2-min counting measurement, 4900
Answer counts are recorded. What is the average
The ratio is counting rate R(cpm) and its uncertainty?
Y = ( Np − N pb ) / ( Ns − N b ) Answer
= (1200 − 400) / (2000 − 200) R = 4900 / 2 = 2450 cpm
= 800 /1800 = 0.44
From Equation 9-22
The percentage uncertainty in the ratio is
(Equation 9-20) σ R = 2450 /2 = 35 cpm

(1200 + 400) (2000 + 200) and from Equation 9-23


VY = + × 100%
(1200 − 400) 2
(2000 − 200) 2
= 5 .6 % VR = 100% / 2450 × 2 ≈ 1.4%

The uncertainty in Y is 5.6% × 0.44 ≈ 0.02; Note from Equations 9-22 and 9-23 that
thus the ratio and its uncertainty are Y = 0.44 longer counting times produce smaller uncer-
± 0.02. tainties in estimated counting rates.

3.  Significance of Differences Between


D.  APPLICATIONS OF STATISTICAL Counting Measurements
ANALYSIS
Suppose two samples are counted and that
counts N1 and N2 are recorded. The difference
1.  Effects of Averaging (N1 – N2) may be due to an actual difference
If n counting measurements are used to between sample activities or may be simply
compute an average result, the average N is the result of random variations in counting
a more reliable estimate of the true value rates. There is no way to state with absolute
than any one of the individual measurements. certainty that a given difference is or is not
The uncertainty in N , σ N , can be obtained by caused by random error; however, one can
combining the rules for sums (Equation 9-11) assess the “statistical significance” of the dif­
and constant multipliers (Equation 9-14). ference by comparing it with the expected
random error. In general, differences of less
σN = N/n (9-21) than 2 σ [i.e., (N1 – N2) < 2 N1 + N 2 ] are
considered to be of marginal or no statistical
The uncertainty in N as an estimator of m significance because there is at least a 5%
therefore is smaller than the uncertainty in a chance that such a difference is simply caused
single measurement by a factor 1/ n. by random error (see Table 9-1). Differences
greater than 3σ are considered significant
2.  Counting Rates (<â•›1% chance caused by random error),
If N counts are recorded during a measuring whereas differences between 2σ and 3σ are in
time t, the average counting rate during that the questionable category, perhaps deserving
interval is R = N/t. Using Equation 9-15, the repeat measurement or longer measuring
uncertainty in the counting rate R is times to determine their significance.
9  •  Nuclear Counting Statistics 131

If two counting rates R1 and R2 are deter­ Therefore Rs = 500 ± 25╯cpm (±5%). Compare
mined from measurements using counting this with the uncertainty in the gross count­
times t1 and t2, respectively, the uncertainty ing rate Rg (from Equation 9-22)
in their difference R1 – R2, can be obtained by
applying Equations 9-11 and 9-22. σ Rg = 1500 / 4 ≈ 19 cpm (∼ 1%)

σ( R1 − R2 ) = R1 / t1 + R2 / t2 (9-24) and to the uncertainty in Rs that would be


obtained if there were negligible background
Comparison of the observed difference to the (Rb ≈ 0),
expected random error difference can again
be used to assess statistical significance, as
σ Rs = 500 / 4 ≈ 11 cpm (∼ 2%)
described in Section B.
4.  Effects of Background
All nuclear counting instruments have back­ Example 9-5 illustrates two important
ground counting rates, caused by electronic points:
noise, detection of cosmic rays, natural radio­ 1. High background counting rates are unde-
activity in the detector itself (e.g., 40K), and so sirable because they increase uncertainties
forth. If the background counting rate, mea­ in net sample counting rates.
sured with no sample present, is Rb and the 2. Small differences between relatively high
gross counting rate with the sample is Rg, counting rates can have relatively large
then the net sample counting rate is uncertainties.
Rs = Rg − Rb (9-25) 5.  Minimum Detectable Activity
The uncertainty in Rs is (from Equation 9-24) The minimum detectable activity (MDA) of a
radionuclide for a particular counting system
σ Rs = Rg / tg + Rb / tb (9-26) and counting time t is that activity that
increases the counts recorded by an amount
The percentage uncertainty in Rs is that is “statistically significant” in compari­
son with random variations in background
VRs =  Rg / tg + Rb / tb /( Rg − Rb )  × 100% counts that would be recorded during the
(9-27) same measuring time. In this instance, statis­
tically significant means a counting rate
If the same counting time t is used for both increase of 3σ. Therefore, from Equation 9-22,
sample and background counting, the counting rate for the MDA is
σ Rs = Rg + Rb / t MDA = 3 Rb / t (9-29)
(9-28)
= Rs + 2 Rb / t
EXAMPLE 9-6
EXAMPLE 9-5 A standard NaI(Tl) well counter has a back­
In 4-min counting measurements, gross ground counting rate (full spectrum) of
sample counts are 6000 counts and back­ approximately 200╯cpm. The sensitivity of the
ground counts are 4000 counts. What are  well counter for 131I is approximately 29╯cpm/
the net sample counting rate and its Bq (see Table 12-2). What is the MDA for 131I,
uncertainty? using 4-min counting measurements?

Answer Answer
Rg = 6000 / 4 = 1500 cpm The MDA is that amount of 131I giving 3 ×
200 cpm /4 ≈ 3 × 7╯cpm = 21╯cpm. Thus
Rb = 4000 / 4 = 1000 cpm
Rs = 1500 − 1000 = 500 cpm MDA = 21 cpm / (29 cpm /Bq)
From Equation 9-28 ≈ 0.7 Bq (i.e., < 1 dps)
σ Rs = 500 + (2 × 1000) / 4
In traditional units (1╯µCi = 37╯kBq), the
= 2500 / 4 = 50 / 2 MDA is ~ 0.00002╯µCi.
= 25 cpm
132 Physics in Nuclear Medicine

background counts are large (B1 >> S1, B2 >>


6.  Comparing Counting Systems S2), Equation 9-31 is approximated by
In Section B.1 it was noted that larger
numbers of counts have smaller percentage V1 S2 B1
≈ (9-33)
uncertainties. Thus in general it is desirable V2 S1 B2
from a statistical point of view to use a count­
ing system with maximum sensitivity (i.e., Both sensitivity and background are impor­
large detector, wide pulse-height analyzer tant in this case. Note that Equations 9-31
window) so that a maximum number of through 9-33 also can be used with counting
counts is obtained in a given mea�suring time; rates (cpm, cps) substituted for counts
however, such systems are also more sensi­ when equal counting times are used for all
tive to background radiation and give higher measurements.
background counting rates as well, which, as
EXAMPLE 9-7
shown by Example 9-5, tends to increase sta­
tistical uncertainties. The tradeoff between A sample is counted in a well counter using 
sensitivity and background may be analyzed a “narrow” pulse-height analyzer window 
as follows: and net sample and background counts are SN
Suppose a counting system provides gross = 500 counts and BN = 200 counts, respec­
sample counts G1, background counts B1, and tively. The sample is counted with the same
net sample counts S1 = G1 – B1 and that a system but using a “wide” window and the net
second system provides gross, background, sample and background counts are SW = 800
and net counts G2, B2, and S2 in the same counts and BW = 400 counts, respectively.
counting time. One can compare the uncer­ Which window setting offers the statistical
tainties in S1 and S2 to determine which advantage?
system is statistically more reliable. The per­
centage uncertainty in S1 is given by Answer
Background counts are neither “very small”
G1 + B1 nor “very large” in comparison with net
V1 = × 100% sample counts; thus Equation 9-31 must be
S1
(9-30) used:
S1 + 2 B1
= × 100%
S1 VN 800 500 + (2 × 200)
= ×
Corresponding equations apply to the second VW 500 800 + (2 × 400)

system. The ratio of the percentage uncer­ = (8 / 5) × 9 /16 = (8 / 5) × (3 / 4)
tainties for the net sample counts obtained
with two systems is therefore = 1 .2

V1 S2 S1 + 2 B1 Thus VNâ•›/â•›VW > 1 and the statistical advantage


= × (9-31)
V2 S1 S2 + 2 B2 belongs to the wider window setting, in spite
of its higher background counting rate.
If V1/â•›V2 < 1, then V1 < V2, in which case system
1 is the statistically preferred system. Con­
versely, if V1/V2 > 1, system 2 is preferred.
If background counts are relatively small 7.  Estimating Required Counting Times
(B1 << S1, B2 << S2), Equation 9-31 can be Suppose it is desired to determine net sample
approÂ�ximated by counting rate Rs to within a certain percent­
age uncertainty V. Suppose further that the
V1 S2 S1 approximate net sample and background

V2 S1 S2 counting rates are known to be Rs′ and R′b,
(9-32) respectively (e.g., from quick preliminary
S2 measurements). If a counting time t is to be

S1 used for both the sample and background
counting measurements, then the time
Thus when background levels are “small,” required to achieve the desired level of statis­
only relative sensitivities are important.  tical reliability is given by
The system with the higher sensitivity gives
the smaller uncertainty. Conversely, if t = [( Rs′ + 2 Rb′ ) /Rs′ 2 ](100% /V )2 (9-34)
9  •  Nuclear Counting Statistics 133

EXAMPLE 9-8 tg /tb = 900 /100 = 3


Preliminary measurements in a sample tg = 3tb
counting procedure indicate gross and back­
ground counting rates of Rg = 900╯cpm and Rb tg + tb = 3tb + tb = 1.25 min
= 100╯cpm, respectively. What counting time
is required to determine net sample counting tb = 1.25 min / 4 ≈ 0.3 min
rate to within 5%?
tg ≈ 1.25 − 0.3 = 0.95 min
Answer

Rs′ = 900 − 100 = 800 cpm The percentage uncertainty in Rs given by


Equation 9-27 is
t = {[800 + (2 × 100)]/ 8002 } × (100 / 5)2
= (1000 / 8002 ) × (100 / 5)2 VRs =  Rg / tg ) + ( Rb / tb ) × 100%  /( Rg − Rb )
= 0.625 min =  (900 / 0.95) + (100 / 0.3) × 10
00%  / 800

This time is used for both sample and back­ ≈ 4. 5%


ground counting. Therefore the total counting
time required is 1.25╯min. Thus a small statistical advantage (4.5% vs.
5%) is gained by using an optimal division
rather than equal counting times in this
8.  Optimal Division of Counting Times example.
In the preceding section it was assumed that
equal counting times were used for the sample
and background measurements. This is not
necessary; in fact, statistically advantageous E.  STATISTICAL TESTS
results may be obtainable by using unequal
times. The difference between two counting In Section D.3, an example was given of a
rates R1 and R2 is determined with the small­ method for testing the statistical significance
est statistical error if the total counting time of the difference between two counting mea­
t = t1 + t2 is divided according to surements. The test was based on the assump­
tion of underlying Poisson distributions for
t1 / t2 = R1′ / R2′ (9-35) the two individual measurements, with vari­
ances σ2 ≈ N. In this section we consider a few
where R′1 and R′2 are counting rates estimated other tests for evaluating statistical parame­
from preliminary measurements. Applying ters of sets of counting measurements. The
this to gross sample and background counting discussion focuses on applications of these
rate estimates, one obtains tests to nuclear counting data; however, as
noted in the discussion, the tests also are
tg /tb = Rg′ /Rb′ (9-36) applicable to other experimental data for
which the underlying random variability is
If (R′gâ•›≈R′b), approximately equal counting described by a Poisson or Gaussian distribu­
times are preferred; however, if the back­ tion. More detailed discussions of statistical
ground counting rate is small (R′b << R′g), it is tests are found in the references and sug­
better to devote most of the available time to gested readings at the end of this chapter.
counting the sample.
1.  The χ2 Test
EXAMPLE 9-9 The χ2 (chi-square) test is a means for testing
In Example 9-8, what is the optimal division whether random variations in a set of mea­
of a 1.25-min total counting time and the surements are consistent with what would 
resulting uncertainty in the net sample count­ be expected for a Poisson distribution. This is
ing rate? a particularly useful test when a set of count­
ing measurements is suspected to contain
Answer sources of random variation in addition to
Applying Equation 9-36, with R′g = 900╯cpm Poisson counting statistics, such as those
and R′b = 100╯cpm, resulting from faulty instrumentation or
134 Physics in Nuclear Medicine

other random variability between samples, P is the probability that random variations
animals, patients, and measurement tech­ observed in a series of n measurements from
niques. The test is performed as follows: a Poisson distribution would equal or exceed
1. Obtain a series of counting measure­ the calculated χ2 value. Conversely, 1 – P is
ments (at least 20 measurements is the pro�bability that smaller variations would
desirable). be observed. A P value of 0.5 (50%) would be
2. Compute the mean “perfect.” It indicates that the observed χ2
value is in the middle of the range expected
n for a Poisson disÂ�tribution. (Note that this cor­
N= ∑N i /n (9-37) responds to χ2 ≈ n – 1.)
i =1 A low P value (<â•›0.01) indicates that there
is only a small probability that a Poisson
and the quantity distribution would give the χ2 value as large
as the value observed and suggests that
n additional sources of random error are


χ2 = ∑ (N i − N )2 / N
(9-38)
present. A high P value (>â•›0.99) indicates
that random variations are much smaller
i =1

= (n − 1) SD /N 2 than expected and also is cause for concern.


For example, it could indicate that periodic
noise (e.g., 60-Hz line frequency) is being
where SD = standard deviation (Equa­ counted. Such signals are not subject to the
tion 9-7). Many pocket calculators have same degree of random variation as are radi­
programs for calculating standard devi­ ation counting measurements and therefore
ations; thus the second form in Equation have very small χ2 values. In general, a
9-38 may be more convenient to use. range 0.05 < P < 0.95 is considered an accept­
3. Refer to a χ2 table or graph (Fig. 9-2). able result. If P falls outside the range
Locate the value corresponding to the (0.01-0.99), one usually can conclude that
number of measurements, n, on the hor­ something is wrong with the measurement
izontal axis. system. If 0.01 < P < 0.05 or 0.95 < P < 0.99,
4. Compare the computed value of χ2 to the results are suspicious but the experi­
the most closely corresponding P-value ment is considered inconclusive and should
curve. be repeated.

100

P-values

10 0.01
0.05
Critical values of 2

0.10

0.50
1

0.90
0.1 0.95

0.99
0.01
1 10 100
Number of measurements, n


FIGURE 9-2  Critical values of χ2 versus number of measurements, n. For a properly operating system, one should

– – –
obtain χ2 ≈ (n – 1). P values indicate probability of obtaining χ2 larger than associated curve value. , P = 0.01-0.99;
, P = 0.05-0.95; , P = 0.10-0.90; , P = 0.5.
9  •  Nuclear Counting Statistics 135

value, which is about the accuracy to which


EXAMPLE 9-10
values can be read from Figure 9-2. When χ2
Use the χ2 test to determine the likelihood values are close to critical values, it is recom­
that the following set of 20 counting mea­ mended that the experiment be repeated. A
surements were obtained from a Poisson useful discussion of the χ2 statistic and appli­
distribution. cations to a variety of tests of nuclear count­
ing systems can be found in reference 1.
3875 3575
3949 4023 2.  The t -Test
3621 3314 The t-test (also sometimes called the Student
3817 3612
t-test) is used to determine the significance of
3790 3705
the difference between the means of two sets
3902 3412
of data. In essence, the test compares the dif­
3851 3520
ference in means relative to the observed
3798 3743
random variations in each set. Strictly speak­
3833 3622
ing, the test is applicable only to Gaussian-
3864 3514
distributed data; however, it is reasonably
reliable for Poisson-distributed data as well
Answer (see Fig. 9-1).
Using a pocket calculator or by direct calcula­ Two different tests are used, depending on
tion, it can be shown that the mean and stan­ whether the two sets represent independent
dard deviation of the counting measurements or paired data. Independent data are obtained
are from two different sample groups, for example,
two different groups of radioactive samples,
N = 3717 two different groups of patients or animals,
and so forth. Paired data are obtained from
SD = 187.4 the same sample group but at different times
or under different measurement conditions,
Thus, from Equation 9-38, such as the same samples counted on two dif­
ferent instruments or a group of patients or
χ 2 = 19 × (187.4)2 / 3717 animals imaged “before” and “after” a proce­

≈ 179.5 dure. The test for paired data assumes that
there is some degree of correlation between
Using Figure 9-2, the calculated value for χ2 the two measurements of a pair. For example,
far exceeds the largest critical value shown in an experiment comparing two different
for n = 20; (critical value ≈ 35 for P = 0.01). radiopharmaceuticals that supposedly have
Hence, we conclude that the probability is an uptake proportional to blood flow, a subject
very small that the observed set of counting with a “high” uptake for one radiopharmaceu­
measurements were obtained from a Poisson tical may have a “high” uptake for the other
distribution (P << 0.01). The observed stan­ as well.
dard deviation, SD = 187.4, also far exceeds To test whether the difference between the
what would be expected for a Poisson distri­ means of two sets of independent measure-
bution, N = 61. These results suggest the ments is significantly different from zero, the
presence of additional sources of random vari­ following quantity is calculated
ation beyond simple counting statistics in the
data. X1 − X 2
t=
Tables of χ2 values are provided in most [(n1 − 1) SD12 + (n2 − 1) SD22 ] /(n1 + n2 − 2)

statistics textbooks. It is possible to deter­ 1
mine more precise P values from these tables ×
than can be read from Figure 9-2, especially (1 / n1 ) + (1 / n2 )
(9-39)
for large values of n. However, it should be
noted that χ2 is itself a statistically variable where X1 and X 2 are the means of the two
quantity, having a standard deviation ranging data sets, SD1 and SD2 are their standard
from approximately 25% for n ~ 30 to approxi­ deviations (calculated as in Equation 9-7),
mately 15% for n ~ 100. Thus it is unwise to and n1 = number of data values in set 1 and
place too much confidence in χ2 values that n2 = number of data values in set 2. The verti­
are within approximately 10% of a critical cal lines bracketing the difference of the
136 Physics in Nuclear Medicine

means indicates that the absolute value obtained if the true means of the underlying
should be used. For n1 ≈ n2 and a reasonably distributions actually were the same, that is,
large number of samples in each group ( 10 m1 = m2. If a “statistically significant differ­
in each), Equation 9-39 reduces to ence” (i.e., a very low P value) is obtained, one
concludes that m1 ≠ m2, which could imply
either that m1 > m2, or that m2 > m1. For
X1 − X 2 example, a two-sided test would be appropri­
t= (9-40)
2( SD12 + SD22 ) /(n1 + n2 − 2) ate if one were concerned only whether the
uptakes of two radiopharmaceuticals were
different.
In either case, the calculated value of t then A one-sided test is used when one is con­
is compared with critical values of the cerned only whether one mean is greater than
t-distribution for the appropriate number of the other (e.g., whether the uptake of one
degrees of freedom, df = n1 + n2 – 2. radiopharmaceutical is greater than that of
Figure 9-3 shows values of t that would be the other). For example, if the experimental
exceeded at various probability levels if the result is X1 > X 2 , one might ask whether this
two sets of data actually were obtained from is consistent with m1 > m2. In this case, for a
the same distribution. For example, for df = given t value, the P values in Figure 9-3 are
10, a value of t  2.2 would be obtained by reduced by a factor of 2. The P value then is
chance with a probability of only 5% (P = 0.05) interpreted as the probability that the
if the underlying distributions actually were observed difference in means of the data
the same. This probability is sufficiently small would be obtained if m1 ≤ m2, that is, if m1 <
that the difference between the means usually m2 or m1 = m2. Statisticians generally do not
would be considered to be “statistically sig­ recommend the use of one-sided tests. For
nificant,” that is, that the underlying distri­ example, a nonsignificant one-sided test for
butions very likely have different means. m1 > m2 may overlook the possibility that m1
The t values given by Equations 9-39 and < m2, which could be an equally important
9-40, and the derivation of associated P values conclusion.
from Figure 9-3 as described earlier, corre­ Note further that, as with the χ2 statistic,
spond to a two-sided test. The P values so t values have their own statistical variations
obtained express the probability that the from one experiment to the next. Thus t
observed difference in means of measured values that are within a few percent of a criti­
data, whether positive or negative, would be cal value should be interpreted with caution.

100
P
0.00
P

1
0.0
1
Critical t-value

P


10
0.
05

P

0.1

1
1 10 100
Degrees of freedom, df
FIGURE 9-3  Critical values of t versus degrees of freedom (df) for different P values. Curves shown are for a two-sided
test of significance.
9  •  Nuclear Counting Statistics 137

For most practical situations, P values can be of the paired differences (calculated as in
read with sufficient accuracy from Figure 9-3. Equation 9-7, with the Nâ•›’s replaced by Δ’s) and
More precise t and P values are provided in n is the number of pairs of measurements. The
tables in statistics textbooks or by many sign of the difference between individual data
pocket calculators. pairs is significant and should be used in cal­
culating the mean of the differences. The cal­
culated value of t is compared with critical
EXAMPLE 9-11 values in the t-distribution table using df = (n
Suppose the two columns of data in Example – 1). Probability values are interpreted in the
9-10 represent counts measured on two differ­ same manner as for independent data.
ent groups of animals, for the uptake of two
EXAMPLE 9-12
different radiopharmaceuticals. Use the t-test
to determine whether the means of the two Suppose that the two columns of data in
sets of counts are significantly different (two- Example 9-10 represent counts measured on
sided test). the same group of animals for the uptake of
two different radiopharmaceuticals; that is,
Answer opposing values in the two columns represent
Using a pocket calculator or by direct calcula­ measurements on the same animal. Use the
tion, the means and standard deviations of t-test to determine whether there is a signifi­
the two sets of data are found to be (1 = left cant difference in average uptake of the two
column, 2 = right column) radiopharmaceuticals in these animals.

X1 = 3830 Answer
The first step is to calculate the difference in
SD1 = 87.8 counts for each pair of measurements. Sub­
X 2 = 3604 tracting the data value in the right-hand
column from that in the left for each pair, one
SD2 = 195.1 obtains for the differences

Thus, from Equation 9-40, 3875 − 3575 = +300

3830 − 3604 3949 − 4023 = −74


t=
2 × (87.8 + 195.1 ) / 18
2 2
etc.
≈ 3.17
The absolute value of the mean difference, ∆ ,
From Figure 9-3, this comfortably exceeds the and standard deviation of the differences are
critical value of t for df = (10 + 10 – 2) = 18 found to be
and P = 0.05 (~2.1) and exceeds as well the ∆ = 240.8

value for P = 0.01 (~2.9). Thus we can con­
clude that it is very unlikely that the means SD∆ = 141.0
of the two sets of data are the same (P < 0.01),
and that they are in fact significantly Using Equation 9-41
different.
240.8
For paired comparisons, the same table of t= ≈ 5 .4
critical values is used but a different method (141.0 / 10 )
is used for calculating t. In this case, the dif­
ferences between pairs of measurements are From Figure 9-3, the critical value of t for df
determined, and t is calculated from = n – 1 = 9 and P = 0.01 is t ≈ 3.3; thus, as in
Example 9-11, we can conclude that the
1 / n∑ i =1 ( X1,i − X 2,i ) means of the two sets of data are significantly
n

t= (9-41) different.
( SD∆ / n )
This discussion of paired data applies for
The numerator is formed by computing the two-sided tests. One-sided tests may be per­
average of the paired differences and taking its formed using the methods outlined in the dis­
absolute value. SDΔ is the standard deviation cussion of unpaired data.
138 Physics in Nuclear Medicine

TABLE 9-2â•…
3.  Treatment of “Outliers” CRITICAL VALUES OF THE THOMPSON
Occasionally, a set of data will contain what CRITERION FOR REJECTION OF A SINGLE
appears to be a spurious, or “outlier,” result, OUTLIER
reflecting possible experimental or measure­
Level of Significance, P
ment error. Although generally it is inadvis­ Number of
able to discard data, statistical tests can be Observations, n .1 .05 .01
used to determine whether it is reasonable,
3 1.15 1.15 1.15
from a statistical point of view, to do so. These
tests involve calculating the standard devia­ 4 1.46 1.48 1.49
tion of the observed data set and comparing 5 1.67 1.71 1.75
this with the difference between the sample 6 1.82 1.89 1.94
mean X and the suspected outlier, X. The
quantity calculated is 7 1.94 2.02 2.10
8 2.03 2.13 2.22
T = ( X − X ) / SD (9-42) 9 2.11 2.21 2.32
10 2.18 2.29 2.41
which then is compared with a table of critical
values (Table 9-2). The interpretation of the 11 2.23 2.36 2.48
result is the same as for the t-test; that is, the 12 2.29 2.41 2.55
critical value is that value of T (also some­
13 2.33 2.46 2.61
times called the Thompson criterion) that
would be exceeded by chance at a specified 14 2.37 2.51 2.66
probability level if all the data values were 15 2.41 2.55 2.71
obtained from the same Gaussian distribu­ 16 2.44 2.59 2.75
tion. Rejection of data must be done with
caution; for example, in a series of 20 mea­ 17 2.47 2.62 2.79
surements, it is likely that at least one of the 18 2.50 2.65 2.82
data values will exceed the critical value at 19 2.53 2.68 2.85
the 5% confidence level.
20 2.56 2.71 2.88
EXAMPLE 9-13 21 2.58 2.73 2.91
In the right-hand column of data in Example 22 2.60 2.76 2.94
9-10, the value 4023 appears to be an outlier,
23 2.62 2.78 2.96
differing by several standard deviations from
the mean of that column (see Example 9-11). 24 2.64 2.80 2.99
Use the Thompson criterion to determine 25 2.66 2.82 3.01
whether this data value may be discarded 30 2.75 2.91
from the right-hand column of data.
35 2.82 2.98
Answer 40 2.87 3.04
From Example 9-11, the mean and standard 45 2.92 3.09
deviation of the right-hand column of data are
50 2.96 3.13
X 2 = 3604, SD2 = 195.1. Using Equation 9-42
60 3.03 3.20
T = (4023 − 3604) /195.1 70 3.09 3.26
= 419 /195.1 80 3.14 3.31
= 2.15 90 3.18 3.35
100 3.21 3.38
According to Table 9-2, for 10 observations Adapted from Levin S: Statistical Methods. In Harbert
and P = 0.05, the critical value of T is 2.29. J, Rocha AFG (eds): Textbook of Nuclear Medicine, Vol 1,
Because the observed value is smaller, we ed 2. Philadelphia, 1984, Lea and Febiger, Chapter 4.
must conclude that there is a relatively high
probability (P > 0.05) that the value could
have been obtained by chance from the
observed distribution, and therefore that it
should not be discarded.
9  •  Nuclear Counting Statistics 139

4.  Linear Regression and X and Y are their means. The summa­
tions ∑ in Equation 9-44 extend over all
Frequently, it is desired to know whether there values of i (1, 2, … n).
exists a correlation between a measured quan­ The quantity SDY . X is “the standard devia­
tity and some other parameter (e.g., counts tion of Y given X,” that is, the standard devia­
versus time, radionuclide uptake versus organ tion of data values Y about the regression
weight, etc.). The simplest such relationship line. It is computed from
is described by an equation of the form
n−1
Y = a + bX (9-43) SDY2 i X = × ( SDY2 − b2 SDX2 ) (9-46)
n−2
Here, Y is the measured quantity and X is the
parameter with which it is suspected to be where SDX and SDY are the standard devia­
correlated. The graph of Y versus X is a tions of X and Y calculated by the usual
straight line, with Y-axis intercept a and methods. The estimated uncertainties (stan­
slope b (Fig. 9-4). dard deviations) in b and a are given by
To estimate values for a and b from a set
of data, the following quantities are SDb = SDY i X /  SDX n − 1 
calculated.*
1 X2 (9-47)
 n∑ X i Yi − ∑ X i ∑ Yi  SDa = SDY i X +
b=  (9-44) n (n − 1) SDX2
 n∑ X i2 − ( ∑ X i )2 
 
Finally, the correlation coefficient, r, is com­
a = Y − bX (9-45)
puted from
Here n is the number of pairs of data values;
Xi and Yi are individual values of these pairs r = b ( SDX /SDY ) (9-48)

The correlation coefficient has a value between


*The equations for regression parameters are interre­
lated and are expressed in a variety of ways in different
±1, depending on whether the slope b is posi­
textbooks. See recommended additional texts at the end tive or negative. A value near zero suggests
of this chapter. no correlation between X and Y, (i.e., b ≈ 0)

4
Y
Y values

3
X

Slope, b  Y/X
2

Intercept  a
1

0
0 1 2 3 4 5 6 7 8
X values
FIGURE 9-4  Hypothetical example of data and linear regression curve.  = data values;
curve; Y = a + bX, a = Y-axis intercept; b = slope, ΔY/Δâ•›X.
— = calculated regression
140 Physics in Nuclear Medicine

and a value near ±1 suggests a strong determine whether the intercept, a, is signifi­
correlation.* cantly different from zero.
An alternative method for evaluating the
strength of the correlation and its statistical
significance is to determine whether b is sig­ REFERENCE
nificantly different from zero. This can be 1. Tries MA, Skrable KW, French CS, Chabot GE: Basic
done by calculating applications of the chi-square statistic using counting
data. Health Phys 77:441-454, 1999.
t = b/SDb (9-49)

and comparing this to critical values of the BIBLIOGRAPHY


t-distribution (see Fig. 9-3). The number of Many useful general statistics texts are available.
degrees of freedom is df = (n – 2) in which n Some that were used for this chapter include the
is the number of ( X,Y ) data pairs. If the cal­ following:
culated value of t exceeds the tabulated criti­ Bevington PR: Data Reduction and Error Analysis for the
cal value at a selected significance level, one Physical Sciences, New York, 1992, McGraw-Hill.
[includes computer disk]
can conclude that the data support the hypoth­ Crow EL, Davis FA, Maxfield MW: Statistics Manual,
esis that Y is correlated with X. A similar New York, 1960, Dover Publications.
analysis can be performed (using SDa) to Snedecor GW, Cochran WG: Statistical Methods, ed 8,
Ames, IA, 1989, Iowa State University Press.
Additional discussion of nuclear counting statistics
*An intuitively attractive interpretation of the correla­ may be found in the following:
tion coefficient is that r 2 is the fraction of the observed Evans RD: The Atomic Nucleus, New York, 1972,
variance of the data set Y that actually is attributable to McGraw-Hill, Chapters 26 and 27.
variations in X and the dependence of Y on X. Thus, r 2 = Knoll GF: Radiation Detection and Measurement, ed 4,
0.64 (r = 0.8) implies that 64% of the observed variance New York, 2010, John Wiley, Chapter 3.
SDY2 actually is caused by the underlying variations in X, Leo WR: Techniques for Nuclear and Particle Physics
with the remaining 36% attributable to “other factors” Experiments, ed 2, New York, 1994, Springer-Verlag,
(including random statistical variations). Chapter 3.
chapter
10 
Pulse-Height
Spectrometry
Most of the radiation measurement systems important to remember that the amplitude of
used in nuclear medicine use pulse-height the signal from a proportional, scintillation,
analysis (Chapter 8, Section C) to sort out the or semiconductor detector depends on the
different radiation energies striking the detec- amount of radiation energy deposited in the
tor. This is called pulse-height or energy spec- detector, which may be less than the full
trometry. It is used to discriminate against energy of the incident particle or photon.
background radiation, scattered radiation, In the case of particulate radiation (e.g., β
and so on, and to identify the emission ener- particles or α particles), energy is transferred
gies of unknown radionuclides. In this chapter to the detector by collisions with atomic elec-
we discuss the basic principles of pulse-height trons in primary ionization events. These elec-
spectrometry and some of its characteristics trons may be given sufficient energy to cause
as applied to different types of detectors. secondary ionizations in collisions with other
atomic electrons (Fig. 10-1A). Approximately
80% of the total ionization from particle-type
A.  BASIC PRINCIPLES radiation is the result of secondary ionization.
The total amount of ionization produced
Pulse-height spectrometry is used to examine (primary plus secondary) determines the
the amplitudes of signals (electrical current amplitude of signal out of the detector (electri-
or light) from a radiation detector to deter- cal current or light). Whether the full energy
mine the energies of radiations striking  of the incident particle is deposited in the
the detector, or to select for counting only detector depends primarily on the range of the
those energies within a desired energy range. particle in the detector material. Particle
This can be accomplished only with those ranges are very short in solids and liquids;
detectors that provide output signals with thus the energy transfer is complete in most
amplitudes proportional to radiation energy solid and liquid detectors—for example,
detected, such as proportional counters, scin- sodium iodide [NaI(Tl)] and liquid scintilla-
tillation detectors, and semiconductor detec- tion detectors—and the amplitude of signal
tors (Chapter 7). A pulse-height, or energy, from the detector is thus proportional to par-
spectrometer consists of such a radiation ticle energy. In gas-filled detectors (e.g., pro-
detector and its high-voltage supply, pream- portional counters), however, or in very thin
plifier, amplifier, and pulse-height analyzer solid detectors (e.g., some semiconductor
(Chapter 8, Section C). A pulse-height spec- detectors) that do not have sufficient thick-
trum is a display showing the number of ness to stop the particle, the energy transfer
events detected (“counts”) versus the ampli- may be incomplete. In this case, the amplitude
tude of those events. This is provided most of the signal from the detector will not reflect
conveniently by a multichannel analyzer the total energy of the incident particle.
(Chapter 8, Section C.4 and Fig. 8-9). In the case of photons (γ rays, x rays,
The spectrum recorded from a radiation bremsstrahlung), energy is transferred to the
source depends not only on the energy of the detector primarily in photoelectric, Compton,
emissions from the source but also on the type or pair-production interactions. A portion of
of radiation detector used. It also depends on the incident photon energy is transferred as
the mechanisms by which the radiation kinetic energy to photoelectrons, Compton
energy is deposited in the detector. It is electrons, or positive-negative electron pairs,
141
142 Physics in Nuclear Medicine

Radiation Radiation
detector detector
e Incident
e e e
Incident photon Compton
particle e e
, ,  e
e e
e e
e e
e
A C

Radiation Radiation 511 keV


detector detector
e e
Photoelectric e e
e e e e  e
Incident  e e
e Incident
photon x ray e e
photon 511 keV
e e e e
Pair production e
B D
FIGURE 10-1  Deposition of radiation energy in a radiation detector. A, Energy transfer from an incident-charged
particle to electrons in multiple ionization events. Filled red circles indicate electrons generated in primary ionization
events and dashed lines are their trajectories; other electrons shown are released in secondary ionization events. B-D,
Energy transfer from incident photon to electrons in photoelectric (B), Compton (C), and pair-production (D)
interactions.

respectively, which in turn transfer their exclusively for detecting photons (γ rays or x
kinetic energy to the detector in secondary rays, primarily), only photon spectrometry is
ionization events (Fig. 10-1B-D). Whether the considered here.
amplitude of the signal out of the detector
reflects the full energy of the incident photon 1.  The Ideal Pulse-Height Spectrum
depends on the fate of the remaining energy, Suppose that a monoenergetic γ-ray source is
which is converted into one or more secondary placed in front of a radiation detector. Assume,
photons (characteristic x ray, Compton- further, that the energy of the γ rays, Eâ•›γ, is
scattered photon, or annihilation photons).  less than 1.022╯MeV, so that pair-production
A secondary photon may deposit its energy  interactions do not occur. The principle γ-ray
in the detector by additional interactions*; interactions with the detector will be by 
however, if it escapes from the detector, then photoelectric absorption and Compton scat-
the energy deposited in the detector and the tering. Most of the photoelectric interactions
amplitude of the signal from the detector do result in full deposition of the γ-ray energy in
not reflect the full energy of the incident the detector (the characteristic x ray usually
photon. The amplitude of the signal from the is also absorbed in the detector). Pulse ampli-
detector reflects only the amount of energy tudes from these events are proportional to Eâ•›γ
deposited in it by the radiation event. (Fig. 10-2A). With an ideal radiation detector,
this would produce a single narrow line in the
pulse-height spectrum, called the photopeak,
B.  SPECTROMETRY WITH NaI(Tl) at a location corresponding to the γ-ray energy
Eγ (Fig. 10-2B). In Compton scattering, only a
Because of its favorable performance-to-cost part of the γ-ray energy is transferred to the
ratio, a NaI(Tl) scintillator [coupled to a  detector, via the Compton recoil electron. If
photomultiplier (PM) tube, or in some cases the scattered γ ray also is absorbed in the
to a photodiode] is the most commonly used detector, the event produces a pulse in the
detector in nuclear medicine (Chapter 7, photopeak, whereas if the scattered γ ray
Section C). The basic principles of pulse- escapes, the energy deposited in the detector
height spectrometry are illustrated for this is less than Eâ•›γ. According to Equation 6-14,
detector. Because NaI(Tl) is used almost the energy deposited in the detector in a
single Compton scattering event ranges from
near zero (small-angle scattering event), up
*Note that multiple interactions arising from a single
to a maximum value Ece, corresponding to the
incident photon occur so rapidly in the detector that they energy of the recoil electron for 180-degree
appear to be a single event. Compton scattering events
10  •  Pulse-Height Spectrometry 143

Photopeak, E 
Ideal

Multiple Compton scattering


spectrum

Relative number of counts

Compton edge, Ece


Photoelectric
Pulse amplitude

Compton region
Multiple Compton
scattering

Single
Compton
scattering

Time Pulse amplitude (energy


deposited in detector)
A B
FIGURE 10-2  Elements of an ideal γ-ray pulse-height spectrum. A, Pulses from the detector representing different
types of γ-ray interactions in the detector. B, Distribution (relative number) of pulses versus amplitude (or energy
deposited in the detector). Only the photopeak represents deposition of the full energy of the γ ray in the detector.

Ece = Eγ2 /( Eγ + 0.2555) (10-1) Compton-scattering interactions in the detec-


tor. Multiple Compton scattering events
where Eâ•›γ and Ece are in MeV. The ideal spec- produce the distribution of pulses with ampli-
trum therefore includes a distribution of pulse tudes in the “valley” between the Compton
amplitudes ranging from nearly zero ampli- edge and the photopeak.
tude up to some maximum amplitude corre-
sponding to the energy given by Equation 2.  The Actual Spectrum
10-1. As shown in Figure 10-2B, this part of In practice, the actual spectrum obtained
the spectrum is called the Compton region. with a NaI(Tl) spectrometer is quite different
The sharp edge in the spectrum at Ece is called from the ideal one shown in Figure 10-2B. For
the Compton edge. example, Figure 10-3 shows a spectrum
Another possibility is that a Compton- obtained from a 137Cs radiation source, which
scattered γ ray may experience additional emits 662-keV γ rays and ~30-keV barium x
Photopeak
(662 keV)

137Cs

100
Relative number of counts

80
Ba x rays

Backscatter peak

Compton edge

60

40

20

0
0 100 200 300 400 500 600 700 800
Energy (keV)
FIGURE 10-3  Actual pulse-height spectrum recorded with a NaI(Tl) detector and 137
Cs (662-keV γ rays, ~30╯keV Ba
x rays). Compare with Figure 10-2B.
144 Physics in Nuclear Medicine

rays. The spectrum was recorded with a mul-

Photopeak
197Hg
tichannel analyzer, 0.01╯V per channel, with 100
the amplifier gain adjusted so that 662╯keV of
energy corresponds to 6.62╯V of pulse ampli-

Relative number of counts


tude. Thus the horizontal axis has been trans- 80
lated from pulse amplitude (~0-8╯V) into
energy (~0-800╯keV). 60
The first feature noted is that the spectrum 

Iodine escape peak


is “smeared out.” The photopeak is not a
sharp line, as shown in Figure 10-2B, but a 40
somewhat broadened peak, and the Compton
edge is rounded. This is caused by the imper-
fect energy resolution of the NaI(Tl) detector, 20
discussed in Section B.7.
Another structure that may appear in the
spectrum is a backscatter peak. This is caused 0
20 40 60 80 100
by detection of γ rays that have been scattered Energy (keV)
toward the detector after undergoing a 180-
degree scattering outside the detector. Certain FIGURE 10-4  Pulse-height spectrum for 197Hg (Eγ =
77.3╯keV) recorded with NaI(Tl). Iodine escape peak
detector configurations enhance the intensity (45-50╯keV) is due to escape of characteristic iodine x ray
of the backscatter peak. For example, in the (~30╯keV) following a photoelectric absorption event in
well counter (Chapter 12, Section A), a γ ray detector.
may pass through the detector without inter-
action, then scatter back into the detector
from the shielding material surrounding it becomes smaller, and it becomes more diffi-
and be detected. cult to distinguish between them.
Note that the energy of the backscatter Lead x-ray peaks sometimes are seen in
peak, Eb, is the energy of the scattered γ ray spectra acquired with systems employing
after 180-degree scattering, whereas the lead shielding and collimation. These peaks
energy of the Compton edge, Ece, is the energy are caused by photoelectric interactions of the
given to the recoil electron in a 180-degree γ rays in the lead. These interactions are fol-
scattering event. Therefore lowed by emission characteristic 80- to 90-keV
lead x rays, which may be recorded by the
Eb + Ece = Eγ (10-2) detector.
If the γ-ray energy exceeds 1.022╯MeV, pair
Equation 10-2 is helpful for identifying back� production interactions can occur. The kinetic
s�catter peaks. energy given to the positive-negative electron
Another structure that may appear is an pair is Eâ•›γ – 1.022╯MeV (see Chapter 6, Section
iodine escape peak. This results from photo- C.4). In most cases, the entire kinetic energies
electric absorption interactions with iodine of both particles are deposited in the detector.
atoms in the NaI(Tl) crystal, followed by When the positron comes to rest, it combines
escape from the detector of the characteristic with an electron to create a pair of 511-keV
iodine K-x ray, which has energy of approxi- annihilation photons. If both of these photons
mately 30╯keV. The iodine escape peak occurs are absorbed in the detector, the event is
at an energy approximately Eγ – 30╯keV; that recorded in the photopeak. If only one is
is, about 30╯keV below the photopeak. Iodine absorbed, the event is recorded in the single
escape peaks may be prominent with low- escape peak, at energy Eâ•›γ – 511╯keV (Fig.
energy γ-ray emitters, for example, 197Hg (Fig. 10-5). If both escape, the event is recorded in
10-4). Low-energy γ rays are detected by the double escape peak, at Eâ•›γ – 1.022╯MeV.
absorption primarily in a thin layer close to Scattering within or around the radiation
the entrance surface of the NaI(Tl) crystal source, or object scatter, changes the distribu-
where there is a reasonable probability that tion of radiation energies striking the detec-
the iodine x ray will escape from the detector. tor. This is especially important in counting
With increasing γ-ray energy, the interactions measurements in vivo and in radionuclide
tend to occur deeper within the detector, and imaging because substantial scattering of
there is less likelihood that the x ray will radiation occurs within the patient. Figure
escape. Also, the relative difference between 10-6 shows spectra for 131I with and without
the photopeak and escape peak energies scattering material around the source. The
10  •  Pulse-Height Spectrometry 145

(1600 keV)
Photopeak
Single escape peak
100

Double escape peak


Relative number of counts
80

60

40

20 511 keV
1022 keV
0
0 200 400 600 800 1000 1200 1400 1600 1800
Energy (keV)
FIGURE 10-5  Pulse-height spectrum for a hypothetical 1.6-MeV (1600-keV) γ-ray emitter. Because γ-ray energy
exceeds 1.022╯MeV (1022╯keV), pair-production interactions can occur in the detector. Escape peaks are due to escape
of one or both annihilation photons from the detector following a pair-production interaction.

Source in air general effect of object scatter is to add events


in the lower-energy region of the spectrum. It
4 cm plastic in front is possible to discriminate against scattered
and behind source radiation by using a pulse-height analyzer to
count only events in the photopeak, as shown
10
photopeak

131I in Figure 10-6.


364-keV

Coincidence summing can occur when a


radionuclide emits two or more γ rays per
8 nuclear disintegration. Figure 10-7 shows
photopeak

spectra recorded with a NaI(Tl) well counter


Relative number of counts

80-keV

for 111In, which emits a 173-keV and a 247-keV


γ ray simultaneously. The peak at 420╯keV
Backscatter

6 seen when the source is inside the well counter


Energy results from simultaneous detection of these
selection two γ rays. Summing between x rays and γ
for scatter rays also can occur. With positron emitters,
photopeak

4
284-keV

rejection coincidence summing between the two 511-keV


annihilation photons also may be observed.
Coincidence summing is especially prominent
2 with detector systems having a high geomet-
ric efficiency (see Chapter 11, Section A.2),
that is, systems in which there is a high prob-
ability that both γ rays will be captured by the
0
0 100 200 300 400 500 detector [e.g., well counters (Chapter 12,
Energy (keV) Section A)].
FIGURE 10-6  Effect of scattering material around the 3.  Effects of Detector Size
source on the pulse-height spectrum for 131I. The red
curve shows the spectrum with the source in air and the The larger the detector crystal size, the more
blue curve shows the spectrum after placing the source likely it is that secondary photons (i.e.,
between 4-cm layers of plastic. For the blue curve, the Compton-scattered γ rays and annihilation
darker shaded area represents counts within the photo-
peak and the lighter shaded area represents counts due
photons) will be absorbed in the crystal. Thus
to γ rays scattered in the plastic. with increasing crystal size, the number of
events in the photopeak versus Compton
regions increases. Figure 10-8 shows this
146 Physics in Nuclear Medicine

173  247 keV


173 keV  111Cd x rays
111In

in well counter

247 keV  111Cd x rays


173 keV
x rays

FIGURE 10-7  Pulse-height spectra

247 keV
recorded for 111In with a NaI(Tl)
111Cd

well counter detector. Top, Coin-


Relative number of counts

cidence summing between the


x-ray and γ-ray emissions results
in additional peaks in the spec-
trum when the source is inside
the well. Bottom, When the
source is outside the well, the
173 keV

Out of well probability of coincidence detec-


tion decreases and the coinci-
247 keV

counter dence peaks disappear.

0 80 160 240 320 400 480


Energy (keV)

effect on the spectrum for 137Cs. Figure 10-8 137Cs


also shows that the “valley” between the
Compton edge and the photopeak at first 662 keV
increases with increasing detector size, due 
to greater likelihood of an incident photon 100
NaI (Tl)
undergoing multiple Compton interactions crystal
size
within the detector. However, the number of
counts in this region eventually decreases due 3.8 diam 
Relative number of counts

2.5 cm
to greater likelihood of complete absorption of
the incident photon’s energy within the detec-
5  5 cm
tor, thereby producing an event in the photo-
peak rather than in the valley. For γ-ray
7.6  7.6 cm
energies greater than 1.022╯MeV, the size of
annihilation escape peaks also decreases with
10
increasing crystal size.
4.  Effects of Counting Rate
Distortions of the spectrum occur at high
counting rates as a result of overlap of detec-
tor output pulses. Pulse pile-up between two
events can produce a single pulse with an
amplitude equal to their sum (see Chapter 8,
Section B.3). Pile-up between photopeak
1
events and lower-energy events causes a 0 200 400 600 800 1000
general broadening of the photopeak (Fig. Energy (keV)
10-9). This also is one of the causes of dead
FIGURE 10-8  Effect of NaI(Tl) crystal size on the pulse-
time losses (see Chapter 11, Section C). There height spectrum for 137Cs. The spectra have been nor�
also may be a shift of the photopeak toward malized to equal photopeak heights. In practice, the
lower energies because of baseline shift in the photopeak height also increases with increasing detector
amplifier at high counting rates. Thus if a size because of increasing detection efficiency (Chapter
11, Section A).
single-channel analyzer (SCA) is set up at low
counting rates on the photopeak and the
10  •  Pulse-Height Spectrometry 147

140 keV
Primary spectrum
Number of counts

15
Scatter spectrum
10 125I

0
0 40 80 120 160
Photon energy (keV) 10
A

Relative number of counts


Baseline shift 197Hg
5
Number of counts

10
Pulse
pileup 99mTc
5

0
0 40 80 120 160
Window 10
B 20% 203Hg

FIGURE 10-9  A, 99mTc spectrum at low counting rate. 5


B, Spectral broadening and shift in apparent photopeak
energy caused by pulse pileup and baseline shift in the  0
spectrometer amplifier at high counting rate.
10
131I
5
detector is used at very high counting rates,
the photopeak can shift out of the SCA window 0
0 100 200 300 400
and an incorrect reading may be recorded. Energy (keV)
5.  General Effects of γ -Ray Energy FIGURE 10-10  Pulse-height spectra recorded with a
NaI(Tl) detector for different γ-ray energies. Primary
Figure 10-10 shows pulse-height spectra for a spectrum refers to γ rays striking the detector without
number of radionuclides emitting γ rays of scattering from objects outside the detector. Scatter spec-
different energies. The solid lines are the trum refers to γ rays that have been scattered by objects
spectra for unscattered γ rays, and the dashed outside the detector, such as from tissues or other materi-
als surrounding the source distribution. (Adapted from
lines are the spectra for object-scattered γ Eichling JO, Ter Pogossian MM, Rhoten ALJ: Analysis of
rays. In general, the relative number of events scattered radiation encountered in lower energy diagnos-
in the Compton region versus the photopeak tic scanning. In Gottschalk A, Beck RN, editors: Funda-
region becomes larger with increasing γ-ray mentals of Scanning. Springfield, IL, 1968, Charles C
Thomas.)
energy because the probability of Compton
versus photoelectric interactions in the detec-
tor becomes larger. Also, as γ-ray energy 6.  Energy Linearity
increases, it becomes easier to separate object Energy linearity refers to the proportionality
scatter from the photopeak. This is because between output pulse amplitude and energy
the change in γ-ray energy with Compton absorbed in the detector. Figure 10-11, taken
scattering increases with γ-ray energy (see from early work on the basic properties of
Chapter 6, Section C.3). For example, at NaI(Tl) detectors, shows a typical relation-
100╯keV and at 500╯keV, Compton scattering ship between apparent energy (pulse height)
through 90 degrees produces scattered photon and actual γ-ray energy for a system cali-
energies of 84╯keV and 253╯keV, respectively. brated with 137Cs (662╯keV). Most NaI(Tl)
In addition, as discussed in Section B.7 below, systems are quite linear for energies between
the energy resolution of NaI(Tl) detectors 0.2 and 2╯MeV, and a single-source energy
improves with increasing γ-ray energy, which calibration usually is acceptable in this range;
provides further improvement in their ability however, one can run into problems by cali-
to discriminate between scattered versus brating a spectrometer with a high-energy
unscattered photons. source (e.g., 137Cs) and then attempting to use
148 Physics in Nuclear Medicine

1
Apparent energy (pulse height)

0.1

0.1 1
-ray energy (MeV)
FIGURE 10-11  Apparent energy (pulse height) versus actual γ-ray energy for a NaI(Tl) scintillation detector calibrated
for one unit of pulse height per MeV at 0.662╯MeV (solid line). Dashed line is line of identity. With this calibration,
detector nonlinearities can lead to 10% to 15% errors in apparent energy for Eγ  0.2╯MeV. (Curve redrawn from Knoll
GF: Radiation Detection and Measurement, ed 3. New York, 2000, John Wiley, p 339.)

it for much lower-energy sources (e.g., 125I or Causes of spectral blurring relating to fabri-
99m
Tc) or vice versa. Modern spectrometers cation of a NaI(Tl) detector assembly include
and gamma cameras frequently have pre� the following:
calibrated push buttons that are set for spe- 4. Nonuniform sensitivity to scintillation
cific radionuclides and that take into account light over the area of the PM tube
any energy nonlinearities. For systems that cathode
are not precalibrated, individual low- and 5. Nonuniform light collection efficiency
high-energy sources should be used to cali- for light emitted from interactions at
brate a spectrometer for measurements that different locations within the detector
span a wide range of energies. crystal
Energy linearity also is an important factor An important but subtle cause of spectral
in energy resolution. This is discussed in the blurring with scintillation detectors is the
following section. following:
6. Nonlinear energy response of the scintil-
7.  Energy Resolution lator, such that the amount of light pro-
Sharp lines and sharp edges in the ideal spec- duced by the lower-energy Compton
trum (Fig. 10-2B) become broadened lines electrons in multiple Compton interac-
and rounded edges in actual spectra (Fig. tions generate a different total amount
10-3). With NaI(Tl) detectors, this spectral of light than is produced by a higher-
blurring (or line broadening) is caused pri- energy photoelectron in a single high-
marily by random statistical variations in the energy photoelectric event, even when
events leading to the formation of the output the total energy deposited in the crystal
signal. For NaI(Tl) coupled to a PM tube, is the same (see Section B.6)
these include the following: Electronic noise contributes to spectral blur-
1. Statistical variations in the number of ring with all types of detectors. With scintil-
scintillation light protons produced per lation detectors read out by a PM tube, the
keV of radiation energy deposited in the principal sources include the following:
crystal 7. Fluctuations in the high voltage applied
2. Statistical variations in the number of pho- to the PM tube
toelectrons released from the photocathode 8. Electrical noise in the PM tube
3. Statistical variations in the electron
multiplication factor of the dynodes in Because of these factors, there are differ-
the PM tube ences in the amplitude of the signal from a
10  •  Pulse-Height Spectrometry 149

scintillation detector for events in which pre- light photons yield photoelectrons from the
cisely the same amount of radiation energy is photocathode. Thus the average number of
deposited in the detector. Instead of a narrow photoelectrons is approximately 10 per keV of
“line,” the photopeak approximates a radiation energy absorbed in the NaI(Tl)
gaussian-shaped curve, as illustrated in crystal. Complete absorption of a 662-keV γ
Figure 10-3. The width of the photopeak, ΔE, ray from 137Cs results in the release on average
measured across its points of half-maximum of approximately 6600 photoelectrons from
amplitude is the energy resolution. This is the photocathode; however, the actual number
referred to as the full width at half maximum varies from one γ ray to the next according to
(FWHM). Usually the FWHM is expressed as Poisson statistics, with a standard deviation
a percentage of the photopeak energy Eγ: of ± 6600 ≈ 81 photoelectrons. This amounts
to a variation of approximately ±1.2% in pulse
FWHM(%) = (∆E/Eγ ) × 100% (10-3) amplitude (see Chapter 9, Section B), which
translates into an FWHM of approximately
Figure 10-12 illustrates this computation. 3% (Equation 10-4).
Although FWHM can be computed for any If this were the only source of variation in
γ-ray energy, it is customary to specify the output pulse amplitude, the energy resolution
value for the γ rays of a commonly used radio- of NaI(Tl) would be proportional to 1/ E ,
nuclide when characterizing the performance because the number of photoelectrons is pro-
of a particular detector. Examples are the portional to the energy deposited in the
662-keV γ rays of 137Cs, the 511-keV annihila- crystal. However, in practice, the effects of
tion photons of positron emitters, or the energy are smaller owing to the presence of
140-keV γ rays of 99mTc. For a gaussian-shaped other sources of pulse amplitude variation.
curve, the FWHM is related to the standard This is evident from a simple comparison of
deviation, SD, according to FWHM achievable with a good-quality scintil-
lation detector at 662╯keV (about 6%) and the
FWHM ≈ 2.35 × SD (10-4)
value predicted from simple photoelectron
For NaI(Tl)-PM tube detectors, a major statistics (approximately 3%). The difference
source of statistical variation in output pulse is due to other sources of amplitude varia-
amplitude is in the number of photoelectrons tions listed earlier. Figure 10-13, showing the
released from the photocathode of the PM observed energy resolution for a NaI(Tl)
tube. On average, approximately 40 visible detector versus a simple 1/ E relationship,
light photons are produced per keV of γ-ray illustrates this point.
energy absorbed in the crystal (see Table 7-2). Analyses suggest that photoelectron statis-
With good-quality PM tubes and efficient tics, PM-tube noise (including electron multi-
optical coupling, approximately 25% of the plication), and nonlinear energy response of
662 keV

137Cs

100

46
Relative number of counts

E
FWHM (%)    100%
80 E 662
 7% Maximum height
E  46 keV

60
FWHM
40
1/2 Maximum
height
20

0
0 100 200 300 400 500 600 700
Energy (keV)
137
FIGURE 10-12  Calculation of full width at half maximum (FWHM) energy resolution of a NaI(Tl) detector for Cs
662-keV γ rays.
150 Physics in Nuclear Medicine

100

FWHM (%)

10

1
0.1 1
-ray energy (MeV)
FIGURE 10-13  Energy resolution versus γ-ray energy for a 7.5-cm-diameter × 7.5-cm-thick NaI(Tl) scintillation detec-
tor. Solid line indicates theoretical 1/ E behavior, fitted to low-energy data points. Experimental data points () from
Birks JB: The Theory and Practice of Scintillation Counting. Oxford, England, 1964, Pergammon Press, p 159.

the scintillator contribute about equally to NaI(Tl), the integration time typically is
overall energy resolution at 662╯keV.1,2 Sig- approximately 1 µsec, in which case the energy
nificant improvements in PM tubes and resolutions mentioned earlier may be achieved.
optical coupling technology have yielded However, for positron coincidence detection,
steady improvements in energy resolution the integration time may be shortened to only
during the past 3 to 4 decades. However, the a few hundred nanoseconds to minimize the
nonlinear energy response of the scintillator number of random coincidences between anni-
may prove to be the limiting factor in achiev- hilation photons that do not actually arise
able energy resolution for NaI(Tl), regardless from the same positron annihilation event
of further technological improvements. Addi- (Chapter 18, Section A.9). With shorter inte-
tional discussions of this complicated issue gration times, the number of photoelectrons
can be found in reference 1 and other recom- contributing to the detected signal is smaller;
mended readings at the end of this chapter. hence, energy resolution is degraded. Typi-
With good-quality PM tubes, energy resolu- cally, the energy resolution at 511╯keV (the
tion of 6% at 662╯keV is achievable with energy of the annihilation photons) may be
NaI(Tl). These detectors have energy resolu- degraded from a value of 6% to 7% with “full
tions of approximately 10% for the 140-keV γ integration” of the detected signal, to a value
rays of 99mTc. With large-area crystals having of approximately 10% with the shortened inte-
multiple PM tubes [e.g., the gamma camera, gration time used in positron coincidence
(see Chapter 13)], the resolution for 99mTc can mode.
be degraded because of slightly different Other factors that can degrade energy res-
responses between PM tubes. However, olution include poor light coupling between
modern gamma cameras employ electronic the NaI(Tl) crystal and the PM tubes, which
and software correction schemes to account can cause a reduction in the number of pho-
for these variations and commonly achieve toelectrons released per keV. Energy resolu-
10% energy resolution for 99mTc as well tion also may be degraded by other conditions
(Chapter 14, Section A.3). that interfere with the efficient collection of
Another factor that affects energy resolu- light from the crystal by the PM tube. For
tion is the integration time used to collect example, a cracked detector crystal causes
signal from the detected event. For routine internal reflections and trapping of light in
imaging or spectrometry applications with the detector crystal. A sudden degradation of
10  •  Pulse-Height Spectrometry 151

energy resolution and loss of output pulse sizes. As well, Ge(Li) must be operated at
amplitude often are the first symptoms of a liquid nitrogen temperatures, which poses
cracked crystal. Deterioration of the optical practical inconveniences, and Si(Li) detectors
coupling grease between the detector crystal are relatively inefficient for the γ-ray energies
and PM tube has similar effects. Poor light commonly used in nuclear medicine.
collection also can occur with detectors having More recently developed “room tempera-
an unusual shape, such as a high aspect ratio ture” semiconductor detectors such as
(long and narrow). cadmium telluride and cadmium zinc tellu-
Good energy resolution is a desirable char- ride (CZT) (Chapter 7, Section B) may provide
acteristic for any spectrometer system because more practical options for nuclear medicine.
it permits precise identification and separa- Although their energy resolution is not equal
tion of γ rays with very similar energies, for to that of Si(Li) or Ge(Li), owing to somewhat
example, for radionuclide identification or lower production of charge carriers, it is sig-
scatter rejection. The best energy resolution nificantly better than NaI(Tl).
is obtained with semiconductor detectors, as Figure 10-15 shows typical pulse-
discussed in the following section. height spectra for 99mTc and 18F (511-keV
annihilation photons) obtained with a CZT
detector. A number of interesting features are
C.  SPECTROMETRY WITH OTHER evident in these spectra. For 99mTc, the energy
DETECTORS resolution is intermediate to that of Ge(Li)
and NaI(Tl) (see Fig. 10-14). For both 99mTc
and 18F, there is evidence of a “tail” on the
1.  Semiconductor Detector low-energy side of the photopeak. This is
Spectrometers caused by “charge trapping” and incomplete
The major advantage of [Si(Li)] and [Ge(Li)] charge collection within the CZT crystal. In
semiconductor detectors (Chapter 7, Section addition to the main photopeak at 140╯keV, a
B) is their superb energy resolution. It is small photopeak is seen at approximately
typically 6-9 times better than proportional 20╯keV. This corresponds to K-x rays of tech-
counters and 20-80 times better than netium emitted after internal conversion
NaI(Tl):PM tube detectors. The output signal events (~7% emission frequency; see Appen-
from a semiconductor detector is a pulse of dix C). This peak is rarely, if ever, seen in
electrical current, the amplitude of which is NaI(Tl) spectra owing to attenuation of these
proportional to the radiation energy depos- x rays by the canning material housing the
ited in the detector. The energy resolution of detector crystal.
Si(Li) and Ge(Li) detectors is determined by The CZT spectrum for 18F shows a well-
statistical variations in the number of charges defined Compton edge (Ece = 341╯keV) and
in this pulse. The average number is approxi- backscatter peak (Eb – 170╯keV). Also present
mately 1 charge (electron) per 3╯eV of radia- are peaks at approximately 73╯keV and
tion energy absorbed (see Table 7-1), as 86╯keV, which were caused by characteristic
compared with only 10 photoelectrons per x rays of lead from shielding material placed
keV in a NaI(Tl):PM tube detector system. around the source in this experiment.
The much larger number of charges produced Note finally that the energy resolution of
in these semiconductor detectors results in the CZT spectra is essentially the same for
99m
much smaller percentage statistical varia- Tc as for 18F, in spite of a nearly fourfold
tions in signal amplitude and hence much difference in their γ-ray energies. With
better energy resolution than NaI(Tl). Figure NaI(Tl), this would result in a significant 
10-14 shows comparative NaI(Tl): PM Table difference in energy resolution, owing to a
and Ge(Li) spectra for 99mTc. The superior similar difference in the number of photoelec-
energy resolution of Ge(Li) permits almost trons emitted by the photocathode of the PM
complete elimination of scattered radiation tube. However, with CZT, the equivalent
by pulse-height analysis and clean separation source of line broadening is in the number 
of multiple photon emissions from single or of charge carriers (electron-hole pairs) pro-
multiple sources. duced, which is a significantly larger number.
Despite their superior performance in The predominating causes of line broadening
terms of energy resolution, Si(Li) and Ge(Li) with CZT are leakage current through 
detectors have not found widespread usage in the detector itself and incomplete (and vari-
nuclear medicine. As explained in Chapter 7, able) collection of the charge carriers. These
they are available only in relatively small factors depend primarily on the operating
152 Physics in Nuclear Medicine

NaI(Tl) detector resolution,


18.3 keV (13.1%) FWHM 20%
window
140 keV
10 Primary
Total

8 Object scatter

2
Relative number of counts

0 20 40 60 80 100 120 140 160

Ge(Li) detector Resolution, 140 keV


10
0.6 keV (0.42%) FWHM

0 20 40 60 80 100 120 140 160


Energy (keV)
FIGURE 10-14  Comparative pulse-height spectra recorded from a 99mTc source with NaI(Tl) and Ge(Li) detectors. In
the NaI(Tl) spectrum (top), the blue curve represents unscattered (primary) γ rays, the orange curve represents γ rays
scattered by materials around the source, and the red curve represents the sum of the primary and scattered γ rays.
For the Ge(Li) detector (bottom), only the spectrum for primary γ rays is shown. Separation of primary from scattered
γ rays is much easier with the semiconductor detector.

voltage and on the specific detector confi� restore a 1/ E relationship in their energy
guration (such as electrode attachments). resolution; however, this also would eliminate
The next most important contributor is elec- the practical benefits of room-temperature
tronic noise. None of these factors depend operation.
directly on γ-ray energy. Thus the approxi-
mate 1/ E relationship seen with NaI(Tl) 2.  Liquid Scintillation Spectrometry
generally does not apply for room-temperature Although NaI(Tl) spectrometers are used in
semiconductor detectors. many different configurations and applica-
The performance of CZT detectors can be tions, both for in vivo and in vitro measure-
improved by operating them at low tempera- ments, liquid scintillation spectrometers are
tures (thereby reducing background leakage used almost exclusively in a single configura-
current). This also would at least partially tion for in vitro sample counting (see Chapter
10  •  Pulse-Height Spectrometry 153

99m
Tc

Counts
FWHM  4.7 keV
(3.4%)
FIGURE 10-15  99mTc (A) and
18
F (B) spectra obtained with a
5 × 5 × 5-mm cadmium zinc tel-
luride (CZT) detector, with 0.6-mm- 
thick Al entrance window and
0 20 40 60 80 100 120 140 160 180 200
CAPture electrode geometry.3
The detector was operated at A Energy (keV)
room temperature with an oper-
ating voltage of 1000╯V for 99mTc
and 1250╯V for 18F. FWHM, full
width at half maximum. (Data
courtesy Paul Kinahan, Univer- 18
sity of Washington, Seattle, WA; FWHM  16.2 keV F
eV Products, Saxonburg, PA; (3.2%)
and James Wear of Lunar Cor-
poration, Madison, WI.)
Counts

0 100 200 300 400 500 600 700 800


B Energy (keV)

12, Section C). Liquid scintillation detectors


662 keV

are used primarily for counting the low-energy 137Cs


β emissions from 3H, 14C, 35S, 45Ca, and 32P. 5
Figure 10-16 shows pulse-height spectra
4
recorded with a liquid scintillation system for
a γ-ray emitter, 137Cs, and for a β emitter, 14C. 3
Liquid scintillators provide poor energy reso-
Relative number of counts

2
lution for γ rays because they produce rela-
tively few scintillation light photons per keV 1
of energy absorbed and hence produce rela-
0
tively few photoelectrons at the PM tube pho- 200 400 600 800 1000
tocathode in comparison with NaI(Tl). Another
factor is the relatively inefficient transfer of
light photons from the scintillator vial to the
(150 keV)

14C
4
PM tubes. The spectrum for a β emitter has
no sharp peak because the energy spectrum 3
for β particles has a broad distribution from
Emax

max
zero up to Eβ for the radionuclide (compare 2


Fig. 10-16 with Fig. 3-2). 1

3.  Proportional Counter Spectrometers 0


40 80 120
Gas-filled proportional counters (Chapter 7, Energy (keV)
Section A.3) have found limited use for spectroÂ� FIGURE 10-16  Pulse-height spectra recorded with a
metry in nuclear medicine. Their energy reso- liquid scintillation detector, for a γ -ray emitter, 137Cs
lution is several times better than NaI(Tl). (top), and a β emitter, 14C (bottom).
154 Physics in Nuclear Medicine

Their major disadvantage is poor detection Hine GJ: Sodium iodide scintillators. In Hine GJ, editor:
efficiency for γ rays (see Chapter 11, Section Instrumentation in Nuclear Medicine, Vol 1, New York,
1967, Academic Press, Chapter 6.
A.3). Some applications of proportional counter
spectrometry are discussed in Chapter 12. Spectrometry with Si(Li) and Ge(Li) semiconductor
detectors is discussed in the following:
REFERENCES TerPogossian MM, Phelps ME: Semiconductor detector
systems. Semin Nucl Med 3:343-365, 1973.
1. Dorenbos P, de Haas JTM, van Eijk CWE: Non-
proportionality of scintillation response and the energy Spectrometry with room-temperature semiconductor
resolution obtainable with scintillation crystals. IEEE detectors is discussed in the following:
Trans Nucl Sci 42:2190-2202, 1995. Schlesinger TE, James RB, editors: Semiconductors for
2. Valentine JD, Rooney BD, Li J: The light yield non- room temperature nuclear detector applications. In
proportionality component of scintillator energy reso- Semiconductors and Semimetals, Vol 43, San Diego,
lution. IEEE Trans Nucl Sci 45:512-517, 1998. 1995, Academic Press. (Chapters 8, 9, and 14 are of
3. Parnham K, Szeles C, Lynn KG, Tjossem R: Perfor- particular interest.)
mance improvement of CdZnTe detectors using modi-
fied two-terminal electrode geometry. SPIE Conference A useful general reference for pulse-height
on Hard X-Ray, Gamma-Ray and Neutron Detector spectrometry is the following:
Physics, Denver, CO, July 1999. Knoll GF: Radiation Detection and Measurement, ed 4,
New York, 2010, John Wiley.
BIBLIOGRAPHY
Additional discussion of NaI(Tl) pulse-height
spectrometry may be found in the following:
Birks JB: The Theory and Practice of Scintillation Count-
ing, New York, 1964, MacMillan.
chapter
11 
Problems in
Radiation Detection
and Measurement

Nuclear medicine studies are performed with A.  DETECTION EFFICIENCY


a variety of types of radiation measurement
instruments, depending on the kind of radia-
tion source that is being measured and the 1.  Components of Detection Efficiency
type of information sought. For example, Detection efficiency refers to the efficiency
some instruments are designed for in vitro with which a radiation-measuring instru-
measurements on blood samples, urine speci- ment converts emissions from the radiation
mens, and so forth. Others are designed for source into useful signals from the detector.
in vivo measurements of radioactivity in Thus if a γ-ray-emitting source of activity A
patients (Chapter 12). Still others are used to (Bq) emits η γ rays per disintegration, the
obtain images of radioactive distributions in emission rate ξ of that source is
patients (Chapters 13, 14, and 17-19).
All these instruments have special design ξ (γ rays/sec) = A (Bq) × 1 (dps/Bq)
characteristics to optimize them for their    (11-1)
specific tasks, as described in the chapters × η (γ rays/dis)
indicated above; however, some consider-
ations of design characteristics and perfor- If the counting rate recorded from this source
mance limitations are common to all of them. is R [counts per second (cps)], then the detec-
An important consideration for any radiation tion efficiency D for the measuring system is
measurement instrument is its detection
efficiency. Maximum detection efficiency is
D = R/ξ (11-2)
desirable because one thus obtains maximum
information with a minimum amount of
radioactivity. Alternatively, if the emission rate ξ and detec-
Also important are the instrument’s count- tion efficiency D are known, one can estimate
ing rate limitations. There are finite counting the counting rate that will be recorded from
rate limits for all counting and imaging the source from
instruments used in nuclear medicine, above
which inaccurate results are obtained because
R = Dξ (11-3)
of data losses and other data distortions. Non-
penetrating radiations, such as β particles,
have special detection and measurement In general, it is desirable to have as large
problems. In this chapter, we discuss some of a detection efficiency as possible, so that a
these general considerations in nuclear medi- maximum counting rate can be obtained from
cine instrumentation. a minimum amount of activity. Detection
155
156 Physics in Nuclear Medicine

efficiency is affected by several factors, includ-


ing the following: 2.  Geometric Efficiency
1. The geometric efficiency, which is the Radiation from a radioactive source is emitted 
efficiency with which the detector inter- isotropically, that is, with equal intensity in
cepts radiation emitted from the source. all directions. At a distance r from a point
This is determined mostly by detector source of γ-ray-emitting radioactivity, the
size and the distance from the source to emitted radiation passes through the surface
the detector. of an imaginary sphere having a surface area
2. The intrinsic efficiency of the detector, 4πâ•›r 2. Thus the flux I of radiation passing
which refers to the efficiency with which through the sphere per unit of surface area,
the detector absorbs incident radiation in units of γ rays/sec/cm2, is
events and converts them into poten-
tially usable detector output signals. I = ξ /4 π r 2 (11-5)
This is primarily a function of detector
thickness and composition and of the where ξ is the emission rate of the source and
type and energy of the radiation to be r is given in centimeters. As distance r
detected. increases, the flux of radiation decreases as
3. The fraction of output signals produced 1/r 2 (Fig. 11-1). This behavior is known as the
by the detector that are recorded by the inverse-square law. It has important implica-
counting system. This is an important tions for detection efficiency as well as for
factor in energy-selective counting, in radiation safety considerations (see Chapter
which a pulse-height analyzer is used to 23). The inverse-square law applies to all
select for counting only those detector types of radio�active emissions.
output signals within a desired ampli- The inverse-square law can be used to obtain
tude (energy) range. a first approximation for the geometric effi-
4. Absorption and scatter of radiation ciency of a detector. As illustrated in Figure
within the source itself, or by material 11-1, a detector with surface area A placed at
between the source and the radiation a distance r from a point source of radiation
detector. This is especially important for and facing toward the source will intercept a
in vivo studies, in which the source fraction A/4πâ•›r2 of the emitted radiation. Thus
activity generally is at some depth its geometric efficiency gp is
within the patient.
gp ≈ A/ 4 π r 2 (11-6)
In theory, one therefore can describe detec-
tion efficiency D as a product of individual where the subscript p denotes a point source.
factors, The approximation sign indicates that the
equation is valid only when the distance from
D= g×ε× f ×F (11-4) the point source to the detector is large in
comparison with detector size, as discussed in
where g is the geometric efficiency of the the following paragraphs.
detector, ε is its intrinsic efficiency, f is the
EXAMPLE 11-1
fraction of output signals from the detector
that falls within the pulse-height analyzer Calculate the geometric efficiency for a detec-
window, and F is a factor for absorption and tor of diameter d = 7.5╯cm at a distance r =
scatter occurring within the source or between 20╯cm from a point source.
the source and detector. Each of these factors
are considered in greater detail in this section. Answer
Most of the discussion is related to the detec- The area, A, of the detector is
tion of γ rays with NaI(Tl) detector systems.
A = π d2 / 4 = π[(7.5)2 / 4] cm 2
Basic equations are presented for somewhat
idealized conditions. Complications that arise Therefore, from Equation 11-6,
when the idealized conditions are not met
also are discussed. An additional factor appli- gp ≈ A/ 4 π r 2
cable for radionuclide imaging instruments 
is the collimator efficiency, that is, the effi- ≈ π (7.5)2 / [4 × 4 π (20)2 ]
ciency with which the collimator transmits ≈ (7.5)2 / [16 × (20)2 ]
radiation to the detector. This is discussed in ≈ 0.0088
Chapter 13.
11  •  Problems in Radiation Detection and Measurement 157

r2
A2

A1
r1

Radiation
source

FIGURE 11-1  Illustration of the inverse-square law. As the distance from the radiation source increases from r1 to r2,
the radiations passing through A1 are spread out over a larger area A2. Because A α r 2, the intensity of radiation per
unit area decreases as 1/r 2.

Thus the detector described in Example


11-1 intercepts less than 1% of the emitted
radiation and has a rather small geometric  Point
efficiency, in spite of its relatively large  source
diameter. At twice the distance (40╯cm), the Detector
geometric efficiency is smaller by another
factor of 4.
Equation 11-6 becomes inaccurate when FIGURE 11-2  Point-source geometric efficiency for a cir-
cular large-area detector placed relatively close to the
the source is “close” to the detector. For source depends on the angle subtended, θ (Equation
example, for a source at r = 0, it predicts 11-7).
gp = ∞. An equation that is more accurate at
close distances for point sources located on
the central axis of a circular detector is Geometric efficiency can be increased by
making θ even larger. For example, at the
gp ≈ (1/ 2)(1 − cos θ) (11-7) bottom of the well in a standard well counter
(Chapter 12, Section A.2) the source is par-
where θ is the angle subtended between tially surrounded by the detector (Fig. 11-3B)
the center and edge of the detector from the so that θ ≈ 150 degrees and gp ≈ 0.93. In a
source (Fig. 11-2). For example, when the liquid scintillation counter (see Chapter 12,
radiation source is in contact with the surface Section C), the source is immersed in the
of a circular detector, θ = 90 degrees and gp = detector material (scintillator fluid), so that θ
1/2 (Fig. 11-3A). = 180 degrees and gp = 1 (Fig. 11-3C).
158 Physics in Nuclear Medicine

gp  1/2 (1-cos )




External Well Internal


detector counter detector
gp  0.50 gp  0.93 gp  1.0
A   90° B   150° C   180°

FIGURE 11-3  Examples of point-source geometric efficiencies computed from Equation 11-7 for different source-
detector geometries.

Equation 11-7 avoids the obvious inaccura- The mass attenuation coefficient µm versus
cies of Equation 11-6 for sources placed close E for NaI(Tl) is shown in Figure 6-17. Numer-
to the detector; however, even Equation 11-7 ical values are tabulated in Appendix D.
has limitations when the attenuation by the Values of µl for Equation 11-9 may be obtained
detector is significantly less than 100%. This by multiplication of µm by 3.67╯g/cm3, the
problem is discussed further in Section A.5. density of NaI(Tl). Figure 11-4 shows intrin-
The approximations given by Equations sic efficiency versus γ-ray energy for NaI(Tl)
11-6 and 11-7 apply to point sources of radia- detectors of different thicknesses. For ener-
tion located on the central axis of the detector. gies below approximately 100╯keV, intrinsic
They also are valid for distributed sources efficiency is near unity for NaI(Tl) thicknesses
having dimensions that are small in com� greater than approximately 0.5╯cm. For
parison to the source-to-detector distance; greater energies, crystal thickness effects
however, for larger sources (e.g., source diam- become significant, but a 5-cm-thick crystal
eter  0.3r) more complex forms are required.1 provides ε > 0.8 over most of the energy range
of interest in nuclear medicine.
The intrinsic efficiency of semiconductor
3.  Intrinsic Efficiency detectors also is energy dependent. Because
The fraction of radiation striking the detector of its low atomic number, silicon (Si, Z=14) is
that interacts with it is called the intrinsic used primarily for low-energy γ rays and x
efficiency ε of the detector: rays (100╯keV), whereas germanium (Ge,
Z=32) is preferred for higher energies. The
no. of radiations interacting with detector effective atomic number of NaI(Tl) is approxi-
ε= mately 50 (Table 7-2), which is greater than
no. of radiations striking detector
(11-8) either Ge or Si; however, comparison with Ge
is complicated by the fact that Ge has a
Intrinsic efficiency ranges between 0 and 1 greater density than NaI(Tl) (ρ = 5.68╯g/cm3
and depends on the type and energy of the vs. 3.67╯g/cm3). The linear attenuation coeffi-
radiation and on the attenuation coefficient cient of NaI(Tl) is greater than that of Ge for
and thickness of the detector. For a point E  250╯keV, but at greater energies the
source located on the central axis of a γ-ray opposite is true; however, differences in cost
detector, it is given by and available physical sizes favor NaI(Tl)
over Ge or Si detectors for most applications.
ε = 1 − e− µl ( E ) x (11-9) The effective atomic numbers of cadmium tel-
luride (CdTe) and cadmium zinc telluride
where µlâ•›(E) is the linear attenuation coeffi- (CZT) detectors are similar to that of NaI(Tl)
cient of the detector at the γ-ray energy of (see Tables 7-1 and 7-2). They also have higher
interest, E, and x is the detector thickness. In densities (ρ ≈ 6╯g/cm3). Thus for detectors of
Equation 11-9 it is assumed that any interac- similar thickness, these detectors have some-
tion of the γ ray in the detector produces a what greater intrinsic detection efficiencies
potentially useful signal from the detector, than Na(Tl).
although not necessarily all are recorded if Gas-filled detectors generally have reason-
energy-selective counting is used, as described ably good intrinsic efficiencies (ε ≈ 1) for par-
in Section A.4. ticle radiations (β or α) but not for γ and x
11  •  Problems in Radiation Detection and Measurement 159

1.0
NaI(Tl)
Thickness (cm)
Intrinsic efficiency, ε 0.8 5

0.6

2.5

0.4

1.3

0.2 0.64

0.31
0.0
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
-ray energy (MeV)
FIGURE 11-4  Intrinsic efficiency versus γ -ray energy for NaI(Tl) detectors of different thicknesses.

rays. Linear attenuation coefficients for most is used for energy-selective counting. For
gases are quite small because of their low example, if counting is restricted to the photo�
densities (e.g., ρ ≈ 0.0013╯g/cm3 for air). In peak, most of the γ rays interacting with the
fact, most gas-filled detectors detect γ rays detector by Compton scattering are not
primarily by the electrons they knock loose counted.
from the walls of the detector into the gas The fraction of detected γ rays that produce
volume rather than by direct interÂ�action of γ output signals within the pulse-height ana-
and x rays with the gas. Intrinsic efficiencies lyzer window is denoted by f. The fraction
for Geiger-Müller (GM) tubes, proportional within the photopeak is called the photofrac-
counters, and ionization chambers for γ rays tion fp. The photofraction depends on the
are typically 0.01 (1%) or less over most of the detector material and on the γ-ray energy,
nuclear medicine energy range. Some special both of which affect the probability of photo-
types of proportional counters, employing electric absorption by the detector. It depends
xenon gas at high pressures or lead or leaded also on crystal size (see Fig. 10-8) because
glass γ-ray converters,* achieve greater effi- with a larger-volume detector there is a
ciencies, but they still are generally most greater probability of a second interaction 
useful for γ- and x-ray energies below approxi- to absorb the scattered γ ray following a
mately 100╯keV. Compton-scattering interaction in the detec-
tor (or of annihilation photons following pair
4.  Energy-Selective Counting production). Figure 11-5 shows the photofrac-
The intrinsic efficiency computed from Equa- tion versus energy for NaI(Tl) detectors of
tion 11-9 for a γ-ray detector assumes that all different sizes.
γ rays that interact with the detector produce If energy-selective counting is not used,
an output signal; however, not all output then f ≈ 1 is obtained. (Generally, some energy
signals are counted if a pulse-height analyzer discrimination is used to reject very small
amplitude noise pulses.) Full-spectrum count-
ing provides the maximum possible counting
*A converter is a thin layer of material with relatively rate and is used to advantage when a single
good γ-ray stopping power that is placed in front of or radionuclide is counted, with little or no inter-
around the sensitive volume of a gas-filled detector.
Recoil electrons ejected from γ-ray interactions in the
ference from scattered radiation. This applies,
converter are detected within the sensitive volume of the for example, to many in vitro measurements
detector. (see Chapter 12).
160 Physics in Nuclear Medicine

1.0

0.8
Photofraction, fp

NaI(Tl) Crystal
0.6 Diam. Thick.
(cm) (cm)
20 10
0.4
10 10

0.2
5 5

0.0
0.1 0.2 0.4 1 2 4 10
-ray energy (MeV)
FIGURE 11-5  Photofraction versus γâ•›-â•›ray energy for cylindrical NaI(Tl) detectors of different sizes.

5.  Some Complicating Factors Source

a.  Nonuniform Detection Efficiency


Equations 11-6, 11-7, and 11-9 are somewhat
idealized in that they assume that radiation
is detected with uniform efficiency across the
entire surface of the detector. In some cases, Detector
this assumption may be invalid. Figure 11-6
shows some examples for different trajecto-
ries from a point source of radiation. For tra-
jectory A, the thickness of detector encountered
by the radiation and employed for the calcula- C A B
tion of intrinsic efficiency in Equation 11-9 FIGURE 11-6  Three possible trajectories for radiations
conforms to what normally would be defined striking a detector from a point source, each having a
as the “detector thickness” in that equation. different intrinsic detection efficiency.
However, for trajectory B, a greater thickness
is encountered and the intrinsic efficiency is
larger. On the other hand, for trajectory C,
near the edge of the detector, a smaller thick- rather than with the simplified equations
ness of detector material is encountered and described thus far. The calculations are
the intrinsic efficiency is smaller. Partial pen- complex and a complete analysis is beyond
etration of the beam for trajectory C some- the scope of this text, but they have been
times is called an edge effect. analyzed in other books.2 A few practical
Thus, unless the attenuation by the detec- implications derived from more advanced cal-
tor is “very high” (essentially 100% within a culations are presented here.
thin layer near the surface), the intrinsic effi- The nonuniform attenuation illustrated in
ciency will vary across the surface of the Figure 11-6 affects both geometric efficiency
detector. As well, the detector diameter (or (edge effects) and intrinsic efficiency. The
area) used for the calculation of geometric parameter that accounts for both of these
efficiency in Equation 11-6 or 11-7 becomes quantities is the total detection efficiency, εt.
ill-defined when edge effects are significant. When idealized conditions apply, this can be
When the complications illustrated in Figure obtained simply by multiplying the result of
11-6 are significant, detection efficiency must Equation 11-6 or 11-7 by the result from
be calculated by methods of integral calculus, Equation 11-9
11  •  Problems in Radiation Detection and Measurement 161

ε t = gp × ε (11-10) rule of thumb for when it is necessary to use


the more advanced equations instead of the
It is reasonable to use Equation 11-10 to simplified equations presented earlier. All of
compute total detection efficiency if the result- these parameters must be considered for
ing discrepancy from a more exact calculation making this determination.
is “small,” for example, less than 10%. If the Figure 11-8 presents a graph that can be
discrepancy is larger, then one must consider helpful for this purpose. It applies to
using the more complex methods of integral 1-cm-thick γ-ray detectors for two photon
calculus. energies (140╯keV and 511╯keV) and two
Figure 11-7 shows three detector profiles detector materials [NaI(Tl) and bismuth ger-
with different levels of effect for the trajecto- manate (BGO)] that are used in nuclear medi-
ries shown in Figure 11-6. As compared with cine. In this graph, a “narrow” detector would
a “box” profile (i.e., one with equal thickness lie toward the left end of the horizontal axis,
and width), a “wide” profile presents a greater and a “wide” one would lie toward the right.
range of potential detector thicknesses (trajec- A “box” detector would have a diameter of
tory B in Fig. 11-6), whereas a “narrow” profile 1╯cm.
has a greater fraction of its area affected by Also indicated on the graph are the intrin-
edge effects (trajectory C in Fig. 11-6). In addi- sic efficiencies, computed from Equation 11-9
tion to the profile of the detector, the extent for the central ray A in Figure 11-6, for differ-
of these effects depends on the attenuation ent com�binations of these photon energies
properties of the detector (material and thick- and detectors. The curves indicate the
ness) and on the source-to-detector distance. minimum source-to-detector distance versus
Thus one cannot provide a “one-size-fits-all” detector diameter at which the total detection

“Narrow” “Box” “Wide”


FIGURE 11-7  Examples of detector profiles with different complications for the computation of total detection
efficiency.

10 511/NaI,   0.3

8
511/BGO,   0.6
Minimum distance (cm)

6 140/NaI,   0.9

140/BGO,   1.0
2

0
0.1 1 5
Detector diameter (cm)
FIGURE 11-8  Minimum distance at which simplified equations for detection efficiency (Equations 11-7, 11-9, and
11-10) can be used with errors of less than 10% for 1-cm–thick detectors of different diameters and different combina-
tions of photon energy-detector material. The graph assumes a point source of radiation is placed on the central axis
of the detector. Photon energies are measured in keV. At closer distances, total detection efficiency must be computed
from more-complicated mathematical models (see reference 2).
162 Physics in Nuclear Medicine

efficiency computed using Equations 11-7 and counting is used, such as with the photopeak
11-9 in Equation 11-10 is accurate to within of one or the other γ ray, the pulse from the
10%. At distances closer than the minimum resulting event could be moved out of the
distance, the simplified calculations are inac- selected analyzer window, thereby decreasing
curate by more than 10%, and the more com- the counting rate for that γ ray (see Fig. 10-7).
plicated methods of integral calculus should Note, however, that simultaneous detection
be used to compute the total detection effi- does not occur when there is a significant
ciency, εt.2 delay before the emission of the second γ ray,
Figure 11-8 shows that for detectors having such as in metastable states (see Chapter 3,
a high value of intrinsic efficiency (e.g., BGO Section E).
detector for 140-keV photons, ε ≈ 1), the sim- A full treatment of the problem of coinci-
plified equations can be used with less than dence detection of cascaded emissions is
10% error at relatively close distances. Even beyond the scope of this text. However, the
for the “narrow” detector profile shown in following discussion provides a first-level
Figure 11-7, they can be used within 2╯cm of analysis and an indication of when it must be
the detector. At the other extreme, for a detec- taken into conÂ�sideration. Suppose that two γ
tor having a low value of intrinsic efficiency rays, which we denote as γ1 and γ2, are emitted
[e.g., NaI(Tl) for 511-keV positron annihila- simultaneously, in cascaded fashion, with
tion photons, ε ≈ 0.3], the simplified equations relative frequencies per disintegration η1 and
fail within approximately 10╯cm from a η2. (Note that it is not necessary that η1 = η2;
“narrow” detector and within about 5╯cm from e.g., η2 could be reduced by alternative decay
a “wide” one. pathways that result in nonÂ�detectable emis-
Figure 11-8 provides general guidance as sions, such as internal conversion.) Suppose
to when the simplified equations can be used further that the total (full-spectrum) detec-
for estimating relative detection efficiencies tion efficiencies for the two γ rays are D1 and
on existing systems in a laboratory or for  D2, respectively. The probability that a single
preliminary design work for a new detector nuclear disintegration will result in the detec-
system. It also can be used for guidance  tion of γ1 is
with other combinations of photon energy 
and detector material having dimensions and p1 = η1 D1 (11-11)
values of ε similar to those indicated on the
graph. For more precise design work, it gener- In the absence of coincidence detection, the
ally is preferable to go directly to the methods counting rate recorded for γ1 would be
of integral calculus. Alternatively, Monte
Carlo techniques, using a computer to simu- R1 = p1 × A (11-12)
late photon trajectories and interactions for a
large number of individual photons originat- where A is the source activity in Bq. Simi-
ing from a radioactive source, can be used to larly, in the absence of coincidence detection,
estimate detection efficiency. the counting rate resulting from detection of
γ2 events would be
b.  Detection of Simultaneously Emitted
Radiations in Coincidence R2 = p2 × A (11-13)
Yet another complicating factor is that some
radionuclides emit multiple γ rays in cascaded Thus, if one did not account for the possibility
fashion from a single nuclear disintegration. of coincidence detection, the predicted full-
In Figure 3-3, for example, β1 may be followed spectrum counting rate for the source would
by the emission of multiple γ rays (e.g., γ5 and be (R1 + R2).
γ2). In this example and in most other cases Taking into account the possibility of coin-
of cascaded γ emissions, the γ rays are emitted cidence detection, the probability that γ1 and
within a few nanoseconds of each other, which γ2 will be detected simultaneously is
is well within the resolving time of most
detectors (see Section C). If the two γ rays are p12 = η1 D1 × η2 D2 (11-14)
detected simultaneously (coincidence detec-
tion), they are recorded as a single event and the counting rate for simultaneously
having an apparent energy equal to the sum detected events is
of the energies deposited in the detector by
the individual γ rays. If energy-selective R12 = p12 × A (11-15)
11  •  Problems in Radiation Detection and Measurement 163

With full-spectrum counting, each coincidence


event removes one event each from R1 and R2, c.  Attenuation and Scatter of
replacing it with an event in R12. Thus the Radiation Outside the Detector
recorded full-spectrum counting rate would A final complication that we consider is the
be (R1 + R2 – R12). possibility of absorption and scatter of radia-
A similar analysis can be performed for tion before it reaches the detector. The analy-
photopeak counting. In this case, the total- sis to this point assumes that radiation passes
spectrum detection efficiency is replaced by unobstructed, without absorption or scatter-
the photopeak detection efficiency for each γ ing, from the source to the detector (e.g., as
ray. The counting rate in each photopeak is in Fig. 11-1). However, when the radiation
reduced by R12; that is, they would be (R1 – source is embedded at depth within an absorb-
R12) and (R2 – R12), and the summation pho- ing and scattering medium, as it is for most
topeak counting rate would be R12. in vivo measurements, the calculation of
In actual practice, calculating the effect of detection efficiency is complicated by attenu-
detecting simultaneously emitted photons on ation and scattering effects.
recorded counting rates is somewhat more Absorption generally causes a decrease in
complicated than indicated by the previous the recorded counting rate, but scattered
equations. For example, for calculating the radiation may lead to a decrease or an
effect on photopeak counting rates, one should increase, depending on whether there is more
take into account the possibility of simultane- scattering away from or toward the detector.
ous detection of events in the Compton portion For example, the counting rate for a source at
of the spectrum, which also could “move” a shallow depth in a scattering medium actu-
events out of the photopeak, or possibly add ally may be greater than for the same source
up to create apparent photopeak events. A in air because the added contribution from
more detailed analysis also would include the backscattering may more than compensate
possibility of angular correlations between for a small reduction in counting rate by
the directions in which the two γ rays are absorption. (See also the discussion of the
emitted. In many cases, this would lead to buildup factor in in Chapter 6, Section D.3).
different values of detection efficiencies for At greater depths absorption effects may
the two γ rays. predominate.
Nevertheless, the first-level analysis pro- Corrections for attenuation and scattering
vided in the preceding discussion can give an for in vivo measurements are complicated
indication of when the effects of coincidence because they depend on several factors, includ-
detection can be significant. For example, ing the γ-ray energy, depth of the source in
from Equations 11-14 and 11-15, it can be the absorbing and scattering medium, use of
seen that the effects depend on the values of energy-selective counting, and so forth. Figure
η1 and η2 and on detection efficiencies D1 and 11-9 shows the general effects versus γ-ray
D2. Thus if the primary emission of interest energy for a point source 7.5-cm deep in tissue-
is γ1, and, η1 >> η2, the effect of γ2 on R1 (or equivalent material and a NaI(Tl) counting
R1 + R2) would be relatively small. As well, the system. The fraction of γ rays emitted from the
effects are most severe in counting systems source that are neither scattered nor absorbed
having high values of detection efficiency. on their way to the detector increases with
An example is the well counter, which gen- γ-ray energy because absorption and scatter-
erally has a high total detection efficiency. ing coefficients decrease with increasing
This is illustrated by Figure 10-7, showing energy. The fraction of γ rays absorbed in the
how the coincidence sum peak for the two γ tissue-equivalent material decreases with
rays of 111In increases dramatically when the energy to a negligible fraction above approxi-
source is moved from a location outside the mately 100╯keV.
well-counter detector where detection effi- Figure 11-9 also shows that the fraction of
ciency is low to a location inside it where it γ rays scattered at first increases with γ-ray
is high. When questions arise, the first-level energy because absorption effects decrease,
analysis presented above can be used to esti- leaving more γ rays to be scattered. This frac-
mate the relative magnitude of the effects  tion reaches a maximum at approximately
of coincidence counting of cascaded γ rays. 100╯keV, after which it also decreases with
Experimental data can further help to resolve increasing energy. If energy-selective count-
the issue, for example, by comparing the ing is used, the fraction of Compton-scattered
spectra with the source at different locations, γ rays recorded in the photopeak decreases
as in Figure 10-7. with increasing γ-ray energy. This reflects the
164 Physics in Nuclear Medicine

Non-absorbed, unscattered  rays


Compton-scattered  rays
100
Absorbed  rays
Compton-scattered  rays in photopeak
80

Fraction of  rays (%)


60

40

20

0
0.02 0.04 0.1 0.2 0.4 1
-ray energy (MeV)
FIGURE 11-9  General effects of γ↜-↜ray energy on the fraction of γ rays scattered or absorbed from a point source 7.5╯cm
deep in tissue and on the fraction of unscattered γ rays and scattered γ rays having sufficient energy to be recorded
with a photopeak window and NaI(Tl) detector. (From Anger HO: Radioisotope cameras. In Hine GJ, editor: Instru-
mentation in Nuclear Medicine, Vol 1. New York, 1967, Academic Press, p 514.)

increasing energy separation between scat- determination usually is made by the com-
tered γ rays and the photopeak (see Fig. mercial supplier of the source.
10-10). With semiconductor detectors (Ge, Si, Detection efficiency can be determined by
CdTe, or CZT), this fraction is much smaller measuring the counting rate recorded from
because of their ability to clearly resolve scat- the calibration source and applying Equation
tered γ rays from the photopeak (see Figs. 11-2. This method generally is satisfactory for
10-14 and 10-15). systems in which a standard measuring con-
Another factor affecting detection efficiency figuration is used and for which the calibra-
is attenuation by the housing material of the tion source accurately simulates the shape
detector. Most γ-ray detectors are fabricated and distribution of the sources usually mea-
with relatively thin entrance windows, such sured with the system. For example, “rod
as thin layers of aluminum, so that their standards” (Fig. 11-10) are used for determin-
attenuation is negligible. Detectors designed ing detection efficiencies of well counters for
for applications involving very-low-energy γ test-tube samples.
rays sometimes are constructed with ultra- Some γ-ray-emitting source materials that
thin (and fragile) entrance windows of alter- are available as calibration standards are
native materials, such as beryllium. However, listed in Table 11-1. Most are quite long-lived.
attenuation can become significant if the Detection efficiencies for short-lived radionu-
detector is used outside the range of its clides can be estimated from measurements
intended applications. Information provided made on a calibration standard having similar
by the manufacturer can be used to estimate emission characteristics. For example, 57Co
this effect in questionable situations. (Eγ = 122╯keV and 136╯keV) frequently is used
Attenuation by the detector housing can be to simulate 99mTc (Eγ = 140╯keV). (Cobalt-57
severe in β-particle counting. This is dis- is sometimes called “mock 99mTc.”) For most
cussed separately in Section B. detection systems, intrinsic efficiencies at
these three energies are virtually identical.
6.  Calibration Sources Therefore the detection efficiency per emitted
Detection efficiencies can be determined γ ray as calculated from Equation 11-2 would
experimentally using calibration sources. A be the same for 99mTc and 57Co (assuming the
calibration source is one for which the activity same energy-selective counting conditions
or emission rate is known accurately. This were used, e.g., photopeak counting for both).
FIGURE 11-10  “Rod standards” containing accu-
rately known quantities of different radionuclides
used for determining the detection efficiencies of well
counters. The sources are meant to simulate radioac-
tivity in test tubes.

TABLE 11-1â•…
PROPERTIES OF SOME γ â•›-↜RAY SOURCES USED AS CALIBRATION STANDARDS

Emission
γ -Ray or x-Ray Energy Frequency
Radionuclide Half-Life (keV)* (γ or x raysâ•›/dis)
22
Na 2.60╯yr 511 1.798
1274 0.999
54
Mn 312 d 834.8 1.000
57
Co 272 d 14.4 0.095
122.1 0.856
136.5 0.105
60
Co 5.27╯yr 1173 0.999
1333 1.000
68
Ge 271 d 511 1.780
85
Sr 64.9 d 514 0.980
109
Cd 463 d 22.0 (Kα x ray) 0.842
24.9 (Kβ x ray) 0.178
88.0 0.037
113
Sn 115 d 24.1 (Kα x ray) 0.794
27.3 (Kβ x ray) 0.172
391.7 0.649
129
I 15.7 × 10 ╯yr
6
29.7 (Kα x ray) 0.571
33.6 (Kβ x ray) 0.132
39.6 0.075
137
Cs 30╯yr 32.0 (Kα x ray) 0.057
36.4 (Kβ x ray) 0.013
661.7 0.851
Data adapted from NCRP Report No. 58: A Handbook of Radioactivity Measurements Procedures, ed 2, Bethesda, MD,
1985, National Council on Radiation protection and Measurements.
*Only predominant photon emissions are listed.
166 Physics in Nuclear Medicine

If the detection efficiency is determined on the problems are especially severe with low-
basis of cps/Bq, one must take into account energy β-particle emitters, such as 3H and 14C.
the differing emission frequencies of the two The preferred method for assay of these radio-
radionuclides. Cobalt-57 emits 0.96 γâ•›/dis (γ nuclides is by liquid scintillation counting
rays per disintegration), whereas 99mTc emits techniques (Chapters 7 and 12); however,
0.89 γâ•›/dis (see Appendix C). Therefore the these techniques are not applicable in all situ-
counting rate per Bq of 99mTc would be a factor ations, such as when surveying a bench top
of 0.89/0.96 = 0.93 smaller than that mea- with a survey meter to detect 14C contamina-
sured per Bq of 57Co. This should be applied tion (Chapter 23). A complete discussion of
as a correction factor to the counting rate per the problems arising in detection and assay
Bq determined for 57Co to obtain the counting of β-particle emitters is beyond the scope of
rate per Bq for 99mTc. this book; however, a few of the practical
Calibration sources also are used in phan- problems are described briefly.
toms simulating the human anatomy for esti- A survey meter can be used to detect
mating the detection efficiency for in vivo surface contamination by β-particle emitters
measurement systems; however, the result is provided it has an entrance window suffi-
only as accurate as the phantom and source ciently thin to permit the β particles to enter
distribution are accurate for simulating the the sensitive volume of the detector. Figure
human subject. For example, a 1-cm discrep- 11-11 shows relative counting rate versus
ancy between source depths in the phantom entrance window thickness for two β-emitting
and in the human subject may result in a 10% radionuclides. Efficient detection of low-
to 20% difference in counting rate (see Chapter energy β emitters requires a very thin
12, Section F.1). entrance window, preferably fabricated from
a low-density material. A typical entrance
window for a survey meter designed for 3H
and 14C detection is 0.03-mm-thick Mylar
B.  PROBLEMS IN THE DETECTION (~1.3╯mg/cm2 thick).* Mica and beryllium also
AND MEASUREMENT OF β PARTICLES
*Thicknesses of detector windows often are specified in
Because of their relatively short ranges in units of mass/area, for example, mg/cm2. To obtain the
solid materials, β particles create special window thickness, divide by the material density using
detection and measurement problems. These the same units (e.g., mg/cm3).

100
32 max
P (E = 1.7 MeV)
80
Relative counting rate

60

40

20 14C max
(E = 0.156 MeV)

0
0 1 2 3 4 5 6 7 8
2
Detector window thickness (mg/cm )
FIGURE 11-11  Relative counting rate versus detector window thickness for some β-emitting radionuclides. (Adapted
from Quimby EH, Feitelberg S, Gross W: Radioactive Nuclides in Medicine and Biology. Philadelphia, 1970, Lea &
Febiger.)
11  •  Problems in Radiation Detection and Measurement 167

are used. Such thin windows are very fragile,


and usually they are protected by an overly-
ing wire screen. Beta particles that are more
energetic (e.g., from 32P) can be detected with Detector
much thicker and more rugged entrance
windows; for example, 0.2-mm-thick alumi-
num (~50╯mg/cm2) provides approximately
50% detection efficiency for 32P.
GM and proportional counters sometimes
are used to assay the activities of β-emitting
radionuclides in small trays (“planchets”) or
similar sample holders. Two serious problems Sample
arising in these measurements are self-
absorption and backscattering, as illustrated
in Figure 11-12. Self-absorption depends on
the sample thickness and the β-particle
energy. Figure 11-13 shows relative counting
rate versus sample thickness for two β emit-
ters. For 14C and similar low-energy β emit-
ters, self-absorption in a sample thickness of
only a few mg/cm2 is sufficient to cause a sig- Sample holder
nificant reduction of counting rate. (Note that FIGURE 11-12  Self-absorption and backscattering in
for water, ρ = 1╯g/cm3; thus 1╯mg/cm2 is 0.001- β-particle counting.
cm thick.) Backscattering of β particles from
the sample and sample holder tends to
increase the sample counting rate and can
amount to 20% to 30% of the total sample
counting rate in some circumstances.
Accurate assay of β-emitting radioactive
samples by external particle-counting tech-
niques requires careful attention to sample
preparation. If only relative counting rates

100

32 max
Relative counting rate (%)

80 P (Eβ = 1.7 MeV)

60

40

20
14C max
(Eβ = 0.156 MeV)

0
1 10 100 1000
Sample thickness (mg/cm2)
FIGURE 11-13  Effect of sample self-absorption on counting rate for two β emitters. (Adapted from Quimby EH,
Feitelberg S, Gross W: Radioactive Nuclides in Medicine and Biology. Philadelphia, 1970, Lea & Febiger.)
168 Physics in Nuclear Medicine

are important, then it is necessary to have liquid scintillation systems have dead times of
sample volumes and sample holders as nearly 0.1–1 µsec.
identical as possible. Other techniques for Dead time losses also occur in pulse-height
dealing with these difficult problems are dis- analyzers, scalers, computer interfaces, and
cussed in reference 3. other components that process pulse signals.
Bremsstrahlung counting can be employed Generally scalers and single-channel analyz-
as an indirect method for detecting β parti- ers have dead times of much less than 1 µsec,
cles using detectors that normally are sensi- whereas multichannel analyzer and computer
tive only to more penetrating radiations such interface dead times are on the order of a few
as x rays and γ rays, for example a NaI(Tl) microseconds. Usually the dead time is given
well counter (Chapter 12). Bremsstrahlung for the counting system as whole; however, if
counting also was employed in some early one of the components has a dead time that
studies using 32P for the detection of brain is long in comparison to the other compo-
tumors and still is used occasionally to map nents, then system dead time is determined
the distribution of 32P-labeled materials by that component.
administered for therapeutic purposes. Brems- 
strahlung counting is effective only for rela- 2.  Mathematical Models
tively energetic β particles (e.g., 32P, Eβmax = Counting systems usually are classified as
1.7 MeV, but not 14C, Eβmax = 0.156╯MeV) and being of the paralyzable or nonparalyzable
requires perhaps 1000 times greater activity type. A nonparalyzable system is one for
than a γ-ray emitter because of the very low which, if an event occurs during the dead time
efficiency of bremsstrahlung production. τ of a preceding event, then the second event
is simply ignored, with no effect on subse-
quently occurring events (Fig. 11-14). Digital
counters, pulse-height analyzers, and com-
C.  DEAD TIME
puter interfaces frequently behave as non-
paralyzable systems. A paralyzable system is
1.  Causes of Dead Time one for which each event introduces a dead
Every radiation counting system exhibits a time τ whether or not that event actually is
characteristic dead time or pulse resolving counted. Thus an event occurring during the
time τ that is related to the time required to dead time of a preceding event would not be
process individual detected events. The pulses counted but still would introduce its own dead
produced by a radiation detector have a finite time during which subsequent events could
time duration, such that if a second pulse not be recorded. A paralyzable system may be
occurs before the first has disappeared, the thought of as one with an “extendable” dead
two pulses will overlap to form a single dis- time. Most radiation detectors behave as par-
torted pulse. With GM detectors, the overlap alyzable systems.
may occur in the detector itself, during the Because of dead time losses, the observed
time that the “avalanche charge” is being col- counting rate Ro (cps) is less than the true
lected from a previous pulse, so that the
second pulse does not produce a detectable
output signal and is lost (see Chapter 7, Dead time 

Section A.4). Input


events
With energy-sensitive detectors (scintilla-
tion, semiconductor, proportional counter), Output:
nonparalyzable
the overlap usually occurs in the pulse ampli- system
fier, causing baseline shift and pulse pile-up
Output:
(see Chapter 8, Section B.3). Shifted or over- paralyzable
lapped pulse amplitudes may fall outside the system Time
selected analyzer window, again resulting in
FIGURE 11-14  Difference in output signals between
a loss of valid events. Such losses are called nonparalyzable and paralyzable systems. Both have dead
dead time losses. The shorter the dead time, time τ indicated in top line. Second line illustrates ran-
the smaller the dead time losses. The dead domly occurring input events. With a nonparalyzable
time for a GM tube is typically 50–200 µsec. system (third line), events are lost if they occur within a
time τ of a preceding recorded event, whereas with a
Sodium iodide and semiconductor detector paralyzable system (↜fourth line) events are lost if they
systems typically have dead times in the range occur within a time τ of any preceding event, regardless
of 0.5–5 µsec. Gas proportional counters and of whether that event has been recorded.
11  •  Problems in Radiation Detection and Measurement 169

counting rate Rt (cps), where the latter is the For a paralyzable system, the observed
counting rate that would be recorded if τ = 0. counting rate rises to a maximum value given
The relationship among Ro, Rt, and τ depends by
on the type of dead time. For nonparalyzable
Romax = 1 / eτ (11-20)
systems,
where e (= 2.718 …) is the base of natural
Ro = Rt /(1 + Rt τ) (11-16) logarithms. Then the observed counting rate
actually decreases with a further increase in
Rt = Ro /(1 − Ro τ) (11-17) true counting rate. This is because additional
events serve only to extend the already long
where τ is given in seconds. If the system has dead time intervals without contributing to
a paralyzable dead time, then additional events in the observed counting
rate. At very high true counting rates, the
Ro = Rt e− Rt τ (11-18) observed counting rate actually approaches
zero. This is called counter paralysis.
There is no analytic equation for Rt as a func- Dead time losses are given by the differ-
tion of Ro for the paralyzable case. ence between observed and true counting
Figure 11-15 shows Ro versus Rt for the rates, Rt – Ro, and percentage losses are given
two types of systems. For a nonparalyzable by
system, the observed counting rate increases
asymptotically toward a maximum value percentage losses = [( Rt − Ro ) / Rt ] × 100%
(11-21)
Romax = 1/τ (11-19)
When the product Rtτ is “small” (0.1), the
At very high true counting rates, greater than percentage losses are “small” (i.e., 10%),
one count per dead time interval, the system and they can be described by the same equa-
simply records one event per dead time inter- tion for both paralyzable and nonparalyzable
val, ignoring all the others that occur during systems
the dead time interval between counted
events. percentage losses ≈ ( Rt τ) × 100%   (11-22)
es
ss
lo
Observed counting rate, Ro

No

R omax  1/τ

Nonparalyzable

R omax  1/eτ

Paralyzable

True counting rate, Rt

FIGURE 11-15  Observed (Ro) versus true (Rt ) counting rate curves for paralyzable and nonparalyzable systems having
the same dead time value, τ.
170 Physics in Nuclear Medicine

EXAMPLE 11-2 3.  Window Fraction Effects


Calculate the percentage losses for a counting With NaI(Tl) and other detectors used for
system having a dead time of 10 µsec at true energy-selective counting, any detected event
counting rates of 10,000 and 100,000╯cps. can cause pile-up with any other event in the
pulse-height spectrum. Thus if a pulse-height
Answer analyzer is used, the number of events lost
At 10,000╯cps, Rtτ = 104╯cps × 10–5╯sec = 0.1. depends on the total-spectrum counting rate,
Because the losses are “small,” Equation not just on the counting rate within the
11-22 can be used: selected analyzer window. With such systems,
the apparent dead time may appear to change
percentage losses ≈ (0.1) × 100% with pulse-height analyzer window setting.
For example, if a certain fraction of detected
≈ 10% events are lost with a given window setting,
the same fraction will be lost when the ana-
The observed counting rate would therefore lyzer window is narrowed, making it appear
be approximately 9000╯cps, that is, 10% less that the dead time per event in the analyzer
than the true counting rate of 10,000╯cps. At window is longer when the narrower window
100,000╯cps, Rtτ = 105╯cps × 10–5╯sec = 1.0; is used.
thus the losses are not “small.” For a non- An approximate equation for apparent
paralyzable system, the observed counting dead time is6
rate would be (Equation 11-16)
τ a = τ /wf (11-23)
Ro = 100, 000 / (1 + 1.0) cps

= 50, 000 cps where τ is the actual dead time per detected
event and wf is the window fraction, that is,
that is, the losses would be 50%. For a para- the fraction of detected events occurring
lyzable system (Equation 11-18) within the selected analyzer window. For
example, if a NaI(Tl) detector system has a
Ro = 105 × e−1.0 cps dead time of 1 µsec (amplifier pulse duration)
but a narrow window is used so that only
= 100, 000 × 0.368 cps
25% of detected events are within the window
= 36, 800 cps (wf = 0.25), the apparent dead time will be
(1/0.25) = 4 µsec. Window fractions also
The losses are therefore 100,000 – 36,800╯cps change with the amount of scattered radia-
= 63,200╯cps, or 63.2% (of 100,000╯cps). tion recorded by the detector because this
also changes the energy spectrum of events
Example 11-2 illustrates that for a given recorded by the detector. In general, increased
dead time and true counting rate, the dead amounts of scattered radiation decrease the
time losses for a paralyzable system are window fraction recorded with a photopeak
greater than those of a nonparalyzable system. window (see Fig. 10-6). The window fraction
This is shown also by Figure 11-15. effect must be considered in specifying 
Many nuclear medicine systems have mul- and comparing dead time values for systems
tiple components in cascade, each with its using pulse-height analysis for energy-
own individual dead time. In some cases, one selective counting.
component of a cascaded system may be 
paralyzable (e.g., the scintillation detector) 4.  Dead Time Correction Methods
whereas the other may be nonparalyzable Measurements made on systems with a stan-
(e.g., a multichannel analyzer interface). In dardized measuring configuration, with little
most cases, one component dominates the or no variation in window fraction from one
system and its behavior adequately describes measurement to the next, can be corrected for
the system behavior. However, if cascaded dead time losses using the mathematical
paralyzable and nonparalyzable components models described in Section C.2. Some in vitro
have similar dead times, both components counting systems are in this category. Given
contribute to dead time losses and the behav- an observed counting rate Ro and a dead time
ior is a hybrid of the two. The analysis of such τ, the true counting rate can be determined
systems is beyond the scope of this text; see from Equation 11-17 if the system is nonpara-
references 4 and 5 for further details. lyzable or by graphical or approximation
11  •  Problems in Radiation Detection and Measurement 171

methods (Equation 11-18 and Fig. 11-15) if it fixed-rate pulser connected to the preampli-
is paralyzable. fier of the radiation detector. The pulser
Dead time τ can be determined using the injects pulses of fixed amplitude (usually
two-source method. Two radioactive sources of larger than the photopeak pulses of interest)
similar activities, for which the dead time into the circuitry, and the counting rate for
losses are expected to be 10% to 20%, are these events is monitored using a separate
needed (Fig. 11-16). The counting rate for single-channel analyzer window (Fig. 11-17).
source 1 is determined, R1 (cps). Without dis- The fractional loss of pulser events is equal to
turbing the position of source 1 (so as not to the fractional loss of radiation events because
change the detection efficiency for source 1), both are subject to the same loss mechanisms.
source 2 is placed in position for counting and The observed counting rate Ro from the γ-ray
the counting rate for the two sources together source is corrected by the ratio of true-to-
is determined, R12 (cps). Then source 1 is observed pulser counting rates, Pt╛/↜Po, to
removed (again, without disturbing source 2), obtain the true γ-ray counting rate,
and the counting rate for source 2 alone is
Rt = Ro ( Pt /Po ) (11-26)
determined, R2 (cps). If the system is non-
paralyzable, the dead time τn in seconds is Dead time losses also affect counting sta-
given by tistics. For example, the standard deviation
in observed counts, No, is not given by No if
τ n ≈ ( R1 + R2 − R12 ) /( R12
2
− R12 − R22 ) (11-24)
there are substantial dead time losses.
If the system is paralyzable, then Detailed discussions of counting statistics
with dead time losses are presented in refer-
τ p ≈ [2 R12 /( R1 + R2 )2 ] ln[( R1 + R2 ) / R12 ] ence 7.
(11-25)

If a short-lived radionuclide is used, decay D.  QUALITY ASSURANCE FOR


corrections can be avoided by making the RADIATION MEASUREMENT SYSTEMS
three measurements R1, R12, and R2, sepa-
rated by equal time intervals.* Radiation measurement systems are subject
Additional measurements are required to to various types of malfunctions that can 
determine whether Equation 11-24 or 11-25 is lead to sudden or gradual changes in their
to be used. For example, a graph of observed
counting rate versus activity might be con-
structed to determine which of the two curves No dead time losses
in Figure 11-15 describes the system.
With dead time losses
For measurements in which the window
fraction is variable (e.g., most in vivo mea- -ray Pulse
surements), the equations given in Section photopeak peak
C.2 can be used only if the window fraction
is known. Another approach is to use a 
Relative number of counts

*Some texts recommend also that a background mea- SCA


surement be made; however, background counting rates windows
generally are negligibly small in comparison to the count-
ing rates used in these tests.

R1 R 12 R2

Source

Source
holder Energy or pulse amplitude
FIGURE 11-17  Principles of dead time correction using
Steps 1 2 3 the fixed-rate pulser method. The fractional loss of events
in the pulse peak (from the fixed-rate pulser) is assumed
FIGURE 11-16  Illustration of the steps followed in to equal the fractional losses of radiation events in the
determining dead time by the two-source method. γ -ray photopeak window. SCA, Single-channel analyzer.
172 Physics in Nuclear Medicine

performance characteristics. For example, counting errors or other instabilities in system


electronic components and detectors can fail performance. Typically, a series of approxi-
or experience a progressive deterioration of mately 20 measurements are made and the χ2
function, leading to changes in detection effi- statistic is calculated. A result with P < 0.01
ciency, increased background, and so forth. or P > 0.99 is taken as evidence of a system
To ensure consistently accurate results, problem. A result with 0.05 < P < 0.95 is con-
quality assurance procedures should be sidered acceptable. A result with a P value in
employed on a regular basis for all radiation the gaps between these ranges is considered
measurement systems. These would include equivocal, and the test should be repeated.
(1) daily measurement of the system’s Quality assurance procedures also are used
response to a standard radiation source (e.g., for imaging systems as described in Chapter
a calibration “rod standard” for a well counter 14, Section E, Chapter 17, Section C.4, and
or a “check source” for a survey meter); (2) Chapter 18, Section E.
daily measurement of background levels; and
(3) for systems with pulse-height analysis REFERENCES
capabilities, a periodic (e.g., monthly) mea- 1. Jaffey AH: Solid angle subtended by a circular aper-
surement of system energy resolution. ture at point and spread sources: Formulas and some
Additional tests may be devised to evaluate tables. Rev Sci Instrum 25:349-354, 1954.
other important characteristics on specific 2. NCRP Report No. 58: A Handbook of Radioactivity
Measurements Procedures, ed 2. Bethesda, MD, 1985,
measuring systems. The results should be National Council on Radiation Protection and Mea-
recorded in a log book for analysis when prob- surements, p 168.
lems are suspected. In some cases, it is helpful 3. Quimby EH, Feitelberg S, Gross W: Radioactive
to make a graph of the results (e.g., counting Nuclides in Medicine and Biology, Philadelphia, 1970,
Lea & Febiger, Chapter 16.
rate for a standard source or for background), 4. Sorenson JA: Deadtime characteristics of Anger
with tolerance limits (e.g., ±â•›2 standard devia- cameras. J Nucl Med 16:284-288, 1975.
tions) to detect subtle, progressive changes in 5. Woldeselassie T: Modeling of scintillation camera
performance. systems. Med Phys 26:1375-1381, 1999.
The statistical tests described in Chapter 9 6. Wicks R, Blau M: The effects of window fraction on the
deadtime of Anger cameras. J Nucl Med 18:732-735,
can be used to assist in this analysis. For 1977.
example, the χ2 test, described in Chapter 9, 7. Evans RD: The Atomic Nucleus, New York, 1955,
Section E.1, is useful for detecting sporadic McGraw-Hill, pp 785-793.
chapter
12 
Counting Systems

Radiation counting systems are used for a for β particles and low-energy x rays or γ
variety of purposes in nuclear medicine. In rays are presented in Section C later in this
vitro (from Latin, meaning “in glass”) counting chapter. Counting systems based on gas
systems are employed to measure radioactivity detectors and semiconductor detectors are
in tissue, blood, and urine samples; for radio- discussed in Sections D and E, respectively.
immunoassay and competitive protein binding Section F deals with counting systems for in
assay of drugs, hormones, and other biologi- vivo applications, including thyroid uptake,
cally active compounds; and for radionuclide sentinel node detection, and intraoperative
identification, quality control, and radioactiv- probes.
ity assays in radiopharmacy and radiochem-
istry. In vitro counting systems range from
relatively simple, manually operated, single- A.  NaI(Tl) WELL COUNTER
sample, single-detector instruments to auto-
mated systems capable of processing hundreds
of samples in a batch with computer process- 1.  Detector Characteristics
ing of the resulting data. The detector for a NaI(Tl) well counter is a
In vivo (from Latin, meaning “in the living single crystal of NaI(Tl) with a hole in one
subject”) counting systems are employed for end of the crystal for the insertion of the
measuring radioactivity in human subjects or sample (Fig. 12-1A). Dimensions of some
experimentally in animals. Different in vivo commonly used well detectors are given in
systems are designed for measuring localized Table 12-1. The 4.5-cm diameter × 5-cm long
concenÂ�trations in single organs (e.g., thyroid, crystal with 1.6-cm diameter × 3.8-cm deep
kidney) and for measurements of whole-body well, the standard well-counter detector, is
content of radioactivity. the most frequently used in nuclear medi-
Most nuclear medicine counting systems cine. It is designed for counting of samples in
consist of the following basic components: a standard-size test tubes. Very large well-
detector and high voltage supply, preampli- counter detectors, up to 13-cm diameter ×
fier, amplifier, one or more single-channel 25-cm length, have been employed for count-
analyzers (SCAs) or a multichannel analyzer ing very small quantities of high-energy γ-ray
(MCA) (“data analysis”), and a digital or emitters (e.g., 40K and 137Cs). Most well-
analog scaler-timer, rate meter, or other data counter systems employ 5╯cm or greater
readout device. The majority of systems thickness of lead around the detector to
employ a computer or microprocessor for data reduce background counting levels. A typical
analysis and readout. manually loaded well-counter system is
At present, the most efficient and econom- shown in Figure 12-1B.
ical detector for counting γ-ray emissions* is Light transfer between the NaI(Tl) crystal
a sodium iodide [NaI(Tl)] scintillation detec- and the photomultiplier (PM) tube is less
tor. The characteristics of various NaI(Tl) than optimal with well-type detectors because
counting systems are discussed in Sections A of reflection and scattering of light by the well
and B in this chapter. Scintillation counters surface inside the detector crystal. Energy
resolution is therefore poorer [10% to 15% full
width at half maximum (FWHM) for 137Cs]
*In this chapter the term γâ•›-ray emission also includes
than obtained with optimized NaI(Tl) detec-
other forms of ionizing electromagnetic radiation (e.g., x tor designs (approximately 6% FWHM) (see
rays, bremsstrahlung, and annihilation radiation). Chapter 10, Section B.7).
173
174 Physics in Nuclear Medicine

TABLE 12-1â•…
DIMENSIONS OF TYPICAL NaI(Tl)
WELL-COUNTER DETECTORS
Test tube Crystal Dimensions Well Dimensions
containing (cm) (cm)
sample
Diameter Length Diameter Depth
4.5* 5.0* 1.6* 3.8*
NaI(Tl)
crystal 5.0 5.0 1.6 3.8
7.6 7.6 1.7 5.2
10.0 10.0 3.8 7.0
12.7 12.7 3.8 7.0
*“Standard” well-counter detector.
Lead
shielding

The intrinsic efficiency ε (Equation 11-8) of


well-counter detectors depends on the γ-ray
energy and on the thickness of NaI(Tl) sur-
PM tube
rounding the sample; however, the calcula-
A tion of intrinsic efficiency is complicated
because different thicknesses of detector are
traversed by γ rays at different angles around
the source. Calculated intrinsic efficiencies
(i.e., all pulses counted) versus γ-ray energy
for 1-mL sample volumes and for different
NaI(Tl) well-counter detectors are shown in
Figure 12-2. Intrinsic efficiency is close to
100% for 1.3- to 4.5-cm wall thickness and E γ
 150╯keV, but at 500╯keV the intrinsic effi-
ciencies range from 39% to 82%.
Intrinsic efficiency can be used to calculate
the counting rate per kBq for a radionuclide
if all pulses from the detector are counted;
however, if only photopeak events are
recorded, then the photofraction fp also must
B be considered (see Chapter 11, Section A.4).
FIGURE 12-1  A, Cross-sectional view of a well-counter The photofraction decreases with increasing
detector containing a radioactive sample. B, Photograph γ-ray energy and increases with increasing
of a manually loaded well counter with a digital readout well-detector size (Fig. 12-3). At 100╯keV, fp ≈
and printer output. (Courtesy Capintec, Inc., Ramsey, NJ.) 100% for all detector sizes. At 500╯keV, fp
ranges from 48% to 83% from the smallest to
the largest common detector sizes (Table
2.  Detection Efficiency 12-1).
The detection efficiency D (see Chapter 11, The intrinsic photopeak efficiency εp is the
Section A) of the NaI(Tl) well counter for most product of the intrinsic efficiency and
γ-ray emitters is quite high, primarily because photofraction
of their near 100% geometric efficiency g. The
combination of high detection efficiency and ε p = ε × fp (12-1)
low background counting levels makes the
well counter highly suitable for counting This may be used to estimate photopeak
samples containing very small quantities counting rates. Figure 12-4 shows εp versus
(Bq–kBq) of γ-ray-emitting activity. The geo- γ-ray energy.
metric efficiency for small (1-mL) samples Table 12-2 lists some detection efficiencies,
in the standard well counter is approximately expressed as counts per minute (cpm) per bec-
93% (see Fig. 11-3). querel, for full-spectrum counting of different
12  •  Counting Systems 175

100

Intrinsic efficiency, ε (%) 80


Wall
thickness
(cm)
Crystal size
4.5
60 Diam. Length
(cm) (cm)
2.6 12.7 12.7
40
7.6 7.6
1.3
20 4.5 5.0

0
0.1 1 10
-ray energy (MeV)
FIGURE 12-2  Intrinsic efficiency (γ -ray absorption efficiency, Equation 11-9) vs. γ -ray energy for different NaI(Tl)
well-counter detectors.

100

Wall
thickness
80
Photofraction, fp (%)

(cm)
4.5
60 Crystal size
Diam. Length
2.6 (cm) (cm)
40
12.7 12.7

7.6 7.6
20
1.3 4.5 5.0

0
0.1 1 10
-ray energy (MeV)
FIGURE 12-3  Photofraction versus γ -ray energy for different NaI(Tl) well-counter detectors.

radionuclides in the standard well counter. geometric efficiency of a well counter depends
These values apply to 1-mL samples in stan- on sample positioning. If a small volume of
dard test tubes. radioactive solution of constant activity in a
test tube is diluted progressively by adding
3.  Sample Volume Effects water to it, the counting rate recorded from
The fraction of γ rays escaping through the the sample in a standard well detector pro-
hole at the end of the well depends on the gressively decreases, even though total activ-
position of the source in the well. The fraction ity in the sample remains constant (Fig. 12-5).
is only about 7% near the bottom of the well In essence, the geometric efficiency for the
but increases to 50% near the top and is even sample decreases as portions of the activity
larger for sources outside the well. Thus the are displaced to the top of the well.
176 Physics in Nuclear Medicine

100

Intrinsic photopeak efficiency, εp (%)


80
Wall
thickness
(cm)
60
4.5

40 Crystal size
Diam. Length
2.6
(cm) (cm)
20 12.7 12.7
1.3
7.6 7.6
4.5 5.0
0
0.1 1 10
-ray energy (MeV)
FIGURE 12-4  Intrinsic photopeak efficiency vs. γ -ray energy for different NaI(Tl) well-counter detectors.

TABLE 12-2â•…
COUNTING EFFICIENCY FOR 1-mL SAMPLES IN A STANDARD SODIUM IODIDE WELL COUNTER
(ASSUMING ALL PULSES COUNTED)

Counting Counts per


γ -ray Energies (MeV) Efficiency per Minute per
Radionuclide (% per Disintegration) Disintegration (%) Becquerel
51
Cr 0.320 (8%) 4.3 2.6
60
Co 1.17 (100%) 1.33 (100%) 43 25.8
198
Au 0.411 (96.1%), 0.68 (1.1%), 1.09 (0.26%) 43.5 26.1
199
Au 0.051 (0.3%), 0.158 (41%), 0.209 (9%) 46 27.6
131
I 0.08 (2%), 0.28 (5%), 0.36 (80%), 0.64 (9%), 0.72 (3%) 48.3 28.9
59
Fe 0.19 (2.8%), 1.10(57%), 1.29 (43%) 27.3 16.4
203
Hg 0.073 (17%), 0.279 (83%) 67 40.3
42
K 1.53 (18%) 4.0 2.4
22
Na 0.511 (180%), 1.28 (100%) 81 48.6
24
Na 1.37 (100%), 2.75 (100%) 38 22.8
Adapted from Hine GJ: γ -ray sample counting. In Hine GJ (ed): Instrumentation in Nuclear Medicine. New York, 1967,
Academic Press, p 282.

If the volume of a sample is increased by  increase in volume, increases the counting
adding radioactive solution at a constant con� rate by only about 1%.
centration, the counting rate first increases Thus sample volume has significant effects
linearly with sample volume (or activity) but on counting rate with well counters. Sample
the proportionality is lost as the volume volumes should be the same when comparing
approaches and then exceeds the top of the two samples. One technique that is used when
well. Eventually there is little change with adequate sample volumes are available is to
increasing sample volume, although the total fill the test tubes to capacity because with full
activity is increasing (see Fig. 12-5). For test tubes, small differences in total volume
example, an increase of sample volume in a have only minor effects on counting rate
standard test tube from 7 to 8╯mL, a 14% (curve B in Fig. 12-5); however, this requires
12  •  Counting Systems 177

5.0
B
4.0

3.0 Constant
concentration
Relative counting rate

2.0

1.0
0.9
0.8 Constant
0.7 total activity
A
0.6
0.5
0 2 4 6 8
Sample volume (mL)
FIGURE 12-5  A, Change in counting rate in a standard NaI(Tl) well counter for a sample of constant activity but
diluted to increasing sample volume in a test tube. B, Change in counting rate with volume for constant
concentration.

that identical test tubes be used for all where R(131I) and R(mock 131I) are the count-
samples, so that the volume of activity inside ing rates recorded in the well counter for 
the well itself does not differ between samples. the sample and the calibration standard,
Absorption of γ rays within the sample respectively.
volume or by the walls of the test tube is not Another commonly used mock standard is
57
a major factor except when low-energy Co (129 and 137╯keV) for 99mTc (140╯keV). If
sources, such as 125I (27-35╯keV) are counted. the 57Co is calibrated in “equivalent Bq of
99m
Identical test tubes and carefully prepared Tc,” then Equation 12-2 can be used for
99m
samples of equal volume should be used when Tc calibrations also. If it is calibrated in
comparing samples of these radionuclides. becquerels of 57Co, however, one must correct
for the differing emission frequencies between
4.  Assay of Absolute Activity 57
Co and 99mTc (0.962 γ rays/disintegration vs.
A standard NaI(Tl) well counter can be used 0.889 γ rays/disintegration, respectively). The
for assay of absolute activity (Bq or Bq/mL) activity X of a sample of 99mTc of unknown
in samples of unknown activity using the cali- activity would then be given by
bration data given in Table 12-2. Alterna- X (Bq) = A(Bq) × [ R( 99 m Tc) /R( 57 Co)]
tively, one can compare the counting rate of
the unknown sample to that of a calibration × (0.962 / 0.889)
source (see Chapter 11, Section A.6). “Mock” (12-3)
sources containing long-lived radionuclides where A is the calibrated activity of the 57Co
are used to simulate short-lived radio�nuclides, standard and R(99mTc) and R(57Co) are the
for example, a mixture of 133Ba (356- and counting rates recorded from the 99mTc sample
384-keV γ rays) and 137Cs (662-keV γ rays) for and the 57Co standard, respectively.
“mock 131I.” Frequently, such standards are
calibrated in terms of “equivalent activity” of 5.  Shielding and Background
the radionuclide they are meant to simulate. It is desirable to keep counting rates from
Thus if the activity of a mock 131I standard is background radiation as low as possible with
given as “A(Bq) of 131I,” then the activity of a the well counter to minimize statistical uncer-
sample of 131I of unknown activity X would be tainties in counting measurements (see
obtained from Chapter 9, Section D.4). Sources of background
include cosmic rays, natural radio�activity in
X (Bq) = A(Bq) × [ R( 131 I) /R(mock 131 I)] (12-2) the detector (e.g., 40K) and surrounding
178 Physics in Nuclear Medicine

shielding materials (e.g., radionuclides of Rn,


Th, and U in lead), and other radiation sources 6.  Energy Calibration
in the room. Additional sources of background Energy selection in a well counter usually is
in a hospital environment include patients accomplished by an SCA (Chapter 8, Section
who have been injected with radionuclides for C.2). Commercial well-counter systems have
nuclear medicine studies or for therapeutic push-button or computer selection of the
purposes. These sources of radiation, although appropriate SCA window settings for differ-
usually located some distance from the counter, ent radio�nuclides. In these systems compen-
can produce significant and variable sources sation has been made by the manufacturer for
of background. External sources of background the nonlinear energy response of the NaI(Tl)
radiation are minimized by surrounding the detector. However, because of the possibility
detector with lead. The thickness of the lead of drifts in the elec�tronics and the PM tube
shielding is typically 2.5-7.5╯cm; however, gain with time, the response of the well
even with lead shielding it is still advisable to counter should be checked regularly with a
keep the counting area as free as possible of long-lived standard source, such as 137Cs, as
unnecessary radioactive samples. a quality assurance measure. Some modern
In well counters with automated multiple- well counters incorporate MCAs, allowing 
sample changers (Section A.9), it also is the entire spectrum to be measured and
important to determine if high-activity analyzed.
samples are producing significant back-
grounds levels in comparison with activity
samples in the same counting rack. In many 7.  Multiple Radionuclide Source
nuclear medicine procedures, background Counting
counting rates are measured between samples, When multiple radionuclides are counted
but if the background counting rate becomes simultaneously (e.g., from tracer studies with
large (e.g., from a radioactive spill or contami- double labels), there is “crosstalk” interfer-
nation of the detector), it can produce signifi- ence because of overlap of the γ-ray spectra of
cant statistical errors even when properly the two sources, as shown in Figure 12-6 for
99m
subtracted from the sample counting rate (see Tc and 51Cr. If SCA windows are positioned
Chapter 9, Section D.4). on the 99mTc (window 1) and 51Cr (window 2)

99mTc

140 keV
51Cr

320 keV
Relative number of counts

Window 1
Window 2

Energy
FIGURE 12-6  Window settings used for simultaneous measurement of 99mTc and 51Cr in a mixed sample. Crosstalk
from 51Cr into the 99mTc window must be corrected for, using methods described in the text.
12  •  Counting Systems 179

photopeaks, a correction for the interference Answer


can be applied as follows: A sample containing The crosstalk interference factors are, for 51Cr
only 51Cr is counted and the ratio R12 of counts crosstalk in the 99mTc window
in window 1 to counts in window 2 is deter-
mined. Similarly, a sample containing only R12 = 15, 000 / 25, 000 = 0.6
99m
Tc is counted and the ratio R21 of counts in
99m 51
window 2 to counts in window 1 is determined. and for Tc crosstalk in the C window
Suppose then that a mixed sample containing
unknown proportions of 99mTc and 51Cr is R 21 = 1000 / 20, 000 = 0.05
counted and that N1 counts are recorded in the
99m
Tc window (window 1) and that N2 counts Therefore the counts in the 99mTc window from
are recorded in the 51Cr window (window 2). 99m
Tc in the mixed sample are (Equation 12-4)
Suppose further that room and instrument
N1 ( 99 m Tc) = (18, 000 − 0.6 × 8000) / (1 − 0.6 × 0.05)
background counts are negligible or have been
subtracted from N1 and N2. Then the number = 13, 200 / 0.97
of counts from 99mTc in window 1 [N1(99mTc)] ≈ 13, 608 counts
can be calculated from
51 51
and the counts in the Cr window from Cr
N1 ( 99 m
Tc) = ( N1 − R12 N2 ) / (1 − R12 R 21 )   (12-4) are (Equation 12-5)

and the number of counts from 51Cr in window N2 ( 51 Cr) = (8000 − 0.05 × 18, 000) / (1 − 0.6 × 0.05)
2 [N2(51Cr)] from
= 7100 / 0.97
N2 ( 51 Cr) = ( N2 − R 21 N1 ) / (1 − R12 R 21 )   (12-5) ≈ 7320 counts

Equations 12-4 and 12-5 permit calculation


of the number of counts that would be recorded 8.  Dead Time
in the photopeak window for each radio� Because NaI(Tl) well counters have such high
nuclide in the absence of crosstalk interfer- detection efficiency, only small amounts of
ence from the other radionuclide. These activity can be counted (typically 102 to
equations can be used for other combinations 104╯Bq). If higher levels of activity are
of radionuclides and window settings with employed, serious dead time problems can be
appropriate changes in symbols. For greatest encountered (see Chapter 11, Section C). For
precision, the ratios R12 and R21 should be example, if the dead time for the system (par-
determined to a high degree of statistical pre- alyzable) is 4 µsec, and 50╯kBq of activity
cision (e.g., ±1%) so that they do not add sig- emitting one γ ray per disintegration is
nificantly to the uncertainties in the calculated counted with 100% detection efficiency, then
results. The technique is most accurate when the true counting rate is 50,000╯cps; however,
crosstalk is small, that is, R12 and/or R21 << 1. the recorded counting rate would be approxi-
Generally, the technique is not reliable for the mately 41,000╯cps because of 18% dead time
in vivo measurements described in Section F, losses (see Equation 11-18).
because of varying amounts of crosstalk
caused by Compton scattering within body
tissue. 9.  Automated Multiple-Sample
Systems
EXAMPLE 12-1 Samples with high counting rates require
A mixed sample containing 99mTc and 51Cr pro- short counting times and provide good statis-
vides 18,000 counts in the 99mTc window and tical precision with little interference from
8000 counts in the 51Cr window. A sample normal background radiation. If only a few
containing 51Cr alone gives 25,000 counts in samples must be counted, they can be counted
the 51Cr window and 15,000 crosstalk counts quickly and conveniently using manual tech-
in the 99mTc window, whereas a sample con- niques; however, with long counting times or
taining 99mTc alone gives 20,000 counts in the large numbers of samples, the counting pro-
99m
Tc window and 1000 crosstalk counts in the cedures become time consuming and cumber-
51
Cr window. What are the counts due to each some. Systems with automated sample
radionuclide in their respective photopeak changers have been developed to alleviate
windows? Assume that background counts this problem (Fig. 12-7). Typically, these
are negligible. systems can accommodate 100 or more
180 Physics in Nuclear Medicine

samples, and each sample is loaded automati-


cally into the counter in a sequential manner.
Most multiple sample systems use a varia-
tion of the well-counter detector known as the
“through-hole” detector. As shown in Figure
12-8, the sample hole passes through the
entire length of the NaI(Tl) crystal, and the
PM tube is connected to the side of the scintil-
lator. A key advantage of the through-hole
detector is that samples can be automatically
positioned at the center of the NaI(Tl) crystal,
irrespective of sample volume. This results in
FIGURE 12-7  A NaI(Tl) well counter with automated the highest detection efficiency and mini-
sample-changing capabilities. Hundreds of samples can mizes efficiency changes with volume. Figure
be loaded and measured in a single run. This system
also incorporates a multichannel analyzer for spectral
12-9 shows the smaller changes in efficiency
analysis. (Courtesy PerkinElmer, Inc. Waltham, MA.) with volume for a through-hole versus a well-
type counter for 59Fe.
Systems with automated sample changers
not only save time but also allow samples to
be counted repeatedly to detect variations
caused by malfunction of the detector or elec-
tronic equipment or changes in background
counting rates. Background counting rates
can be recorded automatically by alternating
sample and blank counting vials. In these

Test tube
containing sample

Photomultiplier tube

Lead shielding

NaI(Tl) crystal

Sample changer

FIGURE 12-8  Schematic cross-sectional drawing of through-hole detector and sample-changing system. Placement of
the sample can be automatically adjusted to center the sample volume in the detector.
12  •  Counting Systems 181

1.05

1
Through-hole
Relative efficiency

0.95

Well-type

0.9

0.85
0 0.5 1 1.5 2
Sample volume (mL)
FIGURE 12-9  Efficiency of a well counter versus a through-hole counter for a constant total activity of 59Fe. The
efficiency of the through-hole detector shows less variation with sample volume because the sample can be centered
in the detector. (Adapted from Guide to Modern Gamma Counting. Packard Instrument Company, Meriden, CT, 1993.)

systems, counting vials loaded into a tray or spectrum from background sources, which
carriage are selected automatically and placed could indicate a radioactive spill or contami-
sequentially in the NaI(Tl) well counter. Mea- nation, or for checking the general condition
surements are taken for a preset time or a of the NaI(Tl) detector.
preset number of counts selected by the user. Modern well-counter systems are inter-
The well counter usually is shielded with 5 to faced to computers or have dedicated circuits
7.5╯cm of lead, with a small hole in the lead that control sample changing, placement and
shielding above and beneath the detector for counting time, and perform corrections for
insertion of the sample. One disadvantage of radionuclide decay and background. Pro-
automated systems is that there is no lead grams for spectral analysis and correction of
shielding directly above or below the sample multiple isotope samples are also generally
being counted. Therefore the system is not as available. All interactions with the well-
well shielded as a manual well counter, which counter system generally are through the
can cause an increase in background counting keyboard, where the user selects from a range
rates, particularly from other samples in the of predefined protocols and provides informa-
carriage. This can be a problem when low- tion regarding the radionuclide, desired
activity samples are counted with high- counting time, and sample volume.
activity samples in the carriage. For very high throughput, there are even
Commercial systems usually have MCAs or multidetector systems that may contain as
multiple SCAs to allow the selection of many many as 10 NaI(Tl) scintillation detectors.
different counting windows. The MCA also This permits 10 samples to be counted simul-
can be used to display the entire spectrum taneously and many hundreds or even thou-
recorded by the NaI(Tl) detector on a com- sands of samples to be counted per hour. The
puter. The displayed spectrum allows the individual detectors are carefully separated
user to inspect visually and select the posi- and shielded from each other by lead to
tions of the single-channel windows for count- prevent crosstalk; however, when counting
ing and to examine crosstalk interference high-energy γ rays (300╯keV) some crosstalk
when multiple radionuclides are counted may occur. This is in addition to the source of
simultaneously. It is also very useful for crosstalk described in Section A.7, which
quickly and reliably checking to see if there occurs from the samples waiting to be counted
are any significant photopeaks in the in the sample changer system. Background
182 Physics in Nuclear Medicine

measurements in one detector while counting high-activity samples in the immediate


a sample in an adjacent detector can be used vicinity.
to estimate the magnitude of this crosstalk. The detection efficiency of a conventional
detector depends on a number of factors, such
10.  Applications as detector-to-sample distance, detector diam-
NaI(Tl) well counters are used almost exclu- eter, and sample size (see Chapter 11, Section
sively to count x-ray or γ-ray-emitting radio- A). If the sample-to-detector distance is large
nuclides. Radionuclides with β emissions can compared with the sample diameter, then
be counted by detecting bremsstrahlung radi- usually the counting efficiency is relatively
ation, but the counting rate per becquerel is constant as the sample size is increased;
small because efficiency of bremsstrahlung however, this cannot always be assumed to be
production is very low (see Example 6-1). Well true, and sample size effects should be evalu-
counters are used pri�marily for radioimmuno- ated experimentally for specific counting con-
assays (e.g., measurement of thyroid hor- ditions to be employed.
mones triiodothyronine and thyroxine), assay
of radioactivity in blood and urine samples, 2.  Liquid and Gas Flow Counting
radiochemical assays, and radiopharmaceuti- NaI(Tl) detectors are used frequently as γ-ray
cal quality control. They also are used for monitors in conjunction with gas or liquid
wipe tests (see Chapter 23, Section E.3) in chromatographs. Chromatographs are used to
radiation safety monitoring. Systems with separate and identify different chemical com-
multiple SCAs or MCAs allow multiple radio- pounds by passing a gas or solution through
nuclide sources to be counted simultaneously. columns containing beads that can selectively
These capabilities, combined with automated retain or control the rate of movement of dif-
sample changing and automatic data process- ferent chemical species based on molecular
ing, make the NaI(Tl) well counter an impor- size (gel filtration chromatography), net elec-
tant tool for nuclear medicine in vitro assays. tric charge (ion exchange chromatography), or
binding characteristics (affinity chromatogra-
phy). By comparing the flow of radioactivity
B.  COUNTING WITH CONVENTIONAL with the flow of chemical species, one can
determine the radiochemical identity of dif-
NaI(Tl) DETECTORS
ferent radioactive species (Fig. 12-10). The
SCA typically is used to count only the photo-
1.  Large Sample Volumes peak to reduce background caused by scat-
The principal restriction on the use of most tered radiation from activity in the flow line
NaI(Tl) well counters is that they are useful outside the detector and in the chromato-
only for small sample volumes (a few millili- graph. MCAs or multiple SCAs also can be
ters, typically) and small amounts of activity employed to detect multiple radionuclides
(100╯kBq). For activities greater than simultaneously.
approximately 100╯kBq of most radionuclides, With simple systems the data output from
the counting rate becomes so high that dead the SCA is recorded with a ratemeter (digital
time losses may become excessive. Large or analog) and sent to some form of data
sample volumes and larger amounts of activ- recorder. With more sophisticated systems
ity can be counted using a conventional the data are collected with computers that
NaI(Tl) detector with the sample at some dis- have extended cap�ability for data analysis.
tance from the detector. Placing the sample at
a distance from the detector decreases the
geometric efficiency (see Example 11-1) and C.  LIQUID SCINTILLATION COUNTERS
allows higher levels of activity to be counted
than with the well detector. The sample-to-
detector distance can be adjusted to accom- 1.  General Characteristics
modate the level of activity to be measured. For liquid scintillation (LS) counting, the
Typically, shielding from background sources radioactive sample is dissolved in a scintilla-
with these arrangements is not as good as tor solution contained in a counting vial and
with the well counter because the front of  placed in a liquid scintillation counter (LSC)
the detector is exposed; however, owing to  that consists of two PM tubes in a darkened
the high counting-rate applications of these counting chamber (Fig. 12-11). LSCs are used
systems, background counting rates usually for counting β emitters, such as 3H and 14C,
are not significant unless there are other which would be strongly absorbed in the glass
12  •  Counting Systems 183

Labeled
compounds

Gas or liquid
chromatograph Dual recorder

Mass
Mass detector signal

Lead shield Radioactivity signal


NaI(Tl)
Amplifier, SCA,
PM tube
rate meter

Effluent
collection
vial
FIGURE 12-10  NaI(Tl) detector system used in conjunction with a gas or liquid chromatograph. The “mass detector”
is used to detect chemical species, and the radiation detector is used to detect the radioactivity associated with these
species for radiochemical identification.

Light guide Light-tight Sample However, this is sufficient for high-efficiency


with reflective chamber vial detection of low-energy x rays, γ rays, and β
coating particles. Because the radioactivity is in
direct contact with the scintillator, LS count-
ing is the preferred method for the detection
PM tube PM tube of low-energy β-emitting radionuclides, such
Preamp Preamp
as 3H and 14C. Numerous other β-emitting
radionuclides, including some (β,γ) emitters,
also are counted with a LSC (Table 12-3).
Coincidence circuit
Positron (β+) emitters, however, are generally

Pulse summation
TABLE 12-3â•…
RADIONUCLIDES COMMONLY COUNTED
Amplifier
WITH LIQUID SCINTILLATION DETECTORS

MCA Maximum β
Trigger Energy
Radionuclide Half-Life (MeV)
Computer 3
H 12.3╯yr 0.019
14
C 5700╯yr 0.156
FIGURE 12-11  Basic components of a liquid scintillation
counter. 35
S 87.5╯d 0.167
45
Ca 163╯d 0.257
65
Zn 243╯d 0.325
or plastic of the test tube used to contain the
59
sample in a standard well counter. They are Fe 45╯d 0.467
also used for counting emitters of low-energy 22
Na 2.6╯yr 0.546
x rays and γ rays, which cannot be detected 131
I 8.06╯d 0.606
efficiently with NaI(Tl) detectors because of
the thickness of canning material required
36
Cl 3 × 10 ╯d5
0.714
around the detector. 40
K 1.3 × 109╯yr 1.300
The LS solution has a low atomic number 24
Na 15.0╯hr 1.392
(Z ~ 6 to 8) and density (ρ ~ 1) in comparison 32
P 14.3╯d 1.711
with other scintillators, such as NaI(Tl).
184 Physics in Nuclear Medicine

counted in a standard well counter, because small. Random coincidence rates Rr (cps) can
of the penetrating 511-keV γ rays produced be determined from
from the annihilation (see Chapter 3, Section
G) of positrons with electrons in the sample,
or in the walls of the tube containing the Rr = (2τ) Rn2 (12-6)
sample.
Because LSC systems are used primarily where 2τ is the resolving time of the coinci-
to count very low-energy particles, the system dence circuit and Rn is the noise pulse rate for
must have very low electronic noise levels. each PM tube (assumed to be equal) caused
For example, with 3H, the energy range of the by PM tube noise and phosphorescence in the
β particle is 0-18╯keV. Under optimal condi- sample. For 2τ = 0.03 µsec and Rn = 1000╯cps,
tions, β particles from 3H decay produce only one obtains Rr = 3 × 10−8 × (103)2 = 0.03╯cps.
0 to 25 photoelectrons at the PM tube photo- Thus most of the noise pulses are rejected by
cathode, with an average of only about eight the coincidence circuit.
( Eβ ≈ 1/ 3 Eβmax ). Background electronic noise is The output signals from the two PM tubes
due mainly to spontaneous thermal emission and preamplifiers are fed into the coincidence
of electrons from the photocathode of the PM circuit as described earlier and also into a
tube. Background noise also is present from summation circuit, which adds the two signals
exposure to light of the scintillator solution together to produce an output signal propor-
during sample preparation. This exposure tional to the total energy of the detected event
can produce light emission (phosphorescence), (see Fig. 12-11). The output signals from the
which persists for long periods (i.e., hours). summing circuit are sent to an amplifier to
Several methods are employed in LS detec- boost the signal, which is then digitized in an
tors to reduce this noise or background count MCA. The output from the coincidence circuit
rate. Thermal emission is reduced by refrig- is fed to the MCA to enable data collection
eration of the counting chamber to maintain only when both PM tubes have registered a
the PM tubes at a constant low temperature pulse, thus rejecting noise. The MCA provides
(typically about −10° C). Constant PM tube a spectrum of the energies of the detected
temperature is important because the photo- events, which can be further processed by a
cathode efficiency and electronic gain of the computer, including routines for separating
PM tube are temperature dependent, and the counts from two radionuclides that are
variations in temperature produce variation being counted simultaneously and for per-
in the amplitude of the output signal. forming quench corrections as discussed in
Pulse-height analysis also may be used to Section C.5.
discriminate against noise because true radi-
ation events usually produce larger signals 2.  Pulse-Height Spectrometry
than thermal emission noise; however, Pulse-height analysis is used with LS count-
thermal emission noise still is superimposed ing to further reduce the background count-
on the radiation signals, which can cause ing rate by selecting only the energy region
deterioration of the energy resolution and lin- corresponding to the radiation of interest or
earity of the system. to select different energy regions when simul-
The most effective reduction of noise is taneous sources are being counted. An
achieved by coincidence detection techniques example of two-energy window analysis for a
(see Fig. 12-11). When a scintillation event source containing 3H and 14C is shown in
occurs in the scintillator, light is emitted in all Figure 12-12. Because of the continuous
directions. Optical reflectors placed around energy distribution in β decay, pulse-height
the counting vial reflect the light into two analysis cannot separate completely the two
opposing PM tubes to maximize light collec- spectra, and there is crosstalk interference.
tion efficiency. Pulses from each of the PM Methods to correct for this situation are dis-
tubes are routed to separate preamplifiers cussed in Section C.4.
and a coincidence circuit (see Chapter 8,
Section F). The coincidence circuit rejects any 3.  Counting Vials
pulse that does not arrive simultaneously Counting vials containing the radioactivity
with a pulse from the other PM tube (i.e., and the liquid scintillator solution usually are
within approximately 0.03 µsec). Noise pulses made of polyethylene or low-potassium-con-
are distributed randomly in time; therefore tent glass. The low-potassium-content glass is
the probability of two noise pulses occurring used to avoid the natural background of 40K.
simultaneously in the two PM tubes is very When standard laboratory glass vials (lime
12  •  Counting Systems 185

Channel 2 Channel 1 Modern LS counters have prestored cali�


brations that enable them to convert the
detected cpm into disintegrations per minute
for a wide range of radionuclides. These cali-
brations, however, depend on the material
Relative number of counts

3H
composition and thickness of the sample vial
and on the effects of quenching, which are
discussed in Section C.5).
Frequently, samples containing a mixture
of two radionuclides (e.g., 3H and 14C) are
14C
counted. By selecting separate energy windows
on each of the β spectra (see Fig. 12-12), the
activities of each of the radionuclides can be
determined. The optimal window for each
radionuclide is determined individually by
using separate 3H and 14C sources. If possible,
the energy windows should be adjusted so
Energy that counts from the lower-energy emitter are
FIGURE 12-12  Example of pulse-height spectra obtained not included in the window used for the higher-
from 3H and 14C by liquid scintillation counting. energy emitter. The method and equations
used to correct for crosstalk interference—
described in Section A.7 for well-counter
glass) are used, the background for 3H and 14C applications—can be also used on the LS
is increased by 30-40╯cpm because of 40K in counter. There are also a number of increas-
the glass. Polyethylene vials frequently are ingly sophisticated methods for dealing with
used to avoid this problem and also to increase samples containing radionuclides with very
light transmission from the liquid scintillator similar spectra. These methods are described
to the PM tubes. Polyethylene vials are excel- in detail in reference 1.
lent for dioxane solvents but should not be
used with toluene as the scintillator solvent 5.  Quench Corrections
because toluene will cause the vials to distort Quenching refers to any process that reduces
and swell, which may jam the sample changer. the amount of scintillation light produced by
Materials such as quartz, Vicor, and others the sample or detected by the PM tubes. The
also are used for counting vials. causes of quenching in LS counting were
Exposure of the vial and liquid scintillator described in Chapter 7, Section C.6. The
solution to strong sunlight produces a back- principal effect of quenching is to cause an
ground of phosphorescence that may take apparent shift of the energy spectrum to
hours to decay; therefore samples frequently lower energies (Fig. 12-13). This results in a
are stored temporarily in a darkened con-
tainer before counting. This is referred to as
dark adaptation of samples.
4.  Energy and Efficiency Calibration
Relative number of counts

Beta emission results in a continuous spec-


trum of β-particle energies from zero to a
maximum β-particle energy Eβmax that is char- Unquenched
acteristic of the nuclide, with a mean value at
approximately Eβ ≈ 1/ 3 Eβmax . Usually, most of
the β-particle spectrum lies above the elec-
Quenched
tronic noise, allowing almost the entire spec-
trum to be used and resulting in detection
efficiencies of 80% or higher. An exception is
3
H. The low-energy β emission of 3H ( Eβmax =
18╯keV) reduces the counting efficiency to
approximately 40% to 60% because some of
the events produce pulses below typical noise Energy
pulse amplitudes that are rejected by pulse- FIGURE 12-13  Effect of quenching on a liquid scintilla-
height analysis (see Section C.1). tion counter pulse-height spectrum.
186 Physics in Nuclear Medicine

loss of counts because events can either be Channel 1


shifted below the noise levels of the LS
counter, or if pulse-height analysis is used, Channel 2
they may be shifted out of the energy
window. Thus inaccurate counting rates are
recorded. The error depends on the amount
of quenching, which may vary from one

Relative number of counts


sample to the next.
To obtain accurate results, it is necessary to
correct the observed counting rate for quench-
caused spectral shifts. Several methods have
been developed.
With the internal standardization method,
the sample-counting rate is determined; then
a known quantity of the radionuclide of inter-
est (from a calibrated standard solution) is
added to the sample and it is recounted. The
counting efficiency, εc, is calculated by
Energy
cps(standard + sample) − cps(sample)
εc = FIGURE 12-14  Setting of energy windows for quench
standard(Bq) (12-7) corrections using the channel ratio method.

From the efficiency, the activity of the sample


is obtained from
cps(sample) Once the correction curve has been
sample(Bq) = (12-8)
εc obtained, only one (dual-channel) counting
measurement per sample is required to deter-
With internal standardization, the sample mine counting efficiency. All causes of quench-
must be counted twice and the added activity ing are corrected by the channel ratio method.
of the standard must be distributed in the A disadvantage of the method is that at very
scintillator solution in the same manner as low counting rates statistical errors in the
the sample. The method is not accurate if the value determined for the channel ratio can be
sample and standard are not dissolved in the large, which may result in significant errors
same way in the scintillator. Also, self- in the estimated quench correction factor.
absorption of the emitted β particle by the Longer counting times may be employed to
labeled molecule might not be accounted for minimize this source of error.
unless the standard is also in the form of the A third approach is called the automatic
labeled molecule. external standardization (AES) method. This
A second approach is called the channel method incorporates features of both internal
ratio method. One channel is set to count an standardization and channel ratio. The sample
unquenched sample as efficiently as possible is first counted and then recounted (usually
(i.e., channel 1 in Fig. 12-14), and a second for 1╯min or less) with an external standard
channel is set to accumulate counts in the γ-ray source (usually 137Cs) placed close to the
lower-energy region of the spectrum (channel sample (some counters count the sample plus
2 in Fig. 12-14). When the spectrum shifts to standard first). Positioning of the standard is
the left because of quenching, the lower automatic. Compton recoil electrons produced
channel gains counts, and the ratio of counts by interactions of the γ rays with the scintil-
in the two channels changes. A series of stan- lator solution are counted in two channels and
dards of known activity are counted, each a channel ratio determined, or
quenched deliberately a little more than the
cpm (sample + STD) − cpm sample channel 2
preceding one by adding a quenching agent, to AES (ratio) =
cpm (sample + STD) − cpm sample channel 1
obtain a quench curve relating counting effi-
(12-9)
ciency (cps per becquerel) to the channel ratio.
Then for subsequently measured samples, the where STD refers to the standard γ-ray source
channel ratio is used to determine the quench- and channels 1 and 2 are as indicated in
corrected counting efficiency. Figure 12-14.
12  •  Counting Systems 187

A series of quenched standards containing


known amounts of the radionuclide of interest 6.  Sample Preparation Techniques
is prepared, and counting efficiency is related Samples can be combined with scintillator
to the AES ratio. The AES ratio is then used solution in several different ways, depending
to correct for quenching on subsequently mea- on the composition, state (liquid or solid) and
sured samples. polarity of the sample compound or material.
The external standard method generally The medium into which the sample is placed
provides a high counting rate and thus small is known as the LS cocktail, of which there
statistical errors in the determination of  are two main groups: Emulsifying cocktails,
the quench correction factor while maintain- also known as aqueous cocktails, consist of an
ing the sensitivity of the channel ratio method organic aromatic solvent, an emulsifier and
for detecting quenching effects. The disad� the scintillator. Organic cocktails, also known
vantage of the AES method is that only chem- as nonaqueous or lipophilic cocktails, consist
ical and color quenching are corrected; of an organic aromatic solvent and the
β-particle self-absorption effects or losses scintillator.
caused by sample distribution effects are not. Liquid scintillators were discussed in
For example, the AES method might not be Chapter 7, Section C.6. The most popular
accurate with multiphase solutions in which and widely used is a combination of 2,5- 
the sample is not soluble in the counting diphenyloxazole (also known as PPO) and
solution. p-bis-(o-methylstyryl)benzene (abbreviated as
Representative AES quench curves and bis-MSB). Traditional aromatic solvents
crosstalk correction factors are shown in include toluene and xylene, and although
Figure 12-15 for 14C and 3H for double-label these are still used, they are gradually being
studies, that is, both radionuclides counted replaced with more environmentally friendly
simultaneously. It is apparent from Figure solvents such as di-isopropylnaphthalene
12-15 that as quenching increases (AES ratio (DIN) and phenylxylylethane (PXE).
decreases), the efficiency for counting both 14C Most radionuclides are present in aqueous
and 3H decreases. Thus even though the true form and therefore are not readily miscible
efficiency may be determined accurately from with aromatic solvents. Detergents or emulsi-
the quench correction curve, counting effi- fiers are used to form a microemulsion, in
ciency deteriorates with increased quenching, which the aqueous solution is dispersed in tiny
resulting in increased statistical errors. droplets through the solvent. Commonly used

80

Efficiencies at AES ratio  0.7


14C efficiency

60
Detection efficiency (%)

14C, 47.8%

40

3H efficiency
3H, 23.1%
20
14C in 3H, 11.3%
14C counts in
3H Channel

0
0.0 0.2 0.4 0.6 0.8 1.0
AES ratio
FIGURE 12-15  Representative quench correction curves based on the automatic external standardization (AES)
method for counting mixed 14C-3H samples. For example, with an AES ratio of 0.7 (vertical dashed line) counts in the
3
H channel must first be corrected for 14C crosstalk by 11.3% of the counts in the 14C channel. The counting efficiency
for the corrected 3H counts is 23.1% and for the 14C counts is 47.8% relative to an unquenched sample. Note that the
AES ratio decreases with increasing quenching.
188 Physics in Nuclear Medicine

detergents include the alkyl phenol ethoxyl- solid scintillator crystals through which the
ates, alkyl and alkylaryl sulfonates, alcohol radioactively labeled gas or liquid is allowed
sulfates, and phosphate esters. Polar com- to flow. The most common scintillator mate-
pounds also can be used by forming insoluble rial for this purpose is the organic scintillator
suspensions. For example, 14CO2 can be pre- anthracene. This technique is used primarily
cipitated as barium carbonate and then sus- for β-emitting radionuclides, typically 14C and
pended in the scintillator solution with the 3
H. The β particles interact with the anthra-
addition of thixatropic jelling agents. Silica cene crystals, and the resulting scintillation
gels from thin-layer chromatography also can is detected in the same manner as from the
be counted in this manner. Samples deposited LS vial.
on filter paper such as from paper chromatog- These systems have been used for monitor-
raphy frequently are counted by placing the ing the effluent from amino acid analyzers,
paper strip in the liquid scintillator. The scin- liquid chromatographs, and gas chromato-
tillator solution also can be dissolved or sus- graphs. To monitor the effluent from gas 
pended in the sample itself. chromatographs, the compounds usually are
Another straightforward approach to count- passed through a gas combustion furnace to
ing complicated organic compounds such as convert them into 14CO2 or 3H2O (vapor).
proteins or sections of acrylamide gel columns Carrier gas from the gas chromatograph (e.g.,
with high efficiency is to combust the sample. He) is used to sweep the 14CO2 or 3H2O through
The 14CO2 and 3H2O released may be collected, the counting cell.
dissolved in scintillator solution, and then Counting rates in these systems depend on
counted. the activity concentration and the flow rate. 
Numerous other techniques have been If fast flow rates and low-activity concentra-
developed for LS sample preparation. More tions are required, the result may be data of
discussion of these techniques is presented in poor statistical quality. Data from flow count-
reference 1. Careful sample preparation is ing represent the time course of some process
critical for accurate application of the LS and usually are displayed as time-activity
technique. curves.
7.  Cerenkov Counting 9.  Automated Multiple-Sample LS
High-energy beta emitters may also be Counters
assayed in LSC systems without the use of a LSC may be used for counting large numbers
liquid scintillator solution by detecting optical of samples or for counting low-level samples
Cerenkov radiation (see Chapter 6, Section for long counting times. To expedite this and
A.5). Beta particles with an energy in excess to remove the tedious job of manually count-
of 263╯keV will produce Cerenkov light in a ing multiple samples, automated multiple-
water solution, which can be detected by the sample LSC systems have been developed.
PM tubes in a LSC system. The calibration of These systems have automated sample chang-
the LSC system for measuring activity from ers that frequently can handle 100 or more
the detected Cerenkov light must account for counting vials (Fig. 12-16). A number of
the directionality of the light cone produced
and the spectral characteristics of the Ceren-
kov light, which is weighted toward the blue
end of the visible spectrum. Because the pro-
duction of Cerenkov light is a physical phe-
nomenon, there is no chemical quenching of
the signal. However, color quenching still
must be accounted for. Cerenkov counting is
used primarily to measure samples contain-
ing 32P ( Eβmax = 1710╯keV) in which the count-
ing efficiency can be in excess of 50%.
8.  Liquid and Gas Flow Counting
In addition to counting individual samples,
LSC systems also can be used for continuous
FIGURE 12-16  A liquid scintillation counter with auto-
monitoring of gas streams or flowing liquids. mated sample loading can efficiently count and analyze
In these systems, the vial of LS solution is hundreds of samples. (Courtesy Beckman Coulter, Inc.,
replaced with a cell filled with finely dispersed Brea, CA.)
12  •  Counting Systems 189

different sample-changing mechanisms have


been developed, but the most common ones
employ either trays or an endless belt for
transport of the samples. Sample vials are
selected automatically and loaded into the
light-tight LS counting chamber. The samples
are counted sequentially in serial fashion.
Empty positions in the sample changer can be
bypassed, and samples below a selectable
low-level counting rate may be rejected auto-
matically to avoid long counting times on
samples that contain an insignificant amount
of activity when preset counts are selected.
Modern automated multiple-sample LSC
systems are provided with many different
ways of handling and presenting the recorded FIGURE 12-17  An ionization chamber dose calibrator.
Samples are inserted into the well in the sealed ioniza-
data. Computer-based systems allow auto- tion chamber. The current is measured and displayed on
matic implementation of quench corrections, a digital readout. (Courtesy Biodex Medical Systems,
efficiency corrections, background subtrac- Shirley, NY.)
tion, statistical analysis, and calculations of
parameters for radioimmunoassay or other
assay analysis.
dose calibrators assay the total amount of
10.  Applications activity present by measuring the total
LSC systems are used in nuclear medicine for amount of ionization produced by the sample.
radioimmunoassays and protein-binding Plug-in resistor modules, pushbuttons, or
assays of drugs, hormones, and other biologi- other selector mechanisms are used to adjust
cally active compounds. LSC systems also are the electrometer readout to display the activ-
commonly used in studies of metabolic or ity of the selected radionuclide directly in
physiologic processes with 3H-or 14C-labeled MBq or kBq units. Because ionization cham-
metabolic substrates or other physiologically bers have no inherent ability for energy dis-
important molecules. They are also used for crimination, they cannot be used to select
wipe tests for radiation-monitoring purposes different γ-ray energies for measurement, as
(see Chapter 23, Section E.3). is possible with detectors having pulse-height
analysis capabilities. One approach that is
used to distinguish low-energy versus high-
energy γ-ray emitters (e.g., 99mTc vs. 99Mo) is
D.  GAS-FILLED DETECTORS
to measure the sample with and without a
few millimeters of lead shielding around the
1.  Dose Calibrators source. Effectively, only the activity of the
Although they are inefficient detectors for high-energy emitter is recorded with the
most γ-ray energies encountered in nuclear shielding in place, whereas the total activity
medicine, gas-filled detectors still find some of both emitters is recorded with the shielding
specialized applications. A dose calibrator is absent. This technique can be used to detect
essentially a well-type ionization chamber tens of kBq quantities of 99Mo in the presence
that is used for assaying relatively large of tens or even hundreds of MBq of 99mTc.
quantities (i.e., MBq range) of γ-ray-emitting As with the NaI(Tl) well counter, dose cali-
radioactivity (Fig. 12-17). Dose calibrators brators are subject to sample volume effects
are used for measuring or verifying the activ- (see Section A.3). These effects should be
ity of generator eluates, patient preparations, investigated experimentally when a new dose
shipments of radioactivity received from sup- calibrator is acquired, so that correction
pliers, and similar quantities of activity too factors can be applied in its use, if necessary.
large for assay with NaI(Tl) detector systems. For example, a quantity of activity can be
The detector for a dose calibrator typically measured in a very small volume (e.g., 0.1╯mL
is an argon-filled chamber, sealed and  in a 1-mL syringe), and that activity can be
pressurized to avoid variations in response diluted progressively to larger volumes in
with ambient barometric pressure (see larger syringes and then in beakers, and so
Chapter 7, Section A.2). Ionization chamber forth to determine the amount by which the
190 Physics in Nuclear Medicine

instrument reading changes with sample and other fields. To date, however, they have
volume. had limited effect on nuclear medicine. Their
Another parameter worth evaluating is lin- disadvantages of small size and high cost out-
earity of response versus sample activity. This weigh their advantage of superior energy
may be determined conveniently by recording resolution in comparison with other detection
the reading for a 99mTc source of moderately systems [e.g., NaI(Tl)] for general-purpose
high activity (e.g., 1╯GBq, or whatever the applications; however, the energy resolution
approximate maximum amount of activity of semiconductor detectors allows the separa-
the dose calibrator will be used to assay), then tion of γ rays differing in energy by only a few
recording the readings during a 24- to 48-hour keV as opposed to 20-80╯keV with NaI(Tl)
period (4-8 half-lives) to determine whether (Fig. 12-18; see also Fig. 10-14). Therefore in
they follow the expected decay curve for 99mTc. applications in which energy resolution is the
Deviations from the expected decay curve critical factor and the relatively small size of
may indicate instrument electronic non� the semiconductor detector is not completely
linearities requiring adjustment or correction restrictive, Ge or Si detectors are the system
of readings. In applying this technique, it is of choice.
necessary to correct for 99Mo contamination Semiconductor detectors are used exten-
using the shielding technique described sively as charged-particle and γ-ray spectrom-
earlier, especially after several 99mTc half-lives eters in physics. Their principal application
have elapsed. in nuclear medicine is for assessment of
radionuclide purity. Si has a lower atomic
2.  Gas Flow Counters number and density than Ge and therefore a
Gas-filled detectors also are used in gas flow lower intrinsic detection efficiency for γ rays
counters, primarily for measurement of with energies â•›40╯keV (see Chapter 11,
β-emitting activity. The detector in these Section A.3). Thus Si detectors are used pri-
systems usually can be operated in either pro- marily for detection of low-energy x rays and
portional counter or Geiger-Müller mode. The Ge, cadmium telluride (CdTe), and cadmium
most frequent application for these systems zinc telluride (CZT) are used for γ rays.
in nuclear medicine is for monitoring the The basic configuration of a semiconductor
effluent from gas chromatographs. Gases system for in vitro analysis is shown in Figure
labeled with 3H or 14C in helium carrier gas 7-12. Except for a special low-noise high-
from the chromatograph are passed through voltage supply, preamplifier, and amplifier,
a combustion furnace to convert them to 3H2O the system components are the same as those
or 14CO2, which then is allowed to flow through of NaI(Tl) counting systems. Usually an MCA
the counter gas volume itself with the count- is employed rather than an SCA with semi-
ing gas (usually 90% He plus 10% methane). conductor detectors because the detectors
This permits a time-course analysis of the most commonly are used to resolve complex
outflow from the chromatograph. These spectra of multiple emissions and multiple
systems have good geometric and intrinsic radionuclides (see Fig. 12-18).
detection efficiencies for low-energy β emit- The superior energy resolution of semiÂ�
ters, such as 3H and 14C; however, their intrin- conductor detectors may result in a signifi-
sic efficiency for γ-ray detection is only cant advantage in sensitivity [i.e., minimum
approximately 1%. Gases labeled with β emit- detectable activity (MDA)] (see Chapter 9,
ters are therefore analyzed using NaI(Tl) Section D.5) in comparison with NaI(Tl)
detectors. detectors for some applications. MDA depends
on the ratio S/ B , in which S is the net
sample counting rate and B is the background
E.  SEMICONDUCTOR DETECTOR counting rate. Because the energy resolution
of a semiconductor detector is 20 to 80 times
SYSTEMS
better than NaI(Tl), a photopeak window 20
to 80 times narrower can be used, resulting
1.  System Components in typically 20 to 80 times smaller background
Semiconductor detectors [germanium (Ge) counting rate. Considering background alone,
and silicon (Si)] (see Chapter 7, Section B) then, the MDA for a semiconductor detector
created revolutionary advances in nuclear could be a factor 20 to 80 smaller than a
physics, nuclear chemistry, radiation chemis- NaI(Tl) detector of comparable size. This
try, nondestructive materials analysis (e.g., advantage is partially offset by the larger
x-ray fluorescence and neutron activation), available detector sizes with NaI(Tl) and,
12  •  Counting Systems 191

NaI(Tl) detector

(122, 136)

(140)
57Co

99mTc
Relative number of counts 8

(392)
Pb x rays

(365)
131I (80)
x rays
6

113mIn

(514)
131I

(662)
4

85Sr
(284)

(637)
137Cs

(723)
131I
2

131I

131I
0
0 200 400 600 800
A Energy (keV)

Ge(Li) detector
x ray
Xe x rays
Rb x rays
(14.4)

In x rays

Ba x rays
spectrum
Tc x rays

Xe x rays
4

Ba x rays
In x rays
(140)

57Co

2
137Cs (662)
99mTc
Relative number of counts

0
Pb x rays

6
57Co (136)

0 15 30
131I (85)

(365)
(392)

(637)

4
×20
131I
(122)

131mIn

(514)
(284)

(723)
131I
57Co

2
85Sr
131I

131I

0
0 200 400 600 800
B Energy (keV)
FIGURE 12-18  Comparative pulse-height spectra of a mixed radionuclide sample recorded with NaI(Tl) (A) and Ge(Li)
(B) detectors. Because of its superior energy resolution, the Ge(Li) detector clearly resolves multiple γ rays and x rays
of similar energies that appear as single peaks with NaI(Tl).

above approximately 200╯keV, by the greater than NaI(Tl), limiting them to situations in
intrinsic photopeak efficiency of NaI(Tl) for which small detector sizes are acceptable.
comparable detector thicknesses (see Chapter
11, Section A.3); however, for lower-energy γ 2.  Applications
rays, measured in a configuration having a The major in vitro applications of semicon-
high geometric efficiency (e.g., sample placed ductor detectors in nuclear medicine have
directly against the detector), there is usually been for tracer studies employing many radio-
an advantage in MDA favoring the semicon- nuclides simultaneously and for the assay of
ductor detector. For higher-energy γ rays, radionuclidic purity of radiopharmaceuticals.
CdTe or CZT semiconductors provide the In both of these applications the superior
advantage of both excellent energy resolution energy resolution of semiconductor detectors,
and good photopeak efficiency, although the illustrated by Figure 12-18, offers a distinct
cost per unit detector volume is much higher advantage. The energy resolution of the Ge
192 Physics in Nuclear Medicine

detector allows unequivocal identification of


radionuclides, whereas the NaI(Tl) spectrum
is ambiguous. Another application of semicon-
ductor detectors is for analysis of samples in
neutron activation analysis.

F.  IN VIVO COUNTING SYSTEMS

In vivo counting systems are used to measure


radioactive concentrations in patients and,
occasionally, in experimental animals.
Systems designed to monitor radioactivity in
single organs or in localized parts of the body
are called probe systems. For example, single-
probe systems, employing only one detector,
are used for measuring thyroidal uptake of
radioactive iodine and for sentinel node detec-
tion in breast cancer. Multiprobe systems,
although less common, have been used for
renal function studies, for lung clearance
studies, for obtaining washout curves from
the brain, and so forth. Probe systems provide
some degree of measurement localization but
without the detail of imaging techniques dis-
cussed in Chapters 13-19. Because the radia-
tion must in general pass through several
centimeters of soft tissue to reach the detec-
tor, most in vivo counting systems are
designed to detect γ rays. FIGURE 12-19  Typical NaI(Tl) probe system for mea-
suring thyroid uptake of radioactive iodine. (Courtesy
1.  NaI(Tl) Probe Systems Capintec, Inc., Ramsey, NJ.)
The simplest probe system consists of a colli-
mated NaI(Tl) detector mounted on a station-
ary or mobile stand that can be oriented and intensity of scattered radiation is another
positioned over an area of interest on the important variable. For example, a source
patient (Fig. 12-19). Such detectors are com- lying outside the direct field-of-view of the
monly used in diagnostic tests for thyroid collimator can contribute to the recorded
disease. The detector is connected to the usual counting rate by Compton scattering in the
NaI(Tl) electronics, including an SCA for tissues surrounding the source distribution.
energy selection and a digital counter or com- To minimize the contribution from scattered
puter that records the number of counts per radiation, measurements usually are made
second. A typical probe system employs a 5-cm with the SCA window set on the photopeak of
diameter × 5-cm thick NaI(Tl) crystal, with the γ-ray emission to be counted. Even this is
a cylindrical or conically shaped collimator, not completely effective for eliminating all the
15-25╯cm long, in front of the detector. variable effects of scattered radiation on the
When calibrating a probe system for in vivo measurement, however, especially when low-
measurements, it is important to account for energy γ rays are counted (see Figs. 10-6 and
the effects of attenuation and scatter on the 10-10).
recorded counting rate (see Chapter 11,
Section A.5). Usually, the depth of the source
distribution within the patient is not known 2.  Miniature γ-Ray and β Probes for
accurately. Because the linear attenuation Surgical Use
coefficient for soft tissue is in the range µl = Miniature, compact γ-ray probes are designed
0.1 to 0.2╯cm−1 for most γ-ray energies in for use in conjunction with surgical proce-
nuclear medicine, a 1- to 2-cm difference in dures, primarily in cancer applications. The
source depth can result in a 10% to 40%  most important application is the detection 
difference in recorded counting rate. The of the sentinel lymph node in patients with
12  •  Counting Systems 193

breast cancer and melanoma. The sentinel better for this application than Si or Ge
node is the most likely initial site for meta- because they have higher stopping power for
static spread of the cancer; thus biopsy of the γ rays and can be operated at room tempera-
sentinel node is important for patient man- ture. A small collimator is used in front of the
agement. The sentinel node is identified by probe to provide directionality.
direct injection of a 99mTc-labeled colloid (a Figure 12-20 shows the components of a
suspension of fine particles labeled with 99mTc) typical γ-ray probe system. The output signals
into the tumor. This colloid is trapped in the from the probes are amplified and sent to an
first lymph node draining the tumor. During MCA. Discriminator levels are set automati-
surgery, the γ-ray probe is used to identify the cally for each different radionuclide. The
sentinel node, from which a biopsy sample is counting rate is presented on a digital display.
taken and sent to a pathology laboratory for Many systems also have an audible output
analysis. proportional to the counting rate. The whole
The second broad class of applications is in unit is battery powered and can run for many
radioguided surgery. Here, tumor-seeking hours on a single charge, eliminating the need
radiopharmaceuticals are injected into the for power cords. Wireless probes also are
patient. The radiopharmaceutical agent is
designed to target and bind to cancer cells
with high selectivity. After waiting for an Collimator
appropriate length of time for selective uptake Si photodiode
CsI(Tl)
of the radiopharmaceutical agent into the
tumor, the patient goes to surgery and the Preamp
surgeon uses the γ-ray probe to assist in locat-
ing and removing the cancerous tissue, while High energy -ray probe
sparing as much healthy tissue as possible. Collimator
This procedure has been applied in para� CZT or CdTe
thyroid surgery and colorectal cancer, and in
detecting lymph node involvement for a range Preamp
of other cancers. Low energy -ray probe
The requirements for γ-ray probes for intraÂ�
operative use are that they have high effi-
ciency (so that radiolabeled tissue can be Amplifier
0000
found quickly in the surgical environment), cpm
that they be lightweight and easy to use, and MCA
that they pose no hazard to the patient. The
probe of choice for high-energy γ emitters, Processing
such as 111In, 131I, and 18F, is a scintillation
detector. A typical probe consists of a 5-mm
diameter × 10-mm high cesium iodide [CsI(Tl)] A
scintillator crystal, coupled to a Si photodiode.
The Si photodiode is a light-sensing semi�
conductor detector that replaces the PM tube
found in conventional scintillation detectors
and converts the scintillation light into an
electrical signal (see Chapter 7, Section C.3).
It is preferred in this application because of
its compact size and low weight compared
with a PM tube. CsI(Tl) is used in place of
NaI(Tl) as the scintillator because its emis-
sion wavelengths are better matched to the
spectral response of the Si photodiode. For
lower-energy γ emitters, such as 99mTc, a semi-
conductor detector made from CZT or CdTe B
(see Chapter 7, Section B) that directly con-
verts the γ rays to electric charge is typically FIGURE 12-20  A, Schematic representation of γ -ray
probes for intraoperative use. B, Four different wireless
used. This is an ideal application for these gamma probes shown with control unit. The geometry of
semiconductor detectors, because the required the probes are tailored to suit specific clinical applications.
detector area is small. CZT and CdTe are (Figure B courtesy IntraMedical Imaging, Los Angeles, CA.)
194 Physics in Nuclear Medicine

available, further facilitating their use in the Another application for whole-body count-
sur�gical environment. References 2 and 3 ing is the measurement of naturally occurring
40
provide a detailed review of counting probe K, which can be used to estimate total-body
systems for intraoperative use. potassium content. This is another high-
Probes for β-particle detection also have energy γ emitter present in very small quanti-
been developed. These are typically used in ties, requiring good detection efficiency for
conjunction with tumor-seeking, positron- accurate measurement. Whole-body counters
emitting radiopharmaceuticals to aid in locat- also are used for detecting and monitoring
ing tumors during surgery or to map tumor possible accidental ingestion of radioactive
margins during surgical resection, helping to materials.
ensure that the tumor is completely removed Most whole-body counters employ rela-
while sparing normal tissue. They differ from tively large NaI(Tl) detectors, 15 to 30╯cm in
the γ-ray probes described previously in that diameter × 5 to 10╯cm thick, to obtain good
these probes directly detect β+ particles (posi- geometric efficiency as well as good intrinsic
trons) rather than the 511-keV annihilation efficiency for high-energy γ rays. Several such
photons. Because of the short range of posi- detectors may be employed. Also the “count-
trons in tissue (see Chapter 6, Section B.2), ing chamber” is well shielded with lead, con-
they can only detect radioactivity that is  crete, steel, and other materials to obtain
very superficial (1-2╯mm) at the surgical site,  minimal background levels, thus ensuring
but have the advantage over γ-ray probes of minimum statistical error caused by back-
being very insensitive to radioactivity that ground counting rates (see Chapter 9, Section
may be contained in adjacent tissues and D.4). Shielding materials are selected care-
organs and that could interfere with the local fully for minimum contamination with back-
measurement. ground radioactivity.
3.  Whole-Body Counters
Another class of in vivo measurement systems
are whole-body counters, which are designed REFERENCES
to measure the total amount of radioactivity A detailed reference on in vitro counting systems
in the body, with no attempt at localization of is the following:
the activity distribution. Many (but not all) of 1. L’Annunciata MF: Handbook of Radioactivity Analy-
these systems employ NaI(Tl) detectors. They sis, ed 2, San Diego, 2003, Academic Press.
are used for studying retention, turnover, and The design and application of miniature γ probes
clearance rates with nuclides such as 60Co and for surgical use are reviewed in detail in the
57
Co (labeled vitamin B12), 24Na, 42K, 47Ca, and following:
59
Fe. Most of these radionuclides emit high- 2. Hoffman EJ, Tornai MP, Janacek M, et al: Intraopera-
energy γ rays, and several have quite long tive probes and imaging probes. Eur J Nucl Med
half-lives. Thus it is important that a whole- 26:913-935, 1999.
3. Povoski SP, Neff RL, Mojzisik CM, et al: A comprehen-
body counter have good detection efficiency, so sive overview of radioguided surgery using gamma
that very small amounts of activity (â•›50╯kBq) detection probe technology. World J Surg Oncol 7:11,
can be detected and measured accurately. 2009.
chapter
13 
The Gamma Camera:
Basic Principles

Radionuclide imaging is the most important little use for imaging because they cannot
application of radioactivity in nuclear medi- penetrate more than a few millimeters of
cine. Radionuclide imaging laboratories are tissue. Therefore they cannot escape from
found in almost every hospital, performing within the body and reach an external radia-
hundreds and even thousands of imaging pro- tion detector, except from very superficial
cedures per month in larger institutions. tissues. Bremsstrahlung (see Fig. 6-1) gener-
In this chapter, we discuss briefly some ated by electron emissions is more penetrat-
general aspects of radionuclide imaging, and ing, but the intensity of this radiation
we describe the basic principles of the most generally is very weak.
widely used imaging device, the gamma Imaging system detectors must therefore
camera, also known as the Anger scintillation have good detection efficiency for γ rays. It is
camera, named after its inventor, Hal Anger also desirable that they have energy discrimi-
(see Chapter 1, Section C and Fig. 1-3). The nation capability, so that γ rays that have lost
performance characteristics of this instru- positional information by Compton scattering
ment are discussed in Chapter 14. The use of within the body can be rejected based on
the gamma camera for tomographic imaging their reduced energy (see Chapter 6, Section
is described in Chapter 17. C.3). A sodium iodide [NaI(Tl)] scintillation
detector (see Chapter 7, Section C) provides
both of these features at a reasonable cost;
A.  GENERAL CONCEPTS OF for this reason it is currently the detector of
RADIONUCLIDE IMAGING choice for radionuclides with γ-ray emissions
in the range of 80-300╯keV.
The purpose of radionuclide imaging is to The first attempts at radionuclide “imaging”
obtain a picture of the distribution of a radio- occurred in the late 1940s. An array of radia-
actively labeled substance within the body tion detectors was positioned on a matrix of
after it has been administered (e.g., by intra- measuring points around the head. Alterna-
venous injection) to a patient. This is accom- tively, a single detector was positioned manu-
plished by recording the emissions from the ally for separate measurements at each point
radioactivity with external radiation detec- in the matrix. These devices were tedious to
tors placed at different locations outside the use and provided only very crude mappings of
patient. The preferred emissions for this the distribution of radioactivity in the head
application are γ rays in the approximate (e.g., left-side versus right-side asymmetries).
energy range of 80 to 500╯keV (or annihilation A significant advance occurred in the early
photons, 511╯keV). Gamma rays of these  1950s with the introduction of the rectilinear
energies are sufficiently penetrating in body scanner by Benedict Cassen (see Fig. 1-2).
tissues to be detected from deep-lying organs, With this instrument, the detector was
can be stopped efficiently by dense scintilla- scanned mechanically in a raster-like pattern
tors, and are shielded adequately with rea- over the area of interest. The image was a
sonable thicknesses of lead (see Fig. 6-17—soft pattern of dots imprinted on a sheet of paper
tissue has attenuation properties similar to by a mechanical printer that followed the
water). Alpha particles and electrons (β par- scanning motion of the detector, printing the
ticles, Auger and conversion electrons) are of dots as the γ rays were detected.
195
196 Physics in Nuclear Medicine

The principal disadvantage of the rectilin- Computer


ear scanner was its long imaging time (typi- compute X, Y and E
cally many minutes) because the image was linearity & uniformity corrections Image
formed by sequential measurements at many
individual points within the imaged area. The Monitor
first gamma-ray “camera” capable of record-
ing at all points in the image at one time was

Amp/ADC

Amp/ADC

Amp/ADC

Amp/ADC

Amp/ADC

Amp/ADC
described by Hal Anger in 1953. He used a
pinhole aperture in a sheet of lead to project
a γ-ray image of the radionuclide distribution
onto a radiation detector composed of a
NaI(Tl) screen and a sheet of x-ray film. The
film was exposed by the scintillation light
PM tube array
flashes generated by the γ rays in the NaI(Tl)
screen. Unfortunately, this detection system Light guide
(especially the film component) was so ineffi- NaI(Tl) crystal
cient that hour-long exposures and therapeu-
tic levels of administered radioactivity were Collimator
needed to obtain satisfactory images.
In the late 1950s, Anger replaced the film-
screen combination with a single, large-area,
NaI(Tl) crystal and a photomultiplier (PM)
tube assembly to greatly increase the detec- Patient
tion efficiency of his “camera” concept. This
instrument, the Anger scintillation camera,1
or gamma camera, has been substantially FIGURE 13-1  Basic principles and components of a
refined and improved since that time. modern gamma camera. The outputs of each photo�
Although other ideas for nuclear-imaging multiplier (PM) tube are amplified and digitized using an
instruments have come along since then, analog-to-digital converter (ADC). The X-Y locations for
none, with the exception of modern positron each gamma ray that interacts in the NaI(Tl) crystal are
computed from the digitized signals. The energy depos-
emission tomography systems (see Chapter ited by the gamma ray, E, which is proportional to the
18), has matched the gamma camera for a total measured pulse amplitude, also is computed by
balance of image quality, detection efficiency, summing the individual PM tube signals. If E falls within
and ease of use in a hospital environment. the selected energy window, the event is accepted and
placed at the appropriate X-Y location in the image.
The gamma camera has thus become the
most widely used nuclear-imaging instru-
ment for clinical applications.
image of the γ-ray distribution on the surface
of the NaI(Tl) crystal (see Section B.3). The
B.  BASIC PRINCIPLES OF THE GAMMA second is that the NaI(Tl) crystal is viewed
by an array of PM tubes, rather than a
CAMERA
single PM tube. Signals from the PM tubes
are fed to electronic or digital position logic
1.  System Components circuits, which determine the X-Y location of
Figure 13-1 illustrates the basic principles of each scintillation event, as it occurs, by
image formation with the gamma camera. using the weighted average of the PM tube
The major components are a collimator, a signals (see Section B.2).
large-area NaI(Tl) scintillation crystal, a Individual events also are analyzed for
light guide, and an array of PM tubes. Two energy, E, by summing the signals from all
features that differ from the conventional PM tubes. When the pulse amplitude of an
NaI(Tl) counting detectors described in event falls within the selected energy window,
Chapter 12 are crucial to image formation. it is accepted and the X and Y values are
The first is that an imaging collimator is binned into a discrete two-dimensional array
used to define the direction of the detected γ of image elements, or pixels. An image is
rays. The collimator most commonly consists formed from a histogram of the number of
of a lead plate containing a large number of events at each possible X-Y location. Large
holes. By controlling which γ rays are numbers of events are required to form an
accepted, the collimator forms a projected interpretable image because each pixel must
13  •  The Gamma Camera: Basic Principles 197

have a sufficient number of counts to achieve reflective material such as TiO2 to maximize
an acceptable signal-to-noise level. Because light output and hermetically sealed inside a
images often are formed in 64- × 64-pixel or thin aluminum casing to protect it from mois-
128- × 128-pixel arrays, the counting require- ture. An optical glass window on the back
ments are some 103 to 104 times higher than surface of the casing permits the scintillation
for a simple counting detector. light to reach the PM tubes. A cross section of
Images are displayed on a computer a typical gamma camera crystal assembly is
monitor, where image brightness and con- shown in Figure 13-2. The choice of thickness
trast may be manipulated and different color of the NaI(Tl) crystal is a trade-off between
tables may be employed. More sophisticated its detection efficiency (which increases with
digital image processing is discussed in increasing thickness) and, as shown in
Chapter 20. Chapter 14, Section A.1, its intrinsic spatial
Most modern gamma cameras are com- resolution (which deteriorates with increas-
pletely digital, in the sense that the output of ing thickness). Most general-purpose gamma
each PM tube is directly digitized by an analog- cameras have crystal thicknesses of approxi-
to-digital converter (ADC). The calculation of mately 9.5╯mm. For lower-energy γ emitters,
X-Y position and pulse-height are performed such as 99mTc and 201Tl, however, detection
in software based on the digitized PM tube efficiency is adequate even with 6-mm-thick
signals, and errors in energy and positioning detector crystals.
caused by noise and pulse distortions caused An array of PM tubes is coupled optically
by the analog positioning circuitry are elimi- to the back face of the crystal with a silicone-
nated. This approach also permits improved based adhesive or grease. Round PM tubes
handling of pulse pile-up at high counting are arranged in a hexagonal pattern to maxi-
rates, as described in Section B.2. mize the area of the NaI(Tl) crystal that is
The gamma camera can be used for static covered. Some cameras use hexagonal (or
imaging studies, in which an image of an rarely, square) cross-section PM tubes for
unchanging radionuclide distribution can be better coverage of the NaI(Tl) crystal. Typical
recorded over an extended imaging time (e.g., PM tube sizes are 5╯cm in diameter. Most
minutes). Single contiguous images of the modern cameras employ between 30 and 100
whole body can be obtained by scanning  PM tubes. Figure 13-3 shows a photograph of
the gamma camera across the entire length of a 30-tube model. The PM tubes are encased
the patient. This can be achieved by moving in a thin magnetic shield (Chapter 7, Section
either the bed or the gamma camera while C.2) to prevent changes in the gain caused by
adjusting the event positioning computation changes in the orientation of the gamma
to account for this movement. Clinically camera relative to the earth’s magnetic field.
important whole-body studies include bone The ultrasensitivity of PM tubes to magnetic
scans of the skeleton, and the localization of fields also makes gamma cameras susceptible
tumors or their metastases in the body. to the stray fields from magnetic resonance
The gamma camera also can be used for imaging systems.
dynamic imaging studies, in which changes
in the radionuclide distribution can be
observed, as rapidly as several images per
second. This allows physiologic information to
be obtained, such as the rate of tracer uptake Scintillation
or clearance from an organ of interest. Images NaI(Tl) crystal light exits to Glass
(typically 6- to PM tubes entrance
also can be synchronized to electrocardiogram 12.5-mm thick) window
signals, permitting images of the heart in dif-
ferent phases of the cardiac cycle to be formed.
These gated images can provide important
information on cardiac function.
2.  Detector System and Electronics
Gamma rays
The gamma camera employs a single, large- enter from
area, rectangular NaI(Tl) detector crystal, Thin aluminum casing this side Reflector
usually 6- to 12.5-mm thick with sizes of up to hermetically seal material
to 60 × 40╯cm. Round crystals of 25 to 50╯cm crystal
in diameter were used in many older systems. FIGURE 13-2  Schematic cross-section of a NaI(Tl)
The NaI(Tl) crystal is surrounded by a highly crystal assembly for a gamma camera.
198 Physics in Nuclear Medicine

FIGURE 13-3  A rectangular gamma camera detector with the cover removed showing the photomultiplier (PM) tubes
mounted on the NaI(Tl) crystal. In this example, the gamma camera detector measures 50 × 15╯cm and is read out by
30 PM tubes 5╯cm in diameter. This is a digital camera in which each of the PM tube outputs is individually digitized.
(Courtesy Dr. Joel Karp, University of Pennsylvania, Philadelphia, PA.)

Many manufacturers employ plastic light The amount of light detected by a particu-
guides between the detector crystal and PM lar PM tube is inversely related to the lateral
tubes, whereas others couple the PM tubes distance between the interaction site and the
directly to the crystal. The functions of the center of that PM tube. This is illustrated in
light guide are to increase the light collection one dimension in Figure 13-4. Ideally, the
efficiency, by channeling scintillation light relationship between signal amplitude and
away from the gaps between the PM tubes, location with respect to the center of a PM
and to improve the uniformity of light collec- tube would be linear. This would enable the
tion as a function of position. The latter effect position of an event to be determined by
is achieved by painting or etching a carefully taking a weighted average or centroid of the
designed pattern onto the entrance face of the PM tube signals using the simple relation-
light guide. The use of the PM tubes with ships shown in Figure 13-4. In practice,
hexagonal or square cross-sections that can however, the response is more complex, with
be tiled without gaps on the NaI(Tl) crystal a plateau directly beneath the PM tube
may in some cases allow elimination of the (because the PM tube is not a “point” detector)
light guide, assuming there is sufficient and long, flat tails caused by reflections of
spreading of the scintillation light in the glass light from the back and side surfaces of the
entrance window of the PM tube for accurate NaI(Tl) crystal. Therefore a calibration for
positioning. spatial nonlinearity is required (see Chapter
The detector crystal and PM tube array are 14, Section B).
enclosed in a light-tight, lead-lined protective Figure 13-5A shows a schematic drawing
housing. In most modern cameras, most of  for an eight-PM tube version of the gamma
the electronics (such as preamplifiers, pulse- camera and is used to illustrate the principles
height analyzers, automatic gain control, of scintillation event localization in an analog
pulse pile-up rejection circuits and ADCs) are detector. The position is determined by split-
mounted directly on the individual PM tube ting the signal from each PM tube onto four
bases within the detector housing to minimize output lines, whose signals are denoted X +,
signal distortions that can occur in long cable X −, Y↜↜+, and Y − (Fig. 13-5B). The fraction of
runs between the detector head and control the PM tube current that goes to each output
console. line is determined by the value of the resistors
13  •  The Gamma Camera: Basic Principles 199

S2
S1

If linear, then:
D1  (S2  D) / (S1  S2)
D2  (S1  D) / (S1  S2)
where D  D1  D2

PM tube array

NaI(Tl) crystal
D1 D2

Collimator

Gamma ray
FIGURE 13-4  Illustration of light sharing between photomultiplier (PM) tubes. The PM-tube signal, S, is inversely
related to the distance of the interaction site, D, from the center of the PM tube. Equations for a linear relationship
are shown.

(R) that are used. By Ohm’s law, this current on the pulse height. Note that the possible
is proÂ�portional to 1/R. A separate circuit sums range of X and Y values is from −1 to +1. The
the outputs of all the PM tubes to form the resistor values shown in Figure 13-5C were
Z-signal. The Z-signal is proportional to the chosen such that the calculated X- and
total amount of light produced by a scintilla- Y-position signals vary linearly with distance
tion event in the crystal, and therefore the in the X and Y directions. In a perfect gamma
total energy deposited by the gamma ray, and camera, measured (X, Yâ•›) values would change
is used for pulse-height analysis. linearly from (−1, −1) in the bottom left-hand
The X +, X −, Y +, and Y − signals are com- corner to (+1, +1) at the top right-hand corner
bined to obtain X-position and Y-position of the camera face. The X and Y values can
signals. The X-position of the scintillation be scaled by the detector size to determine the
event is given by the difference in the X + and absolute position of an event on the gamma
X − signals, divided by the total X signal (X + camera face.
+ X −) However, Equations 13-1 and 13-2 do not
give a perfect mapping of source position
X = ( X + − X − )/( X + + X − ) (13-1) because, as was discussed previously, the PM
tubes signal does not actually vary linearly
Similarly, for the Y-position with interaction position. This gives rise to a
“pincushion” artifact, which is illustrated in
Y = (Y + − Y − ) / (Y + + Y − ) (13-2) Figure 14-9. There are also effects caused
by nonuniformities in the crystal, light 
The X- and Y-position signals are normalized reflections at the edge of the crystal, and non-
to the total X and Y signals, so that the cal- uniform response across the face of the PM
culated position of interaction does not depend tubes that can cause further nonlinearities in
200 Physics in Nuclear Medicine

NaI(Tl) crystal RX RX RY RY


1  12.5 12.5 
Y
2 25 25 12.5 

1 2 3 3 12.5  12.5 
X
4 5 4 50 16.7 25 25

PM tube 6 7 8 5 16.7 50 25 25

6  12.5  12.5
A
7 25 25  12.5

Y 8 12.5   12.5
C
RY

RX RX
X X

RY

Y
B
FIGURE 13-5  Illustration of analog positioning in a gamma camera. A, Schematic representation of an eight-
photomultiplier (PM) tube camera. B, Signals from individual PM tubes are split using resistors onto four output
lines, designated X +, X −, Y +, and Y −. C, Representative resistor values (in kΩ) for the eight PM tubes. Resistor
values are chosen such that the X and Y positions computed from Equations 13-1 and 13-2 vary linearly with inter-
action position in the detector, ranging from a value of −1 in the bottom left hand corner to +1 in the top right corner.

position determination. These effects and cor- significant pulse amplitude, the noise from
rection techniques for them are discussed in the PM tubes that produce negligible signal
Chapter 14, Section B. amplitude (and that therefore contribute
In digital cameras, the output signal from little to position information) is not included
each PM tube is digitized and the event posi- in the position calculation. Second, with
tion is calculated in software. Often, this is signal thresholding, only a small number of
simply analogous to the resistor readout PM tubes surrounding the interaction loca-
described earlier; the inverse of the resistor tion are used for position determination. This
values are used as weighting factors for the allows a gamma camera to detect multiple
individual PM tube signals, and Equations events simultaneously when they occur in dif-
13-1 and 13-2 are used to determine the X ferent portions of the gamma camera and
and Y values. However, digital cameras also their light cones (the projection of the scintil-
can use more sophisticated algorithms that lation light on the PM tube array) do not
incorporate information regarding the non- significantly overlap. This improves the
linearity of PM tube response with position counting rate performance of the gamma
into the weighting factors to provide better camera, reducing dead time losses.
positioning accuracy. Energy selection is important for imaging
A commonly used tactic that is employed in because it provides a means to discriminate
both digital and analog cameras to improve against γ rays that been scattered within the
the positioning accuracy is to include in the body and therefore lost their positional infor-
position calculation only PM tubes with mation. By choosing a relatively narrow pulse-
signals above a certain threshold. This has height analyzer window that is centered on
two important benefits. By using the signal the photopeak, only γ rays that undergo no
only from those PM tubes that produce a scatter or small-angle scatter will be accepted.
13  •  The Gamma Camera: Basic Principles 201

Two different methods can be used to select Energy window Z


the photopeak events. The first approach uses
simple energy discrimination on the Z-signal.
However, because of nonuniformities in the
NaI(Tl) crystal (small variations in light pro-
duction with position), in light collection 

Number of counts
efficiency and in PM tube gains, the position
of the photopeak varies somewhat from posi-
tion to position in the detector. If a single
discriminator level is applied across the whole
detector, the window must be widened to
accommodate the fluctuations in photopeak
position, thus accepting more scatter (Fig.
13-6, top).
In the second method, suitable only for
digital cameras, the photopeak positions and
appropriate discriminator level settings are Pulse height, Z
computed and stored for many different loca-
tions across the detector face (Fig. 13-6,
bottom). When an event is detected, the X, Y Z1
values are calculated based on Equations Z2
13-1 and 13-2, and a look-up table is used to Z3
find the appropriate discriminator levels for
that location. If the event amplitude Z falls
Number of counts

within the pulse-height analyzer settings, the


event is accepted.
A modern gamma camera has an energy
resolution of 9% to 10% at 140╯ keV (99mTc).
Typically, the energy window (the difference
between upper-level and lower-level discrimi-
nators) is set to 14%, or 20╯ keV, centered
around 140╯ keV. The gamma camera soft-
ware adjusts the discriminator levels for
radionuclides other than 99mTc based on the
relationship (approximately linear over a Pulse height, Z
small energy range) between the γ-ray energy FIGURE 13-6  The pulse-height response is not uniform
deposited and the light output of NaI(Tl) (see across the whole face of the gamma camera, leading to
Fig. 10-11). variation in the pulse height of photopeak events. Using
a global energy window requires a wide window that
3.  Collimators leads to the inclusion of larger amounts of scatter and
also results in nonuniform efficiency (top). Using local
To obtain an image with a gamma camera, it energy thresholds, in which the energy window is tai-
is necessary to project γ rays from the source lored to the event location, improves scatter rejection and
uniformity (bottom).
distribution onto the camera detector. Gamma
rays cannot be focused; thus a “lens” principle
similar to that used in photography cannot  Gamma rays not traveling in the proper direc-
be applied. Therefore most practical γ-ray tion are absorbed by the collimator before
imaging systems employ the principle of they reach the detector. This “projection by
absorptive collimation for image formation.* absorption” technique is an inherently ineffi-
An absorptive collimator projects an image of cient method for using radiation because most
the source distribution onto the detector by of the potentially useful radiation traveling
allowing only those γ rays traveling along toward the detector actually is stopped by the
certain directions to reach the detector. absorptive walls between the collimator holes.
This is one of the underlying reasons for the
relatively poor quality of radionuclide images
*An important exception is imaging of the two 511-keV (e.g., as compared to radiographic images), as
annihilation photons from positron-emitting radionu-
clides, in which electronic coincidence detection can be
discussed in Chapter 15.
used to replace the collimator as described in Chapter 18, Four basic collimator types are used with
Section A.1. the gamma camera: pinhole, parallel-hole,
202 Physics in Nuclear Medicine

diverging, and converging. The different smaller than the collimator cone length f; it
types of collimator are introduced subse- is minified when the source distribution is
quently. Their effects on the spatial resolu- farther away. The image size I and object
tion and sensitivity of the gamma camera are (source) size O are related according to
discussed in Chapter 14 , Sections C and D.
A pinhole collimator (Fig. 13-7A) consists I/O = f / b (13-3)
of a small pinhole aperture in a piece of lead,
tungsten, platinum, or other heavy metal The size of the imaged area also changes with
absorber. The pinhole aperture is located at distance from the pinhole collimator. If the
the end of a lead cone, typically 20 to 25╯cm detector diameter is D and the magnification
from the detector. The size of the pinhole can (or minification) factor is I/O (Equation 13-3),
be varied by using removable inserts and is the diameter of the image area projected onto
typically a few millimeters in diameter. the detector, D′, is
The imaging principle of a pinhole collima-
tor is the same as that employed with inex- D
D′ = (13-4)
pensive “box cameras.” Gamma rays passing I/O
through the pinhole project an inverted image
of the source distribution onto the detector Thus a large magnification factor, obtained at
crystal. The image is magnified when the dis- close source-to-collimator distances, results in
tance b from the source to the pinhole is a small imaged area.

I I

f
O

b
O
Pinhole Parallel hole
A B

f
b

O f
I

Diverging Converging
C D
FIGURE 13-7  A-D, Four types of collimators used to project “γ -ray images” onto the detector of a gamma camera.
O, Radioactive object; I, its projected image.
13  •  The Gamma Camera: Basic Principles 203

Image size changes with object-to-pinhole directly “head-on,” it can be positioned closer
distance b. Therefore the pinhole collimator to the patient for better image detail in some
provides a somewhat distorted image of three- imaging studies (e.g., left anterior oblique
dimensional objects because source planes at cardiac views).
different distances from the collimator are A diverging collimator (Fig. 13-7C↜) has
magnified by different amounts. Pinhole col- holes that diverge from the detector face. The
limators are used primarily for magnification holes diverge from a point typically 40-50╯cm
imaging of small organs (e.g., thyroid and behind the collimator, projecting a minified,
heart) and for small-animal imaging. noninverted image of the source distribution
Another type of pinhole collimator, the onto the detector. The degree of minification
multi-pinhole collimator, has an array of mul- depends on the distance f from the front of the
tiple pinholes, typically seven, arranged in  collimator to the convergence point, the dis-
a hexagonal pattern. This collimator was tance b from the front of the collimator to the
employed in the past for tomographic imaging. object (source), and the collimator thickness t
This type of tomography now is seldom used
clinically; however, multi-pinhole approaches I/O = ( f − t) / ( f + b) (13-5)
are being widely employed for some small-
animal imaging applications. where I and O are image and object size,
The parallel-hole collimator (Fig. 13-7B) is respectively. The useful image area becomes
the “workhorse” collimator in most imaging larger as the image becomes more minified
laboratories. Parallel holes are drilled or cast (Equation 13-4).
in lead or are shaped from lead foils. The lead
EXAMPLE 13-1
walls between the holes are called collimator
septa. Septal thickness is chosen to prevent γ What is the minification factor for a diverging
rays from crossing from one hole to the next collimator 5-cm thick, with f = 45╯cm, and a
(see Chapter 14, Section C.2). A magnified source distribution 15╯cm from the collima-
view of a parallel-hole collimator is shown in tor? If the detector diameter is 30╯cm, what is
Figure 13-8. The parallel-hole collimator proj- the imaged area at this distance?
ects a γ-ray image of the same size as the
source distribution onto the detector. A varia- Answer
tion of the parallel-hole collimator is the From Equation 13-5,
slant-hole collimator, in which all of the holes I/O(minification factor)
are parallel to each other but angled, typically
= (45 − 5) / (45 + 15) = 0.67
by approximately 25 degrees, from the per-
pendicular direction. This type of collimator From Equation 13-4,
has characteristics that are similar to those Diameter of imaged area
of the parallel-hole type. Because it views the
= 30 cm/0.67 = 44.8 cm
source distribution from an angle rather than

FIGURE 13-8  Close-up view of a


typical parallel-hole collimator
showing the hole structure. Indi-
vidual holes are approximately
1.9╯mm across in this example.
(Courtesy Nuclear Fields, Des
Plaines, IL.)
204 Physics in Nuclear Medicine

As shown by Example 13-1, a typical diverg-


ing collimator decreases the size of the image
on the detector and increases the diameter of
the imaged area, by approximately one-third
as compared with a parallel-hole collimator.
As with the pinhole collimator, image size
changes with distance; thus there is a certain
amount of image distortion. Diverging colli-
mators are used primarily on cameras with
smaller detectors to permit imaging of large
organs such as the liver or lungs on a single
view. Parallel-hole collimator Converging collimator
A converging collimator (Fig. 13-7D) has
holes that converge to a point 40-50╯cm in FIGURE 13-9  Examples of geometric image distortions
created by the converging collimator.
front of the collimator. For objects between
the collimator face and the convergence point,
the converging collimator projects a magni-
fied, noninverted image of the source distribu-
tion. Image size I and object size O are related cameras having large-area detectors to permit
according to full use of the available detector area for
imaging of small organs.
I/O = ( f + t) / ( f − b) (13-6) Converging collimators project an inverted
magnified image when the object is located
between the convergence point and twice the
where f is the distance from the collimator convergence length of the collimator, and an
face to the convergence point, b is the distance inverted minified image beyond that distance;
from the collimator face to the object, and t is however, they are used rarely at distances
collimator thickness. beyond the convergence point.
Some manufacturers provide a single, One consequence of the magnification or
invertible collimator insert that can be used minification effects of these collimators is
in either converging or diverging mode. that the contribution of the intrinsic detector
resolution (see Chapter 14, Section A) to the
EXAMPLE 13-2 resulting image resolution may be reduced
Suppose the collimator described in Example (magnification > 1) or increased (magnifica-
13-1 is inverted and used as a converging col- tion < 1). Thus magnifying collimators can be
limator to image a source distribution 15╯cm useful in situations in which high spatial
in front of the collimator, also with a 30-cm resolution is required, for instance in imaging
diameter detector. What are the image mag- of small organs such as the thyroid and in
nification factor and the size of the imaged small-animal imaging applications.
area?
4.  Event Detection in a Gamma
Answer Camera
When the collimator is inverted, the back face There are four types of events that may be
becomes the front face, and the convergence  detected by a gamma camera, as illustrated
distance f becomes (45 − 5╯cm) = 40╯cm. Thus in Figure 13-10. Of these, only one provides
from Equation 13-6 correct positional information. The four events
I/O (magnification factor) types (labeled to correspond with Fig. 13-10)
are the following:
= (40 + 5) / (40 − 15) = 1.8
A: valid event—a γ ray is emitted parallel
From Equation 13-4, to the collimator holes, passes through
Diameter of imaged area a hole and interacts photoelectrically in
the NaI(Tl) crystal, depositing all of its
= 30 cm/1.8 = 16.7 cm
energy at a single location.
B: detector scatter event—a γ ray is emitted
Again, because magnification depends on parallel to the collimator holes, passes
distance, there is some image distortion with through a hole and interacts by Compton
the converging collimator (Fig. 13-9). Con- scattering in the NaI(Tl) crystal. The
verging collimators are used primarily with scattered γ ray can either interact a
13  •  The Gamma Camera: Basic Principles 205

PM tubes

Light guide
NaI(Tl) crystal

Collimator

C B A D

Patient with
-emitting
radionuclide
Liver concentrated in
liver

FIGURE 13-10  Illustration of different types of events that may be detected by a gamma camera. Red circles indi-
cate locations of γ ray interactions. A, Valid event. B, Detector scatter event. C, Object scatter event. D, Septal
penetration.

second time in the detector (as illus- the event is mispositioned, often many
trated in Fig. 13-10), in which case the centimeters from the original site of
full energy of the γ ray is deposited, or emission. These events lead to a low-
it may escape the detector, in which case spatial-frequency background in the
only part of the γ-ray energy is depos- images that results in a loss of contrast.
ited. In the former case, energy discrim- (See Chapter 15, Section C.). In clinical
ination cannot be used to reject the imaging situations, a large fraction of
event, and the event will be misposi- the detected events can be due to object
tioned between the two interaction loca- scatter, and good energy resolution in
tions. In the latter case, it is likely that the gamma camera is extremely impor-
the event will be rejected because it does tant (see Chapter 14, Section A.3). The
not satisfy the event energy criteria collimator itself can also be a cause of
established by the upper- and lower- scatter leading to similar effects.
level discriminators. As discussed in D: septal penetration—in this case a γ ray
Chapter 14, Section A.1, these events is emitted toward the collimator, but not 
are relatively rare. parallel to it. Because of incomplete
C: object scatter event—the γ ray is not attenuation by the thin collimator walls
emitted toward the collimator holes but (septal penetration), there is a finite
is scattered within the body, then passes chance that the γ ray will reach the
through a collimator hole and subse- NaI(Tl) crystal and interact with it. This
quently is detected. The γ ray loses again leads to blurring of the image,
energy during scattering and will there- because all events are con�sidered to
fore produce a smaller signal in the have come from a direction perpendicu-
detector. Some of these events will be lar to the collimator face (for parallel-
rejected by energy discrimination, but if hole collimators). This effect becomes
the angle of scatter is small (â•›45 increasingly important when using
degrees), the energy loss is small and high-energy γ emitters or high-resolution
the event may be accepted. In this case collimators with thin septa.
206 Physics in Nuclear Medicine

Considerable effort is expended in the positioned in a flexible way over different


design of gamma cameras to reduce or elimi- regions of the patient’s body. Often, a moving
nate the detection of the events B, C, and D bed is incorporated to permit imaging studies
just described, each of which is a cause of of the whole body. The gamma camera head
blurring and a loss of contrast in the image. often is mounted on a rotating gantry, allow-
Collimators also are carefully designed for ing it to take multiple views around the
specific energies to minimize septal penetra- patient. This feature also is necessary for pro-
tion while maximizing sensitivity for a given ducing tomographic images, or cross-sectional
γ-ray energy (Chapter 14, Section C). images through the body, as discussed in
In addition to the simple cases illustrated Chapters 16 and 17.
in Figure 13-10, a combination of these event Dual-headed gamma cameras are becom-
types can occur (e.g., scatter in the body and ing increasingly popular. In these systems,
septal penetration, or septal penetration fol- two gamma camera heads are mounted onto
lowed by Compton interaction in the detec- the gantry as shown in Figure 13-12. Usually,
tor). Finally, further complications arise when the two heads can be positioned at a variety
pulse pile-up occurs—that is, two or more of locations on the circular gantry. An obvious
events occur almost simultaneously in the advantage of a dual-headed camera is that
gamma camera. This can also lead to event two different views of the patient can be
mispositioning and is discussed in detail in acquired at the same time. For example, in
Chapter 14, Section A.4. Pile-up events can whole-body imaging, the two detector heads
arise from of any combination of the event can be placed at 180 degrees to each other to
types described earlier. provide anterior and posterior views simulta-
neously. Triple-headed systems also exist, pri-
marily for tomographic studies, as described
in Chapters 16 and 17.
C.  TYPES OF GAMMA CAMERAS AND An example of a planar image acquired
THEIR CLINICAL USES with a gamma camera system is presented in
Figure 13-13. Dynamic processes can also be
The most common type of gamma camera is measured by taking multiple planar images
the single-headed system (Fig. 13-11). It con-
sists of a gamma camera detector mounted on
a gantry that allows the camera head to be

FIGURE 13-11  Single-headed gamma camera mounted


on a rotating gantry. The camera is operated from the FIGURE 13-12  A dual-headed gamma camera system
computer (left). The flexible positioning of the camera (top). Note that the camera heads can be placed in differ-
head and the bed (right) allows the system to obtain ent orientations to provide two simultaneous views of an
images of many different parts of the body. (Courtesy GE organ or the body (bottom). (Courtesy Siemens Medical
Medical Systems, Milwaukee, WI.) Systems, Inc., Hoffman Estates, IL.)
13  •  The Gamma Camera: Basic Principles 207

over time. An example of a dynamic study is


shown in Figure 13-14.
Single- and dual-headed gamma cameras
are the workhorses of clinical nuclear medi-
cine laboratories. However, a range of spe-
cialty gamma cameras have been or are being
developed for specific imaging tasks. Exam-
ples are systems designed specifically for
small-organ imaging (e.g., heart, breast, and
thyroid) and mobile systems for use on
patients who are too sick to be moved to the
nuclear medicine department (e.g., from
intensive care). These systems typically have
smaller detector heads and may not have a
built-in bed. An example of a compact gamma
camera for breast imaging and representative
images from it are shown in Figure 13-15. The
detector typically ranges from 10 × 10╯cm2 to
20 × 20╯cm2. A number of different detector
technologies are being exploited for these
small-detector cameras, including traditional
NaI(Tl)/PM tube systems, cameras based on
pixellated NaI(Tl) or cesium iodide [CsI(Tl)]
scintillator arrays (see Fig. 13-15B), and
CsI(Tl) scintillator arrays with read-out by
silicon photodiode arrays. There are also
systems being developed that employ arrays
of cadmium zinc telluride elements (see
Chapter 7, Section B) for direct detection of γ
rays, eliminating the need for a scintillator-
photodetector combination.
FIGURE 13-13  Whole-body bone scan obtained using High-resolution gamma cameras also have
99m
Tc-MDP. These planar images were obtained with a been developed for small-animal imaging.
dual-headed gamma camera on which both anterior (left) The goal is to provide a tool that biologists can
and posterior (right) views can be acquired simultane- use to monitor radiotracers in vivo, particu-
ously. The entire body was imaged by translating the
patient bed through the gamma camera system. (Cour- larly in rats and mice. Most approaches
tesy Siemens Medical Systems, Inc., Hoffman Estates, IL.) involve the use of very small pinhole

Gallbladder

1st minute 2nd minute 3rd minute 4th minute 5th minute

6th minute 7th minute 8th minute 9th minute 10th minute
FIGURE 13-14  Planar gamma camera images over the region of the gallbladder following injection of 99mTc-HIDA. At
approximately 7 minutes, cholecystokinin was given to the patient to stimulate emptying of the gallbladder. The rate
and extent of emptying can be measured from this dynamic sequence of planar images. (Courtesy GE Medical Systems,
Milwaukee, WI.)
208 Physics in Nuclear Medicine

FIGURE 13-15  Example of a compact, mobile


gamma camera system. A, The gamma camera
A head is attached to a cantilevered arm for easy
and flexible positioning. B, Pixellated NaI(Tl)
scintillator array that is coupled to small
position-sensitive photomultiplier tubes to
form the detector head. Each element in the
array is approximately 2 × 2╯mm and is sepa-
rated from its neighbor by a reflective mate-
rial. The inset shows a magnified view of the
pixel elements. C, Clinical images of a breast
cancer patient acquired with this camera 
following the injection of 99mTc-sestamibi. A
tumor is seen as a “hot spot” against the low
background uptake of the normal breast.
B (Photographs and images courtesy Dilon Tech-
Superior nologies, Inc., Annapolis, MD.)

Lateral Medial Inferior

Left craniocaudal Left lateral


C

collimators to provide high spatial resolution. BIBLIOGRAPHY


Tomographic small animal imaging systems The principles of the gamma camera are discussed
based on this approach are discussed in in greater detail in the following:
Chapter 17, Section A.3. Simmons GH: The Scintillation Camera, New York, 1988,
Society of Nuclear Medicine.
REFERENCE
1. Anger HO: Scintillation camera. Rev Sci Instr 29:27-
33, 1958.
chapter
14 
The Gamma Camera:
Performance
Characteristics

The performance of a gamma camera system blurring caused by the collimator, is called the
is defined by the sharpness and detail of the intrinsic spatial resolution of the camera.
images it produces, the efficiency with which Intrinsic resolution is limited primarily by
it detects incident radiation, its ability to two factors. The first is multiple scattering of
measure the energy of the incident γ rays (to γ-ray photons within the detector. If a photon
minimize scatter), and the counting rate it can undergoes Compton scattering within the
handle without significant dead time losses. A detector crystal and the residual scattered
gamma camera is not capable of producing photon also is detected, but at some distance
“perfect” images of the radionuclide distribu- away, the two events are recorded as a single
tion. Certain inherent imperfections arise event occurring at a location along the line
from the performance characteristics of the joining the two interaction sites. This is not 
detector, its associated electronic circuitry, a serious cause of degraded resolution for
and the collimator. Image artifacts also can be photon energies 300╯keV in which multiple
caused by malfunctions of various camera scatter Compton interactions in NaI(Tl) are
components. In this chapter, we describe the almost negligible. Even at 662╯keV, Anger 
major factors that determine gamma camera calculated that for a detector thickness of
performance and examine the limitations that 6.4╯mm, less than 10% of photons are mis-
can lead to artifacts in gamma camera images placed by more than 2.5╯mm as a result of
and their correction. Standard tests of gamma multiple scattering events.1
camera performance also are summarized. The second, and primary, cause of limited
intrinsic resolution is statistical fluctuation
in the distribution of light photons among
A.  BASIC PERFORMANCE photomultiplier (PM) tubes from one scintil-
lation event to the next. The problem is
CHARACTERISTICS
exactly analogous to the statistical fluctua-
tions observed in radioactive decay, discussed
1.  Intrinsic Spatial Resolution in Chapter 9. If a certain PM tube records, on
Spatial resolution is a measure of the sharp- average, N light photons from scintillation
ness and detail of a gamma camera image. events occurring at a certain location in the
Sharp edges or small, pointed objects produce detector crystal, the actual number recorded
blurred rather than sharply defined images. from one event to the next varies with a stan-
Part of the blurring arises from collimator dard deviation given by N . Thus if a very
characteristics discussed in Sections C and D narrow beam of γ rays is directed at a point
and part arises in the sodium iodide [NaI(Tl)] on the detector, the position of each event as
detector and positioning electronics. The limit determined by the positioning circuitry or
of spatial resolution achievable by the detec- computer algorithm is not precisely the same.
tor and the electronics, ignoring additional Rather, they are distributed over a certain
209
210 Physics in Nuclear Medicine

area, the size of which depends on the mag- their distribution are therefore proportional
nitude of these statistical fluctuations. to 1/ N . This causes noticeably greater blur-
A detailed method for measuring and char- ring at lower γ-ray energies. An example of
acterizing intrinsic spatial resolution is dis- the change of intrinsic spatial resolution as
cussed in Section E.1. Typically, a lead mask a function of γ-ray energy is shown in Figure
containing a number of narrow (~1╯mm) slits 14-1.
is placed on the face of the gamma camera Intrinsic resolution also depends on detec-
(without the collimator) and the camera is tor crystal thickness. Thicker detectors result
irradiated using a 99mTc (140-keV) point in greater spreading of scintillation light
source. The resulting image is a series of lines before it reaches the PM tubes. Furthermore,
corresponding to the locations of the slits there is a greater likelihood of detecting 
(e.g., see Fig. 14-10A). The resolution is cal- multiple Compton-scattered events in thicker
culated as the full width at half maximum detectors, particularly with higher-energy
(FWHM) of a profile drawn perpendicular to radionuclides. These are the primary reasons
the image of the lines at various locations in why gamma cameras use relatively thin
the field of view. The intrinsic spatial resolu- detectors in comparison with NaI(Tl) systems
tion of modern large field-of-view gamma that are used for counting applications.
cameras measured with 99mTc in this manner Figure 14-2 shows an example of the intrin-
is in the range of 2.9- to 4.5-mm FWHM. sic spatial resolution versus crystal thickness
Because the resolution is considerably worse for 140-keV γ rays.
than the width of the slits, the contribution of Intrinsic resolution improves with increased
the slits themselves to the measured resolu- efficiency of collection of scintillation photons.
tion is very small (10% for measured resolu- Modern cameras are substantially improved
tion 2.5╯mm). over earlier versions in this regard because of
Intrinsic resolution becomes worse with the use of more efficient PM tubes and of
decreasing γ-ray energy because lower-energy better techniques for optical coupling between
γ rays produce fewer light photons per scinÂ� the detector crystal and the PM tubes. The
tillation event, and smaller numbers of light use of greater numbers of smaller PM tubes
photons result in larger relative statistical  (5-cm-diameter tubes have become the stan-
fluctuations in their distribution (Chapter 9, dard, and some gamma cameras have as
Section B.1). As a rule of thumb, intrinsic many as 110 PM tubes per head) and improved
resolution is proportional to 1/ E, in which electronics also have contributed to this
E is the γ-ray energy. This follows because improvement. Accurate corrections for non-
the number of scintillation light photons linearity (see Section B.1) and nonuniformity
produced, N, is roughly proportional to E (see Section B.2) have also resulted directly
and the relative statistical fluctuations in in improvements in intrinsic resolution, as

4.5
Intrinsic resolution (mm FWHM)

4
FIGURE 14-1  Intrinsic spatial resolution
of a gamma camera as a function of γ-ray
energy for a 6.3-mm-thick NaI(Tl) crystal.
(Compiled with data from Sano RM,
3.5 Tinkel JB, LaVallee CA, Freedman GS:
Consequences of crystal thickness reduc-
tion on gamma camera resolution and sen-
sitivity. J Nucl Med 19:712-713, 1978; and
Muehllehner G: Effect of crystal thickness
3 on scintillation camera performance. J
Nucl Med 20:992-993, 1979.)

2.5
0 50 100 150 200 250 300 350 400
-ray energy (keV)
14  •  The Gamma Camera: Performance Characteristics 211

5.5
FIGURE 14-2  Intrinsic spatial resolution
of a gamma camera at 140╯keV as a function
of crystal thickness. (Compiled with data 5

Intrinsic resolution (mm, FWHM)


from Sano RM, Tinkel JB, LaVallee CA,
Freedman GS: Consequences of crystal
thickness reduction on gamma camera reso- 4.5
lution and sensitivity. J Nucl Med 19:712-
713, 1978; Muehllehner G: Effect of crystal
thickness on scintillation camera perfor-
mance. J Nucl Med 20:992-993, 1979; Royal 4
HD, Brown PH, Claunch BC: Effects of
reduction in crystal thickness on Anger
camera performance. J Nucl Med 20:977- 3.5
980, 1979; Chapman D, Newcomer K,
Berman D, et╯al: Half-inch versus quarter-
inch Anger camera technology: Resolution
3
and sensitivity differences at low photo-
peak energies. J Nucl Med 20:610-611,
1979; and unpublished data from Dr. Joel
Karp, University of Pennsylvania, Philadel- 2.5
phia, PA.) 0 5 10 15 20 25 30
Crystal thickness (mm)

discussed in the following sections. The best 100% efficient for energies up to approxi-
reported intrinsic resolution for a large field- mately 100╯keV for all crystal thicknesses,
of-view gamma camera is just below 3╯mm but then shows a rather marked decrease in
FWHM at 140╯keV ( 99mTc). Significant efficiency at higher energies, depending on
improvements beyond approximately 2╯mm crystal thickness. At 140╯keV (γ-ray energy of
99m
FWHM will be difficult to achieve, owing to Tc), the difference in efficiency between
the ultimate limitation of the light photon 6.4-mm and 12.7-mm-thick crystals is approx-
yield of NaI(Tl). In most practical situations, imately 20% and the photopeak detection 
however, the intrinsic spatial resolution efficiency is in the 70% to 90% range. At
makes a negligible contribution to the overall approximately 500╯keV, the standard gamma
system resolution of the gamma camera, camera (detectors 0.64-0.95-cm-thick) is less
which is largely determined by the resolution than 20% efficient at converting incident γ
of the collimator (see Sections C and D). rays into photopeak pulses.
At high energies, the performance of gamma
2.  Detection Efficiency cameras with 0.64- to 1.27-cm-thick crystals
The gamma camera employs a sodium iodide is limited by decreasing detection efficiency
crystal that is relatively thin in comparison (as well as increasing collimator septal
with most other sodium iodide detectors used penetration—see Section C.2). Deteriorating
in nuclear medicine: 6.4 to 12.7╯mm versus 2 intrinsic spatial resolution becomes the limit-
to 5╯cm for probe counting systems, scanners, ing factor at lower energies. Because of these
and so on. The trade-off in gamma cameras is tradeoffs, the optimal γ-ray energy range is
between detection efficiency (which improves approximately 100 to 200╯keV for most gamma
with thicker crystals) and intrinsic spatial cameras. Some gamma cameras are now fitted
resolution (which improves with thinner with thicker crystals (12.7-25.4╯mm), enabling
crystals—see Fig. 14-2). The gamma camera is them to achieve improved efficiency for
designed to provide acceptable detection effi- imaging positron-emitting radionuclides at
ciency while maintaining high intrinsic spatial 511╯keV (Chapter 18, Section B.4). This comes
resolution in the energy range of 100-200╯keV. at the expense of some loss of intrinsic spatial
As a result, the detection efficiency of the resolution (see Fig. 14-2) when these systems
gamma camera detector is somewhat less than are used in the 100-200-keV energy range.
would be desirable at higher γ-ray energies.
Figure 14-3 shows photopeak detection 3.  Energy Resolution
efficiency versus γ-ray energy for the gamma It is not unusual in a typical patient study for
camera detector for a range of NaI(Tl) crystal there to be more Compton-scattered than
thicknesses. The gamma camera is nearly unscattered γ rays striking the detector (see
212 Physics in Nuclear Medicine

NaI(Tl) thickness (cm)


100
Photopeak detection efficiency (%)

5.08

2.54

10 1.27

0.64

1
0 100 200 300 400 500 600 700
-ray energy (keV)
FIGURE 14-3  Photopeak detection efficiency versus γ -ray energy for NaI(Tl) detectors of different thicknesses.
(Adapted from Anger HO: Radioisotope cameras. In Hine GJ [ed]: Instrumentation in Nuclear Medicine, Vol 1. New
York, 1967, Academic Press, p 506.)

Fig. 11-9). Because the Compton-scattered 500


photons have lower energy, it is possible to 400
Counts

discriminate against them using pulse-height 300 PHA


window
analysis. The energy resolution of the detec- 200
tor determines the efficiency with which this 100
can be accomplished. Good energy resolution
is perhaps the most important performance 0 50 100 150
feature of the camera system for this purpose. Energy (keV)
Energy resolution, like intrinsic spatial FIGURE 14-4  Energy spectrum from a gamma camera
resolution, depends largely on statistical fluc- measured using a point source of 99mTc in air. The energy
tuations in the number of light photons col- resolution at 140╯keV in this example is 10.5%. A typical
15% energy window (approximately 130 to 150╯keV) is
lected from a scintillation event (Chapter 10, shown superimposed on the spectrum. PHA, pulse-height
Section B.7). Thus good light collection  analyzer. (Data courtesy Dr. Magnus Dahlbom, UCLA
efficiency is a prerequisite for good energy School of Medicine, Los Angeles, CA.)
resolution. As well, because the number 
of light photons released in a scintillation
event increases almost linearly with γ-ray
energy, E, (Fig. 10-11), energy resolution 130╯keV should reject 140-keV γ rays that
improves approximately in proportion to have been scattered through angles greater
1/ E (Fig. 10-13). than approximately 45 degrees. However,
The energy resolution for gamma cameras because the spectrum for scattered γ rays is
is typically in the 9% to 11% range for 99mTc. blurred in the same way as the spectrum for
Figure 14-4 shows a typical gamma camera unscattered ones, the rejection efficiency for
spectrum for 99mTc with the pulse-height ana- this scattering angle is only approximately
lyzer (PHA) window set to 130 to 150╯keV. 50%; half of the events produce pulses above
This corresponds to approximately a 15% the threshold, and half below it. This percent-
energy window, which is a common setting for age would apply for 45-degree scattered
clinical studies. As illustrated by the figure, 140-keV γ rays and a 130-keV lower energy
most of the events in the photopeak are level, regardless of the energy resolution of
accepted within this window. According to the detector. Gamma rays scattered through
Equation 6-11, a low-energy threshold of greater angles are rejected more efficiently,
14  •  The Gamma Camera: Performance Characteristics 213

and those scattered through smaller angles cardiac studies. Dead time corrections can be
are rejected less efficiently. applied; however, these corrections generally
Two advantages are obtained with improved become increasingly inaccurate as counting
energy resolution. First, the photopeak losses increase.
becomes narrower, resulting in more efficient Because pulse pile-up can occur between
detection of unscattered photons within the any two events in the pulse-height spectrum,
chosen energy window. This increases the system counting losses are determined by
number of valid events recorded and improves total-spectrum counting rates. Most gamma
the statistical quality of the image. Second,  cameras behave as paralyzable systems. The
γ rays scattered through large angles are apparent dead time for a selected energy
rejected more efficiently, because their energy window depends on the window fraction, that
spread within the pulse-height spectrum is is, the fraction of the total spectrum counting
also smaller. Thus image contrast is improved. rate occurring within that window. The smaller
It also is true that γ rays scattered through the window fraction, the larger the apparent
smaller angles are detected somewhat more dead time. Thus the apparent dead time is
efficiently, because of the narrowing of their longer when a photopeak window is used than
distribution as well. However, the increased when a full-spectrum window is used. The
efficiency for recording photopeak events apparent dead time also is longer when 
more than offsets this effect, in terms of scattered radiation is present, because this
contrast-to-noise ratio (Chapter 15, Section also adds to the counting rate outside the 
D.2). Alternatively, one can take advantage of photopeak window (Fig. 14-5). Therefore,
the improved energy resolution to use a nar- when specifying gamma camera dead time, it
rower PHA window, trading back some of the is important to note the conditions of mea�
increased efficiency for recording photopeak surement. Dead time values as short as 1 to 2
events for improved rejection of small-angle µsec can be obtained in the absence of scatter-
scatter. Either way, improved energy resolu- ing material with a full-spectrum window;
tion results in better image quality. however, under clinically realistic conditions
(99mTc source in scattering material, 15% pho-
4.  Performance at High   topeak window), system dead times of 4 to 8
Counting Rates µsec are more typical. For a dead time of 5 µsec,
At high counting rates, there is increased like- counting losses are approximately 20% for a
lihood of recording two events at the same counting rate of 4 × 104 counts per second (cps).
time. The most troublesome effect is known as Dead time losses are not serious in most
pulse pile-up (Chapter 8, Section B.3). Pulse static imaging studies, but they can be impor-
pile-up has two undesirable effects on gamma tant in certain high-counting-rate applica-
camera performance: counting losses and tions (e.g., first-pass cardiac studies) in which
image distortion. counting rates as high as 105 cps may occur.
Counting losses cause inaccurate counting Pile-up rejection circuitry (see Chapter 8,
rates to be recorded at higher counting rates. Section B.3) is used to achieve higher usable
The inaccuracies are described by conven- counting rates in such situations. Another
tional dead time models (Chapter 11, Section approach for shortening camera dead time is
C) and may be significant in some high-count- by the use of analog buffers, or derandomiz-
rate quantitative studies, such as first-pass ers. These are electronic circuits that “hold” a
Observed counting rate

Source Source
Source behind in air No losses in air
Counts

10 cm water

Source behind 10 cm water

Energy True counting rate


FIGURE 14-5  Effect of scattered radiation on counting losses. Scattered radiation decreases the window fraction
recorded with a photopeak window (left), thus causing an apparent increase in dead time counting losses (right).
214 Physics in Nuclear Medicine

voltage level or pulse from one circuit compo- (see Chapter 13, Section B.2), two events
nent (e.g., an amplifier) until the next circuit detected simultaneously at different locations
in the pulse-processing sequence (e.g., the in the detector are recorded as a single event
PHA) is ready to receive it. with energy equal to the sum of the two
Similarly, in digital gamma cameras, data events, at a location somewhere between
can be buffered in memory until the computer them (Fig. 14-6). If both are valid photopeak
is ready to process them. Both these approaches events, their total energy exceeds the value
result in a decrease in the “apparent” dead that would be accepted by the PHA window
time of the camera by effectively changing the and both events are rejected, resulting in
arrival times of the pulses. This, however, counting losses. On the other hand, it is pos-
means that the simple dead time models and sible for two Compton-scattered γ rays to
corrections presented in Chapter 11, Section have a total energy that falls within the
C can no longer be used, and more complex selected energy window, so that two invalid
modeling of system dead time must be carried events are accepted as a single valid event.
out to produce accurate correction at high The visible result at very high counting rates
counting rates. is to add a diffuse background to the image,
It also is possible to physically shorten the as illustrated in Figure 14-7. Note as well the
dead time of a camera by shortening the image in the upper right-hand corner of this
charge integration time from the PM tubes figure, showing how contrast can be restored
and using electronic circuitry that returns the by shielding high-activity areas outside the
signal to baseline after the chosen integration imaging area of interest (e.g., with a thin
time.2 Clearly, this also decreases the amount sheet of lead).
of signal used for determining event location. Early pile-up rejection methods were based
For example, with a charge integration time on measuring the length of a pulse. If the
of 0.4 µsec, only 81% of the scintillation light pulse did not return close to baseline level
is collected, compared with 98% for a 1-µsec within the time expected given the decay time
integration time. This causes a degradation of of NaI(Tl), it was assumed that pile-up of 
intrinsic spatial resolution and energy resolu- two pulses had occurred and the event was
tion. Some gamma cameras have a variable rejected, resulting in the loss of both γ rays.
integration time, in which the charge integra- This improved image quality but resulted in
tion is automatically shortened as the count- an effective increase in system dead time,
ing rate increases. because many events were rejected at high
Other means for shortening dead time are counting rates.
to bypass altogether the pile-up rejection cir- Many gamma cameras now incorporate cir-
cuits and nonuniformity correction circuitry cuits that continuously monitor the decay of
(see discussion on pile-up correction later in a pulse and use a method based on pulse-tail
this section and on nonuniformity and its cor- extrapolation for pile-up correction. Consider
rection in Section B.3). The signal processing two γ-ray interactions that occur close together
that occurs in these circuits slows down the in time and create overlapping pulses. When
rate at which the camera can handle indi- the second γ ray arrives, the decay of the
vidual events, and bypassing them can pulse created by the first γ ray immediately
shorten system dead time from typical values
of 4 to 8 µsec down to 1 to 3 µsec. Some
cameras provide an optional “high count rate”
mode of operation in which some or all of
these corrections are turned off by software Source
control. This mode is intended specifically for Pile-up
applications requiring high counting rates, Source
such as first-pass cardiac studies. “Normal
mode,” in which all corrections are employed,
is used for routine imaging to obtain the
desired high-quality images. Obviously speci-
fications for gamma camera dead time should
indicate whether any circuits were bypassed
to achieve the reported value.
FIGURE 14-6  Images of two 99mTc point sources of rela-
The second undesirable effect of pulse tively high activities (~370 MBq each). Events appearing
pile-up is image distortion. Using standard in the band between the two point-source locations are
pulse-positioning logic for gamma cameras mispositioned events caused by pulse pile-up.
14  •  The Gamma Camera: Performance Characteristics 215

105

Observed counting rate (cps)


FIGURE 14-7  Demonstration of pile-up
effects on images of a brain phantom. 0.4 min
Times required to record 1.2 × 106 counts 0.4 min
104
are indicated. At very high counting 0.6 min
rates there is a noticeable loss of image
contrast, which can be restored by 0.9 min
shielding useless high-activity areas
from the detector (top right-hand image).
1.8 min

3.2 min
103
1.0 10 100
Activity in phantom (mCi)

deviates from the expected exponential decay of NaI(Tl). At the same time, this extrapo-
and the gamma camera signal is switched to lated tail is also sent to the second amplifier
a second amplifier circuit. Estimator circuitry circuit and subtracted from the second pulse.
in the first amplifier circuit completes the This removes the contribution of the pulse
signal from the first γ ray by extrapolating the generated by the first γ ray from that of the
remainder of the tail of the pulse with an second γ ray. This process is summarized
exponential function based on the decay time in Figure 14-8. The pulse-tail extrapolation

Without pulse-tail extrapolation:

P2 P1 + P2
P1

Amplifier

With pulse-tail extrapolation:

FIGURE 14-8  Illustration of pile-up correc- P2 P1 − Tail


P1
tion using pulse-tail extrapolation techniques. P1
See text for details. (Adapted from Lewellen
TK, Pollard KR, Bice AN, Zhu JB: A new clini-
cal scintillation camera with pulse tail extra�
polation electronics. IEEE Trans Nucl Sci
37:702-706, 1990.) Amplifier 1

Estimator
P2

Subtractor

Amplifier 2

P2 + P1 Tail
216 Physics in Nuclear Medicine

technique results in both events being displacement distance of a radiation source


retained and allows them to contribute to the across the face of the detector. For example,
image, providing they also meet the PHA when a source is moved from the edge of one
requirements. This method is very effective, of the PM tubes toward its center, the light
unless the two pulses occur nearly simultane- collection efficiency of that PM tube increases
ously (within a few tens of nanoseconds of more rapidly than the distance the source is
each other), in which case the extrapolation moved. This causes the image of a line source
is of limited accuracy. crossing in front of a PM tube to be bowed
With modern digital gamma cameras, it toward its center. The result is a characteristic
also is possible to use the spatial distribution pincushion distortion in areas of a gamma
of PM tube signals to further reduce pile-up. camera image lying directly in front of the PM
For pile-up events occurring at different loca- tubes, and barrel distortion between them.
tions in the detector crystal, two distinct clus- Differences in sensitivity among the PM tubes,
ters of PM tubes will produce signals. If the nonuniformities in optical light guides, as well
light distributions produced by the two events as PM tube or electronic malfunctions, also
on the PM tubes do not overlap, or only can cause nonlinearities.
slightly overlap, the events can be clearly Figure 14-10A, shows an image of a
separated and retained. straight-line “test pattern” recorded on a

B.  DETECTOR LIMITATIONS:


NONUNIFORMITY AND
NONLINEARITY

1.  Image Nonlinearity


A basic problem arising in the detector and
electronics is image nonlinearity. Straight-line
objects appear as curved-line images. An
inward “bowing” of line images is called pin-
cushion distortion; an outward bowing is “Pincushion” “Barrel”
called barrel distortion (Fig. 14-9). Non� distortion distortion
linearities result when the X- and Y-position FIGURE 14-9  Appearance of straight-line objects with
signals do not change linearly with “pincushion” and “barrel” distortions.

A B
FIGURE 14-10  A, Illustration of nonlinearities in images of a straight-line test pattern obtained with a gamma camera.
Image demonstrates subtle waviness in the lines. B, Flood-field image obtained by exposing the same camera to a
uniform radiation field. This is the image obtained in the absence of any corrections for nonuniformity. Notice that the
photomultiplier tube pattern can be seen. The gray levels in this image are confined to a narrow display window to
improve visualization of the artifacts. (Images courtesy Dr. Magnus Dahlbom, UCLA School of Medicine, Los Angeles,
CA.)
14  •  The Gamma Camera: Performance Characteristics 217

modern gamma camera to demonstrate the in areas of barrel distortion events are pushed
general appearance of nonlinearities. On outward from the center, causing an apparent
close inspection, some waviness of the lines is “cold spot.” Because of the characteristic pin-
apparent. On properly functioning cameras, cushion distortions occurring in front of PM
including the one illustrated, the nonlineari- tubes, it is common to see a pattern of hot
ties themselves (including the pincushion  spots at the locations of the PM tubes on an
distortions in front of PM tubes) are barely otherwise uniform gamma camera image.
perceptible and rarely interfere directly with Other causes of nonlinearities (e.g., PM tube
image interpretation; however, they can have  failure, crystal cracking, and collimator
significant effects on image nonuniformities, defects) also can result in nonuniformities.
as discussed in the following section. Another characteristic nonuniformity is a
bright ring around the edge of the image. This
2.  Image Nonuniformity artifact, called edge packing, results from a
A more noticeable problem is image non� somewhat greater light collection efficiency
uniformity. Exposing the detector crystal to a for events near the edge versus central regions
uniform flux of radiation produces a flood- of the detector crystal. This is the result of
field image with small but noticeable nonuni- internal reflections of scintillation light from
formities in intensity, even with a properly the sides of the detector crystal back into the
functioning camera. These variations may be PM tubes near the edge. Also, for events
equivalent to counting rate variations of ±10% occurring toward the center of the crystal,
or more. A flood-field image from a gamma there are always PM tubes on either side of
camera demonstrating image nonuniformity the event location, whereas at the edges of the
is shown in Figure 14-10B. Intrinsic flood- crystal there are PM tubes only to one side.
field images are acquired with the colli�mator Thus events at the very edges are not distrib-
removed, using a point source placed far uted uniformly across the edge, but are
enough from the surface of the gamma camera “pulled” toward the center, compounding the
to give uniform irradiation of the surface (dis- edge-packing artifact. The portion of the
tance equal to 4-5 times the camera diame- image demonstrating this artifact usually is
ter). Extrinsic flood-field images are acquired masked on the image display and therefore is
with the collimator in place using a disk or not a part of the useful field of view (UFOV ).
thin flood phantom that covers the area of the Typically, 5╯cm or more of the detector width
detector. 99mTc or 57Co are the two most is eliminated by the mask. When specifying
commonly used radionuclides for flood-field gamma camera detector dimensions, it is
measurements. important to distinguish between the physi-
There are two primary causes of gamma cal dimensions of the crystal and the dimen-
camera nonuniformities. The first is non- sions of the useful imaging area.
uniform detection efficiency arising from (1) Both nonuniformity and edge-packing 
small differences in the pulse-height spec- artifacts are related to the pattern of the 
trum for different PM tubes and (2) position- distribution of scintillation light falling on 
dependent collection efficiency of scintillation the PM tubes. For this reason, they also have
light, particularly for events located over the an energy-dependent component. When the
gaps and dead areas between the PM tubes gamma camera is used to image higher-
compared with events located directly over energy radionuclides, interactions, on average,
the center of a PM tube. The differences in occur deeper in the crystal, closer to the PM
PM tube response can be minimized by careful tubes. This produces a more narrow light
selection and tuning of all of the PM tubes of spread distribution on the PM tubes and gen-
a gamma camera; however, position-dependent erally results in a worsening of detector
effects on the pulse-height spectrum remain. nonuniformity.
If a fixed pulse-height window is used for all
output pulses, the result is an apparent dif- 3.  Nonuniformity Correction
ference in detection efficiency owing to differ- Techniques
ences in the “window fraction” for different All modern gamma cameras incorporate tech-
areas of the crystal (see Fig. 13-6, top). niques that attempt to correct the causes of
The second cause of nonuniformities is nonuniformity described in the preceding
image nonlinearities described in Section section. All of these techniques begin with
B.1. In areas of pincushion distortion events spatially varying energy corrections, normally
are crowded toward the center of the distor- derived from an intrinsic flood-field image.
tion, causing an apparent “hot spot,” whereas The flood-field image is divided into a matrix
218 Physics in Nuclear Medicine

of small, square elements, typically 128 × 128 counts recorded in each pixel are thrown out,
elements (or pixels). Using the PHA, the depending on the relative value for that pixel
channel number (pulse amplitude) of the photoÂ� in the energy-corrected flood-field image. 
peak in the pulse-height spectrum is deter- For example, if the value in the normalized
mined for each element. This information is intensity-correction matrix is 110, then 1 of
stored in a 128 × 128 look-up table and used every 11 counts is subtracted from the patient
to set regionally varying PHA windows for image at that location. This process is some-
subsequent studies on patients. For example, times called count skimming.
if a 20% window is chosen for a patient study, Most modern digital gamma cameras
and the center of the photopeak is found in replace the second step described in the pre-
PHA channel 100 in a particular pixel in  ceding paragraph with a correction for image
the flood-field image, then events at that  nonlinearity, which more directly attacks the
location having Z-signal amplitudes between major underlying cause of image nonunifor-
PHA channels 90 and 110 are accepted in  mity. For nonlinearity corrections, another
patient imaging studies. If the center of the flood-field image is obtained, this time with a
photo�peak is in channel 110 at another loca- sheet of lead having a uniformly spaced array
tion, events for which the Z-signal falls within of small holes (~1-mm diameter, ~â•›4-mm sepa-
the range of 99 to 121 are accepted at that ration) placed directly on the gamma camera
location. The position-dependent PHA window face (no collimator). The locations of the images
corrects for variations in the pulse-height  of these holes are compared with their known
spectrum across the face of the camera detec- locations in the lead sheet to derive a matrix
tor. It also provides a partial correction for of offsets, Δâ•›x and Δâ•›y, for each (X,Y ) location on
image nonuniformity. the detectors, which is stored as another
The second step in the nonuniformity cor- look-up table. When an event is detected, its X
rection is to account for the remaining regional and Y coordinates are computed using conven-
variations in image intensity, largely caused tional positional circuitry or algorithms. These
by detector nonlinearity. In one older method, values then are corrected using the positional
the correction is based directly on variations offsets for that location stored in the look-up
in intensity of the energy-corrected flood-field table. The offsets and the corresponding
image. The number of counts recorded within look-up table usually are measured and gener-
each pixel in that image is stored in a matrix ated at the factory prior to shipment.
and compared to the smallest number Figure 14-11 shows the same data as Figure
recorded in the pixel array. This is used to 14-10, after the corrections for nonuniformity
derive a matrix of normalized intensity values, and nonlinearity described in the preceding
which range from 100 for the “coldest” pixel paragraphs have been applied. Figure 14-12,
to higher values for other pixels. In subse- showing intensity profiles across the flood-
quent patient studies, a certain fraction of the field images in Figures 14-10 and 14-11,

A B
FIGURE 14-11  Straight-line test pattern (A) and uniform flood-field (B) images after nonuniformity corrections are
applied. Compare with Figure 14-10. (Images courtesy Dr. Magnus Dahlbom, UCLA School of Medicine, Los Angeles,
CA.)
14  •  The Gamma Camera: Performance Characteristics 219

1.2 1.2

Normalized pixel intensity 1 1

Normalized pixel intensity


0.8 0.8

0.6 0.6

0.4 0.4

0.2 0.2

0 0
0 50 100 150 200 250 0 50 100 150 200 250
Pixel Pixel
No correction Corrected
FIGURE 14-12  Profiles through the uniform flood-field images in Figures 14-10 and 14-11 showing relative uniformity
of flood-field image with and without nonuniformity correction. The standard deviation is improved from 3.4% to 1.9%
after correction.

clearly illustrates the improvements. The the tube output has changed by more than 1%
examples in these figures are for 99mTc. Note from the original reference value.
that different correction matrices must be In newer gamma cameras, the large
obtained for each radionuclide used, because number of PM tubes makes the manual
the effects corrected for generally vary with method impractical. Many digital gamma
γ-ray energy, for example, because of different cameras therefore contain tuning circuitry
average depths of interaction in the NaI(Tl) that allows the output of each individual PM
crystal. tube to be automatically adjusted to a set of
Improvements in camera uniformity also reference outputs. One automated approach
have contributed to improvements in intrinsic involves the use of light-emitting diodes
resolution. Earlier cameras used thicker light (LEDs) that are coupled to the neck of each
guides and large-diameter PM tubes, in part PM tube. These LEDs are pulsed to produce
to achieve satisfactory uniformity, at the a light signal on the photocathode of the PM
expense of somewhat degraded spatial resolu- tube that does not vary with time. The PM
tion. Because of effective uniformity correc- tube signals are then monitored and the pre-
tions, newer gamma cameras can use thinner amplifier adjusted electronically if the PM
light guides (or eliminate the light guide tube signal has drifted.
entirely) and smaller PM tubes, both of which A second approach uses two narrow energy
contribute to more accurate event localization windows, placed just above the photopeak
and improved intrinsic spatial resolution. position to minimize the influence of scatter
(Fig. 14-13). The count ratio between the two
4.  Gamma Camera Tuning energy windows during flood-field irradiation
The nonuniformity corrections described pre- by the radionuclide of interest is measured for
viously require that the gamma camera each PM tube. This ratio remains constant,
remain very stable over time. However, the unless the PM tube signal drifts over time. If
gain of PM tubes invariably changes as the the count ratio changes, the PM tube pream-
tubes age. The high-voltage supply and ampli- plifier is adjusted electronically to restore the
fier gain can also drift over time. A method to ratio to its original value.
“tune” the PM tubes to ensure consistent per- Some of these tuning methods also can be
formance over time is therefore necessary. adapted so that they are continuous, in the
On many older systems, the tuning is done sense that the camera is tuned dynamically
manually. One method involves irradiation of every few seconds during a patient study.
the gamma camera detector through a lead This can be used to adjust the energy
mask with holes centered over each of the PM windows in real time, compensating for any
tubes. The output of each PM tube is exam- drift that occurs during the course of a study.
ined and the preamplifier gain is adjusted if The major cause of drift on such short
220 Physics in Nuclear Medicine

500 Window 1
400
Window 2

Counts
300
200
100

0 50 100 150
Energy (keV)
FIGURE 14-13  The ratio of counts detected in two narrow energy windows can be used to determine whether a pho-
tomultiplier tube is drifting. The windows are defined on the high side of the photopeak to avoid any contribution from
scatter. The ratio is virtually independent of source distribution and the amount of scattering material present.

timescales usually is related to count-rate the collimator be designed carefully. Poor


effects. At high counting rates, a small base- design can result only in poorer overall per-
line shift can occur in the signal amplitudes formance. Design considerations for parallel-
owing to overlap of pulses, and continuous hole collimators are discussed in this section.
adjustment of the energy window minimizes Design characteristics for converging and
such effects, keeping the energy window cen- diverging collimators are similar to those of
tered over the photopeak irrespective of the the parallel-hole type. Design characteristics
counting rate. Continuous tuning also is of pinhole collimators are not discussed in
important in single photon emission com- detail here but are described in references 4
puted tomographic imaging (Chapter 17), in and 5. The analysis to be presented for
which rotation of the gamma camera through parallel-hole collimators is similar to that
the earth’s magnetic field can result in presented by Anger in reference 1, which may
changes of PM tube gain. A detailed discus- be consulted for a more detailed discussion.
sion of automatic tuning methods can be
found in reference 3. 2.  Septal Thickness
A primary consideration in collimator design
is to ensure that septal penetration by γ rays
C.  DESIGN AND PERFORMANCE crossing from one collimator hole into another
CHARACTERISTICS OF   is negligibly small. This is essential if an
PARALLEL-HOLE COLLIMATORS accurate γ-ray image is to be projected by the
collimator onto the camera detector. No thick-
ness of septal material is sufficient to stop all
1.  Basic Limitations in   γ rays, so the usual criteria is to accept some
Collimator Performance reasonably small level of septal penetration
The collimator is a “weak link” for the perfor- (e.g., ~5%).
mance of a gamma camera system, as indeed The required septal thickness can be deter-
it is in any nuclear medicine imaging system mined by analysis of Figure 14-14. The short-
employing the principles of absorptive colli- est path length for γ rays to travel from one
mation. Collimator efficiency, defined as the hole to the next is w. Septal thickness t is
fraction of γ rays striking the collimator that related to w, and to the length l and diameter
actually pass through it to project the γ-ray d of the collimator holes, by
image onto the detector, is typically only a few
percent or less. Collimator resolution, which t ≈ 2dw/(l − w) (14-1)
refers to the sharpness or detail of the γ-ray
image projected onto the detector, also is If septal penetration is to be less than 5%, the
rather poor, generally worse than the intrin- transmission factor for the thickness w must
sic resolution of the camera detector and be
electronics.
Because it is a limiting factor in camera
system performance, it is important that  e−µw  0.05 (14-2)
14  •  The Gamma Camera: Performance Characteristics 221

upper limit of approximately 150╯keV and


medium-energy collimators of approximately
Detector
400╯keV. High-energy col�limators are used for
imaging positron-emitting radionuclides at
511╯keV.
w Collimator
EXAMPLE 14-1
l septa Calculate the septal thickness required for
low-energy (150╯keV╯) and medium-energy
(400╯keV ) lead collimators having hole diam-
eters of 0.25╯cm and lengths of 2.5╯cm.
d t
Answer
FIGURE 14-14  Minimum path length w for a γ ray The linear attenuation coefficient of lead at
passing through the collimator septa from one hole to the 150╯keV is µl = 1.91╯cm2/g × 11.34╯g/cm3 =
next depends on length l and diameter d of the collimator 21.66╯cm¯1 and at 400╯keV is µl = 0.22╯cm2/g ×
holes and on septal thicknesses t.
11.34╯g/cm3 = 2.49╯cm¯1 (Appendix D). There-
fore from Equation 14-5 for the low-energy
collimator
where µ is the linear attenuation coefficient 6 × 0.25 / 21.66
of the septal material. Because e−3 is approxi- t
mately 0.05, this implies 2.5 − ( 3 / 21.66 )
 0.029 cm
µw 3 (14-3)
and for the medium-energy collimator
w  3/µ (14-4) 6 × 0.25 / 2.49
t
and thus 2.5 − ( 3 / 2.49 )
6d / µ  0.465 cm
t (14-5)
l − (3 / µ ) As shown by this example, thicknesses
It is desirable that septal thickness t be as needed for low-energy collimators are only a
small as possible so that the collimator septa few tenths of a millimeter, which is in the
obstruct the smallest possible area of detector range of lead “foil” thicknesses and approaches
surface and collimator efficiency is maxi- the limits of lead thicknesses that can be used
mized. This objective is realized by using a without loss of necessary mechanical strength.
material with a large value of µ for the colli- Indeed, low-energy collimators generally are
mator septa. Materials of high atomic number quite fragile, and their septa can be damaged
Z and high density ρ are preferred. Lead (Z = easily by mechanical abuse (such as dropping
82, ρ = 11.3╯g/cm3) is the material of choice for or stacking on sharp objects). Medium-energy
reasons of cost and availability; however, collimators require substantially greater
other materials, including tantalum (Z = 73, septal thicknesses, typically a few millimeters
ρ = 16.6╯g/cm3), tungsten (Z = 74, ρ = 19.3╯g/ of lead. Alternatively, medium-energy collima-
cm3), gold (Z = 79, ρ = 19.3╯g/cm3) and even tors can be made thicker (larger l in Equation
depleted uranium (Z = 92, ρ = 18.9╯g/cm3) 14-5).
have been employed in experimental Low-energy γ-ray emitters (e.g., 99mTc,
applications. 140╯keV) can be imaged using medium-energy
As discussed in Chapter 6, Section D.1, collimators. This is done, however, with an
attenuation coefficients of heavy elements unnecessary sacrifice of collimator efficiency
depend strongly on γ-ray energy in the nuclear because the collimator septa are unnecessarily
medicine energy range. Thus the required thick. (See Table 14-1 for comparative efficien-
septal thickness also depends strongly on  cies of low- and medium-energy collimators.)
the γ-ray energy for which the collimator is Low-energy collimators are used whenever
designed to be used. Commercially available possible to obtain maximum collimator effi-
collimators are categorized according to the ciency. When choosing a collimator, however,
maximum γ-ray energy for which their septal one must consider not only the energy of the γ
thickness is conÂ�sidered to be adequate.  rays to be imaged but also the energies of any
Low-energy collimators generally have an other γ rays emitted by the radionuclide of
222 Physics in Nuclear Medicine

interest or by other radionuclides that may be Collimator resolution


present as well (e.g., residual activity from
another study or radionuclide impurities).
Higher-energy γ rays may be recorded by Projected
radiation
Compton downscatter into a lower-energy profile FWHM
analyzer window. If the collimator septa are
too thin, the collimator may be virtually trans-
parent to higher-energy γ rays, causing a rela-
tively intense “foggy” background image to 
be superimposed on the desired image, with  l
a resulting loss of image contrast. Whether 
a low-energy collimator can be used when Multihole
collimator d
higher-energy γ rays are present depends on
the energy and intensity of those emissions
and requires experimental evaluation in spe- b
cific cases.
3.  Geometry of Collimator Holes
Point or
Collimator performance also is affected by the line source
geometry of the collimator holes, specifically,
FIGURE 14-15  Radiation profile (point- or line-spread
their shape, length, and diameter. The pre- function) for a parallel-hole collimator. The full width at
ferred hole shape, to maximize the exposed half maximum (FWHM) of the profile is used to charac-
area of detector surface for a given septal terize collimator resolution.
thickness, is round or hexagonal, with the
holes arranged in a close-packed hexagonal
array, or square holes in a square array. Tri-
angular holes also have been used. to septal penetration. For 2.5-cm thick low-
Collimator hole length and diameter affect energy collimators (150╯keV╛), the difference
strongly both collimator resolution and colli- between effective and actual length is approx-
mator efficiency. Collimator resolution Rcoll is imately 0.1╯cm, whereas for 2.5-cm thick
defined as the FWHM of the radiation profile medium-energy collimators (400 keVâ•›) it is
from a point or line source of radiation pro- app�roximately 0.8╯cm.
jected by the collimator onto the detector (Fig.
EXAMPLE 14-2
14-15). This profile is also called the point-
spread function (PSF) or line-spread function Calculate the resolution (FWHM) of the low-
(LSF). Collimator resolution Rcoll is given by* energy collimator described in Example 14-1,
at source depths b = 0 and b = 10╯cm, assum-
Rcoll ≈ d(leff + b) /leff (14-6) ing it has a septal thickness of 0.03╯cm.

where b is the distance from the radiation Answer


source to the collimator and d is the diameter The effective length of the collimator is
and leff = l − 2µ−1 the “effective length” of the
collimator holes. Here µ is the linear attenu- leff = 2.5 cm − (2 / 21.66) cm ≈ 2.4 cm
ation coefficient of the collimator material.
The effective length of the collimator holes is Thus for b = 0
somewhat less than their actual length owing
Rcoll ≈ 0.25 (2.4 + 0) / 2.4 cm

≈ 0.25 cm
*Some versions of Equation 14-6 include additional cor- and at b = 10 cm
rection terms involving the thickness of the detector
crystal, reflecting the fact that the image actually is Rcoll ≈ 0.25 (2.4 + 10) / 2.4 cm
formed at some depth within the detector crystal. Because
photons of different energies penetrate to different ≈ 1.3 cm
average depths within the crystal, the correction actually
is photon-energy dependent, a point not noted in some This example illustrates the strong depen-
texts. The correction is small and for simplicity is omitted
from Equation 14-6, as well as from Equations 14-10 and dence of collimator resolution on the distance
14-13 for the converging and diverging collimators pre- of the source from the collimator.
sented later in this chapter.
14  •  The Gamma Camera: Performance Characteristics 223

Collimator efficiency g, defined as the frac- camera systems also provide a selection of col-
tion of γ rays passing through the collimator limators with different combinations of resolu-
per γ ray emitted by the source is given by tion and efficiency. Those with good resolution
but poor efficiency generally are described as
g ≈ K 2 (d/leff )2 [ d2 / (d + t)2 ] (14-7) “high-resolution” collimators, whereas those
with the opposite chara�cteristics are described
where t is septal thickness and K is a constant as “high-sensitivity” collimators. Those with
that depends on hole shape (~0.24 for round characteristics intermediate to the extremes
holes in a hexagonal array, ~0.26 for hexago- are referred to as “general purpose,” “all
nal holes in a hexagonal array, ~0.28 for purpose,” or by other similar names.
square holes in a square array1). Equation Equation 14-6 indicates that collimator
14-7 applies to a source in air and assumes resolution becomes poorer as source-to- 
no attenuation of radiation by intervening collimator distance b increases. Thus struc-
body tissues. tures closest to the collimator are imaged
Several aspects of Equations 14-6 and 14-7 with sharpest detail. Figure 14-16 shows
should be noted. First, resolution improves as  graphically the relationship between colli-
the ratio of hole diameter to effective length  mator resolution and source-to-collimator
(d/leff) is made smaller. Long, narrow holes distance for three different collimators pro-
provide images with the best resolution; vided by one commercial manufacturer. Typi-
however, collimator efficiency decreases cally, collimator resolution deteriorates by a
approximately as the square of the ratio of factor of 2 at a distance of 4-6╯cm from the
hole diameter to length (d/leff)2. Thus an collimator.
approximate relationship between collimator On the other hand, according to Equation
efficiency, g, and spatial resolution, Rcoll, is 14-7, collimator efficiency for a source in air
is independent of source-to-collimator dis-
g ∝ ( Rcoll )2 (14-8) tance b. This rather surprising result is
obtained provided the counting rate for the
Therefore for a given septal thickness, colli- entire detector area is measured. The reason
mator resolution is improved only at the for this is illustrated by Figure 14-17. As the
expense of decreased collimator efficiency, source is moved farther away from the colli-
and vice versa. mator, the efficiency with which radiation is
transmitted through any one collimator hole
EXAMPLE 14-3 decreases in proportion to 1/b2 (inverse-square
Calculate the efficiency g of the collimator law), but the number of holes through which
described in Examples 14-1 and 14-2, assum- radiation can pass to reach the detector
ing it has hexagonal holes in a hexagonal increases in proportion to b2. The two effects
array. cancel each other, with the result that total
counting rate—and thus collimator efficiency—
Answer does not change with source-to-collimator dis-
For hexagonal holes in a hexagonal array,  tance. Another illustration of this effect is
K = 0.26. Thus, shown in Figure 14-18. As source-to-collima-
tor distance increases, the maximum height
g ≈ (0.26)2 (0.25 / 2.4)2 × [(0.25)2 / (0.25 + 0.03)2 ] of the PSF or LSF decreases, but the width
≈ (0.0676) × (0.0109) × (0.797) increases (and resolution becomes poorer), so
that the total area under the curve (total
≈ 5.85 × 10−4
detector counting rate) does not change.
(photons transmitted/photons emitted))
Invariance of collimator efficiency with
This example illustrates the relatively small source-to-collimator distance applies to point
fraction of emitted γ rays that are transmitted sources, line sources, and uniform sheet
by a typical gamma camera collimator. sources in air with parallel-hole collimators;
however, it applies only to uniform sheet
Equation 14-7 also demonstrates the effect sources with converging, diverging, or pinhole
of septal thickness on efficiency. Medium- collimators (Section D). When the source is
energy collimators have lower efficiencies embedded at different depths in the patient,
than low-energy collimators because of their attenuation effects also must be considered.
greater septal thicknesses. Septal penetration and scatter of photons
In addition to providing low- and medium- from the walls of the collimator holes also are
energy collimators, manufacturers of gamma not considered in the earlier analysis.
224 Physics in Nuclear Medicine

2.0

1.8

1.6
Collimator resolution FWHM (cm)

1.4
ity
1.2 itiv
ens
hs
1.0 Hig e
pos
al pur
ner
0.8 Ge

0.6 tion
solu
igh re
H
0.4

0.2

0.0
0 2 4 6 8 10 12 14 16
Source-to-collimator distance (cm)
FIGURE 14-16  Collimator resolution versus source-to-collimator distance for three different collimators. (Adapted
from Hine GJ, Paras D, Warr CP: Recent advances in gamma-camera imaging. Proc SPIE 152:123, 1978.)

Single-hole
efficiency  1/b2

FIGURE 14-17  Explanation for con-


Detector stant counting rate (collimator efficiency)
area Radiation versus source-to-collimator distance for a
exposed source point source in air and a parallel-hole
 b2 collimator. Efficiency for a single hole
decreases as 1/b2, but number of holes
b passing radiation (area of detector
exposed) increases as b2.

Collimator
Detector

Counting rate

FIGURE 14-18  Point-spread functions versus dis-


tance for a parallel-hole collimator. Area under
Source-to-collimator curve is proportional to collimator efficiency and
distance does not change with distance.

Distance
14  •  The Gamma Camera: Performance Characteristics 225

TABLE 14-1â•…
PERFORMANCE CHARACTERISTICS OF SOME TYPICAL COMMERCIALLY MANUFACTURED
PARALLEL-HOLE COLLIMATORS

Resolution Rcoll
Recommended Max. (FWHM at
Collimator Type Energy (keV) Efficiency, g 10╯cm)
Low-energy, high-resolution 150 1.84 × 10−4 7.4╯mm
Low-energy, general-purpose 150 2.68 × 10 −4
9.1╯mm
Low-energy, high-sensitivity 150 5.74 × 10 −4
13.2╯mm
Medium-energy, high-sensitivity 400 1.72 × 10−4 13.4╯mm
Adapted from Hine GJ, Erickson JJ: Advances in scintigraphic instruments. In Hine GJ, Sorenson JA (eds):
Instrumentation in Nuclear Medicine, Vol 2. New York, 1974, Academic Press.
FWHM, full width at half maximum.

Table 14-1 summarizes the physical con- differences between system resolutions for
struction and typical performance character- cameras having substantially different intrin-
istics of a number of collimators. Collimator sic resolutions (e.g., 4╯mm vs. 8╯mm), but the
resolution is the FWHM for a source at 10╯cm difference in system resolutions for cameras
from the face of the collimator. Collimator effi- having small differences in intrinsic resolu-
ciency g refers to the relative number of γ rays tions (e.g., 4╯mm vs. 5╯mm) is minor and not
transmitted by the collimator and reaching clinically significant. Small differences in
the detector per γ ray emitted by the source. intrinsic resolution may be apparent on bar-
Note that the approximate relationship pattern images or on images of very superfi-
between collimator efficiency and resolution cial structures in the patient, but they usually
given by Equation 14-8 is verified by these are not apparent on images of deeper-lying
data. Note also the relatively small values for structures.
collimator efficiency. System resolution also is degraded by scat-
tered radiation. This is discussed in Chapter
4.  System Resolution 15, Section C. The method for combining com-
The sharpness of images recorded with a ponent resolutions to determine system reso-
gamma camera is limited by several factors, lution also is discussed in Appendix G.
including intrinsic resolution, collimator reso-
lution, scattered radiation, and septal pene-
tration. In terms of the FWHM of a PSF or D.  PERFORMANCE CHARACTERISTICS
LSF, the most important factors are the OF CONVERGING, DIVERGING, AND
intrinsic resolution Rint of the detector and PINHOLE COLLIMATORS
electronics, and the collimator resolution Rcoll.
The combined effect of these two factors is to Figure 14-20 illustrates the important design
produce a system resolution Rsys that is some- parameters for converging, diverging, and
what worse than either one alone. System pinhole collimators. Equations for collimator
resolution Rsys (FWHM) is given by resolution, Rcoll, and efficiency, g, for these col-
limators are as follows:
Rsys = 2
Rint + Rcoll
2 (14-9)
Converging Collimator:
Because collimator resolution depends on
source-to-collimator distance, system resolu- Rcoll ≈ [ d(leff
′ + b) / leff
′ ][1 / cos θ]
tion also depends on this parameter. Figure (14-10)
× [1 − (leff
′ / 2) /( f + leff
′ )]
14-19 shows system resolution versus source-
to-collimator distance for a typical parallel-
hole collimator and different values of intrinsic g ≈ K 2 (d / leff
′ )2 [ d2 /(d + t)2 ][ f 2 /( f − b)2 ]
resolution. At a distance of 5-10╯cm (typical (14-11)
depth of organs inside the body), system
resolution is much poorer than intrinsic where
resolution and is determined primarily by 
collimator resolution. There are significant ′ ≈ (l − 2µ −1 ) / cos θ ≈ leff / cos θ   (14-12)
leff
226 Physics in Nuclear Medicine

1.8

m
1.6 8m
t

R in m
4m
1.4 t

R in
0
System resolution, FWHM (cm)

t

1.2 R in

FIGURE 14-19  System resolution versus


1.0 source-to-collimator distance for a typical
parallel-hole collimator and different
values of intrinsic resolution. At most
0.8 typical organ depths, system resolution 
is determined primarily by collimator
resolution.
0.6

0.4 Typical
organ
depths
0.2

0.0
0 2 4 6 8 10 12 14 16
Source-to-collimator distance (cm)

f
d d detector

α
l l l
d

b b
b
f 



Converging Diverging Pinhole


FIGURE 14-20  Parameters for collimator resolution Rcoll, and efficiency, g, for Equations 14-10 to 14-18.

Diverging Collimator: Pinhole Collimator:

Rcoll ≈ [ d(leff
′ + b) / leff
′ ][1 / cos θ][1 + (leff
′ / 2 f )] Rcoll ≈ deff ,R (l + b) /l (14-15)
(14-13)
g ≈ K 2 (d / leff
′ )2 [ d2 /(d + t)2 ][( f + l) /( f + l + b)]
(14-14) g ≈ deff ,g 2 cos3 θ/ (16b2 ) (14-16)
14  •  The Gamma Camera: Performance Characteristics 227

where image magnification factor is ×2, the equiva-


ln (2)  α lent FWHM in the imaged plane is 1╯cm.
deff ,R = d+ tan   These equations may be compared with
µ  2 (14-17) Equations 14-6 and 14-7 for the parallel-hole
and collimator. They are similar except for the
presence of additional terms involving colli-
deff ,g = d[ d + (2 /µ) tan(α / 2)] + [(2 /µ 2 ) tan 2 (α / 2)] mator focal lengths f and, for off-axis sources,
(14-18) the angle θ between the source, the focal point
(or pinhole), and the central axis of the colli-
l′eff is the effective collimator length, mator. The equations illustrate that for con-
accounting for septal penetration at different verging and diverging collimators, resolution
off-axis locations (see also Equation 14-6). For is best at the center (θ = 0, cos θ = 1).
the pinhole collimator, deff,R and deff,g are the The performance characteristics of differ-
“effective” pinhole diameters, for resolution ent types of collimators are compared in
and sensitivity, respectively. deff takes into Figure 14-21, which shows system resolution
account the penetration of gamma rays and efficiency versus distance, including
through the edges of the pinhole aperture, but effects of camera intrinsic resolution as well
still assumes parallel rays, normally incident as collimator magnification. Equations 14-10,
on the detector surface.4,5 These expressions 14-13, and 14-15 show that resolution always
for deff also assume that the pinhole aperture is best with the source as close as possible to
has a “knife-edge” geometry, as illustrated in the collimator. Changes in collimator effi-
Figure 14-20. ciency with distance depend on whether the
The equations for collimator resolution Rcoll radiation source is a point source or a uniform
refer to the equivalent FWHM of the PSF or sheet source.
LSF, corrected for magnification or minifica- For a point source (Fig. 14-21, right), col-
tion of the image by the collimator described limator efficiency increases with increasing
by Equations 13-3, 13-5, and 13-6. Thus, if source-to-collimator distance for the con�
the collimator projects a profile with a 2-cm verging collimator. Maximum efficiency is 
FWHM measured on the detector and the obtained at the collimator convergence point 

20 250

Diverging
16 200 Converging
Relative geometric efficiency
System resolution (mm)

Parallel-hole
12 150

Parallel-hole
8 100

Pinhole

4 Converging
50
Diverging
Pinhole

0 0
0 5 10 15 20 0 5 10 15 20
A B
Source-to-collimator distance (cm)
FIGURE 14-21  Performance characteristics ( A, system resolution; B, point-source geometric efficiency in air) versus
source-to-collimator distance for four different types of gamma camera collimators. (Adapted with permission from
Society of Nuclear Medicine from Moyer RA: A low-energy multihole converging collimator compared with a pinhole
collimator. J Nucl Med 15:59-64, 1974.)
228 Physics in Nuclear Medicine

(~35╯cm), where γ rays are transmitted distance; they also have a quite limited field
through all of the collimator holes, and then of view because of magnification effects at
decreases beyond that point. Point-source  typical imaging distances (Equation 13-3).
collimator efficiency decreases with distance  Generally they are used for imaging smaller
for the diverging and pinhole collimators, organs, such as the thyroid and heart, which
more severely for the latter. For an extended, can be positioned close to the collimator. They
large-area sheet source, sufficiently large to also are useful with high-energy γ-ray emit-
cover the entire field of view of the collimator, ters because they can be designed to reduce
efficiency does not change with source-to-  septal penetration problems.
collimator distance for all of these collima- Differences between the resolution and
tors. Again, for sources embedded within a field-of-view obtained at different source-to-
patient, attenuation effects also must be collimator distances with parallel-hole, con-
accounted for. verging, diverging, and pinhole collimators are
Figure 14-21 illustrates that the converg- further illustrated by Figure 14-22. The distor-
ing collimator offers the best combination of tions caused by changing magnification with
resolution and efficiency at typical imaging depth for different structures inside the body
distances (5 to 10╯cm); however, the field-of- sometimes make images obtained with the
view is also somewhat limited at these dis- converging, diverging, and pinhole collimators
tances (Equation 13-6 and Example 13-2), difficult to interpret (see Fig. 13-9).
and for this reason converging collimators are
most useful with cameras having relatively
large-area detectors. Diverging collimators E.  MEASUREMENTS OF GAMMA
offer a larger imaging area (Example 13-1) CAMERA PERFORMANCE
but at the cost of both resolution and effi-
ciency. Pinhole collimators offer very good It is important to define standardized experi-
resolution and reasonable efficiency at close mental protocols for measuring gamma
distances but lose efficiency very rapidly with camera performance that produce consistent

At
collimator
face

10 cm
distance

20 cm
distance

Diverging Parallel-hole Converging


FIGURE 14-22  Bar-pattern images demonstrating changing field size and resolution obtained versus distance for
three collimator types.
14  •  The Gamma Camera: Performance Characteristics 229

results, are easily reproducible, and that do (<10,000 cps for a small field-of-view gamma
not require specialized equipment. Such pro- camera) to avoid pile-up-related mis�
tocols can then be used in comparing one positioning. Two sets of images are taken,
gamma camera with another, in performing with a 90-degree rotation of the test pattern
acceptance testing on a newly installed between acquisitions so that both X and Y
gamma camera, and as part of a quality resolution are measured. Data are acquired
assurance program to ensure that the camera until the peak channel has at least 1000
is always performing to its specifications. counts. Images are acquired in a matrix with
The exact regulations for gamma camera pixel sizes less than 1 10 of the expected reso-
quality assurance and the guidelines for lution (typically <╛0.35╯mm). Profiles through
acceptance testing vary with locality. For the images of the line sources are taken at
example, in the United States, the Joint different locations across the gamma camera
Commission requires that instruments be face and fitted to a Gaussian function
tested prior to initial use and that the per� (Chapter 9, Section B.3). The FWHM (Fig.
formance of a gamma camera be tested at 14-15) and full width at tenth maximum
least once a year. Because of the rapidly (FWTM) of the profiles are measured in both
changing regulatory environment, and differ- X and Y directions. The reported measure-
ences between states and countries, a detailed ments usually are average measurements
review of the requirements of regulatory across the UFOV, and the average across the
agencies is beyond the scope of this book. In central field-of-view (CFOV ) that has linear
this section, we therefore briefly summarize dimensions scaled by 75% with respect to the
the more common measurements that are dimensions of the UFOV. Typical values of
performed to assess gamma camera perfor- intrinsic spatial resolution are 2.5 to 3.5╯mm.
mance (whether they be for acceptance
testing or for quality assurance). The proto- 2.  System Resolution
cols presented here are largely based on the This measurement is made with the collima-
recommendations of the National Electrical tor in place and should be repeated for each
Manufacturers Association.6 A typical quality collimator of interest. The source consists of
assurance program might involve daily mea- two 1-mm-diameter line sources, placed 5╯cm
sures of flood-field uniformity, weekly checks apart at a distance of 10╯cm from the front
of spatial resolution and spatial linearity, face of the collimator. The measurement also
and semiannual checks of other performance can be performed with the addition of a scat-
parameters. It is important that all measure- tering medium by placing 10╯cm of plastic
ments be taken under the same conditions between the sources and the collimator, and
(pulse-height window width, correction algo- 5╯cm of the same material behind the sources.
rithms, and correction circuitry on or off ) as Images are acquired (typically several million
are used for routine clinical studies. More events, at a rate of <â•›30,000 cps to avoid pile-
detailed information on performance mea- up) and profiles taken through the image of
surements, quality assurance, and accep- the line sources are fitted to Gaussian func-
tance testing can be found in references tions to determine FWHM and FWTM as
7 to 9. described for intrinsic resolution. The results
vary widely depending on the exact type of
1.  Intrinsic Resolution collimator used but are typically in the range
Intrinsic resolution is determined without a of 8 to 14╯mm for 99mTc.
collimator using a linearity test pattern, such
as the one shown in Figure 14-10 (left), placed 3.  Spatial Linearity
directly on the surface of the NaI(Tl) crystal This measurement uses the same slit pattern
housing. The width of the strips in the pattern (Fig. 14-10A) and conditions as for the intrin-
is approximately 1╯mm, which is significantly sic resolution measurement. Once again,
smaller than the resolution expected in the measurements are taken with two orienta-
measurement. A point source (usually 99mTc tions of the test pattern, rotated by 90 degrees,
or 57Co) is placed at a distance equal to five to provide linearity measurements in both X
times the UFOV from the gamma camera and Y directions. Two measurements can be
face. The UFOV corresponds to the field of made from the resulting images. The differ-
view of the gamma camera after masking off ential spatial linearity is the deviation of the
the portion of the camera face affected by measured distance di between two slits from
edge-packing effects. Data are acquired with the actual distance D between them calcu-
the system count rate below 30,000 cps lated for each row i in the image. The means
230 Physics in Nuclear Medicine

and the standard deviations are reported for across all rows and columns of the image. It
the X and Y directions across the UFOV and is defined as
the CFOV and are defined as:
( high − low )
Differential Uniformity (%) = 100 ×
n ( high + low )
∑ (d i − D)
(14-19) (14-22)
i =1
Mean =
n where “high” refers to the maximum count
n difference for any five consecutive pixels (row
∑ (d i − D)2   (14-20) or column) in the image and “low” refers to
Standard Deviation = i =1 the minimum count different for any five con-
n −1 secutive pixels. This usually is reported for
the UFOV.
In addition, the absolute spatial linearity is For convenience, uniformity measurements
defined as the maximum deviation of the often are made with the collimator in place
location of the slits from their true location. (extrinsic uniformity). A thin flood-field source
Once again this is assessed for the UFOV of 99mTc or a disk source of 57Co that covers the
and the CFOV. It is not easy to detect small active area of the gamma camera is placed on
nonlinearities using these techniques, and top of the collimator to provide uniform irra-
tests of uniformity (discussed in the next diation. This protocol is more practical for
section) usually are better at revealing the routine quality assurance because the mea-
effects of small nonlinearities. surement can be done without removing the
collimator. Extrinsic uniformity measure-
4.  Uniformity ments also have the advantage that they
Intrinsic uniformity is determined from flood- reveal any defects or problems caused by the
field images acquired without a collimator. A collimator itself.
99m
Tc source is placed at a distance of approxi-
mately 5 × the UFOV from the front face of 5.  Counting Rate Performance
the gamma camera. The source activity is As described in Section A.4, most gamma
such that the counting rate on the gamma cameras behave as paralyzable counting
camera is less than approximately 30,000 cps. systems with the observed count rate described
Flood-field images are acquired so that there as a function of the true count rate by Equa-
are a minimum of 4000 counts in each pixel tion 11-18. The basis for measurement of the
of the image and then smoothed with a 9-point dead time, τ, is the two-source method
(3 × 3) smoothing filter with the following described in Chapter 11, Section C.4. Two
99m
weightings: Tc sources are placed approximately 1.5╯m
away from the camera face. The total activity
1 2 1 should be sufficient to cause approximately a
2 4 2 20% loss in the observed counting rate rela-
tive to the true counting rate. Counting rates
1 2 1 then are measured with both sources present,
and then with each individual source present.
Integral uniformity is based on the Care must be taken that all measurements
maximum and minimum pixel counts in the are performed with exactly the same source
image and is defined as geometry, that pile-up rejection electronics or
any other high counting rate correction cir-
Integral Uniformity (%) cuitry is turned on, and that source decay is
negligible (<1%) during the course of the mea-
max. pixel count − min. pixel count
= 100 × surement. The dead time can then be calcu-
max. pixel count + min. pixel count lated from Equation 11-25. The observed
(14-21) count rate at which a 20% counting rate loss
occurs, R20%, is also often quoted, and this can
This is calculated for the UFOV and CFOV. be computed from Equation 11-18 using the
Integral uniformity values are typically 2%  fact that Ro = 0.8Rt as
to 4%.
Differential uniformity is based on the 0. 8
R20% = − ln(0.8) (14-23)
change in counts of five consecutive pixels τ
14  •  The Gamma Camera: Performance Characteristics 231

6.  Energy Resolution Sensitivity (cps/Bq)


Energy resolution is measured with a flood counts in ROI − background counts in ROI
illumination of the gamma camera face, =
time(sec) × source activity (Bq)
without a collimator, using a 99mTc source sus-
(14-24)
pended 5 × UFOV above the camera face. The
resulting pulse-height spectrum is analyzed
to determine the FWHM of the 99mTc photo- A general-purpose collimator typically has a
peak. It usually is reported in keV or con- sensitivity on the order of 2 to 3 × 10−4 cps/Bq
verted to a percent energy resolution based or 0.02% to 0.03%.
on the energy of the photopeak (see Equation
10-3). Typical values are in the range of 8%
to 11% for 99mTc. REFERENCES
1. Anger HO: Radioisotope cameras. In Hine GJ, editor:
7.  System Sensitivity Instrumentation in Nuclear Medicine, Vol 1. New York,
1967, Academic Press, pp 485-552.
System sensitivity needs to be measured sep- 2. Muehllehner G, Karp JS: A positron camera using
arately for each collimator. In general, the position-sensitive detectors: PENN-PET. J Nucl Med
sensitivity of low-energy collimators is mea- 27:90-98, 1986.
sured with 99mTc (Eγ = 140╯keV ), that of 3. Graham LS: Automatic tuning of scintillation cameras:
A review. J Nucl Med Tech 14:105-110, 1986.
medium-energy colli�mators is measured with 4. Accorsi R, Metzler SD: Analytic determination of the
111
In (Eγ = 172, 247╯keV╯), and 131I (Eγ = resolution-equivalent effective diameter of a pinhole
364╯keV ) is used for high-energy collimators. collimator. IEEE Trans Med Imag 23:750-763, 2004.
A solution of the radionuclide (known total 5. Smith MF, Jaszczak RJ: The effect of gamma ray pen-
activity) is placed in a 10-cm diameter dish to etration on angle-dependent sensitivity for pinhole
collimation in nuclear medicine. Med Phys 24:1701-
a depth of 2 to 3╯mm. The shallow depth mini- 1709, 1997.
mizes self-absorption by the source. The 6. Performance measurements of scintillation cameras. 
source is placed 10╯cm from the front face of Standards Publication No. NU-1-2007. Washington,
the collimator and an image is acquired. The DC, 2007, National Electrical Manufacturers
Association.
sensitivity is calculated by drawing a circular 7. Simmons GH, editor: The Scintillation Camera, New
region of interest around the image of the York, 1988, Society of Nuclear Medicine.
dish and integrating all the counts in that 8. Graham LS: Scintillation camera imaging perfor-
region. A second image is recorded for an mance and quality control. In Henkin RE, Boles MA,
equal imaging time with the source removed Karesh SM, et al, editors: Nuclear Medicine, St. Louis,
1996, Mosby, pp 125-146.
to provide a measure of the background. The 9. Murphy PH: Acceptance testing and quality control of
same region of interest is applied to this gamma cameras, including SPECT. J Nucl Med
image. The sensitivity is given by 28:1221-1227, 1987.
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chapter
15 
Image Quality in
Nuclear Medicine
Image quality refers to the faithfulness with usually involves a tradeoff of decreased colli-
which an image represents the imaged object. mator efficiency (see Chapter 14, Section C)
The quality of nuclear medicine images is and, hence, decreased counting rates and
limited by several factors. Some of these increased image statistical noise.
factors, relating to performance limitations of The second method for characterizing or
the gamma camera, already have been dis- evaluating image quality is by means of
cussed in Chapter 14. In this chapter, we human observer performance studies using
discuss the essential elements of image images obtained with different imaging
quality in nuclear medicine and how it is systems or under different imaging condi-
measured and characterized. Because of its tions. Although observer performance can be
predominant role in nuclear medicine, the characterized objectively, and certainly is
discussion focuses on planar imaging with the related to the physical measures of image
gamma camera; however, the general con- quality described earlier, the relationships
cepts are applicable as well to the tomographic are not well established because of the com-
imaging techniques that are discussed in plexity of the human visual system and other
Chapters 17 to 19. complicating factors, such as observer experi-
ence. Hence, the two methods, though related,
are somewhat independent.
A related approach, known as computer
A.  BASIC METHODS FOR observer performance studies, uses a mathe-
CHARACTERIZING AND EVALUATING matical model that under appropriate condi-
IMAGE QUALITY tions predicts the per�formance of a human
observer and can be used as a surrogate for
There are two basic methods for characteriz- actual human observer studies. Because
ing or evaluating image quality. The first is human observer studies require large numbers
by means of physical characteristics that can of images and therefore are very time consum-
be quantitatively measured or calculated for ing, computer observers often are more practi-
the image or imaging system. Three such cal. Details regarding computer observer
characteristics that are used for nuclear med- models are beyond the scope of this text and
icine image quality are (1) spatial resolution the interested reader is referred to reference
(detail or sharpness), (2) contrast (difference 1 for further information.
in image density or intensity between areas
of the imaged object containing different con-
centrations of radioactivity), and (3) noise B.  SPATIAL RESOLUTION
(statistical noise caused by random fluctua-
tions in radioactive decay, or structured noise,
e.g., resulting from instrument artifacts). 1.  Factors Affecting Spatial Resolution
Although they describe three different aspects Spatial resolution refers to the sharpness or
of image quality, these three factors cannot be detail of the image, or to the ability of the
treated as completely independent parame- imaging instrument to provide such sharp-
ters because improvements in one of them ness or detail. The sample images presented
frequently are obtained at the expense or in Chapters 13 and 14 already have demon-
deterioration of one or more of the others.  strated that nuclear medicine images have
For example, improved collimator resolution somewhat limited spatial resolution, at least
233
234 Physics in Nuclear Medicine

in comparison with photographic or radio- lengthy imaging times required in nuclear


graphic images. A number of factors contrib- medicine and the relatively great excursions
ute to the lack of sharpness in these images. in distance (2-3╯cm) that are possible in these
Collimator resolution is perhaps the prin- instances. Gated-imaging techniques (see
cipal limiting factor when absorptive collima- Chapter 20, Section A.4) have been employed
tors are used for spatial localization (Chapter to minimize motion blurring, especially in
14, Section C). Because collimator hole diam- cardiac studies. Breath-holding also has been
eters must be relatively large (to obtain rea- used to minimize blurring caused by respira-
sonable collimator efficiency), there is blurring tory motion.
of the image by an amount at least as great Nuclear medicine imaging systems acquire
as the hole diameters (Equation 14-6). Colli- data on a discrete matrix of locations, or
mator resolution also depends on source-to- pixels, which leads to pixelation effects in the
detector distance (Figs. 14-16 through 14-22). image. As discussed in Chapter 20, the size of
Note that collimator resolution is not a  the discrete pixels sets a limit on the spatial
factor in positron emission tomography (PET) resolution of the image. In general, it is desir-
imaging, which uses annihilation coincidence able to have at least two pixels per full width
detection for spatial localization (Chapter 18, at half maximum (FWHM) of system resolu-
Section A). tion to avoid creating distracting pixelation
A second factor is intrinsic resolution of the effects and possible loss of image detail.
imaging detector. With the gamma camera,
this limitation arises primarily because of
statistical variations in the distribution of 2.  Methods for Evaluating Spatial
light photons among the photomultiplier Resolution
tubes (Chapter 14, Section A.1). Intrinsic Spatial resolution may be evaluated by sub-
resolution is a function of γ-ray energy with jective or objective means. A subjective evalu-
the gamma camera, becoming poorer with ation can be obtained by visual inspection of
decreasing γ-ray energy (Fig. 14-2). For images of organ phantoms that are meant 
imaging devices with discrete detector ele- to simulate clinical images (e.g., the brain
ments, such as many PET systems (see phantom in Fig. 15-1). Although they attempt
Chapter 18, Section A.3), the size of the indi- to project “what the physician wants to see,”
vidual detector elements largely determines organ phantoms are not useful for quantita-
the intrinsic resolution of the device. tive comparisons of resolution between differ-
Image sharpness also can be affected by ent imaging systems or techniques. Also,
patient motion. Figure 15-1 shows images of because of the subjective nature of the evalu-
a brain phantom obtained with and without ation, different observers might give differ-
motion. Respiratory and cardiac motion can ent interpretations of comparative image
be especially troublesome because of the quality.

Stationary With motion


FIGURE 15-1  Images of a brain phantom obtained with phantom stationary (left) and with random translations
(several mm) and rotations (several degrees) (right) during the imaging procedure, demonstrating motion-blurring
effects. (Adapted from Fulton R et╯al: Accuracy of motion correction methods for PET brain imaging. 2004 IEEE Nuclear
Science Symposium Conference Record, 4226-4230.)
15  •  Image Quality in Nuclear Medicine 235

A phantom that can be used for more objec- A still more quantitative approach to eval-
tive testing of spatial resolution is shown in uating spatial resolution is by means of the
Figure 15-2. Bar phantoms are constructed of point-spread function (PSF) or line-spread
lead or tungsten strips, generally encased in  function (LSF). General methods for record-
a plastic holder. Strips having widths equal  ing these functions were described in Chapter
to the spaces between them are used. For 14, Section E.2. Examples of LSFs are shown
example, a “5-mm bar pattern” consists of in Figure 17-8 for a single-photon emission
5-mm-wide strips separated edge to edge by computed tomography (SPECT) camera and
5-mm spaces. The four-quadrant bar phantom in Figure 18-5 for a PET system. Although the
shown in Figure 15-2 has four different strip complete profile is needed to fully character-
widths and spacings. To evaluate the intrinsic ize spatial resolution, a partial specification
resolution of a gamma camera, the bar is provided by its FWHM (Fig. 14-15). The
phantom is placed directly on the uncollimated FWHM is not a complete specification because
detector and irradiated with a uniform radia- PSFs or LSFs of different shapes can have the
tion field, typically a point source of radio� same FWHM. (Compare, for example, the dif-
activity at several meters distance from the ferent shapes in Figs. 18-5 and 18-7). However,
detector. To evaluate the resolution with a col- the FWHM is useful for general comparisons
limator, the phantom is placed directly on the of imaging devices and techniques. Roughly
collimated detector and irradiated with a point speaking, the FWHM of the PSF or LSF of an
source at several meters distance, or with a imaging instrument is approximately 1.4-2
sheet source of radioactivity placed directly times the width of the smallest resolvable 
behind the bar phantom. Spatial resolution is bar pattern (Fig. 15-3). Thus an instrument
expressed in terms of the smallest bar pattern having an FWHM of 1╯cm should be able to
visible on the image. There is a certain amount resolve 5- to 7-mm bar patterns.
of subjectivity to the eva�luation, but not so In most cases, multiple factors contribute
much as with organ phantoms. to spatial resolution and image blurring. The
To properly evaluate spatial resolution method for combining FWHMs for intrinsic
with bar phantoms, one must ensure that the and collimator resolutions to obtain the
thickness of lead strips is sufficient so that overall system FWHM is discussed in Chapter
they are virtually opaque to the γ rays being 14 , Section C.4 and in Appendix G. In general,
imaged. Otherwise, poor visualization may  if a system has n factors or components that
be due to poor contrast of the test image each contribute independently to blurring,
rather than poor spatial resolution of the individually characterized by FWHM1,
imaging device. For 99mTc (140╯keV╛) and FWHM2, . . ., FWHMn, the FWHM for the
similar low-energy γ-ray emitters, tenth-value system is given by
thicknesses in lead are approximately 1╯mm
or less, whereas for 131I (364╯keV╛), annihila- FWHMsys
tion photons (511╯keV), and so on, they are on ≈ FWHM12 + FWHM22 + … + FWHM2n
the order of 1╯cm (see Table 6-4). Most com-
(15-1)
mercially available bar phantoms are designed
for 99mTc and are not suitable for use with This equation provides an exact result when
higher-energy γ-ray emitters. all of the components have gaussian-shaped

FIGURE 15-2  Design (left) and gamma camera image (right) of a four-quadrant bar phantom used for evaluation of
spatial resolution.
236 Physics in Nuclear Medicine

Radiation intensity
at detector

Total counting
rate
Radiation intensity
or counting rate

Individual bar
pattern counting
rates

Distance
FIGURE 15-3  Counting-rate profiles obtained on a bar pattern phantom with an imaging system having FWHM reso-
lution approximately 1.6 times the width of individual bars and spaces.

blurring functions, but it is an approximation varies with distance (cycles per centimeter or
when nongaussian shapes are involved. Note cycles per millimeter). This is called the
that if the FWHM for any one factor is signifi- spatial frequency of the test pattern, custom-
cantly larger than the others, it becomes the arily symbolized by k.* The modulation of the
dominating factor for system FWHM. Thus, test pattern, which is a measure of its con-
for example, if FWHM1 >> FWHM2, it makes trast, is defined by
little sense to expend substantial effort toward
improving FWHM2. Min = ( Imax − Imin ) / ( Imax + Imin ) (15-2)
The most detailed specification of spatial
resolution is provided by the modulation where Imax and Imin are the maximum and
transfer function (MTF). The MTF is the minimum radiation intensities emitted by the
imaging analog of the frequency response test pattern. Min is the input modulation for
curve used for evaluating audio equipment. the test pattern and ranges from zero (Imax =
In audio equipment evaluations, pure tones of Imin, no contrast) to unity (Imin = 0, maximum
various frequencies are fed to the input of  contrast). Similarly, output modulation Mout is
the amplifier or other component to be tested, defined in terms of the modulation of output
and the relative amplitude of the output image (e.g., image density or counting rate
signal is recorded. A graph of relative output recorded from the test pattern).
amplitude versus frequency is the frequency
response curve for that component (Fig. 15-4). Mout = (Omax − Omin ) / (Omax + Omin )   (15-3)
A system with a “flat” curve from lowest to
highest frequencies provides the most faithful
sound reproduction.
By analogy, one could evaluate the fidelity *Technically speaking, the notation k is used in physics
of an imaging system by replacing the audio to denote “cycles per radian,” and the notation − k or “k-
bar” is used to denote “cycles per distance.” Mathemati-
tone with a “sine-wave” distribution of activ- − = k/2π, because there are 2π radians per cycle.
cally, k
ity (Fig. 15-5). Instead of varying in time For notational simplicity, we use k for cycles per distance
(cycles per second), the activity distribution in this text.

Input signals Output signals Audio frequency


response curve
Frequency
Medium

Low
Relative output

Audio
Medium
Low

High

component

High
Frequency
FIGURE 15-4  Basic principles for generating frequency response curves for an audio system.
15  •  Image Quality in Nuclear Medicine 237

Input Output

Radiation intensity, I
Imax

Counting rate or
image density
Imaging Omax
system

Omin
Imin
1/ k

Distance Distance

ImaxImin OmaxOmin
M in  M out 
ImaxImin OmaxOmin

FIGURE 15-5  Basic principles for determining the modulation transfer function of an imaging instrument. Input
contrast is measured in terms of object radioactivity or emission rate. Output contrast is measured in terms of count-
ing rate, image intensity, etc. Spatial frequency is k.

The ratio of output to input modulation is the but sometimes also for larger objects because
MTF for the spatial frequency k of the test of the importance of edges and sharp borders
pattern, for detection of low-contrast objects and for
accurate assessment of their size and shape.
MTF(k) = Mout (k) /Min (k) (15-4) Figure 15-6 illustrates some typical MTF
curves for a gamma camera collimator. The
The usefulness of the MTF (or frequency MTF curves have values near unity for low
response curve) derives from the fact that any frequencies but decrease rapidly to zero 
image (or audio signal) can be described as a at higher frequencies. Thus the images of a
summation of sine waves of different frequen- radionuclide distribution obtained with this
cies. For audio signals, the sound “pitch” is collimator show the coarser details of the dis-
determined by its basic sine-wave frequency, tribution faithfully but not the fine details.
whereas superimposed higher frequencies Edge sharpness, which is a function of the
create the unique sound characteristics of the high-frequency MTF values, also is degraded.
instrument or human voice producing it. An This type of performance is characteristic of
audio system with a flat frequency response virtually all nuclear medicine imaging systems.
curve over a wide frequency range generates Note also that the MTF curve at higher fre-
an output that matches faithfully the sound quencies decreases more rapidly with increas-
of the instrument or voice producing it. Inex- ing source-to-collimator distance.
pensive audio systems generally reproduce The MTF curve characterizes completely
the midrange audio frequencies accurately and in a quantitative way the spatial resolu-
but have poor response at low and high fre- tion of an imaging system for both coarse and
quencies. Thus they have poor bass response fine details. Images of bar patterns and similar
(low frequencies) and poor sound “quality” test objects are quantitative only for specify-
(high frequencies). ing the limiting resolution of the imaging
An imaging system with a flat MTF curve system, for example, the minimum resolvable
having a value near unity produces an image bar pattern spacing. Bar-pattern images and
that is a faithful reproduction of the imaged MTF curves can be related semiquantitatively
object. Good low-frequency response is needed by noting that the spatial frequency of a bar
to outline the coarse details of the image and pattern having bar widths and spaces of x cm
is important for the presentation and detec- is one cycle per 2x cm. Thus a “5-mm bar
tion of relatively large but low-contrast pattern” has a basic spatial frequency of one
lesions. Good high-frequency response is nec- cycle per centimeter (one bar and one space
essary to portray fine details and sharp edges. per centimeter). Roughly speaking, bar pat-
This is of obvious importance for small objects terns are no longer visible when the MTF for
238 Physics in Nuclear Medicine

1.0
Source-to-collimator
distance
0.8

2.5 cm
0.6
MTF

5 cm
0.4

0.2
10 cm

0
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
Spatial frequency (cm1)
FIGURE 15-6  Modulation transfer function curves for a typical parallel-hole collimator for different source-to-colli-
mator distances. (Data from Ehrhardt JC, Oberly LW, Cuevas JM: Imaging Ability of Collimators in Nuclear Medicine.
Publication No. [FDA] 79-8077. Rockville, MD, U.S. Department of Health, Education, and Welfare, 1978.)

their basic spatial frequency drops below a tomographic instruments in all three spatial
value of approximately 0.1. MTF curves thus directions. Note that in all cases the diameter
can be used to estimate the minimum resolv- or width of the source should be much smaller
able bar pattern for an imaging system. than resolution capability of the imaging
In practice, MTFs are not determined using device (d  FWHM/4). Additional discussions
sinusoidal activity distributions, as illus- about the measurement of MTFs and their
trated in Figure 15-5, which would be difficult properties can be found in references 2 and 3.
to construct. Instead, they are obtained by Another useful feature of MTFs is that
mathematical analysis of the LSF or PSF. they can be determined for different compo-
Specifically, the MTF of an imaging system nents of an imaging system and then com-
can be derived from the Fourier transform bined to determine the system MTF. This
(FT) of the LSF or PSF.* The one-dimensional feature allows one to predict the effects of the
(1-D) FT of the LSF is the MTF of the system individual components of the system on the
measured in the direction of the profile, that MTF of the total system. For example, one
is, perpendicular to the line source. Similarly, can obtain the MTF for the intrinsic resolu-
the 1-D FT of a profile recorded through the tion of the Anger camera detector, MTFint(k),
center of the PSF gives the MTF of the system and another for the collimator, MTFcoll(k). The
in the direction of the profile. Alternatively, a system MTF then is obtained by point-by-
2-D FT of the 2-D PSF provides a 2-D MTF point multiplication of the intrinsic and col-
that can be used to determine the frequency limator MTFs at each value of k:
response of the system at any angle relative
to the imaging detector. This sometimes is MTFsys (k) = MTFint (k) × MTFcoll (k)   (15-5)
useful for imaging systems that have asym-
metrical spatial resolution characteristics, In general, the MTF of a system is the product
such as detector arrays with rectangular ele- of the MTFs of its components.
ments. Some PET detector arrays have this If two systems have MTF curves of the
property (see Chapter 18, Section B). same general shape, one can predict confi-
It also is possible to obtain a 3-D represen- dently that the system with the higher MTF
tation of the MTF from a complete 3-D data values will have superior spatial resolution;
set for the PSF. This is potentially useful for however, the situation is more complicated
characterizing the spatial resolution of when comparing two systems having MTF
curves of different shapes. For example,
Figure 15-7 shows MTF curves for two colli-
*More specifically, the MTF is the modulus, or amplitude,
mators, one of which would be better for visu-
of the FT, the latter generally being a complex number. alizing large low-contrast structures (low
See Appendix F for a more detailed discussion of FTs. frequencies), the other for fine details (high
15  •  Image Quality in Nuclear Medicine 239

1.0

0.8

MTF 0.6

0.4

0.2

0
0.2 0.4 0.6 0.8 1.0
Spatial frequency (cm1)
FIGURE 15-7  Modulation transfer function (MTF) curves for two different collimators. One has better low-frequency
resolution for coarse details (blue line), whereas the other is better for fine details (orange line). (Data from Ehrhardt
JC, Oberly LW, Cuevas JM: Imaging ability of collimators in nuclear medicine. Rockville, MD, U.S. Department of
Health, Education, and Welfare, Publ. No. [FDA] 79-8077, 1978, p 20.)

frequencies). To gain an impression of com- interest, such as a lesion, relative to the signal
parative image quality in this situation, one level in surrounding parts of the image. Thus
would probably have to evaluate organ phan- if Ro is the counting rate over normal tissue
toms or actual patient images obtained with and R is the counting rate over a lesion, the
these collimators. contrast of the lesion is defined as
R − Ro
C = 
C.  CONTRAST Ro
(15-6)
∆R
Image contrast refers to differences in inten- =
Ro
sity in parts of the image corresponding to
different levels of radioactive uptake in the where Δâ•›Râ•› is the change in counting rate over
patient. In nuclear medicine, a major compo- the lesion relative to the surrounding back-
nent of image contrast is determined by the ground.* Contrast sometimes is expressed as
properties of the radiopharmaceutical. In a percentage, for example, C = 0.1 = “10%
general, it is desirable to use an agent having contrast.”
the highest lesion-to-background uptake or Perhaps the major factor affecting contrast
concentration ratio. Some aspects of radio- is added background counting rates that are
pharmaceutical design that affect this issue superimposed more or less uniformly over the
were discussed in Chapter 5, Section F. Phys- activity distribution of interest. For example,
ical factors involved in image formation also suppose that in the absence of background
can affect contrast. In general, factors that counts a certain object (e.g., a lesion) has
affect contrast in nuclear medicine also affect
the statistical noise levels in the image. More
specifically, they affect the contrast-to-noise *This equation is related to, but not the same as, the
ratio (CNR), which is discussed in detail in equations for modulation given in Equations 15-2 and
the next section. Here we focus only on some 15-3. The definition used here has the disadvantage that
it does not apply when Ro = 0. However, this situation
factors that affect contrast. rarely, if ever, applies in nuclear medicine, and the defini-
A general definition of contrast is that it is tion in Equation 15-6 is more straightforward for the
the ratio of signal change of an object of analysis of contrast and CNR.
240 Physics in Nuclear Medicine

 1 
C′ = 0.2 ×  
R  Rb  1 + ( R b / R )
o 
Counting rate

 1 
R = 0 .2 × 
 1 + 1 
Ro  Rb
1
Rb = 0.2 × = 0.1 (10%)
Ro 2

A Distance B Distance Thus contrast is reduced by 50% by the added


FIGURE 15-8  Effect on image contrast of adding a back- background.
ground counting rate Rb.
Example 15-1 illustrates that added back-
ground can reduce image contrast substan-
tially. It should be noted again that background
intrinsic contrast as defined by Equation counting rates also add to the noise levels in
15-6. Suppose then that a uniform back- the image, just as they add to the noise levels
ground counting rate Rb is superimposed on in counting measurements (see Chapter 9,
the image (Fig. 15-8). Then the lesion contrast Section D.4). This is discussed in more detail
becomes in Section D.
Background counting rates can arise from
( R + Rb ) − ( Ro + Rb )
C′ = a number of sources. Septal penetration and
Ro + Rb scattered radiation are two examples. Another
∆R would be inadequately shielded radiation
= sources elsewhere in the imaging environ-
Ro + Rb
ment. Septal penetration is avoided by using
∆R  1  (15-7) a collimator that is appropriately designed for
= ×
Ro  1 + ( Rb / Ro )  the radionuclide of interest (Chapter 14,
1 Section C.2). Scattered radiation can be mini-
 
= C ×   mized by pulse-height analysis; however,
 1 + ( R /bR ) o sodium iodide [NaI(Tl)] systems cannot reject
all scatter, and rejection becomes especially
Comparing the last line of Equation 15-7 with difficult for γ-ray energies below approxi-
Equation 15-6, it can be seen that contrast is mately 200╯keV, as illustrated by Figure
decreased by the additional factor Rbâ•›/Ro in 10-10. Using a narrower analyzer window for
the denominator. scatter rejection also decreases the recorded
counting rate and increases the statistical
EXAMPLE 15-1 noise in the image. A reasonable tradeoff
Suppose that under ideal conditions, a certain between counting efficiency and scatter rejec-
radiopharmaceutical produces lesion and tion for imaging systems using NaI(Tl) detec-
normal tissue counting rates given by Ro and tors is obtained with a 15% energy window
R = 1.2Ro, respectively. Suppose further that centered on the γ-ray photopeak. There has
a background counting rate Rb = Ro then is been continuing interest in applying semicon-
added to the image. Calculate the image con- ductor detectors to nuclear medicine imaging
trast with and without the added background to take advantage of their superior energy
counting rate. resolution for discrimination against scat-
tered radiation by pulse-height analysis (see
Answer Figs. 10-14 and 10-15).
Using Equation 15-6 for the intrinsic contrast Figure 15-9 shows the effect of scattered
without the added background radiation on images of a phantom. With a
very wide analyzer window, there is virtually
(1.2 Ro − Ro )
C = no rejection of scattered radiation and a
Ro noticeable loss of image contrast. The loss of
= 0.2 (20%) contrast can result in degraded visibility of
both large low-contrast objects and fine details
When background amounting to Rb = Ro is in the image. Figure 15-10, for example, illus-
added, according to Equation 15-7 trates the effects of scattered radiation (or
15  •  Image Quality in Nuclear Medicine 241

True activity Unscattered 20% energy 50% energy


distribution photons only window window

250

200

150

100

50

0
10 20 30 40
Voxel Number
True activity distribution 20% energy window
Unscattered photons only 50% energy window
FIGURE 15-9  Effect of scatter and pulse-height analysis on image contrast. The images were generated by Monte
Carlo simulations mimicking a clinical study of myocardial function using the radiotracer 201TlCl. Count profiles
through the images also are shown. These profiles are taken along the line shown in the image of the true activity
distribution. The images also demonstrate blurring of the activity distribution caused by the finite camera resolution.
(Courtesy Dr. Hendrik Pretorius and Dr. Michael King, University of Massachusetts Medical School, Worcester, MA).

septal penetration, which has similar effects) that may already be near the borderline of
on the LSF and MTF of an imaging system. detectability. These effects are apparent in
The addition of long “tails” to the LSF results Figure 15-9, which demonstrates a percepti-
first in the suppression of the MTF curve at ble loss of image sharpness as well as overall
low frequencies. This is reflected in poorer image contrast when the added background
contrast of large objects that would make is present.
large low-contrast objects more difficult to An important contributor to background
detect or characterize. The high-frequency radiation in conventional planar imaging is
portion of the MTF curve also is suppressed, radioactivity above and below the object of
which has the effect of shifting the limiting interest. Image contrast is improved in emis-
frequency for detection of high-contrast sion computed tomography (SPECT and PET)
objects (e.g., bar patterns) to lower frequen- (see Chapters 17 and 18) because it permits
cies. Thus the contrast-degrading effects of imaging of an isolated slice without the super-
added background decrease the visibility of imposed activities in overlying and underly-
all structures in the image, particularly those ing structures. Tomographic techniques offer
242 Physics in Nuclear Medicine

With
Relative counts scatter

Without
scatter
Scatter only

A
6 4 2 0 2 4 6
Distance (cm)

1.0

0.9

0.8

0.7
Without
scatter
0.6

With
MTF

0.5 scatter

0.4

0.3

0.2

0.1

B
0 0.2 0.4 0.6 0.8
Spatial frequency
FIGURE 15-10  Illustration of effects of scatter and septal penetration on line-spread function (LSF) (A) and modula-
tion transfer function (MTF) (B) of an imaging system. The long “tails” on the LSF have the effect of suppressing the
MTF curve at both low and high spatial frequencies.

significant improvements for the detection of The preceding discussion relates to the
low-contrast lesions. Figure 15-11 illustrates effects of various types of background radia-
this effect. Details of emission computed tomo- tion on input contrast to the imaging system.
graphic imaging are presented in Chapters 16 It is possible with computers to apply “back-
to 18; however, even at this point, the benefits ground subtraction” or “contrast enhance-
of removing the interfering effects of overlying ment” algorithms and thereby restore the
and underlying activity should be evident. original contrast, at least in terms of the
15  •  Image Quality in Nuclear Medicine 243

Planar image

SPECT images

FIGURE 15-11  Planar (upper left) and single-photon emission computed tomographic (SPECT) (center) images of a
thoracic phantom. Note the improved contrast and visibility of the voids in the cardiac portion of the phantom when
overlying and underlying activity are removed in the SPECT images. (Courtesy Dr. Freek Beekman, Delft University
of Technology, Netherlands.)

relative brightness levels between a lesion Structured noise also can arise from
and its surrounding area. However, these imaging system artifacts. Nonuniformities in
techniques also enhance the statistical noise gamma camera images (see Fig. 14-10) are
levels in the image as well as the contrast of one example. Various “ring” or “streak” arti-
any underlying artifacts, such as gamma facts generated during reconstruction tomog-
camera image nonuniformities. Thus the crit- raphy are another (e.g., see Figs. 16-11 and
ical parameter to consider regarding com- 16-13).
puter enhancement techniques is their effect
on CNR. This concept is discussed in the fol- 2.  Random Noise and  
lowing section. Contrast-to-Noise Ratio
Random noise, also called statistical noise or
quantum mottle, is present everywhere in a
D.  NOISE
nuclear medicine image. Even when the size
of an object is substantially larger than the
1.  Types of Image Noise limiting spatial resolution of the image, sta-
Image noise generally can be characterized as tistical noise can impair detectability, espe-
either random or structured. Random noise cially if the object has low contrast. The
refers to the mottled appearance of nuclear critical parameter for detectability is the
medicine images caused by random statistical CNR of the object in the image. In the follow-
variations in counting rate (Chapter 9). This ing discussion, we present an analysis and
is a very important factor in nuclear medicine some illustrations of the effects of CNR on
imaging and is discussed in detail in this detectability of objects in 2-D planar nuclear
section. images.
Structured noise refers to nonrandom vari- Suppose that a 2-D image contains a circu-
ations in counting rate that are superimposed lar lesion of area A  having contrast C (Equa-
on and interfere with perception of the object tion 15-6) against a uniform background
structures of interest. Some types of struc- counting rate, Ro (cpsâ•›/cm2). The number of
tured noise arise from the radionuclide distri- counts recorded in a background area of the
bution itself. For example, in planar imaging, same size as the lesion during an imaging
uptake in the ribs may be superimposed over time, t, is
the image of the heart in studies to detect
myocardial infarction with 99mTc-labeled pyro- No = Ro × A × t
phosphates. Bowel uptake presents a type of
structured noise in studies to detect inflam- π (15-8)
= Ro × d2 × t
mation or abscess with 67Ga. 4
244 Physics in Nuclear Medicine

where d is the diameter of the lesion. The Equation 15-12 applies to somewhat idealized
statistical variation of counts in background conditions of more or less circular objects
areas of size A is against a relatively uniform background of
nonstructured noise. Such conditions rarely
σ No = No apply in nuclear medicine. Nevertheless, this
equation can be used to gain some insights
π d2 (15-9)
= Ro × ×t into lesion detectability and the factors that
4 affect it.
EXAMPLE 15-2
Thus the fractional standard deviation of
counts due to random statistical variations is Estimate the minimum contrast for detec-
tion of circular objects of 1-cm and 2-cm
σ No diameter in an area of an image where the
Cnoise =
No background information density is IDo = 400
1 counts/cm2.
= (15-10)
π d2 Answer
Ro × ×t
4 Rearranging Equation 15-12 and inserting
the specified information density,
As indicated by the notation in Equation
15-10, this factor can be considered as the 4 4 0 .2
C ≥ = =
“noise contrast” for a circular area of diameter d IDo 400 d d
d in background areas of the image. The ratio
of lesion-contrast to noise-contrast is defined Thus for a 1-cm diameter object, the minimum
as its CNR. contrast required for detectability is approxi-
C mately 0.2 (20%), whereas for a 2-cm diame-
CNR  = ter object it is approximately 0.1 (10%).
Cnoise
≈ C × d × Ro × t (15-11) Example 15-2 shows that, all other factors
being the same, the contrast required for
≈ C × d × IDo detectability is inversely proportional to
object size.
where we have used the approximation
π/4 ≈ 1. The quantity IDo = (Ro × t) is the EXAMPLE 15-3
background information density of the image Estimate the minimum diameter for detec-
and has units (counts/cm2). The absolute tion of an object that has 10% contrast, |C|
value of contrast, |C|, is used in Equation = 0.1, in an area of the image where the back-
15-11 to indicate that it applies to either posi- ground information density is 100 counts/cm2.
tive or negative contrast.
To detect a lesion or other object in an Answer
image, the observer must be able to distin- Rearranging Equation 15-12 and inserting
guish between the lesion or object and noise- the specified parameters,
generated contrast patterns in background
areas of the same size in the image. A sub- 4 4
d ≥ = = 4 cm
stantial amount of research has gone into this C IDo 0.1 400
subject. The conclusion is that, to be detect-
able, an object’s CNR must exceed 3-5. This Examples 15-2 and 15-3 illustrate that the
factor is known as the Rose criterion, after the minimum size requirement for object detect-
individual who did basic studies on this ability decreases inversely with the square
subject.4 The actual value depends on object root of information density, from 2╯cm with
size and shape, edge sharpness, viewing dis- IDo = 400 counts/cm2 in Example 15-2 to 4╯cm
tance, observer experience, and so forth. with IDo = 100 counts/cm2 in Example 15-3.
Choosing a factor of 4, the requirement for At first glance, it would seem that adding
detectability becomes CNR ≥ 4, and Equation background radiation to an image would
15-11 can be written as improve lesion detectability, by increasing
C × d × Ro × t ≥ 4 information density, IDo. However, as illus-
(15-12) trated by Example 15-1, background radiation
C × d × IDo ≥ 4 also degrades lesion contrast. The following
15  •  Image Quality in Nuclear Medicine 245

example illustrates the overall effect of back- an imaging time of 1╯min. Ignore the effects
ground radiation on object detectability. of attenuation and source-to-detector distance
for this comparison.
EXAMPLE 15-4
Example 15-3 indicates that a 4-cm diameter Answer
object with 10% contrast should be detectable In both cases, the uptake in normal tissues
against a background information density of would generate a background counting rate of
IDo = 100 counts/cm2. Suppose that back- Ro = 10╯cm × 10╯cpm/cm2 per centimeter thick-
ground radiation with the same information ness = 100╯cpm/cm2. For the 1-cm diameter
density, (IDb = 100 counts/cm2) is added to the lesion, the count rate over the center of the
image. Estimate the minimum detectable lesion is
lesion size after this is done.
(9 cm × 10 cpm/cm 2 per cm)
Answer + (1 cm × 20 cpm/cm 2 per cm)

According to Example 15-1, the addition of
background radiation with IDb = IDo decreases = 110 cpm/cm 2
contrast by a factor of 2, from C = 0.1 to Câ•›′ = Thus the contrast of the 1-cm diameter lesion
0.05. At the same time, the background infor- is (110 − 100)/100 = 0.1 (10%). For a 1-min
mation density increases from 100 counts/cm2 imaging time, its CNR (Equation 15-11) is
to 200 counts/cm2. Rearranging Equation
15-12 and inserting these values, one obtains CNR1 cm = 0.1 × 1 × 100 × 1 = 1
4 4 For the 2-cm diameter lesion, the counting
d ≥ = ≈ 5.7 cm
C′ IDo 0.05 200 rate over the center of the lesion is

Example 15-4 illustrates that the minimum (8 cm × 10 cpm/cm 2 per cm )


detectable object size becomes larger (from + (2 cm × 20 cpm/cm 2 per cm )
4╯cm to 5.7╯cm in the example) when back-
= 120 cpm/cm 2
ground radiation is added. This example 
illustrates that the effect of background on Thus the contrast of the 2-cm diameter lesion
degradation of object contrast more than is (120 − 100)/100 = 0.2 (20%). For a 1-min
offsets its effect toward increasing the infor- imaging time, its CNR is
mation density of the image.
These examples and analyses assume that CNR 2 cm = 0.2 × 2 × 100 × 1 = 4
object size (d) and contrast (C) are indepen-
dent variables. This may be true for computer- According to Equation 15-11, when the
generated test images; however, in planar diameter of a planar object is doubled, its CNR
nuclear medicine imaging these parameters increases by a factor of 2 as well. However,
often are intimately linked. In many cases, Example 15-5 shows that when the object is
lesions are somewhat spherical in shape so spherical, so that its thickness is doubled as
that their thickness varies linearly with their well, its CNR increases by another factor of 2,
diameter. Thus a larger lesion not only has a that is, the total change in CNR is a factor of
larger diameter but generates greater con- 4. This example illustrates the strong depen-
trast as well. The following example illus- dence of lesion detectability on lesion size
trates how these two factors operating when its contrast increases with its size. In
together affect lesion CNR and detectability. essence, CNR increases as the square of spher-
ical lesion diameter, not as the first power as
EXAMPLE 15-5 implied by Equation 15-11. Going in the oppo-
Suppose that a certain radionuclide concen- site direction, this factor becomes a significant
trates in normal tissue to a level that provides impediment for the detection of smaller and
a counting rate of 10 cpm/cm2 per cm of tissue smaller lesions in nuclear medicine.
thickness. Suppose further that it concen- Finally, Equations 15-11 and 15-12 and
trates in a certain type of lesion to a level that the discussion thus far assume that detect-
is twice this value, that is, 20╯cpm/cm2 per ability is the same for positive (“hot spot”) and
centimeter of lesion thickness. Compare the negative (“cold spot”) contrast. Indeed, if two
contrast, CNR and detectability of 1-cm diam- objects generate identical levels of contrast,
eter versus 2-cm diameter lesions embedded this is a valid assumption. Again, however,
in normal tissue of total thickness 10╯cm and additional factors come into play in nuclear
246 Physics in Nuclear Medicine

medicine imaging. Specifically, the intrinsic Thus the contrast of the “cold” lesion is (91
contrast of a lesion can depend on whether its − 100)/100 = –â•›0.09 (–9%), in which the minus
contrast is generated by preferential uptake sign indicates “negative” contrast. For a 1-min
or by preferential suppression of uptake rela- imaging time, the CNR for radiopharmaceuti-
tive to surrounding normal tissues. The fol- cal B is
lowing example provides an illustration.
CNR B = 0.09 × 1 × 100 × 1 = 0.9
EXAMPLE 15-6
Suppose that two radiopharmaceuticals are which is well below the threshold of detect-
available for a study. Radiopharmaceutical A ability specified by the Rose criterion.
generates contrast by selective uptake in a
lesion that is 10 times higher than the uptake Example 15-6 illustrates the basis for the
in surrounding normal tissue, whereas radio- generally held (and generally accurate) belief
pharmaceutical B generates contrast by sup- that “cold” lesions are more difficult to detect
pression of uptake in the same lesion, to a than “hot” ones. One way to overcome this
level that is 1/10 (10%) of the uptake in sur- deficit is to inject more radioactivity for 
rounding tissue. Thus the uptake ratio is “cold” lesions; however, the specified levels of
10â•›:â•›1 in both cases. Assume that a 1-cm thick uptake in normal tissue in this example leads
lesion is present in a total thickness of 10╯cm to comparable radiation doses in both cases
of tissue. Ignoring the effects of attenuation and thus the higher level of radioactivity
and source-to-detector distance, calculate the required for radiopharmaceutical B would
CNR generated by the two radiopharmaceu- presumably lead to greater radiation dose.
ticals. For both radiopharmaceuticals, assume Specific comparisons of radiopharmaceuticals
that the uptake in normal tissue generates a vary, depending on details of the uptake dis-
counting rate of 10╯cpm/cm2 per centimeter tribution and properties of the radionuclides
thickness of tissue and that imaging time is involved.
1╯min in both cases. These examples illustrate that contrast
and information density can be limiting factors
Answer for lesion detection, even when the size of the
For both radiopharmaceuticals, the uptake  lesion easily exceeds the spatial resolution
in normal tissues generates a background  limits of the imaging system. Figure 15-12
counting rate of Ro = 10╯cm × 10╯cpm/cm2 per further illustrates this point for images of a
centimeter thickness = 100╯cpm/cm2. For heart phantom. Although spatial resolution
radiopharmaceuÂ�tical A (“hot” lesion), the and contrast are the same for all the images
uptake of the lesion is 10 times greater and the shown in this figure, there are marked differ-
counting rate over the lesion is ences in lesion visibility because of differences
in information density and noise.
(9 cm × 10 cpm/cm 2 per cm) Although not specifically included in the
+ (1 cm × 100 cpm/cm 2 per cm) analysis of CNR presented earlier, spatial
resolution of the imaging system also affects
= 190 cpm/cm 2 the detectability of small, low-contrast objects.
As shown in Figure 15-13, high-resolution col-
Thus the contrast of the hot lesion is (190 − limators (or imaging detectors) provide better
100)/100 = 0.9 (90%). For a 1-min imaging image contrast and improved visibility for
time, its CNR (Equation 15-11) is fine details, even for smaller numbers of
counts in the image. In essence, “sharpening”
CNR A = 0.9 × 1 × 100 × 1 = 9 the edges of lesions lowers the CNR required
for detectability (Rose criterion) specified in
This value easily exceeds the requirement for Equation 15-12.
detectability given by the Rose criterion. Nevertheless, the tradeoff between improved
collimator resolution and decreased collima-
For the “cold” lesion, the uptake by the lesion tor sensitivity (see Equations 14-7 and 14-8),
is 1/10 of the uptake in normal tissue. Thus as well as the requirement for greater infor-
the counting rate over the lesion is mation density, eventually establishes a 
(9 cm × 10 cpm/cm 2 per cm) point of diminishing returns in the effort to
detect smaller and smaller lesions by improve-
+ (1 cm × 1 cpm/cm 2 per cm) ments in imaging resolution. In the end,
= 91 cpm/cm 2 detectability in nuclear medicine is limited by 
15  •  Image Quality in Nuclear Medicine 247

True activity 1106 counts 4106 counts 16106 counts


distribution (~clinical level)
FIGURE 15-12  Example of effects of information density on visibility of a low-contrast lesion (arrow) in a computer-
simulated cardiac phantom. The simulation assumes a 99mTc radiotracer imaged on a gamma camera with a 15% energy
window. Note the region of reduced radiotracer uptake in the myocardium (arrow) that can be clearly visualized only
with the highest information density. (Courtesy Dr. Hendrik Pretorius and Dr. Michael King, University of Massachu-
setts Medical School, Worcester, MA).

impediments to improvements in nuclear


medicine information densities and are the
reason why photographic or radiographic
image quality are unlikely to ever be achieved
in nuclear medicine.
In general, the rules regarding image CNR
and object detectability are the same for
planar images and tomographic images;
however, the approaches for calculating CNR
are different. This is discussed further in
Chapter 16, Section C.3.

E.  OBSERVER PERFORMANCE


STUDIES

The physical measures of image quality dis-


cussed in the preceding sections are helpful
for comparing different imaging systems, as
well as for preparing purchase specifications,
FIGURE 15-13  Demonstration of effects of improved establishing quality assurance parameters,
resolution on contrast and detectability of small objects. and so forth. They also can in some cases
Improved spatial resolution results in improved contrast provide useful estimates of minimum detect-
(lower right), providing improved visibility in spite of
fewer counts in comparison with the other images.
able object size and contrast, as in Examples
Decreased sensitivity of high-resolution collimators ulti- 15-2 through 15-6. In most cases, however,
mately sets practical limits for high-resolution imaging object detectability is determined more accu-
in nuclear medicine. (From Muehllehner G: Effect of reso- rately by direct evaluation, using human
lution improvement on required count density in ECT observers. The general name for such evalu-
imaging: A computer simulation. Phys Med Biol 30:163-
173, 1985.) ations is observer performance studies. They
test both the ability of an imaging device to
produce detectable objects as well as the
information density rather than image reso- ability of individual observers to detect them.
lution. Information densities in planar nuclear Two types of experiments commonly used for
medicine images are typically in the range  this purpose in nuclear medicine imaging are
of 100 to 3000 counts/cm2. This is well below contrast-detail (C-D) and receiver operating
the levels encountered in radiography and characteristic (ROC) studies.
photography, in which information densities
(x-ray or visible light photons detected to  1.  Contrast-Detail Studies
form the image) are on the order of 106 events A contrast-detail, or C-D study is performed
per mm2. Practical limitations on imaging using images of a phantom having a set of
time and the amount of activity that can be objects of different sizes and contrasts. Typi-
administered safely to patients are serious cally, the objects are graded in size along one
248 Physics in Nuclear Medicine

axis of the display and in contrast along the to bias and other sources of differences in the
other. An example is the Rollo phantom, observer’s detection thresholds in different
shown in Figure 15-14A↜. This phantom con- experiments. This is especially true for phan-
sists of solid spheres of four different diame- toms having a design similar to the one illus-
ters immersed in four different thicknesses of trated in Figure 15-14, because the observer
a radioactive solution of uniform concentra- has a priori knowledge of the locations of the
tion. Images of this phantom thus contain simulated lesions. Thus such a phantom does
cold lesions of different sizes and contrasts not test for the possibility of false-positive
(Fig. 15-14B). results, that is, the mistaken detection of
To perform a C-D study with this or a objects that actually are not present in the
similar phantom, images are obtained using image. This is particularly important for
the different imaging systems or techniques noisy images in which noise not only can
to be evaluated. An observer then is given the mask the presence of real objects but also can
images, usually without identification and in create apparent structures that masquerade
random order to avoid possible bias, and as real objects. Finally, C-D phantoms gener-
asked to indicate the smallest diameter of ally are lacking in clinical realism.
sphere that is visible at each level of contrast.
Borderline visibility may be indicated by 2.  Receiver Operating Characteristic
selecting a diameter between two of the diam- Studies
eters actually present in the image. The Some of the deficiencies of the C-D method
results then are presented on a C-D diagram outlined earlier are overcome by the ROC
as illustrated by Figure 15-15. A C-D study method. For an ROC study, a set of images is
can be helpful for comparing detectability of obtained with the different imaging systems
both large low-contrast lesions as well as or techniques to be tested. Phantoms contain-
small high-contrast lesions. For example, in ing simulated lesions can be used, but it also
Figure 15-15, system A would be preferred for is possible to use actual clinical images. In the
the former and system B for the latter. simplest approach, each image contains either
Because of the subjective nature of C-D one or no lesions. The former are called posi-
studies, the use of multiple observers is rec- tive images and the latter are called negative
ommended. Also, because observers may images. The images are given to the observer,
change their detection threshold from one who is asked to indicate whether a lesion is
study to the next or as they gain familiarity present or absent in each image, as well as
with the images, it usually is helpful to repeat where it is and his or her confidence that 
the readings for verification of results. it actually is present. Usually the confidence
C-D studies have a number of limitations. levels are numbered and four different levels
Because they are subjective, they are susceptible are permitted; for example, 1 = definitely present,

Lesion diameter
(inches)
1.0 0.75 0.50 0.375

0.66

0.44

0.33

0.22

A B
FIGURE 15-14  Example of a phantom, the Rollo phantom, which can be used to obtain images for a contrast-detail
study. A, Phantom. B, Example image. (From Rollo FD, Harris CC: Factors affecting image formation. In Rollo FD
[ed]: Nuclear Medicine Physics, Instrumentation, and Agents. St. Louis, 1977, CV Mosby, p 397.)
15  •  Image Quality in Nuclear Medicine 249

Minimum detectable object contrast

Minimum detectable object size


FIGURE 15-15  Hypothetical results of a contrast-detail study comparing two imaging systems, A and B. Reading
horizontally, one can estimate the minimum size of an object that can be detected for a specified level of object contrast.
Reading vertically, one can estimate the minimum contrast required for detection of an object of a specified size. 
In this example, system A provides better detectability for large low-contrast objects, suggesting perhaps a better
lesion-to-noise contrast ratio, whereas system B is better for small high-contrast lesions, suggesting perhaps better
spatial resolution.

2 = probably present, 3 = probably not present, ROC curves are shown in Figure 15-16. The
and 4 = definitely not present. Then the fol- ROC curve should lie above the ascending
lowing results are calculated for each confi- 45-degree diagonal, which would represent
dence level: “guessing.” The farther the curve lies above
the 45-degree line, the better the performance
True-positive fraction (TPF) = fraction of of the imaging system and observer.
positive images correctly identified as posi- An ROC curve shows not only the true-
tive by the observer positive detection rate for an observer or an
imaging system or technique but also its rela-
False-positive fraction (FPF) = fraction of tionship to the false-positive detection rate.
negative images incorrectly identified as Thus it is relatively immune to the sources of
positive by the observer observer bias that can occur in C-D studies,
for example, a tendency to “over-read” to
Two other parameters that are calculated avoid missing a possible lesion or test object.
are the true-negative fraction (TNF) = (1 − It also is applicable to other types of detection
FPF), and the false-negative fraction (FNF) = questions, such as the presence or absence of
(1 − TPF). The TPF is sometimes called the disease, which might be indicated by a general
sensitivity and TNF the specificity of the test pattern of uptake within an organ, as opposed
or the observer. to the simple detection of individual lesions.
The ROC curve then is generated by plot- As with C-D studies, the interpretation of
ting TPF versus FPF for progressively relaxed ROC results sometimes can be challenging.
degrees of confidence, that is, highest confi- For example, the ROC curves for two different
dence = level 1 only, then confidence levels 1 imaging systems can “cross,” leading to some
+ 2, then confidence levels 1 + 2 + 3, and so ambiguity in the results. One approach to sim-
forth. An example of data and the resulting plifying the interpretation is to report the
250 Physics in Nuclear Medicine

1.0

0.8

True-positive fraction (TPF)


Fitted
0.6 curve

Data “Guessing”
0.4

Area under fitted


0.2
curve = Az

0.0
0.0 0.2 0.4 0.6 0.8 1.0
False-positive fraction (FPF)
FIGURE 15-16  Example of results from an ROC study. , data points; orange line, fitted curve; blue line, 45-degree
line, which is equivalent to “guessing.” Area under the curve (shaded in darker blue) is Az, which is one measure of
detection accuracy.

results of an ROC study as a single number. verification of “truth” when clinical images
Most commonly the parameter calculated is are used.
the area under the ROC curve, usually denoted Another potential problem is the possible
by Aâ•›z. This number can range from zero (all presence of multiple lesions on a single image.
readings wrong) to 1 (all readings correct). A Conventional ROC methodology allows only
value of 0.5 indicates an overall accuracy of for a single “yes-no” interpretation of each
50%, which is equivalent to “guessing.” image. This allows straightforward calcula-
An extensive amount of theoretical and tions of false-positive rates. However, if mul-
experimental work has been done on the prop- tiple lesions are possible, as in many clinical
erties of Aâ•›z, including such issues as statisti- images, the potential number of false positives
cal com�parisons of values obtained from is virtually infinite, making the calculation of
different ROC studies. References 5 to 7 false-positive rates difficult, if not impossible.
present detailed analyses of these and other Alternative methods, called the free-response
practical issues in ROC studies. Aâ•›z also has operating characteristic, that allow for the
an interesting practical interpretation: It is presence of multiple lesions have been devel-
the probability that, given a side-by-side pair oped and are discussed in reference 9.
of images, one of which has a lesion or test Finally, even a “perfect” image evaluation
object and the other does not, the observer will technique with a clearly defined outcome
correctly identify the image with the lesion.8 might not provide the final answer regarding
Despite their power and potential useful- the merit or value of an imaging device or
ness, ROC studies also have a number of limi- technique. Even after the physician or scien-
tations. Perhaps the most challenging is the tist has demonstrated that he or she has
verification of absolute “truth” for images developed a truly “better” device or technique
obtained from clinical studies. Ideally, the in terms of lesion or disease detectability,
outcome of the ROC study itself (i.e., the there is still the bottom-line question: “So
tested images) should not be used for this what?” Does the improved detectability alter
determination. This means that other equally the care of the patient or the outcome of that
or even more reliable information about the care? Does it improve the patient’s quality of
presence or absence of disease in the patient life? In an age of cost-consciousness, what are
must be available. Often nonimaging tests the cost-benefit tradeoffs? For example, from
(e.g., surgical results) must be obtained for a public health perspective, is it really worth
15  •  Image Quality in Nuclear Medicine 251

spending a small fortune to detect the next 3. Vayrynen T, Pitkanen U, Kiviniitty K: Methods for
smaller size of lesion, as compared with measuring the modulation transfer function of
gamma camera systems. Eur J Nucl Med 5:19-22,
directing those funds toward simpler health 1980.
measures, such as education and behavior 4. Rose A: Vision: Human and Electronic. New York,
modification? These are difficult questions to 1973, Plenum Press, pp 21-23.
answer, but efforts are being made to develop 5. Swets JA, Pickett RM: Evaluation of Diagnostic
Systems: Methods from Signal Detection Theory, New
methodology for answering them in a quanti- York, 1982, Academic Press.
tative and objective manner. The general 6. Metz CE: ROC methodology in radiologic imaging.
term for these investigations is efficacy Invest Radiol 21:720-733, 1986.
studies. Additional discussion of this topic can 7. Metz CE: Fundamental ROC analysis. In Beutel J,
be found in reference 10. Kundel HL, Nan Metter RL, editors: Handbook of
Medical Imaging, Bellingham, WA, 2000, SPIE,
Chapter 15.
8. Hanley JA, McNeil BJ: The meaning and use of the
REFERENCES area under the receiver operating characteristic
1. Barrett HH, Yao J, Rolland JP, Myers KJ: Model (ROC) curve. Radiology 143:29-36, 1982.
observers for assessment of image quality. Proc Natl 9. Chakraborty DP: The FROC, AFROC, and DROC
Acad Sci 90:9758-9765, 1993. variants of the ROC analysis. In Beutel J, Kundel
2. Cunningham IA: Introduction to linear systems HL, Nan Metter RL, editors: Handbook of Medical
theory. In Beutel J, Kundel HL, Nan Metter RL, Imaging, Bellingham, WA, 2000, SPIE, Chapter 16.
editors: Handbook of Medical Imaging, Bellingham, 10. Fryback DG, Thornbury JR: The efficacy of diagnos-
WA, 2000, SPIE, Chapter 2. tic studies. Med Decis Making 11:88-94, 1991.
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chapter
16 
Tomographic
Reconstruction in
Nuclear Medicine
A basic problem in conventional radionuclide CT, See Chapter 19, Section B). The mathe-
imaging is that the images obtained are  matical basis is the same for ECT and TCT,
two-dimensional (2-D) projections of three- although there are obviously differences in
dimensional (3-D) source distributions. Images details of implementation.
of structures at one depth in the patient  ECT produces images in which the activity
thus are obscured by superimposed images of from overlying (or adjacent) cross-sectional
overlying and underlying structures. One planes is eliminated from the image. This
solution is to obtain projection images from results in a significant improvement in
different angles around the body (e.g., poste- contrast-to-noise ratio (CNR), as already has
rior, anterior, lateral, and oblique views). The been illustrated in Figure 15-11. Another
person interpreting the images then must advantage of SPECT and PET over planar
sort out the structures from the different nuclear medicine imaging is that they are
views mentally to decide the true 3-D nature capable of providing more accurate quantita-
of the distribution. This approach is only  tion of activity at specific locations within the
partially successful; it is difficult to apply to body. This is put to advantage in tracer kinetic
complex distributions with many overlapping studies (Chapter 21).
structures. Also, deep-lying organs may  The mathematics underlying reconstruc-
have overlying structures from all projection tion tomography was first published by
angles. Johann Radon in 1917, but it was not until
An alternative approach is tomographic the 1950s and 1960s that work in radio�
imaging. Tomographic images are 2-D repre- astronomy and chemistry resulted in practical
sentations of structures lying within a selected applications. The development of x-ray CT in
plane in a 3-D object. Modern computed the early 1970s initiated application of these
tomography (CT) techniques, including posi- principles for image reconstruction in medical
tron emission tomo�g�raphy (PET), single imaging. An interesting historical perspective
photon emission tomography (SPECT), and on the origins and development of tomo-
x-ray CT, use detector systems placed or graphic image reconstruction techniques is
rotated around the object so that many differ- presented in reference 1.
ent angular views (also known as projections) Instrumentation for SPECT imaging is dis-
of the object are obtained. Mathematical algo- cussed in Chapter 17 and instrumentation for
rithms then are used to reconstruct images of PET is discussed in Chapter 18. Although the
selected planes within the object from these instruments differ, the same mathematics
projection data. Reconstruction of images can be used to reconstruct SPECT or PET
from multiple projections of the detected images. In this chapter, we focus on the basic
emissions from radionuclides within the body principles of reconstructing tomographic
is known as emission computed tomography images from multiple projections. A detailed
(ECT). Reconstruction of images from trans- mathematical treatment of image reconstruc-
mitted emissions from an external source tion is beyond the scope of this text. The
(e.g., an x-ray tube) is known as transmission reader is referred to references 2 to 4 for more
computed tomography (TCT or, usually, just detailed accounts.
253
254 Physic in Nuclear Medicine

within its line of response. The measured


A.  GENERAL CONCEPTS, NOTATION, quantity (in this case, counts recorded or
AND TERMINOLOGY radioactive content) sometimes is referred to
as the line integral for the line of response. A
We assume initially that data are collected full set of line integrals recorded across the
with a standard gamma camera fitted with a detector is called a projection, or a projection
conventional parallel-hole collimator. (Appli- profile, as illustrated in Figure 16-1.
cations involving other types of collimators Obviously, the assumptions noted earlier
are discussed in Section E.) To simplify the are not totally valid. Some of the effects of 
analysis, several assumptions are made. We the inaccuracies of these assumptions are 
consider only a narrow cross-section across discussed in Chapter 17, Section B and in
the detector. The collimated detector is Chapter 18, Section D.
assumed to accept radiation only from a thin A typical SPECT camera is mounted on a
slice directly perpendicular to the face of the gantry so that the detector can record projec-
detector. This reduces the analysis to that of tions from many angles around the body.
a 1-D detector, as shown in Figure 16-1. Each PET systems generally use stationary arrays
collimator hole is assumed to accept radiation of detector elements arranged in a ring or
only from a narrow cylinder defined by the hexagonal pattern around the body. In either
geometric extension of the hole in front of the case, the detectors acquire a set of projec-
collimator. This cylinder defines the line of tions at equally spaced angular intervals. In
response for the collimator hole. For further reconstruction tomography, mathematical
simplification, we ignore the effects of attenu- algorithms are used to relate the projection
ation and scatter and assume that the counts data to the 2-D distribution of activity within
recorded for each collimator hole are propor- the projected slice. A schematic illustration 
tional to the total radioactivity contained of the data acquisition process is shown in

Sum of
activity
along line
of response
Projection
profile

Gamma
camera

Line of
response

Object

FIGURE 16-1  Cross-section of the response characteristics of an idealized gamma camera. Each collimator hole views
the radioactivity within a cylinder perpendicular to the face of the gamma camera, called its line of response. Under
idealized conditions (such as no attenuation or scatter) the signal recorded by the detector at that point reflects the
sum of activity within the line of response. For a row of holes across the detector, the gamma camera generates a
projection profile as shown. The projection profiles provide the data from which the image is reconstructed.
16  •  Tomographic Reconstruction in Nuclear Medicine 255

1-D projection
profiles at
different angles

Rotating
gamma
camera

ECT
ALGORITHM

Object
f(x,y)

Reconstructed
image of section
through object

FIGURE 16-2  Rotating the gamma camera around the object provides a set of one-dimensional projection profiles for
a two-dimensional object, which are used to calculate the two-dimensional distribution of radioactivity in the object.
ECT, emission computed tomography.

Figure 16-2. Note that the data collected cor- coordinate system and is illustrated in Figure
respond to a slice through the object perpen- 16-3. If the camera is rotated by an angle ϕ
dicular to the bed and that this is called the with respect to the (x,y) coordinate system of
transverse or transaxial direction. The direc- the scanned object, the equations for transfor-
tion along the axis of the bed, which defines mation from (x,y) to (r,s) coordinates can be
the location of the slice, is known as the axial derived from the principle of similar triangles
direction. and are given by
We assume that N projections are recorded
at equally spaced angles between 0 and 180 r = x cos φ + y sin φ (16-1)
degrees. Under the idealized conditions
assumed here, the projection profile recorded and
at a rotation angle of (180 + ϕ) degrees would
be the same (apart from a left-right reversal) s = y cos φ − x sin φ (16-2)
as the profile recorded at ϕ degrees. Thus the
data recorded between 180 and 360 degrees These equations can be used to determine
would be redundant; however, for practical how radioactivity at a location (x,y) in the
reasons (e.g., attenuation), SPECT data often object contributes to the signal recorded at
are acquired for a full 360-degree rotation. location r in the projection acquired at rota-
This is discussed further in Chapter 17. tion angle ϕ.
For purposes of analysis, it is convenient  One commonly used way to display a full
to introduce a new coordinate system that  set of projection data is in the form of a 2-D
is stationary with respect to the gamma matrix p(r,ϕ). A representation of this matrix,
camera detector. This is denoted as the (r,s) generically known as a sinogram, is shown for
256 Physic in Nuclear Medicine

a simple point-source object in Figure 16-4.


p(r,φ) r Each row across the matrix represents an
intensity display across a single projection.
The successive rows from top to bottom rep-
resent successive projection angles. The name
sinogram arises from the fact that the path of
a point object located at a specific (x,y) loca-
tion in the object traces out a sinusoidal path
down the matrix. (This also can be deduced
s y from Equations 16-1 and 16-2.) The sinogram
provides a convenient way to represent the
full set of data acquired during a scan and can
be useful for determining the causes of arti-
facts in SPECT or PET images.
r
f(x,y)

φ B.  BACKPROJECTION AND  


x FOURIER-BASED TECHNIQUES

1.  Simple Backprojection


The general goal of reconstruction tomogra-
phy is to generate a 2-D cross-sectional image
of activity from a slice within the object, fâ•›(x,y),
using the sinogram, or set of projection pro-
files, obtained for that slice. In practice, a set
FIGURE 16-3  The (r,s) coordinate system is rotated by of projection profiles, p(r,ϕi), is acquired at
projection angle ϕ with respect to the (x,y) coordinate
system of the object and is fixed with respect to the
discrete angles, ϕi, and each profile is sampled
gamma camera. at discrete intervals along r. The image is
reconstructed on a 2-D matrix of discrete

 0°

Projection
profiles

Point source

180°

Sinogram Mapping of set of 1-D


projection profiles into
2-D sinogram space
FIGURE 16-4  Two-dimensional (2-D) intensity display of a set of projection profiles, known as a sinogram. Each row
in the display corresponds to an individual projection profile, sequentially displayed from top to bottom. A point source
of radioactivity traces out a sinusoidal path in the sinogram.
16  •  Tomographic Reconstruction in Nuclear Medicine 257

pixels in the (x,y) coordinate system. For together, an approximation of the distribution
mathematical convenience, the image matrix of radio�activity within the scanned slice is
size usually is a power of 2 (e.g., 64 × 64 or obtained. Mathematically, the backprojection
128 × 128 pixels). Pixel dimensions Δâ•›x and Δy of N profiles is described by
can be defined somewhat arbitrarily, but
usually they are related to the number of pro- 1 N
files recorded and the width of the sampling
f ′( x, y) = ∑ p( x cos φi + y sin φi, φi )   (16-3)
N i=1
interval along r.
The most basic approach for reconstructing where ϕi denotes the ith projection angle and
an image from the profiles is by simple back- fâ•›′â•›(x,y) denotes an approximation to the true
projection. The concepts will be illustrated for radioactivity distribution, fâ•›(x,y).
a point source object. Figure 16-5A shows pro- As illustrated in Figure 16-5B, the image
jection profiles acquired from different angles built up by simple backprojection resembles
around the source. An approximation for the the true source distribution. However, there
source distribution within the plane is is an obvious artifact in that counts inevitably
obtained by projecting (or distributing) the are projected outside the true location of the
data from each element in a profile back object, resulting in a blurring of its image.
across the entire image grid (Fig. 16-5B). The The quality of the image can be improved by
counts recorded in a particular projection increasing the number of projection angles
profile element are divided uniformly amongst and the number of samples along the profile.
the pixels that fall within its projection path.* This suppresses the “spokelike” appearance
This operation is called backprojection. When of the image but, even with an infinite number
the backprojections for all profiles are added of views, the final image still is blurred. No
matter how finely the data are sampled,
simple backprojection always results in some
apparent activity outside the true location for
*In practice, counts are assigned to a pixel in proportion the point source. Figure 16-6 shows an image
to the fraction of the pixel area contained within the line
of response for the projection element. However, owing to reconstructed by simple backprojection for a
the complexity of the notation, this part of the algorithm somewhat more complex object and more
is not included here. clearly illustrates the blurring effect.

Backprojection
of profile at 0°
across image
matrix

Backprojection after
Object 2 angles 8 angles 256 angles

A B
FIGURE 16-5  Illustration of the steps in simple backprojection. A, Projection profiles for a point source of radioactivity
for different projection angles. B, Backprojection of one intensity profile across the image at the angle corresponding
to the profile. This is repeated for all projection profiles to build up the backprojected image.
258 Physic in Nuclear Medicine

A B C
FIGURE 16-6  A, Computer-simulation phantom used for testing reconstruction algorithms. B, Sinogram of simulated
data for a scan of the phantom. C, Image of simulation phantom for simple backprojection of data from 256 projection
angles. 1/r blurring is apparent in the object, and edge details are lost. (Computer simulations performed by Dr. Andrew
Goertzen, University of Manitoba, Canada)

Mathematically, the relationship between 1-D image profile as a spatially varying func-
the true image and the image reconstructed tion, fâ•›(x), the profile is represented as a sum-
by simple backprojection is described by mation of sine and cosine functions of different
spatial frequencies, k. The amplitudes for dif-
f ′ ( x, y) = f ( x, y) ∗ (1/r) (16-4) ferent spatial frequencies are represented in
the FT of fâ•›(x), which is denoted by F(k). The
where the symbol * represents the process operation of computing the FT is symbolized
of convolution described in Appendix G. A by
profile taken through the reconstructed
image for a point source that is reconstructed F (k) = F [ f ( x)] (16-5)
from finely sampled data decreases in pro-
portion to (1/r), in which r is the distance The function fâ•›(x) is a representation of the
from the center of the point-source location. image profile in image space (or “object
Because of this behavior, the effect is known space”), whereas F(k) represents the profile
as 1/r blurring. Simple backprojection is in “spatial frequency space,” also called
potentially useful only for very simple situa- k-space. FTs can be extended to 2-D func-
tions involving isolated objects of very high tions, fâ•›(x,y), such as a 2-D image. In this
contrast relative to surrounding tissues, case, the FT also is 2-D and represents
such as a tumor with avid uptake of a radio- spatial frequencies along the x- and y-axes,
pharmaceutical that in turn has very low F(kx, ky), in which kx and ky represent orthog-
uptake in normal tissues. For more compli- onal axes in 2-D k-space. Symbolically, the
cated objects, more sophisticated reconstruc- 2-D FT is represented as
tion techniques are required.
F (kx, ky ) = F [ f ( x, y)] (16-6)
2.  Direct Fourier Transform Mathematically, a function and its FT are
Reconstruction equivalent in the sense that either one can be
One approach that avoids 1/r blurring is derived from the other. The operation of con-
Fourier transform (FT) reconstruction, some- verting the FT of a function back into the
times called direct Fourier transform recon- original function is called an inverse FT and
struction or direct FT. Although direct FT is is denoted by
not really a backprojection technique, it is
presented here as background for introducing F −1
[ F (kx, ky )] = f ( x, y) (16-7)
the filtered backprojection (FBP) technique in
the next section. FTs can be calculated quickly and conve-
Basic concepts of FTs are discussed in niently on personal computers, and many
Appendix F. Briefly, in the context of nuclear image and signal-processing software pack-
medicine imaging, the FT is an alternative ages contain FT routines. The reader is
method for representing spatially varying referred to Appendix F for additional informa-
data. For example, instead of representing a tion about FTs.
16  •  Tomographic Reconstruction in Nuclear Medicine 259

The concept of k-space will be familiar to The projection slice theorem provides a
readers who have studied magnetic resonance means for obtaining 2-D k-space data for 
imaging (MRI), because this is the coordinate an object from a series of 1-D measurements
system in which MRI data are acquired. To in object space. Figure 16-7 and Equation
reconstruct an image from its 2-D FT, the full 16-8 provide the basis for reconstructing an
2-D set of k-space data must be available object from its projection profiles as follows:
(Equation 16-7). In MRI, data are acquired 1. Acquire projection profiles in object space
point-by-point for different (kx, ky) locations in at N projection angles, ϕi, i = 1, 2, …, N as
a process known as “scanning in k-space.” previously described.
There is no immediately obvious way to 2. Compute the 1-D FT of each profile.
directly acquire k-space data in nuclear medi- 3. Insert the values of these FTs at the appro-
cine imaging. Instead, nuclear medicine CT priate coordinate locations in k-space. Note
relies on the projection slice theorem, or that values are inserted in polar coordi-
Fourier slice theorem. In words, this theorem nates along radial lines through the origin
says that the FT of the projection of a 2-D in k-space. For a specific value of kr in the
object along a projection angle ϕ [in other FT of the projection acquired at a rota-
words, the FT of a profile, p(r,ϕ)], is equal to tional angle ϕ, the data are inserted at rect-
the value of the FT of the object measured angular coordinates given by
through the origin and along the same angle,
k′x = kr cos φ
ϕ, in k-space (note, the value of the FT, not
(16-9)
the projection of the FT). Figure 16-7 illus- k′y = kr sin φ
trates this concept. Mathematically, the
general expression for the projection slice where primed notation is used to indicate
theorem is that the coordinate locations do not corre-
spond exactly to points on a rectangular
F [ p(r, φ)] = F (kr , φ) (16-8) grid. The inserted values are closely spaced
near the origin and more widely spaced
where F(krâ•›,â•›ϕ) denotes the value of the FT farther away from the origin. This “over-
measured at a radial distance kr along a line representation” of data near the origin in
at angle ϕ in k-space. k-space is one explanation for the 1/r

1-D Fourier
transform in r
p(r,φ) P(kr ,φ)

r kr

s y ks ky

Inverse
r 2-D Fourier
kr
transform
in k x,k y
φ φ
x kx

f (x, y)
F(k x,k y)

Left Right
FIGURE 16-7  Concepts of the projection slice theorem. (Left) p(r,ϕ) is a one-dimensional (1-D) profile of the 2-D object
fâ•›(x,y) at projection angle ϕ. The theorem states that the 1-D Fourier transform of this projection profile (right) is equal
to the values of the 2-D Fourier transform of the object, Fâ•›(kx, ky), along a line through the origin of k-space at the same
angle ϕ.
260 Physic in Nuclear Medicine

blurring that occurs in simple backprojec- multiplying each projection FT by |kr|, the
tion, as was discussed in Section B.1. absolute value of the radial k-space coordi-
4. Using the values inserted in polar coordi- nate at each point in the FT. Thus the
nates, interpolate values for kx and ky on a value of the FT is increased (amplified) lin-
rectangular grid in k-space. early in proportion to its distance from the
5. Use the interpolated values in k-space and origin of k-space. Figure 16-8 illustrates
a standard 2-D (inverse) FT (Equation the profile of a ramp filter, with filter
16-7) to compute the image of the object. amplitude denoted by H(kr). Applying the
With noise-free data, perfect projection ramp filter produces a modified FT for each
profiles (i.e., line integrals that represent pre- projection, given by
cisely the sum of activity along a line mea-
sured through the object) and perfect P ′ (kr , φ) = kr P (kr , φ) (16-10)
interpolation, the direct FT reconstruction
technique is capable of producing an exact where P(krâ•›,â•›ϕ) is the unfiltered FT.
representation of the object. Additional crite- 4. Compute the inverse FT of each filtered FT
ria regarding the required numbers of projec- profile to obtain a modified (filtered) projec-
tion profiles and sampled points across each tion profile. This is given by
profile are discussed in Section C.
p′(r, φ) = F −1
[ P′(kr, φ)]
A major drawback of direct Fourier recon-
(16-11)
struction is that the interpolation from polar =F −1
[ kr P (kr, φ)]
to rectangular coordinates in k-space is com-
putationally intensive. As well, it can lead to 5. Perform conventional backprojection using
artifacts in the image, if not done carefully. A the filtered profiles. Mathematically, the
more elegant (and practical) approach, called result is
filtered backprojection (FBP), is described in
the next section. 1 N
f ( x, y) = ∑ p′( x cos φi + y sin φi, φi ) (16-12)
N i =1
3.  Filtered Backprojection
Like the direct FT algorithm, FBP employs Step 5 is essentially the same as simple back-
the projection slice theorem but uses the projection, but with filtered profiles. However,
theorem in combination with backprojection unlike Equation 16-3, in which fâ•›′ (x,y) is only
in a manner that eliminates 1/r blurring. The an approximation of the true distribution,
steps are as follows: FBP, when applied with perfectly measured
1. Acquire projection profiles at N projection noise-free data, yields the exact value of the
angles (same as direct FT). true distribution, fâ•›(x,y). Figure 16-9 schemat-
2. Compute the 1-D FT of each profile (same ically illustrates the process of FBP for a
as direct FT). In accordance with the pro- pointlike object.
jection slice theorem (see Fig. 16-7 and The only difference between simple and fil-
Equation 16-8), this provides values of the tered backprojection is that in the latter
FT for a line across k-space. method, the profiles are modified by a recon-
3. Apply a “ramp filter” to each k-space struction filter applied in k-space before they
profile. Mathematically, this involves are backprojected across the image. The effect

H (kr)

FIGURE 16-8  Ramp filter in the spatial-frequency


(k-space) domain. The filter selectively amplifies
high-frequency components relative to low-
frequency components. The filter removes the 1/r
blurring present in simple backprojection and
sharpens image detail, but it also amplifies high-
frequency noise components in the image.

k
kmax
16  •  Tomographic Reconstruction in Nuclear Medicine 261

Backprojection
of filtered
profile at 0°
across image
matrix

Filtered backprojection after


2 angles 4 angles 256 angles

FIGURE 16-9  Illustration of the steps in filtered backprojection. The one-dimensional Fourier transforms of projection
profiles recorded at different projection angles are multiplied by the ramp filter. After taking the inverse Fourier
transform of the filtered transforms, the filtered profiles are backprojected across the image, as in simple
backprojection.

of the ramp filter is to enhance high spatial frequency, this also leads to degradation of
frequencies (large kr) and to suppress low signal-to-noise ratio (SNR). For this reason,
spatial frequencies (small kr). The result of images reconstructed by FBP appear noisier
the filtering is to eliminate 1/r blurring.* One than images reconstructed by simple backpro-
way to visualize the effect is to note that, jection. (This is a general result of any image
unlike unfiltered profiles (see Fig. 16-5), the filtering process that enhances high frequen-
filtered profiles have both positive and nega- cies to “sharpen” images.) In addition, filters
tive values (see Fig. 16-9). The negative por- that enhance high frequencies sometimes
tions of the filtered profiles near the central have edge-sharpening effects that lead to
peak “subtract out” some of the projected “ringing” at sharp edges. This is an unwanted
intensity next to the peak that otherwise byproduct of the positive-negative oscillations
would create 1/r blurring. introduced by the filter, illustrated in the fil-
Amplification of high spatial frequencies in tered profile at the top of Figure 16-9.
FBP also leads to amplification of high- To minimize these effects on SNR and
frequency noise. Because there usually is little artifacts at sharp edges, the ramp filter
signal in the very highest frequencies of a usually is modified so as to have a rounded
nuclear medicine image, whereas statistical shape to somewhat suppress the enhance-
noise is “white noise” with no preferred ment of high spatial frequencies. Figure
16-10 illustrates a ramp filter and two other
commonly used reconstruction filters. Also
shown are the equations describing these
*More precisely, 1/r blurring is the convolution of the true filters. A variety of reconstruction filters have
image with a blurring function, b(r) = 1/r (Equation 16-4). been developed, each with its own theoretical
As discussed in Appendix G, convolution in image space rationale. Filters also play a role in the sup-
is equivalent to multiplying by the FT of the blurring pression of artifacts caused by aliasing in
function in k-space, which for b(r) is B(kr) = 1/|kr|. Thus
multiplying by |kr| in k-space is equivalent to deconvolv-
FT-based reconstruction techniques, as dis-
ing the blurring function in image space, thereby elimi- cussed in Section C. Additional discussions of
nating the blurring effect. these filters can be found in reference 4.
262 Physic in Nuclear Medicine

Ramp: H(k)  | k |
2kcut-off |k|
SheppLogan : H(k)  sin
 2kcut-off

k
Hann : H(k)  0.5 | k | 1cos
kcut-off
1 FIGURE 16-10  Ramp filter and two other recon-
struction filters that are designed to prevent arti-
facts and noise amplification caused by the sharp
0.8 Ramp cut-off of the ramp filter at the maximum frequency
kmax. Note that all of the filters shown have the same
Amplitude H (k /kmax)

response at lower frequencies and that cut-off fre-


0.6 quencies are set so that kcut-off = kmax. However, the
Shepp–Logan Hann and Shepp-Logan filters roll off gradually at
higher frequencies, thereby minimizing artifacts
and noise amplification.
0.4

0.2
Hann
0
0 0.2 0.4 0.6 0.8 1
Frequency (k/kmax)

Because of its speed and relative ease of additional preprocessing or postprocessing


implementation, FBP became a widely used data manipulations that work with varying
reconstruction method in nuclear medicine. degrees of success. They are discussed further
A single 2-D image slice can be reconstructed in Chapter 17, Section B.
in a fraction of a second on a standard com- By contrast, another set of reconstruction
puter. Under idealized conditions (noise-free methods, known as iterative reconstruction
data acquisition, completely sampled data, techniques, can build these steps directly into
and so forth), FBP produces an accurate the reconstruction algorithm and are less
representation of the distribution of radio- prone to the artifacts described in the pre-
activity within the slice. However, FBP is ceding paragraph. These techniques are
not without its limitations. First, it is sus- described in Section D.
ceptible to major artifacts if data from the
object are measured incompletely (possibly 4.  Multislice Imaging
because of collimator defects, portions of the The analysis presented earlier for backprojec-
object outside the FOV of the camera for tion and Fourier-based reconstruction tech-
some projections, etc.). Second, in datasets niques applies to single-slice images. In
that have poor counting statistics or random practice, as described in Chapters 17 and 18,
“noise” spikes (perhaps caused by instrument both SPECT and PET imaging are performed
malfunction), FBP produces annoying “streak with detectors that acquire data simultane-
artifacts.” These artifacts can be suppressed ously for multiple sections through the body.
by employing a k-space filter with a strong Projection data originating from each indi-
roll-off at high spatial frequencies, but this vidual section through the object can be
results in loss of image resolution as well. reconstructed as described. Individual image
Finally, the FBP algorithm cannot readily slices then are “stacked” to form a 3-D dataset,
be modified to take into account various which in turn can be “resliced” using com-
physical aspects of the imaging system and puter techniques to obtain images of planes
data acquisition, such as limited spatial reso- other than those that are directly imaged.
lution of the detector, scattered radiation, Thus 2-D multislice imaging of contiguous
and the fact that the sensitive volume of the slices can be used to generate 3-D volumetric
detector collimator holes actually is a cone images. In many SPECT systems, the dis-
rather than a cylinder, as assumed for the tance between image slices and slice thick-
reconstruction process. These factors require ness can be adjusted to achieve different axial
16  •  Tomographic Reconstruction in Nuclear Medicine 263

resolutions, much the same as the sampling at least twice per cycle. Coarser sampling
interval, Δâ•›r, across the image profile can be does not allow higher spatial frequencies to
adjusted to vary the in-plane resolution. In be recovered and leads to image artifacts
PET systems, the distance between image known as aliasing. Mathematical aspects of
slices and the slice thickness often is fixed by aliasing are discussed in detail in Appendix
the axial dimensions of the segmented scintil- F, Section C.
lator crystals typically used in the detectors Thus the linear sampling distance sets a
(See Chapter 18, Sections B and C). limit on spatial resolution for the imaging
system. This limit (kmax in Equation 16-13)
also is known as the Nyquist frequency, kNyquist
(see also Equation F-9). The highest spatial
C.  IMAGE QUALITY IN FOURIER frequency that is present in an image profile
TRANSFORM AND FILTERED depends on the spatial resolution of the
BACKPROJECTION TECHNIQUES collimator-detector system. Higher resolution
implies higher frequency content. As a rule of
In this section, we discuss some general issues thumb, the sampling requirement for an
involving image quality in reconstruction imaging detector is
tomography based on the direct FT and FBP
techniques. These issues affect all reconstruc- ∆ r ≤ FWHM / 3 (16-14)
tion tomography based on these techniques,
including both x-ray CT and ECT. Additional where FWHM is the full width at half
aspects that are specifically relevant to maximum of its point-spread function (see
SPECT and PET image quality are discussed Chapter 15, Section B.2).
in Chapters 17 and 18, respectively. The Figure 16-11 shows images of a computer-
issues discussed here do not pertain directly simulation phantom that were reconstructed
to iterative reconstruction techniques, which with progressively coarser sampling of the
are discussed separately in Section D. image profiles. Undersampling not only
results in image blurring but also creates
1.  Effects of Sampling on   image artifacts resulting from the effects of
Image Quality aliasing.
Projection data are not continuous functions The Nyquist frequency is the highest
but discrete point-by-point samples of projec- spatial frequency represented in k-space and
tion profiles. The distance between the sample thus defines an upper frequency limit for 
points is the linear sampling distance. In addi- the reconstruction filter. However, a lower-
tion, projection profiles are acquired only at a frequency filter cut-off, kcut-off < kNyquist can be
finite number of angular sampling intervals used in the reconstruction. This improves
around the object. The choice of linear and SNR by suppressing the high-frequency end
angular sampling intervals and the cut-off fre- of the spatial frequency spectrum, where a
quency of the reconstruction filter (see Fig. large fraction of the signal is statistical
16-10), in conjunction with the spatial resolu- noise. Lowering the cut-off frequency also
tion of the detector system, determine the degrades spatial resolution, because the
spatial resolution of the reconstructed image. higher frequencies also contain the fine
The effects of the imaging system depend on details of the image. Thus the choice of the
the type of detector, collimator, and so forth reconstruction filter and its cut-off frequency
and are discussed in Chapters 17 and 18. Here involve a tradeoff between spatial resolution
we discuss briefly those aspects that are and SNR in the image. This is illustrated in
related to the reconstruction process, which Figure 16-12, which shows images of a
are applicable to all types of imaging devices. computer-simulation phantom reconstructed
The sampling theorem5 states that to with a Shepp-Logan filter with different
recover spatial frequencies in a signal up to a cut-off frequencies.
maximum frequency kmax requires a linear The angular sampling interval (angle
sampling distance given by between projections) should provide sampling
around the periphery at approximately the
same intervals as the linear sampling dis-
∆ r ≤ 1/(2kmax ) (16-13)
tance. Thus if projections are acquired around
a FOV of diameter D, the minimum number
This means that the highest spatial frequency  of angular views, Nviews, should be approxi-
to be recovered from the data must be sampled  mately the length of the 180-degree arc over
264 Physic in Nuclear Medicine

∆r = 0.2 cm ∆r = 0.4 cm

FIGURE 16-11  Images of a computer-


simulation phantom reconstructed
with progressively coarser sampling 
of the image profiles. Linear under�
sampling results both in loss of resolu-
∆r = 0.8 cm ∆r = 1.6 cm tion and image artifacts. (Computer
simulations performed by Dr. Andrew
Goertzen, University of Manitoba,
Canada.)

FIGURE 16-12  Filtered backprojec-


tion reconstructions of the computer-
simulation phantom shown in Figure
16-6, using a Shepp-Logan filter with
different cut-off frequencies. A, kcut-off
A B = kmax; B, kcut-off = 0.8 kmax; C, kcut-off =
0.6 kmax; and D, kcut-off = 0.2 kmax. Note
the tradeoff between image detail and
signal-to-noise ratio. (Computer simu-
lations performed by Dr. Andrew
Goertzen, University of Manitoba,
Canada.)

C D
16  •  Tomographic Reconstruction in Nuclear Medicine 265

which projections are acquired (πâ•›D/2) divided For FOV = 30╯cm, this amounts to
by the linear sampling distance, Δâ•›r:
Nsamp ≥ 30 / (1/ 3) ≈ 90 samples per profile
N views ≥ π D/ 2∆ r (16-15)
According to Equation 16-15, the number of
Figure 16-13 illustrates the effect of angular views should be such that
sampling interval on images of a computer-
simulation phantom. Spokelike artifacts  N views ≥ (π × 30) / [2 × (1/ 3)] ≈ 140 views
are evident around high-intensity objects
when the number of angular samples is Thus 140 views over a 180-degree degree 
inadequate. arc, with linear sampling at approximately
0.33-cm intervals, would fully support the
EXAMPLE 16-1 available system resolution.
Suppose you are working with an ECT system
that has spatial resolution FWHM ≈ 1╯cm and The closest power-of-two image reconstruc-
FOV = 30╯cm. Estimate the sampling inter- tion and display matrix that would meet the
val, Δâ•›r, and the number of angular views, sampling requirements in Example 16-1 is 128
Nviews, that would support the available spatial × 128. One possibility would be to interpolate
resolution of the system. the sampled profiles from 90 samples to 128
samples. A more practical option, however, is
Answer to acquire 128 samples over 30╯cm, which
From Equation 16-14, the sampling interval would somewhat exceed the linear sampling
should be requirement. If this were done, Equation 16-15
would suggest that additional views would be
∆r ≤ 1 cm / 3 ≈ 0.33 cm needed to support the smaller value of Δâ•›r;

FIGURE 16-13  Effect of the number of angular samples recorded on the reconstructed image of a computer-simulation
phantom. Spokelike streak artifacts are evident when an inadequate number of projections are used. (Computer simu-
lations performed by Dr. Andrew Goertzen, University of Manitoba, Canada.)
266 Physic in Nuclear Medicine

however, 140 views still would provide the and some positron emission mammography
number of angular views needed to support systems).
the system resolution and this number would A second requirement for coverage is that
not have to be increased. On the other hand, the entire object (or at least the parts contain-
going in the opposite direction, that is, acquir- ing radioactivity) must be included in all pro-
ing only 64 samples and fewer angular samples jections. If some parts of the object are not
for reconstruction on a 64 × 64 matrix would included in all projections, the data will be
lead to a loss of image detail and introduce the inconsistent between different projections.
possibility of image artifacts, as illustrated in There are a number of ways in which this can
Figures 16-11 and 16-13. happen. For example, the FOV of the detector
may be insufficient to provide full coverage
2.  Sampling Coverage and   from all directions. Figure 16-15 illustrates
Consistency Requirements the effect of incomplete coverage of the object
In addition to meeting the requirements during some parts of the scan.
described in the preceding section regarding Two other possible sources of inconsistency
linear and angular sampling intervals, the between projections are patient movement
data acquired must provide full coverage of and missing or distorted values in individual
the object. Thus it is necessary that data be profiles caused by instrumentation failures,
acquired over a full 180-degree arc. If an arc such as an unstable element in a detector
less than 180 degrees is used, geometric dis- array. Figure 16-16 illustrates some effects of
tortions are produced. Figure 16-14 demon- these types of inconsistencies.
strates that an inadequate angular-sampling
range causes data to flare out past the true 3.  Noise Propagation, Signal-to-Noise
objects and produces geometric distortions Ratio, and Contrast-to-Noise Ratio
perpendicular to the direction of the absent Noise propagation, SNR, and CNR differ in
projections. This is a problem for a number ECT from their behavior in conventional
of systems developed in nuclear medicine planar imaging. In conventional planar
that are classified as “limited-angle tomogra- imaging, the SNR for an individual pixel is
phy” (e.g., rotating slant-hole tomography essentially equal to Npixel , in which Npixel is

FIGURE 16-14  Effects of angular


sampling range on images of a
computer-simulation phantom. Images
obtained by sampling over 45 degrees,
90 degrees, 135 degrees, and 180
degrees. Sampling over an interval of
less than 180 degrees distorts the
shape of the objects and creates arti-
facts. (Computer simulations per-
formed by Dr. Andrew Goertzen,
University of Manitoba, Canada.)
16  •  Tomographic Reconstruction in Nuclear Medicine 267

FIGURE 16-15  Effects of having some profiles that do not cover the entire object. Left, Sinogram of computer-
simulation phantom. Right, Reconstructed image. (Computer simulations performed by Dr. Andrew Goertzen, University
of Manitoba, Canada.)

FIGURE 16-16  Effects of missing projection elements on reconstructed image. Left, Sinogram of computer-simulation
phantom. Right, Reconstructed image. This simulation would apply to a SPECT image reconstructed from profiles
acquired over a 180-degree sampling range with a single-headed camera, with one region of the detector “dead.” (Com-
puter simulations performed by Dr. Andrew Goertzen, University of Manitoba, Canada.)

the number of counts recorded for that pixel. square matrix of size D × D = D2 with pixel
In ECT, the computation of noise and SNR is size Δâ•›r × Δâ•›r = Δâ•›r 2. It can be shown that the
much more complicated because the intensity SNR for an individual pixel in the resulting
level for each pixel is derived by computations image of the object is given by6
involving different views and many other
pixels in the image. In addition, a variety of 12 N image
mathematical manipulations, such as filtering SNR pixel ≈ (16-16)
operations, are performed along the way. As a π2 ( D / ∆ r ) 3
result, although SNR still depends on the
square root of the total number of counts Equation 16-16 indicates that SNR decreases
recorded during the imaging procedure, the when pixel size, Δâ•›r, is made smaller, that is,
relationship between those counts and the as spatial resolution is improved.* The
SNR of individual pixels is more complicated.
Suppose that an ECT image is acquired of
a cylindrical object of diameter D containing
*Note that Equation 16-16 specifically assumes that pixel
a uniform concentration of radioactivity. width is the same as the sampling interval, Δâ•›r. Often in
Suppose further that projection data are nuclear medicine, interpolation techniques are used to
acquired with a linear sampling interval Δ r generate images with pixels that are smaller than the
across all projection profiles, that a total  sampling interval. Equation 16-16 is valid in these situ-
ations provided that the sampling interval rather than
of Nimage counts are recorded during the pixel size is used in the equation. Some texts describe Δâ•›r
imaging procedure, and that the image is as the “resolution element” to avoid confusing it with
reconstructed by FBP with a ramp filter on a pixel size.
268 Physic in Nuclear Medicine

dependence is relatively strong, as illustrated consistent with conventional counting statis-


by the following example. tics. However, as compared with conventional
planar imaging (or photon counting), there is
EXAMPLE 16-2 an additional factor equal to the fourth root
Suppose that an image of a 20-cm diameter of the total number of pixels (or resolution
cylinder containing a uniform distribution of elements) in the denominator of the equation.
activity is generated by FBP reconstruction. This places stronger requirements on count-
The image is reconstructed on a square ing statistics for reconstruction tomography
matrix, 20 × 20╯cm in size with 1 × 1╯cm pixel as compared with planar imaging, to achieve
size. A total of 1 million counts are acquired a specified level of SNRpixel, as illustrated in
for the image. Calculate the number of counts the following example.
required to generate an image with the same
EXAMPLE 16-3
SNR per pixel if both the sampling interval
and pixel size are reduced to 0.5╯cm. Consider two images of a cylindrical cross-
section 20╯cm in diameter with a uniform con-
Answer centration of radioactivity, one a planar image
For the image with 1╯cm resolution, from and the other generated by FBP reconstruc-
Equation 16-16 tion with a ramp filter. Each image is 20 ×
20╯cm in size with 1 × 1╯cm pixel size, and a
12 × 106 total of 1 million counts are acquired for each
SNR pixel ≈
π 2 × (20 / 1)3 image. What is the percent noise level, rela-

tive to signal level, in each image?
≈ 12.33
Answer
To maintain the same value of SNRpixel with For both images,
0.5-cm pixels, the required number of counts percent noise level
in the image, N0.5â•›cm, must be such that
= (noise/signal) × 100%
= 100% /SNR pixel
12 × N0.5 cm
≈ 12.33
π × (20 / 0.5)3
2
For the planar image, the average number of
counts per pixel within the area occupied by
Solving this equation yields the requirement the 20-cm diameter object is
of N0.5â•›cm = 8 million counts.
npixel = [106 / (π × 102 )] counts/cm 2 × 1 cm 2 /pixel
Example 16-2 indicates that if Δâ•›r is
decreased by a factor of 2 (to Δâ•›r/2), the total ≈ 3180 counts/pixel
number of counts required to keep the SNR
per pixel constant increases by a factor of 8, This yields an SNR given by
that is, as the inverse cube of the size of the
pixel. npixel
SNR pixel = = npixel
The total number of pixels in the recon- npixel

structed image is npixels = (D/Δâ•›r)2. Equation
16-16 can be rewritten as = 3180 = 56

< Npixel > from which the percent noise level is 100%/56
SNR pixel ≈ 12 / π 2 ×   (16-17) ≈ 1.8%.
4 npixels For the image reconstructed by FBP, the
result is as given in Example 16-2:
where <â•›Nâ•›pixelâ•›> is the average number of
counts recorded per reconstructed pixel in the SNR pixel ≈ 12.33
object. This can be simplified even further by
noting that 12 /π 2 = 1.103 ≈ 1, for more from which the percent noise level is
approximate work. 100%/12.33 ≈ 8.1%.
Equation 16-17 indicates that SNR per
pixel improves in proportion to the square The “noise enhancement” factor for recon-
root of the average number of counts recorded struction tomography illustrated in Example
per pixel. This part of the equation is  16-3 is the result of noise propagation from
16  •  Tomographic Reconstruction in Nuclear Medicine 269

pixels at many locations in the imaged object image is < Npixel> ≈ 10 counts per minute (cpm)
into the pixel of interest in the backprojection × 1╯min = 10. Thus from Equation 16-17, the
process, as well as the ramp filtering SNR per pixel for the ECT image would be
operation.
Example 16-3 applies to the SNR of a single 10 10
SNR pixel ≈ ≈ ≈1
pixel in images of a uniform object. The result 4
100 10
would seem to imply a statistical disadvan-
tage for the detection of low-contrast objects Using the definition given in Equation 15-6,
by ECT. However, for purposes of applying the contrast of the lesion in the ECT image is
the Rose criterion for detectability of lesions
and other objects (see Chapter 15, Section C = (1 − 10) /10 = −0.9
D.2) this must be converted to CNR for the
object of interest. Using the definitions given Substituting these values into Equation
in Chapter 15, it can be shown that the CNR 16-18, one obtains
for a lesion that occupies n pixels in an ECT
image is CNR  ≈ −0.9 × 1 × 1 ≈ 0.9

CNR  ≈ C × n × SNR pixel (16-18) which is the same result as obtained for
planar imaging. In neither case would the
where the absolute value indicates that CNR lesion be detectable using the Rose criterion.
always is a positive quantity. Although the
noise characteristics in ECT differ somewhat Example 16-4 shows that, for the same
from those of planar imaging (particularly level of object contrast and total number of
regarding possible artifacts), the same general counts in the image, and in the absence of
rules for detectability apply for ECT and attenuation and distance effects, there is no
planar images, that is, CNR ≥ 4. intrinsic difference in CNR between ECT and
planar imaging. This result is obtained, in
spite of the apparent statistical disadvantage
EXAMPLE 16-4 of ECT illustrated in Example 16-3, because
Consider the situation described for radio- of the increased contrast of the low-contrast
pharmaceutical B in Example 15-6. In that lesion in an ECT image as compared with a
example, the radiopharmaceutical produced projection image. On the other hand, the
“cold” lesions with uptake that was 10% of the sophisticated data manipulations of ECT do
surrounding normal tissue and a CNR of only not improve the detectability of the lesion.
0.9 for a 1-cm diameter lesion. Using the This is not too surprising, because it should
same parameters, estimate the CNR that not be possible to improve CNR when noise is
would be achieved using the same radiophar- generated by counting statistics by applying
maceutical, spatial resolution, and total mathematical manipulations (e.g., recon-
imaging time with ECT. Assume that the struction tomography and contrast enhance-
normal tissue fills a volume of (10 × 10 × ment) of otherwise comparable data.
10╯cm) and, as in Example 15-6, ignore the Thus it is inaccurate to conclude that ECT
effects of attenuation and source-to-detector improves detectability of lesions or other
distance. objects by improving CNR. Rather, the
primary advantage of ECT for detecting low-
Answer contrast lesions derives from its ability to
The planar image described for Example 15-6 remove confusing overlying structures that
could be obtained by facing the detector may interfere with detectability of those
toward any face of the cubic volume of tissue lesions, such as ribs overlying a lesion in the
and acquiring counts for a 1-min imaging lungs. Not only does an object become more
time. For purposes of computing the SNR of detectable when overlying clutter is removed
an ECT image, many projection views would by ECT, but its shape and borders become
be required (e.g., 60 1-sec views), but the total more clear.
number of counts recorded in 1╯min of imaging An additional advantage of ECT is the
time, in the absence of attenuation and dis- ability to determine more accurately the con-
tance effects, would be the same as for planar centration of radioactivity in a particular
imaging. The total number of pixels in the volume of tissue. For example, in Example
ECT image is npixels = 10 × 10 = 100, and 16-4, the same planar image would be
the average number of counts per pixel in the obtained if the lesion were twice as thick
270 Physic in Nuclear Medicine

along the viewing direction, but with half the and precomputing factors), reconstruction
uptake suppression and thus twice the con- times have become practical and iterative
centration as originally specified in Example methods are finding their way into more
15-6. However, such a difference would be general use.
readily evident on the ECT image (assuming
the CNR requirements for detectability were
met). Some appreciation for all of these advan- 1.  General Concepts of Iterative
tages can be gained by inspection of Figure Reconstruction
15-11. The general concepts of iterative reconstruc-
tion are outlined in Figure 16-17. In essence,
the algorithm approaches the true image, 
D.  ITERATIVE RECONSTRUCTION f (x,y), by means of successive approximations,
ALGORITHMS or estimates, denoted by f╛╛*(x,y). Often the
initial estimate is very simple, such as a blank
A viable and increasingly used alternative  or uniform image. The next step is to compute
to FBP is a class of methods known as  the projections that would have been mea-
iterative reconstruction. These methods are sured for the estimated image, using a process
computationally more intensive than FBP called forward projection. This process is
and for this reason have been more slowly exactly the inverse of backprojection. It is per-
adopted in the clinical setting. However, as formed by summing up the intensities along
computer speeds continue to improve, and the potential ray paths for all projections
with a combination of computer acceleration through the estimated image. The set of 
techniques (e.g., parallel processors), and projections (or sinogram) generated from 
intelligent coding (e.g., exploiting symmetries the estimated image then is compared with

Measured
projection data
sinogram p (r,φ)
Object
f(x,y)

ECT system

Forward
Image projection Calculated
estimate Compare
projection converged?
f *(x,y) data p(r,φ) Yes

No
Reconstructed
image

Update
image
estimate

FIGURE 16-17  Schematic illustration of the steps in iterative reconstruction. An initial image estimate is made and
projections that would have been recorded from the initial estimate then are calculated by forward projection. The
calculated forward projection profiles for the estimated image are compared to the profiles actually recorded from the
object and the difference is used to modify the estimated image to provide a closer match. The process is repeated until
the difference between the calculated profiles for successively estimated images and the actually observed profiles
reaches some acceptably small level.
16  •  Tomographic Reconstruction in Nuclear Medicine 271

the actually recorded projections (or sino- image and the profiles actually recorded from
gram). Most likely, they will not agree, because the scanned object. The second component is
it is unlikely that the initial estimate of f╛╛*(x,y) performed by the search or update function,
closely resembles the true image. However, which uses the output of the cost function to
the difference between the estimated and update the estimated image. A general goal of
actual projections can be used to adjust the algorithm development is to devise versions
estimated image to achieve closer agreement. of these functions that produce convergence
The update-and-compare process is of the estimated image toward the true image
repeated until the difference between the as rapidly and accurately as possible. One
forward-projected profiles for the estimated area of algorithmic differences is the method
image and the actually recorded profiles falls for dealing with statistical noise. For example,
below some specified level. With proper design some algorithms give more weight to portions
of the image updating procedure, the esti- of projections (or sinograms) that contain the
mated image progressively converges toward highest number of counts, and thus the lowest
the true image. Figure 16-18 shows the prog- percentage levels of statistical noise (see
ress of the estimated image during iterative Chapter 9, Section B.1). Another approach is
reconstruction with an increasing number of to incorporate some sort of “prior informa-
iterations. tion,” such as the expected shape or smooth-
The two basic components of iterative ness of the image. Some algorithms also
reconstruction algorithms are (1) the method “force” the reconstructed image to be non-
for comparing the estimated and actual pro- negative. A concise history and review of iter-
files and (2) the method by which the image ative reconstruction methods are presented in 
is updated on the basis of this comparison. In reference 7.
generic terms, the first component is per- Two factors make iterative reconstruction
formed by the cost function, which measures computationally more intensive than FBP.
the difference between the profiles generated First, most iterative algorithms require
by forward projections through the estimated several iterations to converge to an acceptable

Iteration 1 Iteration 3 Iteration 5

Iteration 10 Iteration 20 Iteration 30

FIGURE 16-18  Brain images generated for different numbers of iterations by an iterative reconstruction algorithm.
Image resolution progressively improves as the number of iterations increases. In practice, the iterations are performed
until an acceptable level of detail is achieved or until further iterations produce negligible improvement. (Courtesy Dr.
Richard Leahy, University of Southern California, Los Angeles, CA.)
272 Physic in Nuclear Medicine

image, and each of these iterations is essen- profile.) Because of the statistical weighting
tially equivalent to a separate backprojection factor, the algorithm often is referred to as the
procedure. Backprojection is the most time- ML-EM method. A detailed discussion of this
consuming part of the FBP algorithm but only algorithm and its theoretical underpinnings
needs to be done once for FBP. Forward pro- are beyond the scope of this text but can be
jection is similarly time-consuming in itera- found in references 8 and 9. Here we present
tive reconstruction algorithms. only a description of how it is implemented.
Second, iterative algorithms often incorpo- In the EM algorithm, the reconstruction
rate factors that account for the specific char- process is formulated as follows
acteristics of the imaging device, such as
collimator and object scatter, system geome-
try, and finite detector resolution. Simple p j = ∑ Mi, j fi (16-19)
forward projection along a single ray path no i

longer is used to calculate the projection pro-


files for the estimated image. Instead, all where fi is the intensity (or activity) in the ith
image pixels are considered to have a finite pixel in the image, pj is the measured inten-
probability of contributing data to virtually sity in the jâ•›th projection element, and Mi,j is
all ray paths. In practice, very distant pixels the probability that radiation emitted from
might not be considered. Nevertheless, this the iâ•›th pixel will be detected in the jâ•›th projec-
adds to the computing time, because the tion element. Note that, unlike previous uses
reconstruction must include effects not only of i and j to represent different (x,y) locations
from pixels directly along a ray path but from in a 2-D image (or a set of projections), the
pixels outside that ray path as well. indices here each apply to the full set of the
A number of methods have been developed subscripted quantities. Thus, if the image is
to speed up these advanced algorithms. One reconstructed on a grid of 128 × 128 pixels,
of the most popular is called ordered subsets. the subscript i runs from 1 to 16,348 (128 ×
In this method only a small number (or 128). If the imaging system records projec-
subset) of projection angles are used in the tions at 128 different angles around the object,
initial iterations. As the image is refined,  and each projection has 256 elements, the
a larger number of projection angles are index j runs from 1 to 32,768 (128 × 256). In
included. This speeds up the algorithm, essence, all of the image pixels and projection
because the time per iteration is directly pro- elements are “strung together” to form a
portional to the number of projection profiles single list for each set. The matrix M is very
that must be computed. The ordered-subsets large, even for a single-slice image (16,384 ×
approach can be used to speed up both simple 32,768 in the previous example). It can be
forward projection-based iterative algorithms extended to three dimensions as well, in
as well as the advanced algorithms that use which case it becomes even larger.
complex modeling of the imaging system. The matrix approach described above pro-
Although they are more challenging to vides a potentially much more accurate model
implement compared with FBP, iterative for relating projection profiles to the under�
algorithms have the potential for providing lying source distribution than simple forward
quantitatively more accurate reconstructions. projection. The matrix could be determined by
An example of one algorithm is presented in calculations, simulations, or a combination of
the following section. both. For example, one could position a point
source at all locations within the imaged slice
2.  Expectation-Maximization (or volume) and record the counts in all ele-
Reconstruction ments of all possible projection profiles.
The expectation-maximization (EM) algo- However, this would be very time consuming.
rithm incorporates statistical considerations Symmetry considerations could somewhat
to compute the “most likely,” or maximum- shorten the project. In practice, many of the
likelihood (ML), source distribution that geometric effects can be calculated from
would have created the observed projection simple models (e.g., collimator response—see
data, including the effects of counting statis- Fig. 14–15) and others, such as collimator
tics. Specifically, it assigns greater weight to scatter, can be simulated or derived from the-
high-count elements of a profile and less oretical models.
weight to low-count regions. (By comparison, Once the matrix M has been determined
backprojection algorithms assign a uniform and projection profiles have been recorded,
statistical weighting to all elements of a the operating equation for computing the 
16  •  Tomographic Reconstruction in Nuclear Medicine 273

estimated intensity value f of pixel i in the of angular views results in a more or less
(k + 1)st iteration of the EM algorithm is as uniform loss of spatial resolution across the
follows: reconstructed image. If only partial angular
coverage of the object is obtained (e.g., from
fik pj
fik+1 = × ∑ Mi, j 0 to 120 degrees instead of over the full
∑ Mi, j j  k
 ∑ Ml, j fl 
(16-20) 180 degrees), the resolution is likely to be
j
l
degraded along the direction of the missing
data. Because iterative algorithms are non-
where k refers to the immediately preceding linear in nature, the exact effects of under-
kth iteration. The term in parentheses in sampling are object and algorithm
the denominator on the right hand side of dependent.
Eq. 16-20 represents a summation over all
image pixels. This term must be evaluated
first before the summation over the j projec- E.  RECONSTRUCTION OF FAN-BEAM,
tion elements can be computed. Therefore  CONE-BEAM AND PINHOLE SPECT
it is given a different pixel index, l, instead DATA, AND 3-D PET DATA
of i, to avoid confusion.
The number of iterations can be fixed, or The discussion thus far has focused on recon-
the iteration process can be terminated when structing projection data in which the acquired
some measure of the difference between rays for a given projection angle are parallel
images from one iteration to the next (e.g.,  and the projection data arises from parallel
the sum of the squares of differences for all sections through the body. This is the situa-
pixels in the reconstructed image) falls below tion when a parallel-hole collimator is used.
some predetermined value. In theory, with Tomographic reconstruction also can be per-
perfectly measured noise-free data and an formed using data acquired with fan-beam,
exact matrix M, the algorithm eventually cone-beam, or pinhole collimators. The ratio-
would converge to the point where the esti- nale for using these collimators is that they
mated projection data, ∑ l Ml, j flk exactly can provide higher spatial resolution
equals the measured projection data, pj, for (converging-hole or pinhole collimators) or
each profile. At that point greater coverage (diverging-hole collimators—
see Chapter 14, Section D). However, these
fik+1 = fik (16-21) collimators introduce an added degree of com-
plexity for reconstruction tomography of
that is, there is no further change in the esti- SPECT data, because they do not provide
mated image and the estimated activity image simple parallel-ray line integral projections
is identical to the true activity distribution. such as were illustrated in Figure 16-2.
In practice, this never happens, owing to inac- Similar issues arise in PET scanning. In addi-
curacies or simplifications in M and statisti- tion to acquiring projection data for trans-
cal noise. Therefore some practical limit must verse sections through the body, PET scanners,
be set for an acceptable difference that will be as discussed in Chapter 18, Section C, also are
used to terminate the reconstruction process. capable of acquiring additional projection
The computational issues relating to itera- data at oblique angles with respect to these
tive reconstruction techniques already have transverse slices. Accurately incorporating
been mentioned. Equation 16-20 (which rep- this additional projection data requires 3-D
resents only a single-slice version of the algo- reconstruction algorithms.
rithm) illustrates this point. Nevertheless,
the ML-EL algorithm can produce high- 1.  Reconstruction of Fan-Beam Data
quality images with good quantitative accu- We should first distinguish between fan-beam
racy and is now a selectable option on many versus cone-beam collimators. Figure 16-19
PET and SPECT cameras. schematically illustrates the difference. Con-
The sampling and noise-propagation rules sider first the fan-beam collimator shown at
summarized in Section C do not apply to the top of the figure. In this collimator, each
iterative reconstruction. Although insuffi- row of holes across the collimator has its own
cient sampling also has consequences for focal point. Sequential rows of collimator
iterative algorithms, the aliasing and streak- holes are stacked and evenly spaced, parallel
ing artifacts associated with FBP are not to each other, along the z-axis of the object.
seen. More typically, undersampling in the Apart from overlapping coverage resulting
linear sampling distance or in the number from the finite diameters of the collimator
274 Physic in Nuclear Medicine

z r

Fan-beam

z r

Cone-beam

FIGURE 16-19  Schematic illustrations of fan-beam and cone-beam collimators. Cross-sections are shown for perpen-
dicular viewing angles.

holes, each row of holes provides its own  rotation around the object. However, whereas
independent and nonoverlapping projection complete coverage can be obtained with a
profile. 180-degree rotation using a parallel-hole col-
Data from a fan-beam collimator cannot be limator, the required rotation for a converging-
inserted directly into algorithms used for beam collimator is (180 + θ) degrees, in which
reconstructing data acquired with a parallel- θ is half the fan angle for the collimator (see
beam collimator. However, the data can be Fig. 14-20). Conversely, for a diverging colli-
rearranged so that these algorithms can be mator, the required angle of rotation is (180
used. One approach is to re-sort the fan-beam − θ) degrees.
data into parallel-beam data. Figure 16-20
illustrates how this is done for a few elements
of adjacent projection profiles. Once the  2.  Reconstruction of Cone-Beam  
data have been re-sorted, any of the algo- and Pinhole Data
rithms discussed in the preceding sections for In a cone-beam collimator (Fig. 16-19, bottom),
parallel-beam collimators can be used. Alter- all of the holes are directed toward (or away
native, and more elegant, approaches refor- from) a common focal point. Each row of holes
mulate the FBP algorithm itself to handle across the center of the collimator provides a
fan-beam data. These are discussed in refer- projection profile, but the profiles all intersect
ences 2 and 7. at the center. (This also applies to the pinhole
A fan-beam collimator provides complete collimator.) It is not possible to re-sort the
3-D coverage of a volume of tissue in a single data acquired from a single rotation of a
16  •  Tomographic Reconstruction in Nuclear Medicine 275

Fan-beam
data sets

Re-sorted into
parallel-ray
data sets
FIGURE 16-20  Procedure for creating parallel-beam projections from a set of fan-beam projections.

cone-beam collimator around the object into a 3-D cone-beam data; however, computing
full set of parallel-ray projections. Only one time increases dramatically as compared with
set (corresponding to the projections acquired already time-consuming single-slice iterative
from a single slice across the center of colli- algorithms. The matrix M (Equation 16-19)
mator, oriented perpendicular to the axis of becomes very large for a full 3-D algorithm
rotation) can be re-sorted in this way. There- and, even with accelerated approaches and
fore to obtain complete projection coverage of specialized computer hardware, full 3-D
a volume of tissue to allow accurate recon- image reconstructions are typically at least
struction of multiple slices, a more complex an order of magnitude slower than multislice
rotation is required. 2-D image reconstructions.
One approach is to perform a helical scan
around the object, translating the collimator 3.  3-D PET Reconstruction
along the z-axis as it rotates about that axis. PET scanners typically consist of multiple
This provides a dataset that can be re-sorted detector rings (see Chapter 18, Section B).
into a complete set of parallel projections for Projection data acquired within a given detec-
multiple slices through the object. An alterna- tor ring can be reconstructed into a trans-
tive approach is to use approximations and verse image with the methods described
interpolations to convert the cone-beam data previously in Sections B and D. However,
into fan-beam data. The most popular of these PET scanners also can acquire projection
methods is called the Feldkamp algorithm, data at oblique angles between detector rings
described in reference 10. These methods (see Chapter 18, Section C and Fig. 18-24). To
work best when the cone angle is small. incorporate these additional projection angles
Finally, iterative algorithms, conceptually requires some form of 3-D reconstruction
similar to those described in Section C, have algorithm. 3-D algorithms have been devel-
been developed for direct reconstruction of oped based on both FBP and iterative 
276 Physic in Nuclear Medicine

detector projection-ray
rings measured oblique rebinned into the
projection-ray transverse plane at
axial location (ab)/2

direction
axial
transverse
direction
FIGURE 16-21  Illustration of single-slice re-binning in which an oblique projection-ray between the detector pair a
and b is “re-assigned” to the projection data for the non-oblique slice corresponding to a transverse detector pair at
axial location (a + b)/2.

reconstruction methods. A detailed descrip- An alternative approach is to formulate


tion of these algorithms is beyond the scope the iterative reconstruction equations (Eqs.
of this text. However, some general concepts 16-19 to 16-21), for fully 3-D reconstruction,
will be presented. thus implicitly accounting for the exact ori-
One common approach is to “re-bin”   entation of each line of response. Because of
the 3-D dataset, such that each oblique pro- the additional dimensionality of the projec-
jection ray is placed within the projection tion data, and the fact that the images are
data for a particular nonoblique 2-D trans- being reconstructed into a 3-D volume rather
verse slice. In effect, the 3-D dataset is col- than a 2-D slice, the matrix M in Equation
lapsed back into a multislice 2-D dataset. 16-19 becomes very large. The number of
The most simple method to accomplish this elements can be in the range of 1013 to 1015
is to assign each ray to its average axial with modern PET scanners that have large
location.11 Thus an oblique projection-ray numbers of detector rings. Furthermore, the
between a detector at location a and a detec- backprojection and forward-projection steps
tor at location b would be positioned as if it must now be performed in 3-D, tracing each
were a projection from a directly opposed ray though a volume rather than across a
pair located halfway between them, i.e., at 2-D slice.
location (aâ•›+â•›b)/2 (Fig. 16-21). Processing of Thus the computational challenges are for-
all the projection rays in this manner results midable, although great progress has now
in a series of sinograms of parallel-ray pro- been made in reducing the matrix size using
jections, each corresponding to different sparse storage techniques and symmetry
axial locations through the object. Each sino- arguments, and multiprocessor hardware and
gram can then be reconstructed using the efficient coding have produced fast methods
2-D FBP or iterative algorithms described for 3-D backprojection and forward projection.
previously. This method is known as single- Fully 3-D iterative algorithms are now avail-
slice rebinning. able on some systems, especially small-animal
Figure 16-21 illustrates that for events imaging systems in which the small FOV
originating close to the center of the field of typically leads to more manageable projection
view (FOV) of the scanner, only small errors dataset sizes.
in positioning are made by this approxima-
tion. However, for events originating close to REFERENCES
the edge of the scanner, and for projections at
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made in the axial direction using this method. 2. Kak AC, Slaney M: Principles of Computerized Tomo-
To overcome this, more accurate methods that graphic Imaging, Philadelphia, 2001, SIAM.
include more sophisticated re-binning algo- 3. Herman GT: Fundamentals of Computerized Tomog-
raphy: Image Reconstruction from Projections, ed 2,
rithms and an axial filtering step12 or that use London, 2009, Springer-Verlag.
Fourier re-binning techniques13 have been 4. Natterer F: The Mathematics of Computerized
developed. Tomography, New York, 1986, Wiley.
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5. Oppenheim AV, Wilsky AS: Signals and Systems, 9. Lange K, Carson R: EM reconstruction algorithms for
Englewood Cliffs, NJ, 1983, Prentice-Hall, pp emission and transmission tomography. J Comput
513-555. Assist Tomogr 8:306-316, 1984.
6. Hoffman EJ, Phelps ME: Positron emission tomogra- 10. Feldkamp LA, Davis, LC, Dress JW: Practical cone-
phy: Principles and quantitation. In Phelps ME, beam algorithm. J Opt Soc Am 1:612-619, 1984.
Mazziotta JC, Schelbert HR, editors: Positron Emis- 11. Daube-Witherspoon ME, Muehllehner G: Treatment
sion Tomography and Autoradiography: Principles of axial data in three-dimensional PET. J Nucl Med
and Applications for the Brain and Heart, New York, 28:1717-1724, 1987.
1986, Raven Press, pp 237-286. 12. Lewitt RM, Muehllehner G, Karp JS: Three-
7. Leahy RM, Clackdoyle R: Computed tomography. In dimensional image reconstruction for PET by multi-
Bovik A, editor: Handbook of Image and Video Pro- slice rebinning and axial image filtering. Phys Med
cessing, Burlington, MA, 2005, Elsevier Academic Biol 39:321-339, 1994.
Press, pp 1155-1174. 13. Defrise M, Kinahan PE, Townsend DW, Michel C, 
8. Shepp LA, Vardi Y: Maximum likelihood reconstruc- Sibomana M, Newport DF: Exact and approximate
tion for emission tomography. IEEE Trans Med Imag rebinning algorithms for 3D PET data. IEEE Trans
1:113-122, 1982. Med Imag 16:145-148, 1997.
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chapter
17 
Single Photon
Emission Computed
Tomography

As discussed in Chapter 16, a rotating gamma are reconstructed on a matrix of 64 × 64 or 128


camera can be used to acquire data for com- × 128 pixels. Cross-sectional images are pro-
puted tomographic (CT) images. This approach duced for all axial locations (slices) covered by
to tomography, which is employed with radio- the field of view (FOV) of the gamma camera,
nuclides that emit single γ rays or multiple resulting in a stack of contiguous 2-D images
γ rays with no angular correlations, is known that form a 3-D image volume.
as single photon emission computed tomogra- The number of angular projections (or
phy (SPECT). In this chapter, we describe views) needed when using a standard parallel-
the design features and performance charac- hole collimator can be calculated using
teristics of SPECT systems. We also discuss Equation 16-15. Because the resolution of
some practical aspects of SPECT imaging and a general-purpose parallel-hole collimator is
some of its major clinical applications. A approximately 1╯cm at a distance of 10╯cm
second form of tomographic nuclear medicine from the collimator (see Fig. 14-16), the
imaging, positron emission tomography (PET), number of views required generally is between
uses radionuclides that decay by positron 64 and 128, for a FOV ranging from 20 to
emission. PET imaging systems and their 60╯cm in diameter. Although data acquired
characteristics are discussed in Chapter 18. over an arc of 180 degrees are sufficient for
Multimodality systems that combine SPECT tomographic reconstruction in SPECT, there
or PET with x-ray CT are discussed in  are advantages in terms of resolution unifor-
Chapter 19. mity and correction for γ-ray attenuation in
acquiring data over a full 360-degree arc. This
is discussed in Section B.1.
The sensitivity of a SPECT system can be
A.  SPECT SYSTEMS
improved by incorporating multiple detector
heads in the system. Both dual-headed 
1.  Gamma Camera SPECT Systems and triple-headed SPECT systems are avail-
Almost all commercially available SPECT able, with dual-headed systems being the
systems are based on the gamma camera most commonly encountered. These systems
detector that was described in detail in Chap- allow two or three angular projections to be
ters 13 and 14. A single gamma camera head, acquired simultaneously. For the same total
mounted on a rotating gantry, is sufficient to data acquisition time, each projection can be
acquire the data needed for tomographic recorded two or three times, leading to a
images. The gamma camera acquires two- twofold or threefold increase in the total
dimensional (2-D) projection images at equally number of counts acquired for the image.
spaced angular intervals around the patient. Alternatively, a multihead system can be
These images provide the 1-D projection data used to acquire the same number of counts in
needed for reconstructing cross-sectional one half or one third the time needed with a
images using the techniques described in single-head system. This can be useful for
Chapter 16. Typically, clinical SPECT images dynamic SPECT imaging to observe changes
279
280 Physics in Nuclear Medicine

in the distribution of a radiopharmaceutical Gamma camera


as a function of time (Section D). One also
could replace the parallel-hole collimator with
a converging collimator to obtain improved
sensitivity (see Fig. 14-21); however, this
results in a smaller FOV (see Fig. 13-7).
Photographs of single-headed and dual-
headed gamma cameras that are capable of Circular
SPECT imaging are shown in Figures 13-11 orbit
and 13-12. In dual-headed SPECT systems,
the detector heads are typically placed at 180 Patient
degrees relative to each other for whole-body
SPECT imaging, and at 90 degrees relative 
to each other for cardiac imaging. In some
systems the location of the detector heads is
fixed, whereas in others, they can be adjusted
by the operator. Figure 13-12 shows a system
in which the detector head orientations can
be changed. In addition to mechanical capa-
bilities for rotating the detector heads, gamma Gamma camera
camera systems intended for SPECT imaging
must be provided with computer capabilities
and software for image reconstruction, for
attenuation and scatter corrections, and for
display and analysis of 3-D image volumes.
The ability to perform conventional planar Contoured
imaging as well as tomographic imaging is a orbit Patient
very useful feature of these cameras.
Many SPECT systems have more sophisti-
cated gantries that allow the detector heads
to trace out elliptical rather than circular FIGURE 17-1  Illustration of circular (top) and contoured
(bottom) orbits for SPECT imaging. The contoured orbit
orbits. Some even allow orbits that follow the minimizes the distance of the detector from the patient,
contours of the patient. The body contour can thus optimizing spatial resolution.
be determined by an initial scout scan that,
for example, uses an infrared light source and
camera to trace the outline of the patient and several minutes. For imaging fast biologic
the bed as a function of angle. The importance processes, it would be desirable to acquire a
of this feature is evident from Figure 14-16, full set of projections in a few seconds. Fur-
which shows the rapid degradation in spatial thermore, traditional collimator design limits
resolution with increasing distance of the reconstructed spatial resolution to 1╯cm or
object from the collimator. As shown in Figure greater, which is inadequate for some applica-
17-1, elliptical orbits or orbits that follow tions in the human brain. A number of efforts
the contours of the patient allow the detector have been made toward addressing these
to pass closer to the patient than would be  limitations. Although they involve specialized
the case with circular orbits, which can  systems that are not currently commercially
lead to significant improvements in spatial available, we describe briefly some of the con-
resolution. cepts involved to illustrate possible alterna-
tives to performing SPECT with a rotating
2.  SPECT Systems for Brain Imaging gamma camera.
A disadvantage common to all of the SPECT The University of Michigan SPRINT II
systems described in the preceding section is system1 employs 11 γ-ray detectors in a polyÂ�
that the detector heads must be rotated gonal arrangement, each detector consisting 
around the patient to record the multiple  of 44 thin bars of sodium iodide [NaI(Tl)] 
projections required for tomographic recon- scintillator (dimensions 3-mm-wide × 13-mm-
struction. Because of the mechanical motions deep × 15-cm-long) coupled to an array
involved and the bulk of the detector head or of twenty 38-mm-diameter photomultiplier
heads, the shortest time in which a complete (PM) tubes arranged behind the NaI(Tl) bars
set of projections can be recorded generally is in a close-packed hexagonal array. In-slice
17  •  Single Photon Emission Computed Tomography 281

collimation is achieved using a lead aperture SPECT in smaller clinics, dedicated and
ring, with 12 equally spaced 2.4-mm-wide compact cardiac SPECT systems with high
slits, that rotates in front of the stationary sensitivity have been developed. In contrast
detector array (Fig. 17-2A). Axial collimation to the SPECT systems discussed so far, the
is achieved using a set of stacked stationary majority of these cardiac systems involve 
lead foils. As the collimator ring rotates the patient sitting upright in a chair during
through one slit interval (30 degrees), the the examination.
system acquires a complete set of fan-beam Figure 17-3A shows a triple-headed SPECT
projection data. system designed for cardiac applications.3
A system based on similar principles is the Note the much smaller size of the detector
CERASPECT system.2 In this case, the detec- heads compared with general-purpose SPECT
tor is a single annular NaI(Tl) crystal (31╯cm systems. The detector heads use pixelated
inner diameter × 8╯mm thick × 13╯cm wide) cesium iodide [CsI(Tl)] scintillator crystals,
coupled to 63 5-cm diameter PM tubes via read out by avalanche photodiodes (Chapter
glass light guides (Fig. 17-2B). A parallel-hole 7, Section C.3). The size of each CsI(Tl) pixel
collimator with six segments rotates in front is 6╯mm, and there are 768 pixels in each
of the detector, simultaneously providing six detector head, providing a detector FOV of
angular views. Each collimator segment has approximately 16╯cm × 20╯cm. In this system
a different FOV. This gives a higher weight- the detectors are fixed and the patient chair
ing to activity at the center of the object rotates to provide the necessary angular sam-
(which is viewed by all six collimator seg- pling for tomographic reconstruction. The 
ments) in comparison to activity toward the distance between the detectors and the chair
periphery of the object (which is seen by a can be adjusted to accommodate patients 
smaller number of collimator segments). This of different size. With a low-energy, high-
nonuniform weighting helps compensate for resolution (LEHR) collimator (see Table 14-1),
the effects of photon attenuation (see Sections the reported spatial resolution of the SPECT
B.1 and B.2) and provides more uniform images is 11╯mm (for a 20-cm detector-object
signal-to-noise ratio across the image. separation) and the sensitivity for each detec-
Both of these systems were designed pri- tor head is ~72 cps/MBq (160 cpm/µCi).
marily for brain imaging applications, and Because of the vertical orientation of the
both provide better image resolution than a patient, the entire system can fit in a room as
conventional SPECT system by placing the small as 2.4╯m × 2.4╯m.
collimated detector relatively close to the Another type of cardiac SPECT system
head. The reconstructed spatial resolution is replaces standard scintillation Anger camera
approximately 8╯mm at the center of the designs with detector heads made up of pixels
brain, improving to approximately 5╯mm at of the dense semiconductor cadmium zinc tel-
the edge of the brain. By comparison, a typical luride (CZT) (Chapter 7, Section B).4 This
single-head SPECT system operated with a system contains 10 small detector heads, dis-
radius of rotation of 12.5╯cm (appropriate for tributed in an arc over the chest of the patient
brain imaging) would have a resolution of (Fig. 17-3B). Each detector head [2-mm CZT
approximately 12.5╯mm full width at half pixels tiled on a 40-mm (transaxial) by 160-mm
maximum (FWHM) at the center of the brain (axial) area] is equipped with a parallel-hole
(see Fig. 14-16). These systems also have collimator and can rotate independently to
roughly twofold to threefold higher sensitivity sample different projection angles, enabling a
than a single-headed gamma camera with  complete projection dataset to be acquired for
a general-purpose parallel-hole collimator, tomographic reconstruction. The patient chair
because multiple sets of projection data can is stationary. The reconstructed spatial reso-
be acquired simultaneously. This enables lution is quite dependent on the location in the
higher resolution to be achieved without FOV, and is nonisotropic, ranging between
injecting more radioactivity or lengthening approximately 8 and 14╯mm. The sensitivity
the imaging time. of the system is on the order of ~400 cps/MBq
(900 cpmâ•›/â•›µCi) for each detector head. The
3.  SPECT Systems for Cardiac Imaging high sensitivity derives from the use of a
One of the most common uses for SPECT is shorter collimator with larger holes compared
to image myocardial function in patients with with the LEHR collimator.
a range of cardiovascular diseases. Because of A third design employs principles similar to
the relatively small FOV required for this the brain system shown in Figure 17-2A and
application, and the increasing use of cardiac described in Section 2. A multislit collimator
282 Physics in Nuclear Medicine

Field-of-view

Aperture ring
Scintillator bars
Detector module

Slice collimation

Detector

Collimator

Fields-of-view

B
FIGURE 17-2  Cross-sectional views showing the design of two SPECT systems designed for brain imaging. A, The
SPRINT system developed at the University of Michigan. This system employs a rotating collimator with 12 axial slits.
Transverse and axial views are shown. B, The CERASPECT system developed by Digital Scintigraphics, Inc., Cam-
bridge, MA. In this system, each collimator segment has a different field-of-view diameter. (A, From Rogers WL,
Clinthorne NH, Shao L, et╯al: SPRINT II: A second-generation single-photon ring tomograph. IEEE Trans Med Imag 7:291-297,
1988; B, From Genna S, Smith AP: The development of ASPECT, an annular single-crystal brain camera for high-efficiency
SPECT. IEEE Trans Nucl Sci 35: 654-658, 1988.)
17  •  Single Photon Emission Computed Tomography 283

Detector
heads

Patient
chair

Rotating
CZT
detector

FIGURE 17-3  Photographs of dedicated cardiac SPECT scanners: A, A system with three detector heads. The patient
sits upright in the chair and the chair rotates in front of the detectors to acquire the projection angles necessary for
tomographic reconstruction. B, A system comprising nine cadmium zinc telluride detector heads arranged in an arc
around the patient. Each detector head rotates independently to provide different angular views. The patient remains
stationary in the chair. (A, Courtesy Digirad Corp., Poway, CA; B, Courtesy Spectrum Dynamics Ltd. Caesarea, Israel.)

rotates in front of an arc-shaped gamma evaluation of new radiopharmaceuticals


camera that employs traditional continuous being developed for diagnostic purposes, or
NaI(Tl) crystals read out by PM tubes.5 This the use of established radiopharmaceuticals
rotating collimator gives rise to the different to measure functional, physiologic, or meta-
projection angles, with slice collimation pro- bolic processes in an animal model to monitor
vided by a stationary stack of thin concentric or understand the response to a new thera-
lead rings. For a source-to-aperture distance peutic approach.
of 20╯cm, this system can provide recon- The challenge is the small size of the organs 
structed spatial resolution in the range of 6 to (a few millimeters in diameter) in commonly
7╯mm. used experimental animals such as mice and
rats, relative to the spatial resolution typi-
cally obtained with SPECT systems. However,
4.  SPECT Systems for Small-Animal two key factors can be exploited to obtain
Imaging much higher spatial resolution with SPECT
In addition to their widespread clinical role, in small animals compared with what can be
SPECT systems also are used for appli� achieved in human imaging. The first is the
cations in biomedical research involving  small volume of tissue to be imaged, which,
small animals. Typical applications are the depending on the detector size used, can
284 Physics in Nuclear Medicine

permit high magnification of the object onto detector heads, each with a single pinhole col-
the detector with pinhole or converging hole limator, that rotate around the animal and
collimators (see Fig. 13-7). The second related translate along the animal to produce the
factor is that the organ of interest can always angular projections required for reconstruc-
be positioned within a few millimeters (rather tion tomography.
than many centimeters in humans) of the col- More advanced systems employ collimators
limator. Because of the strong dependence of with multiple pinholes to improve sensitivity.
spatial resolution on source-to-collimator dis- Such collimators also can increase the FOV 
tance (see Fig. 14-16), much higher resolution along the axial direction without the need
can therefore be obtained. Furthermore, if to translate the animal. In the most straight-
pinhole collimation is used, the sensitivity forward implementation, the pinholes are
also increases rapidly as objects of interest arranged with sufficient distance between
are moved close to the pinhole aperture (see them such that the image of the animal
Fig. 14-21B and Equation 14-16). projected through adjacent pinholes does not
Thus the most common approach to small- overlap on the detector (Fig. 17-4, left). In
animal imaging with SPECT has been to use some systems, the projections are allowed
pinhole collimation, with some magnification. to overlap to a certain degree, which enables
Indeed, standard clinical SPECT systems more pinholes to be used for a given detec-
have been used to great effect in small-animal tor area and magnification (Fig. 17-4, right).
imaging using a pinhole or multipinhole col- However, this leads to ambiguity in the pro-
limator. However, to achieve optimal resolu- jection data in the region of overlap, and
tion and sensitivity performance, in a compact tomographic reconstruction into SPECT
device suited to a laboratory environment, images must use algorithms that properly
dedicated small-animal SPECT systems have model this ambiguity.
been developed. Although there are many  Some multipinhole animal SPECT systems
different designs, these systems commonly are completely stationary and designed such
consist of a series of compact detector heads, that they simultaneously acquire sufficient
with interchangeable pinhole collimators that angular data for tomographic reconstruction
have apertures ranging from approximately with no moving parts. This type of system is
0.3╯mm to 2╯mm in diameter, allowing the particularly suited for rapid dynamic studies,
operator to trade off between improved spatial often of interest when evaluating the biodis-
resolution (smaller pinholes) or improved sen- tribution of a novel radiotracer in the first
sitivity (larger pinholes) (see Equations 14-15 seconds and minutes after injection. These
and 14-16). The detector heads often use pix- systems consist of an annular collimator
elated NaI(Tl) or CsI(Tl) scintillator arrays sleeve containing many pinholes each project-
(similar to those shown in Fig. 13-15B) or ing a different angular view of the radionu-
arrays of CZT semiconductor elements to clide distribution onto a detector that sits
achieve high intrinsic spatial resolution. The behind the collimator. Figure 17-5 shows one
simplest systems consist of two opposing such collimator and a drawing showing how

Object

Pinhole
apertures

Detector

Regions of
overlap
FIGURE 17-4  Illustration of multiple pinhole systems used for small-animal SPECT. Left, Two pinholes spaced far
enough apart to avoid overlap of projections. Right, Increased number of pinholes provides increased sensitivity, but
comes at the expense of a partial overlap in the projection data viewed through adjacent pinholes.
17  •  Single Photon Emission Computed Tomography 285

A B

FOV

CFOV

Pinhole

Cylindrical
C collimator

FIGURE 17-5  A, Photograph of multiple-pinhole collimator for a stationary small-animal SPECT system. There are
75 pinholes viewing the object from different angles. B, Cut-away view of the pinhole collimator showing angulation
of pinholes and dense sampling in the central region. C, Transverse and axial sections through the center of the
collimator showing sensitive region for each pinhole and extent of field of view. (Courtesy MILabs, Utrecht, The
Netherlands).

the pinholes are angled to cover a large FOV applications. A useful review of small-animal
without the need for any movement. SPECT systems is given in reference 6.
Using these approaches, small-animal
SPECT systems routinely reach a resolution
in the range of 1╯mm, and in some instances B.  PRACTICAL IMPLEMENTATION  
are able to produce images with a recon- OF SPECT
structed resolution much smaller than 1╯mm.
Sensitivity can be high as well, because of the Ideally, the signal level for a voxel in a SPECT
large number of pinholes used. Numbers are image is linearly proportional to the amount
commonly in the 0.5 to 2 × 103 cps/MBq of activity contained within the volume of
(~1000-4000 cpm/â•›µCi) range, but depend tissue in the patient that corresponded to the
strongly on the number and diameter of the location of that voxel. This would be useful
pinhole apertures used, and the source-to- not only for quantitative applications, such as
pinhole distance. For systems in which the perfusion studies, but also for visual interpre-
projections overlap, the measured sensitivity tations of the image. In practice, this ideal
must be interpreted with caution, as the result is not achieved because the realities of
information content of an event detected in a data acquisition do not match the idealized
region of overlap is not as high as for an event assumptions made for the development of
in a system in which the projections do not reconstruction algorithms. As shown in Figure
overlap. Almost all small-animal systems use 16-1, it was assumed that the line of response
some form of iterative reconstruction algo- (or a projection element) for a single hole in a
rithm with detailed modeling of the collima- parallel-hole collimator is an extended cylin-
tor apertures for reconstructing images at  der, but the actual response resembles a
the highest possible resolution. Figures 17-6A diverging cone. It was further assumed that
and B show photographs of two SPECT the signal recorded was proportional to the
systems designed for small-animal imaging total activity within the line of response, but
286 Physics in Nuclear Medicine

A B

C
FIGURE 17-6  Photographs of two small-animal SPECT systems: A, This stationary system uses the cylindrical multiÂ�
pinhole collimator shown in Figure 17-5, and views are projected onto three large-area Anger cameras with no overlap
between projections. With no need to move the detectors, fast dynamic studies can be performed. B, This system
employs four 12.7╯cm × 12.7╯cm pixelated cadmium zinc telluride (CZT) detector heads and multipinhole collimators.
Some rotation of the detectors is necessary to obtain all projection angles. The use of CZT provides excellent energy
resolution. C, Photograph of one detector module from the system shown in B. The detector measures 2.54╯cm × 2.54╯cm
and has a 16 × 16 array of CZT elements on a 1.59-mm pitch. The CZT thickness is 5╯mm. Twenty-five of these modules
are tiled together to form a 12.7╯cm × 12.7╯cm detector head. (A, Courtesy MILabs, Utrecht, The Netherlands; B, Copyright
Gamma Medica, Northridge, CA and GE Healthcare, Waukesha, WI; used with permission of GE Healthcare; C, Copyright
Gamma Medica, Northridge, CA.)

in fact the signal from activity closest to the activity present. They also can lead to arti-
detector is more heavily weighted than from facts and seriously degraded image quality. To
deeper-lying activity, because of attenuation avoid this, one must use somewhat modified
by overlying tissues. Finally, it was assumed approaches to data acquisition or apply post-
that activity outside the line of response did processing of the acquired data. This is always
not contribute to the signal for the projection the case when backprojection algorithms are
element, whereas there may be crosstalk used, because they are rigorously grounded 
between elements resulting from scattered in the idealized assumptions noted earlier.
radiation or septal penetration through the Some of the discrepancies can be accounted
collimator. To further complicate matters, for with iterative algorithms, such as the
most of the discrepancies vary with the energy maximum likelihood-expectation maximiza-
of the γ rays involved. tion algorithm (see Chapter 16, Section D.2),
Some of the discrepancies between the ide- which can incorporate these factors in its
alized assumptions and the actual situation probability matrix. In this section, we describe
in SPECT are illustrated in Figure 17-7. The some general approaches that are valid and
discrepancies distort the desired linear rela- potentially useful for all reconstruction
tionship between signal level and amount of algorithms.
17  •  Single Photon Emission Computed Tomography 287

5 cm
10 cm
T0.46 15 cm
20 cm

T0.21

water T0.10

Transmission T  ex
B for 140-keV  rays in water, 0.155 cm1

A
FIGURE 17-7  A, Volumes of tissue viewed by a collimator hole at two different angles separated by 180 degrees. Differ-
ences in the volumes viewed results in different projections from the two viewing angles. B, Attenuation leads to further
differences in these two projections, emphasizing activity that is close to the gamma camera compared with activity
further away that has to penetrate more tissue to reach the gamma camera. Values are shown for the attenuation of the
140-keV γ rays from 99mTc in water.

response. A source that is located relatively


1.  Attenuation Effects and Conjugate close to the detector from one view will be
Counting relatively far away in the opposing view.
The attenuation of γ rays in SPECT imaging Hence, the response profile will be narrower
depends on the distance the γ rays have to and attenuation by overlying tissues will be
travel through the tissue to reach the detec- smaller in the first view and larger in the
tor. Figure 17-7B illustrates the depth- second, with partially offsetting effects.
dependent nature of this attenuation for Conjugate counting in SPECT requires
point sources located at different positions that views be obtained over a full 360-degree
within the body. The transmission factor for range around the object. Data from opposing
a source at a certain depth can be calculated views then are combined to yield the equiva-
using Equation 6-22. For 140-keV γ rays, the lent of a single 180-degree scan. Conjugate
linear attenuation coefficient of tissue is counts (or views) generally are combined in
0.155╯cm-1; therefore γ rays that are emitted one of two ways. The first is to use the arith-
from a depth of 10╯cm in the body would only metic mean. If I1 and I2 are the counts recorded
have a probability of 0.21 (e-10 × 0.155) of emerg- from opposing directions for a particular line
ing from the body in their original direction. of response through the object, the arithmetic
The attenuation of γ rays is even more severe mean is given by
in parts of the body containing significant ( I1 + I2 )
amounts of bone, because the linear attenu- IA = (17-1)
ation coefficient of bone is ~0.25╯cm-1 at 2
140╯keV. An alternative is the geometric mean, given
One approach to reducing both the diver- by
gence of the response profile (Fig. 17-7A) and
the effects of tissue attenuation (Fig. 17-7B) IG = I1 × I2 (17-2)
is conjugate counting. Conjugate counting
refers to acquiring data (or image profiles) Figure 17-8 shows response profiles versus
for directly opposing views and then combin- source depth for a 99mTc line source for a
ing these data into a single dataset or line of single-view projection and for projections
288 Physics in Nuclear Medicine

99m
Tc-Line source response Water
Air
26

26 22

22 18
100
100 18 14
14
10
10
6
6
2
2
−30 −20 −10 0 10 20 30 mm
−20 −10 0 10 20 30 mm

Water
Arithmetic-mean
Air 26

26
22

22
18
100
18 14
100
14 10

10
6

6
2

2 −30 −20 −10 0 10 20 30 mm


−20 −10 0 10 20 30 mm

Geometric-mean
Air Water

26
26

22
22
18
18
100
100 14
14

10
10
6
6
2
2
−30 −20 −10 0 10 20 30 mm
−20 −10 0 10 20 30 mm

FIGURE 17-8  Line-spread functions versus distance in air (left) and in water (right) for high-resolution parallel-hole
collimator on a gamma camera. The line source measured 2.5╯mm in diameter and was mounted inside a tank measur-
ing 410╯mm in length, 310╯mm in width, and 300╯mm in thickness. Measurements were made either with the tank
empty (in air) or filled with water. Top, single detector only; middle, arithmetic mean of opposing detector profiles;
bottom, geometric mean of opposed detector profiles. (From Larsson SA: Gamma camera emission tomography: Development
and properties of a multisectional emission computed tomography system. Acta Radiol Suppl 363:1-75, 1980.)

created from the arithmetic and geometric resolution with distance from the collimator
means of opposing views. The profiles across that is characteristic for a parallel-hole 
the top are for a single view with the source collimator (see also Figs. 14-18 and 14-19).
in air and for the same view with the  The profile for the source in water shows
source in water. The profile for the source in similar degradation of spatial resolution with
air illustrates the degradation of spatial increasing distance but, in addition, shows
17  •  Single Photon Emission Computed Tomography 289

decreasing amplitude of response owing to attenuation are only partially corrected for by
attenuation of photons by the overlying thick- the arithmetic mean.
ness of water. The response profile for the arithmetic
The middle row of Figure 17-8 shows response mean has its minimum amplitude when the
profiles for the arithmetic mean. The profiles source is near the center of the water phantom.
for the source in air show significantly improved Figure 17-9 shows simulated SPECT images
uniformity of spatial resolution with depth, as of a water-filled cylinder containing a solution
compared with the single-view profile directly of uniform concentration of activity for differ-
above it. The profiles for the source in water ent γ-ray energies, using the arithmetic mean
show similar improvement in uniformity of of opposing views. Also shown are profiles of
spatial resolution with depth; however, there the images across the center of the phantom.
still is marked variation in the amplitude of As one might expect from the profiles illus-
the profile versus distance (and depth in trated in Figure 17-8, there is a marked
water), indicating that the effects of photon decrease in intensity at the center of the

99mTc 131I 201TI No


attenuation

Tc-99m
I-131
0.8 TI-201
No attenuation

0.6
Pixel value

0.4

0.2

0 4 8 12 16 20
Radial position (cm)
FIGURE 17-9  Top, Simulated SPECT images of 20-cm diameter water-filled cylinders containing uniform concentra-
tions of 99mTc (140╯keV), 131I (364╯keV), and 201Tl (70╯keV). Bottom, Arithmetic mean of count profiles through the center
of the simulated images. Note the reduction in image intensity at all points in the image caused by attenuation, with
the largest reduction occurring at the center of the cylinder. The amount of attenuation is energy dependent, with
greatest attenuation occurring at the lower γ-ray energies.
290 Physics in Nuclear Medicine

phantom. The strongest effect occurs for the The bottom row of Figure 17-8 shows pro-
lowest energy γ rays. It is apparent from files in air and in water for the geometric
Figure 17-9 that relatively strong attenuation mean of opposing views. In this case, both the
effects are present with the arithmetic mean amplitude and the width of the profile remains
for all of the photon energies commonly used nearly constant at all distances and depths in
in SPECT imaging. the water phantom.
Figure 17-10 shows simulated images and Tables 17-1 and 17-2 summarize numerical
profiles for phantoms of different sizes with  data derived from the profiles in Figure 17-8.
µ = 0.155╯cm-1, corresponding to the attenua- From this summary, it can be seen that 
tion of 140-keV photons of 99mTc in water. As attenuation has much stronger effects than
the diameter of the phantom increases, the distance. The combined effects of distance
images and count profiles demonstrate pro- and attenuation result in a 100-fold range 
gressively greater suppression at the center in counts recorded with a single detector 
of the image. (see Fig. 17-8, top right). With the arithmetic

10 cm 20 cm 30 cm

1 10 cm

20 cm

0.8 30 cm

0.6
Pixel value

0.4

0.2

−15 −10 −5 0 5 10 15
Radial position (cm)
FIGURE 17-10  Top, Simulated SPECT images of water-filled cylinders of different diameters containing uniform
concentrations of 99mTc (140╯keV). Bottom, Count profiles through the centers of the images. The strong dependence of
attenuation on cylinder size is evident.
TABLE 17-1â•…
NUMERICAL DATA FOR FIGURE 17-8 (LEFT COLUMN) 99mTc LINE SOURCE IN AIR

Distance from Relative Maximum Resolution


Collimator (cm) Response* in Air (%) FWHM (mm)
99m
Tc line-source response 2 100 7.4
6 84 8.6
10 66 10.0
14 58 12.5
18 49 14.7
22 44 17.2
26 38 20.0

Arithmetic mean 2-28 100 8.5
6-24 93 10.6
10-20 84 12.3
14-16 84 13.2
18-12 82 12.7
22-8 90 11.2
26-4 99 9.8
Geometric mean 2-28 100 9.4
6-24 98 10.8
10-20 94 12.4
14-16 94 13.2
18-12 93 12.7
22-8 97 11.7
26-4 100 10.4
Adapted from Larsson SA: Gamma camera emission tomography: Development and properties of a multisectional
emission computed tomography system. Acta Radiol Suppl 363:1-75, 1980.
FWHM, full width at half maximum.
*Value at peak of profile.

For arithmetic and geometric means, paired values refer to the distance between the source and collimator for the
two conjugate views.

mean (see Fig. 17-8, middle), the range is I1 × I2 = ( I01 × I02 ) e− µ × ( a + b)


reduced to a factor of five. With the geometric (17-5)
mean (see Fig. 17-8, bottom), the variations = ( I01 × I02 ) e− µD / 2
with depth are virtually eliminated, although
there still is a small reduction in relative Thus the geometric mean of counts from
counts when the source is at the deepest loca- opposed detectors depends on total tissue
tion in the phantom. thickness, D, but not on source depths, a and
The constancy of amplitude for the geo� b. This result is exact only for a point or plane
metric mean can be understood from the fol- source, but corrections can be applied as
lowing analysis. Consider the arrangement of approximations for simple extended sources
the radioactive source and detectors shown in (e.g., uniform volume sources).7 The geometric
Figure 17-11. The attenuation of photons mean also depends on the unattenuated
directed toward detector 1 is given by counts, I01, and I02, which may change with a
and b because of distance effects; however,
I1 = I01 ( e− µa ) (17-3)
for systems using parallel-hole collimators,
and for those directed toward detector 2 by such as SPECT gamma camera systems, unat-
tenuated counts do not change with distance
I2 = I02 (e− µb ) (17-4) (see Chapter 14, Section C.3 and Fig. 14-17).
In this case, I01 = I02 = I0 and Equation 17-5
where a and b are the source depths. Note reduces to
that a + b = D. Taking the geometric mean of
I1 and I2, one obtains I1 × I2 = I0 e−µD / 2 (17-6)
292 Physics in Nuclear Medicine

TABLE 17-2â•…
NUMERICAL DATA FOR FIGURE 17-8 (RIGHT COLUMN) 99mTc LINE SOURCE IN WATER

Distance from Relative Maximum Resolution


Collimator (cm) Response* in Water (%) FWHM (mm)
99m
Tc line-source response 2 100 7.5
6 47 9.4
10 23 11.2
14 10 13.9
18 8.1 16.3
22 1.9 19.1
26 0.8 21.6
Arithmetic mean 2-28† 100 7.8
6-24 50 8.6
10-20 25 11.5
14-16 17 14.3
18-12 21 13.0
22-8 34 10.4
26-4 71 8.1
Geometric mean 2-28 100 9.9
6-24 93 11.7
10-20 95 13.3
14-16 93 14.3
18-12 95 14.1
22-8 93 13.2
26-4 96 11.9
Adapted from Larsson SA: Gamma camera emission tomography: Development and properties of a multisectional
emission computed tomography system. Acta Radiol Suppl 363:1-75, 1980.
FWHM, full width at half maximum.
*Value at peak of profile.

For arithmetic and geometric means, paired values refer to the distance between the source and collimator for the
two conjugate views.

a b
Detector 1 Detector 2
Point source
of activity

FIGURE 17-11  Point source of activity within an attenuating medium of thickness D. The attenuation can be com-
pensated for by using the geometric or arithmetic mean and a correction for total tissue thickness, D.
17  •  Single Photon Emission Computed Tomography 293

These analyses and equations are accurate must be modified for more complicated source
for a single radioactive source. When multiple distributions.7
sources are present, the situation is more
complicated, as shown in Example 17-1.
2.  Attenuation Correction
EXAMPLE 17-1 Conjugate-counting techniques, especially
Derive the equation for the geometric mean using the geometric mean, can substantially
of counts from two point sources located along reduce the variation of width and amplitude
a line between two detectors, and show why of counting rate profiles that are present in
it cannot be described only in terms of the single-view profiles. However, even with the
unattenuated counts, I01, and I02, and µ and D geometric mean, there are residual scaling
(distance between the detectors) as can be factors caused by attenuation [exp(−µâ•›D/2) in
done for a single point source (Equation 17-5). Equation 17-6]. Thus, for quantitative accu-
Assume that a parallel-hole collimator is racy, attenuation corrections are required.
being used and therefore that the unattenu- A relatively simple method for attenuation
ated counts do not depend on distance. correction is to correct projection profiles gen-
erated with the geometric or arithmetic mean
Answer before reconstruction using an estimate for
tissue thickness, D. The attenuation correc-
D tion is particularly simple for the geometric
mean (Equation 17-6) and is given by multi-
a b plying the projection profiles by an attenua-
Detector 1 A1 A2 Detector 2 tion correction factor (ACF) of
c d 1
ACF = = eµ D / 2
− µD / 2
(17-7)
e
A constant value for µ, the linear attenua-
Referring to this figure: tion coefficient of tissue, is assumed. An esti-
mate for tissue thickness D can be derived
a+b= D from a preliminary uncorrected image or by
assuming a standard body size and shape.
c+d = D
As demonstrated in Example 17-1, simply
We represent the unattenuated counts from generating profiles using the geometric mean
source A1 as I01 and from source A2 as I02. The does not correctly deal with attenuation in
measured counts at detector 1 will be the general case in which γ rays are emitted
at different locations in the FOV. An alterna-
I1 = I01 e− µa + I02 e− µc tive approach is to calculate an ACF for each
The measured counts at detector 2 will be pixel after image reconstruction. In this
method, an initial image, fâ•›′(x,y), is recon-
I2 = I01 e− µb + I02 e− µd structed by filtered back-projection without
any attenuation correction. The contours of
The geometric mean is this image are used to obtain an estimate of
the attenuation path length through the
I1 × I2 = [ I01
2 − µ ( a +b)
e 2 − µ ( c +d )
+ I02 e + I01 I02 e− µ ( a + d) tissue for all projection views. Once again, it
is assumed that the linear attenuation coef-
+ I01 I02 e− µ (c + b) ]
1/2
ficient at a given energy is constant for 
= [( I01 all body tissues. The ACF for each pixel 
2
+ I02
2
) e− µD + I01 I02 e− µ(a+ d) (x,y) in the reconstructed image then is cal-
+ I01 I02 e− µ (c + b) ]
1/ 2
culated by
1
Only the first term in the last expression ACF ( x, y) = N
1 (17-8)
depends solely on I01, I02, µ, and D. The other
two terms contain exponential terms e−µ(c+b)
∑ e− µdi
N i =1
and e−µ(a+d) that depend on the relative loca-
tions of the two sources between the detec- where di is the attenuation path length for the
tors. Therefore attenuation effects depend on pixel at projection view i and µ is the assumed
the source distribution, and the simple correc- constant value for the attenuation coefficient.
tion scheme for point sources and line sources The reconstructed image fâ•›′(x,y) is corrected on
294 Physics in Nuclear Medicine

a pixel-by-pixel basis by multiplying it by the SPECT images of a cylinder that contains a


ACF uniform concentration of radionuclide before
and after attenuation correction with the
f ( x, y) = f ′ ( x, y) × ACF ( x, y) (17-9) Chang method.
Methods based on the Chang approach are
This technique is known as Chang’s multipli- used in most commercial SPECT systems and
cative method.8 yield reasonable results in the brain and
There also is a more involved implementa- abdomen, where the assumption of a uniform
tion of the Chang method in which the image attenuation coefficient is not unreasonable
obtained with the first-order correction (the amount of bone and any air spaces are
described by Equation 17-8 is forward- small). These methods do not work well in the
projected (see Chapter 16, Section D.1), with thorax or in the pelvic region, where the pres-
appropriate attenuation of the image counts ence of the lungs and significant amounts of
corresponding to the path length through the bone, respectively, can lead to significant
tissue.9 The forward-projected profiles pfp(r, ϕ) errors. SPECT projection profiles must be
are subtracted from the original measured acquired over a full 360 degrees to use these
projection profiles p(r,â•›ϕ) to form an “error pro- methods.
jection” Perror(r, ϕ)

Perror (r, φ) = p(r, φ) − pfp (r, φ) (17-10)


3.  Transmission Scans and  
Attenuation Maps
This error projection is itself reconstructed An alternative approach for SPECT imaging
with filtered backprojection to form an error in regions of the body that have variable atten-
image, ferror(x,y). The final attenuation cor- uation is to actually measure tissue attenua-
rected image is given by tion using an additional scan known as a
transmission scan.10,11 This scan can be per-
f ( x, y) = f ′ ( x, y) × ACF ( x, y) formed using the same detector system as is

+ ferror ( x, y) × ACF ( x, y) used for acquiring the emission data. An exter-
nal source of radiation is used to acquire trans-
(17-11) mission profiles that can be used to reconstruct
Adding the two images together is made pos- cross-sectional images reflecting the linear
sible by the fact that filtered backprojection attenuation coefficient of the tissue, often
is a linear algorithm. Figure 17-12 shows referred to as an attenuation map. This is
equivalent to an x-ray CT scan, although the
quality of the image is poorer, because of the
No attenuation correction
limited resolution of the gamma camera and
the low-photon flux used to obtain the trans-
mission image. As well, the higher energy of
the γ rays, as compared with most diagnostic
x-ray beams, leads to lower contrast.
Approaches that use x-ray CT scans for atten-
uation correction are discussed in Chapter 19,
Section E.
Transmission data can be acquired using a
Chang correction (  0.15 cm1) collimated flood source, line source, multiple
line sources, or a moving line source. Several
possible acquisition geometries for transmis-
sion scans are shown in Figure 17-13. The
data usually are acquired with a parallel-hole
collimator on the detector, although on triple-
headed cameras, a single line source some-
FIGURE 17-12  SPECT images of a 20-cm diameter cyl- times is used in conjunction with a fan-beam
inder containing a uniform concentration of 99mTc with collimator. The radionuclide chosen for the
and without attenuation correction (Chang method with transmission sources usually has an emission
narrow-beam attenuation coefficient of µ = 0.15╯cm−1). energy that is different from 99mTc, to allow
Profiles are through the center of the images. The appar-
ent overcorrection of attenuation is due to scattered
for simultaneous emission imaging of 99mTc,
events in the dataset. (Courtesy Dr. Freek Beekman, Delft as described later. A radionuclide with a long
University of Technology, The Netherlands.) half-life is convenient so that the source does
17  •  Single Photon Emission Computed Tomography 295

A B

C D
FIGURE 17-13  Examples of transmission source geometries that are being employed for attenuation correction in
SPECT. The black arrows show the direction of γ rays emitted from collimated transmission source; the gray arrows
show the direction of motion of moving line sources. A, Flood source. B, Collimated moving line source. C, Two orthogo-
nal moving collimated line sources on dual-headed gamma camera. D, Stationary line source (collimated in axial
direction irradiating opposite detector head (fan-beam collimator) in a triple-headed gamma camera.

not require frequent replacement. 153Gd (T1/2 scan is acquired with the object of interest in
= 242 days, Eγ = 97 and 103╯keV) and 123mTe the FOV. This is the transmission scan. The
(T1/2 = 120 days, Eγ = 159╯keV) are among the relationship between the reference (Iref) and
radionuclides suitable for this purpose. transmission (Itrans) counts in any particular
To obtain an attenuation map, two sepa- projection element is given by the usual expo-
rate scans are acquired with the transmission nential relationship for γ-ray attenuation
source. Typically one of the geometries shown
in Figure 17-13 is used and the gamma Itrans = Iref e−µx (17-12)
camera system is rotated through 360 degrees
to acquire a full set of projection views. The Taking the natural logarithm of the ratio of
first scan is acquired with no object in the the two scans results in
FOV of the SPECT camera. This is referred
to as the blank or reference scan. The second ln( Iref /Itrans ) = µx (17-13)
296 Physics in Nuclear Medicine

Projection profiles of µâ•›x represent the sum of therefore attenuation) between the transmis-
the attenuation coefficients along each line of sion and emission photons must be taken into
response account in applying the information from the
transmission map.
µx = ∑ µ i ∆ xi (17-14) Emission and transmission scans can be
i
acquired simultaneously if the separation
between the photon energies of the transmis-
where µâ•›i is the linear attenuation coefficient sion source and the emission radionuclide is
for the iâ•›th pixel and Δâ•›xâ•›i is the pathlength of sufficient to allow them to be acquired in two
the line of response through the ith pixel. This separate energy windows. This is shown sche-
is analogous to the standard emission projec- matically in Figure 17-15. Even if two differ-
tion profiles that represent the sum of the ent windows are used, however, some events
radioactivity along each line of response. from the higher-energy radionuclide will be
Using the methods described in Chapter 16, recorded in the lower-energy window. This
Section B, the projection profiles of µâ•›x (calcu- effect, known as downscatter, arises from two
lated from the transmission scan profiles causes. The first is spillover from higher-
using Equation 17-13) are reconstructed, energy events into lower-energy regions of the
resulting in images of µâ•›i. Figure 17-14 shows spectrum (e.g., see Fig. 10-3). These events
a SPECT attenuation map reconstructed from may arise from partial absorption of higher-
transmission and reference scans. energy photons in the detector or from natural
The attenuation map can be used to more broadening of the photopeak.
accurately compute the ACFs in the Chang A second cause is γ rays that have experi-
algorithm (Section B.2) by taking into account enced a partial loss of energy in Compton-
the nonuniform attenuation at each source scattering interactions in the body. For
location in Equation 17-8. It can also be incor- emission scans using 99mTc (140╯keV), down-
porated in the forward-projection step of the scatter from a 123mTe transmission source
modified Chang algorithm to more accurately (159╯keV) can appear in the emission source
compute the error term. More commonly, window. Conversely, when 153Gd is used as the
tissue attenuation information is directly transmission source, downscatter from 99mTc
incorporated into iterative reconstruction can appear in the transmission source window.
algorithms (Chapter 16, Section D) in which Even if the emission and transmission scans
it becomes another factor in the calculation of are acquired sequentially, rather than simul-
the probability matrix M in Equation 16-19. taneously, the patient normally is injected
The probability for γ rays emitted from a with a 99mTc-labeled radiopharmaceuÂ�tical
given pixel i reaching projection element j is prior to transmission imaging, and hence
reduced by the probability of attenuation in downscatter is still an issue with 153Gd trans-
the tissue lying between the point of emission mission sources.
and the detection point in the gamma camera. Downscatter can be estimated and correc-
For both filtered backprojection and iterative tions can be applied for it in ways that are
algorithms, the difference in energy (and similar to the methods used for correcting for
scattered radiation in the emission scan. For
example, one can use an energy window
between the transmission and emission
windows to estimate the level of downscatter.
These methods are similar to those employed
for scatter corrections, which are discussed in
the following section.
4.  Scatter Correction
The idealized model used for developing the
filtered backprojection reconstruction algo-
rithms described in Chapter 16 assumed that
only radioactivity within the line of response
for a projection element contributed to the
FIGURE 17-14  Attenuation map of the thorax recon- signal for that element. In practice, the signal
structed from the reference and transmission scans
obtained with a moving line transmission source. (Data
can include events that have been scattered
courtesy Dr. Freek Beekman, Delft University of Technology, into the line of response from radioactivity
The Netherlands.) elsewhere in the body. With the typical 20%
17  •  Single Photon Emission Computed Tomography 297

Counts
100 keV
153Gd

events

140 keV

99mTc

events

Downscatter

Energy
Transmission Emission
window window
FIGURE 17-15  Dual-energy windows used to simultaneously acquire SPECT emission (99mTc) and transmission (153Gd)
data. Note the presence of downscatter from the 99mTc activity in the 153Gd window. The magnitude of the downscatter
contamination depends on the relative amounts of 99mTc activity in the body and 153Gd activity in the transmission
source, the amount of scattering material in the field of view, the details of how the transmission source is collimated,
and the precise energy windows that are used.

pulse-height analyzer (PHA) window that is only rarely for energies 100╯keV, the total
used for 99mTc, events that have scattered absorption) of γ rays. Because of the broad-
through angles as large as 50 degrees still beam geometry (Chapter 6, Sections D.2 and
have a 50% probability of being accepted. D.3) of SPECT imaging systems, some of the
Compared with the effects of attenuation, scattered γ rays are detected, leading, on
the effects of scattering are of lesser magni- average, to a reduction in the “apparent”
tude. Nevertheless, Compton scattering, and attenuation coefficient that is measured rela-
at low γ-ray energies (100╯keV) coherent scat- tive to narrow-beam attenuation coefficients.
tering (see Chapter 6, Section C.5), still can One can provide an averaged correction for
have a significant effect on image quality and scatter by using the apparent or broad-beam
on the quantitative relationship between the value for µ in Equations 17-7 and 17-8. For
reconstructed image intensity and source example, for the 140-keV γ rays from 99mTc in
activity. In a typical patient study with a 99mTc- a typical patient, the broad-beam attenuation
labeled radiopharmaceutical, even using a coefficient is ~0.12╯cm−1 as compared with a
narrow 15% PHA window, the ratio of the narrow-beam value of 0.155╯cm−1. Although
number of detected scattered photons to the this works well in objects with uniform radio-
number of nonscattered photons may be as activity distributions in a uniform attenua-
large as 40%. The presence of scattered events tion medium (Fig. 17-16), it does not properly
results in reduced image contrast (the tails of
the point-spread function [PSF] are elevated
Chang correction (  0.12 cm1)
with respect to the peak) and leads to an over-
estimation of the concentration of radioactivity
in the pixel (see Fig. 17-12, bottom). The loss
of image contrast may obscure clinically 
important details, particularly “cold” areas in
the images, for example, areas of low radio�
pharmaceutical accumulation in the heart FIGURE 17-16  Effect of Chang attenuation correction on
caused by coronary artery disease or infarction. 20-cm uniform cylinder data in Figure 17-12 using a
A first-order correction for scatter can be broad-beam attenuation coefficient of µ = 0.12╯cm−1. Note
the improvement in the uniformity of the profile, which
made by recognizing that scatter and attenu- is due to compensation for scattered events. (Data courtesy
ation are part of the same phenomenon. Dr. Freek Beekman, Delft University of Technology, The
Attenuation is caused by the scattering (and Netherlands.)
298 Physics in Nuclear Medicine

take into account the spatial distribution  general on the size of the source, the exact
of the scattered events and is therefore of settings of the energy windows, and the
limited accuracy in more realistic imaging energy resolution of the gamma camera detec-
situations. tor. The accuracy of this method is limited by
A second simple method that has been used the fact that γ rays in the scatter window are
to correct for scattered events involves mea- more likely to have undergone multiple
suring the scatter component in the projec- Compton interactions than scattered events
tion profiles using a line source (or point in the photopeak window; therefore the
source) immersed in a scattering medium spatial distributions of the scatter recorded in
that is representative of the dimensions of the the two energy windows may differ.
body. By measuring projection profiles of the Many variants on the use of multiple-energy
source with and without the scattering windows for scatter correction have been
medium, the distribution of scattered events developed. Some SPECT systems use as many
in the projection profile can be determined. as 32 separate energy windows to more accu-
This can be considered to be the line-spread rately model the scatter distribution. Accurate
function (LSF) of the scattered events and can scatter corrections require very good spatial
be deconvolved (see Appendix G) from the linearity and uniformity of the gamma camera
measured projection profiles measured in detector (Chapter 14, Section B) to avoid creat-
patient studies to correct for scatter. The ing artifacts in the scatter correction process.
accuracy of this correction is limited by differ- Scatter corrections also increase the statisti-
ences in radioactivity distribution and atten- cal noise in the reconstructed image because
uation distribution between the phantom in of the inevitable propagation of noise in the
which the scatter response is measured, and subtraction process (Chapter 9, Section C.1).
the patient, and by the spatially invariant Note that for all the corrections described
nature of the correction. here, if scattered events are not “removed”
One of the most commonly used methods prior to applying attenuation corrections, the
to correct for scattered γ rays is to simultane- scattered events also are amplified during the
ously acquire counts with a photopeak window attenuation correction procedure. Therefore it
and a lower-energy scatter window. For is important that scatter corrections precede
example, the photopeak window for 99mTc attenuation corrections.
might be set to 127-153╯keV and the scatter Attenuation maps, described in the preced-
window to 92-125╯keV (Fig. 17-17). The result- ing section, also can be used in conjunction
ing scatter projection profiles then are multi- with iterative reconstruction algorithms to
plied by a weighting factor and subtracted correct for scattered radiation. In essence, the
from the photopeak profiles to obtain scatter- matrix M in Equation 16-19 can be modified
corrected projection data. The weighting to account for the probability of scatter from
factor applied to the counts in the scatter a source at a location (x,y) into a specified
window for the subtraction process must be detector element. This probability can be 
determined experimentally and depends in calculated by combining knowledge of the
Counts

Unscattered
events

Scattered
events

Scatter Photopeak Energy


window window
FIGURE 17-17  Diagrammatic sketch showing dual-energy windows superimposed on the spectral distribution of
unscattered and scattered events for a patient-sized phantom filled with 99mTc.
17  •  Single Photon Emission Computed Tomography 299

distribution of the attenuation coefficients effect is illustrated in Figure 17-18, in which


from the attenuation map, along with the objects of identical concentration are seen to
probability of Compton scattering at different decrease in intensity, and thus in apparent
angles (see Fig. 6-13), and a model of the concentration, with decreasing size.
camera and collimator geometry, as well as This partial-volume effect is important for
the energy resolution of the camera. both qualitative and quantitative interpre�
Because computing the scatter probability tation of SPECT images. Although they 
from every source location in the subject, to may be visible in the image, small objects
every possible detector location, is computa- near the resolution limits of the device appear
tionally expensive, simplifying approxima- to contain smaller concentrations of radio�
tions often are made. Nonetheless, iterative activity than they actually do. The ratio 
algorithms in conjunction with patient-specific of apparent concentration to true concentra-
attenuation maps offer a powerful approach tion is called the recovery coefficient (RC).
to quantitative SPECT imaging in the pres- Figure 17-19 illustrates RC versus object
ence of nonuniform attenuating and scatter- size for the cylinders in Figure 17-18. In prin-
ing media. This is of particular value in cardiac ciple, if a SPECT system has a known and
imaging, in which the mixture of soft tissue uniform spatial resolution and if the size of
and lungs in a cross-section of the thorax  the object is known, an RC correction factor
can cause major artifacts and quantitative can be applied to correct for the partial-
errors if accurate corrections for attenuation volume underestimation of concentrations for
and scatter are not employed. Scatter correc- small objects. Although this approach works
tion methods are discussed in more detail in well in phantom studies in which object sizes
reference 11. are well characterized, the sizes of in vivo
objects usually are too poorly defined for this
5.  Partial-Volume Effects method to be useful, unless high-resolution
Ideally, the intensity of each pixel in a SPECT anatomic information is available from
image would be proportional to the amount of another modality such as CT or magnetic
radioactivity within the corresponding volume resonance imaging.
of tissue in the patient. The methods described In some situations, RC can be greater than
in the preceding sections described how this one. This occurs when the object of interest
can be facilitated by corrections for attenua- has low radiotracer accumulation relative to
tion and scatter. Even with these corrections, surrounding structures (e.g., an area of
however, there still may be errors in assign- reduced blood flow in the heart) and activity
ing activity and concentration values to small from these surrounding areas “spills over”
sources and small tissue volumes. into the structure of interest as a result of the
As described in Section C, a SPECT system same resolution effects described previously.
has a characteristic “resolution volume” that This is commonly known as spillover. The net
is determined by the combination of its effect of partial-volume effects in all cases is
in-plane (x-y) and axial (z) resolutions. For to reduce the contrast between areas of high
systems that produce a stack of contiguous radiotracer uptake and those of low uptake
2-D images, this volume has an approximately and to lead to underestimation or overestima-
cylindrical shape of height = 2 × FWHM axial tion of radiotracer concentrations. This can be
resolution and diameter = 2 × FWHM in-plane the dominant source of error in quantitative
resolution. For sources or measurement SPECT studies of small structures and must
volumes of the size of the resolution volume be carefully considered when comparing
or larger, the intensity of images produced by images of different-sized objects, or sequential
the SPECT system reflect both the amount images of objects that are changing size (e.g.,
and concentration of activity within that tumor shrinkage caused by therapy).
volume. For smaller objects that only par-
tially fill a resolution-volume element, the
sum of the intensities of all the pixels that are C.  PERFORMANCE CHARACTERISTICS
attributable to that object still reflects the OF SPECT SYSTEMS
total amount of activity within it. However,
the intensities of the individual pixels no The following sections provide representative
longer accurately reflect the concentration of methods for characterizing the performance
activity contained within them, because the and for quality assurance of SPECT systems.
signal is distributed over a volume that is A complete description of these measure-
larger than the actual size of the source. This ments can be found in reference 11.
300 Physics in Nuclear Medicine

48 mm 36 mm 30 mm 24 mm 18 mm 12 mm 9 mm 6 mm

300

250
Counts (arb. units)

200

150

100

50

0
FIGURE 17-18  Illustration of partial-volume effect. The cylinders shown in the top row have diameters ranging from
48╯mm down to 6╯mm, and each contains the same concentration of radionuclide. The middle row shows a simulation
of the images that would result from scanning these cylinders on a SPECT system with an in-plane spatial resolution
of 12-mm full width at half maximum. The cylinders are assumed to have a height much greater than the axial resolu-
tion. The bottom row shows count profiles through the center of the images. Although each cylinder contains the same
concentration of radionuclide, the intensity, and therefore the apparent concentration, appears to decrease when the
cylinder size approaches and then becomes smaller than the resolution of the SPECT system. The integrated area
under the count profiles does, however, accurately reflect the total amount of activity in the cylinders.

0.8
FIGURE 17-19  Recovery coefficient
versus object size [in units of 
size/full width at half maximum
(FWHM)] using the data from Figure
Recovery coefficient

0.6 17-18. A recovery coefficient of 1 is


obtained when the size of the object
is â•›2 × FWHM. Note that the recov-
ery coefficient depends on the radio-
nuclide concentration in the objects
0.4 of interest and in the surrounding
tissue. For example, if the cylinders
in Figure 17-18 contained no radio-
nuclide and were placed in a back-
ground containing a uniform level of
0.2 radionuclide, the recovery coeffi-
cients would be the reciprocal of
those shown here.

0
0 0.5 1 1.5 2 2.5 3 3.5 4
Cylinder diameter / FWHM
17  •  Single Photon Emission Computed Tomography 301

however, it is useful for general comparisons


1.  Spatial Resolution of imaging systems. A more complete specifica-
Spatial resolution in SPECT is characterized tion is provided by the modulation transfer
using profiles through the reconstructed function, which can be obtained by taking the
image of a line or point source. Because the Fourier transform of the PSF (Chapter 15,
reconstructed images usually are stacked into Section B.2). PSFs and FWHMs usually are
a 3-D volume, two components of spatial reso- measured along the three orthogonal direc-
lution should be reported. In-plane or trans- tions x, y, and z through the image of the point
axial resolution refers to the component source. The average FWHM for the x- and
within the plane of a reconstructed slice (x- y-axis profiles gives the transaxial resolution,
and y-direction). Axial resolution refers to the whereas the FWHM of the z-axis profile gives
component that is perpendicular to the slice, the axial resolution.
along the axis of rotation of the SPECT The ramp filter provides the best achiev-
scanner (z-direction). The latter sometimes is able resolution for a specific collimator.
referred to as slice thickness. However, as described in Chapter 16, Section
In-plane resolution is determined by the B.3, it also enhances noise and often is not
intrinsic resolution of the gamma camera, the used clinically for this reason. If so, the mea-
resolution of the collimator, the angular and surement should be repeated for the recon-
linear sampling intervals used for acquiring struction filters that are used in clinical
the projection data, and the shape and cut-off practice. The measurement is repeated for
frequency of the reconstruction filter. Of different locations in the camera FOV to
these, the dominant factor almost always is provide information about the uniformity of
the collimator resolution (Chapter 14, Section the reconstructed image resolution.
C). Axial resolution depends on the intrinsic The PSF provides resolution values along
resolution of the gamma camera, the resolu- three orthogonal directions. However, point
tion of the collimator, and the linear-sampling sources can be difficult to manufacture, and
interval along the axis of rotation of the PSFs provide values only for one image plane.
gamma camera. Reconstructed spatial resolu- Line sources and LSFs are an alternative
tion is typically measured as follows: solution for both of these limitations. If the
A small 57Co or 99mTc point source is placed line source is aligned parallel to the axis of
in the FOV of the SPECT camera at the loca- the SPECT scanner, the in-plane resolution
tion of interest. To measure spatial resolution components can be measured simultaneously
accurately, the diameter of the test source for all image planes. However, a second mea-
should be much smaller than the resolution surement with the line source rotated so that
capability of the imaging instrument (e.g., it lies perpendicular to the scanner axis then
source diameter <â•›1/4 of the expected FWHM is necessary to obtain the axial resolution.
resolution). Generally, measurements are
made with the source at the center of the FOV 2.  Volume Sensitivity
and at several peripheral locations in both  The volume sensitivity measurement gives
the axial and transaxial directions. SPECT the number of events detected by the SPECT
images of the point source then are acquired system per second per unit of concentration
using linear and angular sampling intervals of radionuclide uniformly distributed in a
normally employed in clinical practice. The 20-cm-diameter cylinder. The result depends,
image is reconstructed using a ramp filter among other things, on the efficiency of col-
and a pixel size that is less than 20% of the limator, the energy window setting, the energy
anticipated spatial resolution (FWHM). Thus, resolution of the detector, the thickness of 
for a SPECT system with 12-mm FWHM  the NaI(Tl) crystal, the radionuclide, and the
resolution, the point-source size should be number of gamma camera heads in the
smaller than ~3╯mm and the pixel size should SPECT system.
be smaller than ~2.4╯mm. The measurement uses a 20-cm-diameter ×
The reconstructed image of the point source 20-cm-tall (outer dimensions) acrylic fillable
is a nearly spherical dot within the 3-D image phantom with a wall thickness between 8 and
volume. A profile drawn directly through the 12╯mm. The phantom is filled with a known
center of the image of the point source yields and uniform concentration A (becquerels per
the PSF. Usually, spatial resolution is charac- milliliter) of the radionuclide of interest
terized by the FWHM of the PSF. The FWHM (determined by using a dose calibrator or
is not a complete specification because PSFs of other calibrated radiation detector). The
different shapes can have the same FWHM; activity used in the cylinder is chosen such
302 Physics in Nuclear Medicine

that it leads to a gamma camera counting even smaller nonuniformities can lead to
rate of ~10,000 cps. At this counting rate, major artifacts in reconstructed images. The
dead time and pile-up effects are negligible. artifacts often appear as rings in images
The well-mixed phantom is placed at the acquired with single-headed SPECT systems
center of the axis of rotation of the SPECT or as arcs in images acquired with multi-
system. A 360-degree circular orbit SPECT headed systems. The intensity of the artifact
scan, with a radius of rotation of 150╯mm, is is inversely proportional to the distance of the
performed. Typically 128 projection views are nonuniformity from the axis of rotation. This
acquired, with each projection view contain- is because nonuniformities in peripheral
ing on the order of 100,000 counts. Uniformity areas are spread across a larger area of the
corrections, or any other corrections that may image during reconstruction, whereas a non-
alter the number of counts in the projection uniformity near the axis of rotation affects 
images, are turned off. a concentrated area near the center of the
The total time T required to complete the image, which can lead to strong artifacts.
acquisition and the total number of counts N Flood-field uniformities of 1% or better are
recorded across all the projection views are desirable for gamma camera detectors used
determined. The system volume sensitivity for SPECT. To detect nonuniformities at this
(SVS) is then given by level, it is necessary that sufficient counts be
acquired to ensure that the measurement is
N (counts) / T (sec) not limited by counting statistics. Poisson
SVS(cps/Bq/mL) =
A(Bq/mL) counting statistics dictate that 10,000 counts
(17-15) are required per image element to reach an
uncertainty of 1% in a planar image (Equa-
Sometimes, the measurement is reported as tion 9-6). If an image matrix of 64 × 64 is used,
the volume sensitivity per axial centimeter, in a total of ~41 million counts will be required
which case Equation 17-15 is divided by the in the uniformity image.
axial length of the phantom, in this case In many cases, it also is instructive to
20╯cm. measure the reconstructed image uniformity
of a SPECT system. At the present time, there
is no specific National Electrical Manufactur-
3.  Other Measurements   ers Association procedure for this measure-
of Performance ment, but a reasonable approach would be to
Other important performance parameters of use the data acquired using the methods
a SPECT system are energy resolution, count- described in Section C.2 for measuring volume
rate performance, and dead time. These sensitivity. An image of the uniform cylinder
parameters are the same, irrespective of would be reconstructed with appropriate
whether a gamma camera is used for planar attenuation and scatter corrections and with
imaging or for SPECT; therefore the measure- the use of clinically relevant reconstruction
ments described in Chapter 14, Sections E.5 algorithms and filters. The reconstructed
and E.6, are equally applicable to SPECT. images are visually inspected for any notice-
able artifacts or structured noise. Care must
4.  Quality Assurance in SPECT be taken to ensure that the scatter and atten-
As described in Chapter 14, Section E, quality uation corrections themselves are not the
assurance programs are important to ensure cause of any artifacts.
that an imaging system is functioning cor- A test that is specific to SPECT systems is
rectly. Many of the quality assurance proce- the measurement of system alignment. It is
dures used for gamma cameras also serve to critical that the mechanical center of rotation
ensure high-quality images when the gamma (COR) coincide with the COR defined for the
camera is used for SPECT. However, there are projection data used for reconstruction. If the
certain differences in the requirements and camera detector sags or wobbles as it rotates
additional measurements that should be around the patient, additional blurring or ring
made when a gamma camera is used for artifacts may be introduced into the image.
SPECT imaging. Because it is extremely difficult to make a
One difference relates to the specifications mechanically or rotationally perfect gantry,
of flood-field uniformity discussed in Chapter most manufacturers measure the alignment
14, Section E.4. In planar imaging, nonunifor- of their systems prior to shipment and incor-
mities of a few percent are acceptable for pro- porate software that corrects on a projection-
ducing images of diagnostic quality. In SPECT, by-projection basis for any small deviations
17  •  Single Photon Emission Computed Tomography 303

from the COR. An additional requirement for multiheaded SPECT systems, differences in
multiheaded systems is that all the heads  ErrCOR and ErrAX between detector heads
be accurately aligned in the axial direction. must also be assessed to determine any rela-
Otherwise, each head records data from a dif- tive misalignment of the heads. The recom-
ferent slice, which leads to additional blurring mended methods for doing this can be found
or artifacts in the axial direction. in reference 12.
System alignment errors can be measured
by recording profiles from different projection
angles for a point source placed off-center in D.  APPLICATIONS OF SPECT
the FOV of the SPECT system. A typical pro-
tocol involves recording an even number  It is estimated that there are more than 
of projection profiles N at equal angular inter- 5,000 SPECT-capable systems worldwide.
vals over 360 degrees. For example, projec- Not surprisingly, the major uses of SPECT as
tions could be acquired at 0, 90, 180, and  opposed to planar imaging are for situations
270 degrees. For each projection profile, the involving organs with complex geometry or
centroid (rcen, zcen) of the image of the point structure, for which accurate 3-D localization
source on the gamma camera face is deter- of signals is critical for patient diagnosis and
mined, in which r is the radial coordinate (as management.
defined in Fig. 16-3) and z is the axial coordi- The most frequent use of SPECT is for
nate. The average COR error (ErrCOR) is then studies of myocardial perfusion for assessing
given by coronary artery disease and heart muscle
damage following infarction. Figure 17-20
1 N shows a series of SPECT images that reflect
ErrCOR = ∑ rcen
N n =1
(17-16)
perfusion of the heart. It is common to perform
cardiac perfusion studies both under resting
The individual x and y components of the conditions and also following a “stress” to the
COR error are given by averaging rcen for the heart created by exercise or by the injection
projection data at ϕ = 0 degrees and 180 of a drug that causes vasodilation (e.g., ade-
degrees for x and ϕ = 90 degrees and 270 nosine). These are called rest/stress studies.
degrees for y, in which the projection angle is In some cases, SPECT studies are gated to
defined as shown in Figure 16-3. The average the electrocardiogram signal from the heart,
axial deviation ErrAX of the detector heads and data from specific portions of the cardiac
(caused by detector tilt) can be calculated cycle (e.g., end-systolic or end-diastolic) can
from be isolated. This reduces blurring caused by
1 N motion of the heart and leads to improved
ErrAX = ∑ z − zcen
N n =1
(17-17) image sharpness and contrast. However, the
number of events contributing to the image
are reduced (data are acquired only for a 
in which zcen is the PSF centroid in the z direc- fraction of the cardiac cycle), leading to 
tion and z is the mean value of zcen. In poorer signal-to-noise ratio for a fixed data

FIGURE 17-20  SPECT images showing perfusion in the heart muscle of a normal adult using 99mTc-sestamibi as the
radiopharmaceutical. The image volume has been resliced into three different orientations as indicated by the schemat-
ics on the left of each image row. SPECT data were acquired over 64 views with a data acquisition time of 20╯sec/view.
Images were reconstructed with filtered backprojection onto a 128 × 128 image array. (Images courtesy Siemens Medical
Systems USA, Inc., Hoffman Estates, IL.)
304 Physics in Nuclear Medicine

acquisition time. Figure 17-21 shows a com- disorders, brain tumors, and psychiatric
parison between gated and ungated SPECT disease (Fig. 17-22). Commonly used radio-
images of the heart. Myocardial perfusion tracers are 99mTc-hexamethylpro pyleneamine
studies usually are carried out using 201Tl, oxime (99mTc-HMPAO) and 99mTc-ethyl cystein-
99m
Tc-sestamibi, or 99mTc-tetrofosmin. ate dimer (99mTc-ECD). A number of research
Cerebral perfusion studies with SPECT also groups also are developing novel SPECT radio-
are widespread, with applications including tracers that bind to specific receptor popula-
cerebrovascular disease, dementia, seizure tions in the brain, enabling the imaging of

Gated

Ungated

FIGURE 17-21  Comparison of gated (top row) and ungated (bottom row) SPECT images showing perfusion in the heart
muscle of a normal adult following the injection of 1100 MBq of 99mTc-sestamibi. Images were acquired on a triple-
headed gamma camera with low-energy, high-resolution parallel-hole collimators. Ninety projection views were acquired
in 4-degree steps (30 projections per head), and the total imaging time was approximately 20 minutes. Data acquisition
started 30 minutes after radiotracer injection. Short-axis views of the heart are shown. In the gated study, the cardiac
cycle is divided into eight equal time intervals. Based on the electrocardiographic trigger, events are histogrammed
into the appropriate interval. The gated images in this figure correspond to the time interval that represents end-
diastole. Cardiac gating leads to a small improvement in apparent image contrast by reducing blurring caused by
cardiac motion. (Images courtesy Dr. Steve Meikle, University of Sydney, Australia.)

FIGURE 17-22  Transaxial SPECT images showing perfusion in the brain of a normal adult following injection of 890
MBq of 99mTc-HMPAO. Data were acquired on a triple-headed gamma camera with low-energy, high-resolution
fan-beam collimators. One hundred twenty projection views were collected in 3-degree increments (40 views per camera
head) with an imaging time of 40╯sec/view. Total imaging time was approximately 30 minutes, with acquisition 
commencing 50 minutes after radiotracer injection. (Courtesy Dr. Steve Meikle, University of Sydney, Australia.)
17  •  Single Photon Emission Computed Tomography 305

important receptors such as dopamine recep-


tors and serotonin receptors. 1 mm
A third important application of SPECT is heart
in oncology. Radiotracers such as 67Ga, 201Tl,
and 99mTc-sestamibi often show accumulation
in cancerous cells, and both primary and met-
astatic lesions can be visualized in SPECT
images. SPECT (in comparison with planar
imaging) is particularly useful for tumor
imaging in the thorax, abdomen, or brain,
where the tomographic information aids in
tumor detection and localization against a
complex background of heterogeneous tissues.
New radiopharmaceuticals such as 99mTc-
depreotide and 111In-pentetreotide, which are liver
specifically targeted to somatostatin recep-
tors that are overexpressed on many malig- FIGURE 17-23  SPECT image showing myocardial per-
fusion in a mouse obtained with a small-animal system.
nant cells (as well as in areas of inflammation), The injected radiotracer is 99mTc-sestamibi and the study
have become available and appear promising. was electrocardiogram-gated. (Courtesy Bioscan Inc.,
There also is interest in using radiolabeled Washington D.C.).

1 2 3 C 4 5

D
A

6 7 8 9 10

E A. Vena cava inferior


B. Heart
C. Carotid artery
11 12 13 14 15 D. Liver
E. Gallbladder
F. Duodenum

1 cm

16 17 18 19 20

FIGURE 17-24  Dynamic SPECT images showing a single reconstructed coronal image slice over time following the
intravenous injection of 34 MBq of 99mTc-HIDA into a mouse. Each image represents a 15-second acquisition over a period
of 300 seconds starting at the time of injection. The dynamic sequence of images shows the temporal sequence of uptake
and clearance of the radiopharmaceutical in the liver. (Courtesy Félicie Sherer, Université Libre de Bruxelles, Belgium; Steven
Staehlens, Ghent University, Belgium; and Freek Beekman, Delft University of Technology, The Netherlands).
306 Physics in Nuclear Medicine

antibodies and peptides for tumor localiza- 2. Genna SG, Smith AP: The development of ASPECT,
tion, and ultimately also for tumor therapy by an annular single-crystal brain camera for high-
efficiency SPECT. IEEE Trans Nucl Sci 35:654-658,
substituting the imaging radionuclide with a 1988.
β emitter that can cause localized cell death. 3. Babla H, Bai C, Conwell R: A triple-head solid state
Other areas in which SPECT is used camera for cardiac single photon emission tomogra-
include imaging of infection and inflamma- phy (SPECT). Proc SPIE 6319:63190M, 2006. DOI:
10.1117/12.683765.
tion and measurement of liver and kidney 4. Erlandsson K, Kacperski K, van Gramberg D, Hutton
function. An extensive discussion of the  BF: Performance evaluation of D-SPECT: a novel
clinical applications of both planar gamma SPECT system for nuclear cardiology. Phys Med Biol
camera imaging and SPECT can be found in 54:2635-2649, 2009.
reference 13. 5. CardiArc. Accessed October 11, 2011 from http://
www.cardiarc.com.
SPECT also has seen growing use for pre- 6. Meikle SR, Kench P, Kassiou M, Banati RB: Small-
clinical studies and basic biomedical research, animal SPECT and its place in the matrix of molecu-
often with dedicated small-animal SPECT lar imaging technologies. Phys Med Biol 50:R45-61,
systems such as those described in Section 2005.
7. Sorenson JA: Quantitative measurement of radio�
A.4. Studies may be performed in small activity in vivo by whole-body counting. In Hine GJ,
animals to study the biodistribution over time Sorenson JA, editors: Instrumentation of Nuclear
of a potential new therapeutic entity, for Medicine, Vol 2, New York, 1974, Academic Press, pp
example peptides, antibodies, nanoparticles, 311-348.
or cells that have been radiolabeled to allow 8. Chang LT: A method for attenuation correction in
radionuclide computed tomography. IEEE Trans
them to be imaged. A second common use is to Nucl Sci 25:638-643, 1978.
measure the effect of a new therapy. For 9. Jaszczak RJ, Chang LT, Stein NA, Moore FE: Whole-
example, the ability of implanted stem cells to body single-photon emission computed tomography
improve myocardial perfusion could be moni- using dual, large-field-of-view scintillation cameras.
Phys Med Biol 24:1123-1142, 1979.
tored by SPECT in an animal model using the 10. Bailey DL: Transmission scanning in emission
same radiotracers for perfusion that are used tomography. Eur J Nucl Med 25:774-787, 1998.
in the clinic. Figure 17-23 shows perfusion 11. King MA, et al: Attenuation, scatter and spatial reso-
images of the myocardium in a mouse obtained lution compensation in SPECT. In Wernick MN,
with a small-animal SPECT system. Figure Aarsvold JN, editors: Emission Tomography: The
Fundamentals of PET and SPECT, Amsterdam,
17-24 shows a single image slice from a fast 2004, Elsevier Academic Press, pp 473-498.
dynamic SPECT study showing the uptake  12. Performance Measurements of Scintillation Cameras:
of the radiopharmaceutical 99mTc-HIDA (see National Electrical Manufacturers Association
Table 5-5) in the liver following injection into (NEMA) Standards Publication NU 1-2007. Rosslyn,
VA, 2007, NEMA.
a mouse. Some of the major applications for 13. Sandler MP, et al, editors: Diagnostic Nuclear Medi-
small-animal SPECT systems are discussed cine, ed 4, Baltimore, 2002, Lippincott Williams &
in reference 14. Wilkins.
14. Franc BL, Acton PD, Mari C, Hasegawa BH: Small- 
animal SPECT and SPECT/CT: Important tools for
REFERENCES preclinical investigation. J Nucl Med 49:1651-1663,
2008.
1. Rogers WL, et al: SPRINT II: A second-generation
single-photon ring tomograph. IEEE Trans Med Imag
7:291-297, 1988.
chapter
18 
Positron Emission
Tomography
The second major method for tomographic simultaneously, in 180-degree opposing direc-
imaging in nuclear medicine is positron emis- tions, usually within a few tenths of a mm to
sion tomography (PET). This mode can be a few mm of the location where the positron
used only with positron-emitting radionu- was emitted, depending on the energy and
clides (see Chapter 3, Section G). PET detec- range of the positrons. Near-simultaneous
tors detect the “back-to-back” annihilation detection of the two annihilation photons
photons that are produced when a positron allows PET to localize their origin along a line
interacts with an ordinary electron. Although between the two detectors, without the use 
the annihilation photons could be detected of absorptive collimators. This mechanism 
using single photon emission computed is called annihilation coincidence detection
tomography (SPECT) systems operating in (ACD). Detection of a pair of annihilation
conventional single-photon counting mode, photons in opposing detectors actually defines
these systems are not optimally designed for the volume from which they were emitted.
the relatively high energy of annihilation Most ACD detectors have square or rectangu-
photons (511╯keV). They have relatively low lar cross sections. Thus the volume is essen-
detection efficiencies at these energies and tially a box of square or rectangular cross
require relatively inefficient high-energy col- section, with dimensions equal to those of the
limators. As well, SPECT systems do not take detectors (Fig. 18-1).
advantage of the back-to-back directional Coincidence logic (Chapter 8, Section F and
characteristics of annihilation photons. This Fig. 8-15) is employed to analyze the signals
unique feature is exploited advantageously from the opposing detectors. For many PET
with special annihilation-coincidence detector scanners, this is accomplished by having the
systems for PET. electronics attach a digital “time stamp” to
PET has gained widespread clinical accep- the record for each detected event. Typically,
tance and now is firmly established alongside this is done with a precision of approximately
planar imaging and SPECT in clinical nuclear 1 or 2 nanoseconds (1 nsec = 10−9 sec). The
medicine. In this chapter, we describe the coincidence processor examines the time
basic features of annihilation coincidence stamp for each event in comparison with
detection, the design and performance char- events recorded in the opposing detectors. A
acteristics of PET detectors and scanners, coincidence event is assumed to have occurred
and some of the important clinical applica- when a pair of events are recorded within a
tions of PET. specified coincidence timing window, which
typically is 6 to 12 nanoseconds.
Although annihilation photons are emitted
A.  BASIC PRINCIPLES OF  
simultaneously, a small but finite coincidence
PET IMAGING window width is needed to allow for differ-
ences in signal transit times through the
1.  Annihilation Coincidence Detection cables and electronics, as well as different
When a positron undergoes mutual annihila- distances of travel by the two photons from
tion with a negative electron, their rest the annihilation event to the detectors (see
masses are converted into a pair of annihila- Section A.2). In addition, the detectors in a
tion photons (see Fig. 3-7). The photons have PET scanner do not have perfect timing preci-
identical energies (511╯keV) and are emitted sion and therefore have a finite timing
307
308 Physics in Nuclear Medicine

Annihilation event

Detector Detector

Object containing
positron-emitting
radionuclide
Accepted by coincidence detection
Rejected by coincidence detection
FIGURE 18-1  Volume (╛╛green shaded area) from which a pair of simultaneously emitted annihilation photons can be
detected in coincidence by a pair of detectors. Not all decays in this volume will lead to recorded events, because it is
necessary that both photons strike the detectors. Outside the shaded volume, it is impossible to detect annihilation
photons in coincidence unless one or both undergo a Compton scatter in the tissue and change direction.

resolution. Uncertainties that govern the The ability of ACD to localize events on the
timing resolution can arise from the statisti- basis of coincidence timing, without the need
cal nature of the signal (which is produced by for absorptive collimation, is referred to as
the conversion of 511-keV photons into light, electronic collimation. As was discussed in
electrons, or electron-hole pairs in the detec- Chapter 14, Section C, the lead septa in stan-
tor) and from electronic noise in the detector dard parallel-hole collimators, which are nec-
and associated circuits. Uncertainties also essary to obtain adequate spatial localization,
can arise from the electronic method used to also are responsible for the relatively low sen-
determine the time at which the interaction sitivity of these collimators. Because ACD
occurred (see Chapter 8, Section F). For a pair does not require a collimator to define spatial
of similar detectors, the timing uncertainties location, its sensitivity (number of events
typically are well described by a gaussian dis- detected per unit of activity in the object) is
tribution, and the timing resolution is defined much higher than is obtainable with the
as the full width at half maximum (FWHM) absorptive collimators used for conventional
of this distribution. For scintillation detec- planar imaging and for SPECT. For compa-
tors, the timing uncertainty is reduced, and rable midplane resolution, the sensitivity of
the timing resolution improved, by using PET is many times higher than for SPECT.
brighter and faster scintillators that produce In addition, by incorporating multiple
a large number of light photons over a short opposing detectors in a complete ring or other
time interval immediately after an interac- geometric array around the patient, and oper-
tion occurs. Timing resolution is typically in ating each detector in the array in coincidence
the range of 0.5 to 5 nsec, depending on which with multiple detectors on the other side of
scintillator and photodetector is used. the array, data for multiple projection angles
The need for a finite window width permits can be acquired simultaneously (Fig. 18-2).
other types of events to occur in coincidence, Indeed, with a stationary ring or geometric
as discussed in Section A.9. Also, as discussed array that completely surrounds the patient,
in Section A.4, the annihilation photons are it is possible to acquire data for all projection
not always emitted in precise back-to-back angles simultaneously. This allows the perfor-
directions. The effects of these deviations mance of relatively fast dynamic studies and
from the ideal are discussed in the sections the reduction of artifacts caused by patient
indicated. motion.
18  •  Positron Emission Tomography 309

FIGURE 18-2  Array of detectors operating in electronic coincidence with detectors on the opposite side of the ring.
This allows simultaneous acquisition of projection views from many different angles. Solid and dotted lines illustrate
two simultaneously acquired projection views.

level of timing resolution. As well, the finite


2.  Time-of-Flight PET number of photoelectrons generated when an
In theory, it is possible to determine the loca- annihilation photon is detected gives rise to a
tion along a line between the two ACD detec- “time jitter” during the rise time that adds to
tors at which the annihilation photons the uncertainty in event timing. This effect
originated by determining the difference in becomes more severe with detectors that have
the time at which they are detected by the two relatively low light output.
detectors. This technique, which would allow With the fastest available scintillators and
the formation of tomographic images without careful design of electronic components and
mathematical reconstruction algorithms, is connections, it is possible to achieve timing
called time-of-flight PET. If the difference in accuracy at the level of a few hundred pico-
the arrival times of the photons is Δt, the loca- seconds. Although this is adequate to achieve
tion of the annihilation event, with respect to localization only to within a few centimeters,
the midpoint between the two detectors, is images reconstructed from data acquired at
given by this level of timing resolution have a higher
∆t × c signal-to-noise ratio than images recon-
∆d = (18-1) structed without time-of-flight information.
2 This is because individual events can be con-
where c is the velocity of light (3 × 1010╯cmâ•›/ strained to lie within a smaller volume in the
sec). According to this equation, to achieve image reconstruction process. Figure 18-3
1-cm depth resolution would require timing illustrates how the backprojection of data
resolution of approximately 66 picoseconds  along one particular line of response is con-
(1 psec = 10−12 sec = 0.001 nsec). Although strained to a smaller region of the recon-
electronic circuits are capable of measuring structed image matrix by the addition of
this timing difference, the rise times of light time-of-flight information. To provide practi-
output from scintillators currently available cally useful levels of time-of-flight informa-
for PET imaging are too slow to provide this tion, only the fastest and brightest scintillators,
310 Physics in Nuclear Medicine

FIGURE 18-3  A, A pair of anni-


hilation photons are emitted from
a source (red dot) and detected in
coincidence by opposing detectors.
B, In the absence of time-of-flight
information, there is no informa-
tion about the location of the
source along the line joining the
A two detectors. During reconstruc-
tion, the event is backprojected
High with equal probability of having
probability occurred in all pixels along that
line. C, With time-of-flight infor-
mation, some limited localization
of the event is possible and events
are backprojected with probabili-
ties that follow a Gaussian distri-
bution, centered on pixel Δ d
(Equation 18-1) from the center of
the scanner and with a full width
at half maximum equal to the
timing resolution of the detector
Low pair.
probability
Conventional Using time-of-flight
backprojection information
B C

such as LSO and LaBr3, can be used (see a rectangular box of area d × h at the face of
Tables 7-2 and 18-2). Several commercially either detector. Between these extremes, it is
built systems incorporate some level of time- the frustum of a pyramid with lower base size
of-flight information using these materials. equal to the size of the detectors and upper
Although there are scintillators with even base size increasing linearly from zero at mid-
faster decay components, such as BaF2, these plane to the size of the detectors at their face.
are not favored because the signal-to-noise Alternatively, consider an uncollimated
improvements that can be realized from time- pair of gamma camera detectors, also operat-
of-flight information is typically more than ing in coincidence mode (Fig. 18-4B). If their
offset by their lower density and therefore intrinsic spatial resolution (see Chapter 14,
lower efficiency for detecting 511-keV annihi- Section A.1) is a gaussian function with
lation photons. FWHM = Rint, then the spatial resolution of
the detector pair for ACD also is a gaussian
3.  Spatial Resolution: Detectors function with FWHM = Rint / 2 at midplane.
The spatial resolution of ACD with discrete The ACD response profile becomes wider as
detector elements is determined primarily by the source moves toward either detector, with
the size of the individual detector elements. its FWHM eventually becoming equal to Rint
As shown in Figure 18-4A, for elements of at the face of either detector. Assuming that
width d, a one-dimensional (1-D) slice through the resolution of the imaging detector is the
the ACD point-source response profile at  same in all directions, the 2-D ACD response
midplane between the detector pair is a  profile is obtained by rotating the 1-D gauss-
triangle. The detector resolution, Rdet has a ian function around its center.
FWHM = d/2. As the source moves toward For both discrete or gamma camera–type
either detector, the response profile becomes detectors, the spatial resolution of ACD varies
trapezoidal, eventually becoming a box of by only approximately 30% in the central 60%
width d at the face of either detector. Consid- of the space between the detectors (Fig. 18-5).
ering a 2-D detector with width d and height By comparison, the resolution of a parallel-
h, the ACD response profile becomes a 3-D hole collim�ator can vary by several hundred
function, which is a pyramid at midplane and percent over a comparable range (see Fig.
18  •  Positron Emission Tomography 311

Intrinsic resolution
FWHM  R int

FWHM  d FWHM  R int

FWHM  3 d/4 FWHM  0.85R int

FWHM  d/2
FWHM  R int / 2

Source

Intrinsic resolution
FWHM  R int

Discrete Continuous
A detectors B detectors
FIGURE 18-4  Spatial resolution of detector pair (Rdet) for coincidence detection. A, For discrete detectors, spatial reso-
lution is determined by the width of the detector element, d. At midplane, the coincidence response function is a triangle
with full width at half maximum (FWHM) = d/2. As the source is moved closer to one of the detectors, the response
function becomes trapezoidal in shape, eventually becoming a rectangle of width, d. B, For continuous detectors, spatial
resolution is determined by the intrinsic resolution of the detector, Rint. At the midplane, the coincidence response
function is approximately gaussian, with FWHM = Rint / 2 . Near the face of a detector, it becomes FWHM = Rint.
312 Physics in Nuclear Medicine

14-19). When profiles obtained from opposing


views in SPECT are combined using the geo- 4.  Spatial Resolution: Positron Physics
metric mean, the variation in resolution The spatial resolution of an ACD system is
within the space between the opposing detec- degraded from the values derived from simple
tors is reduced to a level comparable to ACD geometry indicated in Figure 18-4 by two
(see Fig. 17-8). The key difference is that the factors relating to the basic physics of positron
resolution of ACD is determined primarily by emission and annihilation. The first is the
the size of the detector element or the intrin- finite range of positron travel before it under-
sic resolution of the camera detector, whereas goes annihilation. ACD defines the line along
for SPECT, the resolution is primarily deter- which the annihilation event took place, which
mined by the collimator resolution at the mid- is not precisely the location from which the
point between the two detectors. The latter is decaying radioactive nucleus emitted the posi-
substantially degraded from its value at the tron. The range of travel for a positron before
face of the detector. This means that the col- it undergoes annihilation is essentially the
limator must have very high resolution at its same as the range of travel of an ordinary
face to achieve even moderately good resolu- electron (or β particle) of similar energy (see
tion at midplane between the detectors. In Chapter 6, Section B.2). Figure 6-10 and Table
turn, the requirement for high spatial reso� 6-1 show the extrapolated range versus
lution leads to relatively low detection efficiÂ� maximum energy for β particles, Eβmax . The
ency with absorptive collimators (see Chapter maximum energies of the positrons emitted
14, Section C). As discussed in Section A.8, from radionuclides used for nuclear medicine
this results in relatively low sensitivity for  are in the range of 0.5 to 5╯MeV (Table 18-1;
a SPECT system as compared with a PET see also Appendix C). Thus their extrapolated
system with comparable spatial resolution. ranges are in the 0.1- to 2-cm range.

12.9

12

11.7

8
)
m

10.5
(c
nt

8
oi
-p
id
m
m
Relative count rate

6
fro
e
nc

4
ta
is

4
D

9.8

0 0
20 0 20
Distance (mm)
FIGURE 18-5  Measured line-spread functions for a pair of 17-mm-wide coincidence detectors as a function of source
position between the two detectors. The detector separation was 42╯cm. The FWHM varies by only 30% within the
central 24╯cm (57%) of the space between the two detectors. (From Hoffman EJ, Huang S-C, Plummer D, Phelps ME:
Quantitation in positron emission computed tomography: VI. Effect of nonuniform resolution. J Comput Assist Tomogr
6:987-999, 1982.)
18  •  Positron Emission Tomography 313

TABLE 18-1â•…
SOME POSITRON-EMITTING NUCLIDES USED FOR IN VIVO IMAGING

Maximum
Radionuclide Half-Life β+ fraction β+ Energy How Produced
11
C 20.4╯min 0.99 960╯keV Cyclotron
13
N 9.96╯min 1.00 1.19╯MeV Cyclotron
15
O 123╯sec 1.00 1.72╯MeV Cyclotron
18
F 110╯min 0.97 635╯keV Cyclotron
62 62
Cu 9.74╯min 0.98 2.94╯MeV Generator (from Zn)
64
Cu 12.7╯hr 0.19 580╯keV Cyclotron
68 68
Ga 68.3╯min 0.88 1.9╯MeV Generator (from Ge)
76
Br 16.1╯hr 0.54 3.7╯MeV Cyclotron
82 82
Rb 78╯sec 0.95 3.35╯MeV Generator (from Sr)
124
I 4.18 days 0.22 1.5╯MeV Cyclotron

The extrapolated range applies to the result is that the average distance measured
highest-energy positrons emitted by a radio- from the origin of the positrons to the end of
nuclide. However, positrons, like β particles, their path is significantly smaller than their
are emitted with a spectrum of energies. Only extrapolated range.
a small fraction have the full amount of For purposes of defining the spatial resolu-
energy available from the decay (see Fig. 3-2). tion of ACD, the distance of interest is the
In addition, the extrapolated range is the effective positron range. This is the average
maximum distance that the electron would distance from the emitting nucleus to the end
travel if it were not significantly deflected  of the positron range, measured perpendicu-
in any of its interactions and traveled in lar to a line defined by the direction of the
essentially a straight line to the end of its annihilation photons (Fig. 18-6). This dis-
range. In reality, most electrons (and posi- tance always is smaller than the extrapolated
trons) travel a tortuous path, often with mul- range for the positrons emitted by the
tiple large-angle deflections (see Fig. 6-4). The radionuclide.

Positron-emitting
radionuclide

Positron

Actual
positron Positron
range path
Effective
positron
range

511 keV
photon

511 keV
photon

Annihilation event
FIGURE 18-6  Blurring caused by positron range effects. The perpendicular distance from the decaying atom to the
line defined by the two 511-keV annihilation photons is referred to as the effective positron range.
314 Physics in Nuclear Medicine

Figure 18-7 shows the positron range dis- A second factor involving the physics of
tribution for point sources of 18F ( Eβmax = positrons is that the annihilation photons
0.635╯MeV) and 15O ( Eβmax = 1.72╯MeV). Accord- almost never are emitted at exactly 180-
ing to Figure 6-10, the extrapolated ranges degree directions from each other (Fig. 18-9).
for these positrons in water would be appro� This effect, which is due to small residual
ximately 2╯mm and 8╯mm, respectively; momentum of the positron when it reaches
however, the FWHMs of their distribution the end of its range, is known as noncolinear-
profiles are only 0.1╯mm and 0.5╯mm. ity. The angular distribution is approximately
Note as well that the positron range distri- gaussian with FWHM approximately 0.5
butions shown in Figure 18-7 have long tails degree. The effect on spatial resolution,
and thus are not well described by gaussian expressed in terms of FWHM, is linearly
functions. Therefore the FWHM is not the best dependent on the separation of the ACD
indicator of the effect of positron range on ACD detectors, D, and is given by
spatial resolution. Instead, the root mean
square (rms) effective range often is used. R180° = 0.0022 × D (18-2)
Figure 18-8 shows the general relationship
between rms effective range and maximum A typical value of D for a whole-body PET
positron energy. Typical rms effective ranges scanner is 80╯cm. Thus the FWHM for blur-
(and thus the blurring caused by positron ring caused by noncolinearity is approxi-
ranges) are on the order of 0.5 to 3╯mm. Note mately 2╯mm.
that positron range is inversely proportional The system resolution of an ACD or PET
to the density of the absorber. Thus rms ranges detector system is obtained by combining the
would be proportionately higher in lung tissue individual resolution components, in the same
and airways (ρ ~ 0.1-0.5╯g/cm3) and lower in manner as the component resolutions are
dense tissues such as bone (ρ ~ 1.3-2╯g/cm3). combined to determine the system resolution

10 2500
18F (Emax  635 keV) 100,000 Events 18F
2000
5

1500
Events

0
1000 0.102 mm FWHM

5 500 1.03 mm FWTM

10,000 Events 0
10
10 5 0 5 10 2 1 0 1 2
End point coordinate (mm) End point coordinate (mm)
10 800
15O (Emax  1720 keV) 100,000 Events 15O
700
5 600
500
Events

400
0
300 0.501 mm FWHM
200 4.14 mm FWTM
5
100

10,000 Events 0
10
10 5 0 5 10 8 6 4 2 0 2 4 6 8
End point coordinate (mm) End point coordinate (mm)
FIGURE 18-7  Results of Monte Carlo simulations showing the distribution of annihilation sites for positron-emitting
point sources in water for 18F ( Eβmax = 0.635╯MeV) and 15O ( Eβmax = 1.72╯MeV). The profile of the distribution is broader
for 15O because of its higher average positron energy, which leads to a longer positron range prior to annihilation.
(From Levin CS, Hoffman EJ: Calculation of positron range and its effect on the fundamental limit of positron emission
tomography system spatial resolution. Phys Med Biol 44:781-799, 1999.)
18  •  Positron Emission Tomography 315

82
Rb
2.5

rms range in water (mm)


2

FIGURE 18-8  Root mean square


range for positrons in water versus  1.5
Eβmax . (Data from Derenzo SE: Math- 68
Ga
ematical removal of positron range
blurring in high-resolution tomogra-
phy. IEEE Trans Nucl Sci 33:565- 1
569, 1986.)
11
C
0.5
18
F

0
0 0.5 1 1.5 2 2.5 3 3.5
Maximum  energy (MeV)

Positron

Non-colinearity

511 keV
photon 511 keV
photon
Annihilation event
Error due
to non-colinearity
FIGURE 18-9  Noncolinearity of annihilation photons resulting from residual momentum of the electron and positron
at annihilation. Noncolinearity leads to positioning errors. Angles are exaggerated in this example for purposes of
illustration. Actual range of angles is about ±0.25 degree, centered at 180 degrees.

for a gamma camera system (see Chapter 14, the discrete detector elements or the intrinsic
Section C.4). Thus resolution of continuous detectors (see Section
A.3 and Fig. 18-4). For typical whole-body
Rsys ≈ 2
Rdet + Rrange
2
+ R180
2
° (18-3) PET scanners, with either discrete detector
elements or gamma camera detectors, the
where Rdet is the spatial resolution of the effects of positron range and noncolinearity
detector system, as determined by the size of combine to add anywhere from a few tenths
316 Physics in Nuclear Medicine

of a millimeter to a few millimeters to system situation 2, the system resolution becomes


resolution. ~1.7╯mm, so the effects of positron range and
noncolinearity still are substantial (~70%).
EXAMPLE 18-1
What fraction of PET system resolution at  For situation 3, Rdet = 3 / 2 ≈ 2.12╯mm (see
the center of the scanner bore is caused by  Fig. 18-4) while other factors remain the same
positron range and noncolinearity blurring in as in situation 2. Thus
the following three situations? (1) 6-mm-wide 

discrete detectors, separated by 80╯cm, using Rsys ≈ 32 / 2 + 1.22 + 1.322 ≈ 2.77 mm
18
F; (2) 2-mm-wide discrete detectors sepa-
rated by 60╯cm, using 68Ga; (3) gamma camera Positron range and noncolinearity increase
detectors with 3-mm intrinsic resolution at the system resolution by approximately 30%
511╯keV, separated by 60╯cm, using 68Ga. relative to detector resolution in this
situation.
Assume that the positron range distribution
can be approximated by a gaussian function From Example 18-1, one can conclude that
and use the rms effective range to represent positron range and noncolinearity have a rel-
the FWHM of that function. atively small effect on system resolution for
whole-body systems, which usually have
Answer larger detector elements (situation 1) or only
For situation 1, the spatial resolution at the moderately high spatial resolution (situation
midpoint between 6-mm-wide discrete detec- 3). This is especially true for 18F, the radionu-
tors is given by clide most commonly used for clinical applica-
tions. However, their effects can be important
Rdet = d/ 2 = (6 mm)/ 2 = 3 mm limitations for high-resolution brain imaging
or small-animal imaging devices (see Section
The rms range for 18F is Rrange ≈ 0.2╯mm (see B.5) that employ small discrete detector ele-
Fig. 18-8), and the noncolinearity for an 80-cm ments, especially for applications involving
separation is higher-energy positrons (situation 2).
Because they do not depend on technology,
positron range and non colinearity create bar-
R180° = 0.0022 × 800 mm = 1.76 mm
riers for improving the spatial resolution of
PET systems that cannot be overcome simply
Using Equation 18-3, the system resolution is by using smaller detector elements. For
example, independent of the detectors used,
the blurring caused by non�colinearity will
Rsys ≈ 32 + 0.22 + 1.762 ≈ 3.5 mm
limit the achievable spatial resolution for a
Thus resolution blurring caused by positron whole-body PET scanner to approximately
range and noncolinearity for situation 1 adds 2╯mm, because a bore size of 80-90╯cm is
approximately 17% to the system resolution, required to accommodate the human body.
relative to the detector resolution. Example 18-1 also demonstrates that when
system resolution is dominated by one compo-
For situation 2, using the same equations nent, the gains achieved by improving other
and Figure 18-8, the spatial resolution of components of resolution may be small.
2-mm-wide discrete detectors is Rdet = 1╯mm,
the rms range for 68Ga is Rrange ≈ 1.2╯mm and
the noncolinearity blurring for the 60-cm sep- 5.  Spatial Resolution:  
aration is 1.32╯mm. Thus the system resolu- Depth-of-Interaction Effect
tion is A substantial thickness of scintillator mate-
rial is required to efficiently stop 511-keV
annihilation photons. In a gamma camera,
Rsys ≈ 12 + 1.22 + 1.322 ≈ 2.05 mm typical NaI(Tl) detector crystal thicknesses
are 1.25╯cm or less. PET systems generally
In this situation, the additional blurring employ 2- to 3-cm-thick scintillators with
caused by positron range and noncolinearity greater stopping power, such as BGO or LSO.
approximately doubles the system resolution For PET systems using arrays of detectors in
relative to detector resolution. Note that if multiple coincidence mode around the object,
68
Ga is replaced by the lower-energy 18F in the relatively thick detector elements lead to
18  •  Positron Emission Tomography 317

a degradation of resolution known as the at which an interaction has occurred within


depth of interaction (DOI) effect. Although the the detector crystal. The spatial resolution
effect also occurs in the axial direction in (FWHM) then becomes R′det = d′/2. Using
scanners that use cross-plane coincidence Equation 18-4, this can be written as
detection for 3-D data acquisition (see Section
C.2), the primary effect is in the radial direc- ′ ≈ ( d / 2) × [ cos θ + ( x / d ) sinθ ]
Rdet
tion, and the discussion focuses on this aspect ≈ Rdet × [ cos θ + ( x / d) sin θ] (18-5)
of the problem.
Figure 18-10 illustrates the cause of the From this equation it can be seen that the
problem for a detector system that uses a DOI effect is described by a multiplicative
circular array of elements, all or most ele- factor applied to the value of detector resolu-
ments of which operate in multicoincidence tion at the midpoint between a pair of directly
mode with other elements in the array. For a opposed detectors.
source located near the center of the scanner, Equation 18-5 is only an approximation
spatial resolution is determined by the width because the thickness of detector material is
of the detector element, Rdet = d/2, as described not constant across the width of the detector
in Section A.3 and illustrated in Figure 18-4. element seen by the source. Note as well that,
However, for a source located away from the for thin detector elements [(x/d) << 1], it is
center, the apparent width of the detector possible that R′det < Rdet. The same would be
element becomes true for a very efficient detector material (or
a very thin detector) that would stop most of
d ′ = d cos θ + x sin θ (18-4) the annihilation photons in a thin layer at the
entrance to the detector. However, these con-
where d, x, and θ are as indicated in Figure ditions never apply in practice. Typically, x ~
18-10. The apparent change in width results 2 to 3╯cm and d ~ 0.3 to 0.6╯cm. For a whole-
from the angulation between the detectors body PET scanner with 4-mm-wide detectors
and from lack of knowledge about the depth on a diameter of 80╯cm, the DOI effect causes

FIGURE 18-10  Apparent width of a


detector element, d′, increases with
increasing radial offset in a PET
scanner consisting of a circular array
of detector elements. Because the
depths at which the γ rays interact

within the scintillation crystal are
unknown, the annihilation event for
a pair of photons recorded in coinci-
dence could have occurred anywhere D
within the shaded volume. The mag-
nitude of the effect depends on the d
source location, the diameter of the
scanner, D, the length of the crystal
elements, x, and the width of the
detector elements, d.
318 Physics in Nuclear Medicine

appr�oximately a 40% degradation of resolu- d


tion at a distance of 10╯cm from the center of
the field of view (FOV).
The DOI effect is somewhat different for
systems that use hexagonal or octagonal
arrays as opposed to circular arrays of detec-
tor elements. With hexagonal or octagonal
arrays, as the source moves away from the
center of the scanner, some portion of an
opposing array still remains perpendicular to
it, at least over a distance comparable to the
width of a segment of the array. Consequently,
there is less variation in the DOI effect across
the FOV. At the center of the FOV, the effect
is somewhat larger than at the center for a
circular array of the same diameter, whereas
at the periphery it is somewhat smaller. On A
average, the DOI effect is comparable for both
segmented and circular arrays.
Note also in Equations 18-4 and 18-5 that,
for a given radial distance away from the
center of the scanner, θ and sin θ become
smaller (and thus R′det becomes smaller) as
the diameter of the detector ring becomes
larger. Because of the DOI effect, PET scan-
ners often are built with detector arrays that
are of larger diameter than would be neces-
sary to fit the patient, which in turn increases
detector costs.
6.  Spatial Resolution: Sampling
In ACD, the FWHM of the detector resolution
is one-half the width of a detector element B
(see Fig. 18-4). For a stationary array of detec-
tor elements, each of width d, the sampling
interval between parallel projection lines also
is d (Fig. 18-11A). Considering only detector
resolution, it can be shown that this leads to
undersampling of object profiles, which in
turn leads to a distortion of the high-frequency
content (i.e., the fine details) of the recon-
structed image (see Fig. 16-11 and Section C).
According to Equation 16-14, three samples
should be acquired per FWHM of spatial reso-
lution. In theory, this would translate into a
requirement for six samples over an interval
equal to the width of a detector element.
However, as described elsewhere in this
section, system resolution is degraded from
the theoretical limits established by intrinsic C
resolution by other factors, so that coarser
FIGURE 18-11  A, For a stationary array of discrete
sampling is acceptable. Nonetheless, some detector elements, the linear sampling distance is the
additional sampling is required beyond that same as the detector element width, d, which is insuffi-
illustrated in Figure 18-11A. cient to support the resolution of the detectors (~d/2). B,
In practice, two samples usually are acquired Linear sampling distance is reduced to d/2 when coinci-
dences with immediately adjacent detectors are allowed.
per detector element width. Although less C, For image reconstruction, these samples are treated
than the theoretical ideal, this results in little as if they came from a set of virtual detectors offset by
noticeable distortion of clinical images. Some half the detector width relative to the actual detectors.
18  •  Positron Emission Tomography 319

earlier scanners actually incorporated a spatial filtering required to achieve an accept-


mechanical shift to acquire two sets of data able noise level in the image. As discussed in
with the detector elements shifted by half the the following section and in Section B, PET
width of a detector element between acquisi- systems, especially those employing multiple
tions. This approach was mechanically cum- detector rings and multi-ring coincidence
bersome. The modern approach is to use detection, have substantially higher detection
coincidence events in adjacent pairs of detec- efficiencies (by orders of magnitude) than is
tor elements, thereby creating additional achievable with typical SPECT systems. Thus
samples between the detector elements, as PET images usually can be reconstructed
illustrated in Figure 18-11B. These are treated with higher cut-off frequencies, and their
as samples acquired with a virtual set of final spatial resolution generally is superior
detectors located between the actual detector to SPECT images.
elements, as shown in Figure 18-11C. The ray
paths for the additional samples are not quite
parallel to those for directly opposed detec- 8.  Sensitivity
tors, but this seems to have little effect on  The sensitivity of PET, like that of all imaging
the reconstructed image across most of the devices, is determined primarily by the absorp-
useful FOV. tion efficiency of the detector system and its
Note that combining data for adjacent solid angle of coverage of the imaged object.
pairs of detectors into a single projection view The true coincidence rate, Rtrue, for a positron-
as illustrated in Figure 18-11B and C, reduces emitting source located in an absorbing
the number of projection angles available medium between a pair of coincidence detec-
from a stationary ring of detectors by half. tors is given by
Note also that PET systems that use continu-
ous (i.e., gamma camera type) detectors (see Rtrue = E ε 2 gACD e − µT (18-6)
Section B.3) can use arbitrarily chosen sam-
pling intervals and thus can avoid some of the where E is the source emission rate (positrons/
sampling problems associated with discrete sec); ε is the intrinsic efficiency of each detec-
detector arrays. tor, that is, the fraction of incident photons
detected (Equation 11-9, assumed to be the
same for both detectors); and µ and T are the
7.  Spatial Resolution: Reconstruction linear attenuation coefficient and total thick-
Filters ness of the object, respectively. gACD is the
The discussions in the preceding sections geometric efficiency of the detector pair, that
describe the spatial resolution achievable is, the fraction of annihilation events in which
with PET systems, as determined by the phys- both photons are emitted in a direction to be
ical characteristics of the imaging device and intercepted by the detectors.
the basic physics of positron decay. However, As shown in Figure 18-4, the shape as well
as discussed in Chapter 16, Sections B.3 and as the amplitude of the point-source response
C.3, spatial filters are applied to the recorded profile (i.e., gACD for a point source) varies
projection profiles to suppress noise in the with the location of the source between the
reconstructed image (see Fig. 16-12). Inevita- two detectors. In one dimension, the profile is
bly, this results in some degradation of spatial triangular at the midpoint between the detec-
resolution. In general, the fewer the number tors, rectangular at the face of either detector,
of counts recorded in an image, the lower the and trapezoidal at locations between. In two
filter cut-off frequency (kcut-off) and the greater dimensions, the ACD response at the mid-
the loss of spatial resolution. point is a pyramid, whereas at the surface of
The selection of cut-off frequency depends either of the detectors it is a rectangular box.
in part on the type of study. Thus a brain scan At points between, it is the frustum of a
might be reconstructed with a cut-off fre- pyramid. In all cases, the lower base is equal
quency yielding 6-mm spatial resolution, to the area of the detectors.
whereas an abdominal scan, with more tissue Maximum geometric efficiency for ACD is
attenuation and generally lower count densi- obtained for a point source located precisely
ties, might be reconstructed with a filter at the midpoint of the centerline between the
yielding 10-mm spatial resolution. As well, two detectors. However, as illustrated in
the sensitivity (number of counts recorded per Figure 18-4, this value does not apply when
unit of activity in the patient) affects the sta- the point source is moved even slightly away
tistical quality of the image and the degree of from the centerline, or from the midpoint of
320 Physics in Nuclear Medicine

that line. Thus a more appropriate measure hexagonal, or octagonal arrays. Each detector
for distributed sources is the average geomet- element is operated in coincidence with many
ric efficiency within the sensitive volume for detectors on the opposing side of the ring, as
ACD. Midway between the two detectors, this shown in Figure 18-12. This multicoincidence
is given by operation has useful and important conse-
quences for both the magnitude and unifor-
1 mity of geometric efficiency.
g ACD ≈ 2 × × [ Adet / π D2 ] The simplest way to visualize its effects on
3
(18-7) geometric efficiency is to consider a complete
2 Adet ring of detectors on a diameter D, with detec-

3π D 2 tor height h in the axial dimension and detec-
tor width d << D in the plane of the ring.
where D is the distance between the detectors Assume that any interdetector gaps are “very
and Adet is the area of the detector facing the small,” so that the individual elements form a
source. virtually continuous ring of detector material.
The term in brackets in Equation 18-7 is For a point source located precisely at the
the geometric efficiency for a single detector center of the ring, the geometric efficiency
for a point source located at the midpoint of would be equal to the solid angle subtended
the centerline between the detectors. (As dis- by the ring, because if either annihilation
cussed in Chapter 11, Section A.2, this expres- photon is intercepted by the ring, it is virtually
sion is valid when the detector dimensions assured that the second photon is traveling
are “small” in comparison with the source-to- the proper direction to be intercepted as well.
detector distance.) The factor of 2 accounts for From simple geometric considerations, if h <<
the fact that two detectors are used and that D, it can be shown that the solid angle, and
if one photon is emitted in a proper direction thus the geometric efficiency, for a point source
toward one detector, the other photon is virtu- precisely at the center of the ring is given by
ally assured of being emitted in the proper
direction toward the other. The factor of 1/3 gACD,RING ≈ h/D (18-8)
is the average geometric efficiency across the
sensitive volume at midplane, that is, the Under the conditions described, geometric
average height of a pyramid. efficiency is relatively constant as the source
Actual PET systems typically employ many is moved away from the center of the ring but
small detector elements arranged in circular, still in its center plane; however, as the source

Useful field-
of-view

FIGURE 18-12  Ring of detectors in


which individual elements are oper-
ated in coincidence with multiple ele-
ments on the opposite side of the ring.
In multicoincidence operation, each
detector element is associated with a
fan-beam acquisition, shown for two
individual detector elements in the
drawing. Data are recorded simulta-
neously for all possible fan beams. The
inner circle formed by edges of all such
fan beams defines the useful field-of- 
view.
18  •  Positron Emission Tomography 321

is moved axially toward the ends of the ring, photons onto the detectors and by gaps
the geometric efficiency still has a triangular between detector elements. Corrections for
shape. Thus the average geometric efficiency this and other image nonuniformities are
for a source distributed within the sensitive described in Section D.1.
volume for ACD across the width of the  It is noteworthy that, by segmenting large
ring is half the value given by Equation 18-8, detectors into smaller elements and operating
that is, them in coincidence with multiple elements
h in the opposing array, it is possible to improve
g ACD, RING ≈ (18-9) the spatial resolution in PET with only a
2D modest loss of geometric efficiency. This effect
Equations 18-8 and 18-9 also are valid for is seen in Equation 18-9, in which geometric
polygonal arrays, with D representing the efficiency depends on the diameter of the ring,
diameter of a circle drawn tangential to the D, but not on the width d of the individual
surface of the array. As long as h << D, they detector elements. Most of the loss of sensitiv-
also apply to continuous detectors that use ity that does occur is due to the requirement
gamma camera electronics, rather than dis- for interelement spacing and shielding, which
crete detector elements, to determine event is only approximately 0.2 to 0.3╯mm in practi-
locations. cal systems. For comparison, from fundamen-
In addition to increasing geometric effi- tal principles, the geometric efficiency of
ciency and improving its uniformity, multico- absorptive collimators is degraded approxi-
incidence detection with a ring or polygonal mately as the square of spatial resolution
array of detectors also allows simultaneous (Equation 14-8). This presents a formidable
acquisition of multiple projection views challenge for improving spatial resolution in
without moving the detectors. Suppose the imaging applications based on single-photon
ring consists of N individual detector ele- counting, including SPECT.
ments. When each detector in the ring or  The benefits of multicoincidence operation
array is operated in coincidence with a bank extend as well to the third (axial) dimension
of detectors on the opposite side, as illustrated in multi-ring PET systems. This is discussed
in Figure 18-12, a total of N/2 fan-beam further in Section C.
projections are acquired. These fan-beam pro- As is the case for any imaging system, the
jections typically are arranged to form parallel- sensitivity of a PET system also depends 
beam profiles, as illustrated in Figures 16-20 critically on the detection efficiency of the
and 18-2. However, as illustrated in Figure detector, which enters as a squared term 
18-11, data from adjacent pairs of detector in Equation 18-6. As was discussed in Chapter
usually are assigned to the same projection 11, Section A.3, detection efficiency is given
profile, thereby decreasing the number of by
views to N/4.
The number of detectors that are enabled ε = 1 − e− µ x
l (18-10)
for multicoincidence detection determines the
width of the fan-beam projections and thus where µl is the linear attenuation coefficient
the diameter of the useful FOV. Sources of the detector material and x is the detec�
located within the circle illustrated in Figure tor thickness. Values of µl for several detector
18-12 are seen in all projections. Once a materials of interest for PET are given in
source is included within the useful FOV, a Table 18-2. Also indicated are values of ε for
further increase in fan-beam width does not 2-cm-thick detectors of each material, without
increase the counts recorded from that source. a low-energy threshold and with an energy
Sources outside the circle are not seen in threshold that eliminates 50% of the detected
some views, which could be a cause of image pulses. Values for ε2 in this table are useful
artifacts (see Chapter 16, Section C.2). Typical for calculating scanner sensitivity and ACD
PET systems operate with each detector in counting rates (Equation 18-6). These values
coincidence with approximately two-thirds illustrate why materials such as BGO, LSO,
the total number of detectors in the ring. and LYSO (Chapter 7, Section C.4) are pre-
Geometric efficiency varies somewhat ferred over NaI(Tl) for PET imaging.
across the useful FOV of the detector ring. In Overall sensitivities for PET systems for a
part, this is because the solid-angle for coin- small-volume source of activity located near
cidence detection changes with source posi- the center of the scanner range from 0.2% 
tion. There also are geometric effects caused to 0.5% (0.002-0.005╯cps/Bq) for single-ring sys�
by differences in angle of incidence of the tems or for multi-ring systems operated in 
322 Physics in Nuclear Medicine

TABLE 18-2â•…
LINEAR ATTENUATION COEFFICIENTS AND DETECTION EFFICIENCIES FOR SOME
SCINTILLATORS AT 511╯keV*

Scintillator µl(511╯keV) cm–1 ε (2╯cm)† ε2 (2╯cm) ε50 (2╯cm)‡ ε 50


2
(2╯cm)
NaI(Tl) 0.34 0.49 0.24 0.25 0.061
BGO 0.95 0.85 0.72 0.43 0.18
LSO, LYSO 0.88 0.83 0.69 0.41 0.17
GSO 0.70 0.75 0.57 0.38 0.14
BaF2 0.44 0.58 0.34 0.29 0.086
*Efficiency values are for 2-cm thick crystals.

Detection efficiency (see Equation 18-10), assuming no low-energy threshold (all pulses counted).

Detection efficiency, assuming low-energy threshold is used, with 50% of pulses counted (f = 0.5 in Equation 11-4).

2-D acquisition mode (one slice per ring; events are called prompt coincidences. The
Section C.1). For multi-ring systems in which discussion and analysis presented thus far
coincidences between rings are allowed for 3-D assumes that all prompt coincidences arise
data acquisition (see Section C.2), the sensitiv- from a pair of photons produced from the
ity typically is 2% to 10% (0.02-0.10╯cps/Bq). same annihilation event and that the anni-
For comparison, the sensitivities for SPECT hilation event occurs somewhere within the
systems with a general-purpose parallel-hole coincidence volume between the detectors
collimator are in the range of 0.01% to 0.03% (see Fig. 18-1). These events are called true
(0.0001-0.0003╯cps/Bq), depending on the number coincidences. Equation 18-6 describes the
of detector heads (see Chapter 14, Section E.7). sensitivity of the system for these events.
The substantially greater sensitivity of PET However, other prompt coincidence events
versus SPECT systems is due primarily to also can occur within the resolving time of
their ability to achieve a high degree of spatial the detector system.
resolution without the use of absorptive Two examples are shown in Figure 18-13.
collimators. Random coincidences (also called accidental
coincidences) occur when annihilation photons
from two unrelated positron annihilation
9.  Event Types in Annihilation events are detected in two different detectors,
Coincidence Detection within the coincidence timing window, and
ACD produces an output whenever two recorded as a single coincidence event. This
events are recorded within a specified coinci- can happen if one photon from each annihila-
dence timing window. Generically, any such tion event is detected in each detector element.

True coincidence Scatter coincidence Random coincidence

FIGURE 18-13  True coincidence event (left), scatter coincidence event (center), and random or accidental coincidence
(right). Scatter and accidental coincidences yield incorrect positional information and contribute a relatively uniform
background to the image that results in a loss of contrast. (Courtesy Dr. Magnus Dahlbom, University of California—
Los Angeles.)
18  •  Positron Emission Tomography 323

Random coincidences are not rare events, In actual PET scanners, the ratio of
because the volume of tissue from which the random-to-true coincidence counting rates
photons for a random coincidence event could typically ranges from approximately 0.1 to 0.2
arise generally is much larger than the poten- for brain imaging to greater than 1 for appli-
tial volume for true coincidence events. cations where large amounts of activity may
The random coincidence counting rate in a be nearby, but outside the true coincidence
detector pair is given by volume of the scanner. The latter could apply,
for example, to some types of abdominal
Rrandom = ∆T × Rsingle,1 × Rsingle,2 (18-11) imaging when large amounts of activity are
excreted into the bladder. Random coinci-
where ΔT is the coincidence timing window dences occur more or less uniformly across
used by the system* and Rsingle,1 and Rsingle,2 the FOV of the scanner, causing a loss of
are the single-channel counting rates in the image contrast as well as inaccuracies in
two detectors of the pair. Unlike true coinci- quantification of activity within the patient.
dence events, which can occur only when the Methods for correcting for random coinci-
source is located within the volume that is dences are discussed in Section D.2.
geometrically defined by the sides of the A second category of nonvalid prompt
detector pair (see Fig. 18-1), random coinci- coincidences are scatter coincidences. These
dences can arise from activity anywhere in occur when one (or both) of the photons from
the region between the detectors, including an annihilation event outside the sensitive
activity outside the useful FOV for a ring or volume for true coincidence events under-
array of detectors. Thus the single and goes scattering and is detected in a detector
random coincidence counting rates depend in other than the one that would be appropri-
a complicated way on both the source and ate for a true coincidence event. The scatter-
detector geometry. A detailed analysis of these ing event shown in Figure 18-13 occurs
factors is beyond the scope of this text. Refer- within the patient, but it also can occur
ence 1 provides a more comprehensive analy- within components of the scanner. Because
sis. Nonetheless, some general observations the two annihilation photons were emitted
can be made. simultaneously, they reach the detectors vir-
In general, the greater the total amount of tually simultaneously, apart from small
activity used in a study, the higher the ratio time-of-flight differences (see Section A.2).
of random-to-true coincidence rates. This is Because these differences are very small, the
because the random coincidence rate increases detector system and its associated coinci-
as the square of the amount of activity present dence logic cannot typically distinguish them
(product of single-channel counting rates in from valid events.
Equation 18-11), whereas the true coincidence As is the case for the random-to-true coin-
rate increases only linearly with the amount cidence ratio, the ratio of scatter-to-true 
of activity administered (Equation 18-6). A coincidence counting rates depends in a com-
second general observation is that the ratio of plicated way on the source distribution and
random-to-true coincidence rates decreases in detector geometry. Placement of lead shield-
proportion to the width of the coincidence ing on either side of the detector ring, or of
timing window. However, as noted in Sections thin tungsten septa between detector rings in
A.1 and A.2, there are lower limits for this a multi-ring PET system, reduces the likeli-
value, because of electronic and time-of-flight hood of accepting scattered photons. However,
considerations. Finally, a general way to unlike the random-to-true ratio, the scatter-
reduce the single-channel counting rate from to-true ratio does not depend on the amount
activity outside the true coincidence volume is of activity administered, because both the
to use tungsten septa to restrict the FOV of scatter and true coincidence rates increase
individual detectors (see Section B.3). In turn, linearly with this parameter. It also does not
this reduces the random coincidence rate. depend on the width of the coincidence timing
window because scatter coincidences arise
from the same positron annihilation event,
*The value of ΔT used here refers to the time separation and the two photons actually do arrive almost
between any two events that is determined by the elec- simultaneously at the two detectors. In clini-
tronics to indicate a prompt coincidence event (see cal studies, the scatter-to-true coincidence
Chapter 8, Section F). This differs from the definitions
used in some articles and texts and leads to an additional
ratio ranges from 0.2 to 0.5 for brain imaging
factor of 2 in the version of Equation 18-11 in those and from 0.4 to 2 for abdominal imaging. The
publications. higher end of these ranges applies for 3-D
324 Physics in Nuclear Medicine

acquisitions, which do not use interplane The block detector, designed in the mid-
septa (see Section C.2). 1980s by Casey and Nutt,3 allows small detec-
Scatter coincidences provide incorrect tor elements to be used (improving spatial
localization of the positron annihilation event. resolution) while reducing the number of
The degree of position error depends on the PMTs required to read them out (controlling
scattering angle and location of the scatter cost). Figure 18-14 shows a typical block
event. Scatter coincidences lead to a broad detector. A large piece of scintillator (most
distribution of mispositioned events, gener- commonly BGO, LSO, or LYSO), is segmented
ally peaked toward the center of the object. into an array of many elements by making
Methods for minimizing the acceptance of partial cuts through the crystal with a fine
scattered photons and for correcting for resid- saw. The cuts between the elements are filled
ual scatter coincidences are discussed in with a reflective material that serves to reduce
Section D.3. and control optical cross-talk between scintil-
lator elements. The array of crystals is read
out by four individual PMTs. The depth of the
B.  PET DETECTOR AND SCANNER saw cuts is determined empirically to control
DESIGNS the light distribution to the four PMTs in a
fairly linear fashion.
As discussed in Section A.6, detection effi- To determine the segment of the crystal in
ciency (Equation 18-10) is an important which an annihilation photon is detected, the
parameter in PET scanner sensitivity and per- signals from a four-PMT array are combined
formance. Sodium iodide detectors, which are as follows:
the “workhorse” for many nuclear medicine
applications, also have been used for PET ( PMTA + PMTB ) − ( PMTC + PMTD )
X=
scanners. Indeed, as discussed in Section B.3, PMTA + PMTB + PMTC + PMTD
it is possible to use appropriately modified
dual-headed SPECT systems for PET imaging. ( PMTA + PMTC ) − ( PMTB + PMTD )
Y=
However, because of the relatively high energy PMTA + PMTB + PMTC + PMTD
of the 511-keV annihilation photons, sodium
iodide generally is not the detector material of (18-12)
choice for PET imaging. For these reasons,
most PET scanners use denser higher-Z scin- where PMTA, PMTB, and so forth are the
tillation detectors arranged in rings or banks signals from different PMTs. It will be recog-
of discrete elements around the scanned object. nized that these are essentially identical to
These systems not only provide a high detec- Equations 13-1 and 13-2 for position localiza-
tion efficiency but they allow the simultaneous tion for an Anger camera, except that only
collection of data for all projection angles with four PMTs are used here. The X and Y signals
a completely stationary set of detectors. In this then are used to determine the subelement of
section, we discuss the design of modern PET the array in which the annihilation photon
detector systems and scanners. Reference 2 is was detected.
a useful review describing emerging detector Figure 18-15 shows the image obtained
technologies for PET. from uniform irradiation of a block detector.
The image is not uniform. Rather, the calcu-
lated locations for recorded events are clus-
1.  Block Detectors tered in small localized areas corresponding
Early PET systems used individual detector to the individual detector elements. There is
units consisting of a piece of scintillator a small amount of overlap, but the individual
coupled to a photomultiplier tube (PMT). The elements are clearly resolved. Although the
individual detectors were arranged in a ring array pattern is nonlinear, the separation is
or in multiple rings around the subject. As sufficiently clear to allow each (x,y) location
illustrated in Figure 18-4, the response profile in the image to be assigned to a specific detec-
at midplane of a pair of coincidence detectors tor element in the array, for example, by using
is a triangle with FWHM equal to one half the a look-up table.
width of the detector. Thus to improve  The major advantage of the block detector
the intrinsic resolution of a PET scanner, the is that it enables many detector elements
detectors must be made smaller. However,  (e.g., 8 × 8 = 64) to be decoded using only four
the cost increases rapidly if each detector PMTs. This dramatically lowers the cost per
element requires its own PMT. detector element while providing high spatial
18  •  Positron Emission Tomography 325

Segmented block of BGO


or LSO scintillator

Reflector material
packed in saw cuts

Four single-channel
photomultiplier tubes

PMTC
Y PMTA

PMTD PMTB
X
FIGURE 18-14  Block detector commonly used in clinical PET scanners. A piece of BGO or LSO scintillator is cut into
an array of smaller elements that are read out using four single-channel photomultiplier tubes (PMTs). The cuts in
the material are filled with an opaque reflective material that, along with the depths of the cuts, helps control the
distribution of scintillation light reaching the PMTs.

resolution. Typical block detectors are made


from 20- to 30-mm-thick BGO, LSO, or LYSO
scintillator crystals (see Chapter 7, Section
C.4), with 4- to 6-mm-wide sub-elements.
2.  Modified Block Detectors
Two important modifications have been made
to the basic design of the block detector. The
first is to use proportionately larger PMTs
positioned so they overlap portions of adja-
cent blocks (Fig. 18-16). Thus each block still
is monitored by four PMTs, but each PMT also
monitors the corners of four different blocks.
This approach, known as quadrant sharing,
reduces the total number of PMTs required
for the array by approximately a factor of four
as compared with the basic block design
described in the preceding section. (The actual
reduction is slightly smaller, as a result of
edge effects.)
FIGURE 18-15  Flood-field image obtained by uniformly
irradiating a block detector with 511-keV annihilation Quadrant sharing is used to create large
photons. Individual block detector elements appear as planar detector panels that can be combined
distinct “blobs” in the image, allowing separation of in hexagonal or other polygonal arrangements 
events recorded within individual detector elements. in a PET system. These detector panels closely
resemble a standard gamma camera detector
326 Physics in Nuclear Medicine

Standard block detector

Quadrant sharing detector


FIGURE 18-16  Right, Quadrant-sharing detector, in which each scintillator block straddles the corners of four photo-
multiplier tubes (PMTs). This allows larger PMTs to be used as compared to a standard block detector (left). For large
panels, this leads to almost a fourfold reduction in the number of PMTs required to read out a given number of scintil-
lator elements.

(Chapter 13, Section B), with the continuous the overall detector performance is slightly
scintillator plate replaced by an array of dis- degraded as compared with a detector of the
crete scintillator elements. Although this same dimensions made purely from LSO. The
approach reduces the cost per detector phoswich design also can be combined with
element of a PET system (by reducing the the quadrant-sharing approach.
number of PMTs and electronic channels
required compared with a block detector), it 3.  Whole-Body PET Systems
has the disadvantage of higher dead time Figure 18-18 illustrates several different
losses, because each PMT views signals from whole-body PET scanner designs that have
a larger volume of scintillator. been developed, some using block detectors
The second modification of the basic block comprising discrete scintillator elements as
detector design is to use layers of two differ- introduced previously (A, B, C) and others
ent scintillator materials, creating what is that use continuous large-area gamma camera
known as a phoswich (Fig. 18-17). This approach detectors (D, E, Fâ•›). Systems that use a sta-
makes use of the difference in decay times of tionary ring or polygonal array of detectors (A,
the two scintillators. By monitoring the decay C, E, and Fâ•›), with the detectors operating in
time of the pulse, the event can be localized multicoincidence mode, can acquire data for
into either the upper or lower layer. For all projection angles simultaneously and these
example, combinations of LSO (decay time designs have been the basis for most commer-
~╛40╯nsec) and GSO (decay time ~╛60╯nsec) cial systems. Others (B, D) use only a few
scintillators can be used. Because the location opposing banks of detectors, which must be
of photon interaction can be determined to rotated to get full tomographic information.
within half the total scintillator thickness, Most PET systems use a ring diameter of 80
this reduces the DOI effects (described in to 90╯cm. After inserting scatter shielding and
Section A.5) by approximately a factor of 2. a shroud to cover the detectors and other com-
The disadvantage of this approach is that ponents, the clear bore of the scanner typically
manufacturing of the detectors is more is 55 to 60╯cm, which is sufficient to comfort-
involved and that the light output and stop- ably accommodate most patients. The FOV in
ping power of GSO are worse than LSO. Thus the axial direction is determined by the axial
Scintillator 1

Scintillator 2

Signals

Four single-channel
photomultiplier tubes

FIGURE 18-17  Phoswich detector constructed from two scintillator materials with different decay times. By analyzing
pulse decay time, an event can be assigned to either the upper or lower layer, reducing the effective thickness of the
detector by one half and providing some depth of interaction information.

A B C

D E F
FIGURE 18-18  PET scanner geometries based on discrete scintillator elements (top row) or continuous scintillator
plates (bottom row). A, Full ring of modular block detectors. B, Partial ring of modular block detectors. C, Hexagonal
array of quadrant-sharing panel detectors. D, Dual-headed gamma camera with coincidence circuitry. E, Hexagonal
array of gamma camera detectors. F, Continuous detectors using curved plates of NaI(Tl). A complete set of profiles
can be acquired without motion with systems shown in A. C, E, and F, whereas detector motion is required with systems
shown in B and D.
328 Physics in Nuclear Medicine

extent of the detectors and typically is in the (thickness). The inside diameter of the detec-
range of 15 to 40╯cm. tor ring is 92.7╯cm and the clear bore of the
Figure 18-19 shows schematically the design of scanner is 59╯cm. The 18 crystals (three rings
a representative whole-body PET scanner based of three blocks) in the axial direction cover an
on block detectors. This scanner employs 336 axial FOV of 15.2╯cm. The gantry can be tilted
BGO block detectors, arranged in three rings ± 20 degrees from the vertical, which can
of 112 blocks per ring.4 Each block is cut into be useful for aligning the scan planes with the
a 6 × 6 array of elements, with element sizes optimal viewing angle for an organ of interest.
of 4╯mm (transaxial) × 8.1╯mm (axial) × 30╯mm The system contains a set of tungsten interplane

BGO block Patient


detector bore

Septa

68Ge rod
source

Lead end
shielding

Septa

15.2 cm
68Ge rod
source
BGO block
detector

59 cm

92.7 cm

~120 cm

FIGURE 18-19  Drawings showing transaxial (top) and axial (bottom) cross-sections through a representative whole-
body PET scanner.
18  •  Positron Emission Tomography 329

septa of 1-mm thickness and 12-cm length direction and uses the scintillator LYSO. Its
between the crystal rings. The septa can  design and performance capabilities are
be extended or retracted to provide varying broadly similar to those of the scanner des�
levels of scatter rejection, as described in more cribed previously. The trend in recent years
detail in Section C.2. They also provide shield- has been to improve spatial resolution by
ing from potential high concentrations of further reducing the dimensions of the detec-
activity outside the scanning volume of inter- tor elements (4╯mm × 4╯mm is current state-
est, which helps control the random and of-the-art), and to increase the number of
scatter coincidence rates, as described in detectors along the axial direction to improve
Section A.9. axial coverage of the body, increase sensitivity
The scanner also incorporates a rod source and thus reduce imaging times for studies
made from 68Ge (T1/2 = 273 days) to perform that cover the whole body. A second trend has
transmission scans for attenuation correc- been to improve the detectors and electronics
tions. The source is permanently mounted in to provide sufficient timing resolution that
the system and is retracted into a lead shield time-of-flight information (see Section A.2)
when not in use. This is discussed further in can be extracted. Commercial systems with a
Section D.4. Typically, the system uses a coin- coincidence timing resolution of better than
cidence timing window of 12.5 nanoseconds 600 psecs (corresponding to a spatial localiza-
and an energy window of 300 to 650╯keV. The tion of ~9╯cm) are now available.
intrinsic spatial resolution of the detectors is Gamma camera technology similar to that
approximately 3╯mm, whereas the system used for conventional planar imaging and
resolution is approximately 4.5╯mm near the SPECT (see Chapters 13, 14, and 17) also has
center of the FOV and approximately 6.2╯mm been employed for PET imaging. In one
near the periphery of the scanner bore, the approach, coincidence timing circuitry has
difference being due primarily to DOI effects been installed between the heads of dual-
(see Section A.5). The axial (slice thickness) headed scanners and the collimators removed
resolution is approximately 4.2╯mm at the for PET imaging. The spatial localization pro-
center of the scanner, whereas near the periph- vided by the detector heads allows many coin-
ery of the FOV, approximately 20-cm distance cidence lines to be acquired simultaneously.
axially from the center, it is approximately The basic concept is illustrated in Figure
6.9╯mm. The scanner simultaneously acquires 18-18D. These systems can still be used for
data for 35 slices, separated center-to-center planar or SPECT imaging, by replacing the
by 4.25╯mm, in 2-D acquisition mode. In 3-D collimators.
acquisition mode (see Section C.2), the number The performance of standard gamma
of slices and slice thickness in the axial direc- cameras for PET suffers from a number of
tion can be chosen arbitrarily. limitations. Chief among these is the rela-
Figure 18-20 shows photographs for tively low detection efficiency of the camera
another whole-body PET scanner, which is detectors for 511-keV annihilation photons
described in reference 5. This system has (see Figs. 11-4 and 11-5). As well, although
smaller detector dimensions in the axial removing the collimator allows simultaneous

A B
FIGURE 18-20  A, Modular cassette from a PET scanner containing eight block detectors. These cassettes are mounted
on the PET scanner gantry to form complete rings of detector blocks that surround the patient. B, Clinical PET scanner
based on rings of these block detectors. (Courtesy GE Healthcare, Waukesha, WI.)
330 Physics in Nuclear Medicine

data acquisition for many projection angles,


the resulting high counting rates can lead to 4.  Specialized PET Scanners
significant dead time losses and pile-up Specialized PET systems also have been devel-
effects. An event detected anywhere in the oped for high-resolution brain imaging and for
detector can affect all other events detected breast imaging. These systems have smaller-
at the same time. By contrast, dedicated PET diameter detector rings or arrays for improved
systems use blocks of detectors that operate geometric efficiency. They also generally have
essentially independently from each other. smaller detector elements for higher spatial
Random and scatter coincidence rates, both of resolution. Figure 18-21 shows a scanner
which increase with the geometric efficiency designed for brain imaging that incorporates
for detecting events outside the true- 2.1-mm × 2.1-mm dimension scinÂ�tillator elements
coincidence volume (see Section A.9), also in a phoswich configuration (Fig. 18-17) to
tend to be high when the collimators are limit DOI degradation of spatial resolution.6
removed from the camera heads. The detectors are based on the quadrant
Some manufacturers addressed these limi- sharing design (Fig. 18-16) and eight detector
tations by incorporating thicker NaI(Tl)  panels are arranged in an octagonal configura-
crystals (up to 2.5╯cm) into systems intended tion around the head. The reconstructed
for PET usage, and by employing more spatial resolution of images from this system
sophisticated circuitry in their gamma is ~2.5╯mm, superior to the 4- to 6-mm resolu-
cameras to minimize dead time and suppress tion that can be obtained on whole-body PET
pile-up effects (see Chapter 14, Section A.4). systems. Blurring caused by noncolinearity is
Other manufacturers have developed gamma reduced, as the detector separation in this
camera detectors specifically for use in PET. brain imaging system is only 47╯cm.
One such scanner used six curved gamma Figure 18-22 shows an example of a PET
camera detector plates, arranged in a ring system developed for breast imaging.7 This
around the object (Fig. 18-18F ). At the system uses two scanning detector panels
present time, PET scanners based on con- (area 16.4╯cm × 6╯cm) to image the breast
tinuous gamma camera detectors are not under mild compression. With scanning
widely used. motion, the FOV can be adjusted up to 16.4╯cm
PET systems have been integrated with × 24╯cm. The system uses LYSO scintillator
x-ray computed tomography (CT) technology elements with dimensions of 2╯mm × 2╯mm ×
to create combined PET/CT scanners in a 13╯mm and these are read out using position-
single gantry. Almost all PET scanners sold sensitive PMTs. Not all projection angles are
today are combined with CT. These multi� measured, as the detectors do not rotate about
modality systems are discussed in Chapter 19. the breast. However, as all points on one

C B
FIGURE 18-21  A, Photograph of a high-resolution brain imaging system. B, Interior of the scanner, showing the eight
panels of detectors arranged in an octagonal geometry that are made up of phoswich detectors read out by photo�
multiplier tubes in a quadrant-sharing configuration. C, Phantom images from this system (right) compared with those
obtained from a typical whole-body PET scanner (left). The improvement in spatial resolution arising from the smaller
detector dimensions is apparent. (Courtesy Dr. Adriaan Lammertsma VU Medical Center, Amsterdam, Netherlands,
and Siemens Medical Solutions, Knoxville, TN.)
18  •  Positron Emission Tomography 331

also has additional constraints because of


positron physics and the DOI effects discussed
in Sections A.4 and A.5. Fortunately, for small
diameter systems, the blurring caused by
noncolinearity (see Section A.4) is signifi-
cantly reduced compared with whole-body
clinical scanners. For a scanner with a 15-cm
detector separation, this blurring is only
0.33╯mm.
Most small-animal PET scanners use small
scintillator elements decoded with position-
sensitive or multichannel PMTs. The dimen-
sions of the scintillator elements are typically
on the order of 1 to 2╯mm to achieve high spatial
resolution. To avoid major DOI blurring, most
systems only use a thickness of 10 to 15╯mm
of scintillator, and keep the ring diameter
quite large (12 to 20╯cm) compared with 
the size of the subject. Despite this, good sen-
sitivity can be obtained, as high geometric
efficiency can be achieved with relatively
small amounts of detector material and the
FOV required to cover the animal is quite
small.
FIGURE 18-22  A PET system designed for breast A typical small-animal PET scanner based
imaging. Two detector panels scan back and forth to
acquire an image of the breast under mild compression.
on such technology is shown in Figure 18-23.
(Courtesy Naviscan Inc., San Diego, CA.) The detector in this system consists of a block
of LSO scintillator segmented into 1.5-mm ×

detector are in coincidence with all points on


the opposing detector, there is sufficient
angular information for approximate tomo-
graphic reconstruction using iterative recon-
struction algorithms. The spatial resolution
achievable with such systems is on the order
of 2 to 2.5╯mm for image planes parallel to the
detector plates. In addition to improving geo-
metric efficiency, the cost of dedicated breast
PET systems is lower compared with whole-
body scanners, because the volume of detector
material is much smaller. Attenuation effects
also are reduced, as the annihilation photons
only need traverse the breast tissue, and not
the entire cross-section of the body, for
detection.
5.  Small-Animal PET Scanners
PET scanners that are designed for small-
animal imaging studies also are available.
These are typically being used to evaluate
and optimize new diagnostic and therapeutic
agents destined for human use. The challenge
is to obtain sufficiently high spatial resolution
and sensitivity for imaging in mice and rats.
Unlike SPECT imaging of small animals with
FIGURE 18-23  A PET scanner designed specifically for
pinhole collimators (Chapter 17, Section A.4), small-animal imaging. Such systems can achieve a
PET cannot readily improve the image resolu- spatial resolution on the order of 1.5╯mm. (Courtesy
tion through magnification techniques, and Siemens Preclinical Solutions, Knoxville, TN.)
332 Physics in Nuclear Medicine

1.5-mm × 10-mm elements in a 20 × 20 matrix, With slight or no modification of the lengths


and read out by a position-sensitive PMT, of the septa, PET scanners also can acquire
which has six anodes in the X-direction and data from immediately adjacent rings, as
six anodes in the Y-direction. The scanner shown in Figure 18-24, B. These are known
uses 64 of these detector blocks arranged in as cross planes. At the center of the scanner,
four rings of 16 detector blocks per ring. The the cross planes fall exactly halfway between
transaxial FOV of the system is 10╯cm and the direct planes that are defined by indi-
the axial FOV is 12.7╯cm. The system oper- vidual crystal rings. For purposes of analysis,
ates exclusively in 3-D acquisition mode (see the cross-plane data can be assumed to have
Section C.2). The reconstructed spatial reso- been acquired with a virtual ring of detectors
lution of this system is approximately 1.4╯mm, shifted by half the detector width along the
and the sensitivity is 7.4% for an energy axial direction relative to the direct planes.
window of 250-750╯keV.8 For a scanner with n detector rings, this leads
Some small-animal PET systems incorpo- to a total of (2n – 1) image planes in the axial
rate alternative detector technologies. Suc- direction. Because the cross planes receive
cessful devices have been constructed based  data from two different lines of response, they
on avalanche photodiode detectors (Chapter 7, have roughly twice the sensitivity (and there-
Section C.3), multiwire proportional chamber fore twice the counting rates) as the direct
detectors with high-density converters to planes. They also are “x-shaped,” but the
improve the efficiency of these detectors for amount of this distortion is too small to have
511-keV photons (Chapter 7, Section A.3), or a practical effect, except at the periphery of
direct detection using the semiconductor the FOV, where it leads to additional blurring
cadmium zinc telluride (Chapter 7, Section B). in the axial direction.
A review of selected small-animal PET tech- Cross-plane data are reconstructed in the 
nology is presented in references 9 and 10. same manner as direct-plane data. In PET
scanners with very small detector elements,
the number of cross planes can be increased
even further to include crystal ring differ-
C.  DATA ACQUISITION FOR PET ences of ± 2, ± 3, and so forth (Fig. 18-24C).
As larger ring differences are accepted, the
1.  Two-Dimensional Data Acquisition sensitivity increases; however, there is a loss
Originally, most PET scanners were designed of spatial resolution in the axial direction,
with axial collimators or septa between each because of the superposition of data that come
ring of detectors (see Fig. 18-19). As shown in from axially disparate locations.
Figure 18-24A, the septa allow only those
photons that are emitted parallel to the plane 2.  Three-Dimensional Data Acquisition
of the detector ring to be detected. This is Multi-slice 2-D data acquisition as described
known as 2-D data acquisition. The septa earlier rejects any photons that have an obliq-
provide efficient rejection of annihilation uity of more than the maximum accepted ring
photons that have been scattered in the body. difference (typically ± 2 or 3 rings). This is
They also reduce the single-channel counting very wasteful because the annihilation
rate, thereby lowering the random coinci- photons from many potentially valid coinci-
dence rate (Equation 18-11) and minimizing dence events are absorbed by the septa. In
dead time losses. 3-D acquisition mode, the interplane septa
Because each crystal ring collects data are removed from the PET scanner and data
from a single slice (oblique lines of response are obtained for all possible lines of response,
are not allowed because of the septa), 2-D as shown in Figure 18-24D. Typically, this
projection data are analogous to the data leads to a fourfold to eightfold improvement
obtained with a rotating gamma camera  in sensitivity; however, the number of scat-
with a parallel-hole collimator used for  tered photons and the single-channel count-
SPECT imaging. Thus the images can be ing rates also are increased. In brain scans
reconstructed using filtered backprojection using 3-D acquisition mode, 30% to 40% of the
(Chapter 16, Section B) or iterative approaches detected photons will have been scattered in
(Chapter 16, Section D). Using a scanner that the head prior to reaching the detectors. The
employs multiple detector rings, one obtains axial sensitivity profile for 3-D acquisition is
a series of contiguous 2-D transaxial image determined geometrically and is a triangular
planes that can be stacked together to form function, peaked at the center of the FOV. 
an image volume. In 3-D mode, it is important to place the
18  •  Positron Emission Tomography 333

2-D direct planes only   0 Sensitivity

A
2-D direct and cross planes   /1

2-D high sensitivity   /3

3-D data acquisition

D
FIGURE 18-24  Two-dimensional (2-D) and 3-D data acquisition schemes for PET. Axial cross-sections through a multi-
ring scanner are shown on the left and corresponding axial sensitivity profiles on the right. A, 2-D direct plane data
acquisition. B, 2-D direct and cross-plane data acquisition. C, 2-D high-sensitivity data acquisition. D, Full 3-D data
acquisition. For clarity, lines of response are shown only for selected axial positions in C and D.
334 Physics in Nuclear Medicine

structures of interest as close to the center of compared with Equation 18-9, this adds
the axial FOV as possible. Multi-ring PET another factor of 2 to the sensitivity at the
systems have relatively high overall sensitiv- center of the FOV. The final result is
ity, as shown by the following example.
EXAMPLE 18-2 Sensitivity 3D ≈ 32 × 2 × 0.18 × 0.00409

Consider a 32-ring PET scanner with BGO ≈ 0.047 = 4.7%
detector elements that are 6-mm-wide × 6-mm
axial height × 2-cm-thick. The crystals are For an extended source, for example, a line
tightly packed on a 73.3-cm-diameter ring, source that has length comparable to the total
such that each ring contains 384 crystals. In thickness of the 32-ring array, the average
single-slice mode, each ring is operated in sensitivity of the scanner across the axial
coincidence only with other detector elements FOV is given by Equation 18-9, and the 3-D
within the same ring. In 3-D acquisition result given previously would be reduced by
mode, each ring is operated in coincidence a factor of 2.
with all other rings. Estimate the sensitivity
for a source located at the center of scanner The estimated sensitivity in Example 18-2
bore for single-slice and 3-D modes. Assume for 3-D operation is 2-3 orders of magnitude
that the source is comparable in size to the greater than the sensitivity achieved with a
axial length of the detector crystals, and that gamma camera for single-photon imaging
a low-energy threshold that passes 50% of with absorptive collimation (see Chapter 14,
detected events is used. Section E.7). Note as well that the additional
rings extend the volume of coverage, so that
Answer a volume of tissue can be imaged in less time
For a small-volume source, comparable in size  with a multi-ring scanner, as compared with
to the axial thickness of a single detector ring, a single-ring device.
Equation 18-9 applies. For such a source, the Reconstruction of 3-D PET data also is
average geometric efficiency at the center of more complex, because the projection data
a single-ring is arises not only from transverse slices used 
for 2-D reconstruction, but also from many
1 6 mm oblique angles through the subject. Thus the
g RING ≈ × ≈ 0.00409 = 0.409% full 3-D image volume must be considered
2 733 mm during the reconstruction process. Fully 3-D
Fourier-based and iterative reconstruction
From Table 18-2, the intrinsic efficiency algorithms are both available; however, com-
(squared) for coincidence detection with putation times are roughly an order of mag-
2-cm-thick BGO crystals and an energy nitude longer than for 2-D reconstructions,
threshold that passes 50% of detected pulses because they involve backprojections and
is 0.18. When combined with geometric effi- computations in three dimensions rather
ciency (Equation 18-6), this gives a total than two. Approximate 3-D reconstruction
detection efficiency (sensitivity) for single- algorithms have been developed in which the
slice acquisition of 3-D dataset is reduced to a 2-D dataset using
rebinning methods (see Chapter 16, Section
E.3). In many situations, any loss in accuracy
Sensitivity RING ≈ 0.18 × 0.00409
resulting from the approximations made in
≈ 0.00074 = 0.074% these algorithms is small when compared
with the benefit of enabling 3-D PET data 
In 3-D mode, all 32 rings are operated in to be reconstructed in clinically acceptable
coincidence with each other (Fig. 18-24D). timeframes.
Because of the increased solid-angle of cover- Despite the increased computational and
age, this immediately increases the geometric data storage requirements for 3-D PET, the
efficiency for a source located at the center of large increases in sensitivity that it produces
the axial FOV by approximately a factor of 32 has resulted in it being offered as an option on
(ignoring small geometric effects). As well, a all commercial whole-body PET systems. In
small-volume source at the center of the axial some systems, interplane septa have been
FOV more closely approximates a true point completely eliminated and only 3-D acquisi-
source, for which Equation 18-8 applies. As tion is possible. All small-animal and breast
18  •  Positron Emission Tomography 335

imaging systems currently operate in 3-D


mode. Reference 11 provides further details D.  DATA CORRECTIONS AND
on 3-D data acquisition and reconstruction in QUANTITATIVE ASPECTS OF PET
PET.
One goal of tomographic imaging is that the
intensity of the reconstructed image should
be proportional to the amount or concentra-
3.  Data Acquisition for Dynamic tion of activity at the corresponding location
Studies and Whole-Body Scans in the object. This is desirable for accurate
PET scanners having detectors that surround comparisons of activity levels in different
the patient can acquire profiles simultane- organs or in diseased versus normal tissues.
ously for all of the projection angles required It is essential for some types of dynamic
for reconstruction. This allows dynamic studies (see Chapter 21). A number of correc-
studies to be performed with frame times of tions are required to achieve this goal in
just a few seconds. For a dynamic scan, the SPECT, as described in Chapter 17, Section
number of time frames required and the B. In this section, we describe similar correc-
length of each frame typically are entered tions that are needed in PET.
into the computer. The scan starts as the
tracer is being injected and the location to
which the data are sent in the computer 1.  Normalization
memory is incremented at the end of each PET scanners that are based on gamma
frame. camera detectors require corrections for non-
Some systems allow what is called list- linearity and nonuniformity similar to those
mode acquisition. In this mode, each coinci- that are employed in SPECT (see Chapter 17,
dence event is written sequentially to a Section C.4). Inaccurate correction of these
computer disk, along with a time stamp that factors can lead to rings or other artifacts in
indicates when the even occurred. After the reconstructed images.
scan is completed, the result is a single file A typical PET scanner may have 10,000 to
with a list of coincidence events in the order 20,000 individual detector elements, which
that they were received. The events in this may have small variations in dimensions or
list can then be integrated over any time in the fraction of scintillation light that is
interval, allowing the number and duration of coupled to the PMTs. There also may be dif-
frames to be chosen and altered as necessary, ferences in the effective thickness of crystal
after a scan has been completed. For example, seen by photons traveling along different
this may allow the elimination of segments of angles of incidence for different cross planes.
data where a patient moved. Correction for these variations is known as
Once the projection data have been orga- normalization.
nized into frames, each corresponding to a Conceptually, the most straightforward
certain time interval, the frames are individ- approach to normalization would be to record
ually reconstructed into tomographic images the number of counts detected by each coinci-
using the methods described in Chapter 16. dence detector pair while exposing all pairs to
In many studies, the dynamics of tracer deliv- the same radiation source. This could be
ery, accumulation, and clearance are impor- accomplished, for example, using a rod source
tant indicators of tissue function. The data that extends through the axial FOV and
often are analyzed using mathematical models rotating it around the periphery of the FOV
described in Chapter 21. (see Fig. 18-19). (This could be the same
Whole-body studies are performed by source that is used for attenuation correction,
translating the patient through the scanner described in Section D.4.) One revolution of
and acquiring data at multiple axial loca- the rod source around the FOV would expose
tions. This is achieved by using a computer- all detector pairs to the same number of anni-
controlled bed. In 3-D PET, to improve the hilation photon pairs.
uniformity in sensitivity along the axial In an ideal scanner, each detector pair (i,â•›j)
direction, bed positions are typically over- would record the same number of counts 
lapped by 1/4 or 1/3 of the axial FOV. The N (within statistical limits) in the rod source
data from different bed positions then are scan. In practice, some detector pairs 
“stitched” together to form a single whole- record more counts and some record less
body image. counts because of efficiency variations. The
336 Physics in Nuclear Medicine

normalization factor for a specific pair of the end of each clock cycle (typically 256
detectors is computed from nanoseconds), the computer checks to see if
any events have occurred, and if so, whether
N i, j they occurred with arrival times within ΔT
Normi, j = (18-13)
<N> nanoseconds of each other, where ΔT is width
of the coincidence timing window (typically 4
where <â•›Nâ•›> is the average value of Nâ•›(â•›iâ•›,â•›j) for to 12 nanoseconds). If two photons arrive
all of the coincidence detector pairs in the within this time interval, they are recorded
scanner. Hence, the average normalization as a valid event and the appropriate memory
factor is equal to 1. location corresponding to that particular
The normalization factor then is used to detector pair is incremented by +1.
correct the counts recorded for each detector An estimate of the random coincidence rate
pair in a scan of a patient, C(i,â•›j), as follows: can be obtained by delaying the coincidence
timing window by a time that is much greater
Ci, j than its width. For example, the coincidence
CNorm i, j = (18-14) timing window might be delayed by 64 nano-
Normi, j
seconds, for example, from 64 to 76 nano�
where CNormâ•›iâ•›,â•›j are the corrected counts. This seconds for a 12-nanosecond window. With this
correction is applied to the projection (sino- amount of time delay, only events that have
gram) data prior to image reconstruction. arrival times separated by between 64 and 76
Statistical errors caused by the finite nanoseconds are accepted. No true (or scat-
number of counts in the normalization scan tered) prompt coincidences will be detected in
will increase the noise levels in the corrected the delayed window, because photons from the
data, which is undesirable. In 3-D mode, PET same decay will always arrive at the detectors
scanners can have on the order of 108 lines of within a few nanoseconds of each other.
response. To achieve a statistical uncertainty However, the rate of random coincidences will
of ~3% in the normalization factor would be the same in the delayed and undelayed
therefore require a normalization scan with a windows because the rate at which uncorre-
total of approximately 1000 × 108 = 1011 counts. lated photons strike the detector is the same
Even at relatively high total counting rates of for both windows. Thus the delayed window
approximately 500,000╯cps, this would require count provides an estimate of the number of
approximately 55 hours of scanning time. random coincidence events. This number is
Thus the straightforward approach outlined subtracted from the total number of coinci-
previously must be modified to reduce the dence events for the detector pair. The correc-
number of counts required without increasing tion occurs on-line in most PET systems and
statistical noise. Most of the modified methods usually is transparent to the user.
are based on computing the efficiencies of the The events recorded in the delayed window
individual detector elements (rather than all are not the same ones as are recorded in 
possible detector pairs) and then combining the undelayed window. Rather, the delayed
them to estimate the efficiency of the detector window provides a separate and independent
pairs. Details of these methods are beyond measure of the random event rate. Subtract-
the scope of this text but are discussed in ing the number of random events recorded in
reference 12. the delayed window results in an increase in
the statistical noise level for the measure-
2.  Correction for Random Coincidences ment (see Chapter 9, Section C.1). Specifi-
As discussed in Section A.9, random coinci- cally, if Ntrue is the number of true coincidence
dences add a relatively uniform background events recorded, Nscatter the number of scatter
across the reconstructed image, suppressing coincidences, and Nrandom is the number of
contrast and distorting the relationship random coincidences subtracted from the
between image intensity and the actual total, the uncertainty in the remaining (true
amount of activity in the image. There are two plus scatter) coincidences is
approaches to estimating the random coinci-
dences so that they can be subtracted from the σ( Ntrue + Nscatter ) = ( Ntrue + Nscatter ) + (2 × Nrandom)
measured projection data: the delayed window
method and the singles method. (18-15)
In most PET scanners, the arrival time of
each photon is recorded and “tagged” with an Thus even if accurate corrections can be
accuracy of approximately 2 nanoseconds. At made, the random coincidence rate should be
18  •  Positron Emission Tomography 337

minimized to avoid unduly increasing the sta- It is not possible to distinguish between
tistical noise level of the image. scatter events in the body versus scatter
The second method for estimation of events in the detector crystal on the basis of
random coincidences is based on Equation pulse amplitude. Therefore simple correction
18-11. If the rate at which single (not coinci- schemes based on dual-energy windows are
dence) events occur in each detector is mea- far less successful in PET imaging than in
sured, and the coincidence timing window ΔT SPECT imaging. Two main approaches cur-
is known, then the rate of random coinci- rently are used for scatter correction in PET.
dences for any pair of detectors can be com- The first approach uses information from the
puted. Because the rate of single events is original scatter-contaminated image and
typically at least an order of magnitude higher transmission image (see Section D.4) to derive
than the rate of coincidence events, the sta- the correction. The emission image shows the
tistical noise level in the estimate of the distribution of the activity in the subject. The
number of random events is small in compari- transmission image reflects the attenuation
son with that in the measurement of the coefficient of the tissue. At 511╯keV, virtually
number of prompt coincidences, and the all attenuation is due to Compton scatter.
uncertainty in the remaining coincidences Using these two images and computer model-
after random coincidences have been sub- ing of photon interaction physics (see Chapter
tracted is given by 6, Section C.3) with some simplifying assump-
tions, it is possible to derive an estimate of
σ( N true + Nscatter ) ≈ N true + Nscatter + N random the underlying distribution of scattered
events and their contribution to individual
(18-16) profiles. The estimated contribution of scat-
tered radiation then is subtracted from the
This method requires that each detector projection profiles and the reconstruction is
module continuously monitors the rate at repeated with the scatter-corrected data.
which it is detecting single events. As described in Chapter 19, Section E, with
the advent of hybrid PET/CT scanners, the
3.  Correction for Scattered Radiation scatter distribution also can be computed
Scattered radiation in PET imaging leads to from the registered CT images, in which the
a hazy background in the reconstructed CT image is used in place of a PET transmis-
images, generally more concentrated toward sion image. This method works very well
the center of the image. As with random coin- when all the sources of radioactivity that
cidences, this leads to a decrease in image could lead to detected scatter events are con-
contrast and to errors in the quantitative tained within the FOV of the scanner. When
relationship between image intensity and the large amounts of activity are just outside the
amount of activity in the object. The fraction FOV of the scanner, problems can arise.
of scattered events in PET can be very high, Another drawback of this approach is that it
especially in 3-D imaging of the abdomen, is computationally intensive.
where it may be as high as 60% to 70%. This A second method for scatter correction is
large value has three major causes. First, based on an examination of projection profiles
only one of the two annihilation photons immediately outside the object. After correct-
needs to be scattered for a scatter coincidence ing for random coincidences, the only events
to occur. Second, the energy resolution of PET that should fall into these projection elements
detectors using dense scintillators such as are those that are mispositioned because of
BGO and LSO is inferior to NaI(Tl) detectors scatter. Based on the premise that scatter is
because of their lower light output. This a low-frequency phenomenon with little struc-
requires the use of a wider pulse-height ana- ture, data from the tails of the projection 
lyzer window to capture the photopeak events. profiles can be extrapolated using simple
Finally, the predominant mode of interaction smoothly varying functions across the entire
in scintillators at 511╯keV is Compton scatter- projection. Both gaussian and cosine func-
ing, and many unscattered annihilation tions have been used for this purpose. The
photons deposit less than 511╯keV of energy extrapolated scatter distribution then is sub-
in the detector. Thus to increase the detection tracted from the projections prior to image
efficiency for photons that undergo Compton reconstruction. This method is rapid and,
scattering in the crystal, the analyzer window because it involves a direct measurement of
is widened even further to capture these scatter levels, it accounts for scatter from
events. radioactivity outside the FOV. However, it can
338 Physics in Nuclear Medicine

only approximate the true scatter distribu- measurement, called the blank scan, is made
tion and, in situations in which the scatter without the subject in the scanner. The subject
distribution is complex, or when the object then is placed in the scanner and the mea-
fills the whole FOV with no portion of the surement is repeated. This is known as 
profile to examine outside the object, the  the transmission scan. The attenuation
technique may result in significant errors. correction factor A for a detector pair (i,â•›j) is
These can range from a few percent for brain given by
imaging to tens of percent at the heart-lung
interface. Blanki, j
Ai, j = (18-18)
Transi, j
4.  Attenuation Correction
Attenuation correction is by far the largest where Blankiâ•›,â•›j and Transiâ•›,â•›j are the counts in
single correction in PET. Fortunately, the cor- the blank and transmission scans for the
rection is relatively easy to derive. Consider detector pair.
a source located at a depth x inside an object To obtain transmission data for all coinci-
of thickness T as shown in Figure 18-25. Both dence detector pairs, it is necessary to scan
of the photons from an annihilation event in the transmission source around the scanning
the source must be detected to record a valid volume for both the blank and transmission
event. Assuming that they are emitted in  scans. Typically, a rod source, with its length
the appropriate directions, the probability extending along the axis of the scanner, is
that both photons will reach the detector is placed in a holder near the surface of the
given by the product of their individual scanner bore, and the holder rotates around
probabilities the central axis so that data are acquired for
all pairs. The most commonly used source
Pdet = e− µx × e− µ (T − x) material is 68Ge (parent of 68Ga, T1/2 = 273
(18-17) days). The blank scan needs to be performed
= e − µT
only once a day because it remains constant
where µ is the linear attenuation coefficient over a period that is short compared with
of tissue at 511╯keV and is approximately the half-life of the radionuclide in the 
0.095╯cm−1 for soft tissue, 0.12 to 0.14╯cm−1 for rod source. The transmission scan is per-
bone, and 0.03 to 0.04╯cm−1 for lung. Note that formed prior to injecting the patient with 
the probability that both photons will reach the radiotracer. It is important that the
the detector is independent of the source loca- patient not move between the transmission
tion along the line joining the two detectors. and emission scan. Otherwise serious arti-
Equation 18-17 is similar to Equation 17-5 facts can occur, including the appearance of
for the geometric mean in SPECT, except that areas of abnormally high or low radiotracer
it applies for all source distributions, whereas uptake.
the geometric mean equation applies only for Conceptually, the simplest approach is to
point or plane sources at a fixed depth, x. As obtain the transmission scan before injecting
was the case for SPECT, transmission mea- the radiotracer to be imaged. This eliminates
surements can be used to correct for attenu- any possible interference between the activity
ation in PET. In PET, two measurements are that is present for the two scans.
taken with a source located on a line joining A second approach, called postinjection
each pair of coincidence detectors. The first transmission scanning, is to perform the

x
Detector 1 Detector 2
Point source
of activity

FIGURE 18-25  Parameters involved in the derivation of attenuation correction for PET (equation 18-17 in the text).
18  •  Positron Emission Tomography 339

transmission scan immediately after the  Although these techniques work well, the
emission scan but while there is still radio- widespread use of hybrid PET/CT scanners
tracer activity in the patient. This can save has significantly reduced the use of transmis-
a significant amount of time, because the sion scans using external radionuclide sources
patient does not have to be on the table for attenuation correction. Instead, informa-
waiting for uptake after the transmission tion from the CT scan is used to perform
scan before the emission scan is performed. attenuation correction. The methods for
Another advantage of this approach is that CT-based attenuation correction are discussed
it reduces the chances of patient motion and in Chapter 19, Section E.
misalignment between the emission and
transmission scans. However, it requires the 5.  Dead Time Correction
ability to distinguish transmission events Like all radiation detectors, PET detectors
from emission events caused by residual exhibit dead time and pile-up effects at high
radiotracer in the body. This is possible counting rates. The mispositioning of events
because the emission radiations generally caused by pile-up and possible approaches for
are emitted from locations spread through- minimizing pile-up described in the context of
out the body, whereas the transmission radi- the gamma camera (see Chapter 14, Section
ations are emitted from a very small volume. A.4) apply as well to block detectors used for
Thus the transmission source irradiates only PET. Dead time corrections must be applied.
a small subset of detector pairs at any one Otherwise, the amount or concentration of
time, and its counting rate in those irradi- radioactivity will be underestimated at high
ated pairs generally is much higher than the counting rates. Most PET scanners use empir-
counting rate in the same detectors caused ical dead time models in which the observed
by emission radiations. To implement this counting rate as a function of radioactivity
method, the scanner must have the means  concentration is measured for a range of object
to track the location of the transmission sizes and at different energy thresholds. The
source and identify which detectors are resulting data are then fit with paralyzable or
being irradiated by it. A disadvantage of the nonparalyzable dead time models (see Chapter
postinjection approach is that the count-rate 11, Section C.2). Some systems apply a global
performance of the detectors must be suffi- dead time correction factor for the system,
cient to handle the emission and transmis- whereas others apply corrections to individual
sion activities simultaneously. pairs of detector modules.
Finally, it is possible to acquire transmis- Dead time losses are dominated by the
sion and emission data at the same time. single-channel counting rate, which are much
This approach, known as simultaneous higher than the coincidence counting rate.
emission/transmission scanning, is the most Corrections can be as large as a factor of 2,
efficient way to use scanner time in many although generally it is desirable to keep
situations. As with postinjection transmis- them below this level. Situations in which the
sion scanning, it is necessary to track the corrections can be large include first-pass
location of the rod source. Because the rod cardiac studies, imaging studies near the
source irradiates only a small and known bladder when there are high levels of excreted
subset of detector pairs at any one time, radioactivity, and studies with very short-
emission data can be acquired simultane- lived radiotracers, such as 15O, which require
ously from the remaining nonirradiated high starting levels of activity to maintain
pairs. For irradiated detector pairs, the adequate counting statistics over the course
counting rate from the transmission source of a study.
is much higher than the emission counting
rate, so the emission counts do not seriously
affect the accuracy of the transmission data. 6.  Absolute Quantification of PET
A disadvantage of simultaneous emissionâ•›/ Images
transmission scanning is that the relatively All of the corrections described earlier are
“hot” transmission source can contribute applied to the projection or sinogram data
random and scatter coincidence events to the prior to reconstruction of the image. If accu-
emission data. Even with corrections, these rately applied, after reconstruction, the voxel
events contribute to statistical noise and intensity in the image will be directly propor-
some degradation of image quality. For this tional to the amount of radioactivity in that
reason, postinjection transmission scanning voxel. Calibration to absolute concentrations
generally is the preferred approach. of radioactivity usually is accomplished by
340 Physics in Nuclear Medicine

scanning a cylinder containing a uniform scattered coincidences. The NECR is defined


solution of a known concentration. The cali- as the equivalent counting rate that gives rise
bration factor CAL is defined as to the same statistical noise level as the
observed counting rate after random and scat-
CAL = counts per pixel/radionuclide tered coincidences have been corrected for.
A PET scanner measures a prompt coinci-
concentration in cylinder (kBq/cm 3 )
dence rate (Rprompt) that comprises true coin-
(18-19) cidences (Rtrue), scatter coincidences (Rscatter)
and random coincidences (Rrandom). The rate of
The voxel intensity in the image of the subject true coincidence events is given by
is divided by the calibration factor to obtain
calibrated images in kBq/cm3. To obtain the Rtrue = Rprompt − Rscatter − Rrandom (18-20)
absolute amount of activity in the voxel (bec-
querels), one would have to multiply this The NECR is defined as13
result by the voxel volume.
2
Quantification in PET is subject to the Rtrue
NECR =
same partial-volume effects as were discussed Rtrue + aRscatter + bRrandom
in Chapter 17, Section B.5, for SPECT
(18-21)
imaging. This effect occurs for structures of
size smaller than 2 × FWHM of the imaging It usually is plotted as a function of activity,
system. Structures that have dimensions as both the rate of random coincidences and
smaller than this will have their radioactivity count losses caused by dead time are activity
concentrations either overestimated or under- dependent. The constant a is the fraction of
estimated depending on the regional distribu- the projection that is occupied by the object
tion of the radioactivity. An example of where being imaged. The constant b is equal to 1 if
this becomes important is in the quantifica- the singles method is used for randoms esti-
tion of activity in thin layers of cerebral mation and 2 if the delayed windows method
cortex. is used (see Section D.2).
The prompt and random coincidence rates
are measured. The rate of scattered coinci-
E.  PERFORMANCE CHARACTERISTICS dences is estimated by imaging a phantom
OF PET SYSTEMS that contains a line source. Events in the pro-
jection data that do not intersect the known
A set of standardized methodologies have location of the line source (after random coin-
been agreed upon for measuring important cidences already have been subtracted) must
parameters that describe the performance of have been scattered.
PET scanners. Published standards exist It has been demonstrated that the NECR
both for clinical whole-body scanners13 and is roughly proportional to the square of the
for small-animal scanners.14 In a similar signal-to-noise ratio of the reconstructed
fashion to the tests described for SPECT activity values when the object is a cylinder
systems (see Chapter 17, Section C), mea- with a uniform activity concentration.
surements of spatial resolution and sensitiv- Figure 18-26 shows typical NECR curves
ity are based on carefully designed acquisition for a particular PET scanner and phantom.
and reconstruction protocols that enable At higher activities, the NECR actually
some degree of comparison of performance decreases because the rate of random coinci-
across different systems. Protocols for mea- dences increases as roughly the square of the
suring the fraction of scattered and random activity, and dead time losses also reduce the
coincidences, losses resulting from dead time, observed counting rate. Often the peak NECR
image quality, and quantitative accuracy of rate, and the activity concentration at which
attenuation and scatter corrections also are it is achieved, is reported. However, the values
prescribed. Full details can be found in refer- strongly depend on the size of the object that
ences 13 and 14. is imaged, and other factors such as the
A commonly quoted performance parame- energy and timing windows, and the activity
ter, incorporated in these standards, is the distribution within the phantom. Nonethe-
noise equivalent counting rate (NECR). This less, assuming the phantom used to acquire
parameter, which is specific to PET systems, the NECR data is a reasonable approximation
accounts for the additional statistical noise of the object that is to be imaged in a par�
introduced by the correction for random and ticular clinical or research task, the NECR
18  •  Positron Emission Tomography 341

103
600

400 Rtrue
Count/sec

Rrandom

Rscatter

NECR
200

0
0 2 4 6 8 10
Activity (Ci/cc)
FIGURE 18-26  Example of various coincidence counting rates and noise equivalent counting rate (NECR) for a clinical
whole-body scanner. These data predict that for the phantom used in this study, the best signal-to-noise (corresponding
to the peak of the NECR curve) in the reconstructed image would be achieved with an activity concentration of ~4 µCi/
cc (~150╯kBq/cc).

provides a useful guide for estimating the


activity concentrations that provide the
highest signal-to-noise ratio images. In some
cases, it may not be possible to reach this
activity concentration because of radiation
dosimetry considerations (see Chapter 22).
Measurements of NECR for a well-defined
phantom can be useful for comparing the per-
formance of different scanners, and estima-
tions of NECR also can help guide the design
and development of new PET scanners.

F.  CLINICAL AND RESEARCH


APPLICATIONS OF PET

PET has major clinical applications in oncol-


ogy, neurology, and cardiovascular disease. 18F-
fluorodeoxyglucose (FDG) is by far the most
commonly used radiotracer for clinical studies.
The uptake of FDG reflects glucose metabo-
lism in tissues. Many pathologic conditions
can cause regionally specific alterations in
glucose metabolism that can be detected using
FDG-PET. PET’s most widespread applica-
tion has been for the detection and staging of
FIGURE 18-27  Whole-body 18F-fluorodeoxyglucose PET
cancer, for which whole-body FDG studies scan (injected activity 370╯MBq) of a patient with cancer,
have become an important tool in staging showing widespread metastatic disease (dark spots). The
patients and for deciding patient manage- scan took 14 minutes to acquire (7 overlapping bed posi-
ment. A whole-body FDG study is shown in tions to cover thorax and abdomen, 2 minutes per bed
position), with imaging commencing 60 minutes post-
Figure 18-27. injection. (Courtesy Dr. Paul Shreve, Spectrum Health,
FDG also is used diagnostically in con� Grand Rapids, MI and Siemens, Medical Solutions USA,
junction with blood flow tracers such as Inc., Knoxville, TN.)
342 Physics in Nuclear Medicine

13
N-ammonia or 82RbCl to evaluate myocar- Control Alzheimer’s disease
dial viability and stratify patients with coro-
nary artery disease with regard to bypass
surgery. In the brain, PET is used diagnosti-
cally in a range of neurodegenerative diseases
(Alzheimer’s disease, Parkinson’s disease)
and dementia, for epilepsy, neurodevelopmen-
tal disorders and in psychiatric disorders.
Metabolic FDG images of a patient with
Alzheimer’s disease compared with those of a
normal control are shown in Figure 18-28.
Many other PET radiotracers are used for
research studies and are being developed for
future clinical use. These include radioligands
that bind to specific receptors systems in the
brain, and radiotracers that target cell-surface
molecules specific to certain types of tumors.
Positron-emitting radionuclides also have
been used to radiolabel cells (e.g., stem cells)
and drug delivery vehicles such as nanopar-
ticles. Many of these radiotracers are first
FIGURE 18-28  Transaxial image slices showing 18F-
evaluated in animal models using a dedicated fluorodeoxyglucose uptake at two different levels of the
animal PET scanner. Figure 18-29 shows an brain in a normal volunteer (control) and in a patient at
image of the binding of the radioligand an early stage of Alzheimer’s disease. Data acquisition
11
C-raclopride to dopamine receptors in the times were ~╛30 minutes and injected doses were 370╯MBq
rat brain. (10╯mCi). Arrows indicate metabolic deficits in the
patient’s images. This distinct pattern of reduced metab-
olism is seen in all patients with Alzheimer’s disease and
increases in severity and extent are seen as the disease
progresses.

FIGURE 18-29  Coronal image of rat brain acquired on a small-animal PET scanner following injection of 11C-raclopride.
The location of the brain is indicated by the ellipse. This radiotracer binds to the dopamine receptors in the brain,
which are located primarily in the striatum (arrows). Images were acquired before (left) and after (right) a pharmaco-
logic intervention that damages the dopaminergic neurons on one side of the brain. A clear reduction in the binding
of the radiotracer is observed on that side.

REFERENCES 3. Casey ME, Nutt R: A multicrystal two-dimensional


1. Hoffman EJ, Phelps ME: Positron emission tomogra- BGO detector system for positron emission tomogra-
phy: Principles and quantitation. In Phelps ME, phy. IEEE Trans Nucl Sci 33:460-463, 1986.
Mazziotta JC, Schelbert HR, editors: Positron Emis- 4. Lewellen TK, Kohlmyer SG, Miyaoka RS, et al:
sion Tomography and Autoradiography: Principles Investigation of the performance of the General Elec-
and Applications for the Brain and Heart, New York, tric ADVANCE positron emission tomograph in 3D
1986, Raven Press, pp 237-286. mode. IEEE Trans Nucl Sci 43:2199-2206, 1996.
2. Lewellen TK: Recent developments in PET detector 5. Brambilla M, Secco C, Dominietto M, et al: 
technology. Phys Med Biol 53:R287-317, 2008. Performance characteristics obtained for a new
18  •  Positron Emission Tomography 343

3-dimensional lutetium oxyorthosilicate-based whole-  12. Badawi RD, Marsden PK: Developments in component- 
body PET/CT scanner with the national electrical based normalization for 3D PET. Phys Med Biol 44:
manufacturers association NU 2-2001 standard.  571-594, 1999.
J Nucl Med 46:2083-2091, 2005. 13. Performance Measurements of Positron Emission
6. De Jong HWAM, van Velden FHP, Kloet RW, et al: Tomographs: National Electrical Manufacturers
Performance evaluation of the ECAT HRRT: an LSO- Association (NEMA) Standards Publication NU2-
LYSO double layer high resolution, high sensitivity 2007, Rosslyn, VA, 2007, NEMA.
scanner. Phys Med Biol 52:1505-1524, 2007. 14. Performance Measurements of Small Animal Posi-
7. MacDonald L, Edwards J, Lewellen T, et al: Clinical tron Emission Tomographs: National Electrical Man-
imaging characteristics of the positron emission ufacturers Association (NEMA) Standards Publication
mammography camera: PEM Flex Solo II. J Nucl NU4-2008, Rosslyn, VA, 2007, NEMA.
Med 50:1666-1675, 2009.
8. Constantinescu CC, Mukherjee J: Performance eval-
uation of an Inveon PET preclinical scanner. Phys BIBLIOGRAPHY
Med Biol 54: 2885-2899, 2009.
Additional general references are the texts indi-
9. Rowland DJ, Cherry SR: Small-animal preclinical
cated in references 1 and 11. Also pertinent are the
nuclear medicine instrumentation and methodology.
following:
Sem Nucl Med 38:209-222, 2008.
10. Larobina M, Brunetti A, Salvatore M: Small animal Phelps ME, editor: Molecular Imaging and its Biological
PET: A review of commercially available systems. Applications, New York, 2004, Springer-Verlag.
Curr Med Imag Rev 2:187-192, 2006. Zanzonico P: Positron emission tomography: A review of
11. Bendriem B, Townsend DW: The Theory and Practice basic principles, scanner design and performance, and
of 3D PET, Netherlands, Kluwer, 1998, Dordrecht. current systems. Sem Nucl Med 34:87-111, 2004.
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chapter
19 
Hybrid Imaging:
SPECT/CT and PET/CT

Virtually all modern positron emission tomog- decrease in the accumulation of a radiotracer
raphy (PET) scanners and an increasing for example), but also on knowing precisely
number of single photon emission computed where that signal originated, it has been
tomography (SPECT) systems are integrated common practice for several decades to com-
with an x-ray computed tomography (CT) plement tomographic nuclear medicine scans
scanner. These hybrid imaging systems are with CT or MRI scans. Typically, these scans
capable of acquiring PET or SPECT images, were acquired on separate instruments, pos-
along with spatially registered CT images, in sibly days apart. Thus correlating informa-
quick succession. This chapter discusses the tion in the two studies was hampered by the
features of these hybrid systems and describes difficulty of spatially registering the images
how the CT scans not only provide anatomic and the effect of any changes in the patient’s
context to improve diagnostic interpretation condition (especially during active treatment)
of nuclear medicine studies, but also can be during the time that elapsed between the two
used as the basis for performing corrections studies.
for photon attenuation and scatter in PET The power of hybrid imaging systems, in
and SPECT. which a PET or SPECT scanner is integrated
with a CT scanner, is that the two scans are
acquired in quick succession, and thus the
A.  MOTIVATION FOR HYBRID data can be considered to be in fairly good
SYSTEMS spatial and temporal registration (see Sec-
tions C and D). With good spatial registration,
Both SPECT and PET provide functional it also becomes possible to consider using the
information, using radiotracers that are CT scan, which provides a map of tissue
designed to measure physiologic or metabolic attenuation values (Section B), to compute
parameters, or that bind or interact with  the corrections for photon attenuation and
specific molecular targets on the cell surface, scatter for the PET and SPECT studies (see
or within cells. Although for some radio� Section E). It also is more convenient for the
tracers, the regional anatomy is obvious (e.g., patient and more efficient from a scheduling
cardiac perfusion studies), there are many perspective, as both datasets are acquired in
cases in which the nuclear medicine study a single imaging session. Hybrid systems also
does not provide much in the way of ana- are common in small-animal and preclinical
tomic information. Even in cases in which imaging studies. Just as in the clinical envi-
there is some anatomic information, the ronment, the anatomic information provided
spatial resolution is poor compared with by CT can be helpful both for interpreting and
techniques such as CT and magnetic reso- quantitatively analyzing PET and SPECT
nance imaging (MRI), both of which can studies.
provide images of the human body at a reso- To date, the focus has been largely on the
lution of 1╯ mm or better. integration of PET and SPECT with x-ray CT.
Because clinical decisions may depend not As described in Sections C and D, from a
only on detecting a signal (an increase or technical perspective it has been relatively
345
346 Physics in Nuclear Medicine

straightforward to integrate these modalities Because the flux of x rays is so high, images
with only minor modifications to the hard- with excellent counting statistics can be
ware for either system. Much of the integra- acquired very rapidly, on the order of seconds.
tion in hybrid PET/CT or SPECT/CT systems This section provides a very brief overview of
occurs at the software and system control x-ray CT to aid in the discussion of hybrid
level. Hybrid systems that combine PET  PET/CT and SPECT/CT systems that follows.
and MRI also are under development. MRI More details on x-ray CT can be found in
has advantages over CT for some structural Reference 1.
imaging applications because of the high 
contrast it can produce in soft tissues; 1.  X-ray Tube
however, integration is much more challeng- The x-ray tube is a vacuum tube containing a
ing, and the cost of a combined device could cathode, which consists of a filament (helical
be high. Nonetheless, human scanners have coil of tungsten wire) through which a current
been installed and a brief overview of the is passed. As the filament is heated, electrons
status of hybrid PET/MRI systems is given in are liberated, and are accelerated and focused
Section F. by an applied bias voltage towards a high-
density metal (typically tungsten) anode (Fig.
19-1). When the electrons interact in the
B.  X-RAY COMPUTED TOMOGRAPHY anode material, they produce both continuous
bremsstrahlung radiation (see Chapter 6,
X-ray CT is a form of transmission computed Section A.1) as well as discrete characteristic
tomography that is based on the reconstruc- x rays at energies that correspond to the elec-
tion techniques described in Chapter 16. It tron binding energies of the anode material
shares many of the features of transmission (see Chapter 2, Section C.2).
scanning that already have been described  The current passing though the filament
for attenuation correction for SPECT (see controls the number of electrons emitted from
Chapter 17, Section B.3) and PET (see the filament, and thus the current flowing
Chapter 18, Section D.4) imaging. However, through the x-ray tube (the tube current) as
instead of an external radionuclide source, a well as the flux of x rays produced when these
CT scanner uses an x-ray tube that generates electrons strike the anode. The tube current
a high flux of x rays in a relatively narrow typically is approximately 10% to 20% of the
beam that are transmitted through the body. current passed through the heating filament.

Hot cathode
filament (0 V)
Electron beam
Rotating tungsten anode
(~80-140 kV)
X rays

Focal spot

Vacuum enclosure

Rotor

FIGURE 19-1  Schematic of an x-ray tube with a rotating anode. An alternating current is passed through the cathode
filament, heating it up and releasing electrons. The electrons are accelerated by the potential difference between the
cathode and anode, and strike the tungsten anode producing x rays. The anode rotates such that the location of the
focal spot on the tungsten anode changes over time to avoid melting the anode at high x-ray tube currents. For further
details, see text.
19  •  Hybrid Imaging: SPECT/CT and PET/CT 347

The voltage applied between the coil and the 30


anode determines the energy spectrum of the
x rays. The highest (peak) x-ray energy that 25
can be produced equals the x-ray tube bias
voltage setting in kV. Thus an applied voltage

X-ray flux (arb. units)


20
of 120╯kV (often denoted as kVp—peak voltage 
120 kVp
in kilovolts) can produce x rays with a 100 kVp
15
maximum energy of 120 keV. By varying the 80 kVp
x-ray tube current and bias voltage, the inten-
sity and energy spectrum of the x-ray beam 10
transmitted through the subject can be con-
trolled. In general, higher energy x rays are 5
used for penetrating larger thicknesses of
tissue. On the other hand, image contrast is 0
typically better for lower energy x rays. Thus 0 10 20 30 40 50 60 70 80 90 100 110 120
there is a trade-off in choosing the appropri- Energy (keV)
ate x-ray energy that also must carefully con- FIGURE 19-2  Representative x-ray spectra from a tung-
sider the radiation dose given to the tissues. sten anode tube operated at three different bias voltages.
The x-ray beam is filtered by passing the  Low-energy x rays are removed by the use of an alumi-
x rays through a sheet of metal (typically num filter. The sharp spikes in the spectrum correspond
2.5╯mm of aluminum for the x-ray energies to the production of characteristic x rays from the tung-
sten anode. The continuous spectrum arises from brems-
used in CT) prior to reaching the patient to strahlung radiation. Changes in the x-ray tube current,
remove the lowest energy x rays. Such x rays for a given bias voltage, do not change the shape of the
have a very small probability of penetrating spectrum, just the magnitude of the x-ray flux. Thus
through the body, and therefore contribute doubling the tube current doubles the x-ray flux at all
energies.
mostly radiation dose to the patient, without
providing any useful signal. The x-ray beam
also is collimated such that x rays irradiate scanners, the typical focal-spot size is on the
only the tissue slices of interest. This is one order of 0.5 to 1╯mm. To avoid overheating of
fundamental way in which x-ray imaging the anode by the intense electron beam, the
differs from nuclear medicine imaging. With anode is rotated continuously such that the
x rays, radiation dose can be limited to the beam location on the anode material itself is
areas being imaged, whereas in nuclear medi- constantly changing.
cine, the radiotracer generally distributes
throughout the body and delivers a radiation 2.  X-ray Detectors
dose everywhere. Radiation dosimetry is dis- The detectors used in a CT scanner typically
cussed in Chapter 22. are scintillator materials [e.g. CsI(Tl) or
Figure 19-2 shows the typical spectrum ceramic scintillators] read out by silicon pho-
from an x-ray tube as the high voltage is todiodes (see Chapter 7, Section C). Some
varied. Typical values for the x-ray tube set- older or low-cost CT systems employ detectors
tings for CT examinations are a voltage of consisting of thin ionization chambers con-
120╯kV, and a tube current ranging between taining high-pressure xenon gas (Chapter 7,
120 and 300╯mA, depending on the amount of Section A.2). Because the x-ray photons arrive
tissue the x rays must penetrate. A lower tube at the detectors at very high rates, individual
current is used for CT imaging of the head and pulses cannot be separated for each interact-
neck, and a larger current for the abdomen. ing x-ray photon. Therefore, unlike nuclear
The number of x rays that are used to form an medicine detectors that operate in pulse
image is proportional to the product of the mode, x-ray detectors operate in an integrat-
x-ray tube current and the exposure time for ing current mode. That is, they produce an
a given tissue slice and is given in units of output current proportional to the x-ray flux
milliamps × seconds, commonly abbreviated impinging on them.
to mAs for short. The time for which a slice of Older single-slice CT scanners consisted 
tissue is exposed to x rays in a CT examination of a single linear detector array, with ele-
typically is on the order of 0.5 to 2 seconds. ments measuring, for example, 1╯mm in the
One factor that ultimately limits the spatial transaxial direction and 15╯mm in the axial
resolution of x-ray techniques is the spot  direction. Slice thickness was controlled by
size of the electron beam on the anode target collimating the x-ray beam and therefore
(also called the focal spot). For clinical CT could be considerably smaller than the
348 Physics in Nuclear Medicine

physical height of the detector in the axial gantry (Fig. 19-3). Low-voltage power is sup-
direction. Slice thicknesses of 1 to 5╯mm were plied to the gantry via slip-ring technology
typical. To acquire multiple image slices, the rather than by cables. The slip rings consist
patient bed was stepped incrementally of conductive brushes that slide over the
through the system. surface connections providing continuous
Two-dimensional (2-D) detector arrays are electrical contact and allowing the gantry to
used in most modern scanners, allowing mul- rotate continuously. Data can be taken off the
tiple slices through the body to be acquired gantry in the same way or, more commonly, by
simultaneously. To ensure complete sampling wireless transmission. This enables very fast
for tomographic reconstruction, the patient data acquisition as the patient moves through
bed usually is translated while the detectors the gantry while it rotates at speeds of 1 to 3
rotate about the patient, creating a helical revolutions per second. A large axial stack of
trajectory. Individual detector sizes are small, images can be acquired in just a few seconds.
typically in the range of 0.25 to 1.25╯mm, 
in order to achieve high spatial resolution. 4.  CT Reconstruction
Systems typically come with 16, 32, or 64 The projection data for CT typically are col-
rows of detectors, allowing this many slices to lected as the scanner performs a helical tra-
be obtained in a single rotation of the system. jectory, where the patient bed is translated
Each row may consist of approximately 1000 through the scanner while the x-ray tube and
detector elements; thus modern multi-slice detector rotate. They are readily sorted into
CT scanners can have a total of approximately stacks of sinograms with each sinogram con-
10,000 to 100,000 individual detector ele- taining the data for a single transaxial section
ments. Signals from smaller detectors some- through the patient. Images commonly are
times may be binned together to improve reconstructed using the same types of filtered
signal-to-noise ratio or reduce dose at the backprojection methods discussed in Chapter
expense of spatial resolution. For example, 16, Section B.
signals from 2 × 2 detectors of size 0.5 × For CT, the measured projection data cor-
0.5╯mm2 may be combined to create a “virtual” respond to the transmission of x rays through
detector measuring 1 × 1╯mm2. the subject. For a given line of response (a ray
CT detectors have very high efficiency for connecting the x-ray focal spot and a detector
the x-ray energies of interest (40-140╯keV). element), the measured intensity, I, is
Virtually all x-rays incident on a detector − ∑ µi ∆ xi
I = I0 e i (19-1)
element interact and produce a signal.
However, small gaps between the individual where I0 is the initial x-ray intensity directed
detector elements cause the overall efficiency along the line of response, µi is the linear
to be less than 100%. attenuation coefficient (Chapter 6, Section D)
for the ith pixel and Δxi is the pathlength of the
3.  X-ray CT Scanner line of response through the i th pixel. X-ray CT
The CT scanner consists of the x-ray tube and seeks to reconstruct the linear attenuation
a step-up high-voltage power supply, along coefficient µ; therefore the measured data
with the detector, mounted on a rotating must be transformed prior to reconstruction

Transaxial view Axial view

X-ray tube

X-ray beam

Patient Patient

Patient bed

Detector array
FIGURE 19-3  Schematic showing the components and geometry of a CT scanner. The x-ray tube and detector rotate
in the transaxial plane while the patient bed translates along the axial direction, resulting in a helical trajectory of
the x-ray beam around the patient. Multiple image slices can be rapidly acquired.
19  •  Hybrid Imaging: SPECT/CT and PET/CT 349

by taking the logarithm of the ratio of the this normalization results in roughly equiva-
incident x-ray intensity with respect to the lent pixel intensities in the reconstructed CT
measured intensity. The transformed projec- image, independent of x-ray tube and filtra-
tion, p, used in the reconstruction algorithm tion settings.
is therefore given by: CT numbers calculated from Equation 19-3
I are called Hounsfield units (HU), named after
p = log 0 = ∑ µ i ∆ xi (19-2) the inventor of medical CT scanning. By defi-
I i nition, water has a value of 0╯HU, air spaces
The reconstruction of these projections in the lungs have values that can approach
yields images in which the pixel values cor- –1000╯HU, and bone can have values as high
respond to µ, the linear attenuation coeffi- as 3000╯HU.
cient of the tissue in that pixel. Thus a CT CT projection data are subject to the same
scan provides an image of the linear attenu- sampling requirements as nuclear medicine
ation coefficients inside the body. data (see Chapter 16, Section C.1). Angular
Given the x-ray energies used and the rela- projection data are captured as the system
tively low atomic number of most tissue con- rotates and acquired at ~1000 to 2500 projec-
stituents, the majority of x-ray interactions in tion angles. The linear sampling distance is
the body are by Compton scatter (see Chapter governed by the detector element spacing and
6, Section C.3). Because Compton scatter typically is in the range of 0.25 to 1╯mm. Thus
depends primarily on tissue density (see the sampling of projection data in CT data�sets
Chapter 6, Section D.1), the pixel value in CT is sufficient to support much higher spatial
images is roughly proportional to tissue resolution than is obtained in nuclear medi-
density. Higher-density materials such as cine studies; however, the size of the projec-
bone show up with high pixel values, whereas tion datasets also is much larger. In practice,
lower-density tissues such as lung show up the spatial resolution obtained in CT is limited
with low pixel values. by the focal-spot size of the x-ray tube and also
Note that the reconstructed values repre- by radiation dose considerations. A recon-
sent some average of µ across the range of structed spatial resolution of approximately
energies present in the x-ray beam (see Fig. 1╯mm is typical in many clinical scenarios.
19-2) and therefore depend strongly on the Figure 19-4 shows examples of recon-
x-ray tube voltage and filtration. For this structed CT images of the human body. In
reason, pixel values in CT images usually are this study, a large number of transverse
expressed on a normalized scale, with respect slices were obtained to produce a volumetric
to the values for water, as follows: dataset covering the entire abdominal region.
A transverse and coronal view are shown. In
µ ( x, y) − µ water many clinical studies, native tissue contrast
CT number ( x, y) = 1000 ×
µ water is augmented by the injection or ingestion 
of a contrast agent. These agents, typically
(19-3) containing high-Z elements such as iodine
For soft tissues (which are fairly similar to (injected agents) or barium (ingested agents),
water in density and attenuation coefficient), serve to increase x-ray attenuation in tissues

Liver

FIGURE 19-4  Examples of


volumetric clinical CT images.
A, Transaxial section at level Aorta
of liver. B, Coronal section,
obtained by slicing through a Liver
contiguous stack of transaxial
Intestines
slices, showing liver, descending
aorta, intestines, and other Spine
structures. (Courtesy GE Health-
care, Waukesha, WI.)
Bladder Pelvis
A B
350 Physics in Nuclear Medicine

in which they are present. They are used to based on high-purity germanium, that could
increase contrast in the vasculature, in be used both to efficiently detect the gamma-
highly perfused organs and tissues with ray emissions from radionuclides as well as x
leaky blood vessels (e.g., tumors), to detect rays. Although a prototype system was devel-
internal bleeding, or to highlight the diges- oped, the challenge of devising a single detec-
tive and excretory tracts of the body. tor technology that could span the quite
differing requirements of SPECT (e.g., good
C.  SPECT/CT SYSTEMS energy resolution) and CT (e.g., high x-ray
flux) was considerable. Therefore approaches
that integrated existing SPECT and CT
1.  Clinical SPECT/CT Scanners systems were pursued. Figure 19-5 shows the
Early attempts to develop hybrid SPECT/  first such system, developed at the University
CT systems were pioneered by Dr. Bruce of California–San Francisco, by combining a
Hasegawa and co-workers in the early 1990s.2 single-headed SPECT system with a single-
One concept was to develop a single detector, slice CT scanner.3

FIGURE 19-5  A, First prototype


SPECT/CT scanner, developed at
the University of California–San
Francisco. On the left is a single-
headed rotating gamma camera,
which is placed immediately adja-
cent to a single-slice x-ray CT
scanner. B, Images obtained with
this system show the distribution 
of the radiopharmaceutical 111In-
prostascint (SPECT) in a patient
A with prostate cancer and the corre-
sponding anatomic image slice (CT).
(Courtesy of the late Dr. Bruce
Hasegawa, University of California–
San Francisco, San Francisco, CA.)

B
CT SPECT
19  •  Hybrid Imaging: SPECT/CT and PET/CT 351

Modern hybrid SPECT/CT scanners typi- with a low-energy, high-resolution collimator


cally consist of a dual-headed SPECT system to image a source at a distance of 10╯cm 
combined with a multi-slice CT system. Com- from the collimator face, the sensitivity is
pared with earlier systems, the detectors and reported to be ~200 cpm/µCi. The recon-
electronics now are integrated in a single structed spatial resolution using the same colli-
gantry with a single computer controlling mator is approximately 10╯mm. The x-ray tube
data acquisition. Typically, the imaging fields- has a focal spot measuring 0.8╯mm × 0.7╯mm.
of-view of the two modalities are offset from The tube voltage can be selected as 80, 110,
each other in the axial direction; thus scans or 130╯kVp and the tube current varied
are acquired sequentially, with a displace- between 20 and 345╯mA. The detectors consist
ment of the patient bed between the CT  of a ceramic scintillator with 16 rows of detec-
scan and the SPECT scan to place the organ  tor elements by 1472 detectors per row. A
or region of interest in the appropriate scanner complete rotation can be performed in as little
field-of-view. The SPECT detector heads can as 0.5 second, collecting data from 16 slices
be placed in different orientations (e.g., 90° simultaneously with a slice thickness of either
and 180° configurations; see Fig. 13-12) for 0.6╯mm or 1.2╯mm.
different types of studies. Integration of the A second example is shown in Figure 19-6B.
SPECT system with a CT system typically This system employs two gamma camera
does not result in any compromise in SPECT heads, each with an active area of 54╯cm in
performance. The major practical issue is the the transaxial direction and 40╯cm in the
increase in physical size of the system that axial direction. The two heads can be config-
may cause siting challenges in departments ured in a variety of orientations with respect
designed for more compact SPECT-only to each other. In this system, the x-ray CT is
systems. High-end CT scanners in tandem coplanar with the SPECT detector heads;
with a dual-headed SPECT camera may thus the SPECT and CT imaging fields-of-
require rooms as large as 7.5╯m × 5╯m. view coincide with each other. The x-ray tube
A wide range of different CT systems are operates with a tube voltage of up to 120╯kVp
employed in hybrid SPECT/CT scanners. and a tube current of 5-80╯mA. The focal spot
Some manufacturers use relatively simple CT size is 0.4╯mm.
scanners with a single or small number of The flat panel x-ray detector uses columnar
slices, and with the detectors mounted on a CsI(Tl) scintillator coupled onto an amor-
slowly rotating gantry that does not employ phous silicon photodetector with detector
slip-ring technology. In other cases, state-of- pixels measuring 0.2 × 0.2╯mm. The x-ray
the-art 64-slice CT scanners with fast helical detector measures 40╯cm (transaxial direc-
acquisition have been integrated with SPECT. tion) by 30╯cm (axial direction) and can
The choice of system at any given institution acquire images as fast as 60 frames per
depends on a number of factors, including second. The x-ray system rotates through
intended clinical use, whether the purpose of 360° in 12 seconds and provides CT images
the CT is to provide diagnostic-quality scans over a 14-cm axial field-of-view with a slice
or primarily for attenuation correction (see thickness that can be varied from 0.3 to 2╯mm.
Section E), cost, throughput, and any site Because of the large axial field-of-view of this
limitations. detector, the data collected are no longer
Two commercially available SPECT/CT appro�ximated well by 2-D parallel slices, and
systems are shown in Figure 19-6. The system 3-D cone-beam reconstruction methods are
in Figure 19-6A combines a dual-headed used. These algorithms are entirely analo-
SPECT system in tandem with a 16-slice CT gous to the 3-D reconstruction methods
scanner (1-, 2-, and 6-slice versions also are described for cone-beam and pinhole collima-
available). The axial separation between the tors in SPECT in Chapter 16, Section E.2.
SPECT and CT field-of-view is 136╯cm. The SPECT/CT systems are being employed for
SPECT system consists of two gamma camera a range of clinical applications. Studies in the
detectors with a 9.5-mm-thick 59-cm × 44-cm literature have shown that SPECT/CT can
NaI(Tl) scintillator crystal read out by 59 improve both the sensitivity and specificity of
50-mm-diameter hexagonal photomultiplier nuclear medicine studies, and also reduce the
(PM) tubes. This provides a detector head incidence of indeterminate scans.4 The advan-
with an active detector area 53╯cm transaxi- tages of SPECT/CT versus SPECT alone have
ally by 39╯cm axially. The energy resolution been shown for a range of oncologic applica-
(full width at half maximum) of the detectors tions (e.g., thyroid cancer, skeletal cancers
is approximately 9.5% at 140 keV. When used and neuroendocrine cancers arising in organs
352 Physics in Nuclear Medicine

CT gantry Gamma camera


(X-ray tube and heads
detectors inside)

Gamma camera
heads

X-ray tube

X-ray detector

Rotating gantry

B
FIGURE 19-6  Examples of two clinical SPECT/CT scanners. A, The two gamma camera heads are mounted on a
rotating gantry that is separate from the high-speed slip-ring CT system. B, Two gamma camera heads and the x-ray
tube and detector are mounted on a common rotating gantry. See text for further details on these two systems.  
(A, Courtesy Siemens Medical Solutions, Malvern, PA. B, Courtesy Philips Healthcare, Andover, MA.)

such as the pituitary), and initial data on  components of these systems typically use
the use of SPECT/CT in the heart and brain lower-voltage (up to 80╯kVp) and lower-flux
has appeared. An example of a SPECT/  x-ray tubes compared with clinical systems,
CT imaging application is shown in Figure because of the smaller size of the objects being
19-7. SPECT/CT also has potential as a useful imaged. Generally, they also use x-ray tubes
tool for computing indi�vidualized radiation with a smaller focal-spot size (typically 50-100
dosimetry for radionuclide therapies and is microns), and higher-resolution detectors to
increasingly used in the research setting  improve spatial resolution. Resolution also
for evaluating the biodistribution of new can be improved by increasing the object-to-
radiotracers. detector distance and magnifying the projec-
tions on the detector when the subject is
2.  Small-Animal SPECT/CT Scanners significantly smaller in dimensions than the
SPECT/CT systems also have been developed  detector area.
for small-animal imaging. An example of such Most systems employ a 2-D x-ray detector
a system is shown in Figure 19-8A. The CT that co-rotates with the x-ray tube around the
19  •  Hybrid Imaging: SPECT/CT and PET/CT 353

SPECT Fused SPECT/CT CT

FIGURE 19-7  SPECT/CT image of a patient with osteomyelitis (infection of the bone) behind the right eye. The SPECT
scan was performed following the injection of 22.2╯MBq (600╯µCi) of 111In-labeled white blood cells. The helical CT scan
used 140╯kVp x rays with an exposure of 30╯mAs per slice. A single transaxial slice is shown. The SPECT scan shows
accumulation of the radiolabeled white blood cells at the site of infection, and the fused SPECT/CT scan (SPECT in
pseudocolor, CT in grayscale) allows the precise anatomic location of the infection to be determined. Total acquisition
time for the two scans was approximately 20 minutes. (Courtesy GE Healthcare, Waukesha, WI.)

subject. The resulting projection data corre- Currently, small-animal SPECT/CT


spond to a cone-beam geometry (similar to systems do not use slip-ring technology and
that obtained from a cone-beam or pinhole thus rotate more slowly than clinical CT
collimator in SPECT; see Chapter 16, Section systems. They can undergo only one rotation
E.2) and must be reconstructed using appro- before the gantry must be reversed because of
priate 3-D algorithms. Some systems employ the attached cables that supply the high
a helical scanning mode similar to those used voltage and read out the detector. Data are
in clinical systems. acquired either in “step-and-shoot mode”

Kidneys
Tumor

A B
FIGURE 19-8  A, SPECT/CT system for small-animal imaging. The SPECT system consists of four gamma camera
detector heads with multi-pinhole collimators. B, SPECT/CT images of an 111In-labeled radiotracer targeted to a tumor
in a mouse model of cancer. The SPECT image (â•›pseudocolor) shows accumulation of the radiotracer in the tumor, as
well as excretion via the kidneys. The CT image (grayscale) shows the underlying mouse anatomy (A, Courtesy
Professor Stephen Mather, Barts Cancer Institute, London.)
354 Physics in Nuclear Medicine

(rotating gantry stops after each small D.  PET/CT


angular increment and data are then acquired)
or in “continuous mode” (sequential projection
angle images acquired continuously while 1.  Clinical PET/CT Scanners
gantry slowly rotates around subject). The The first prototype hybrid PET/CT scanner
former produces higher resolution (no blur- was developed in the late 1990s by David
ring caused by rotation during acquisition), Townsend, Ron Nutt, and colleagues.6 The
whereas the latter is faster (data is acquired system consisted of a partial-ring PET scanner
continuously and there is no need to start and and a single-slice CT scanner, with all compo-
stop rotation). Typical scan times range from nents mounted on a single rotating gantry
tens of seconds to several minutes for a com- (Fig. 19-9) to provide the necessary angular
plete 180° or 360° set of projection angles. projection views for tomographic reconstruc-
Reconstructed spatial resolution in the tion. Methods also were developed for rapid,
range of 0.1 to 0.5╯mm is quite typical for in low-noise attenuation correction of the PET
vivo applications. For imaging biological spec- data using the CT images (see Section E). The
imens (e.g., an excised piece of bone from an ability of hybrid PET/CT systems to accu-
animal model), for which radiation dose is of rately identify the anatomic location of “hot
no concern and there is no motion, resolution spots” seen in 18F-fluorodeoxyglucose (FDG)
on these systems can approach tens of whole-body cancer studies (such as the
microns. Reference 5 provides a useful over- example shown in Fig. 18-27) and to provide
view of small-animal CT systems and attenuation-corrected images led to the rapid
applications. introduction of commercial systems by the
The SPECT components of these small- major medical imaging companies at the 
animal systems are the same as those already start of the 21st century. At present, hybrid 
described in Chapter 17, Section A.4, and will PET/CT technology has been more widely
therefore not be repeated here. Most systems adopted than SPECT/CT technology. Although
use two or more gamma camera heads with many hospitals still use stand-alone SPECT
multi-pinhole collimators. Virtually all com- systems, since 2006 essentially all clinical
mercial small-animal SPECT systems now PET scanners sold have come combined 
come with the option of a CT component for with CT.
hybrid imaging. Modern clinical PET/CT scanners are con-
Figure 19-8B shows images from a small- figured in a tandem (“back-to-back”) arrange-
animal SPECT/CT system. Such systems are ment, with the center of the field-of-view of
used for a variety of research applications, the PET and CT components separated in the
including imaging of the biodistribution of axial direction by a distance on the order of
novel radiotracers. SPECT/CT systems also 60 to 120╯cm. These hybrid systems consist of
are used in the pharmaceutical industry to separate PET and CT components, with some
evaluate new therapeutic agents. mechanical integration related to the motion

CT component PET component Hybrid PET/CT scanner

X-ray tube X-ray Slip rings PET


detector (for CT) detectors
FIGURE 19-9  The first hybrid PET/CT scanner. The CT component (left) consists of a x-ray tube and single row of x-ray
detectors mounted on a rotating gantry. The PET detector system (center) is mounted on the rear of the same rotating
gantry and consists of a partial ring of block detectors made from the scintillator bismuth germanate. The photograph
on the right shows the completed prototype system (Courtesy Dr. David Townsend, University of Singapore.)
19  •  Hybrid Imaging: SPECT/CT and PET/CT 355

of the patient bed through the two systems number of CT slices available in their PET/
and a large degree of software integration CT scanners.
that controls the position of the patient bed Figure 19-10 shows an example of a modern
and sequential acquisition of PET and CT clinical PET/CT scanner.7 The PET compo-
data, as well as image reconstruction, attenu- nent of this system employs 28,336 LYSO
ation correction, and visualization and analy- scintillator elements, each with dimensions of
sis of the reconstructed PET/CT datasets. 4 × 4╯mm in cross-section, by 22╯mm in thick-
One important practical consideration, result- ness. These elements are arranged in 28 flat-
ing from the long travel length of the patient panel modules, each consisting of a 23 × 44
bed, is to ensure that the bed deflection does array of elements, and read out by 15 PM
not change as the bed is cantilevered through tubes. Anger logic (see Chapter 18, Section
the two imaging systems, which would result B.1 and B.2) is used to determine the element
in misalignment of PET and CT images. in which an interaction took place. The
Mechanical designs typically incorporate a scanner has an axial field-of-view of 18╯cm, a
rail system or additional supports for the bed transverse field-of-view of 57.6╯cm, and a
to prevent this. patient port diameter of 71.7╯cm.
The description of PET scanner designs The scanner also incorporates time-of-
and configurations presented in Chapter 18, flight information (see Chapter 18, Section
Section B, applies also to the PET component A.2), with a timing resolution on the order of
of current hybrid PET/CT systems. These 600 psecs. The CT component most commonly
PET systems all consist of multiple circumfer- has a 16- or 64-slice detector. The 64-slice
ential rings of scintillation detectors arranged detector consists of 64 rows of 690 detectors
around the patient to provide a complete set in each row, with each detector measuring
of projection angles without any rotation of 0.625╯mm in the axial direction, giving an
the detectors. axial coverage of 64 × 0.625╯mm = 400╯mm.
The CT component may range from a rela- The x-ray tube used with this system has a
tively simple single-slice system to state-of- maximum voltage of 140╯kV. At this voltage,
the-art 64-slice CT scanners. These systems the maximum x-ray tube current is 430╯mA.
use slip-ring technology (see Section B.3) to At a voltage of 120╯kV, the x-ray tube can be
permit rapid rotation of the x-ray tube and operated at a current of up to 500╯mA. Rota-
detectors, and are capable of acquiring  tion times can be as fast as 0.4 seconds.
complete angular projections for a large The primary application of PET/CT is for
number of contiguous slices in times ranging whole-body imaging of cancer patients with
from a few seconds to a few minutes, depend- the radiotracer FDG. The CT component
ing on how many slices can be acquired simul- helps to identify the precise anatomic location
taneously (which depends on the number of of foci of increased FDG uptake that may be
rows of x-ray detector elements). Most manu- due to primary tumors or their metastases.
facturers offer a range of options for the An example of such a study is shown in Figure

CT PET

FIGURE 19-10  Hybrid PET/CT scanner. The axial separation between the PET and CT components is adjustable.
(Courtesy Philips Healthcare, Andover, MA.)
356 Physics in Nuclear Medicine

19-11. Images of tissue attenuation from the scanner. This design allows each modality to
CT scan usually are used to derive the PET be used separately if desired. Like small-
attenuation correction factors (see Section E). animal SPECT/CT, applications of PET/CT
However, some PET/CT systems also still relate to imaging the biodistribution of new
have an option to use radionuclide transmis- radiopharmaceuticals, studying the biodistri-
sion sources for attenuation correction as bution of new therapeutics, and monitoring
described in Chapter 18, Section D.4. the effect of new therapeutics in animal
models of human disease.
2.  Small-Animal PET/CT Scanners
CT scanners, identical or very similar to those
offered in small-animal hybrid SPECT/CT E.  ATTENUATION AND SCATTER
systems (see Section C.2), also are available CORRECTION USING CT
with the small-animal PET scanners described
in Chapter 18, Section B.5. Figure 19-12 One of the key advantages of hybrid SPECT/
shows a PET/CT scanner that consists of CT or PET/CT scanners is the ability of CT 
independent PET and CT components that to rapidly acquire transmission images of 
can be docked together to form a hybrid high statistical quality that can be used for 

Transverse slice

Fused PET/CT PET

Coronal slice

PET CT Fused PET/CT


18
FIGURE 19-11  Whole-body F-fluorodeoxyglucose (FDG) study performed on a hybrid PET/CT scanner. The top row
shows images of a single transverse section through the body at the level of the thorax. In the fused PET/CT image,
the PET image is displayed using a hotwire color scale (red, yellow, white in order of increasing pixel values) and is
superimposed on the CT scan, which is shown in grayscale. A primary lung tumor shows up in the left lung as a site
of increased FDG accumulation (large arrows). There also is a small region of suspicious uptake in the posterior part
of the right lung (small arrows) that may be a metastasis. The bottom row shows images of a coronal slice to illustrate
the large fraction of the body covered in this PET/CT examination. The primary tumor is indicated with an arrow. The
PET scan was obtained 60 minutes after the injection of 455╯MBq (12.3╯mCi) of FDG. The scan consisted of nine
overlapping bed positions and took approximately 15 minutes to complete. The helical CT scan was acquired with a
tube voltage of 140╯kV and an exposure of 44╯mAs/slice with 5-mm slices. (Courtesy Philips Healthcare, Andover, MA,
and University Hospitals Case Medical Center, Cleveland, OH.)
19  •  Hybrid Imaging: SPECT/CT and PET/CT 357

CT

PET

B
A
FIGURE 19-12  A, Dockable PET/CT scanner for small-animal imaging. B, Example image from such a system in which
the PET (â•›pseudocolor) and CT (grayscale) data have been fused and rendered in 3D. The PET scan shows accumulation
of the radiopharmaceutical 64Cu-Oxo-DO3A-trastuzumab in a tumor growing on the flank of a mouse (arrow). (A,
Courtesy Siemens Preclinical Solutions, Knoxville, TN. B, Courtesy D. Yapp, C. Ferreira, and F. Benard, The British
Columbia Cancer Agency and Nordion.)

attenuation correction and for scatter correc- A simple approach is to use image segmen-
tion of PET and SPECT studies. The CT  tation (see Chapter 20, Section B.5) to sepa-
scan replaces the need for a lengthy transmis- rate tissues based on their pixel values in the
sion scan using external radionuclide sources CT scan into three broad classes: air, soft
(see Chapter 17, Section B.3, and Chapter tissue, and bone. Then the known linear
18, Section D.4) and thus decreases total attenuation coefficients for each of these
imagi n g time for attenuation-corrected PET materials at the emission energy of the radio-
and SPECT studies. As was shown in Chap- nuclide can be substituted for the CT number
ters 17 and 18, attenuation correction is criti- to yield an attenuation map appropriate for
cal for reconstructing quantitatively accurate attenuation correction at that energy. This
SPECT or PET images. Even for more quali- attenuation map then is used in iterative
tative clinical evaluation, attenuation correc- reconstruction algorithms or forward-projected
tion often is necessary to avoid distracting into sinogram space, to compute the attenua-
artifacts and nonuniformities, and to enable tion correction factors to apply to the emission
accurate diagnostic interpretation. Reference study in the same way that transmission
8 discusses the methods by which CT scans scans acquired using external radionuclide
are used for attenuation correction and com- sources were applied in Chapter 17, Section
pares them with attenuation correction based B.3. This approach suffers from significant
on the use of external radionuclide transmis- limitations, because pixels at tissue boundar-
sion sources. ies can contain a mixture of materials (e.g.,
bone and soft tissue) and do not fall into 
any of these three categories. Also, many
1.  Computing Attenuation Correction tissues, most notably the lung, have a range
Factors from CT Scans of densities, which causes the linear atten�
Use of the CT scan to correct for photon atten- uation coefficient to vary from location to
uation in PET or SPECT requires that the location.
pixel intensity in the CT image (expressed as Therefore more sophisticated techniques,
CT numbers in HU; see Section B.4) be con- which provide a continuous mapping from CT
verted into the linear attenuation coefficient, number to µ at the radionuclide emission
µ(E), at the photon emission energy E of the energy, typically are used to create the atten-
radionuclide used in the nuclear medicine uation map. Two factors, however, complicate
study. For PET, this energy always is 511 keV. this mapping. First, the x-ray beam consists
For SPECT, the energy depends on the radio- of photons with a range of energies with
nuclide used. varying attenuation coefficients. Fortunately,
358 Physics in Nuclear Medicine

a relatively straightforward solution is to use effective x-ray energy of 80 keV to the 511-keV
the effective energy of a known x-ray spec- energy appropriate for PET is shown, although
trum. The effective energy is defined as the conceptually the same approach can be taken
energy of a monochromatic (single-energy) for radionuclides such as 99mTc (140-keV emis-
x-ray beam having the same attenuation coef- sion) used in SPECT. Pixels in the CT scan
ficient as the polychromatic x-ray spectrum with CT numbers â•›60╯HU are scaled to µ(E)
used in the measurement. For example, for  using a linear fit to the data points for air,
a filtered 130-kVp x-ray spectrum suitable  water and soft tissue. Pixels with CT numbers
for CT, the effective energy is approximately â•›60╯HU are scaled with a second linear fit
80 keV. that passes through data points for bone. This
The second problem is that the energy plot provides a continuous mapping from
scaling for pixels containing significant reconstructed CT number to the energy-
amounts of bone is quite different than that specific attenuation coefficient µ(E). Note that
for pixels containing primarily soft tissue, the slopes of the fitted lines are energy-
blood, or air (Fig. 19-13). This is because bone, dependent and must be computed for each
with its relatively high atomic number (caused radionuclide energy. Furthermore, the slope
by its calcium content) has a significant prob- of the line for bone varies somewhat with
ability of causing photoelectric interactions at x-ray tube voltage and filtration and, strictly
x-ray energies. However, at typical nuclear speaking, should be computed for each differ-
medicine energies (140 keV and above), the ent kVp setting used.
strong drop in photoelectric absorption prob-
ability with increasing energy (see Chapter 6,
Section D) means that almost all interactions 2.  Possible Sources of Artifacts for
are by Compton scatter. Interactions in the CT-Based Attenuation Correction
lower-Z soft tissues, on the other hand, are There are a number of possible sources for
almost exclusively by Compton scatter, at introducing artifacts or biases when using
both x-ray and nuclear medicine energies. For CT-based attenuation correction in nuclear
this reason, no single energy-scaling relation- medicine:
ship holds across all tissue types. • The CT image typically is acquired at
Therefore a bilinear fitting approach often much higher spatial resolution than the
is taken, as illustrated in Figure 19-13. In PET or SPECT study. If the resolutions
this specific example, the mapping from an are not matched, then artifacts can occur

0.20

0.18

0.16 Bone

0.14
(cm1) at 511 keV

0.12
Soft tissues
0.10
Water
0.08

0.06

0.04

0.02
Air
0.00
1000 500 0 500 1000 1500
HU (80 keV effective x-ray energy)
FIGURE 19-13  Plot of the linear attenuation coefficient at 511 keV versus CT number in Hounsfield units for an
effective x-ray energy of 80 keV for soft tissues, air, water, and bone. A bilinear fit to these points commonly is used
to scale the CT numbers for attenuation correction of the PET data. See text for further details. Data obtained from
reference 9.
19  •  Hybrid Imaging: SPECT/CT and PET/CT 359

at tissue boundaries. Therefore the CT scan showing these types of artifacts


attenuation map derived from the CT is provided in Figure 19-14A. One solu-
images typically is rebinned into large tion for reducing such artifacts is to use
pixels or blurred to match the resolution respiratory gating (see Chapter 20,
of the PET or SPECT images to which it Section A.4) for the nuclear medicine
will be applied. study. This, however, reduces the statis-
• A fundamental assumption in applying tical quality of the data for a fixed
CT-based attenuation correction is that acquisition time.
the patient is positioned identically in • In some instances, especially in the
the two systems and that the images region of the shoulders, the CT field-of-
are therefore in perfect spatial registra- view may be smaller than the patient,
tion. Any movement of the patient leading to truncation of the images (see
between the sequential CT and PET/ Fig. 19-14B). Tissue outside the CT field-
SPECT studies can result in artifacts. of-view that attenuates the PET signal is
Even if the patient does not move, respi- not visualized in the CT scan; therefore
ratory motion is a problem. Fast, helical attenuation correction factors are under-
CT scans typically take several seconds estimated. Artifacts may also occur
and are acquired under “breath-hold” because of artifacts in the reconstructed
conditions to reduce artifacts that would CT image at the edges of the field-of-view
occur if different projection angles were caused by missing data in some projec-
acquired at different times during the tion angles.
respiratory cycle. Nonetheless, respira- • Many diagnostic CT examinations are
tory artifacts are not uncommon, as  performed with the administration of a
the “breath-hold” state is hard for some contrast agent. Intravenous contrast
patients to maintain for the duration of agents typically contain iodinated com-
the CT scan. Nuclear medicine studies pounds, whereas oral contrast agents
typically take several minutes, and  usually are based on barium. Both these
the images thus represent an average agents increase x-ray attenuation (and
over many respiratory cycles, which therefore CT numbers) where present,
results in motion blurring. The use of because of their high-Z values relative to
breath-hold CT images to reconstruct soft tissues. In turn, this leads to an
motion-blurred nuclear medicine images increase in the probability of photoelec-
can lead to noticeable artifacts, espe- tric absorption. However, their presence
cially around the diaphragm and the has very little effect on the attenuation
top of the liver. An example of a PET/ coefficient at nuclear medicine energies;

Truncation
and artifacts

B
A
FIGURE 19-14  Two sources of artifacts in CT-based attenuation correction of PET data. A, Respiratory motion artifacts
in the CT scan (arrow) leads to artifacts in the activity distribution in the reconstructed PET images. B, Truncation
of the body in a CT scan leads to underestimation of attenuation from the missing tissues and artifacts at the edge of
the field-of-view. Both of these factors can introduce substantial quantitative errors and artifacts in PET images recon-
structed with attenuation correction based on the CT images. (Images courtesy Dr. Paul Kinahan, University of Wash-
ington, Seattle, WA.)
360 Physics in Nuclear Medicine

thus they change the relationship transmission maps can be used for scatter
between CT number and µ(E) shown in correction in SPECT and PET respectively.
Figure 19-13. Although this is theoreti-
cally a problem, empirically, it is rare
that CT-based attenuation correction F.  HYBRID PET/MRI AND SPECT/MRI
leads to artifacts from exogenous con-
trast administration. Furthermore, if the There are many clinical situations in which
CT scan is acquired solely for attenua- MRI,10 rather than CT, is the anatomic
tion correction and anatomic localiza- imaging technique of choice. Furthermore,
tion, it will often be performed as a MRI can image functional and physiologic
low-dose study without administration of processes and, via magnetic resonance spec-
contrast agent. troscopic imaging, can also study metabolic
• For similar reasons, care must be exer- pathways. Thus an argument for the integra-
cised when imaging patients that have tion of nuclear medicine tomography with
surgical or dental implants made from MRI systems appears to be compelling.
high-Z materials. These have the poten- However, a number of considerations led to
tial to cause local artifacts because their CT-based hybrid systems emerging first, and
appearance on the CT image (high  only in 2005 were the first practical hybrid
CT number) will not lead to the correct PET/MRI systems produced.11 SPECT/MRI
prediction of their effect on the attenua- systems are even less well developed.
tion of photons at nuclear medicine The integration of PET and SPECT with
energies. In addition to leading to the MR is challenging for a number of reasons.
wrong scaling, large metal implants  First, clinical MRI systems typically have
can also cause significant artifacts in magnetic field strengths of 1 to 3╯T,* whereas
the CT images that can propagate into the field strengths of research and small-
the attenuation maps used for attenua- animal systems may be over 10T. Strong mag-
tion correction. Modern CT scanners, netic fields exist not only inside but often
however, use algorithms that can sig- around the edges of a MR system as well. The
nificantly reduce these artifacts and PM tube detector technology used in most
their effects on CT-based attenuation nuclear medicine systems is highly sensitive
correction. to even small magnetic fields. For example, in
• At the time of the CT scan, the patient SPECT, the PM tubes are shielded to guard
often already has been injected with the against magnetic field effects when rotating
radiopharmaceutical for the nuclear the gamma camera detector heads though the
medicine scan. However, the flux of earth’s magnetic field, which measures a
photons from the radiopharmaceutical is mere 30 to 60╯µT. Most PM tubes cannot
so low compared with the x-ray flux that operate at all in fields higher than approxi-
there is no detectable bias to the x-ray mately 0.01 T. Thus PM tube-based detectors
measurements and this potential must be kept far away from the magnet;
problem can be ignored. however, they can still be used in hybrid PET/
Although these factors need to be consid- MRI systems in which the two scanners are
ered, the advantages of the speed and high physically separate, and a bed on rails moves
statistical quality of CT-based attenuation the patient from one scanner into the other.
correction almost always outweigh such Second, unlike CT, magnetic resonance is 
concerns. a relatively slow modality for acquiring high-
resolution, diagnostic-quality images over
3.  Scatter Correction large tissue volumes. Typical clinical exami-
In addition to being used for attenuation cor� nations require several minutes, much like
rection, the scaled attenuation map also can PET and SPECT. This makes sequential
be used for calculation of a correction for  imaging (which is the standard approach in
scattered radiation in the tomographic  PET/CT and SPECT/CT) less attractive,
nuclear medicine study. At nuclear medicine because the total time of the examination can
energies, virtually all interactions in biologi- be rather long. Simultaneous imaging to
cal tissues are by Compton scatter, and thus improve throughput is possible, but only by
the attenuation map of µ(E) is equivalent to
a map of the coefficients for Compton scatter
interactions. Chapter 17, Section B.4, and
Chapter 18, Section D.3, describe how these *T, Tesla: the standard unit of magnetic field strength.
19  •  Hybrid Imaging: SPECT/CT and PET/CT 361

creating a very compact PET or SPECT stand-alone systems to reduce magnetic field
system that can fit inside the bore of a magnet, and radiofrequency interference to acceptable
and operate in very strong magnetic fields. levels. As well, it combines two expensive
Early approaches used long light guides or diagnostic imaging modalities. It has yet to be
optical fibers to transport scintillation light demonstrated whether clinical applications
from PET detectors residing inside the bore will justify the cost of these systems. None-
of the magnet, to PM tubes placed several theless, PET/MRI is likely to emerge as a
meters outside the MRI scanner where the powerful tool for biomedical research. Figure
fringe magnetic field is low enough for their 19-15 shows an early hybrid PET/MRI system
operation. More recently, practical hybrid designed for imaging the human brain, and
PET/MRI systems have been developed for examples of the images it produces.
both small-animal and human applications
using detectors based on scintillator elements REFERENCES
read out by avalanche photodiodes (see 1. Bushberg JT, Seibert JA, Leidholdt EM, Boone JM: 
Chapter 7, Section C.3), which are relatively The Essential Physics of Medical Imaging, ed 3,
immune to magnetic field effects. Chapter 10, Philadelphia, PA, 2012, Lippincott Wil-
Third, cost is an important consideration liams & Wilkins.
2. Lang TF, Hasegawa BH, Liew SC, et al: Description
in the clinical adoption of hybrid PET/MRI of a prototype emission-transmission computed
scanners. Integration of PET and MRI typi- tomography imaging system. J Nucl Med 33:1881-
cally requires at least some modification of 1887, 1992.
3. Tang HR, et al: Implementation of a combined x-ray
CT-scintillation camera imaging system for localizing
and measuring radionuclide uptake: experiments in
phantoms and patients. IEEE Trans Nucl Sci 46:551-
557, 1999.
PET 4. Buck AK, Nekolla S, Ziegler S, et al: SPECT/CT. 
J Nucl Med 49:1305-1319, 2008.
5. Badea CT, Drangova M, Holdsworth DW, Johnson
GA: In vivo small animal imaging using microCT and
digital subtraction angiography. Phys Med Biol
53:R319-350, 2008.
6. Beyer T, Townsend DW, Brun T, et al: A combined
PET/CT scanner for clinical oncology. J Nucl Med
MRI 41:1369-1379, 2000.
7. Surti S, Kuhn A, Werner ME, et al: Performance of
Philips Gemini TF PET/CT scanner with special con-
sideration for its time-of-flight imaging capabilities.
J Nucl Med 48:471-480, 2007.
8. Kinahan PE, Hasegawa BH, Beyer T: X-ray based
attenuation correction for positron emission
A tomography/computed tomography scanners. Semin
Nucl Med 33:166-179, 2003.
9. Hubbell JH, Seltzer SM: Tables of x-ray mass attenu-
ation coefficients and mass-energy absorption coeffi-
cients from 1 keV to 20╯MeV for elements Z = 1 to 92
and for 48 additional substances of dosimetric inter-
est. Available at http://physics.nist.gov/PhysRefData/
XrayMassCoef/cover.html [accessed August 26th, 
2011].
10. Bushberg JT, Seibert JA, Leidholdt EM, Boone JM:
B The Essential Physics of Medical Imaging, ed 3,
Chapters 12 and 13,, Philadelphia, PA, 2012, Lip-
FIGURE 19-15  A, Hybrid PET/MRI scanner. The PET
pincott Williams & Wilkins.
scanner is inserted inside the bore of the magnet to allow
11. Cherry SR, Louie AY, Jacobs RE: The integration of
simultaneous acquisition of PET and MRI images of the
positron emission tomography with magnetic reso-
brain. The field strength of the MRI scanner is 3╯T. 
nance imaging. Proc IEEE 96:416-438, 2008.
B, Simultaneously acquired 18F-fluorodeoxyglucose PET
images (red color scale) superimposed on MRI images
(grayscale) in a normal subject. A single transverse, BIBLIOGRAPHY
coronal, and sagittal slice from the three-dimensional
The following is an informative general review on
PET/MRI dataset is shown. (Courtesy Dr. Ciprian Catana
hybrid imaging:
and Dr. A. Gregory Sorenson, MGH/HST, Athinoula A.
Martinos Center for Biomedical Imaging, Charlestown, Townsend DW: Multimodality imaging of structure and
MA.) function. Phys Med Biol 53:R1-R39, 2008.
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chapter
20 
Digital Image
Processing in Nuclear
Medicine

Image processing refers to a variety of tech- purpose microprocessor. Such devices can be
niques that are used to maximize the infor- programmed to perform a wide variety of
mation yield from a picture. In nuclear tasks, but they are relatively large and not
medicine, computer-based image-processing very energy efficient. For very specific tasks,
techniques are especially flexible and power- an application-specific integrated circuit often
ful. In addition to performing basic image is used. ASICs are compact and energy effi-
manipulations for edge sharpening, contrast cient, but their functionality is hardwired
enhancement, and so forth, computer-based into their design and cannot be changed.
techniques have a variety of other uses that Examples of their uses include digitizing
are essential for modern nuclear medicine. signals (analog-to-digital converters) and
Examples are the processing of raw data for comparing signal amplitudes (pulse-height
tomographic image reconstruction in single analyzers and multichannel analyzers). Other
photon emission computed tomography categories of microprocessors include digital
(SPECT) and positron emission tomography signal processors (DSPs) and graphics pro-
(PET) (see Chapters 16 to 18), and correcting cessing units. These devices have limited pro-
for imaging system artifacts (e.g., Chapter 14, grammability, but they are capable of very
Section B, and Chapter 18, Section D). fast real-time signal and image processing,
Another important example is time analysis such as 3-D image rotation and similar types
of sequentially acquired images, such as is of image manipulations.
done for extracting kinetic data for tracer The technology of microprocessors and
kinetic models (see Chapter 21). Computer- computers is undergoing continuous and
based image displays also allow three- rapid evolution and improvement, such 
dimensional (3-D) images acquired in SPECT that a “state-of-the-art” description rarely 
and PET to be viewed from different angles is valid for more than a year or, in some 
and permit one to fuse nuclear medicine cases, even a few months. However, the end
images with images acquired with other result is that the usage of computers and
modalities, such as computed tomography microprocessors in nuclear medicine is ubiq-
(CT) and magnetic resonance imaging (MRI) uitous. They are used not only for acquisi-
(see Chapter 19). Computer-based acquisition tion, reconstruction, processing, and display
and processing also permit the raw data and of image data but also for administrative
processed image data to be stored digitally applications such as scheduling, report gen-
(e.g., on computer disks) for later analysis eration, and monitoring of quality control
and display. protocols.
All of these tasks are performed on silicon- In this chapter, we describe general con-
based processor chips, generically called cepts of digital image processing for nuclear
microprocessors. The central processing unit medicine imaging. Additional discussions of
(CPU) of a general purpose computer, such as specific applications are found in Chapters 13
a personal computer, is called a general to 19 and Chapter 21.
363
364 Physics in Nuclear Medicine

A.  DIGITAL IMAGES a location x = 4.8╯cm, y = 12.4╯cm, the appro-


priate pixel location for this event would be
1.  Basic Characteristics and x-pixel location = 4.8 cm/ 0.3125 cm/pixel
Terminology
= int(15.36) = 15
For many years, nuclear medicine images
were produced directly on film, by exposing y-pixel location = 12.4 cm/ 0.3125 cm/pixel
the film to a light source that produced flashes = int(39.68) = 40
of light when radiations were detected by the
imaging instrument. As with ordinary photo- where int(x) denotes the nearest integer
graphs, the image was recorded with a virtu- of x, and the pixels are labeled from 0-127
ally continuous range of brightness levels and with the coordinate system defined as shown
x-y locations on the film. Such images some- in Figure 20-2.
times are referred to as analog images. Very A similar format is used for digital multi�
little could be done in the way of “image pro- slice tomographic images, except that the dis-
cessing” after the image was recorded. crete elements of the image would correspond
Virtually all modern nuclear medicine to discrete 3-D volumes of tissue within a
images are recorded as digital images. This is cross-sectional image. The volume is given by
required for computerized image processing. the product of the x- and y-pixel dimensions
A digital image is one in which events are multiplied by the slice thickness. Thus they
localized (or “binned”) within a grid compris- are more appropriately called volume ele-
ing a finite number of discrete (usually square) ments, or voxels. However, when discussing
picture elements, or pixels (Fig. 20-1). Each an individual tomographic slice, the term
pixel has a digital (non�fractional) location or pixel still is commonly used. In tomographic
address, for example, “x = 5, y = 6.” For a images, the “intensity” of each voxel may or
gamma camera image, the area of the detector may not have a discrete integer value. For
is divided into the desired number of pixels example, voxel values for a reconstructed
(Fig. 20-2). For example, a camera with a field- image will generally have noninteger values
of-view of 40╯cm × 40╯cm might be divided into corresponding to the calculated concentration
a 128 × 128 grid of pixels, with each pixel of radionuclide within the voxel.
therefore measuring 0.3125╯mm × 0.3125╯mm. Depending on the mode of acquisition (dis-
Each pixel corresponds to a range of possible cussed in Section A.4), either the x-y address
physical locations within the image. If an of the pixel in which each event occurs, or the
event were determined to have interacted at pixel value, p(x,╛╛y), is stored in computer
memory. For 3-D imaging modes, such as 3-D
SPECT or PET, individual events are localized
within a 3-D matrix of voxels, and the recon-
structed value in a voxel is denoted as v(x,â•›y,â•›z).
Depending on how data are acquired and pro-
cessed by the imaging system, the pixel or
voxel value may correspond to the number of
counts, counts per unit time, the reconstructed
pixel or voxel value, or absolute radionuclide
concentrations (kBq/cc or µCi/cc).
Although most interactions between the
user and a computer system involve conven-
tional decimal numbers, the internal opera-
tions of the computer usually are performed
p (x, y)
using binary numbers. Binary number repre-
sentation uses powers of 2, whereas the com-
monly used decimal number system uses
L
powers of 10. For example, in decimal repre-
sentation, the number 13 means [(1 × 101) + (3
× 100)]. In the binary number system, the
FIGURE 20-1  A digital image consists of a grid or matrix same number is represented as 1101, meaning
of pixels, each of size L × L units. Each pixel has an x-y
address location, with pixel value, p(x,y), corresponding
[(1 × 23) + (1 × 22) + (0 × 21) + (1 × 20)], or (8 +
to the number of counts or other quantity associated with 4 + 0 + 1) = 13. Each digit in the binary number
that pixel. representation is called a bit (an abbreviation
20  •  Digital Image Processing in Nuclear Medicine 365

Active area of
gamma camera Detected Pixel corresponding
radiation event to event location

For each event detected:


1) Digitize PM tube
PM tube signals
signals 2) Compute event x-y
location
3) Determine x-y pixel
y location and increment
that pixel by 1 count

x Image matrix
FIGURE 20-2  Subdivision of the gamma camera detector area for generating a digital image. The photomultiplier
tube signals are analyzed using analog-to-digital converters to assign the digital matrix location for each detected
event.

for “binary digit”). In general, an n-bit binary in a pixel exceeds the allowed pixel depth, the
number can represent decimal numbers with count for that pixel is reset to 0 and starts over,
values between zero and (2n − 1). which can lead to erroneous results and image
Binary numbers are employed in computer artifacts.
systems because they can be represented con- Pixel depth also affects the number of gray
veniently by electronic components that can shades (or color levels) that can be repre-
exist only in an “on” or “off ” state. Thus an sented within the displayed image. In most
n-bit binary number can be represented by computer systems in use in nuclear medicine,
the “on” or “off ” state of a sequence of n such 8 bits equals a byte of memory and 16 bits
components. To communicate sensibly with equals a word of memory. The pixel depth,
the outside world, the binary numbers used therefore, frequently is described as “byte”
within the computer must be converted into mode or “word” mode.*
decimal integers or into decimal numbers and
fractions. The latter are called floating point 2.  Spatial Resolution and Matrix Size
numbers. The methods by which binary The spatial resolution of a digital image is
numbers are converted to decimal format are governed by two factors: (1) the resolution of
beyond the scope of this presentation and can the imaging device itself (such as detector or
be found in more advanced texts on computer collimator resolution) and (2) the size of the
systems. pixels used to represent the digitized image.
Digital images are characterized by matrix For a fixed field-of-view, the larger the number
size and pixel depth. Matrix size refers to the of pixels, that is, the larger the matrix size,
number of discrete picture elements in the the smaller the pixel size (Fig. 20-3). Clearly,
matrix. This in turn affects the degree of a smaller pixel size can display more image
spatial detail that can be presented, with detail, but beyond a certain point there is no
larger matrices generally providing more further improvement because of resolution
detail. Matrix sizes used for nuclear medicine limitations of the imaging device itself. A
images typically range from (64 × 64) to (512 question of practical importance is, At what
× 512) pixels. Matrix size virtually always point does this occur? That is, how many
involves a power of 2 (26 and 29 in the previous pixels are needed to ensure that significant
examples) because of the underlying binary detail is not lost in the digitization process?
number system used in the computer. The situation is entirely analogous to that
Pixel depth refers to the maximum number presented in Chapter 16 for sampling require-
of events that can be recorded per pixel. Most ments in reconstruction tomography. In par-
systems have pixel depths ranging from 8 bits ticular, Equation 16-13 applies—that is, the
(28 = 256; counts range from 0 to 255) to 16 bits
(216 = 65,536; counts range from 0 to 65,535).
Note again that these values are related to the *Most modern computer CPUs have 32-bit or 64-bit pro-
cessors. This means they can process data 32 or 64 bits
underlying binary number system used in the at a time; however, this is largely independent of image
computer. When the number of events recorded display and how pixel values are stored.
366 Physics in Nuclear Medicine

FIGURE 20-3  Digital images of the liver and


256 × 256 128 × 128 spleen (posterior view) displayed with different
matrix sizes. The larger the matrix size, the
smaller the pixels and the more detail that is
visible in the image. (Original image courtesy
GE Medical Systems, Milwaukee, WI.)

64 × 64 32 × 32

linear sampling distance, d, or pixel size, larger pixels) to diminish the visibility of
must be smaller than or equal to the inverse noise in the final digitized image.
of twice the maximum spatial frequency, kmax,
EXAMPLE 20-1
that is present in the image:
What is the approximate spatial resolution
d = 1/(2 × kmax ) (20-1) that can be supported for a 30-cm diameter
field-of-view using a 64 × 64 matrix? A 128 ×
This requirement derives directly from the 128 matrix? Assume that the original data
sampling theorem discussed in Appendix F, are noise free.
Section C.
Once this sampling requirement is met, Answer
increasing the matrix size does not improve
spatial resolution, although it may produce  64 × 64 matrix
a cosmetically more appealing image with
less evident grid structure. If the sampling A 64 × 64 image matrix results in a pixel size
requirements are not met (too coarse a  of 300╯mm/64 = 4.69╯mm. From Equation
grid), spatial resolution is lost. The maximum 20-2, this would be suitable for image resolu-
spatial frequency that is present in an image tion given by
depends primarily on the spatial resolution FWHM  3 × pixel size = 14.06 mm

of the imaging device. If the resolution of 
the device is specified in terms of the full 128 × 128 matrix
width at half maximum (FWHM) of its line-
spread function (Chapter 15, Section B.2), FWHM  3 × 300 mm/128 = 7.03 mm
then the sampling distance (pixel size) should
not exceed about one third of this value to The values calculated in Example 20-1 rep-
avoid significant loss of spatial resolution, resent the approximate levels of imaging
that is, system resolution that could be supported
FWHM without loss of imaging resolution for the
d (20-2) specified image and matrix sizes. The practi-
3 cal effects of undersampling depend as well
This applies for noise-free image data. With on the information contained in the image
added noise it may be preferable to relax the and whether it has a significant amount of
sampling requirement somewhat (i.e., use actual spatial frequency content near the
20  •  Digital Image Processing in Nuclear Medicine 367

resolution limit of the imaging device. Practi- independently generated red, green, and blue
cal experimentation sometimes is required to color channels].
determine this for a particular type of imaging One commonly used color scale, the pseudo�
procedure. color scale (sometime known as the rainbow
or spectrum color scale), assigns different
3.  Image Display colors from the visible spectrum, ranging
Digital images in nuclear medicine are dis- from blue at the low (“cool”) end, through
played on cathode ray tubes (CRTs) or flat- green, yellow, and red (“hot”), for progres-
panel displays such as liquid crystal displays sively increasing pixel values. This is an
(LCDs). In addition to their use at the site of intrinsically nonlinear scale, because the
the imaging device, displays are an essential viewer does not perceive equal significance for
component of picture archival communica- successive color steps. A somewhat more
tions systems (PACS) networks, for remote natural scale, the so-called heat or hot-body
viewing of images (see Section C). The spatial scale, assigns different shades of similar
resolution of the display device should exceed colors, such as red, yellow, and white, to pro-
that of the underlying images so as not to gressively increasing pixel values, corre-
sacrifice image detail. In general, the display sponding to the colors of an object heated to
devices used in nuclear medicine computer progressively higher temperature. In both
systems and in radiology-based PACS net- examples, the colors are blended to produce a
works comfortably exceed this requirement. gradual change over the full range of the
Typical high-resolution CRTs have 1000 or scale. Figure 20-4 shows the same image dis-
more lines and a typical LCD might have played with different color scales.
1536 × 2048 elements. The major problem with the use of color
Individual pixels in a digital image are dis- scales to represent pixel count levels is that
played with different brightness levels, they are somewhat unnatural and also can
depending on the pixel value (number of produce contours, such as apparently sharp
counts or reconstructed activity in the pixel) changes in pixel values, where none actually
or voxel value. On grayscale displays, the exist. A more practical use of color displays is
human eye is capable of distinguishing for color coding a second level of information
approximately 40 brightness levels when they on an image. For example, in combined-
are presented in isolation and an even larger modality imaging of PET or SPECT with CT
number when they are presented in a sequence (see Chapter 19), the anatomic (CT) image
of steps separated by sharp borders. Image often is displayed using a standard gray scale,
displays are characterized by the potential whereas the functional (PET) image is shown
number of brightness levels that they can using a color scale. Such a display clearly dif-
display. For example, an 8-bit grayscale ferentiates between the two types of images,
display can potentially display 28 = 256 differ- whereas a simple overlay of two grayscale
ent brightness levels. Such a range is more images would be confusing.
than adequate in comparison with the capa- Hard-copy images can be produced on
bilities of human vision. In practice, the effec- black-and-white transparency film from a
tive brightness scale often is considerably less CRT display. Single-emulsion films are used
than the physical limits of the display device to minimize blurring of the recorded image,
because of image noise. For example, if an especially when images are minified for
image has a root mean square noise level of compact display on a single sheet of film. The
1%, then there are not more than 100 signifi- CRT display intensity must be calibrated to
cant brightness levels in the image, regard- compensate for the sensitometric properties
less of the capabilities of the display device. of the recording film to match the monitor
Digital images also can be displayed in display. Computer printers are now commonly
color by assigning color hues to represent dif- used to record hard-copy images and a range
ferent pixel values. The human eye can dis- of different technologies and media are avail-
tinguish millions of different colors, and color able depending on requirements such as
displays are capable of producing a broader quality (resolution and gray-scale range), cost
dynamic range (i.e., number of distinguish- and printing speed.
ably different levels) than can be achieved in
black-and-white displays. For example, a 4.  Acquisition Modes
true-color display with 24-bit graphics can Digital images are acquired either in frame
generate nearly 16.8 million different colors mode or in list mode. In frame-mode acquisi-
[224 = (28)3, in which the 3 represents the tion, individual events are sorted into their
368 Physics in Nuclear Medicine

A C

B D
FIGURE 20-4  The same reconstructed transaxial image slice rendered in different color scales. A, Grayscale, high-
intensity white; B, inverted grayscale, high-intensity black; C, hot-wire or hot-body scale; D, pseudocolor spectral scale.
The slice is from a PET scan of the brain using the radiotracer 18F-fluorodeoxyglucose. (Original image courtesy Siemens
Molecular Imaging, Knoxville, TN).

appropriate x-y locations within the digital improved, but the total counts per frame and
image matrix immediately after their position per pixel are reduced compared with slower
signals are digitized. After a preset amount of frame rates.
time has elapsed or after a preset number  In list-mode acquisition, the incoming x
of counts have been recorded, the acquisition and y position signals from the camera are
of data for the image is stopped and the pixel digitized, but they are not sorted immediately
values [p(x,y) = number of counts per pixel] into an image grid. Instead, the x and y posi-
are stored in computer memory. tion coordinates for individual events are
When a series of such images is obtained stored, along with periodic clock markers
sequentially, individual images in the (e.g., at millisecond intervals). This permits
sequence are referred to as “frames.” Clearly, retrospective framing with frame duration
the image matrix size (e.g., 64 × 64, 128 × 128, chosen after the data are acquired.
and so forth) must be specified before the List-mode acquisition permits greater flex-
acquisition begins. Additionally, the time ibility for data analysis. However, it is not an
duration of the frame sets a limit on the tem- efficient method for using memory space
poral accuracy of the data. For example, if  during acquisition for conventional imaging,
the frame is acquired during a 1-minute especially for high-count images, because
period, the number of counts recorded in each every recorded event occupies a memory loca-
pixel represents the integrated number of tion. Thus a 1-million count 128 × 128 image
counts during the 1-minute acquisition period recorded in list mode would require 1 million
and cannot be subdivided retrospectively into memory locations, whereas in frame mode 
shorter time intervals. When faster framing the same image would require only approxi-
rates are used, such as for cardiac blood-pool mately 16,000 memory locations. However,
imaging, temporal sampling accuracy is list mode can actually be more efficient in
20  •  Digital Image Processing in Nuclear Medicine 369

some situations. This would apply, for


example, if the average number of counts is 1.  Image Visualization
less than 1 per pixel in an image frame. In Commonly, a single projection image, or in the
this case, list mode would require fewer case of tomographic data, a set of contiguous
memory locations to record the image than image slices, are displayed on the screen. The
frame mode. Such situations can arise (e.g., display of the images can be manipulated in
in fast dynamic studies). a number of ways to aid in interpretation.
Another commonly used acquisition mode This includes changing from a linear gray
is called gated imaging. In this mode, data are scale to a color scale or to a nonlinear (e.g.,
acquired in synchrony with the heart beat or logarithmic) gray scale, or limiting the range
with the breathing cycle, so that all images of pixel values displayed. The latter is known
are acquired at the same time during the as windowing. For example, if greater con-
motion cycle. This helps reduce blurring and trast is desired in one region of an image, the
other possible image artifacts induced by full brightness range of the display device can
body motion (see Fig. 15-1). To perform gated be used to display only the range of pixel
imaging, it is necessary to have some sort of values found within that region (Fig. 20-5).
monitoring system in place, such as electro- This increases the displayed contrast in the
cardiogram leads for the heart beat or a pneu- selected area, but other parts of the image
matically operated “belly band” that produces may have diminished contrast as a result (i.e.,
an electrical signal when it expands during the counts per pixel may be beyond the upper
the breathing cycle. or lower range of the selected grayscale
In frame-mode gated imaging, the signals window). Whenever image data are displayed
from the motion-monitoring device are used or reproduced, it is desirable to show a gray-
to initiate an image-acquisition cycle. The scale or color-scale bar that has undergone the
“cycle” may consist of several images, each of same manipulations as the images, so that
which represents the object at the same loca- the viewer can interpret the image in the
tion, assuming the motion is repeated repro- context of how the display has been
ducibly during the cycle. With list-mode modified.
acquisition, retrospective synchronization is Tomographic nuclear medicine data con-
possible by recording the motion-monitoring sists of a 3-D volume that can be displayed in
signal along with the signals from the detec- conventional transaxial views or in coronal or
tor. In either case, data usually are acquired sagittal views (Fig. 20-6). Often it is useful to
over a large number of cycles and the images display all three views simultaneously on the
are added together, until the total number of screen. Typically, a point within the object is
counts is sufficient to provide adequate count- chosen using the cursor, and the three orthog-
ing statistics. onal images that pass through that point are
displayed. As the cursor is moved, the trans-
axial, coronal, and sagittal images are
B.  DIGITAL IMAGE-PROCESSING updated. This is an efficient way of navigating
TECHNIQUES through a large 3-D dataset. The dataset also
can be resliced at an arbitrary orientation to
All modern nuclear medicine systems are pro- provide oblique views. This is useful for
vided with fairly sophisticated software for objects whose line of symmetry does not fall
displaying and processing the images that are naturally along one of the perpendicular axes
acquired on those systems. There also are of the 3-D volume. An example is reslicing the
many “third-party” software packages avail- 3-D dataset to provide short axis views of the
able that incorporate extensive tools for image heart.
processing and allow images from different Another useful visualization tool for 3-D
manufacturers and different modalities to be tomographic datasets is the projection tool.
analyzed. A variety of digital image-processing This collapses the 3-D dataset into a single
techniques are used in nuclear medicine, 2-D image for a specified viewing angle and
some of which are fully automatic (i.e., per- allows all the data to be seen at once. An
formed entirely by the computer), whereas example is shown in Figure 20-7. A number of
others are interactive (i.e., require some user different algorithms are available to “render”
input). In this section, we describe briefly  the projection images. The simplest approach
a subset of the major image-processing  is to simply sum the intensities along the
tools that are commonly used in nuclear projection direction. This is essentially equiv-
medicine. alent to what would be obtained by acquiring
370 Physics in Nuclear Medicine

FIGURE 20-5  Effect of changing the distribution of gray levels on image contrast. Left, Original image with uniform
distribution of gray levels. Center, Gray scale compressed (fewer levels) in high-count (dark) regions to improve the
visualization of soft tissues. Right, Gray scale compressed in low-count (light) regions to suppress soft tissues and
visualize only bone. (Image courtesy Siemens Medical Solutions, USA, Inc.)

Sagittal plane

Coronal plane
Transverse plane

Transverse Sagittal Coronal

B
FIGURE 20-6  A, Orientation of transverse (also known as transaxial), coronal and sagittal sections. B, Orthogonal
views (transverse, coronal, sagittal) of an 18F-fluorodeoxyglucose PET brain study in which the imaging field-of-view
covers the entire head. (A, Reproduced from http://en.wikipedia.org/wiki/File:Human_anatomy_planes.svg#file. B,
Images courtesy CTI PET Systems, Inc., Knoxville, TN.)
20  •  Digital Image Processing in Nuclear Medicine 371

Projection image

Individual coronal slices


18
FIGURE 20-7  Whole-body F-fluorodeoxyglucose PET study displayed as a single projection image (top) and as a
series of coronal image slices (bottom row). The projection image shows the distribution of radiotracer in all slices
(arrows correspond to metastatic disease in this patient with cancer), but image resolution and contrast are lost rela-
tive to the individual tomographic slices. Projection images often are a convenient way to initially view large tomo-
graphic datasets, after which individual tomographic slices can be used for more detailed examination or quantitative
analysis. (Courtesy Dr. Magnus Dahlbom, University of California–Los Angeles.)

2-D views of the object from many projection combine images acquired with different radio-
directions. Another approach is to display only nuclides or acquired with different modali-
the surface pixel values (surface rendering). ties. Most image-processing software allows
An approach that highlights internal features one to add, subtract, multiply, and divide
is to display only the pixel with the maximum single images or 3-D image volumes. These
value along the projection direction (maximum operations typically are applied on a pixel-by-
intensity projection). pixel basis. Figure 20-8 is an example of a
By computing projection views at a set of simple frame arithmetic operation: subtrac-
angles around the object and presenting them tion. The study illustrated is a visual stimula-
in a continuous loop, one can create movies in tion using 15O-labeled water as a flow tracer.
which it appears that the object is rotating in Visual stimulation, created by having the
space. This sometimes is called cine mode. subject view a strobe light, caused an increase
These and other rendering and display algo- in blood flow to the occipital (visual) cortex,
rithms are discussed in some of the suggested while the remainder of the brain remained
readings at the end of the chapter. largely unaffected. Subtraction of an image
Another important application of image taken from a resting control study from the
processing is image arithmetic. There are a image obtained in the stimulation study pro-
number of applications in which one wishes vides a display of the blood flow changes
to see differences between images or to occurring as a result of stimulation.
372 Physics in Nuclear Medicine

Baseline Visual stimulation Subtraction

FIGURE 20-8  Cerebral blood-flow images (H215O PET) acquired in the resting state (left) and during visual stimula-
tion using a flashing light (center). The stimulus causes a small increase in blood flow in the visual cortex that is virtu-
ally invisible on the image acquired during visual stimulation; however, the increase is clearly visible when the
resting-state image is subtracted from it (right).

Most digital images in nuclear medicine radiotracer distribution in the body. Conven-
are, in essence, pictures of the count density tional 2-D images also can provide informa-
in the organ or tissue of interest. Instead of tion about the relative concentration of
presenting the data in this format, one may radiotracer in different areas. Regions of
desire to first process the image data on a interest (ROIs) are used to extract numerical
pixel-by-pixel basis using a model that repre- data from these images. The size, shape, and
sents the functional process and display the position of ROIs can be defined and positioned
calculated result. Such an image, in which the by the user, using a selection of predefined
pixel values represent a calculated parame- geometric shapes (e.g., rectangles, circles).
ter, sometimes is called a parametric image. Alternatively, irregular ROIs can be created
For example, a digital ventilation image can using a cursor on the image display. The com-
be divided by a perfusion image to produce a puter then reports ROI statistics such as the
parametric image that shows the ventilation/ mean pixel value, the standard deviation of
perfusion ratio. Other examples of calculated the pixel values, and the number of pixels in
functional parameters are discussed in the ROI (Fig. 20-9). Software tools that use
Chapter 21. edge-detection algorithms also are available
for automated definition of ROIs (see Section
2.  Regions and Volumes of Interest B.5).
Care must be taken in the use of ROIs to
Both PET and SPECT can provide semiquan- accurately place them on the tissues of inter-
titative, or when all appropriate corrections est, especially for applications in which
are applied, quantitative images of the  radiotracer uptake or concentration are

FIGURE 20-9  Manually drawn region of


interest (ROI) placed over the right stria-
REGION OF INTEREST
tum (a small, gray matter structure deep in
Mean: 684.3 counts the brain) in an 18F-fluoroDOPA PET brain
Max: 723.5 counts study. This tracer reflects dopamine synthe-
Min: 648.9 counts sis and accumulates in the dopaminergic
S.D.: 18.3 counts (dopamine-producing) neurons of the stria-
tum. Typically, ROI software programs
Number of pixels: 112 provide a set of statistics on the number of
Area: 450 mm2 counts per pixel per second (proportional to
the radioactivity concentration) and the
area of the ROI.
20  •  Digital Image Processing in Nuclear Medicine 373

monitored during a longer period. Such mea-


surements sometimes are made, for example, 4.  Image Smoothing
to observe and monitor the metabolic status All nuclear medicine computer systems
of a tumor. Automated methods are provided provide image-smoothing algorithms. Figure
on some computer systems to assist with 20-11 illustrates the effect of smoothing on an
this task. However, even with an automated image that has a poor SNR in the unpro-
method, one must be aware of and careful to cessed state. Smoothing operations are, in
avoid errors caused by the partial-volume essence, techniques that average the local
effects discussed in Chapter 17, Section B.5. pixel values to reduce the effect of pixel-to-
For example, an important question for pixel variation. Two simple algorithms for 2-D
staging in tumor imaging is the concentra- images are 5-point and 9-point smoothing, in
tion of radiotracer in the tumor. A “small” which a pixel value is averaged with its
tumor with high uptake (Bqâ•›/cm3) is different nearest 4 or 8 neighbors (Fig. 20-12).
from a somewhat larger tumor with low In the previous examples, all four or eight
uptake. An apparent increase in radiotracer neighboring pixels, as well as the center pixel,
concentration in a “small” tumor (one that is are given equal weight in the smoothing
near the resolution limits of the imaging process. Image smoothing also can be per-
device) during a longer period actually could formed using filters that are weighted accord-
be due to tumor growth in size and an asso- ing to the distance from the pixel that is being
ciated reduction in partial-volume effects. smoothed. One such example is a gaussian
ROI analysis is therefore particularly diffi- smoothing filter. In general, one can write the
cult when the volume of tissue that is of following:
interest is changing with time. smoothed image
Most structures of interest extend in all (20-3)
three dimensions and cover multiple image = original image ∗ smoothing filter
planes in a tomographic dataset. To obtain where ∗ represents the operation of convolu-
the best signal-to-noise ratio (SNR), and to tion (see Appendix G). Although smoothing
ensure that the ROI values are representa- frequently produces a more appealing image
tive of the entire structure, it is necessary to by reducing noise (and improving the SNR),
draw ROIs on multiple contiguous image it also results in blurring and potential loss
planes that contain the object. In some soft- of image detail. Sometimes it is convenient to
ware these ROIs can be connected to form a perform analytic studies (e.g., integrating
volume of interest (VOI). Automated tools for pixel count values over an area) on an
defining VOIs also have been developed. unsmoothed image after identifying ROIs on
a smoothed image. In such applications, a
3.  Time-Activity Curves practical compromise between resolution and
As discussed in Chapter 21, the rate of change visual appeal must be reached.
of radiotracer uptake in a specific organ or
tissue often is of interest. To determine this, 5.  Edge Detection and Segmentation
the data are acquired as a series of frames Edge detection and segmentation are two
over time (see Section A.4). The data typically image-processing tools that can be used to
are analyzed by defining an ROI on one frame, assist in automatically defining ROIs. They
or on the sum of all frames, and then copying also are used for classifying different types 
the ROI across all of the frames. This is accu- of tissue based on their radiotracer uptake
rate provided that the patient has not moved and for defining the body and lung contours
between frames. The process is illustrated in for attenuation correction (see Chapter 17,
Figure 20-10 for a time series of images of the Section B.2).
brain following the injection of 18F-fluoro Edge-detection algorithms work best with
DOPA, a compound that localizes in the stria- edges that are very clearly defined as a result
tum whose uptake is related to the rate at of a sharp boundary in radiotracer uptake.
which dopamine is synthesized. One of the most common is the Laplacian
The ROI data from a series of frames can technique. The 2-D Laplacian is defined by
be used to create a time-activity curve (TAC),
showing the radiotracer concentration as a ∂2 ∂2
Laplacian = + 2 (20-4)
function of time in the tissue defined by the ∂x 2
∂y
ROI. Figure 20-10 also shows the TAC
extracted from the ROI data in the time series where ∂2/∂x2 represents the second partial
of images. derivative of the function [i.e., the pixel
374 Physics in Nuclear Medicine

0.0 min 0.75 min 1.25 min 1.75 min 2.25 min 2.75 min

4.5 min 7.5 min 10.5 min 13.5 min 20 min 30 min

40 min 50 min 60 min 75 min 95 min 115 min

0.3

0.25
Striatum
Radioactivity (µCi/mL)

0.2

0.15

Cerebellum
0.1

0.05

0
0 20 40 60 80 100 120
Time (min)
FIGURE 20-10  Top, PET images of the same two-dimensional (2-D) slice through the brain at different times after
administration of a bolus injection of 18F-fluoroDOPA. A region of interest (ROI) is drawn over the right striatum on
the last image and then copied to all other time points. Bottom, Time-activity curve (TAC) showing the mean value in
the ROI, converted with a calibration factor from counts per second per pixel to absolute concentration of radioactivity,
versus time for the striatum. Also shown is a TAC for the cerebellum, taken from a different 2-D image slice, demon-
strating how different brain regions can have different kinetics. Analysis of such TACs is discussed in Chapter 21.
(Adapted from Cherry SR, Phelps ME: Positron emission tomography. In Sandler MP, Coleman RE, Patton JA, et╯al
[eds]: Diagnostic Nuclear Medicine, 4th ed. Baltimore, Williams & Wilkins, 2002, p. 79.)
20  •  Digital Image Processing in Nuclear Medicine 375

FIGURE 20-11  Effect of image smoothing using a gaussian filter with a full width at half maximum of 4╯mm (center)
and 8╯mm (right). Smoothing improves the signal-to-noise ratio in the images but at the expense of spatial
resolution.

radiotracer uptake. The simplest method of


segmentation is just to select pixels having
values within a specified range: A < p(x,â•›y) < B.
Because of image noise, this simple method
rarely is sufficient for accurate segmentation.
More sophisticated algorithms that consider
the underlying resolution and noise proper-
ties of the images and that also seek clusters
of contiguous pixels usually are employed.
5-point smoothing 9-point smoothing Edge-detection algorithms also can be used in
segmentation. For example, an edge-detection
FIGURE 20-12  Illustration of pixels used in 5-point and
9-point smoothing. The value in the pixel of interest
algorithm can be used to define the contours
(dark blue) is averaged with the values in the surround- of the lungs and all pixels within that contour
ing pixels (light blue). defined as lung tissue. Other examples of
edge-detection and segmentation algorithms
are discussed in the suggested readings at the
end of the chapter.
values, p(x,y)], with respect to spatial coordi-
nate x, and similarly for the spatial coordi- 6.  Co-Registration of Images
nate y. An analogous definition can be made It is quite common to perform multiple nuclear
for the 3-D Laplacian, which would be applied medicine imaging studies at different times
to 3-D datasets. As illustrated by the 1-D on the same subject. This is useful, for
example presented in Figure 20-13, the point example, to monitor the progression of
at which the Laplacian crosses zero repre- Alzheimer’s or Parkinson’s disease, to measure
sents a region with a high rate of change the change in tumor blood flow or metabolism
between neighboring pixel values and there- following cancer treatment, or to study the
fore reflects an edge. In practice, the operator response of brain blood flow to various stimuli.
often specifies a starting point for the algo- To accurately compare nuclear medicine
rithm, which then searches in all possible studies on the same subject performed at 
directions and constructs a line (edge) where different times (e.g., by subtraction of the
the Laplacian crosses zero. Eliminating small images), it is necessary that the images be
changes (i.e., setting limits) in the Laplacian accurately aligned. This is known as intra�
reduces the effect of noise. Figure 20-14 shows subject intramodality image co-registration.
an image in which the lung contours have Many algorithms have been developed to
been defined automatically by the Laplacian co-register nuclear medicine studies. They
algorithm. have been particularly successful in the brain,
The goal of image segmentation is to group because the brain is rigidly held within the
all pixels that have certain defined character- skull and the transformations required to
istics. In nuclear medicine, this usually refers co-register the images are limited to simple
to pixels that have a certain range of pixel translations and rotations. Co-registration
intensities and thus a certain level of accuracy can be as high as 1 to 2╯mm. Figure
376 Physics in Nuclear Medicine

20-15 shows co-registered PET images of the


same subject acquired at different times.
Outside the brain, image co-registration
becomes much more difficult, because organs
can shift relative to each other depending on
the exact positioning of the patient on the
Pixel value, p

bed. In general, this requires nonlinear


co-registration algorithms that attempt to
“warp” one image to fit with the other.
Intrasubject, cross-modality co-registration
involves registering a nuclear medicine study
with a study of the same subject performed
with a different imaging modality (e.g., MRI
or CT). This requires more sophisticated algo-
0 rithms because the information content of the
images as well as their spatial resolution and
SNR characteristics are different. Nonethe-
less, algorithms have been successful for
co-registering PET and SPECT studies onto
MRI or CT images, thereby providing
co-registered volumetric datasets that reflect
First derivative

both biologic function (PET or SPECT) and


anatomy (CT or MRI). Again, because of its
dp/dx

precise geometric relationship to the skull,


the most successful applications of these algo-
rithms have been in brain imaging.
There also is interest in intersubject co- 
registration of nuclear medicine images for
comparisons between multiple subjects. For
example, this can be used to create images
0 based on a large database of subjects, showing
the distribution of a radiotracer across a spe-
cific population of subjects. If such a database
of images of normal subjects is available for
a particular radiotracer, a patient then can be
Laplacian
crosses zero – compared with the normal database to see if
the distribution is significantly different from
Second derivative

location of edge
normal controls. A summary of modern image
d 2p/dx 2

co-registration techniques is provided in ref-


0
erence 1.

C.  PROCESSING ENVIRONMENT

The digital image-processing environment


may be limited to a single gamma camera, or,
in a large department, it may involve a collec-
Pixel location tion of gamma cameras and tomographic
FIGURE 20-13  A one-dimensional example showing a imaging devices. For all modes of imaging,
count profile of pixel value p versus pixel location x across digital image processing involves several
a boundary with two different activity levels. The first steps: (1) acquisition, (2) processing, (3) display,
and second (Laplacian) derivatives of the count profile
with respect to x are shown. The first derivative is the (4) archiving (storing the raw or processed
difference between neighboring pixel values, or equiva- data or images), and (5) retrieval. Acquisition
lently the local slope of the count profile. At an edge, pixel obviously takes place on the imaging device
values are changing rapidly with location and the slope itself; however, it is useful if the other steps in
has a high absolute value. The second derivative, the
Laplacian, is the difference between adjacent first deriva- the chain can be performed not only on the
tive values. The x-location where this second derivative imaging system console but also on any other
crosses zero defines the location of the edge. computers in the hospital or laboratory. In
20  •  Digital Image Processing in Nuclear Medicine 377

FIGURE 20-14  Series of images illustrating the segmentation of the lungs on a transmission scan acquired on a
single-photon emission computed tomography system. (Original image courtesy Dr. Freek Beekman, University Medical
Delft University of Technology, The Netherlands.)

FIGURE 20-15  Top three rows, Co-registered slices from three 18fluorodeoxyglucose PET scans acquired at 1-year
intervals on the same subject. Images in each column represent the same anatomic slice, after co-registration. Bottom
row, Corresponding co-registered slices from a magnetic resonance imaging scan acquired at the time of the third PET
scan (intermodality co-registration). Images were co-registered using the Automated Image Registration software
developed by Roger Woods of the University of California-Los Angeles. Note the excellent agreement in structures
included and their locations in each slice. Some images were truncated (particularly in the left column) because parts
of the brain were outside the field-of-view in some scans. (From Woods RP, Mazziotta JC, Cherry SR: Optimizing
activation methods: Tomographic mapping of functional cerebral activity. In Thatcher RW, Hallett M, Zeffiro T, et╯al
[eds]: Functional Neuroimaging: Technical Foundations. San Diego, Academic Press, 1994, p. 54.)
378 Physics in Nuclear Medicine

addition to freeing up the image acquisition imaging equipment support this standard.
computer for additional studies, it allows a The objective of DICOM is to enable vendor-
variety of other activities to proceed simulta- independent communication not only of
neously. For example, it allows a medical phys- images but also of associated diagnostic and
icist to reprocess a study from his or her office therapeutic data and reports.
while physicians are viewing the same images A true archival system not only should
in the reading room or even at a different hos- store the image or processed image data but
pital and researchers are downloading the also should be organized around a logical
studies onto a computer in the research retrieval system that permits correlation of
laboratory. images with other types of data (e.g., reports)
Many nuclear medicine departments there- for a given patient study. That is, it should
fore employ high-speed networks to connect have the capacity of a computer database
their imaging systems together with other system and interface seamlessly with radiol-
computer systems in the institution and, via ogy, nuclear medicine, and hospital informa-
the Internet, to the outside world. These tion systems. In addition, the system must be
departments use PACS to store and move capable of protecting patient information by
images from acquisition sites to more conve- providing access only to authorized users.
nient viewing stations and to provide a
common basis for handling nuclear medicine
and all other diagnostic imaging modalities.2 REFERENCES
PACS systems in hospitals with large radiol- 1. Hill DLG, Batchelor PG, Holden M, Hawkes DJ:
ogy and nuclear medicine departments must Medical image registration. Phys Med Biol 46:R1-R45,
be capable of handling huge amounts of data, 2001.
typically several gigabytes per day (1 Gb = 2. Bick U, Lenzen H: PACS: The silent revolution. Eur
Radiol 9:1152-1160, 1999.
1012 bytes). 3. Mildenberger P, Eichelberg M, Martin E: Introduction
To facilitate the exchange and handling of to the DICOM standard. Eur Radiol 12:920-927, 2002.
images from multiple different imaging
modalities and from different vendors each
with their own custom software, image file BIBLIOGRAPHY
format standards have been developed. The General references on image processing
central standard in radiology is the Digital Gonzalez RC, Woods RE: Digital Image Processing, ed 3,
Upper Saddle River, NJ, 2008, Pearson Prentice Hall.
Imaging and Communications in Medicine (Chapters 2, 3, 6, and 10 are especially relevant.)
(DICOM) standard described in reference 3, Robb RA: Biomedical Imaging, Visualization, and Analy-
and all manufacturers producing diagnostic sis, ed 2, New York, 1999, Wiley-Liss.
chapter
21 
Tracer Kinetic
Modeling
The spatial distribution of a radiotracer in the Tracer kinetic models may be very simple.
body is time varying and depends on a number For example, one method for evaluating renal
of components such as tracer delivery and function is to measure the uptake of 99mTc-
extraction from the vasculature, binding to labeled dimercaptosuccinic acid (DMSA) using
cell surface receptors, diffusion or transport a single region of interest (ROI) positioned
into cells, metabolism, washout from the over each kidney at one instant in time. “Func-
tissue, and excretion from the body. Thus the tion” in this case is determined in relative
temporal component often is very important rather than absolute physiologic units. A more
in nuclear medicine studies, and the timing rigorous approach for evaluating kidney func-
of the imaging relative to the administration tion is to measure glomerular filtration rates
of the radiopharmaceutical must be carefully (GFRs), in mLâ•›/min, using a tracer that is fil-
chosen such that the images reflect the bio- tered by the kidneys, such as 99mTc-labeled
logic process of interest. Furthermore, the diethylene triamine pentaacetic acid (DTPA).
rate of change of radiotracer concentration In this case, it is necessary to obtain serial
often provides direct information on the rate images of the kidneys and also to collect blood
of a specific biologic process. This chapter dis- samples to measure tracer concentration in
cusses how the temporal information that can the blood as a function of time. Using these
be obtained from nuclear medicine studies is data and applying an appropriate mathemati-
incorporated to provide quantitative mea- cal model, one can then calculate the GFR.
sures of physiologic parameters, biochemical Each of these approaches permits an
rates, or specific biologic events. Further assessment of “renal function” that is based
examples are provided in reference 1. on a different model for the behavior of the
kidneys. The approach of choice depends on
the medical or biologic information desired, as
A.  BASIC CONCEPTS well as on the equipment available and accept-
able level of technical complexity. Developing
Dynamic nuclear medicine studies enable a model requires the investigator to synthe-
the radiotracer concentration to be measured size a large amount of biologic information
as a function of time, as shown in Figure into a comprehensive description of the
20-10. With an understanding of the biologic process of interest. This chapter summarizes
fate of the radiotracer in the body, it is pos- some of the principles and techniques in
sible to construct mathematical models with developing these models and presents some
a set of one or more parameters that can be examples of tracer kinetic models currently
fit to explain the observed time-activity used in nuclear medicine.
curves. In some cases the model parameters The following example illustrates the prin-
can be related directly to physiologic or bio- ciple of tracer kinetic techniques. Figure 21-1
logic quantities. Examples include tissue shows a hollow tube with a substance flowing
perfusion (measured in mLâ•›/minâ•›/g) and the through it. If a small amount of tracer is
rate of glucose use (measured in mol/min/g). injected instantaneously at time t and at
The mathematical models that describe the point A and the measured activity at point B
time-varying distribution of radiopharma- is plotted as a function of time, the resultant
ceuticals in the body are known as tracer time-activity curve represents a histogram of
kinetic models. the transit times for the tracer molecules
379
380 Physics in Nuclear Medicine

A B

Flow

Activity

Activity
t Time t Time
FIGURE 21-1  Illustration of use of tracer kinetics for measurement of flow. The system consists of a hollow tube
characterized by flow in the direction indicated. A bolus of tracer introduced at time t and point A produces a time-
activity curve at location B that depends on flow. Relatively higher flow (solid line) results in less dispersion and a
shorter average transit time, whereas a lower flow rate (dashed line) produces a longer average transit time. (Adapted
from Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission Tomography and Autoradiography: Principles and
Applications for the Brain and Heart. New York, 1986, Raven Press.)

from point A to point B. If the flow rate radiotracers or radiopharmaceuticals. For


through the tube is decreased (dashed curve simplicity, we refer to them as tracers in the
in Fig. 21-1), then the tracer molecules will remainder of this discussion. Tracers can be
on average take longer to get from point A to naturally occurring substances, analogs of
point B and the shape of the measured time- natural substances (i.e., substances that
activity curve will change accordingly. This mimic the natural substance), or compounds
simple example illustrates conceptually how that interact with specific physiologic or bio-
the kinetic information (i.e., the time-activity chemical processes in the body. Examples
curve) varies in response to a change in a include diffusible tracers for blood flow,
parameter in the system (flow rate). The flow tracers that follow important metabolic path-
rate, F, through the tube can be calculated as ways in cells, and tracers that bind to specific
receptors on cell surfaces. Table 21-1 lists
F (mL / min) = V (mL) /τ (min) (21-1) some examples of tracers that are used in
nuclear medicine and their applications.
where V is the volume of the tube and τ is the Some specific requirements for an ideal
mean transit time of the tracer molecules tracer include the following:
between points A and B. This is known as the 1. The behavior of the tracer should be
central volume principle. identical or related in a known and pre-
dictable manner to that of the natural
substance.
B.  TRACERS AND COMPARTMENTS 2. The mass of tracer used should not alter 
the underlying physiologic process being
Most applications of tracer kinetic principles studied or should be small compared
in nuclear medicine are based on compart- with the mass of endogenous compound
mental models. In this section, we review the being traced (a typical “rule of thumb”
basic principles of compartmental modeling. is that the mass of tracer should be <1%
of the endogenous compound).
1.  Definition of a Tracer 3. The specific activity of the tracer 
A tracer is a substance that follows (“traces”)  should be sufficiently high to permit
a physiologic or biochemical process. In this imaging and blood or plasma activity
chapter, tracers are assumed to be radio� assays without violating the first two
nuclides or, more commonly, small molecules requirements.
or larger biomolecules (e.g., antibodies and 4. Any isotope effect (see Chapter 3, Section
peptides) that are labeled with radionuclides. B) should be negligible or at least quan-
These labeled molecules are also known as titatively predictable.
21  •  Tracer Kinetic Modeling 381

TABLE 21-1â•…
SELECTED EXAMPLES OF TRACERS USED IN NUCLEAR MEDICINE

Process Tracer
Blood flow/perfusion:
  Diffusible (not trapped) H215O, 133
Xe, 99m
Tc-teboroxime (heart)
201 99m
  Diffusible (trapped) TlCl (heart), Tc-sestamibi (heart),
13 82 99m
NH3 (heart), RbCl, Tc-ECD (brain),
99m
Tc-tetrofosmin (heart), 62Cu-PTSM, 99m
Tc-HMPAO (brain)
99m
  Nondiffusible (trapped) Tc-macroaggragated albumin (lung)
11
Blood volume CO, 51Cr-RBC, 99m
Tc-RBC
99m 99m
Ventricular function Tc-pertechnetate, Tc-DTPA
99m
Esophageal transit time/reflux Tc-sulphur colloid
99m 111
Gastric emptying Tc-sulphur colloid, In-DTPA
99m 99m
Gallbladder dynamics Tc-disofenin, Tc-mebrofenin
111
Infection In-WBC, 67Ga-citrate, 99m
Tc-WBC
133 81 99m
Lung ventilation Xe, Kr, Tc-technegas™
Metabolism:
15
  Oxygen O2
11
  Oxidative C-acetate
18
  Glucose F-fluorodeoxyglucose
11 123
  Free fatty acids C-palmitic acid, I-hexadecanoic acid
99m 18 –
  Osteoblastic activity Tc-MDP, F
18
Hypoxia F-fluoromisonidazole, 62Cu-ATSM
18
Proliferation F-fluorothymidine
11
Protein synthesis C-leucine, 11C-methionine
Receptor systems:
18
  Dopaminergic F-fluoro-L-dopa, 11C-raclopride, 18
F-fluoroethylspiperone, 11C-CFT
18
  Benzodiazepine F-flumazenil
11
  Opiate C-carfentanil
11
  Serotonergic C-altanserin
123
  Adrenergic I-mIBG
111
  Somatostatin In-octreotide
18
  Estrogen F-fluoroestradiol
ATSM, diacetyl-bis (N4-methylthiosemicarbazone); CFT, [N-methyl-11C]-2-β-carbomethoxy-3-β-(4-fluorophenyl)-tropane;
DOPA, 3,4-dihydroxyphenylalanine; DTPA, diethylenetriamine penta-acetic acid; ECD, ethyl cysteinate dimer; HMPAO,
hexamethyl propylene amine oxime; MDP, methylene diphosphonate; mIBG, metaiodobenzylguanidine; PTSM,
pyruvaldehyde bis(N4-methylthiosemithiocarbazone); RBC, red blood cell; WBC, white blood cell.

If a tracer is labeled with an element not investigation. One common use of tracers in
originally present in the compound (this is clinical nuclear medicine is to examine gross
often the case with radionuclides such as 99mTc, function and distribution, including blood flow,
123
I, and 18F), it should behave similarly to the filtration, and ventilation. Although the ele-
natural substance or in a way that differs  ments represented by radionuclides such as
99m
in a known manner. The strictness of this Tc, 67Ga, 111In, and 123I are not normally
requirement depends on the process under present in biologic molecules, it is possible to
382 Physics in Nuclear Medicine

incorporate these radionuclides in physiologi-


cally relevant tracers that can measure simple 2.  Definition of a Compartment
parameters that are related to distribution, A compartment is a volume or space within
transport, and excretion. which the tracer rapidly becomes uniformly
However, these same elements are not nor- distributed; that is, it contains no significant
mally present in human biochemistry (iodine concentration gradients. In some cases, a
is an exception when used to study thyroid compartment has an obvious physical inter-
metabolism). It is therefore much more diffi- pretation, such as the intravascular blood
cult to mimic a biochemical reaction sequence pool, reactants and products in a chemical
with these radionuclides. The biochemical reaction, substances that are separated by
systems of the body are more specific than the membranes, and so forth. For other compart-
transport processes that move or filter fluids ments, the physical interpretation may be
or gases. Biochemical systems can selectively less obvious, such as a tracer that may be
require that compounds be of one optical metabolized or trapped by one of two differ-
polarity versus the other; that compounds fit ent cell populations in an organ, thus defin-
within angstroms in the cleft of an enzyme; ing the two populations of cells as separate
that chemical bond angles, lengths, and compartments. Additionally, although the
strengths are appropriate; and so forth. When definition of a particular compartment may
a compound is labeled with a foreign species, be appropriate for one tracer [e.g., the distri-
such as 99mTc, one cannot be sure that it will bution of labeled red blood cells (RBCs) in
retain its natural properties and a careful the intravascular blood pool], it might not
examination and characterization of the com- apply for a different tracer (e.g., the dis�
pound must be undertaken. One of the advan- tribution of thallium or rubidium, which 
tages of radionuclides that represent elements has both an intravascular and an extra�
normally involved in biochemical processes, vascular distribution). Thus the number,
such as 11C, 13N, and 15O, is that they gener- inter�relationship, organization, and defini-
ally do not alter the behavior of the labeled tion of compartments in a compartmental
compound. model must be developed from knowledge of
Analog tracers are compounds that possess physiologic and biochemical principles.
many of the properties of natural compounds
but with differences that change the way the
analog interacts with biologic systems. In 3.  Distribution Volume and  
many cases, analog tracers are deliberately Partition Coefficient
created to simplify the analysis of a biologic A compartment may be closed or open to a
system. For example, analogs that participate tracer. A closed compartment is one from
through only a limited number of steps in a which the tracer cannot escape, whereas an
sequence of biologic reactions have been devel- open compartment is one from which it can
oped in biochemistry and pharmacology. escape to other compartments. Whether a
Analogs are used to decrease the number of compartment is closed or open depends on
variables that must be measured, to increase both the compartment and the tracer. Indeed,
the specificity and accuracy of the measure- a compartment may be open to one tracer and
ment, or to selectively investigate a particular closed to another. If a tracer is injected into a
step in a biochemical sequence. In other cases closed compartment, such as a nondiffusible
analog tracers are used because of the need to tracer in the vascular system, conservation of
label the tracer with an element that is not mass requires that after the distribution of
normally present in the molecule of interest. the tracer reaches equilibrium or steady-state
As discussed earlier, this can lead to very sig- conditions, the amount of tracer injected, A
nificant deviations in the biologic properties (in becquerels or other units of activity), must
(particularly in small molecules) compared equal the concentration of the tracer in the
with the natural compound. Correction factors compartment, C (in Bq/mL), multiplied by the
based on the principles of competitive sub- distribution volume, Vd, of the compartment.
strate or enzyme kinetics are employed in Thus,
studies using analog tracers to account for dif-
ferences between the analog and the natural Vd = A /C (at equilibrium ) (21-2)
compound. A well-known and widely used
example of an analog tracer in nuclear medi- This equation is the basis for the dilution
cine is 2-deoxy-2[18F]fluoro-D-glucose (FDG) to principle, which provides a convenient method
measure glucose metabolism (see Section E.5). for determining the distribution volume of a
21  •  Tracer Kinetic Modeling 383

closed compartment, as shown by the follow-


ing example.
EXAMPLE 21-1
Tissue Ct
What is the distribution volume of the RBCs
if 1╯MBq 51Cr-labeled RBCs is injected into
the blood stream and an aliquot of blood taken
after an equilibration period (10 minutes)
contains 0.2 kBq/mL? Assume the hematocrit, Blood Cb
H (fraction of the total blood volume occupied λ  Ct /C b
by RBCs), is 0.4. A

Answer
From Equation 21-2:
Vd = (1000 kBq) / (0.2 kBq/mL)

= 5000 mL Tissue
Vt
This result gives the total distribution volume, Cb V1
that is, total blood volume. The RBC volume
is given by Cb
Blood
VRBC = H × Vd
B λ  V1/Vt
= 0.4 × 5000 mL
= 2000 mL FIGURE 21-2  A, Partition coefficient, λ, for tracers that
can diffuse or be transported into tissue from blood. The
value of λ is given by the ratio of tissue-to-blood concen-
More commonly, a compartment will be trations of the tracer when it has reached an equilibrium
open; that is, the tracer will be able to escape or steady-state condition. B, Partition coefficient also
from it. This applies, for example, to tracers equals the ratio of the apparent distribution volume in
that are distributed and exchanged between tissue, V1, assuming the same tracer concentration as
blood-to-tissue volume (or mass), to Vt. (From Phelps ME,
blood and tissue. In this case, after the tracer Mazziotta JC, Schelbert HR: Positron Emission Tomog-
reaches its equilibrium distribution,* the con- raphy and Autoradiography: Principles and Applications
centration in blood will typically be different for the Brain and Heart. New York, 1986, Raven Press.)
from that in the tissue (Fig. 21-2A). The ratio
of tissue concentration Ct (Bq/g) to blood con-
centration Cb (Bq/mL) at equilibrium, is called mass) of tissue; therefore combining these
the partition coefficient, λ, defined by relationships and Equation 21-3 yields

λ(mL / g) = Ct (Bq/g) /Cb (Bq/mL) (21-3) λ = V1 /Vt (21-4)

The equilibrium blood concentration, Cb, can Thus another interpretation of the partition
be directly measured by taking blood samples. coefficient is that it is the distribution volume
If one assumes that the concentration of per unit mass of tissue for a diffusible sub-
tracer in tissue is the same as the concentra- stance or tracer. This interpretation is
tion in blood (Fig. 21-2B), and applies Equa- employed in some models for estimating blood
tion 21-2, this leads to an apparent distribution flow and perfusion, as discussed in Section E.
volume in tissue given by V1 = Atâ•›/Cb, in which
At is the activity in the tissue. One also knows 4.  Flux
that At = Ct × Vt, in which Vt is the volume (or Flux refers to the amount of substance that
crosses a boundary or surface per unit time
(e.g., mgâ•›/min or molâ•›/â•›min) (Fig. 21-3). It also
can refer to the transport of a substance
*Note that “equilibrium” in this case means that the between different compartments in terms of
concentration of the tracer in the compartments has flux per unit volume or mass of tissue (e.g.,
reached a constant value with time. It does not imply molâ•›/minâ•›/mL or mgâ•›/minâ•›/g).
equilibrium in the thermodynamic sense, that is, that
there is no further transport of tracer between tissue and Flux is a general term that can refer to a
blood. Thus tracer equilibrium is synonymous with the variety of processes. For example, the total
term steady state (see Section B.6). mass of RBCs moving through a blood vessel
384 Physics in Nuclear Medicine

Capillary
membrane
Blood “Free” tracer “Product” in FIGURE 21-3  Three-compartment system consist-
in tissue tissue ing of reactants in blood (Rb) and tissue (Rt) and
product in tissue (P). Fluxes between the compart-
ments, indicated by arrows, are products of the first-
k1  [Rb] k3  [Rt] order rate constants and the respective compartmental
Rb Rt concentrations. (Adapted from Phelps ME, Mazziotta
P
JC, Schelbert HR: Positron Emission Tomography
k2  [Rt] k4  [P] and Autoradiography: Principles and Applications for
the Brain and Heart. New York, 1986, Raven Press.)

per unit time is a flux. The “boundary” or the half-time of turnover, t1/2, that is, the time
“surface” in this case could be any transverse required for the original amount of tracer in
plane through the vessel. The amount of the compartment to decrease by 50% (assum-
glucose moving across a cell membrane per ing no back transfer into the compartment),
unit time also is a flux. Fluxes therefore may is given by
either be closely related or unrelated to blood
flow.
t1 / 2 = 0.693 /k (21-6)
5.  Rate Constants
Rate constants describe the relationships Thus the fractional rate constant k is anal-
between the concentrations and fluxes of a ogous to the decay constant λ for radioactive
substance between two compartments. For decay, whereas the mean transit time is anal-
simple first-order processes, the rate constant, ogous to the average lifetime of a radionuclide
k, multiplied by the amount (or concentra- (see Chapter 4, Section B.3). In first-order
tion) of a substance in a compartment deter- models, transport out of a compartment
mines the flux: through a single pathway (without back-
transport) is described by a single exponential
flux = k × amount of substance in compartment function, e–kt, analogous to the radioactive
(21-5) decay factor e–λ t.
If there is more than one potential pathway
For first-order processes, the units of k are for a tracer to leave a compartment, each
(time)–1. If “amount” refers to the mass of characterized by a separate rate constant, ki,
tracer in the compartment, the units of flux then the turnover time of the tracer in the
are mass/time (e.g., mg/min). If “amount” compartment is the inverse of the sum of all
refers to con�centration of tracer in the com- these rate constants and the half-time of
partment, the units of flux are mass/time per turnover is
unit of compartment volume (e.g., mg/min/
mL), or mass/time per unit of compartment t1 / 2 = 0.693 / (k1 + k2 + … + km ) (21-7)
mass (e.g., mg/min/g). Note that, as illus-
trated by Figure 21-3, different directions of where m is the number of pathways by which
transport between two compartments can be the tracer can leave the compartment.
characterized by different rate constants. Most compartment models used in nuclear
A first-order rate constant also may repre- medicine are based on the assumption that
sent the fractional rate of transport of a sub- first-order kinetics describe the dynamics of
stance from a compartment per unit time. For the system of interest. The tracer kinetics of
example, a rate constant of 0.1╯min–1 corre- such systems are linear. That is, doubling the
sponds to a transport of 10% of the substance input (amount or concentration) doubles the
from the compartment per minute. The output (flux) of the system. As shown in
inverse of the rate constant, 1/k, is sometimes Section E, linear first-order tracer kinetic
referred to as the turnover time, or mean models adequately describe many systems
transit time, τ, of the tracer in the compart- even when the dynamics of the natural sub-
ment (in this example, 10 minutes). Similarly, stances are nonlinear.
21  •  Tracer Kinetic Modeling 385

A more general expression for the relation- back into blood without undergoing any bio-
ship among rate constants, fluxes, and con- chemical reactions. This is a common occur-
centrations (or masses) is rence in actual biochemical systems and
introduces a reserve capacity into the system
flux = k × (mass or concentration of substance) n that can accommodate changes in metabolic
(21-8) supply and demand (e.g., by changing k3).
Figure 21-4 illustrates the relationship
where n refers to the order of the reaction. between first-order rate constants and the
The units of rate constants for nth order reac- relative concentrations of the substrates in a
tions (in terms of concentration) are biochemical sequence. If a substrate (S) and
[concentrations(1—n) • time–1]. Thus only first- enzyme (E) combine to form a substrate-
order rate constants represent a constant enzyme complex (SE), which then dissociates
fractional turnover and Equations 21-6 and into a product (P) with release of the enzyme,
21-7 apply only to first-order processes. the fluxes of the first-order reaction steps are
Figure 21-3 illustrates a three-compartment concentrations multiplied by the correspond-
system consisting of a blood compartment ing rate constants. If a small amount of
separated by a membrane barrier (e.g., capil- labeled substrate is introduced into the
lary wall) from two sequential tissue com- system at time zero, the tracer will go through 
partments. R and P refer to chemical reactant the reaction steps, producing concentrations
and product, whereas the subscripts b and t of labeled S, SE, and P as shown in the graphs
refer to reactant in blood and tissue compart- in Figure 21-4. If k3 (the forward rate con-
ments, respectively. [Rb],* [Rt], and [P] are the stant for the reaction converting SE to E and
blood and tissue concentrations of reactant P) is reduced by 50% with all the other rate
and product, whereas the fluxes between the constants remaining unchanged, the concen-
compartments are the first-order rate con- trations of labeled S, SE, and P are then rep-
stants, k1, k2, k3, and k4, multiplied by corre- resented by the dotted orange lines in Figure
sponding concentrations. The thicknesses of 21-4. Decreasing k3 causes a slower produc-
the arrows in Figure 21-3 are proportional to tion of P and causes a compensatory increase
the magnitude of the corresponding rate con- in labeled S and SE.
stant. In this example, the rate constants into
and out of tissue are larger than the corre- 6.  Steady State
sponding rate constants between the reactant The term steady state refers to a condition
and product compartments in tissue. Thus in which a process, parameter, or variable is 
the majority of the reactant initially trans- not changing with time. For example, a flux
ported into the tissue space is transported through a biochemical pathway is said to be in
a steady state when the concentration of reac-
tants and products are not changing with time.
*The notation [X] is used to denote the concentration In all tracer kinetic models, it is assumed that
(usually in units of g/mL or mol/mL) of substance X. the underlying process that is being measured

k0 k1 k3 k5
k2 k4

[S] [SE] [P]


Concentration

Time (t) t t
FIGURE 21-4  Illustration of tracer kinetics of a chemical reaction sequence. First-order rate constants (k0, k1, k2, k3,
k4, k5) characterize the various reaction steps, whereas S refers to substrate, E refers to enzyme, P is product, and SE
is the substrate-enzyme complex. The time-activity relationships for concentrations of labeled S, SE, and P are shown
for a particular value of k3 (solid purple line) and with k3 reduced by 50% (dotted orange line). (From Phelps ME,
Mazziotta JC, Schelbert HR: Positron Emission Tomography and Autoradiography: Principles and Applications for the
Brain and Heart. New York, 1986, Raven Press.)
386 Physics in Nuclear Medicine

by the tracer is in a steady state. Because of D


biorhythms, steady states almost never exist
fD
in the body; however, if the magnitude or tem-
poral period of change is small compared with A B C
the process being measured, then the steady-
state assumption is reasonable. In many cases, fE
the experimental sampling rate is slow com- E
pared with the biorhythm (e.g., blood sam- FIGURE 21-5  Example of a multistep reaction sequence
pling rate vs. pulsatile nature of blood flow) that branches into two pathways. The terms fD and fE are
and it is not perceived in the measured data. the branching fractions for the corresponding pathways
In these cases, the measured parameters rep- ( fD + fE = 1).
resent average values of the function mea-
sured. However, if the experimental sampling
rate is fast compared with the biorhythm, sig- where
nificant errors can be introduced in the model
calculations. In this case, the calculated fD + fE = 1 (21-12)
parameters typically do not represent a simple
average of the non-steady-state values.
Steady state of a process should not be con-
fused with steady state of the tracer. Measure- C.  TRACER DELIVERY AND
ments of the tracer commonly are made when TRANSPORT
the tracer itself is not in steady state but
rather while it is distributing through the A tracer that is injected into the body must
process under study. Some tracer kinetic follow several steps in sequence before it can
models are used in which measurements are enter a biochemical pathway: delivery to the
made when both the tracer and process studied capillary via blood flow, extraction across the
are in a steady state. These methods usually capillary wall into the tissue space, and
are referred to as “equilibrium” models. finally, incorporation into a biochemical reac-
An important and useful property of a tion sequence. Although only one of the steps
steady-state condition is that the rates (fluxes) in a process may be of interest in a particular
of all steps in a nonbranching transport or application, it may be influenced by other
reaction sequence are equal. Thus if a tracer steps in the process of tracer delivery. In this
technique is used to measure one step in a section we examine tracer techniques for
sequence, the rate for each step in the entire describing these processes.
sequence can be determined. If the reaction
branches into two or more separate pathways
then the sum of each pathway must equal the 1.  Blood Flow, Extraction, and
rate of the preceding step. In this case, if one Clearance
determines the rate of any of the preceding Blood flow through vessels is described in
steps and also knows the branching fractions, units of volume per unit time (usually in units
then the rate of each branch can be deter- of mLâ•›/min). For regional tissue measure-
mined by multiplying the rate of the preced- ments it is blood flow per mass of tissue that
ing step by the branching fraction. For is determined (mLâ•›/minâ•›/g). Blood flow per
example, if the reaction sequence in Figure mass of tissue is more properly referred to as
21-5 is in a steady state and the rate of disap- perfusion; however, in the literature the term
pearance of A is RA, the rates of formation of blood flow is used to indicate both blood flow
B, C, D, and E are RB, RC, RD, and RE, respec- and blood flow per mass of tissue. In both
tively, and fd and fe are the branching fraction cases the basic phenomenon is still blood flow.
down the corresponding pathways, then Thus relationships involving blood flow apply
equally to blood flow and perfusion, provided
RA = RB = RC = ( RD + RE ) (21-9) that care is taken to ensure that the units are
consistent. For example, in the relationship
and between blood flow and blood volume (see
Section E.4), if blood flow is in units of
RD = fD × RC (21-10) mLâ•›/â•›min, then blood volume must be in units
of mL. If blood flow is in units of mLâ•›/minâ•›/g,
then blood volume must be in units of volume
RE = fE × RC (21-11) per mass of tissue (mLâ•›/g). In this text, the
21  •  Tracer Kinetic Modeling 387

term blood flow, symbolized by F, is used to extraction are useful for studying the trans-
denote either blood flow or blood flow per port properties of substrates and drugs.
mass of tissue. The units indicate which An important concept relating the pro-
quantity is being discussed. cesses of blood flow, flux, and extraction is
In addition to its dependence on blood the Fick principle. This principle is based on
flow, the uptake of a tracer by tissue depends the conservation of mass and states that,
on tissue extraction and clearance. Extrac- under steady-state conditions, the net uptake
tion is defined in two different contexts: net of a tracer (or other substance) is simply the
and unidirectional. Net extraction refers to difference between the input to and output
the difference in steady-state tracer concen- from the organ or tissue. If the input (arte-
trations between the input and output blood rial) concentration of the tracer is CA (mg/
flow of an organ. If the input (arterial) con- mL) and the output (venous) concentration is
centration is CA, and the output (venous) CV (mgâ•›/mL), and the blood flow to the organ
concentration is CV, the net extraction frac- is F (mLâ•›/min), then the net uptake rate, U
tion, En, is defined as (mg/min), is given by

En = (CA − CV ) /CA (21-13) U = F × (CA − CV ) (21-14)

If there is no metabolism of the tracer, that As an example, if the arterial and venous
is, if all the tracer delivered to the tissue concentrations of oxygen and the blood flow
eventually is returned to the blood, the net to an organ are measured, Equation 21-14
extraction is zero. This situation applies, for can be used to determine the oxygen utiliza-
example, to inert diffusible blood flow tracers tion rate for that organ. If blood flow F in
when steady-state conditions for the tracer Equation 21-14 is replaced by blood flow per
are reached. mass of tissue (perfusion), then the uptake or
Unidirectional extraction refers to the utilization is given in units of utilization per
amount of tracer extracted only from blood to mass of tissue (mg/min/g).
tissue. It does not include the amount trans- The Fick principle can be employed only
ferred back from tissue to blood. Thus the under steady-state conditions. An alternative
unidirectional extraction fraction, Eu, gener- approach that is applicable to non–steady-
ally is larger than the net extraction fraction. state conditions is the Kety-Schmidt method,
An exception to this general rule occurs with which is discussed in Section E.4.
O2. Virtually all oxygen extracted by tissue is The extraction of tracers generally occurs
metabolized; thus the net and unidirectional across membranes or through the fenestra-
extraction fractions are the same. For essen- tions* found in capillaries. The extraction
tially all other substances, a major portion of fraction of a tracer depends on the capillary
what is extracted by the tissue is transported surface area, S, the capillary permeability for
back to blood. This is the situation repre- the tracer, P, and blood flow through the capil-
sented by the bidirectional transport in the laries, F. A simple model relating these quan-
model shown in Figure 21-3. tities was developed by Renkin2 and Crone.3
Extraction fractions are expressed as frac- Figure 21-6 illustrates an idealized capillary
tions or as percentages and can be measured
using tracer kinetic techniques. To determine
net extraction, it is necessary to measure the
input and output concentrations of the tracer
in the blood under steady-state conditions, F F
that is, after the concentrations have reached
constant values. The route of administration
of the tracer is unimporÂ�tant in this case. For P×S
example, the tracer can be administered by
FIGURE 21-6  Renkin-Crone capillary model. The capil-
constant infusion or as a bolus into a periph- lary is assumed to be a rigid tube, and extraction from
eral vein. blood to tissue is characterized by the product of the
Unidirectional extraction can be measured permeability, P, and surface area, S. Blood flow through
by observing the rate of uptake by the tissue the capillary is F.
or organ immediately after injection of 
the tracer, that is, when the blood concentra-
tion is maximum and the tissue concentration *Fenestrations are small gaps found between the junc-
is zero. Measurements of unidirectional tions of cells in the capillary wall.
388 Physics in Nuclear Medicine

(i.e., rigid tube) through which is passing a wall, P × S, or decreasing the blood flow
tracer with flow F. It is assumed that the through the capillary. For a given value of P
concentration of tracer across the cross- × S, the greater the flow, F, the shorter the
section of the capillary at any point along its residence time of the tracer in the capillary,
length is constant and that the extraction of and, thus, the less the chance that the tracer
tracer from the capillary to the tissue at any will escape through the capillary wall. This is
point is proportional to the concentration of illustrated graphically in Figure 21-7.
the tracer in the blood. It is further assumed On the other hand, the amount of material
that extraction is unidirectional; that is, there entering the tissue depends on the product of
is no back-transfer of the tracer from tissue blood flow times extraction fraction, F × E.
to blood. This product is sometimes referred to as
For this simple model, it can be shown that clearance and has the same units as flow (i.e.,
the unidirectional extraction fraction Eu for mLâ•›/min or mLâ•›/minâ•›/g). In essence, it repre-
the capillary is given by sents “virtual flow” from the capillary into the
tissue. Typically the increased amount of
Eu = 1 − e− ( P × S/F ) (21-15) tracer that is delivered to the capillary with
increasing blood flow more than offsets the
Thus the extraction fraction depends only  decrease in the extraction fraction, with the
on the permeability-surface area product, P × net result that clearance increases with flow.
S (mLâ•›/min), and on flow, F. This equation also This is illustrated graphically in Figure 21-8.
can be stated in terms of perfusion, by replac- Note that for small values of P × S, that is,
ing blood flow with perfusion (mLâ•›/minâ•›/g) and low flow across the capillary membrane, clear-
the permeability-surface area product with P ance is low and reaches a plateau value for
× S for a capillary network per mass of tissue relatively low values of capillary blood flow,
(mLâ•›/minâ•›/g). F, whereas for large values of P × S, clearance
continues to increase with increasing flow
EXAMPLE 21-2 through the capillaries. This indicates that
What is the unidirectional extraction fraction the clearance or deposition of a tracer into
for the diffusible tracer 13NH3 in the brain if tissue will have a high or low dependence on
P × S = 0.25╯mLâ•›/minâ•›/g and blood flow to the blood flow, depending on whether it has a
brain (perfusion) is 0.50╯mLâ•›/minâ•›/g? high or low value of P × S.
Clearance of tracers from tissue to blood
Answer also is used in tracer kinetic modeling. The
From Equation 21-15: most common use of tissue-to-blood clearance
is in the measurement of bidirectional trans-
Eu = 1 − e− (0.25 / 0.50) = 0.39 port and blood flow.

The Renkin-Crone model is not completely


realistic, because it assumes no back-transfer
of tracer from tissue to blood, that the 1.0
permeability-surface area product, P × S,
does not depend on blood flow, and that the
Unidirectional extraction

capillary is a rigid tube. Nevertheless, it is


instructive for illustrating the relationships
between extraction fraction, blood flow, and
the permeability-surface area product.
The ratio [(P × S)/F ] sometimes is referred
to as the extraction coefficient. One interpre-
tation of the product, P × S, is that it repre-
sents the flow of the tracer from blood to
tissue through the capillary wall, whereas F
represents flow through the capillary itself. 0.0
These two “flows” represent competing pro- Flow
cesses for removal of the tracer from the capil-
FIGURE 21-7  Unidirectional extraction fraction versus
lary. Thus the fraction of a substance that is flow for the Renkin-Crone model. The extraction fraction
extracted by tissue can be increased either by is 1 when flow is near zero and decreases toward zero as
increasing the flow through the capillary flow increases.
21  •  Tracer Kinetic Modeling 389

2.0
P × S  5.0

1.6

Clearance (E × F )
1.2 P × S  2.0

0.8 P × S  1.0

0.4 P × S  0.5

P × S  0.2

0.0
0.4 0.8 1.2 1.6 2.0 2.4 2.8
Flow (mL/min/g)
FIGURE 21-8  Clearance (flow × unidirectional extraction fraction) versus flow for various values of the permeability-
surface area product, P × S, for the Renkin-Crone model (solid red lines, Equation 21-15) and for a compartmental
model description (dashed red lines, Equation 21-20). P × S is in units of mLâ•›/minâ•›/g. The solid blue line corresponds
to the situation where E=1. (From Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission Tomography and Auto-
radiography: Principles and Applications for the Brain and Heart. New York, 1986, Raven Press.)

2.  Transport diffusion constant, D. Membrane permeabil-


Three different mechanisms exist for the ity is related to the diffusion constant by
transport of substances across a membrane or
capillary wall. Active transport mechanisms P (cm/min) = D (cm 2 /min) /x (cm) (21-16)
require energy and can move substances
against concentration gradients. Usually the where x is the thickness of the membrane or
energy source is adenosine triphosphate. the diffusion path length. One usually deals
Examples of active transport are the sodium- with the P × S product rather than P itself
potassium “pump” that maintains the differ- because in most applications the regional cap-
ence between intracellular and extracellular illary surface area S is not known accurately.
concentrations of these ions and the renal The larger the value of D (or P × S), the more
tubular reabsorption of glucose. rapid the passive diffusion process and the
Passive transport mechanisms do not greater the clearance of the substance from
require energy and move substances in the blood to tissue or from tissue to blood (Fig.
same direction as the concentration gradient. 21-8). Many substances and in vivo processes
The passive mechanisms include carrier- depend on passive diffusion mechanisms,
mediated diffusion, such as glucose and amino such as water, oxygen, ammonia, and carbon
acid transport from blood to brain, and passive dioxide.
diffusion, which depends only on the exis- Carrier-mediated diffusion is somewhat
tence of a concentration gradient, such as the more complicated. It also transports sub-
diffusion of 99mTc-pertechnetate from blood to stances in the same direction of a concentra-
brain through a disrupted blood-brain barrier. tion gradient and is characterized by the
Bulk flow across fenestrations in capillaries following reaction process:
also accounts for a fraction of passive trans- k1 k3
port but varies from tissue to tissue; for 
S+C←  → SC ←
  → C + S (21-17)

k 2 k 4
example, it is insignificant in the brain when
the blood-brain barrier is intact, but it is a where S is the substrate and C is the carrier
major source of capillary/tissue transport in molecule. SC is a carrier/substrate complex
the heart. that physically moves across the membrane
Simple passive diffusion for a given mem- and then dissociates into C and S, and k1, k2,
brane and molecule is characterized by a k3, and k4 are first-order rate constants that
390 Physics in Nuclear Medicine

characterize the respective steps of the Typically, compartment A would represent


process. Because only a finite number of the vascular compartment and compartment
carrier molecules are available, this type of B might represent the amount of tracer
transport process can be saturated. The rate present in the tissue. The parameters k1 and
of the process increases as the substrate con- k2 can be estimated numerically with a tech-
centration S increases, but only to the point nique known as regression analysis. The input
of saturating the number of available carrier function CA(t) is directly measured from blood
sites. Generally, the carrier C is a protein samples or images of the blood (typically the
enzyme that is neither created nor destroyed left ventricular blood pool is chosen because
in the reaction but only enhances its rate.  of its large size), and the time course of activ-
The kinetics of carrier-mediated diffusion are ity in tissue CB(t) is determined from a time
described further in Section E.5. sequence of nuclear medicine images (see Fig.
20-10) or other counting measurements. A
detailed discussion of regression analysis and
D.  FORMULATION OF A other numerical methods related to tracer
COMPARTMENTAL MODEL kinetic models is beyond the scope of this
chapter, and the interested reader is referred
Most models commonly in use in nuclear med- to reference 1 for further details (see also
icine are compartmental models with first- Chapter 9, Section E.4).
order rate constants describing the flux of The simple compartmental model illus-
material between compartments. Consider trated in Figure 21-10 also can be used to
the simple two-compartment model illus- describe the relationship between extraction
trated in Figure 21-9. If a tracer is present in and blood flow discussed in Section C.1 in
compartment A with concentration defined by reference to the Renkin-Crone model (Equa-
CA(t) (e.g., a tracer administered as a bolus tion 21-15). In the compartmental model, the
injection so that the concentration in A is time vascular space in the capillary is assumed to
dependent), then the rate of change in concen- be a compartment of uniform concentration.
tration of compartment B [i.e., dCB(t)/dt] is The extraction and venous blood flow compete
described by through the common vascular pool for removal
of tracers. According to this compartmental
dCB (t) /dt = flux into B − flux out of B (21-18) model, the extraction E is related to flow F
and the P × S product as:
Because first-order kinetics apply, the flux
into B is simply k1CA(t) and the flux out of B E = ( P × S) / [( P × S) + F ] (21-20)
is k2CB(t); therefore
Tissue extraction as a function of blood flow
dCB (t) /dt = k1 CA (t) − k2 CB (t) (21-19) for this compartmental model is illustrated by
the dashed red lines in Figure 21-8. The
This first-order ordinary differential equa- amount of extraction predicted with the com-
tion with constant coefficients is a typical, partmental model is lower than that predicted
although simple, example of the equations with the Renkin-Crone model for a given P ×
necessary to mathematically define a tracer S value. In addition, the change in extraction
kinetic model. The time course of the tracer with blood flow is somewhat different. In most
in the delivery compartment (usually the
blood) [CA(t)] is known as the input function,
whereas the rate constants k1 and k2 are Arterial Venous
model parameters. flow F Vascular flow F
space in
capillaries

Tissue
k1 extraction P × S

A B FIGURE 21-10  Compartmental model of capillary in


which tissue extraction is competing with the venous flow
k2 for the tracer that is delivered by the arterial blood flow.
(From Phelps ME, Mazziotta JC, Schelbert HR: Positron
Emission Tomography and Autoradiography: Principles
FIGURE 21-9  Transport between two compartments, A and Applications for the Brain and Heart. New York,
and B, is described by rate constants k1 and k2. 1986, Raven Press.)
21  •  Tracer Kinetic Modeling 391

modeling applications of interest in nuclear model (a three-compartment model with three


medicine, the Renkin-Crone model (Equation rate constants) illustrate how the shape of the
21-15) and the compartmental model (Equa- tissue response curve changes as the shape of
tion 21-20) of capillary extraction yield sub- the input function changes. In both cases, the
stantially equivalent results. kinetics of the tracer in tissue are identical,
In nuclear medicine studies, there gener- but the temporal response in tissue is influ-
ally are two sources of data that can serve as enced by the input function (e.g., changing the
input to a tracer kinetic model: the time rate of injection could produce this pattern).
course of the injected radiotracer in whole The parameters of the model (the rate con-
blood or plasma (the input function), and the stants) are unchanged in these two situations.
measured amount of activity in tissue (the If one did not measure the input function in
tissue response), usually obtained from ROI this example and measured only the tissue
analysis of a dynamic series of images. The response function, the different tissue response
ROI count values are equivalent to local functions might be interpreted incorrectly as
tissue concentrations of the tracer of interest a change in the rate of the physiologic or bio-
if appropriate corrections are made for atten- chemical process in the tissue.
uation and other causes of counting inaccu- The second example (bottom row of Figure
racy. Additionally, the devices used to measure 21-11), shows a four-compartment model
radioactivity in blood and tissue (e.g., a well representing a more-complicated biological
counter and a gamma camera) must be cali- process. This model produces a different tissue
brated so corrections can be made to account response when presented with the same input
for their differences in counting efficiencies. function as the first example.
Figure 21-11 illustrates the relationships Thus Figure 21-11 shows that the shape of
between input function and tissue response the tissue response is a function of both the
curves for two different models and two differ- input function and a characteristic of the
ent input functions. The curves for the first tissue “system” called the impulse response.

Input Function Tissue Response Tracer Kinetic Model


1.2
Count rate

0.8

0.4
k1
k3
0.0 1 2 3
1.2 k2
Count rate

0.8

0.4

0.0
1.2
k1
k3
2 3
Count rate

0.8
k2
1 k4
0.4 4
k5
0.0
0 20 40 60 80 100 0 20 40 60 80 100
Time (min) Time (min)
FIGURE 21-11  Input function and tissue response (sum of the tracer concentration in tissue) for two different models
and for two different shapes of input functions. Different input functions produce different tissue responses for a given
model configuration (top two rows), whereas the same input function produces different tissue responses for two dif-
ferent model configurations (bottom two rows). (From Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission
Tomography and Autoradiography: Principles and Applications for the Brain and Heart. New York, 1986, Raven Press.)
392 Physics in Nuclear Medicine

The impulse response of a linear system is the the radiotracer distribution are generated
system’s response when presented with an and an appropriate model is applied.
impulse as an input function. An impulse is in Once the RBCs have distributed uniformly
essence a function of infinitely short duration throughout the vascular system (i.e., equilib-
with an undefined magnitude at the origin and rium is reached), the gamma camera images
that has an integrated value of one if summed will reflect regional blood volume. If the dis-
over all time. It can be thought of as an “ideal- tribution of activity over the left ventricle is
ized bolus” input given instantaneously (i.e., plotted as a function of time by gating the
beyond zero time it has a zero value). In reality, acquisition to the electrocardiogram signal,
a practical “impulse” delivery of tracer to a changes in ventricular volume caused by
system has a duration shorter than the short- cardiac contractions can be seen (Fig. 21-12).
est vascular transit time through the organ. This permits calculation of the ventricular
In this case there is no significant clearance ejection fraction (EF) because the relative
of the tracer from the organ until after all the number of counts within the ventricle is pro-
tracer has been delivered. portional to the blood volume of the ventricle
(see Section B.3).
E.  EXAMPLES OF DYNAMIC IMAGING EXAMPLE 21-3
AND TRACER KINETIC MODELS 99m
Tc-labeled RBCs are injected intravenously
and the number of counts within the left ven-
In this section we show examples of the use tricle are plotted as a function of time (Fig.
of dynamic imaging and tracer kinetic models 21-12) after the labeled RBCs have equili-
that are relatively simple and instructive. In brated within the blood pool. Calculate the
research applications of nuclear medicine, a left ventricular EF using the data shown.
wide variety of more complex models are
employed that are beyond the scope of this Answer
text. In many cases, there is considerable The EF is defined as the difference between
debate over the exact formulation of these the end-diastolic volume (EDV) and the end-
complex models and the interpretation of the systolic volume (ESV) divided by EDV.
model parameters. Research in this area is of Therefore,
continued importance, particularly with the EF = (EDV − ESV ) /EDV
ongoing development of new radiotracers.
= (13 − 7) /13
1.  Cardiac Function and Ejection = 46%
Fraction
99m
Tc-labeled RBCs are used for dynamic
(first-pass) and equilibrium-gated studies of 2.  Blood Flow Models
the heart. If a bolus of 99mTc-labeled RBCs is Many tracer kinetic methods and models to
injected intravenously and their distribution measure blood flow exist. Virtually all such
through the thorax as a function of time is methods are included in one of three 
imaged dynamically with a gamma camera,
the images will show the flow of blood
through the venous system into the right
atrium and right ventricle, to the lungs, and
then to the left atrium, left ventricle, and out
through the aorta to the systemic circulation.
counts/frame

13
Abnormalities in this flow pattern (such as
Relative

those produced by structural defects in the 10


heart that cause intracardiac shunts) result 7
in an abnormal distribution of the bolus of
activity. For example, a ventricular septal EDV ESV
defect with shunting of blood from the right
to the left ventricle will result in an early 0
Time
appearance of the bolus of activity in the left
ventricle as some of the blood (and labeled FIGURE 21-12  Sinusoidal curve illustrating relative
counts per frame in a gated blood-pool image. The counts
RBCs) bypasses the lungs and travels directly measured at the peaks and troughs of the curve are
to the left ventricle. The amount of shunting proportional to end-diastolic volume (EDV) and end-
can be estimated if time-activity curves of systolic volume (ESV), respectively.
21  •  Tracer Kinetic Modeling 393

categories: trapping, clearance, and equilib- If labeled microspheres are injected into
rium techniques. These techniques can be the left atrium or ventricle, they are distrib-
implemented by administering compounds uted to individual organs in proportion to the
labeled with either gamma-emitting or blood flow to the organ. If the total activity of
positron-emitting isotopes and imaging their microspheres injected is At, blood flow to an
distribution with gamma cameras, single- organ can be calculated from
photon emission computed tomography
(SPECT), or positron emission tomography F (mL / min) = C.O.(mL / min) × ( A o /At )
(PET) scanners (see Table 21-1). All three (21-21)
techniques require measuring the concentra-
tion of tracer in arterial blood if quantitative where Ao is the activity of microspheres accu-
estimates of blood flow in units of mLâ•›/min or mulated in the organ (assuming 100% are
mLâ•›/minâ•›/g (perfusion) are desired. trapped) and C.O. is the cardiac output (mL
In trapping methods, tracers are used that of blood per minute). Ao is determined by
are distributed to organs in proportion to tissue sampling or from quantitative imaging
blood flow but that are then trapped, either measurements. Cardiac output must be mea-
physically in the circulation (e.g., trapping of sured independently as described later. Organ
macro�aggregated albumin labeled with 99mTc perfusion, that is, blood flow per gram of
in the pulmonary capillaries in lung perfusion tissue, is then given by
studies), or metabolically in tissue (e.g., 13NH3
and 99mTc-sestamibi). F (mL / min / g) = C.O. × [( A o /mo ) At ]
Clearance methods require injecting meta-
bolically inert labeled tracers that also are (21-22)
distributed in proportion to flow but that do
not remain trapped in the vascular or tissue where Ao╛╛/mo is the concentration of activity
spaces. The rate of washout, or clearance, of in the organ or the measured tissue sample.
these tracers depends on blood flow. Either If the labeled microspheres are not 100%
nondiffusible tracers that remain within the trapped, Ao will be reduced and Equations
vascular compartment or diffusible tracers 21-21 and 21-22 will lead to underestimations
that distribute in both the tissue and vascu- of flow or organ perfusion. This effect is illus-
lar compartments can be used. As discussed trated graphically in Figure 21-8 for tracers
later, with both classes of tracers, the math- with a P × S product below the value required
ematical approach to measuring blood flow is for 100% clearance over the blood flow range
similar. studied.
Equilibrium techniques require adminis- Frequently, cardiac output is difficult to
tering a continuous supply of a diffusible measure. In such cases, flow to a single organ
blood flow tracer, waiting until a tracer steady can be determined by a modification of the
state has been reached, and then imaging the method just described, known as the reference
distribution. This approach uses very short sample technique. In this technique, arterial
half-life radionuclides such as 15O (T1/2 = 122 blood is withdrawn at a rate S (mLâ•›/min) during
seconds) in which equilibrium is established the time when the microspheres are flowing to
by removal of the tracer from tissue by the the organ, and the total activity of the blood
rate of blood flow and the rate of radioactive sample withdrawn, As, is determined. Blood
decay. This method is not commonly used and flow to the organ then is calculated from
is not discussed further here.
F = S(mL / min) × ( A o /As ) (21-23)
3.  Blood Flow: Trapped Radiotracers
A simple trapping method for measuring where Ao is the activity of microspheres
blood flow employing nondiffusible tracers is trapped in the organ. Perfusion of blood into
the labeled microsphere technique. Micro- the organ is calculated from
spheres are spherical or irregularly shaped
small particles that are larger than capillar- F = S × [( A o /mo ) /As ] (21-24)
ies and embolize (become lodged in) the first
capillary bed they encounter. They remain Although the microsphere technique is con-
within the capillary system for a time that is ceptually simple, it requires injection of the
sufficiently long so that particle breakdown tracer into the left atrium (rather than intra-
and excretion are insignificant during the venously) to avoid extraction of particles 
measurement period. by the lungs. This technique also causes
394 Physics in Nuclear Medicine

microembolization of capillaries exposed to


EXAMPLE 21-5
the particles, blocking blood flow through
those capillaries. To minimize perturbation of Assume in the situation of Example 21-4 that
the system being studied, only a small number the cardiac output is unknown. After injecting
of microspheres are injected. An example of 500,000 microspheres into the left atrium,
the labeled microsphere technique is the use arterial blood is sampled at a rate of 10╯mL╛/
of labeled albumin (which dissolves with min. The average microsphere concentration
time) to determine lung perfusion or to detect in the whole brain is again 50 microspheres
right-to-left cardiac shunts. The microsphere per gram. Assume the microspheres are 100%
technique is used infrequently in humans but trapped in capillaries in one pass through the
is quite commonly used in research studies circulation (e.g., in 1 minute). A total of 1000
involving animals. microspheres are counted in the radial arte-
More commonly, diffusible tracers that do rial sample obtained in a 1-minute period.
not remain within the vascular space and What is the average brain blood flow per gram
that are trapped in tissue are used to trace of tissue?
and quantitate blood flow in human studies.
Indeed, all tracers injected into the vascular Answer
system initially behave as “blood flow tracers” From Equation 21-24:
to some degree, but not all tracers permit
convenient quantitation of blood flow inde- 10 (mL / min) × 50 (microspheres/g)
F=
pendent of other processes such as extraction, 1, 000 microspheres
metabolism, and so forth. A good diffusible = 0.50 mL / min
n/g
tracer used to estimate blood flow by the trap-
ping method must have high first-pass extrac-
tion into the tissue (Equation 21-15) so that
4.  Blood Flow:  
tissue uptake reflects blood flow. It must also
be rapidly trapped in tissue, minimizing the Clearance Techniques
amount of tracer that can be transported back Most clearance techniques for measuring
out of the tissue and into the blood. Examples blood flow are based on the central volume
of diffusible tracers that are trapped in tissue principle, which was defined in Equation
in proportion to blood flow include 99mTc- 21-1. In the case of blood flow in units of mLâ•›/
sestamibi, 13NH3, 62Cu-PTSM, 201TlCl, and min, V is in units of mL. For blood flow in
82
RbCl. Blood flow can be estimated using units of mLâ•›/minâ•›/g, V is in units of mLâ•›/g
Equation 21-24 as long as a reference arterial (volume per mass of tissue).
blood sample is available. For a nondiffusible tracer, that is, one that
stays within the vascular space, V is the blood
EXAMPLE 21-4 volume in mL or mLâ•›/g, depending upon the
Suppose that microspheres are labeled with a units of blood flow. The determination of F
radionuclide that permits quantitative mea- with a nondiffusible tracer requires the mea-
surement of concentrations in tissues (e.g., surement of both the transit time, τ, and V.
18
F measured by PET). For simplicity, assume Normally, with nondiffusible tracers only τ is
that these measurements can be related to measured, which thus provides a measure of
the actual number of microspheres present. F/V. Because F changes with both τ (τ
Calculate blood flow per gram of tissue (i.e., decreases as F increases) and V (V increases
perfusion) to the brain if 500,000 micro- as F increases), there is a nonlinear relation-
spheres are injected into the left atrium, and ship between F/V and τ, with the magnitude
the average concentration of microspheres of changes in τ being less than the magnitude
measured in the brain is 50 microspheres/g. of changes in F.
Assume the cardiac output is 5╯L╛/min. It is more common and easier to measure
blood flow with freely diffusible tracers. Freely
Answer diffusible tracers are those that have 100%
From Equation 21-22, blood flow per gram of extraction from blood to tissue during a single
tissue is given by transit through the vascular bed of the tissue.
Extraction occurs almost exclusively at the
5000(mL / min) × 50(microspheres/g ) level of capillaries because of their large vas-
F=
500, 000 microspheres cular surface area. If the tracer is chemically
= 0.50 mL
L / min / g inert, it will be cleared from tissue in propor-
tion to blood flow and F can be determined by
21  •  Tracer Kinetic Modeling 395

Equation 21-1. For diffusible tracers, V is the F = λ / τ = 1.0 mL / g / τ (min)


volume into which the tracer is distributed. (21-27)
= τ −1 (mL / min / g)
The fraction of the total tissue that a diffus-
ible tracer will occupy depends on the specific The technique thus requires measuring the
diffusion and solubility properties of the mean transit time of the gas through the
tracer. This volume is denoted by V1, as brain. The original technique involved giving
described in Section B.3. Thus, by substitut- a subject a continuous inhalation of the gas
ing V1 for V in Equation 21-1 and and sampling the gas concentrations in the
rearranging, arterial supply to the brain (i.e., any conve-
nient arterial source) and the venous drain-
F/V1 = 1/τ (21-25) age (internal jugular bulb). Gas was breathed
until an equilibrium (or near equilibrium)
Multiplying each side of Equation 21-25 by concentration was reached in the brain and
V1/Vt, in which Vt is the total tissue volume, blood. The law of conservation of mass (Fick
gives principle, Equation 21-14) states that the
total amount of tracer in the brain at equilib-
( F/V1 )(V1 /Vt ) = (1/τ)(V1 /Vt ) rium must be the difference between the
(21-26)
F/Vt = λ / τ cumulative input and output. Therefore

where V1/Vt is the partition coefficient (λ) for ∞ ∞


V × CE = F ∫ CA (t) dt − F ∫ CV (t) dt (21-28)
the tracer as given by Equation 21-4. As dis- 0 0
cussed earlier, λ typically is measured using
Equation 21-3. F/Vt is blood flow per volume But λâ•›/F = τ (Equation 21-26); therefore
or mass of tissue (perfusion). As discussed  rearranging Equation 21-28 and writing it in
in Section B.1, by convention in the literature terms of blood flow per volume of tissue
F/Vt is also referred to as blood flow, F.
Thus Equation 21-26 also may be written as ∞

F = λâ•›/τ. λ
=
∫ 0
(CA (t) − CV (t)) dt
= τ (21-29)
The problem of V varying with flow, dis- F CE
cussed earlier for nondiffusible tracers, does
not exist to any significant degree with diffus- where CA(t) and Câ•›Vâ•›(t) are the arterial and
ible tracers. The term V with diffusible tracers venous concentrations as a function of time
is the tissue volume that does not change and CE is the equilibrium concentration in the
appreciably with changes in blood flow. Thus blood, usually approximated by a venous
changes in 1/τ are directly proportional to value at a selected time (e.g., 10 minutes)
flow. In addition, τ is longer for diffusible after the initiation of the inhalation. Typical
tracers (i.e., 30 to 100 seconds for brain) than values for this approach are τ = 2 minutes,
for nondiffusible tracers (3 to 6 seconds for which, from Equation 21-27 yields a flow of
brain). Because of the longer values of τ and approximately 0.5╯mLâ•›/minâ•›/g of brain tissue.
the linear relationship between τ and blood A completely analogous approach with nuclear
flow with diffusible tracers, they usually medicine imaging devices (e.g., PET and
provide more accurate and convenient mea- SPECT) permits one to perform these calcula-
surements of blood flow than those obtained tions regionally in the brain or other tissues
with nondiffusible tracers. However, λ usually and also produces estimates of blood flow
is measured in normal tissue, and it may vary using compartmental modeling approaches
from this value in pathologic tissues. For with a measured arterial input function and
example, 15O-labeled water has little variabil- serial images of the tissue (i.e., venous efflux
ity,1 whereas 133Xe has considerable variabil- concentration measurements are not neces-
ity4 between normal and diseased tissue. sary).6 Freely diffusible tracers used for
An example of the application of the central studies of cerebral blood flow include 15O-
volume principle is the Kety-Schmidt method water and 15O-butanol, and these are typi-
for measuring cerebral blood flow with cally introduced into the body by intravenous
inhaled, diffusible, inert gasses (e.g., nitrous bolus injection. Equilibrium approaches to
oxide or krypton).5 This approach is based on measuring blood flow using continuous infu-
the assumption of a constant partition coef- sion of short half-life (usually 15O-labeled) dif-
ficient of 1╯mL╛/g in the case of nitrous oxide fusible tracers also have been developed.7
and krypton in the brain. Blood flow is given One very simple method for determining
by (Equation 21-26) the mean transit time in nuclear medicine
396 Physics in Nuclear Medicine

studies (and if the partition coefficient is

A (0)
known, blood flow) is the “area/height”
method. A very short bolus of a freely diffus-
ible tracer such as 133Xe is injected. A gamma
camera then is used to image the washout of

A (t )
the tracer from the organ of interest over
time. It can be shown that the mean transit
time is8

λ
=τ=
∫0
A(t) dt
(21-30)
Time (min)
F A(0)
FIGURE 21-13  Tissue time-activity curve following
in which A(t) is the amount of the tracer in bolus injection of a blood flow tracer. The total amount of
activity detected in a given tissue region is plotted as a
tissue as a function of time after the injection function of time. The maximum activity at time zero
and A(0) is the amount of tracer in the tissue represents A(0). From Equation 21-30, the mean transit
just after the bolus has been delivered. Figure time, τ, is given by the area under the curve divided by
21-13 illustrates this approach graphically. the height of the curve, A(0). This method often is referred
to as the “area/height” method.

5.  Enzyme Kinetics:  


Glucose Metabolism
Enzymes catalyze many biochemical reac- enzymes for conversion of P back to S for
tions that are of interest from the modeling additional regulation of reaction sequences.
standpoint. An example is the hexokinase- The reaction rate R (conversion of S to P)
catalyzed phosphorylation of glucose that  is
is the step initiating glycolysis and also is
the focal reaction for the deoxyglucose and Vm × [S]
R= (21-32)
2-deoxy-2[18F]fluoro-D-glucose (FDG) model [S] + K m
for determining rates of glucose metabolism
(references 1 and 9). FDG is by far the most and is known as the Michaelis-Menten equa-
commonly used PET radiopharmaceutical in tion. The term Vm (mg/min) is the maximum
clinical studies, because many different dis- rate of the reaction, whereas Km is the concen-
eases can result in changes in glucose tration of S that produces a reaction rate of
metabolism (see Chapter 18, Section F). The one half the maximum value, as shown in
model for determining the rate of glucose Figure 21-14.
use from a PET study therefore is one of the Equation 21-32 predicts that the reaction
most studied tracer kinetic models in nuclear rate approaches the maximum value Vm as
medicine. [S] approaches infinity. It is clear from Equa-
The Michaelis-Menten hypothesis states tion 21-32 and Figure 21-14 that the reac-
that an intermediate complex is formed tion rate is not a linear function of [S];
between a reactant (also known as the sub- however, it still is possible to model such
strate) and an enzyme. This complex then is processes with linear tracer compartmental
converted to the chemical product with release models because of the following relationship.
of the enzyme. The reaction can be written in If more than one substrate is competing for
form similar to that for carrier-mediated the enzyme E (i.e., S and S′), it can be shown1
transport (Equation 21-17): that the reaction rates R and R′ for the com-
peting processes are
k1 k3

S+E←  → SE ←
  → P + E (21-31)
 Vm × [S]/K m
k 2
R= (21-33)
([S]/K m ) + ([S ′]/K m′ ) + 1
where S is the substrate, P is the product, E
is the enzyme, and k1, k2, and k3 are the rate Vm′ × [S ′ ]/K m′
R′ = (21-34)
constants for the steps of the reaction process. ([S]/K m ) + ([S ′ ]/K m′ ) + 1
Note that it is generally assumed that there
is no reverse association of P and E; therefore where Vm′ and K m′ are the Michaelis-Menten
no k4 rate constant is present. However, in constants for the reaction with substrate S′.
biologic systems there usually are separate If S′ represents a tracer of the original
21  •  Tracer Kinetic Modeling 397

Vm

Reaction rate, R Vm/2

0.0
Km 0.4 0.8 1.2 1.6 2.0 2.4 2.8
Substrate concentration (mg/mL)
FIGURE 21-14  Graphical illustration of Michaelis-Menten enzyme kinetics. The rate of a reaction (i.e., the reaction
flux R) is plotted against substrate concentration [S] using Equation 21-32. Note that when the substrate concentration
equals Km, the reaction rate is Vm/2. As the substrate concentration increases, the reaction rate gradually approaches
Vm. (From Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission Tomography and Autoradiography: Principles
and Applications for the Brain and Heart. New York, 1986, Raven Press.)

substrate S, then [S′] is of a much lower value As an example of an analog tracer approach
than [S]. Therefore to modeling an enzymatic process, consider
the Sokoloff deoxyglucose method9 or the
Vm × [S] analogous approach with PET using 18F-labeled
R≅ (21-35)
[S] + K m FDG for measuring glucose metabolism in the
brain.10 Glucose supplies 95% to 99% of the
Vm′ × K m /K m′ brain’s energy in normal physiologic states,
R′ ≅ [S ′ ] (21-36)
[S] + K m and the rate of glucose use is an excellent
indicator of energy-requiring functions of the
R is simply the original rate of the process brain.
(Equation 21-32) unaffected by the presence FDG is an analog of glucose that is similar
of the tracer S′, whereas R′ is a linear function to glucose in several respects. Like glucose, it
of [S′] as long as [S′] remains much less than is transported from the blood to the brain by
[S] (i.e., as long as the tracer condition holds). a carrier-mediated diffusion mechanism.
Therefore the tracer concentration [S′] is lin- HexoÂ�kinase catalyzes the phosphorylation of
early related to the reaction rate R′ and linear glucose to glucose-6-PO4 and FDG to FDG-
modeling techniques are appropriate for 6-PO4. In both the transport and phosphoryla-
describing this process. Dividing Equation tion steps, FDG is a competitive substrate
21-36 by Equation 21-35 yields with glucose. FDG-6-PO4, however, is not a
significant substrate for further metabolism.
R′ Vm′ × K m [S ′ ] As shown in Figure 21-15, it is not converted
= (21-37)
R Vm × K m′ [S] into glycogen to any significant extent and is
not further metabolized in the glycolytic
The reaction rate of the measured or pathway. The FDG-6-PO4 also does not diffuse
“traced” process, R′, is therefore directly across cell membranes and is therefore meta-
related to the “natural” or unknown rate R by bolically trapped in tissues, which is conve-
a ratio of the Michaelis-Menten constants and nient both from an imaging and modeling
the relative concentrations of S and S′. In viewpoint.
some cases (e.g., direct isotopic substitution If glucose metabolism in the tissue of inter-
labeling of biologic compounds such as 11C for est is assumed to be in a steady state (i.e., it
12
C), the Michaelis-Menten constants for the has a constant rate), then the rate of the hexo-
tracer and natural substance are essentially kinase reaction will be the rate of the entire
the same and Equation 21-37 would reduce to process of glycolysis (see Section B.6). A com-
a simple ratio of [S′] to [S]. With analog tracers partmental configuration for the FDG model
the Michaelis-Menten constants are different is shown in Figure 21-16. The three-
than the natural substance but Equation compartment model consists of FDG in
21-37 still applies. plasma, FDG in tissue, and FDG-6-PO4 in
398 Physics in Nuclear Medicine

Glycogen

Glucose-1-PO4
Hexokinase
Glucose

Glucose Glucose-6-PO4
Glucose

Fructose-6-PO4

CO2H2O

Vascular Capillary “Free” Metabolic


compartment membrane compartment compartment

Hexokinase
FDG

FDG FDG FDG-6-PO4

FIGURE 21-15  Transport and metabolic pathways for glucose and 2-deoxy-2[18F]fluoro-D-glucose (FDG). Physically,
the “free” compartment represents a combination of the interstitial space and the cytosol (the fluid component inside
the cell, excluding the nucleus) in both of which unphosphorylated glucose and FDG are uniformly distributed. The
red crosses indicate that FDG-6-PO4, unlike glucose-6-PO4, is not further metabolized.

tissue corresponding to comparable distribu- indices, whereas the corresponding terms for
tions of glucose, although glucose continues glucose do not have an asterisk.
on through metabolism. The first-order rate Let MRGlc* (µmol/min/g) refer to the meta-
constants k1* and k2* describe the transport of bolic rate of FDG and MRGlc (µmol/min/g) be
FDG from the blood to brain and brain to the metabolic rate for glucose. If Ct is the
blood, respectively, whereas the first-order concentration of free (unphosphorylated)
rate constants k3* and k4* describe the phos- glucose in the tissue space and Ct* is the cor-
phorylation of FDG and dephosphorylation of responding concentration for FDG (second
FDG-6-PO4. The asterisk refers to FDG compartment, top row, Fig. 21-16), then, from

FDG k *1 FDG k *3 FDG-6-PO4


in plasma in tissue in tissue

k *2 k *4
C *p C *t C *m

Glucose k1 Glucose k3 Glucose-6-PO4


in plasma in tissue in tissue
Glucose
metabolism
k2 k4
Cp Ct Cm

FIGURE 21-16  Three-compartment FDG model with the four first-order rate constants describing transport between
the compartments. Cp, Ct, and Cm are the concentrations of glucose in plasma, tissue, and metabolized glucose (glucose-
6-PO4) in tissue, respectively. Cp*, Ct* , and Cm* are the corresponding concentrations for FDG.
21  •  Tracer Kinetic Modeling 399

Equation 21-37 and the fact that the rate of a tissue uses FDG and glucose. The full
phosphorylation (i.e., flux as described in Sec- expression of LC also includes an additional
tions B.4 and B.5) equals k3 × Ct for glucose term including the influence of dephosphory-
and k3* × Ct* for FDG, it follows that lation of glucose on the net metabolic rates
of FDG and glucose. This latter term is nor-
MRGlc* Vm* × K m × Ct* k3* × Ct* mally quite close to 1 but is intrinsically
MRGlc = =
k3 × Ct (21-38) included in the measured values of LC by
* × Ct
Vm × K m Equation 21-42.
Although the lumped constant describes
Equation 21-38 assumes that k4* and k4 are the differences between FDG and glucose
very small and the forward rate of phosphory- metabolism, it is actually glucose metabolism
lation of glucose and FDG approximate the net itself that is of interest physiologically. It can
metabolic rates. Vm and Km are the Michaelis- be shown that MRGlc is given by1
Menten constants for the hexokinase-mediated
phosphorylation of FDG (*) and glucose (no *). Cp  k1* k3* 
If the ratio of terms defined by Equation MRGlc =   (21-43)
21-38 is a constant, then LC  k2* + k3* 

MRGlc = MRGlc*/constant (21-39) The term k1* / (k2* + k3* ) is the partition coeffi-
cient (λ*) for FDG. To understand this, con-
If plasma glucose (Cp) and plasma FDG ( Cp*) sider the tracer steady state when the flux of
concentrations are constant and both sides of FDG into tissue is balanced by the flux out.
Equation 21-38 are multiplied by Cp /Cp*, then Thus,
MRGlc* / Cp* Vm* × K m × Ct* / Cp* flux in = flux out (21-44)
MRGlc / C = (21-40)
p Vm × K m* × Ct / Cp
k1* Cp* = k2* Ct* + k3* Ct* (21-45)
But, from Equation 21-3, the ratios Ct* /Cp*
and Ctâ•›/Cp are the partition coefficients (i.e., k1* Ct*
tissue-to-blood concentration ratios) of FDG = (21-46)
(λ*) and glucose (λ). If the numerator and k2* + k3* Cp*
denominator of the left side of Equation 21-40
are divided by blood flow (F ), the numerical It is apparent from Equation 21-46 that the
value of the equation does not change; thus, partition coefficient, k1* / (k2* + k3* ) , is simply
with these substitutions, the tissue-to-plasma concentration ratio.
Because LC is the correction factor that con-
MRGlc* /(Cp* × F ) Vm* × K m × λ* verts the transport and phosphorylation steps
= (21-41) measured with FDG to those for glucose, one
MRGlc /(Cp × F ) * ×λ
Vm × K m can perform the following transformation
from values for FDG to those for glucose:
This ratio of terms is defined as the lumped
constant (LC) of the FDG model. The left side [ k1* / (k2* + k3* )] × k3*
= [ k1 /(k2 + k3 )] × k3 (21-47)
of Equation 21-41 is simply the net extraction LC
* ) divided by the net (i.e., steady-
of FDG ( Enet
state) extraction of glucose (Enet). Therefore, Since k1/(k2 + k3) = Ct/Cp, the tissue concentra-
tion of glucose, Ct, can be obtained from the
* ) / ( Enet )
LC = ( Enet (21-42) plasma concentration, Cp, by

That is, the lumped constant of the FDG Cp × k1 / (k2 + k3 ) = (Ct /Cp ) × Cp = Ct (21-48)
model is just the steady-state ratio of the net
extraction of FDG to that of glucose at con- Thus, from the general equation for calculat-
stant plasma levels of FDG and glucose. The ing fluxes (Equation 21-5),
lumped constant is a direct consequence of
Equation 21-37 and illustrates the principle MRGlc (µmol/g/min) = k3 × Ct (21-49)
of competitive enzyme kinetics applied to
tracer kinetic modeling. Intuitively, the Equations 21-43 and 21-49 are valid only if
lumped constant is simply a correction term the dephosphorylation rate is negligible com-
that measures the net difference in the way pared with the rate of phosphorylation.
400 Physics in Nuclear Medicine

Models that include dephosphorylation are In words, Equation 21-50 can be expressed
described in reference 1. as
Equation 21-43 produces a local estimate
of MRGlc if Cp (the steady-state plasma  Regional Glucose
glucose value) is measured, if LC is known  Metabolic Rate 
and if the rate constants for FDG (k1*, k2*, and
k3*) are determined for each region of organ of  Plasma Glucose Conc. 
=
interest. The equations and procedures for  Lumped Constant 
measuring these rate constants are given in   Total 18 F   Free 18 FDG   (21-51)
references 1 and 10. Although this technique   in Region  −  in Region  
generates local estimates of MRGlc, it does × 
require imaging the organ over time and iter-   Total Net 18 FDG 
atively solving for the rate constants in Equa-   
 Transported to the Region 
tion 21-43. In actual practice, an operational
equation for the FDG model usually is The total 18F minus free 18FDG equals the
employed that uses predetermined popula- tissue concentration of the reaction product,
tion values for the FDG rate constants and FDG-6-PO4.
requires only a single tissue measurement of Equation 21-50 requires knowledge of the
the total tissue concentration of 18F (18FDG + typical kinetics of the transport and phos-
18
FDG-6-PO4) obtained from ROI analysis of phorylation processes to make intelligent
the image data. This operational equation decisions about scan duration and imaging
originally was developed by Sokoloff and time. Typically, approximately 40 minutes
coworkers9 for autoradiographically deter- are required for the tracer to reach a near
mining MRGlc with 14C-deoxyglucose. This steady state in tissue after a bolus intrave-
technique still requires knowledge of the time nous injection of FDG. A PET image usually
course of FDG input function [Cp* (t) ], the is obtained at this time. The ROI value over
plasma glucose concentration Cp, the lumped the tissue or organ of interest, together with
constant value (LC ), and average values of the other model parameters described
the rate constants. The Sokoloff operational earlier, is then used to calculate local values
equation of the deoxyglucose model, which of MRGlc. Figure 21-17 illustrates a para-
does not include the dephosphorylation of metric image of MRGlc in the brain obtained
DG-6-PO4, is given by using Equation 21-50 with data from an
FDG PET image. A parametric image is one
in which the parameter of interest (in this
MRGlc =
case MRGlc) is calculated on a pixel-by-pixel
T
C i* (T ) − [ k1* × e− ( k2 + k3 ) T × ∫ C p* (t ) × e( k2 + k3 ) t dt]
* * * * basis.
0
The FDG model contains several simplifi-
 T C p* (t ) * (t )
T Cp  cations based on the approaches outlined in
LC  ∫ dt − e− ( k2 + k3 ) T × ∫
* * * *
× e( k2 + k3 ) t dt  the preceding sections. The strategy of using
 0 C p 0 Cp
 an analog tracer effectively eliminates many
alternative biochemical pathways for glucose
(21-50) metabolism and makes possible the simple
three-compartment model. Additionally, the
where Ci*(T ) is the total 18F tissue concentra- transport (between the first two compart-
tion at time T. ments) and phosphorylation steps (between
The quantities highlighted in blue in Equa- the second two compartments) represent com-
tion 21-50 are measured in each study. bined steps of more complicated multistep
Average estimates of the rate constants and processes. The exchange between substruc-
LC obtained from separate experiments are tures within each compartment is assumed to
used as a part of the routine calculation of be rapid compared with exchange between
MRGlc with Equation 21-50. The use of compartments.
average estimates of the rate constants over Even though blood flow has a major effect
the normal range of MRGlc values causes on tracer delivery, it is not included in the
little error at late times (i.e., imaging  FDG model explicitly. The extraction of FDG
40 minutes after injection) because they normally is low enough (i.e., low value of P ×
appear with terms in Equation 21-50 with S) that the delivery of FDG has a low depen-
negative exponentials that become small dence on blood flow. In addition, the initial
when T becomes large. flow dependence on the delivery of FDG
21  •  Tracer Kinetic Modeling 401

0.6 µmol/min/g

FIGURE 21-17  Parametric image of a trans-


verse section through the brain showing MRGlc
calculated on a pixel-by-pixel basis using Equa-
tion 21-50. (Image courtesy Dr. Henry Huang,
University of California–Los Angeles, Los
Angeles, California.)

progressively diminishes with time after an imaging study, the radioligand and recep-
injection. tor are likely to disassociate. The discussion
In the tracer kinetic model, the FDG con- that follows assumes this case.
centration in the vascular compartment A simple model for the interaction of a
shown in Figure 21-16 is measured by taking radioligand, L, with a receptor, R, is
blood samples from the systemic circulation. kon
Typically, it is assumed that the measured 
L+R ←  → RL
 (21-52)
koff
tissue data contain no significant counts from
activity in the vascular space. In Equation where kon and koff are the rate of association
21-50 this is a good approximation at the and dissociation of L and R, respectively. At
typical imaging time of 40 minutes after injec- equilibrium, if the system is closed, there is
tion. Models have been developed that add no net change in the concentrations, and
the vascular compartment to equations therefore
describing the tissue time-activity curve
because in kinetic studies for measuring the kon [L][R ] = koff [RL] (21-53)
rate constants, the amount of FDG in the
tissue vascular pool is significant at early where [L], [R], and [RL] are the equilibrium
times after injection. concentrations of the unbound ligand, the recep-
The deoxyglucose and FDG methods have tor, and the bound receptor-ligand complex,
been used to measure exogenous glucose use respectively. The ratio koffâ•›/kon is known as the
in many organs and tissues using autoradiog- equilibrium dissociation constant and is given
raphy and PET, respectively. Examples the notation Kd. The total concentration of
include brain, heart, tumors, liver, kidney, receptors is given by [R] + [RL] and is com-
and peripheral tissues. monly denoted as Bmax. Rearranging Equation
21-53 in terms of Kd and Bmax yields
6.  Receptor Ligand Assays
Cell-surface receptors are important molecu- Bmax [L ]
[RL ] = (21-54)
lar targets that may be overexpressed or underÂ�-  [L ] + K d
expressed in a range of important diseases
states, for example in Parkinson’s disease and It is possible to measure [RL] as a function 
many cancers. PET and SPECT can provide of [L] in vitro and then fit the data to estimate
images of the distribution of these receptors both Kd and Bmax. Thus quantitative informa-
by using tracers known as radioligands that tion on the receptor concentration, and the
are designed to bind specifically to the recep- strength of binding of the ligand to the recep-
tor of interest.11,12 In most cases the binding tor (commonly known as the affinity, and
is reversible, that is, over the time course of given by 1/Kd), can be obtained. In humans,
402 Physics in Nuclear Medicine

such a study is impractical because it would estimate a parameter related to the in vitro
require several injections of radioligand at BP as defined by Equation 21-55. Under the
different concentrations. As well, at higher assumption that Kd does not change signifi-
concentrations of the ligand there would be cantly with disease progression or treatment,
concerns about possible pharmacologic effects images of BP will roughly reflect the relative
resulting from the high levels of receptor concentration of receptors, Bmax, in tissue.
occupancy. However, if a PET or SPECT study Such techniques have been widely applied to
is carried out at tracer levels such that [RL] studies of receptor systems in the brain.
is small compared with [R] (i.e., the fraction To see how the parameter BP is related to
of receptors occupied by the ligand is, for quantities that can be measured in a PET or
example, 10% or less), then Bmax ≈ [R], and SPECT scan, we start with a compartmental
now from Equation 21-53, we see that model as shown in Figure 21-18A. The injected
radioligand is delivered via the flowing blood
Bmax [RL ] (plasma compartment) and is extracted with
= (21-55)
Kd [L ] rate constant K1 into the free compartment in
the tissue. The rate constant K1 represents
The ratio Bmax/Kd is known as the binding the product of the blood flow and the uni�
potential (BP) and equals the ratio of bound directional extraction fraction (see Section
radioligand to free radioligand concentration C.1) and has units of mLâ•›/minâ•›/g.*
at equilibrium in this simple model. Although
the situation in vivo following injection of a
radioligand is quite complex, it turns out with *By convention, K1 is denoted by a capital K because it
appropriate modeling of dynamically acquired has different units than the other rates constants, which
PET or SPECT data that it is possible to are in units of inverse time.

Plasma
compartment Free Bound
compartment compartment

K1 k3

Cplasma Cfree Cbound

k2 k4
FIGURE 21-18  A, A general four-compartment
model describing a radioligand that reversibly binds
k5 k6
to a specific receptor. The rate constants for the
exchange of the radioligand between compartments
are denoted by K1 through k6, and the concentration
of the radioligand in each compartment is denoted
Cnon-specific by C. B, A simplified version of the model in A in
which the exchange between the “free” and “nonspe-
cifically bound” compartments is assumed to be
rapid (k5 and k6 >> k3 and k4) allowing these two
Non-specifically bound compartments to be combined into a single compart-
A compartment ment representing nondisplaceable radioligand.
This reduces the number of model unknowns to four,
Plasma increasing the robustness with which kinetic param-
compartment eters can be estimated. This model is used in the
Non-displaceable Bound analysis of many radioligand studies with PET and
compartment compartment SPECT.

K1 k3

Cplasma CND Cbound

k2 k4

B
21  •  Tracer Kinetic Modeling 403

Once in the tissue, there are four possible K1 Cplasma (t) + k4 Cbound (t) =
fates for the radioligand. It can continue to
exist in free form, it can bind to the receptor k2 k4 Cbound (t)
+ k4 Cbound (t)
of interest, it can bind nonspecifically in the k3
tissue to other proteins, or it can be trans- C K k (21-59)
ported back to the blood. Because any binding ⇒ bound = 1 3
is reversible, there are rate constants both for Cplasma k2 k4
binding of the ligand and for its dissociation.
In sum, this model has four different com- This is the ratio of the specifically bound
partments and six different rate constants. radioligand to the radioligand concentration
Because of the limited temporal resolution in plasma at equilibrium. This is another
and signal-to-noise characteristics of nuclear form of BP and is given the symbol BPP. Both
medicine images, it is not possible to robustly definitions for BP can be found in the litera-
estimate six different kinetic rate constants ture and only recently has consensus emerged
from a dynamic PET or SPECT study. The on nomenclature.13
model therefore is simplified by making  Equations 21-58 and 21-59 relate a param-
the assumption that there is rapid exchange eter closely related to the in vitro equilibrium
between the free and nonspecifically bound BP to kinetic rate constants that may be mea-
compartments, and that these two com� sured individually, or in combination, from a
partments can be combined together. This is dynamic sequence of reconstructed PET or
a reasonable assumption if the radioligand SPECT scans. There are several computa-
has only low affinity binding to nonspecific tional approaches for taking radioactivity
targets such that it associates and dissoci- values from such a dynamic sequence and
ates rapidly (that is, k5 and k6 are large converting them into estimates of the BP
compared with k3 and k4). This combined through the integration of Equations 21-56
compartment often is referred to as the non- and 21-57. The method used depends on the
displaceable compartment. This results in available data, for example, whether arterial
the simplified kinetic model in Figure blood samples were taken during the scan
21-18B, which consists of three compart- such that the Cplasma(t) is known, and must
ments with four rate constants. also account for the fact that neither PET or
Based on conservation of mass, we can SPECT can differentiate between radioactiv-
write simple differential equations for the ity in CND and Cbound. Rather, the measure-
concentration in the “nondisplaceable” and ments are the sum of the radioligand in these
“specifically bound” compartments as two compartments as a function of time.
Methods for computing BP from PET and
dCND (t) SPECT data are reviewed in some detail in
= K1 Cplasma (t) − k2 CND (t)
dt (21-56) references 11 and 12. These types of approaches
− k3 CND (t) + k4 Cbound (t) that integrate carefully designed radioli-
gands, experimental protocols, and kinetic
dCbound (t) models are being used to study a number of
= k3 CND (t) − k4 Cbound (t) (21-57)
dt important receptor systems, particularly in
the brain (see Table 21-1). A representative
At equilibrium, there would be no net trans- example of such a study is shown in Figure
fer of radioligand between compartments; 21-19.
therefore, from Equation 21-57,

Cbound k3 F.  SUMMARY


k3 CND = k4 Cbound ⇒ = (21-58)
CND k4
Tracer kinetic methods provide unique and
Cbound/CND is the ratio of the specifically accurate methods for measuring rates of phys-
bound radioligand to the radioligand in the  iologic, biochemical, and pharmacokinetic pro-
nondisplaceable tissue compartment at equi- cesses. This chapter has stressed some of the
librium. Thus it is closely related to the defi- principles of tracer kinetic modeling in nuclear
nition of the in vitro BP (Equation 21-55) and medicine and their relationship to measure-
by convention13 is called BPND. Examining ments and descriptions of underlying physio-
Equation 21-56, at equilibrium, and using the logic processes. Many modeling approaches
relationship derived in Equation 21-58, one exist, and the complexity of the model that is
also obtains used depends on the state of knowledge
404 Physics in Nuclear Medicine

1.0

0.9

0.8

0.7
[11C]MRB (baseline)
0.6

0.5

0.4

0.3
[11C]MRB (10 mg methylphenidate)
0.2

0.1

0.0
Binding
potential
MRI
FIGURE 21-19  Images showing pixel-by-pixel calculations of binding potential (BPND) averaged over 11 healthy sub-
jects for (S,S)-[11C] methylreboxetine (MRB), a radioligand that selectively binds to the norepinephrine transporter (top
row). This transporter is responsible for removing the neurotransmitters norepinephrine and dopamine from the syn-
apses between neurons and is known to play an important role in several neurologic disorders, including attention
deficit–hyperactivity disorder (ADHD). In this study, a decrease in binding potential was observed after administration
of 10╯mg of methylphenidate 75 minutes prior to radioligand injection (middle row). Methylphenidate is a drug that
is used to treat ADHD. This study shows that methylphenidate binds to the norepinephrine transporter, thereby reduc-
ing the availability of receptor sites to which the radioligand may become bound. Sagittal, coronal, and transverse
views are shown with corresponding anatomic slices from magnetic resonance imaging (bottom row). (Adapted from
Hannestad J, Gallezot J-D, Planeta-Wilson B, et al: Clinically relevant doses of methylphenidate significantly occupy
norepinephrine transporters in humans in vivo. Biol Psych 68:854-860, 2010.)

regarding the fate of the tracer in a biologic 2. Renkin EM: Transport of potassium-42 from blood to
system and the quality of the image data that tissue in isolated mammalian skeletal muscles. Am
J Physiol 197:1205-1210, 1959.
are used as input to the model. In nuclear 3. Crone C: Permeability of capillaries in various 
medicine, it rarely is possible to extract more organs as determined by use of the indicator 
than three or four independent parameters in diffusion method. Acta Physiol Scand 58:292-305,
a model because of the finite temporal resolu- 1963.
4. Lassen NA: Tracer Kinetic Methods in Medical Physi-
tion and signal-to-noise ratio of the ROI data. ology, New York, 1979, Raven Press.
In situations in which the fate of the tracer is 5. Kety SS, Schmidt CF: The nitrous oxide method for
complex (multiple metabolites, multiple modes the quantitative determination of cerebral blood flow
of transport, and so forth), there can be consid- in man: Theory, procedure, and normal values. J Clin
erable debate on the appropriate formulation Invest 27:476-483, 1948.
6. Holden JE, Gatley SJ, Hichwa RD, et al: Regional
of the model and the exact physiologic or func- cerebral blood flow using positron emission tomo-
tional meaning of the derived parameters. graphic measurements of fluoromethane kinetics. 
Once rigorous investigative studies are carried J Nucl Med 22:1084-1088, 1981.
out to validate a tracer kinetic model, it often 7. Huang S-C, Phelps ME, Hoffman EJ, Kuhl DE: 
A theoretical study of quantitative flow measure-
is possible to use simplified versions of the ments with constant infusion of short-lived isotopes.
model that provide semiquantitative indices Phys Med Biol 24:1151-1161, 1979.
for use in the clinical setting, where it may not 8. Zieler K: Equations for measuring blood flow by
be possible to acquire dynamic sequences of external monitoring of radioisotopes. Circ Res 16:309-
images or obtain blood samples. 321, 1965.
9. Sokoloff L, Reivich M, Kennedy C, et al: The [C-14]
deoxyglucose method for the measurement of local
cerebral glucose utilization: Theory, procedure, and
REFERENCES normal values in the conscious and anesthetized
albino rat. J Neurochem 28:897-916, 1977.
1. Gambhir SS: Quantitative assay development for 10. Huang SC, Phelps ME, Hoffman EJ, et al: Nonin�
PET. In Phelps ME, editor: PET: Molecular Imaging vasive determination of local cerebral metabolic 
and Its Biological Applications, New York, 2004, rate of glucose in man. Am J Physiol 238:E69-E82,
Springer-Verlag, pp 125-216. 1980.
21  •  Tracer Kinetic Modeling 405

11. Slifstein M, Laruelle M: Models and methods for deri-


vation of in vivo neuroreceptor parameters with PET BIBLIOGRAPHY
and SPECT reversible radiotracers. Nucl Med Biol
28:595-608, 2001. Additional discussion of the theory, mathematical
12. Ichise M, Meyer J, Yonekura Y: An introduction to formulation, and application of compartmental
PET and SPECT neuroreceptor quantification modeling, including mathematical techniques in
models. J Nucl Med 42:755-763, 2001. estimation theory for modeling, can be found in the
13. Innis RB, Cunningham VJ, Delforge J, et al: Consen- following:
sus nomenclature for in vivo imaging of reversibly Cobelli C, Foster D, Toffolo G: Tracer Kinetics in Biomedi-
binding radioligands. J Cerebr Blood Flow Metabol cal Research: From Data to Model, New York, 2001,
27:1533-1539, 2007. Kluwer Academic Press.
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chapter
22 
Internal Radiation
Dosimetry

Absorption of energy from ionizing radiation


A.  RADIATION DOSE AND
can cause damage to living tissues. This is EQUIVALENT DOSE: QUANTITIES  
used to advantage in radionuclide therapy, AND UNITS
but it is a limitation for diagnostic applica-
tions because it is a potential hazard for the Radiation dose, D, refers to the quantity of
patient. In either case, it is necessary to radiation energy deposited in an absorber per
analyze the energy distribution in body gram of absorber material. This quantity
tissues quantitatively to ensure an accurate applies to any kind of absorber material,
therapeutic prescription or to assess potential including body tissues. The basic unit of radi-
risks. The study of radiation effects on living ation dose is the gray, abbreviated Gy*:
organisms is the subject of radiation biology
(or radiobiology) and is discussed in several 1 Gy = 1 joule energy deposited per kg absorber
excellent texts, some of which are listed at the (22-1)
end of this chapter.
One of the most important factors to be The traditional unit for absorbed dose is the
evaluated in the assessment of radiation rad, an acronym for radiation absorbed dose:
effects on an organ is the amount of radiation
energy deposited in that organ. Calculation of 1 rad = 100 ergs energy deposited per g absorber
radiation energy deposited by internal radio- (22-2)
nuclides is the subject of internal radiation
dosimetry. There are two general methods by Since 1 joule = 107 ergs, 1╯Gy is equi�valent
which these calculations may be performed: to 100 rads or, alternatively, 1 rad = 10–2╯Gy
the classic method and the absorbed fraction = 1╯cGy. As is the case for units of activity,
method. Although the classic method is some- progress in the transition from traditional to
what simpler, and the results by the two SI units varies with geographic location, with
methods are not greatly different, the absorbed SI units dominating practice in Europe,
fraction method (also known generally as the whereas traditional units still are common-
MIRD method, after the Medical Internal place in the United States. In this chapter,
Radiation Dose Committee of the Society of radiation doses are presented in grays, with
Nuclear Medicine) is more versatile and gives values in rads also indicated in selected
more accurate results. Therefore it has gained examples.
wide acceptance as the standard method for Equivalent dose, symbolically indicated by
performing internal dosimetry calculations. HT, is a quantity that takes into account the
The procedures to be followed in using the relative biologic damage caused by radiation
absorbed fraction method are summarized in interacting with a particular tissue or organ.
this chapter. Dosimetry calculations for exter- Tissue damage per gray of absorbed dose
nal radiation sources as well as health physics
aspects of radiation dosimetry are discussed
in Chapter 23. Some radiation dose estimates *This unit is named after Harold Gray, a British medical
for nuclear medicine procedures are summa- physicist best known for his discovery of the “oxygen
rized in Appendix E. effect” in radiation therapy.
407
408 Physics in Nuclear Medicine

depends on the type and energy of the radia- For radiations of interest in nuclear medicine
tion, and how exactly the radiation deposits (γ rays, x rays, electrons, and positrons) the
its energy in the tissue. For example, an α radiation weighting factor is equal to 1.
particle has a short range in tissue and depos- Therefore the equivalent dose or dose equiva-
its all of its energy in a very localized region. lent in Sv (or rem) is numerically equal to the
In contrast, γ rays and electrons deposit their absorbed dose in Gy (or rads).
energy over a wider area. Table 22-1 shows
the radiation weighting factors, wR, used to
calculate equivalent dose for different types B.  CALCULATION OF RADIATION
and energies of radiation. The SI unit of DOSE (MIRD METHOD)
equivalent dose is the sievert* (Sv). It is
related to the average absorbed dose D in an
organ or tissue, T, by 1.  Basic Procedure and Some Practical
Problems
HT = D T × wR (22-3) The absorbed fraction dosimetry method
allows one to calculate the radiation dose
Equivalent dose replaces an older quantity delivered to a target organ from radioactivity
known as the dose equivalent. The dose equiv- contained in one or more source organs in the
alent is based on the absorbed dose at a point body (Fig. 22-1). The source and target may
in an organ (rather than an average across be the same organ, and, in fact, frequently the
the whole organ) and is weighted by quality most important contributor to radiation dose
factors, Q, that are similar to wR. The unit for is radioactivity contained within the target
dose equivalent also is the Sv. organ itself. Generally, organs other than the
The traditional unit for dose equivalent is target organ are considered to be source
the roentgen-equivalent man (rem). The con- organs if they contain concentrations of radio-
version factor between traditional and SI activity that exceed the average concentra-
units is tion in the body.
The general procedure for calculating the
1 rem = 10−2 Sv = 1 cSv = 10 mSv radiation dose to a target organ from radioÂ�
(22-4) activity in a source organ is a three-step
process, as follows:
*This unit is named after Rolf M. Sievert, best known for 1. The amount of activity and time spent
his development of elaborate mathematical models, by the radioactivity in the source organ
including the Sievert integral, which for many years pro- are determined. Obviously, the greater
vided the basis for calculating radiation doses from the activity and the longer the time that
implanted radium needles. He also constructed and per-
formed many basic measurements with ionization it is present, the greater is the radiation
chambers. dose delivered by it.
2. The total amount of radiation energy
emitted by the radioactivity in the
TABLE 22-1â•… source organ is calculated. This depends
WEIGHTING FACTORS FOR DIFFERENT primarily on the energy of the radio�
TYPES OF RADIATION IN THE nuclide emissions and their frequency of
CALCULATION OF EQUIVALENT DOSE† emission (number per disintegration).
Radiation
3. The fraction of energy emitted by the
Weighting source organ that is absorbed by the
Type of Radiation Factor, wR target organ is determined. This depends
on the type and energy of the emissions
x rays 1
(absorption characteristics in body
γ rays 1 tissues) and on the anatomic relation-
Electrons, positrons 1 ships between source and target organs
Neutrons Continuous function
(size, shape, and distance between them).
of neutron energy Each of these steps involves certain difficul-
ties. Step 2 involves physical characteristics of
Protons >2╯MeV 2 the radionuclide, which generally are known
α particles, fission 20 accurately. Step 3 involves patient anatomy,
fragments, heavy which can be quite different from one patient
ions to the next. Step 1 is perhaps the most trouble-
†Data from reference 1. some. Such data on radiopharmaceutical
22  •  Internal Radiation Dosimetry 409

Source
organs

FIGURE 22-1  Absorbed dose delivered to a


target organ from one or more source organs con-
taining radioactivity is calculated by the absorbed
fraction dosimetry method.

Target
organ

distribution as are available usually are which the activity is present. The product of
obtained from studies on a relatively small these two factors is the cumulated activity  A
number of human subjects or animals. There in the source organ. The SI unit for cumulated
are variations in metabolism and distribution activity is the becquerel • sec (Bq • sec). The
of radionuclides among human subjects, espe- corresponding traditional unit is the µCi • hr
cially in different disease states. Also, the dis- (1╯µCi = 3.7 × 104 Bq; 1╯hr = 3600╯sec; there-
tribution of radioactivity within an organ may fore, 1╯µCi • hr = 3.7 × 104 × 3600 = 1.332 ×
be inhomogeneous, leading to further uncer- 108 Bq • sec = 1.332 × 102╯MBq • sec). Cumu-
tainties in the dose specification for that organ. lated activity is essentially a measure of the
Because of these complications and vari- total number of radioactive disintegrations
ables, radiation dose calculations are made for occurring during the time that radioactivity
anatomic models that incorporate “average” is present in the source organ. The radiation
anatomic sizes and shapes. The radiation dose delivered by activity in a source organ is
doses that are calculated are average values proportional to its cumulated activity.
of D for the organs in this anatomic model. Each radiotracer has its own unique spatial
An exception is made when one is specifically and temporal distribution in the body, as
interested in a surface dose to an organ from determined by radiotracer delivery, uptake,
activity contained within that organ, for metabolism, clearance and excretion, and 
example, the dose to the bladder wall result- the physical decay of the radionuclide. The
ing from bladder contents. This is considered amount of activity contained in a source organ
to have a value one-half the average dose  therefore generally changes with time. If the
to the organ or, in this case, the bladder time-activity curve is known, the cumulated
contents. activity for a source organ is obtained by mea-
In spite of the refined mathematical models suring the area under this curve (Fig. 22-2).
used in the absorbed fraction model, the Mathematically, if the time-activity curve is
results obtained are only estimates of average described by a function A(t), then
values. Thus they should be used for guide-

line purposes only in evaluating the potential 
radiation effects on a patient. A ≈ ∫ A(t) dt (22-5)
0
2.  Cumulated Activity, 
A where it is assumed that activity is adminis-
The radiation dose delivered to a target organ tered to the patient at time t = 0 and is mea-
depends on the amount of activity present in sured to complete disappearance from the
the source organ and on the length of time for organ (t = ∞).
410 Physics in Nuclear Medicine

AreaA
Activity (Bq)

FIGURE 22-2  Hypothetical time-activity curve


for radioactivity in a source organ. Cumulated
activity 
A in Bq • sec is the area under the curve
(equivalent to the integral in Equation 22-5).

Time (sec)

EXAMPLE 22-1
To estimate the radiation dose received
from a particular radiotracer, time-activity What is the cumulated activity in the liver for
curves for all the major organs are required. an injection of 100╯MBq of a 99mTc-labeled
These can be obtained from animal studies sulfur colloid, assuming that 60% of the
(which are then extrapolated with some injected colloid is trapped by the liver and
uncertainty to the human), imaging studies retained there indefinitely?
in normal human subjects, prior knowledge of
the tracer kinetics, or some combination of Answer
these approaches. Time-activity curves can be
quite complex, and thus Equation 22-5 may 
A = 1.44 × 100 MBq × 0.60 × 6.0 hr
be difficult to analyze. Frequently, however,
= 518.4 MBq i hr
certain assumptions can be made to simplify
this calculation. = 1.87 × 106 MBq i sec
Situation 1: Uptake by the organ is “instan-
taneous” (i.e., very rapid with respect to the Situation 2: Uptake is instantaneous, and
half-life of the radionuclide), and there is no clearance is by biologic excretion only (no
biologic excretion. The time-activity curve physical decay, or physical half-life very long
then is described by ordinary radioactive in comparison with biologic excretion). In
decay (Equations 4-7 and 4-10): this situation, biologic excretion must be
carefully analyzed. Frequently, it can be
A(t) = A 0 e−0.693t / Tp (22-6) described by a set of exponential excretion
components, with a fraction f1 of the initial
where Tp is the physical half-life of the radio- activity A 0 being excreted with a (biologic)
nuclide and A0 is the activity initially present half-life Tb1, a fraction f2 with half-life Tb2,
in the organ. Thus and so on (Fig. 22-4). The cumulated activity
∞ then is given by

A ≈ A 0 ∫ e−0.693t / Tp dt ∞

A ≈ A 0 ∫ f1 e−0.693t / Tb1 dt
0
(22-7) 0
Tp A 0 ∞
= = 1.44Tp A 0 + A 0 ∫ f2 e−0.693t / Tb 2 dt + …
0.693
0

The quantity 1.44Tp is the average lifetime = 1.44Tb1 f1 A 0 + 1.44Tb 2 f2 A 0 + …


of the radionuclide (see Chapter 4, Section
(22-8)
B.3). Thus the cumulated activity in a source
organ, when eliminated by physical decay EXAMPLE 22-2
only, is the same as if activity were present at
a constant level A0 for a time equal to the Suppose that 100╯MBq of 99mTc-labeled micro-
average lifetime of the radionuclide (Fig. spheres are injected into a patient, with
22-3). essentially instantaneous uptake of activity
22  •  Internal Radiation Dosimetry 411

A0
Area within
rectangle
0.8A0
equals

Activity
FIGURE 22-3  Illustration of relation- 0.6A0
ship between  A and average lifetime Area under
(1.44 Tp) of a radionuclide for simple red curve
exponential decay. 0.4A0
1.44T1/2
0.2A0

0
0 1 2 3 4 5 6
Time (number of half-lives)

A0
f1 A0

f2 A0
Total
Activity

FIGURE 22-4  Illustration of a multicomponent


exponential excretion curve. Fraction f1 is 0.1A0
excreted with biologic half-life Tb1, f2 with half-
f3 A0
life Tb2, f3 with half-life Tb3, and so on.

Tb1 Tb2 Tb3

0.01A0
Time

by the lungs. What is the cumulated activity Situation 3: Uptake is instantaneous but
in the lungs if 60% of the activity is excreted clearance by both physical decay and biologic
from the lungs with a biologic half-life of 15 excretion are significant. In this case, if
minutes and 40% with a biologic half-life of biologic excretion is described by a single- 
30 minutes? component exponential curve with biologic
half-life Tb, and the physical half-life is Tp,
Answer then the total clearance is described by a 
Because 99mTc physical decay is much slower single-component exponential curve with an
than the biologic excretion process, we may effective half-life Te given by*
assume that no physical decay occurs during
the time that activity is present in the lungs. 1 1 1
= + (22-9)
Thus (Equation 22-8) Te Tp Tb

A = (1.44 × 1/ 4 hr × 0.60 × 100 MBq)
+ (1.44 × 1/ 2 hr × 0.40 × 100 MBq)
= (21.6 + 28.8) MBq i hr
*Equation 22-9 can be derived from Equations 4-2 and
= 50.4 MBq i hr 4-9 by treating biologic excretion as the equivalent of a
= 1.81 × 105 MBq i sec second pathway in a “branching” radioactive decay
scheme.
412 Physics in Nuclear Medicine

or arises with radionuclides that have a slow


pattern of uptake in comparison with their
Tp Tb physical half-life. Frequently, uptake can be
Te = (22-10)
(Tp + Tb ) described by an exponential equation of the
form
Cumulated activity is given by
A(t) = A 0 (1 − e−0.693t / Tu ) (22-12)


A ≈ 1.44Te A 0 (22-11)
where Tu is the biologic uptake half-time. In
this case, cumulated activity is given by
If there is more than one component to 
the biologic excretion curve, then each compo- 
A ≈ 1.44 A 0 Te (Tue / Tu ) (22-13)
nent has an effective half-life given by Equa-
tion 22-9 for that component, and the
cumulated activity is computed with effective where Te is the effective excretion half-life
half-lives replacing biologic half-lives in (Equation 22-10) and Tue is the effective
Equation 22-8. uptake half-time
Tu Tp
Tue = (22-14)
EXAMPLE 22-3 Tu + Tp
Suppose in Example 22-2 that because of a
EXAMPLE 22-4
metabolic defect 60% of the activity is excreted
from the lungs with a half-life of 2 hours and A radioactive gas having a half-life of 20
40% with a half-life of 3 hours. What is the seconds is injected in an intravenous solu-
cumulated activity in the lungs for a 100╯MBq tion. It appears in the lungs with an uptake
injection for this patient? half-time of 30 seconds and is excreted (by
exhalation) with a biologic half-life of 10
Answer seconds. What is the cumulated activity in
The effective half-lives for the two compo- the lungs for a 250-MBq injection?
nents of biologic excretion are (Equation
22-10) Answer
The effective uptake half-time is (Equation
Te1 = 6 × 2 / (6 + 2) = 1.5 hr 22-14)

Te 2 = 6 × 3 / (6 + 3) = 2 hr Tue = 20 × 30 / (20 + 30) = 12 sec

and the effective excretion half-life is


Thus applying Equation 22-8, with Te replac-
ing Tb, Te = 20 × 10 / (20 + 10) = 6.7 sec

 Thus, from Equation 22-13,


A = (1.44 × 1.5 hr × 0.60 × 100 MBq)
+ (1.44 × 2 hr × 0.40 × 100 MBq) 
A = 1.44 × 250 MBq × 6.7 sec
= (129.6 + 115.2) MBq i hr
× (12 sec/ 30 sec)
= 244.8 MBq i hr
= 964.8 MBq i sec
= 8.81 × 105 MBq i sec

Situation 4: Uptake is not instantaneous.


3.  Equilibrium Absorbed Dose
The equations developed thus far will overÂ� Constant, Δ
estimate radiation doses when uptake by  Given A for the source organ, the next step is
the source organ is not rapid in comparison to calculate the radiation energy emitted 
with physical decay, that is, if a significant by this amount of cumulated activity. Energy
amount of physical decay occurs during the emitted per unit of cumulated activity is 
uptake process, before the activity reaches given by the equilibrium absorbed dose con-
the source organ of interest. This situation stant Δ. The factor Δ must be calculated for
22  •  Internal Radiation Dosimetry 413

each type of emission for the radionuclide. It Answer


is given by* The total energy emitted per Bq • sec is the
sum of the equilibrium absorbed dose con-
∆ i = 1.6 × 10−13 Ni Ei (Gy i kg / Bq i sec) stants for the β, γ, conversion electron and
(22-15) x-ray emissions:

where Ei is the average energy (in MeV) of the ∆ = ∆β + ∆ γ + ∆ e + ∆ x


ith emission and Ni is the relative frequency = 8.0 × 10−14 Gy i kg/Bq i sec
of that emission (number emitted per disinte-
gration) by the radionuclide. In traditional = 8.0 × 10−8 Gy i kg/MBq i sec
units, the equilibrium absorbed dose constant
is The cumulated activity is 9.65 × 102╯MBq •
sec. Using these values and Equation 22-1,
∆ i = 2.13 N i Ei (rad i g / µCi i hr) (22-16) the total energy emitted is

A × ∆ = 9.65 × 102 MBq i sec × 8.0
EXAMPLE 22-5
× 10 −8 Gy i kg/MBq i sec
A certain radionuclide decays by emitting β
particles in 100% of its disintegrations with = 7.72 × 10 −5 Gy i kg
Eβ = 0.3╯MeV. This is followed immediately in = 7.72 × 10−5 joules
80% of its disintegrations by emission of a
0.2-MeV γ ray and in 20% by emission of a
0.195-MeV conÂ�version electron and a 0.005- Values of Δ are presented in Appendix C for
MeV characteristic x ray. What are the equi- some of the radionuclides of interest in nuclear
librium absorbed dose constants for the medicine. A full listing can be found in refer-
emissions of this radionuclide? ence 2.

Answer 4.  Absorbed Fraction, ϕ


The final step is to determine the fraction of
∆ β = (1.6 × 10−13 ) × 1.0 × 0.30 the energy emitted by the source organ that
is absorbed by the target organ. This is given
= 4.80 × 10−14 Gy i kg/Bq i sec by the absorbed fraction ϕ. The absorbed
∆ γ = (1.6 × 10 −13 ) × 0.80 × 0.20 fraction depends on the amount of radiation
energy reaching the target organ (tissue and
= 2.56 × 10 −14 Gy i kg/Bq i sec distance attenuation between source and
∆ e = (1.6 × 10−13 ) × 0.20 × 0.195 target organs) and on the volume and com-
position (e.g., lung, bone) of the target organ.
= 6.24 × 10−15 Gy i kg/Bq i sec
Thus it depends on the type and energy of
∆ x = (1.6 × 10 −13 ) × 0.2 × 0.005 the emission and on the anatomic relation-
ship of the source-target pair. In a dosimetry
= 1.60 × 10 −16 Gy i kg/Bq i sec
calculation, a value of ϕ must be determined
for each type of emission from the radionu-
The product of cumulated activity  A and clide and for each source-target pair in the
equilibrium absorbed dose constant Δi is the calculation. The notation ϕi(rk ← rh) is used
radiation energy emitted by the i th emission, to indicate absorbed fraction for energy
in Gy • kg, during the time that radioactivity delivered from a source organ (or region), rh,
is present in a source organ. to a target organ, rk, for the ith emission of
the radionuclide.
EXAMPLE 22-6 The total energy absorbed by a specific
Assume that the radionuclide in Example target organ thus is given by
22-5 is used for the problem described in
Example 22-4. What is the total amount of Total energy absorbed (Gy i kg) =
energy emitted from radioactivity contained
in the lungs in Example 22-4?


A φi (rk ← rh )∆ i
i
(22-17)

*Essentially the energy emitted per nuclear disintegra- The summation Σi includes values of ϕi and Δi
tion: 1╯MeV/dis = 1.6 × 10−13╯Gy • kg/Bq • sec. for all the emissions of the radionuclide and
414 Physics in Nuclear Medicine

values of ϕi(rk ← rh) for the source-target pair. Eckerman are given in Table 22-2. Most of the

A is the cumulated activity in the source values for their adult male model are similar
organ h. The energy absorbed by the target to the model originally developed by the
organ divided by the target organ mass mt MIRD committee; however, there are some
gives the average absorbed dose in grays to significant differences as well, such as in the
the target organ from activity in the source mass and values of ϕ for bone marrow. Con-
organ: sequently, the Cristy and Eckerman models
now have replaced the older MIRD model.

A Calculations of ϕ are complex, and the
D(rk ← rh ) =
mt
∑ φ (r
i k ← rh )∆ i tables are quite lengthy for “penetrating”
i
(22-18) radiations (photons with energy 10 keV )
because of the energy dependence of photon
The total dose to the target organ then is attenuation and absorption; however, the sit-
obtained by summing the doses from all of the uation is simpler for nonpenetrating radia-
source organs, h, in the body. tions (photons with energy 10 keV and
Values of ϕ have been calculated for math- electrons), for which it can be assumed that
ematical humanoid models incorporating all of the emitted energy is “locally absorbed,”
organs and anatomic structures of “average” that is, within the source organ itself. For
size and shape (Fig. 22-5). The model used for these emissions, ϕ = 1 when the target and
many years was that published by the MIRD the source are the same organ, ϕ = 0 other-
committee of the Society of Nuclear Medi- wise. In dosimetry calculations, it is useful to
cine.3 Cristy and Eckerman4 subsequently sum the equilibrium absorbed dose constants
developed a series of models representing for the nonpenetrating radiations and treat
newborn, 1-year-old, 5-year-old, 10-year-old, them as a single parameter, Δnp, because the
15-year-old, and adult individuals. Stabin absorbed fractions for all of these emissions
and associates extended the model to women are equal (unity when the source and target
and pregnant women.5 Organ masses for the are the same organ, zero otherwise).
adult male phantom developed by Cristy and
EXAMPLE 22-7
Compute the absorbed dose delivered to the
ANTERIOR VIEW OF THE PRINCIPAL ORGANS IN THE
HEAD AND TRUNK OF THE PHANTOM
lung by nonpenetrating radiations in the
problem described by Examples 22-4 and
0 5 10 ORGANS NOT 22-5.
centimeters SHOWN
Adrenals Answer
Brain
Stomach The nonpenetrating radiations are the β par-
Marrow
Pancreas
ticles (Δβ= 4.80 × 10–14╯Gy • kg/Bq • sec), conver-
Skull
Skin sion electrons (Δe = 6.24 × 10–15╯Gy • kg/Bq •
Spine Spleen sec), and 5 keV characteristic x-rays (Δx = 1.60
Ovaries × 10–16╯Gy • kg/Bq • sec). Thus Δnp = 5.44 ×
Arm bone Testes 10–14╯Gy • kg/Bq • sec. Cumulated activity is  A
Thymus
Ribs Thyroid = 9.65 × 108 Bq • sec. Lung mass is 1╯kg (see
Lungs Uterus Table 22-2). Thus the average radiation dose
Leg bones delivered by these emissions to the lungs is
Heart
Kidneys D = (9.65 × 108 Bq i sec)
Liver
Small intestine × (5.44 × 10 −14 Gy i kg/Bq i sec)
Upper large
intestine Lower large × (φ = 1) /1 kg
intestine
Pelvis
= 5.25 × 10−5 Gy (5.25 mrad)
Bladder

5.  Specific Absorbed Fraction, Φ, and


FIGURE 22-5  Representation of an “average man” used
for MIRD dose calculations and tables. (Adapted with the Dose Reciprocity Theorem
permission from Snyder WS, Fisher HL Jr, Ford MR, The specific absorbed fraction is given by
Warner GG: Estimates of absorbed fractions for monoen-
ergetic photon sources uniformly distributed in various φ
organs of a heterogenous phantom. J Nucl Med Suppl 3:9, Φ= (22-19)
1969.) mt
22  •  Internal Radiation Dosimetry 415

TABLE 22-2â•…
ORGAN MASSES FOR THE CRISTY AND ECKERMAN ADULT MALE PHANTOM

Organ Mass (g) Organ Mass (g)


Adrenals 16.3 Lungs 1000
Brain 1420 Ovaries 8.71
Breasts (excluding skin) 351 Pancreas 94.3
Gallbladder contents 55.7 Skeleton
Gallbladder wall 10.5 Active marrow 1120
Gastrointestinal Tract Cortical bone 4000
Lower large intestine contents 143 Trabecular bone 1000
Lower large intestine wall 167 Skin 3010
Small intestine contents and wall 1100 Spleen 183
Stomach contents 260 Testes 39.1
Stomach wall 158 Thymus 20.9
Upper large intestine contents 232 Thyroid 20.7
Upper large intestine wall 220 Urinary bladder contents 211
Heart contents 454 Urinary bladder wall 47.6
Heart wall 316 Uterus 79.0
Kidneys 299 Remaining tissue 51,800
Liver 1910
From Cristy M, Eckerman K: Specific Absorbed Fractions of Energy at Various Ages From Internal Photon Sources
(ORNL Report ORNL/TM-8381 V1–V7). Oak Ridge, TN, 1987, Oak Ridge National Laboratory.

It is the fraction of radiation emitted by the The dose reciprocity theorem is useful
source organ that is absorbed per gram of when tables for ϕ are not available for all
target organ mass. The absorbed dose equa- source-target organ pairs. If ϕ (rk ← rh) is
tion can be written using specific absorbed known, then ϕ (rh ← rk) can be obtained from
fractions as the dose reciprocity theorem. Rewriting Equa-
tion 22-21 in terms of ϕ:
A∑ Φ i (rk ← rh )∆ i (22-20)
D(rk ← rh ) = 
i
φ(rh ← rk ) φ(rk ← rh )
The dose reciprocity theorem says that for = (22-22)
a given organ pair the specific absorbed frac- mh mk
tion is the same, regardless of which organ is
the source and which is the target: mh
φ(rh ← rk ) = × φ(rk ← rh ) (22-23)
Φ i (rk ← rh ) = Φ i (rh ← rk ) (22-21) mk

This simply says that the energy absorbed per


gram is the same for radiation traveling from The specific absorbed fractions for a range of
rh to rk as it is for radiation traveling from rk different phantoms are available in refer-
to rh, a fact that seems intuitively obvious.* ences 4 and 6.

6.  Mean Dose per Cumulated Activity, S


*Strictly speaking, the dose reciprocity theorem is pre-
cisely correct only when both the source and target mate- Radiation dose calculations for penetrating
rials are homogeneous absorbing materials. However, radiations can be quite tedious, especially
this requirement is not stringent and the theorem is suf- when there are multiple emissions to con-
ficiently accurate (<â•›1% error) for most applications in the sider. The problem has been simplified by the
human body. One situation in which the required condi-
tions are not met is when red marrow is a source or target
intro�duction of S (sometimes also known as
organ. This is evident in Tables 22-3 to 22-5, which are the dose factor, DF), the mean dose per unit
discussed in the next section. cumulated activity:
416 Physics in Nuclear Medicine

1 Therefore, the absorbed doses are


S ( rk ← rh ) =
mk
∑ φ (r
i k ← rh ) ∆ i
i
D(LI ← LI) = (1.87 × 106 MBq i sec)
= ∑ Φ (ri k ← rh ) ∆ i
× (3.16 × 10 −6 mGy/MBq i sec)
i

(22-24) = 5.91 mGy


D(LI ← SP) = (9.33 × 105 MBq i sec)
The quantity S has units of Gy/Bq • sec. It
has been calculated for different source-target × (7.22 × 10 −8 mGy/MBq i sec)
organ pairs for a wide variety of radionuclides = 6.74 × 10 −2 mGy
of interest in nuclear medicine.7 Tables 22-3
to 22-5 present values of S for 99mTc, 131I, and D(LI ← RM) = (3.11 × 105 MBq i sec)
18
F, respectively. Given the values of S and × (8.96 × 10−8 mGy/MBq i sec)
cumulated activity, Ã, the average dose to an
organ is given by = 2.79 × 10 −2 mGy

The average total dose to the liver is


D(rk ← rh ) = 
A × S(rk ← rh ) (22-25) therefore
D = 5.91 + 6.74 × 10 −2 + 2.79 × 10 −2 mGy

= 6.01 mGy (∼0.6 rads)
EXAMPLE 22-8
Calculate the radiation dose to the liver (LI) Example 22-8 demonstrates that most 
to an average adult male for an injection of of the dose delivered to an organ that 
100╯MBq of 99mTc sulfur colloid. Assume that concentrates the radionuclide arises from 
60% of the activity is trapped by the liver, the radioactivity in the target organ itself
30% by the spleen (SP), and 10% by red bone [ D(LI ← LI) ].
marrow (RM), with instantaneous uptake and
EXAMPLE 22-9
no biologic excretion.
An adult male patient is to be treated with 131I
Answer for hyperthyroidism. It is determined by prior
The cumulated activities for the three source studies with a tracer dose of 131I that the
organs are (Equation 22-5) patient’s thyroidal iodine uptake is 60% and
the biologic half-life of iodine in the thyroid
 gland is 2 days. Assuming instantaneous
ALI = 1.44 × 6.0 hr × 0.60 × 100 MBq uptake (Tu << Tp = 8 days), what is the dose to
= 518.4 MBq i hr the thyroid (THY) from radioactivity contained
= 1.87 × 106 MBq i sec in the thyroid for this patient, per MBq 131I?

Answer

ASP = 1.44 × 6.0 hr × 0.30 × 100 MBq The effective half-life of 131I in the thyroid for
= 259.2 MBq i hr this patient is (Equation 22-10)

= 9.33 × 105 MBq i sec
Te = 8 × 2 / (8 + 2) = 16 /10 days


ARM = 1.44 × 6.0 hr × 0.10 × 100 MBq = 1.38 × 105 sec

= 86.4 MBq i hr
Therefore the cumulated activity per MBq
= 3.11 × 105 MBq i sec administered is (Equation 22-11)
99m

A = 1.44 × (1.38 × 105 sec)
The values of S for Tc are (see Table 22-3)
× 0.60 × 1 MBq
= 1.19 × 105 MBq i sec/MBq adminisstered
S(LI ← LI) = 3.16 × 10 −6 mGy/MBq i sec

S(LI ← SP) = 7.22 × 10−8 mGy/MBq i sec The dose per MBq • sec is (see Table 22-4):

S(LI ← RM) = 8.96 × 10−8 mGy/MBq i sec S(THY ← THY ) = 1.57 × 10−3 mGy/MBq i sec
22  •  Internal Radiation Dosimetry 417

Thus the average absorbed dose for the medicine procedure with that from other
thyroid is medical procedures that use radiation sources.
For these reasons, it would be convenient to
D (THY ← THY ) condense radiation dose estimates such as
those in Table 22-6 into a single number.
= (1.19 × 105 MBq i sec/MBq administered) There are two different approaches to doing
× (1.57 × 10−3 mGy/MBq i sec) this: whole-body (or total-body) dose and effec-
tive dose.
= 187 mGy/MBq administered
The whole-body or total-body dose is the
(or 692 rads/mCi) total energy deposited in the body divided by
the total mass of the body, or in terms of the
One could include the radiation dose to the S factor for the total body (TB):
thyroid from activity in other organs in the
calculation performed in Example 22-9; D(TB ← TB) = 
A × S(TB ← TB)
however, inspection of Table 22-4 reveals that
in comparison to the thyroid as the source (22-26)
organ, other organs have much smaller values This parameter was used for many years as
of S (by approximately a factor of 500). This, the standard for evaluating the risks of dif-
plus the fact that other organs concentrate ferent nuclear medicine procedures. However,
much less of the activity than the thyroid, the whole-body dose does not take into account
eliminates the need to consider them as the nonuniformity of dose distribution among
source organs in this calculation. the organs in the body, and its validity for
Examples 22-8 and 22-9 represent simpli- comparing the risks of different nuclear medi-
fied situations in which only a few organs are cine procedures is therefore questionable.
involved and where the cumulated activities The effective dose, E, was introduced by
of the organs are relatively easy to estimate. the International Commission on Radiologi-
In many cases, the calculations are more cal Protection (ICRP)1,10 as an attempt to
involved, with complex time-activity curves characterize a nonuniform internal dose by a
and more widespread distribution of the single number. This quantity was intended
radiopharmaceutical among different organs. primarily for estimating radiation risks and
To facilitate dosimetry calculations, a soft- doses received by radiation workers, although
ware program8 has been developed to calcu- its extension to clinical nuclear medicine
late the absorbed dose to major organs from studies has been supported by the ICRP. The
commonly employed radionuclides using the effective dose represents the whole-body dose
Cristy and Eckerman4 and Stabin5 phantom that would result in the same overall risk as
models of human anatomy. This greatly sim- the nonuniform dose distribution actually
plifies dose calculations, although it still is delivered. This is achieved by assigning dif-
necessary to provide the cumulated activity ferent weighting factors to the doses delivered
data for each organ for the radiopharmaceuti- to individual organs. The most recent recom-
cal of interest. Estimated radiation doses for mended values for the tissue weighting
a large number of commonly used radio� factors, wT, are shown in Table 22-7. The
pharmaceuticals are available from the Oak effective dose, which has units of sieverts, is
Ridge Institute for Science and Education.9 calculated from
By way of example, radiation dose estimates
E = ∑ wT × DT × wR = ∑ wT × HT
for 18F-fluorodeoxyglucose (FDG) PET studies
based on the Cristy and Eckerman adult male T T
(22-27)
phantom are reproduced in Table 22-6. where DT is the average absorbed dose in
organ T, wT is the tissue weighting factor for
organ T, and the summation is over all the
7.  Whole-Body Dose and Effective organs listed in Table 22-7. HT is the equiva-
Dose lent dose defined in Section A. As noted in
The complete output of a dose calculation is Section A, wR = 1 for all radiations used in
an estimate of the radiation dose for all the diagnostic nuclear medicine procedures. An
major organs in the body. This provides a older quantity, effective dose equivalent (HE),
large amount of information that is difficult which uses slightly different tissue weighting
to assimilate into a perception of the risk  factors, may be encountered in publications
of a specific radiopharmaceutical study, or for and in regulations established prior to 1991.
comparison of the dose from a nuclear Text continued on page 424
418
Physics in Nuclear Medicine
TABLE 22-3â•…
S VALUES (mGy/MBq • sec) FOR Tc-99m IN THE ADULT MALE PHANTOM*

Source Organs

Lower Upper
Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Adrenals 1.80E-04 4.18E-10 5.05E-08 3.13E-07 2.25E-08 7.46E-08 2.73E-07 9.58E-08 2.53E-07 2.85E-07 7.24E-07 4.35E-07 2.33E-07 1.12E-07
Brain 4.18E-10 4.23E-06 3.17E-09 1.49E-10 1.57E-11 3.91E-11 4.27E-10 4.68E-11 3.14E-09 2.54E-09 1.58E-10 8.16E-10 7.63E-09 2.21E-08
Breasts 5.05E-08 3.17E-09 1.14E-05 3.33E-08 2.28E-09 7.35E-09 5.73E-08 8.00E-09 2.41E-07 2.61E-07 1.99E-08 6.82E-08 2.33E-07 4.25E-08
Gallbladder wall 3.57E-07 1.54E-10 3.41E-08 3.37E-05 6.49E-08 4.38E-07 3.05E-07 7.53E-07 1.03E-07 1.22E-07 4.09E-07 8.70E-07 7.46E-08 1.19E-07
Lower large intestine wall 1.98E-08 1.32E-11 2.42E-09 5.93E-08 1.23E-05 5.92E-07 9.10E-08 2.14E-07 4.06E-09 4.90E-09 5.50E-08 1.44E-08 3.29E-09 1.34E-07
Small intestine 7.46E-08 3.91E-11 7.35E-09 4.58E-07 7.16E-07 4.22E-06 2.08E-07 1.25E-06 1.57E-08 2.06E-08 2.13E-07 1.16E-07 1.35E-08 1.12E-07
Stomach wall 2.85E-07 2.52E-10 5.93E-08 2.93E-07 1.24E-07 2.13E-07 8.53E-06 2.86E-07 1.66E-07 2.65E-07 2.53E-07 1.48E-07 1.19E-07 1.09E-07
Upper large intestine wall 9.41E-08 4.76E-11 7.51E-09 7.78E-07 3.10E-07 1.36E-06 2.65E-07 8.37E-06 2.12E-08 2.65E-08 2.12E-07 1.88E-07 1.81E-08 1.10E-07
Heart wall 2.85E-07 2.54E-09 2.61E-07 1.04E-07 5.42E-09 2.06E-08 2.33E-07 2.97E-08 5.48E-06 1.19E-05 8.22E-08 2.33E-07 4.40E-07 9.20E-08
Kidneys 7.24E-07 1.58E-10 1.99E-08 3.89E-07 7.10E-08 2.13E-07 2.73E-07 2.12E-07 6.45E-08 8.22E-08 1.32E-05 2.93E-07 6.66E-08 9.79E-08
Liver 4.35E-07 8.16E-10 6.82E-08 8.20E-07 1.80E-08 1.16E-07 1.47E-07 1.87E-07 2.13E-07 2.33E-07 2.93E-07 3.16E-06 1.97E-07 7.52E-08
Lungs 2.33E-07 7.63E-09 2.33E-07 7.09E-08 4.50E-09 1.35E-08 1.10E-07 1.77E-08 4.59E-07 4.40E-07 6.66E-08 2.09E-07 3.57E-06 9.36E-08
Muscle 1.12E-07 2.21E-08 4.25E-08 1.14E-07 1.23E-07 1.12E-07 9.96E-08 1.07E-07 8.83E-08 9.20E-08 9.79E-08 7.52E-08 9.34E-08 1.93E-07
Ovaries 3.14E-08 1.52E-11 2.61E-09 1.11E-07 1.26E-06 9.23E-07 5.85E-08 7.71E-07 4.55E-09 6.15E-09 7.02E-08 3.81E-08 5.39E-09 1.44E-07
Pancreas 1.09E-06 4.15E-10 6.22E-08 6.75E-07 5.21E-08 1.42E-07 1.23E-06 1.62E-07 2.65E-07 3.57E-07 4.97E-07 3.86E-07 1.74E-07 1.24E-07
Red marrow 2.53E-07 1.01E-07 5.52E-08 1.02E-07 2.01E-07 1.79E-07 7.50E-08 1.43E-07 1.11E-07 1.11E-07 1.71E-07 8.32E-08 1.11E-07 9.07E-08
Bone surfaces 2.67E-07 2.99E-07 7.76E-08 1.14E-07 1.82E-07 1.49E-07 1.03E-07 1.27E-07 1.60E-07 1.60E-07 1.62E-07 1.24E-07 1.66E-07 1.84E-07
Skin 3.41E-08 3.97E-08 7.63E-08 3.09E-08 3.62E-08 3.01E-08 3.41E-08 3.09E-08 3.41E-08 3.70E-08 3.79E-08 3.62E-08 4.02E-08 5.72E-08
Spleen 4.58E-07 5.19E-10 4.37E-08 1.33E-07 6.53E-08 1.01E-07 7.83E-07 1.05E-07 1.24E-07 1.67E-07 6.63E-07 7.22E-08 1.64E-07 1.03E-07
Testes 1.54E-09 1.46E-12 0.00E+00 6.91E-09 1.40E-07 2.61E-08 2.90E-09 1.92E-08 5.16E-10 6.16E-10 3.10E-09 1.57E-09 3.67E-10 9.89E-08
Thymus 5.66E-08 6.88E-09 2.29E-07 1.43E-08 2.04E-09 4.66E-09 3.65E-08 5.43E-09 8.87E-07 7.35E-07 1.73E-08 5.93E-08 2.85E-07 1.06E-07
Thyroid 8.11E-09 1.35E-07 3.01E-08 2.45E-09 2.48E-10 4.87E-10 2.62E-09 7.69E-10 5.17E-08 4.33E-08 2.95E-09 8.64E-09 8.82E-08 1.16E-07
Urinary bladder wall 7.55E-09 6.02E-12 1.33E-09 4.22E-08 4.98E-07 2.12E-07 1.73E-08 1.61E-07 2.22E-09 2.17E-09 1.87E-08 1.16E-08 1.33E-09 1.40E-07
Uterus 1.89E-08 1.31E-11 2.62E-09 1.16E-07 5.17E-07 8.37E-07 5.05E-08 3.97E-07 4.87E-09 5.47E-09 6.42E-08 3.29E-08 4.10E-09 1.43E-07
Total body 1.72E-07 1.25E-07 1.03E-07 1.36E-07 1.49E-07 1.59E-07 1.17E-07 1.41E-07 1.17E-07 1.65E-07 1.58E-07 1.59E-07 1.44E-07 1.33E-07
Source Organs

Lower Upper
TABLE 22-3 CONTINUED Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle

Source Organs

Cortical Trabecular Cortical Trabecular Urinary


Red Bone Bone Bone Bone Bladder Total
Target Organs Ovaries Pancreas Marrow Surfaces Surfaces Volume Volume Spleen Testes Thymus Thyroid Contents Uterus Body
Adrenals 3.14E-08 1.09E-06 2.41E-07 1.07E-07 1.07E-07 1.07E-07 1.07E-07 4.58E-07 1.54E-09 5.66E-08 8.11E-09 8.41E-09 1.89E-08 1.67E-07
Brain 1.52E-11 4.15E-10 8.08E-08 1.17E-07 1.17E-07 1.17E-07 1.17E-07 5.19E-10 1.46E-12 6.88E-09 1.35E-07 5.94E-12 1.31E-11 1.21E-07
Breasts 2.61E-09 6.22E-08 5.12E-08 3.10E-08 3.10E-08 3.10E-08 3.10E-08 4.37E-08 0.00E+00 2.29E-07 3.01E-08 1.30E-09 2.62E-09 1.00E-07
Gallbladder wall 9.91E-08 8.14E-07 1.15E-07 4.41E-08 4.41E-08 4.41E-08 4.41E-08 1.35E-07 6.71E-09 2.65E-08 2.64E-09 3.45E-08 1.15E-07 1.77E-07
Lower large intestine wall 1.12E-06 4.17E-08 1.98E-07 7.25E-08 7.25E-08 7.25E-08 7.25E-08 4.65E-08 1.96E-07 1.61E-09 2.06E-10 5.78E-07 4.97E-07 1.73E-07
Small intestine 9.23E-07 1.42E-07 1.86E-07 5.74E-08 5.74E-08 5.74E-08 5.74E-08 1.01E-07 2.61E-08 4.66E-09 4.87E-10 2.24E-07 8.37E-07 1.77E-07
Stomach wall 5.85E-08 1.26E-06 8.23E-08 3.89E-08 3.89E-08 3.89E-08 3.89E-08 7.75E-07 4.43E-09 3.61E-08 3.71E-09 2.10E-08 5.53E-08 1.58E-07
Upper large intestine wall 8.29E-07 1.69E-07 1.55E-07 5.02E-08 5.02E-08 5.02E-08 5.02E-08 1.06E-07 1.78E-08 5.31E-09 7.69E-10 1.60E-07 4.17E-07 1.72E-07
Heart wall 6.15E-09 3.57E-07 1.09E-07 5.74E-08 5.74E-08 5.74E-08 5.74E-08 1.67E-07 6.16E-10 7.35E-07 4.33E-08 2.22E-09 5.47E-09 1.61E-07
Kidneys 7.02E-08 4.97E-07 1.70E-07 6.22E-08 6.22E-08 6.22E-08 6.22E-08 6.63E-07 3.10E-09 1.73E-08 2.95E-09 2.00E-08 6.42E-08 1.54E-07
Liver 3.81E-08 3.86E-07 8.96E-08 4.82E-08 4.82E-08 4.82E-08 4.82E-08 7.22E-08 1.57E-09 5.93E-08 8.64E-09 1.17E-08 3.29E-08 1.55E-07
Lungs 5.39E-09 1.76E-07 1.09E-07 6.67E-08 6.67E-08 6.67E-08 6.67E-08 1.65E-07 3.67E-10 2.97E-07 8.82E-08 1.04E-09 4.10E-09 1.41E-07
Muscle 1.44E-07 1.24E-07 9.07E-08 7.45E-08 7.45E-08 7.45E-08 7.45E-08 1.03E-07 9.89E-08 1.06E-07 1.16E-07 1.30E-07 1.43E-07 1.31E-07
Ovaries 3.22E-04 3.65E-08 2.13E-07 6.54E-08 6.54E-08 6.54E-08 6.54E-08 3.85E-08 0.00E+00 1.94E-09 2.29E-10 5.41E-07 1.57E-06 1.81E-07
Pancreas 3.65E-08 3.73E-05 1.48E-07 6.54E-08 6.54E-08 6.54E-08 6.54E-08 1.28E-06 2.58E-09 6.13E-08 7.28E-09 1.38E-08 3.73E-08 1.79E-07
Red marrow 2.13E-07 1.40E-07 1.79E-06 2.01E-07 6.38E-07 2.01E-07 3.88E-07 8.43E-08 2.69E-08 8.25E-08 7.94E-08 8.02E-08 1.39E-07 1.31E-07

22  •  Internal Radiation Dosimetry


Bone surfaces 1.66E-07 1.67E-07 1.01E-06 2.73E-06 3.15E-06 7.26E-07 1.21E-06 1.26E-07 1.02E-07 1.23E-07 1.97E-07 1.05E-07 1.30E-07 2.59E-07
Skin 3.09E-08 3.01E-08 4.20E-08 4.68E-08 4.68E-08 4.68E-08 4.68E-08 3.49E-08 1.03E-07 4.39E-08 4.38E-08 3.90E-08 3.01E-08 9.14E-08
Spleen 3.85E-08 1.28E-06 9.19E-08 4.94E-08 4.94E-08 4.94E-08 4.94E-08 2.24E-05 2.17E-09 3.89E-08 7.83E-09 8.40E-09 2.57E-08 1.54E-07
Testes 0.00E+00 2.58E-09 3.09E-08 4.09E-08 4.09E-08 4.09E-08 4.09E-08 2.17E-09 8.64E-05 1.91E-10 2.31E-11 3.73E-07 0.00E+00 1.28E-07
Thymus 1.94E-09 6.13E-08 8.45E-08 4.83E-08 4.83E-08 4.83E-08 4.83E-08 3.89E-08 1.91E-10 1.50E-04 1.62E-07 8.06E-10 1.81E-09 1.43E-07
Thyroid 2.29E-10 7.28E-09 7.54E-08 7.67E-08 7.67E-08 7.67E-08 7.67E-08 7.83E-09 2.31E-11 1.62E-07 1.49E-04 9.56E-11 2.14E-10 1.45E-07
Urinary bladder wall 5.49E-07 1.38E-08 9.18E-08 4.01E-08 4.01E-08 4.01E-08 4.01E-08 8.04E-09 3.85E-07 8.14E-10 9.65E-11 1.10E-05 1.28E-06 1.67E-07
Uterus 1.57E-06 3.73E-08 1.54E-07 4.89E-08 4.89E-08 4.89E-08 4.89E-08 2.57E-08 0.00E+00 1.81E-09 2.14E-10 1.24E-06 4.70E-05 1.83E-07
Total body 1.87E-07 1.85E-07 1.52E-07 1.40E-07 1.40E-07 1.40E-07 1.40E-07 1.59E-07 1.32E-07 1.48E-07 1.49E-07 1.18E-07 1.88E-07 1.39E-07
*Data from References 6 and 7.

419
420
TABLE 22-4â•…

Physics in Nuclear Medicine


S VALUES (mGy/MBq • sec) FOR I-131 IN THE ADULT MALE PHANTOM*

Source Organs

Lower Upper
Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Adrenals 1.97E-03 3.40E-09 1.65E-07 8.41E-07 7.95E-08 2.20E-07 7.93E-07 2.54E-07 6.95E-07 7.91E-07 2.05E-06 1.21E-06 6.71E-07 3.31E-07
Brain 3.40E-09 2.91E-05 1.43E-08 1.88E-09 2.62E-10 5.20E-10 3.50E-09 6.17E-10 1.68E-08 1.56E-08 1.47E-09 5.53E-09 3.34E-08 7.10E-08
Breasts 1.65E-07 1.43E-08 1.01E-04 1.09E-07 1.40E-08 3.33E-08 1.83E-07 3.85E-08 7.32E-07 7.97E-07 7.53E-08 2.18E-07 6.73E-07 1.36E-07
Gallbladder wall 9.04E-07 1.51E-09 1.15E-07 3.12E-04 1.79E-07 1.18E-06 8.17E-07 1.99E-06 2.79E-07 3.49E-07 1.09E-06 2.35E-06 2.16E-07 3.40E-07
Lower large intestine wall 7.68E-08 2.21E-10 1.42E-08 1.56E-07 1.19E-04 1.62E-06 2.52E-07 6.49E-07 1.91E-08 2.40E-08 1.67E-07 5.21E-08 1.65E-08 3.79E-07
Small intestine 2.20E-07 5.20E-10 3.33E-08 1.21E-06 1.94E-06 4.01E-05 5.41E-07 3.45E-06 5.72E-08 7.44E-08 5.93E-07 3.28E-07 5.05E-08 3.18E-07
Stomach wall 7.22E-07 2.68E-09 1.93E-07 7.80E-07 3.66E-07 5.96E-07 7.04E-05 7.97E-07 4.61E-07 7.00E-07 6.98E-07 4.24E-07 3.26E-07 3.13E-07
Upper large intestine wall 2.58E-07 6.23E-10 3.31E-08 2.07E-06 8.60E-07 3.80E-06 7.01E-07 7.57E-05 7.68E-08 9.14E-08 5.82E-07 5.16E-07 6.40E-08 3.11E-07
Heart wall 7.91E-07 1.56E-08 7.97E-07 2.88E-07 2.60E-08 7.44E-08 6.71E-07 9.44E-08 4.20E-05 1.09E-04 2.29E-07 6.37E-07 1.19E-06 2.64E-07
Kidneys 2.05E-06 1.47E-09 7.53E-08 1.03E-06 2.22E-07 5.93E-07 7.22E-07 5.85E-07 2.01E-07 2.29E-07 1.18E-04 8.19E-07 1.97E-07 2.89E-07
Liver 1.21E-06 5.53E-09 2.18E-07 2.20E-06 6.41E-08 3.28E-07 4.11E-07 5.29E-07 5.81E-07 6.37E-07 8.19E-07 2.15E-05 5.48E-07 2.21E-07
Lungs 6.71E-07 3.35E-08 6.74E-07 1.94E-07 2.19E-08 5.05E-08 3.07E-07 6.16E-08 1.25E-06 1.19E-06 1.97E-07 5.49E-07 3.40E-05 2.67E-07
Muscle 3.31E-07 7.10E-08 1.36E-07 3.27E-07 3.48E-07 3.18E-07 2.85E-07 3.03E-07 2.50E-07 2.64E-07 2.89E-07 2.21E-07 2.67E-07 1.42E-06
Ovaries 1.13E-07 2.65E-10 1.45E-08 2.99E-07 3.52E-06 2.47E-06 1.81E-07 2.08E-06 2.59E-08 3.16E-08 2.17E-07 1.20E-07 2.67E-08 4.07E-07
Pancreas 2.88E-06 4.18E-09 1.97E-07 1.83E-06 1.41E-07 3.98E-07 3.32E-06 4.46E-07 6.94E-07 9.41E-07 1.41E-06 1.03E-06 4.76E-07 3.53E-07
Red marrow 7.32E-07 2.77E-07 1.83E-07 3.07E-07 6.10E-07 5.14E-07 2.38E-07 4.27E-07 3.36E-07 3.36E-07 5.18E-07 2.63E-07 3.37E-07 2.75E-07
Bone surfaces 4.79E-07 5.34E-07 1.50E-07 1.90E-07 3.09E-07 2.46E-07 1.77E-07 2.14E-07 2.70E-07 2.70E-07 2.83E-07 2.17E-07 2.96E-07 3.28E-07
Skin 1.15E-07 1.40E-07 2.49E-07 1.02E-07 1.14E-07 9.94E-08 1.15E-07 1.02E-07 1.15E-07 1.20E-07 1.34E-07 1.18E-07 1.30E-07 1.89E-07
Spleen 1.25E-06 5.74E-09 1.51E-07 3.38E-07 1.77E-07 2.93E-07 2.09E-06 2.78E-07 3.26E-07 4.39E-07 1.87E-06 2.16E-07 4.54E-07 3.01E-07
Testes 1.02E-08 4.79E-11 0.00E+00 3.33E-08 4.43E-07 9.10E-08 1.86E-08 7.48E-08 4.30E-09 4.95E-09 1.91E-08 1.03E-08 3.16E-09 3.02E-07
Thymus 1.86E-07 3.52E-08 8.03E-07 5.65E-08 1.20E-08 2.20E-08 1.34E-07 2.73E-08 2.41E-06 1.98E-06 6.83E-08 1.77E-07 7.95E-07 3.11E-07
Thyroid 3.16E-08 4.21E-07 1.03E-07 1.50E-08 2.38E-09 3.04E-09 1.57E-08 5.97E-09 1.43E-07 1.36E-07 1.93E-08 3.51E-08 2.54E-07 3.38E-07
Urinary bladder wall 3.53E-08 1.34E-10 9.12E-09 1.60E-07 1.30E-06 5.76E-07 7.23E-08 4.55E-07 1.30E-08 9.31E-09 7.47E-08 5.03E-08 8.80E-09 3.97E-07
Uterus 8.02E-08 2.41E-10 1.70E-08 3.31E-07 1.39E-06 2.18E-06 1.51E-07 1.03E-06 2.53E-08 2.96E-08 2.00E-07 1.04E-07 2.03E-08 4.04E-07
Total body 8.01E-07 6.71E-07 6.33E-07 4.02E-07 6.01E-07 6.98E-07 4.26E-07 5.47E-07 4.33E-07 7.86E-07 7.71E-07 7.71E-07 7.22E-07 7.11E-07
Source Organs

Lower Upper
TABLE 22-4 CONTINUED Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle

Source Organs

Cortical Trabecular Cortical Trabecular Urinary


Red Bone Bone Bone Bone Bladder Total
Target Organs Ovaries Pancreas Marrow Surfaces Surfaces Volume Volume Spleen Testes Thymus Thyroid Contents Uterus Body
Adrenals 1.13E-07 2.88E-06 7.32E-07 3.31E-07 3.31E-07 3.31E-07 3.31E-07 1.25E-06 1.02E-08 1.86E-07 3.16E-08 4.16E-08 8.02E-08 8.00E-07
Brain 2.65E-10 4.18E-09 2.60E-07 3.74E-07 3.74E-07 3.74E-07 3.74E-07 5.74E-09 4.79E-11 3.52E-08 4.21E-07 1.33E-10 2.41E-10 6.71E-07
Breasts 1.45E-08 1.97E-07 1.78E-07 1.09E-07 1.09E-07 1.09E-07 1.09E-07 1.51E-07 0.00E+00 8.03E-07 1.03E-07 7.58E-09 1.70E-08 6.32E-07
Gallbladder wall 2.97E-07 2.07E-06 3.36E-07 1.34E-07 1.34E-07 1.34E-07 1.34E-07 3.46E-07 3.23E-08 9.17E-08 1.53E-08 1.20E-07 3.32E-07 8.28E-07
Lower large intestine wall 3.20E-06 1.30E-07 5.80E-07 2.23E-07 2.23E-07 2.23E-07 2.23E-07 1.34E-07 5.69E-07 9.83E-09 2.00E-09 1.54E-06 1.29E-06 8.16E-07
Small intestine 2.47E-06 3.98E-07 5.21E-07 1.67E-07 1.67E-07 1.67E-07 1.67E-07 2.93E-07 9.10E-08 2.20E-08 3.04E-09 5.77E-07 2.18E-06 8.28E-07
Stomach wall 1.86E-07 3.45E-06 2.46E-07 1.22E-07 1.22E-07 1.22E-07 1.22E-07 2.03E-06 2.27E-08 1.29E-07 2.17E-08 7.34E-08 1.73E-07 7.86E-07
Upper large intestine wall 2.23E-06 4.37E-07 4.42E-07 1.49E-07 1.49E-07 1.49E-07 1.49E-07 2.84E-07 6.84E-08 2.99E-08 5.97E-09 4.36E-07 1.09E-06 8.16E-07
Heart wall 3.16E-08 9.41E-07 3.23E-07 1.74E-07 1.74E-07 1.74E-07 1.74E-07 4.39E-07 4.95E-09 1.98E-06 1.36E-07 1.03E-08 2.96E-08 7.83E-07
Kidneys 2.17E-07 1.41E-06 5.16E-07 1.93E-07 1.93E-07 1.93E-07 1.93E-07 1.87E-06 1.91E-08 6.83E-08 1.93E-08 8.05E-08 2.00E-07 7.70E-07
Liver 1.20E-07 1.03E-06 2.68E-07 1.50E-07 1.50E-07 1.50E-07 1.50E-07 2.16E-07 1.03E-08 1.77E-07 3.51E-08 4.82E-08 1.04E-07 7.71E-07
Lungs 2.67E-08 4.76E-07 3.35E-07 2.06E-07 2.06E-07 2.06E-07 2.06E-07 4.55E-07 3.16E-09 7.96E-07 2.54E-07 6.19E-09 2.03E-08 7.22E-07
Muscle 4.07E-07 3.53E-07 2.75E-07 2.30E-07 2.30E-07 2.30E-07 2.30E-07 3.01E-07 3.02E-07 3.11E-07 3.38E-07 3.70E-07 4.04E-07 7.11E-07
Ovaries 3.63E-03 1.22E-07 5.99E-07 1.91E-07 1.91E-07 1.91E-07 1.91E-07 1.13E-07 0.00E+00 1.20E-08 2.36E-09 1.39E-06 3.99E-06 8.36E-07
Pancreas 1.22E-07 3.59E-04 4.44E-07 1.98E-07 1.98E-07 1.98E-07 1.98E-07 3.61E-06 1.52E-08 1.75E-07 3.22E-08 5.46E-08 1.24E-07 8.31E-07
Red marrow 5.99E-07 4.36E-07 1.55E-05 6.11E-07 6.91E-06 6.11E-07 5.08E-06 2.71E-07 9.62E-08 2.55E-07 2.38E-07 2.40E-07 4.07E-07 6.10E-07

22  •  Internal Radiation Dosimetry


Bone surfaces 2.79E-07 2.91E-07 8.20E-06 1.42E-05 1.83E-05 5.62E-06 1.05E-05 2.18E-07 1.86E-07 2.19E-07 3.42E-07 1.78E-07 2.13E-07 9.26E-07
Skin 1.02E-07 9.94E-08 1.46E-07 1.71E-07 1.71E-07 1.71E-07 1.71E-07 1.22E-07 3.29E-07 1.52E-07 1.45E-07 1.27E-07 9.94E-08 6.07E-07
Spleen 1.13E-07 3.61E-06 2.76E-07 1.50E-07 1.50E-07 1.50E-07 1.50E-07 1.95E-04 1.31E-08 1.05E-07 3.12E-08 4.30E-08 9.33E-08 7.71E-07
Testes 0.00E+00 1.52E-08 1.01E-07 1.32E-07 1.32E-07 1.32E-07 1.32E-07 1.31E-08 8.53E-04 2.02E-09 4.14E-10 1.03E-06 0.00E+00 7.10E-07
Thymus 1.20E-08 1.75E-07 2.57E-07 1.50E-07 1.50E-07 1.50E-07 1.50E-07 1.05E-07 2.02E-09 1.57E-03 4.42E-07 6.07E-09 1.14E-08 7.40E-07
Thyroid 2.36E-09 3.22E-08 2.33E-07 2.37E-07 2.37E-07 2.37E-07 2.37E-07 3.12E-08 4.14E-10 4.42E-07 1.57E-03 1.19E-09 2.22E-09 7.40E-07
Urinary bladder wall 1.45E-06 5.80E-08 2.56E-07 1.22E-07 1.22E-07 1.22E-07 1.22E-07 4.04E-08 1.03E-06 6.06E-09 1.19E-09 8.85E-05 3.45E-06 8.07E-07
Uterus 3.99E-06 1.24E-07 4.26E-07 1.48E-07 1.48E-07 1.48E-07 1.48E-07 9.33E-08
Continued 0.00E+00 1.14E-08 2.22E-09 3.28E-06 4.35E-04 8.42E-07
Total body 8.37E-07 8.31E-07 7.47E-07 7.14E-07 7.14E-07 7.14E-07 7.14E-07 7.71E-07 7.11E-07 7.41E-07 7.41E-07 3.65E-07 8.43E-07 7.16E-07
*Data from References 6 and 7.

421
422
TABLE 22-5â•…

Physics in Nuclear Medicine


S VALUES (mGy/MBq • sec) FOR F-18 IN THE ADULT MALE PHANTOM*

Source Organs

Lower Upper
Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Adrenals 2.59E-03 1.13E-08 4.60E-07 2.06E-06 2.06E-07 5.70E-07 2.06E-06 6.48E-07 1.74E-06 2.05E-06 5.22E-06 3.01E-06 1.74E-06 8.54E-07
Brain 1.13E-08 4.62E-05 3.99E-08 6.70E-09 9.01E-10 1.78E-09 1.06E-08 2.11E-09 4.95E-08 4.78E-08 4.84E-09 1.76E-08 9.70E-08 1.90E-07
Breasts 4.60E-07 3.99E-08 1.46E-04 3.01E-07 4.30E-08 9.55E-08 4.92E-07 1.13E-07 1.90E-06 2.06E-06 2.07E-07 5.85E-07 1.74E-06 3.64E-07
Gallbladder wall 2.21E-06 5.00E-09 3.17E-07 4.38E-04 4.59E-07 3.00E-06 2.06E-06 4.89E-06 6.98E-07 9.32E-07 2.84E-06 5.85E-06 5.54E-07 8.70E-07
Lower large intestine wall 2.06E-07 7.54E-10 4.30E-08 3.97E-07 1.64E-04 4.11E-06 6.64E-07 1.74E-06 5.57E-08 7.00E-08 4.28E-07 1.40E-07 4.93E-08 9.65E-07
Small intestine 5.70E-07 1.78E-09 9.55E-08 3.00E-06 4.74E-06 5.49E-05 1.34E-06 8.69E-06 1.59E-07 2.06E-07 1.50E-06 8.38E-07 1.40E-07 8.07E-07
Stomach wall 1.74E-06 9.18E-09 5.23E-07 1.90E-06 9.34E-07 1.52E-06 1.03E-04 2.06E-06 1.16E-06 1.74E-06 1.74E-06 1.11E-06 8.23E-07 8.07E-07
Upper large intestine wall 6.81E-07 2.11E-09 9.54E-08 5.21E-06 2.21E-06 9.64E-06 1.74E-06 1.07E-04 2.06E-07 2.38E-07 1.47E-06 1.31E-06 1.75E-07 7.91E-07
Heart wall 2.05E-06 4.78E-08 2.06E-06 7.29E-07 7.64E-08 2.06E-07 1.74E-06 2.38E-07 6.32E-05 1.53E-04 5.86E-07 1.58E-06 3.00E-06 6.80E-07
Kidneys 5.22E-06 4.84E-09 2.07E-07 2.68E-06 5.85E-07 1.50E-06 1.74E-06 1.47E-06 5.39E-07 5.86E-07 1.68E-04 2.06E-06 5.08E-07 7.44E-07
Liver 3.01E-06 1.76E-08 5.85E-07 5.53E-06 1.75E-07 8.38E-07 1.04E-06 1.36E-06 1.45E-06 1.58E-06 2.06E-06 3.40E-05 1.38E-06 5.70E-07
Lungs 1.74E-06 9.70E-08 1.74E-06 4.91E-07 6.36E-08 1.40E-07 7.92E-07 1.74E-07 3.16E-06 3.00E-06 5.08E-07 1.38E-06 4.69E-05 6.80E-07
Muscle 8.54E-07 1.90E-07 3.64E-07 8.38E-07 8.86E-07 8.07E-07 7.28E-07 7.75E-07 6.33E-07 6.80E-07 7.44E-07 5.70E-07 6.80E-07 2.21E-06
Ovaries 2.69E-07 9.16E-10 4.47E-08 7.75E-07 9.02E-06 6.17E-06 4.90E-07 5.22E-06 7.81E-08 9.21E-08 5.70E-07 3.17E-07 7.62E-08 1.04E-06
Pancreas 7.11E-06 1.39E-08 5.23E-07 4.73E-06 3.65E-07 1.03E-06 8.22E-06 1.12E-06 1.74E-06 2.37E-06 3.64E-06 2.53E-06 1.23E-06 9.02E-07
Red marrow 1.90E-06 6.96E-07 4.91E-07 7.91E-07 1.58E-06 1.31E-06 6.32E-07 1.12E-06 8.85E-07 8.85E-07 1.34E-06 6.96E-07 8.85E-07 7.12E-07
Bone surfaces 1.06E-06 1.20E-06 3.49E-07 3.95E-07 6.65E-07 5.22E-07 3.79E-07 4.58E-07 5.85E-07 5.85E-07 6.17E-07 4.74E-07 6.64E-07 7.28E-07
Skin 3.17E-07 3.81E-07 6.65E-07 2.70E-07 3.01E-07 2.70E-07 3.17E-07 2.70E-07 3.17E-07 3.17E-07 3.65E-07 3.18E-07 3.48E-07 5.07E-07
Spleen 3.16E-06 1.91E-08 4.12E-07 8.25E-07 4.59E-07 7.59E-07 5.21E-06 6.96E-07 8.07E-07 1.11E-06 4.75E-06 5.54E-07 1.14E-06 7.75E-07
Testes 3.19E-08 1.66E-10 0.00E+00 9.69E-08 1.18E-06 2.54E-07 5.73E-08 2.06E-07 1.39E-08 1.59E-08 5.88E-08 3.20E-08 1.03E-08 7.91E-07
Thymus 4.90E-07 1.03E-07 2.21E-06 1.59E-07 3.66E-08 6.20E-08 3.65E-07 7.94E-08 6.02E-06 4.91E-06 1.90E-07 4.60E-07 2.06E-06 8.07E-07
Thyroid 8.92E-08 1.11E-06 2.86E-07 4.62E-08 7.87E-09 9.46E-09 4.78E-08 1.92E-08 3.64E-07 3.64E-07 5.87E-08 9.67E-08 6.65E-07 8.70E-07
Urinary bladder wall 1.03E-07 4.63E-10 2.87E-08 4.43E-07 3.16E-06 1.44E-06 2.06E-07 1.17E-06 3.98E-08 2.71E-08 2.06E-07 1.43E-07 2.71E-08 1.01E-06
Uterus 2.21E-07 8.35E-10 5.26E-08 8.54E-07 3.47E-06 5.38E-06 3.97E-07 2.53E-06 7.48E-08 8.74E-08 5.23E-07 2.70E-07 5.88E-08 1.03E-06
Total body 1.49E-06 1.17E-06 1.10E-06 9.67E-07 1.21E-06 1.34E-06 9.19E-07 1.14E-06 9.10E-07 1.46E-06 1.43E-06 1.43E-06 1.30E-06 1.28E-06
Source Organs

Lower Upper
TABLE 22-5 CONTINUED Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle

Source Organs

Cortical Trabecular Cortical Trabecular Urinary


Red Bone Bone Bone Bone Bladder Total
Target Organs Ovaries Pancreas Marrow Surface Surface Volume Volume Spleen Testes Thymus Thyroid Contents Uterus Body
Adrenals 2.69E-07 7.11E-06 1.90E-06 8.70E-07 8.70E-07 8.70E-07 8.70E-07 3.16E-06 3.19E-08 4.90E-07 8.92E-08 1.19E-07 2.21E-07 1.49E-06
Brain 9.16E-10 1.39E-08 6.96E-07 9.97E-07 9.97E-07 9.97E-07 9.97E-07 1.91E-08 1.66E-10 1.03E-07 1.11E-06 4.63E-10 8.35E-10 1.17E-06
Breasts 4.47E-08 5.23E-07 4.91E-07 3.01E-07 3.01E-07 3.01E-07 3.01E-07 4.12E-07 0.00E+00 2.21E-06 2.86E-07 2.23E-08 5.26E-08 1.10E-06
Gallbladder wall 7.59E-07 5.21E-06 8.68E-07 3.48E-07 3.48E-07 3.48E-07 3.48E-07 8.71E-07 9.37E-08 2.38E-07 4.62E-08 3.17E-07 8.40E-07 1.57E-06
Lower large intestine wall 8.22E-06 3.32E-07 1.49E-06 5.85E-07 5.85E-07 5.85E-07 5.85E-07 3.48E-07 1.46E-06 3.03E-08 6.59E-09 3.79E-06 3.16E-06 1.54E-06
Small intestine 6.17E-06 1.03E-06 1.31E-06 4.27E-07 4.27E-07 4.27E-07 4.27E-07 7.59E-07 2.54E-07 6.20E-08 9.46E-09 1.44E-06 5.38E-06 1.57E-06
Stomach wall 5.07E-07 8.69E-06 6.33E-07 3.16E-07 3.16E-07 3.16E-07 3.16E-07 5.06E-06 6.52E-08 3.65E-07 6.36E-08 1.90E-07 4.60E-07 1.47E-06
Upper large intestine wall 5.54E-06 1.09E-06 1.11E-06 3.80E-07 3.80E-07 3.80E-07 3.80E-07 6.97E-07 1.90E-07 9.06E-08 1.92E-08 1.09E-06 2.69E-06 1.54E-06
Heart wall 9.21E-08 2.37E-06 8.38E-07 4.58E-07 4.58E-07 4.58E-07 4.58E-07 1.11E-06 1.59E-08 4.91E-06 3.64E-07 3.03E-08 8.74E-08 1.46E-06
Kidneys 5.70E-07 3.64E-06 1.34E-06 5.06E-07 5.06E-07 5.06E-07 5.06E-07 4.75E-06 5.88E-08 1.90E-07 5.87E-08 2.22E-07 5.23E-07 1.43E-06
Liver 3.17E-07 2.53E-06 6.96E-07 3.95E-07 3.95E-07 3.95E-07 3.95E-07 5.54E-07 3.20E-08 4.60E-07 9.67E-08 1.35E-07 2.70E-07 1.43E-06
Lungs 7.62E-08 1.23E-06 8.85E-07 5.53E-07 5.53E-07 5.53E-07 5.53E-07 1.14E-06 1.03E-08 2.06E-06 6.65E-07 1.92E-08 5.88E-08 1.30E-06
Muscle 1.04E-06 9.02E-07 7.12E-07 6.01E-07 6.01E-07 6.01E-07 6.01E-07 7.75E-07 7.91E-07 8.07E-07 8.70E-07 9.49E-07 1.03E-06 1.28E-06
Ovaries 4.72E-03 3.17E-07 1.53E-06 4.90E-07 4.90E-07 4.90E-07 4.90E-07 2.69E-07 0.00E+00 3.67E-08 7.87E-09 3.47E-06 9.96E-06 1.58E-06
Pancreas 3.17E-07 4.97E-04 1.15E-06 5.22E-07 5.22E-07 5.22E-07 5.22E-07 9.16E-06 4.62E-08 4.42E-07 8.90E-08 1.49E-07 3.17E-07 1.57E-06

22  •  Internal Radiation Dosimetry


Red marrow 1.53E-06 1.15E-06 2.04E-05 1.58E-06 1.04E-05 1.58E-06 8.44E-06 7.28E-07 2.69E-07 6.65E-07 6.17E-07 6.17E-07 1.06E-06 1.21E-06
Bone surfaces 5.85E-07 6.32E-07 1.14E-05 1.59E-05 1.98E-05 8.73E-06 1.31E-05 4.75E-07 4.12E-07 4.75E-07 7.59E-07 3.64E-07 4.42E-07 1.59E-06
Skin 2.70E-07 2.70E-07 3.96E-07 4.75E-07 4.75E-07 4.75E-07 4.75E-07 3.33E-07 8.71E-07 4.12E-07 3.81E-07 3.33E-07 2.70E-07 1.03E-06
Spleen 2.69E-07 9.16E-06 7.28E-07 3.96E-07 3.96E-07 3.96E-07 3.96E-07 2.81E-04 3.99E-08 2.71E-07 8.72E-08 1.27E-07 2.54E-07 1.43E-06
Testes 0.00E+00 4.62E-08 2.69E-07 3.48E-07 3.48E-07 3.48E-07 3.48E-07 3.99E-08 1.17E-03 6.76E-09 1.45E-09 2.53E-06 0.00E+00 1.28E-06
Thymus 3.67E-08 4.42E-07 6.65E-07 3.96E-07 3.96E-07 3.96E-07 3.96E-07 2.71E-07 6.76E-09 2.11E-03 1.11E-06 1.92E-08 3.51E-08 1.35E-06
Thyroid 7.87E-09 8.90E-08 6.17E-07 6.33E-07 6.33E-07 6.33E-07 6.33E-07 8.72E-08 1.45E-09 1.11E-06 2.11E-03 4.04E-09 7.39E-09 1.35E-06
Urinary bladder wall 3.63E-06 1.58E-07 6.47E-07 3.16E-07 3.16E-07 3.16E-07 3.16E-07 1.19E-07 2.53E-06 1.92E-08 4.04E-09 1.31E-04 8.69E-06 1.52E-06
Uterus 9.96E-06 3.17E-07 1.06E-06 3.79E-07 3.79E-07 3.79E-07 3.79E-07 2.54E-07 0.00E+00 3.51E-08 7.39E-09 8.21E-06 6.07E-04 1.60E-06
Total body 1.58E-06 1.57E-06 1.36E-06 1.28E-06 1.28E-06 1.28E-06 1.28E-06 1.43E-06 1.28E-06 1.35E-06 1.35E-06 8.66E-07 1.60E-06 1.28E-06

*Data from References 6 and 7.

423
424 Physics in Nuclear Medicine

EXAMPLE 22-10
Although effective dose is regarded as a
Estimate the effective dose E for an adult better indicator of overall radiation risk than
male following the injection of 250╯MBq of whole-body dose for radiation protection pur-
18
F-FDG. Assume any organs or tissues not poses, there still is debate about its relevance,
shown in Table 22-6 have a radiation dose and care should be taken in its use and inter-
of 1.5 × 10–2 mGy/MBq (approximately the pretation. In particular, effective dose is not
average of those that are listed). recommended for use in radionuclide therapy
applications, nor should it be used to evaluate
Answer the risk from a radionuclide study to a specific
Using the available dose values in Table 22-6 individual. This is because calculations of E
and the tissue weighting factors in Table 22-7, are based on an “average” human, whereas
and assuming that wR = 1, then the effective the actual dose can vary considerably with
dose is given by: body shape and size, as well as the specific
E = 0.12 × (1.3 × 10 −2 mGy/MBq) distribution of the radionuclide in the indi-
× 250 MBq (red marrow) vidual. This, along with some other general
limitations of internal radiation dose esti-
+ 0.12 × (3 × 10 −2 mGy
y/MBq) mates, is discussed in the next section.
× 250 MBq (colon, as sum of upper
and lower large intestine walls) 8.  Limitations of the MIRD Method
+ 0.12 × (1.7 × 10 mGy/MBq)
−2
There are a number of important limitations
× 250 MBq (lung) in the MIRD approach for calculating radia-
tion dose. Although Equation 22-18 is funda-
+ 0.12 × (1.3 × 10−2 mGy/MBq) mentally correct, the values of ϕ are currently
× 250 MBq (stomach) based on simplistic models of human anatomy
that assume specific relationships in the
+ 0.12 × (9.2 × 10−3 mGy/MBq) shape, size, and location of various organs
× 250 MBq (breast) (see Fig. 22-5). More realistic models of the
+ 0.08 × (1.3 × 10−2 mGy/MBq) human body, based on medical imaging data
and advanced computer modeling, are cur-
× 250 MBq (gonads) rently under development for dosimetry pur-
+ 0.04 × (1.9 × 10−1 mGy/MBq) poses. The MIRD formulation also implicitly
assumes that activity is distributed uniformly
× 250 MBq (bladder) within each organ and, furthermore, that
+ 0.04 × (1.5 × 10−2 mGy/MBq) energy is uniformly deposited throughout the
× 250 MBq (esophagus) organ. The assumption can cause a signifi-
cant error in the calculated dose from nonpen-
+ 0.04 × (1.6 × 10−2 mGy/MBq) etrating radiation (e.g., Auger electrons) when
× 250 MBq (liver) the activity is taken up in specific regions or
cell types within an organ. Local radionuclide
+ 0.04 × (1.0 × 10−2 mGy/MBq) concentrations and, hence, the absorbed dose

× 250 MBq (thyroid) can be much higher than organ average cal-
culations might suggest.
+ 0.01 × (1.2 × 10−2 mGy/MBq)  , also
Calculation of cumulated activity, A
× 250 MBq (bone surfaces) is problematic. Initially, with a new radio-
+ 0.01 × (1.9 × 10−2 mGy/MBq) pharmaceutical, this must be determined
from animal studies. There can be significant
× 250 MBq (brain) differences between the kinetics of a tracer in
+ 0.01 × (1.5 × 10−2 mGy/MBq) an animal model and in the human. Once a
radiopharmaceutical is approved for human
× 250 MBq (salivary glands) use, it is possible to obtain human data to
+ 0.01 × (8.4 × 10 −3 mGy/MBq) estimate A. However, values for healthy sub-
× 250 MBq (skin) jects may differ widely from those for patients
and from one patient to the next because of
+ 0.00923 × (2.67 × 10 −1 mGy/MBq) pathophysiologic effects on uptake, clearance,
× 250 MBq (sum of 13 listed and excretion of the radiopharmaceutical.
remainder tissues) Despite these limitations, the MIRD
method is a useful tool for comparing the
= 5.8 mSv (or 0.58 rem) average dose to various organs in patients for
22  •  Internal Radiation Dosimetry 425

TABLE 22-6â•…
RADIATION DOSE ESTIMATES FOR 18F-FLUORODEOXYGLUCOSE IN AN ADULT SUBJECT*

Organ mGy/MBq Organ mGy/MBq


Dose Administered Dose Administered
Adrenals 1.3 × 10–2 Muscle 1.1 × 10–2
Brain 1.9 × 10–2 Ovaries 1.7 × 10–2
Breasts 9.2 × 10–3 Pancreas 2.6 × 10–2
Gallbladder wall 1.4 × 10 –2
Red marrow 1.3 × 10–2
Lower large intestine wall 1.7 × 10–2 Bone surfaces 1.2 × 10–2
Small intestine 1.4 × 10 –2
Skin 8.4 × 10–3
Stomach 1.3 × 10–2 Spleen 3.7 × 10–2
Upper large intestine wall 1.3 × 10 –2
Testes 1.3 × 10–2
Heart wall 6.0 × 10–2 Thymus 1.2 × 10–2
Kidneys 2.0 × 10–2 Thyroid 1.0 × 10–2
Liver 1.6 × 10 –2
Urinary bladder wall 1.9 × 10–1
Lungs 1.7 × 10–2 Uterus 2.3 × 10–2
*Data from reference 9.

TABLE 22-7â•… applications should incorporate data acquired


TISSUE WEIGHTING FACTORS USED FOR on the specific patient, as described in Example
CALCULATION OF EFFECTIVE DOSE (â•›Eâ•›)* 22-9.

Organ wT
Red marrow, colon, lungs, stomach, 0.12 each REFERENCES
breast Society of Nuclear Medicine (MIRD) and ICRP pub-
Gonads 0.08 lications, along with data available from refer-
ences 6 and 9, provide the basic data for calculating
Bladder, liver, esophagus, thyroid 0.04 each absorbed doses:
Brain, skin, salivary glands, bone 0.01 each 1. International Commission on Radiological Protec-
surfaces tion: Recommendations of the International Commis-
sion on Radiological Protection. ICRP Publication
Remainder tissues (adrenals, 0.12 total 103; Ann ICRP 37(2-4), 2007.
extrathoracic region, gallbladder, (0.00923 2. Eckerman KF, Endo A: MIRD: Radionuclide Data
heart, kidneys, lymphatic nodes, each) and Decay Schemes, New York, 2008, Society of
muscle, oral mucosa, pancreas, Nuclear Medicine.
prostate [males], small intestine, 3. Snyder W, Ford M, Warner G: Estimates of Specific
spleen, thymus, uterus/cervix   Absorbed Fractions for Photon Sources Uniformly
[females]) Distributed in Various Organs of a Heterogeneous
Phantom [MIRD Pamphlet No. 5 (revised)], New
*From reference 1. York, 1978, Society of Nuclear Medicine.
4. Cristy M, Eckerman K: Specific Absorbed Fractions
of Energy at Various Ages from Internal Photon
Sources (ORNL Report ORNL/TM-8381 V1-V7),
Oak Ridge, TN, 1987, Oak Ridge National
a wide variety of nuclear medicine procedures. Laboratory.
It also is an essential tool in the approval 5. Stabin, M, Watson E, Cristy M, et al: Mathematical
process for new radiopharmaceuticals. In cir- Models of the Adult Female at Various Stages of Preg-
nancy (ORNL Report ORNL/TM-12907), Oak Ridge,
cumstances in which the assumptions on TN, 1995, Oak Ridge National Laboratory.
which the MIRD approach is based are unac- 6. Radiation Dose Assessment Resource (RADAR):
ceptable, more complex and involved methods http://www.doseinfo-radar.com [accessed December
can be used. For example, microdosimetric 17, 2011].
(cellular level) calculations should be done for 7. Stabin MG, Siegel JA: Physical models and dose
factors for use in internal dose assessment. Health
radiopharmaceuticals that have very nonuni- Phys 85: 294-310, 2003.
form uptake in radiosensitive organs. As well, 8. Stabin MG, Sparks RB, Crowe E: OLINDA/EXM: The
radiation dose estimates for therapeutic second generation personal computer software for
426 Physics in Nuclear Medicine

internal dose assessment in nuclear medicine. J Nucl A general guide for performing internal dosimetry
Med 46: 1023-1027, 2005. calculations with the MIRD approach is the
9. Stabin MG, Stubbs JB, Toohey RE: Radiation Dose following:
Estimates for Radiopharmaceuticals (ORNL Report
Loevinger R, Budinger T, Watson E: MIRD Primer for
NUREG/CR-6345), Oak Ridge, TN, 1996, Oak Ridge
Absorbed Dose Calculations, New York, 1991, Society
Institute for Science and Education. Also available
of Nuclear Medicine.
electronically at http://orise.orau.gov/files/reacts/
dosetables.pdf [accessed December 17, 2011]. The following book is useful for MIRD calculations
10. International Commission on Radiological Protec- at the cellular level:
tion: 1990 Recommendations of the International
Goddu SM, Howell RW, Bouchet LG, et al: MIRD Cellular
Commission on Radiological Protection (ICRP Publi-
S Values, New York, 1997, Society of Nuclear
cation No. 60), New York, 1991, Pergamon Press.
Medicine.

BIBLIOGRAPHY Recommended textbooks on basic radiation biology


are the following:
An excellent overview of the topics in this chapter
is provided by the following detailed text: Hall EJ: Radiobiology for the Radiologist, ed 7, New York,
2011, Lippincott, Williams & Wilkins.
Stabin MG: Fundamentals of Nuclear Medicine Dosime- Forshier S: Essentials of Radiation Biology and Protec-
try, New York, 2008, Springer. tion, ed 2, Clifton Park, NY, 2008, Delmar Cengage
A comprehensive collection of materials and data Learning.
can be found at the Radiation Dose Assessment
Resource website:
http://www.doseinfo-radar.com [accessed December 17,
2011].
chapter
23 
Radiation Safety and
Health Physics

Chapter 22 dealt with the radiation dose have a beneficial effect on health, resulting
received by patients undergoing nuclear med- from stimulation of the immune system.4 This
icine procedures. This chapter deals primarily effect is known as radiation hormesis. A vigor-
with the exposure of personnel who work in ous debate about the biologic consequences of
nuclear medicine clinics and research labora- low levels of ionizing radiation, the relevance
tories and who are exposed to radiation in of absorbed dose estimates in assessing health
their normal working environment. Stored risks, and the effect of these findings on regu-
radioactive materials, handling of calibration lations pertaining to radiation exposure is
sources, preparation of radioactive materials likely to continue for some years to come.
for patients and phantoms, and proximity to Whatever the outcome of this debate, and
patients or phantoms to whom these prepara- even though the risks to personnel occupa-
tions have been administered all are potential tionally exposed to ionizing radiation in the
sources of radiation exposure. An additional nuclear medicine environment clearly are
problem is the potential for radiation expo- small (based on decades of historic data),
sure to nonlaboratory personnel, such as common sense dictates that radiation expo-
patient relatives, attending nursing staff, and sures in and around the nuclear medicine
even passers-by in the hallways adjacent to laboratory be kept as low as is reasonably
the laboratory. achievable.
The quantities of radioactive material used When considering possible health effects to
and radiation levels encountered in a nuclear nuclear medicine patients or occupationally
medicine laboratory generally are well below exposed personnel, it also is important to
what is necessary to cause any type of “radia- place the dose received in perspective by con-
tion sickness.” Of more concern are the long- sidering the radiation dose received by all of
term effects that may possibly result from us from natural background sources. These
chronic exposures to even low levels of radia- sources include naturally occurring radionu-
tion. The most important of these effects  clides in the body (e.g., 40K), cosmic radiation,
are genetic damage to cells (mutagenesis), and radionuclides that occur naturally in the
damage to chromosomes (clastogenesis), and environment. Effective doses to individuals
carcinogenesis. per year from these natural sources average
Presently, our understanding of the effects approximately 2.4╯mSv (typical range
of chronic exposure to low levels of radiation 1-13╯mSv).5 As shown in Example 22-10, a
is far from complete. Radiation protection 250-MBq injection of 18F-fluorodeoxyglucose
regulations and guidelines currently are leads to an effective dose of roughly 5.8╯mSv
based on a linear nonthreshold (LNT) model, (equal to the dose that would be received in
which assumes that there is no “threshold approximately 1.7 years from nature). The
dose” for these long-term effects and that the average effective dose to the extremities of
risk increases linearly with radiation dose.1 nuclear medicine technical personnel is on
There also are experiments, data, and pro- the order of 4╯mSv per year.6
posed radiation injury models that are incon- The analysis of problems in the handling
sistent with the LNT model.2,3 Some scientists of radiation sources and the development of
argue that studies involving low levels of safe handling practices are the general con-
radiation suggest that low doses actually cerns of the broad field of health physics. The
427
428 Physics in Nuclear Medicine

practices that are prescribed by this analysis radiation effects than are adults. The
are sometimes expressed formally as regula- developing embryo and fetus are espe-
tions and sometimes as “common sense” rec- cially sensitive.
ommendations. In this chapter we primarily 4. The type of radiation involved. In
discuss aspects of health physics and radia- general, densely ionizing radiation [i.e.,
tion safety practices as they apply to the high-linear energy transfer radiation
nuclear medicine laboratory. However, a (see Chapter 6, Section A.4)] such as α
further responsibility arises because nuclear particles, fission fragments, and other
medicine scientists and practitioners often nuclear particles, are more damaging
are among the first people contacted (e.g., by per gray of absorbed dose than is less
the media) for information on public-health densely ionizing radiation, such as β
radiation issues. Therefore it is wise to know particles and γ rays.
where reliable sources of information can be The dose-modifying factors in this list are
found. A number of international organiza- taken into account in preparing regulations
tions such as the International Commission and making recommendations for handling
on Radiological Protection (ICRP), the United of radioactive materials. For example, regu-
Nations Scientific Committee on the Effects lations specify different dose limits for differ-
of Atomic Radiation and the International ent parts of the body, for different time
Atomic Energy Agency provide useful reports periods, and for different age groups. To
and literature. Selected references and web- account for the differing hazards of different
sites are provided at the end of this chapter. types of radiation, the equivalent dose,
defined previously (see Chapter 22, Section
A.  QUANTITIES AND UNITS A), is used. For most of the radiation encoun-
tered in nuclear medicine, the equivalent
dose in sieverts (or rems) is numerically
1.  Dose-Modifying Factors equal to the absorbed dose in grays (or rads),
For health physics purposes, specification of although it must be emphasized that equiva-
the radiation absorbed dose in grays (see lent dose and absorbed dose are not the
Chapter 22, Section A) is inadequate for a same quantity and have different units. To
complete and accurate assessment of poten- account for differing hazards for different
tial radiation hazards. Although the relative organs and tissue types, the equivalent dose
risk of potential injury increases with increas- is modified by organ-specific weighting
ing absorbed dose values, several other dose- factors to compute the effective dose (see
modifying factors also must be taken into Chapter 22, Section B.7) to an individual.
account. In some older texts, and in current United
1. The part of the body exposed. Total-body States federal regulations (see Section B),
exposure carries a greater risk than the related quantities dose equivalent (in
partial-body exposure. Exposure of place of equivalent dose) and effective dose
major organs in the trunk of the body is equivalent (in place of effective dose) may be
more serious than exposure to the encountered. The conceptual difference is
extremities. The active blood-forming that equivalent dose is based on the average
organs, the gonads, and the lens of the absorbed dose in a specific tissue or an organ,
eye are especially sensitive to radiation whereas dose equivalent is based on the
damage. A superficial dose to the skin absorbed dose at a point in tissue. There also
(e.g., from an external source of β par- are differences in the scaling factors used to
ticles) is less hazardous than the same convert the absorbed dose into these quanti-
dose delivered to greater depths (e.g., ties. These quantities are summarized in
from an external source of γ rays or from Table 23-1. Broadly speaking, for nuclear
internally deposited radioactivity). medicine applications, equivalent dose and
2. The time span over which the radiation dose equivalent, as well as effective dose and
dose is delivered. A given number of effective dose equivalent, have similar numer-
grays delivered over a short period (e.g., ical values.
minutes or hours) has a greater poten-
tial for damage than the same dose 2.  Exposure and Air Kerma
delivered over a long period (e.g., months For the purpose of describing radiation levels
or years). in a radiation environment, an additional
3. The age of the exposed individual. Chil- quantity—exposure—has traditionally been
dren are more susceptible to injurious used. Exposure refers to the amount of
23  •  Radiation Safety and Health Physics 429

TABLE 23-1â•…
QUANTITIES USED IN HEALTH PHYSICS

Quantity Symbol Units Definition Comment


Equivalent dose HT Sv Average absorbed dose across a Replaces dose equivalent. See
tissue or organ T with weighting ICRP Publication 60 and
factors that depend on the type updated radiation weighting
and energy of radiation. See factors in ICRP Publication 103.
Chapter 22, Section A.
Effective dose E Sv Measure of absorbed dose to whole See ICRP Publication 60 (1991)
body based on multiplying and updated tissue weighting
equivalent dose by organ-specific factors in ICRP Publication 103
weighting factors. See Chapter 22, (2007).
Section B.7.
Dose equivalent H Sv Absorbed dose at a point in an Replaced by equivalent dose in
organ, with quality factors that ICRP Publication 60 but still
depend on the type of radiation. used in U.S. Federal regulations
See ICRP Publication 51. in 2012.
Effective dose HE Sv Introduced in ICRP Publication 26 Replaced by effective dose in ICRP
equivalent (1977) as a measure of effective Publication 60 (1991) but still
radiation dose to the whole body. used in U.S. Federal regulations
Is based on dose equivalent values in 2012.
multiplied by tissue weighting
factors.
Exposure X C/kg Amount of charge liberated per kg Traditional units were the
of air by a γ -ray or x-ray source. Roentgen (R) in which 1R = 2.58
× 10−4╯C/kg. Exposure replaced
by air kerma.
Air kerma K Gy Amount of kinetic energy released For radionuclides used in nuclear
per kg of air by uncharged medicine, the conversion
ionizing radiation (photons and between air kerma and exposure
neutrons). is K(Gy) ≈ X(C/kg) × 33.7.

References:
ICRP Publication 26: Ann ICRP 1: 3, 1977.
ICRP Publication 51: Ann ICRP 17: 2-3, 1987.
ICRP Publication 60: Ann ICRP 21: 1-3, 1991.
ICRP Publication 103: Ann ICRP 37: 2-4, 2007.
ICRP, International Commission on Radiological Protection.

ionization of air caused by a γ-ray or x-ray quantity known as air kerma. Kerma stands
source. The traditional unit of exposure is the for kinetic energy released in media. Exposure
roentgen (R), with subunits of milliroentgens refers to the ionization charge produced in air,
(1╯mR = 10−3╯R), microroentgens (1╯µR = whereas air kerma refers to the amount of
10−6╯R), and so on. An exposure of 1╯R implies kinetic energy released in air (Table 23-1).
ionization liberating an amount of charge More precisely, the air kerma is the sum of
equal to 2.58 × 10−4 coulombs/kg of air, or the kinetic energy of all charged particles pro-
approximately 2 × 109 ionizations per cc of dry duced by interactions from a source of x rays
air at standard temperature and pressure. An or γ rays (through Compton scatter, photoelec-
exposure rate of 1╯R╛/min implies that this tric absorption, or pair production) per kg of
amount of ionization is produced during 1 air. The units of air kerma are grays ( J/kg),
minute. The SI unit for exposure is the the same as for absorbed dose. If all of the
coulomb/kg, with no special name. Thus 1 photon energy transferred to charged parti-
coulomb/kg ≈ 3876╯R and 1╯R = 2.58 × 10−4 cles is deposited locally (in air, bremsstrah-
coulombs/kg. lung production is negligible, so this is a
The use of the SI units for exposure is cum- reasonable assumption), then the absorbed
bersome, and therefore in the transition to SI dose in air has the same value as the air
units, exposure is being replaced by a related kerma. Using the fact that 33.7╯eV of energy
430 Physics in Nuclear Medicine

is required to produce an ion pair in air (see The factor f depends on the mass attenua-
Table 7-1), and assuming bremsstrahlung tion coefficients (Chapter 6, Section D.1) of the
losses can be ignored, the relationship medium of interest and of air and is energy
between exposure, X, and air kerma, K, can dependent. Figure 23-1 shows the value of f as
be calculated as: a function of energy for bone and for soft
tissues. For soft tissues, f ≈ 1.1. The value is
K (Gy) ≈ X (C/kg) × 33.7 (23-1) close to unity because the mass attenuation
properties of soft tissues and air are similar.
The conversion between traditional units of For low-energy photons (E  100╯keV), the
exposure and air kerma is given by: value of f for bone is greater than unity.
Because of photoelectric absorption by the
K (Gy) ≈ X (R) × 0.00869 (23-2) heavier elements in bone (Ca and P), energy
absorption in bone is greater than energy
Exposure and air kerma are useful quanti- absorption by air at these energies; however,
ties because they can be measured using  for most of the γ-ray energies commonly
ionization chambers, which are basically employed in nuclear medicine, the value of f
ionization-measurement devices (Chapter 7, for bone also is close to 1.
Section A.2). Specific instruments used for Thus for practical purposes air kerma (in
health physics measurements are described grays) is approximately equal numerically to
in Section E. the absorbed dose in grays that would be
If the air kerma in Gy is known at a certain received by an individual at that location, and
location, the absorbed dose in Gy that would in turn, as described in Section A.1, the
be delivered to a person at that location can absorbed dose in grays is numerically equal
be estimated by means of a scaling factor, f. to the equivalent dose in sieverts. Because of
This factor is defined as the ratio of the their approximate numerical equivalence,
absorbed dose in the medium of interest, Dmed, grays and sieverts, or in traditional units,
to the absorbed dose in air, Dair: roentgens, rads and rems, are sometimes
(mis)used as approximately interchangeable
f = Dmed /Dair ≈ Dmed /K (23-3) quantities; however, one should be aware that

5.0

4.0
Water

3.0 Muscle

Bone
Scaling factor, f

2.0

1.0

0.5
0.01 0.10 1.00 10.00

Photon energy (MeV)


FIGURE 23-1  Scaling factor f versus photon energy for water, muscle, and bone.
23  •  Radiation Safety and Health Physics 431

they represent distinctly different physical limited-scope licenses. The NRC permits the
quantities. institutional radiation safety committee to
authorize individuals to use radionuclides
under the license rather than requiring them
B.  REGULATIONS PERTAINING TO to be listed specifically on the license.
THE USE OF RADIONUCLIDES The NRC also issues regulations that must
be observed by licensees in the use of radio�
Regulations for the transport, handling, and active materials. These regulations are pub-
exposure to ionizing radiation vary from lished in Title 10 of the Code of Federal
country to country. The discussion in this Regulations (CFR). Two of the more relevant
section limits itself to the regulations in place sections of these regulations for nuclear medi-
in the United States in 2012 and uses selected cine are Part 20 (10CFR20), covering radia-
regulations to highlight important regulatory tion protection, and Part 35 (10CFR35),
concepts. A complete discussion of the many covering medical uses. The NRC regulations
regulations involved is beyond the scope of are based primarily on the recommendations
this chapter. Also, the regulations are under of two advisory bodies, the ICRP and the
constant review and subject to periodic National Council on Radiation Protection 
changes. Therefore the regulations presented and Measurement (NCRP), as discussed in
in this section should not be used to deter- Section B.7. The NRC also periodically issues
mine compliance without checking that they regulatory guides to assist licensees in the
are still current. Further information may  interpretation and implementation of its
be obtained in the references at the end  regulations.
of the chapter or from institutional health In addition to the NRC, several other gov-
physicists. ernment agencies are involved in the regula-
tion of radioactive materials, such as the U.S.
Department of Transportation (shipping reg-
1.  Nuclear Regulatory Commission ulations) and the U.S. Food and Drug Admin-
Licensing and Regulations istration (pharmaceutical aspects).
The use and distribution of radioactive mate-
rials in the United States are under the 2.  Restricted and Unrestricted Areas
primary control of the Nuclear Regulatory The NRC regulations prescribe different
Commission (NRC). The NRC issues licenses maximum radiation limits for restricted and 
to individuals and to institutions to possess unrestricted areas. A restricted area is one 
and use radioactive materials. In addition to “… access to which is controlled by the licensee
medical uses, industrial, research, educa- for the purposes of protection of individuals
tional, and other uses of radioactive materials from exposure to radiation and radioactive
also require NRC licensing. In some states, materials.” Normally, restricted areas are not
the NRC has entered into an agreement to accessible to the general public, and generally
transfer its regulatory and licensing functions they are occupied only by individuals whose
to a radiation control agency within the state. employment responsibilities require them to
Such states are called agreement states. work with radioactive materials and other
Medical licenses generally fall into one of radiation sources. Such individuals (e.g.,
two categories: specific licenses of limited nuclear medicine physicians, technicians, and
scope or specific licenses of broad scope. radiochemists) are said to be occupationally
Limited-scope licenses are for limited kinds exposed. Administrative staff, janitorial per-
and quantities of radionuclides, which are sonnel, and facilities maintenance personnel
listed specifically in the license. They may be generally are not included in this category.
issued to individual physicians (e.g., in private Restricted areas must be clearly marked with
offices) or to institutions (e.g., hospitals). radiation warning signs.
Licenses issued to institutions also list the of
individuals authorized to practice under the 3.  Dose Limits
license. The dose limits specified in 10CFR20 are
Broad-scope licenses are issued to larger based on the general recommendations by the
institutions that require greater licensing ICRP and NCRP (Section B.7) that an indi-
flexibility (e.g., basic research as well as vidual’s total effective dose (see Chapter 22,
medical uses in a university setting). Broad- Section B.7) should not exceed 50╯mSv (5╯rem)
scope licenses generally cover more radio� per year. Furthermore, 10CFR20 requires
nuclides and greater quantities than do that the deep-dose equivalent (dose
432 Physics in Nuclear Medicine

equivalent at a depth of 1╯cm in tissue) to any limits are shown in Table 23-2 for radionu-
individual organ or tissue (excluding the lens clides that are used in nuclear medicine.
of the eye) should not exceed 500╯mSv (50╯rem)
per year. The limit for shallow-dose equiva- 5.  Environmental Concentrations and
lent (dose equivalent at a depth of 0.007╯cm Concentrations for Sewage Disposal
in tissue) to the skin and extremities also is The NRC regulations also specify the environ-
500╯mSv (50╯rem) per year. The most restric- mental concentrations of radioactivity in air
tive limit is to the lens of the eye, which has and water and the concentration of radio�
an annual limit of 150╯mSv (15╯rem). The nuclides disposed of into sewage water, which
annual occupational dose limits for minors would lead to the annual dose limits described
(<18 years of age) are 10% of the annual dose in Section B.3 for the general public. Radio�
limits specified for adult workers. The dose active concentrations in sewage are of concern
equivalent to an embryo or fetus should not because they may eventually reach public
exceed 5╯mSv (0.5╯rem). water supplies. These limits assume continu-
These dose limits, which apply to occupa- ous inhalation or ingestion by the general
tionally exposed personnel, are called occupa- public over a period of 1 year, and they further
tional dose limits. Occupational dose limits do assume that the average person breathes 2 ×
not include radiation doses received by the 104╯mL of air per minute and has an annual
occupationally exposed individual while that water intake of 7.3 × 105╯mL. Sewer water is
individual is undergoing a medical examina- assumed to be diluted by a factor of 10 before
tion, nor do they include any radiation dose it is ingested. The methods for calculating
from natural radiation sources, such as cosmic these concentrations are described in
rays and naturally occurring radioactivity in 10CFR20. Table 23-3 shows these concentra-
the environment. tions for several radionuclides of interest.
Note that the regulations require the
licensee to control radiation doses not only 6.  Record-Keeping Requirements
from licensed materials but from “other The NRC regulations require that rather
sources in the licensee’s possession” as well extensive records be kept by the licensee.
(e.g., nonlicensed radioactive materials or an These include, among others, personnel
x-ray generator). Thus a licensee would be in dosimetry and radiation survey records
violation of the regulations if the occupation (Section E), wipe testing records for sealed
limits were exceeded even if most of the  sources, summaries of quality control checks
radiation dose were caused by nonlicensed on radiation monitoring equipment, inventory
sources.
For individual members of the public, the
annual effective dose equivalent limits are
1╯mSv (0.1╯rem). Radiation levels in un�
restricted areas should deliver a radiation TABLE 23-2â•…
dose of less than 0.5╯µSv/hr (0.05╯mrem/hr), CONCENTRATION OF AIRBORNE
assuming continuous occupation of the area. RADIOACTIVITY THAT WOULD RESULT IN
Transient radiation levels of up to 20╯µSv/hr THE ANNUAL DOSE LIMITS DESCRIBED IN
(2╯mrem/hr) are permitted. SECTION B.3 FOR OCCUPATIONALLY
EXPOSED PERSONNEL
4.  Concentrations for Airborne
Radioactivity in Restricted Areas Air Concentration
A particular problem in nuclear medicine Radionuclide µCi/mL kBq/mL
laboratories is the potential for leakage or 3
H 2 × 10 −5
0.74
escape of radioactive gases (e.g., 133Xe used in
pulmonary function studies) or volatile radio- 11
C 2 × 10−4 7.4
active material (e.g., concentrated 131I solu- 14
C 1 × 10 −6
3.7 × 10−2
tions). The NRC regulations specify the 18
F 3 × 10−5 1.1
concentrations for airborne radioactive mate-
rials that would result in the annual dose
99m
Tc 6 × 10 −5
2.2
limits described in Section 3. These calcula- 125
I 3 × 10 −8
1.1 × 10−3
tions assume that the workers are chronically 131
I 2 × 10 −8
7.4 × 10−4
exposed to these concentrations during a
2000-hour working year and that 2 × 104╯mL
133
Xe 1 × 10−4 3.7
of air is breathed per minute. Concentration Data from 10CFR20, Appendix B, Table 1.
23  •  Radiation Safety and Health Physics 433

TABLE 23-3â•…
ENVIRONMENTAL CONCENTRATIONS (AIRBORNE AND WATER) AND SEWAGE
CONCENTRATIONS THAT WOULD RESULT IN THE ANNUAL DOSE LIMITS DESCRIBED IN
SECTION B.3 FOR THE GENERAL PUBLIC IF CONTINUOUSLY INHALED OR INGESTED

Environmental Concentrations
Air Water Sewage Concentration
Radionuclide µCi/mL kBq/mL µCi/mL kBq/mL µCi/mL kBq/mL
3
H 1 × 10 −7
3.7 × 10 −3
1 × 10−3
3.70 × 10 1
1 × 10 −2
3.70 × 102
11
C 6 × 10 −7
2.2 × 10 −2
6 × 10−3
2.22 × 10 2
6 × 10 −2
2.22 × 103
14
C 3 × 10−9 1.1 × 10−4 3 × 10−5 1.11 × 100 3 × 10−4 1.11 × 101
18
F 1 × 10−7 3.7 × 10−3 7 × 10−4 2.59 × 101 7 × 10−3 2.59 × 102
99m
Tc 2 × 10 −7
7.4 × 10 −3
1 × 10−3
3.70 × 10 1
1 × 10 −2
3.70 × 102
125
I 3 × 10−10 1.1 × 10−5 2 × 10−6 7.40 × 10−2 2 × 10−5 7.40 × 10−1
131
I 2 × 10 −10
7.4 × 10 −6
1 × 10−6
3.70 × 10 −2
1 × 10 −5
3.70 × 10−1
133
Xe 5 × 10−7 1.9 × 10−2 — — — —
Data from 10CFR20, Appendix B, Tables 2 and 3.

and disposal records, minutes of radiation C.  SAFE HANDLING OF RADIOACTIVE


safety committee meetings, and records of MATERIALS
training in radiation safety of laboratory per-
sonnel. Maintenance of proper records is one
of the major activities of an NRC licensee. 1.  The ALARA Concept
Radiation dose limits and other restrictions
7.  Recommendations of Advisory specified in NRC regulations are legal limits
Bodies that must not be exceeded at any time by an
The NRC regulatory limits are based on rec- NRC licensee; however, they should not be
ommended radiation dose limits published by considered as thresholds below which expo-
various advisory bodies. These bodies include sure to radiation is of no concern. Presently,
the NCRP, a U.S. organization, and two inter- although the radiation hazards associated
national groups, the ICRP and the Inter� with the limits specified in the regulations are
national Commission on Radiological Units very small, they are not assumed to be totally
(ICRU). The last group is concerned mostly risk free, and any reasonable technique for
with definitions of radiologic units. Recom- reducing radiation dose may have potential
mendations from these groups do not carry the benefits in the long run.
force of law; however, there is a tendency of Recognizing this, the NCRP as early as
regulatory agencies such as the NRC to convert 1954, and more recently the NRC regulations,
them into law. Therefore, it is worthwhile to have recommended as an operating philoso-
keep abreast of their recommendations. phy that the objective of radiation safety prac-
Some titles of NCRP and ICRP reports that tices should be not simply to keep radiation
are applicable to nuclear medicine are listed doses within legal limits but to keep them “as
in the references at the end of the chapter. low as reasonably achievable” (ALARA). In
Table 23-4 lists the dose limits currently rec- its regulations, the NRC has defined ALARA
ommended by the NCRP and the ICRP. Note to mean “as low as reasonably achievable
that their coverage is somewhat broader than taking into account the state of technology
those appearing in the NRC regulations. Note and economics of improvement in relation to
also the restrictive limits placed on pregnant benefits to the public health and safety, and
women with respect to the fetus. A pregnant, other societal and socioeconomic consider-
occupationally exposed woman may require ations, and in relation to the use of atomic
special work restrictions to ensure that this energy in the public interest.” NRC Regula-
dose limit for the fetus is not exceeded during tory Guides 8.10 (“Operating Philosophy for
her pregnancy. Maintaining Occupational Exposures as Low
434 Physics in Nuclear Medicine

TABLE 23-4â•… The concept of ALARA has long been the


DOSE LIMITS RECOMMENDED BY THE operational objective of radiation safety prac-
INTERNATIONAL COMMISSION ON tices in well-run nuclear medicine laborato-
RADIOLOGICAL PROTECTION AND THE ries, and they have now taken on regulatory
NATIONAL COUNCIL ON RADIATION force. ALARA principles can be applied to the
PROTECTION AND MEASUREMENT handling of radiation sources, to storage and
shielding techniques, and to the design and
NCRP* layout of the laboratory. Some of the basic
(1993) ICRP† (2007)
techniques for keeping radiation doses
Occupational “ALARA” are discussed later.
Exposure
Effective dose: 50╯mSv 20╯mSv/year
2.  Reduction of Radiation Doses from
Annual averaged over  
5 years, no External Sources
more than Types of Sources. External sources are those
50╯mSv in any that deliver a radiation dose from outside the
one year body. The principal sources are γ-ray- and
Effective dose: 10╯mSv × age 100╯mSv in any x-ray-emitting radionuclides in patients,
Cumulative (years) 5-year period syringes, vials, waste disposal areas, and so
Equivalent   150╯mSv to 150╯mSv to   forth. Unshielded emitters emitting particles
dose: Annual lens of eye lens of eye of sufficient energy to travel some distance in
500╯mSv to 500╯mSv to air (e.g., 32P, but not 14C) also constitute an
skin, hands, skin, hands, external hazard, although β particles gener-
and feet and feet ally deliver only a superficial radiation dose
General Public to the skin.
Exposure Air Kerma Rate Constant. The air kerma
Effective dose: 1╯mSv if 1╯mSv; higher caused by γ-ray and x-ray emitters can be
Annual continuous if needed as estimated from the air kerma rate constant,
5╯mSv if long as average Γ. This constant has a specific value for each
infrequent over 5 years radionuclide and is defined as the air kerma
does not exceed caused by γ-ray and x-ray emissions, in mGy
1╯mSv per hour, at a distance of 1╯m from an
Equivalent dose: 50╯mSv to 15╯mSv to lens unshielded 1-GBq point source of that radio-
Annual skin, hands, of eye nuclide. The units for Γ are mGy • m2/Gbq •
and feet 50╯mSv to skin hr. Calculation of the air kerma rate constant
Embryo-Fetus is based on the number of γ-ray and x-ray
emissions from the radionuclide (number per
Equivalent 0.5╯mSv per Same as disintegration) and their energies, and on the
dose month once general public
absorption coefficient of air at these energies.
pregnancy exposure, even
declared for occupational Values of Γ for some radionuclides used in
exposure nuclear medicine are summarized in Table
23-5. For practical health physics purposes,
ICRP, International Commission on Radiological
Protection; NCRP, National Council on Radiation the calculation of Γ should only include γ and
Protection and Measurement. x rays above a certain minimum energy value
*Limitation of Exposure to Ionizing Radiation (NCRP because photons of a lower energy have such
Report No. 116), 1993. low penetrating power (e.g., through the

2007 Recommendations of the International Commission walls of a syringe or vial) that they pose a
on Radiological Protection (ICRP Publication No. 103). negligible external hazard. The minimum
Annals of the ICRP, 2-4, 2007. energy used to compute the values in Table
23-5 is 20╯keV.
To estimate the air kerma rate KR(mGy/hr)
at a distance d(m) from an activity A(GBq) of
as Reasonably Achievable”) and 8.18 (“Infor- a radionuclide having an air kerma rate con-
mation Relevant to Ensuring that Occupa- stant Γ(mGy • m2/GBq • hr), the following
tional Radiation Exposures at Medical equation is used:
Institutions will be as Low as Reasonably
Achievable”) provide practical advice on
implementation of ALARA principles. KR = AΓ/d2 (23-4)
23  •  Radiation Safety and Health Physics 435

TABLE 23-5â•…
γ RAY AIR KERMA RATE CONSTANTS FOR SEVERAL RADIONUCLIDES OF INTEREST IN
NUCLEAR MEDICINE

Radionuclide Γ (mGy · m2/GBq · hr) Radionuclide Γ (mGy · m2/GBq · hr)


11 99m
C 0.1393 Tc 0.0141
13 111
N 0.1394 In 0.0831
15 123
O 0.1395 I 0.0361
18 125
F 0.1351 I 0.0377
57 131
Co 0.0141 I 0.0522
60 133
Co 0.3090 Xe 0.0143
67 137 137
Ga 0.0195 Cs/ Ba 0.0821
68 201
Ga 0.1290 Tl 0.0102
99 99m
Moâ•›/â•› Tc (at equilibrium) 0.0336
Data from Ninkovic MM, Raicevic JJ, Adrovic F: Air kerma rate constants for gamma emitters used most often in
practice. Radiat Prot Dos 115:247-250, 2005.

The appearance of d2 in the denominator of air kerma rates. The relationship between the
Equation 23-4 is an expression of the inverse- two is given by
square law (see Chapter 11, Section A.2).
Because γ rays and x rays are emitted isotro-
XR (R/hr) ≈ KR (mGy/hr) × 0.115 (23-5)
pically (e.g., with no preferred direction) radi-
ation intensity and dose levels decrease as the
square of the distance from the source. The equivalent dose rate to a particular
tissue or organ and the effective dose rate to
EXAMPLE 23-1 an individual can be estimated from the air
Calculate the air kerma rates at 10-cm and kerma rates using the appropriate radiation
300-cm distances from a syringe containing weighting factors and tissue weighting factors
1╯GBq of 99mTc. (see Chapter 22, Sections A and B.7), but
strongly depend on patient geometry and the
Answer direction from which the radiation is incident
The air kerma rate constant Γ is 0.0141╯mGy on the individual. Some publications estimate
2
• m /GBq • hr (see Table 23-5). Therefore from dose equivalent rates in mSv/hr using simpli-
Equation 23-4, at 10╯cm fied tissue models. These values are numeri-
cally higher than the air kerma rates as they
KR = 1 GBq × 0.0141 mGy i include the conversion from air kerma to
tissue absorbed dose (a factor of ~1.11 in soft
m2 /GBq i hr ÷ (0.12 ) m2 tissue), and also are increased by the contri-
= 1.41 mGy/hr butions of Compton-scattered photons within
the body.
and at 300╯cm, Equation 23-4 is accurate for distances
that are large in comparison to the physical
KR = 1 GBq × 0.0141 mGy i size of the source; however, it is not valid at
very small distances. For example, it predicts
m2 /GBq i hr ÷ (32 ) m2 that the air kerma rate, and therefore the
= 1.57 × 10 −3 mGy/hr equivalent dose, becomes infinite as d
= 1.57 µGy/hr approaches zero. A practical situation in
which this problem arises is in the estimation
of equivalent dose rates on contact with the
The strong effect of distance on radiation dose source, for example, equivalent dose rates to
equivalent rate is illustrated by Example 23-1. the hand while handling syringes and vials.
In some texts, exposure rates, XR These equivalent dose rates have been deter-
(roentgens/hr), may be encountered instead of mined experimentally for 99mTc. They range
436 Physics in Nuclear Medicine

from about 0.14╯mSv/MBq • hr on the surface As shown by Example 23-1, distance can
of larger syringes (10 to 20╯mL) up to approxi- have a marked effect on radiation levels.
mately 0.7╯mSv/MBq • hr for smaller syringes Increasing distance always has a dose-
(1 to 2╯mL).7 Equivalent dose rates to the reduction effect. Direct contact with radiation
hands on contact with syringes containing  sources should be avoided by any available
~1000╯MBq of 99mTc can be in the range of means, such as by using tongs to handle vials.
several mSv/min, an obvious matter of concern Patient study areas (e.g., imaging rooms)
in operations requiring handling of these should be arranged to permit the technician
sources. The use of syringe shielding there- to operate instrumentation at reasonable dis-
fore is indicated and can significantly reduce tances (e.g., 2╯m) from the patient. Separate
the radiation dose. waiting areas should be provided for patients
Time, Distance, Shielding (TDS) Rules. who have been injected with radioactivity and
The basic principles for reducing radiation for relatives, orderlies, and patients not
doses from external sources are described by requiring radioactive injections. Reception
the “TDS” rules, for time, distance, and areas should not be used as waiting areas for
shielding: radioactive patients. Storage areas for gen-
1. Decrease the time of exposure. erators, radioactive trash, and other high-
2. Increase the distance from the source. level sources should be remote from regularly
3. Use shielding when practical and occupied areas of the laboratory. Special
effective. attention should be given to their location in
Time of exposure is decreased by working relation to unrestricted areas. (They also
with or in the vicinity of radiation sources as should be remote from imaging rooms and
rapidly as possible, consistent with good tech- counting rooms to minimize instrument back-
nique. Personnel should spend as little time ground levels.)
as possible in “hot labs” and other high-level Examples of effective use of shielding are
radiation areas. In particular, these areas lead pigs for storage of vials and generators,
should not be used for visiting, discussing lead-lined syringe holders, lead aprons, lead
problems unrelated to activities in the area, bricks for lining storage areas, and lead- 
and so on. Laboratory monitors should be lined drawing stations (Fig. 23-2). Leaded
used in these areas to warn personnel when glass provides comfortable viewing and radia-
high-level radiation sources are present. tion protection simultaneously, especially 

FIGURE 23-2  Examples of protective shielding devices used in nuclear medicine. Left, Shielded syringe holder
designed for positron-emitting radionuclides. Right, Lead-lined drawing station for preparing and handling low-energy
gamma-emitting radioactive materials (150╯keV) such as 99mTc. Lead-lined glass provides a good view of the work
area. (Photographs courtesy Biodex Medical Systems, Inc., Shirley, NJ.)
23  •  Radiation Safety and Health Physics 437

for low-energy γ-ray and x-ray emitters workers. Patient sweat or excreta, linens
(200╯keV). Dose calibrators should be used on imaging tables, spillage occurring
enclosed in a shielded area, using lead sheets during transfer of activity between containers
or bricks, to avoid unnecessary exposure and syringes, radioactive trash, and radio�
during measurement of radiopharmaceutical active gases released during pulmonary func-
activity. tion tests are examples of potential sources.
Table 6-4 lists tenth-value thicknesses A radioactive material that has been acci-
of lead for several γ-ray and x-ray emitters. dentally or carelessly ingested is an “uncon-
Small thicknesses of lead (1╯mm) provide trolled source”; once it is inside the body,
effective shielding for low-energy emitters there is very little that can be done to reduce
(e.g., 133Xe and 99mTc). Lead-lined aprons, the radiation dose that it will deliver. (Tech-
which usually contain 0.25-mm- or 0.5-mm  niques developed by the weapons and reactor
-equivalent lead thicknesses, provide a modest industries for speeding the elimination of
amount of radiation protection, but probably radioactive materials from the body generally
not enough to warrant their routine use in the are slow to act and thus are useful only for
nuclear medicine laboratory; however, they very long-lived radionuclides, and impractical
may be useful for specific applications, such for nuclear medicine.) The cardinal rule for
as during handling of large quantities of  keeping radiation doses from internal sources
133
Xe (Eγ = 81╯keV) or during elution of a 99mTc ALARA is to prevent the entry of the radioÂ�
generator (Eγ = 140╯keV). Greater thickness active material into the body in the first place.
(>1╯cm) is required for higher-energy γ-ray To a certain extent, this is a matter of careful
emitters, such as 131I (Eγ = 364╯keV); however, design of laboratory facilities, but equally as
lead is still an effective shielding material at important, it is a matter of developing good
these energies. Concrete and similar materi- laboratory work habits.
als find limited use for general purpose shield- Some basic rules for avoiding internal radi-
ing in nuclear medicine. ation doses are the following:
Shielding is very effective for β emitters. A 1. No eating, drinking, smoking, or apply-
few millimeters of almost any solid material ing of cosmetics should occur in areas
will stop even the most energetic β particles where open sources may be present
(see Fig. 6-10 and Table 6-1). In this (e.g., hot labs and patient study areas).
case, however, low-Z materials (e.g., plastic,  2. Lab coats and gloves should be worn
ordinary glass) are preferred over high-Z when handling radioactive sources.
materials (e.g., leaded glass) to minimize Gloves should be handled so as to avoid
bremsstrahlung production (see Equation contamination of their inside surfaces.
6-1). A good shielding arrangement for a high- Lab coats, aprons, and other protective
energy β emitter, such as 32P, is to use a plastic clothing should stay in the laboratory
or glass container for the radioactive material (i.e., they should not worn outside the
to stop the β particles and then to place this in lab or taken home).
a lead container to absorb the bremsstrahlung 3. No foodstuffs or drinks should be stored
radiation (see Fig. 6-3). A similar approach can where radioactive sources are kept,
be employed with positron emitters; however, such as in laboratory refrigerators.
the thickness of the lead must be substantial 4. Pipetting should never be done by
(tenth-value thickness for 511-keV photons is mouth.
13.4╯mm) to provide effective shielding against 5. Personnel should wash their hands
the annihilation radiation. after working with radioactive sources
(a sink should be available in the labo-
ratory), and they should be checked 
3.  Reduction of Radiation Doses from for contamination on a laboratory radi-
Internal Sources ation monitor (Section E.1). Hands
Types of Sources. Nearly all nuclear medicine should also be monitored before going
personnel are required at one time or another to lunch or on breaks and before leaving
to work with radioactive sources in open or at the end of the day.
poorly sealed containers. There is always the 6. Work should be performed on absor-
possibility that in these operations some of bent pads to catch spills and prevent
the radioactive material will find its way into spattering of liquids.
the body, where it delivers a radiation dose as 7. Work with radioactive gases or other
an internal radiation source, or back to offices volatile materials (e.g., concentrated
or other areas accessible to nonradiation iodine solutions) should be performed
438 Physics in Nuclear Medicine

in a ventilated fume hood. These mate- offices, and so on, and away from imaging
rials also should be stored in a hood. and low-level counting rooms.
8. Work areas should be kept tidy. Radio- 2. Work surfaces and floors should be con-
active trash, contaminated pads, and structed using smooth, nonabsorbent
so forth should be disposed of promptly. materials free from cracks and crevices.
9. Radioactive storage areas (e.g., hot 3. Workbenches should be sufficiently
labs) should not be used to store other sturdy to support lead shielding.
materials, such as office supplies or 4. Washbasins and sinks should be conve-
linens. niently available where unsealed radio-
10. Needless contamination of light active materials are handled. It is
switches, doorknobs, and other items desirable that sinks in hot labs have
that could result in unsuspected con- foot- or elbow-operated controls.
tamination to personnel should be 5. The laboratory design should permit
avoided. separate storage of glassware and 
11. Containers with sharp or broken edges work tools (e.g., tongs, stirring devices)
should not be used for radioactive not used with radioactive materials 
materials. to prevent needless contamination or
12. Radioactive materials should be stored mixture with similar items used with
when they are not in use. radioactive preparations.
Studies with radioactive gases, such as
133
Xe, require special attention because of the 5.  Procedures for Handling Spills
potential for escape of radioactivity into the Accidental spills of radioactive materials are
laboratory and beyond. Optimally, the labora- infrequent occurrences in well-run nuclear
tory ventilation system should be designed to medicine laboratories. Also, the quantities of
maintain the laboratory under negative pres- radioactivity used in nuclear medicine do not
sure relative to its surroundings and should create “life-threatening” hazards. Neverthe-
be separate from other ventilation systems to less, radioactive spills should not be treated
prevent spread of airborne activity into other as events completely without hazard, and
areas of the hospital. A gas-trapping system laboratory personnel should be aware of the
should be used to collect gases exhaled by the appropriate procedures to follow when spills
patient. do occur.
Most of the rules listed earlier in this The steps to follow in dealing with a radio-
section are of the common-sense variety and active spill are (1) to inform, (2) to contain,
perhaps seem obvious; however, it is surpris- and (3) to decontaminate.
ing how often they are violated through for- 1. Individuals in the immediate work area
getfulness or indifference. This may explain should be informed that a spill has
the surprisingly high incidence of internal occurred so they can avoid contamina-
radionuclides found in some studies of nuclear tion if possible. Individuals outside the
medicine laboratory personnel (e.g., >70% immediate area should be warned so
incidence of radioactive iodine in thyroid they do not enter it. The radiation officer
glands).6 Clearly, adherence to proper labora- should be informed so that he or she
tory work rules is fundamental to the ALARA may begin supervising further action as
concept. soon as possible.
2. By whatever means are reasonably pos-
4.  Laboratory Design sible, but without risking further hazards
The principles of ALARA are enhanced by to themselves, laboratory personnel
careful attention to laboratory design. Several should attempt to contain the spill to
design aspects have been mentioned already prevent further spread of contamination.
in relation to other problems, such as negative A flask that has been tipped over should
relative air pressure in laboratories employing be uprighted. Absorbent pads should be
volatile or gaseous radioactive materials and thrown over a liquid spill. Doors should
availability of a fume hood with its own be closed to prevent the escape of air-
exhaust system for storage of these materials. borne radioactivity (e.g., gases, powders).
Some additional principles to be considered in The spill area should be closed off to
laboratory design are the following: prevent entry, especially by persons who
1. Hot labs and radioactive storage areas might not be aware of the spill. Personnel
should be located away from other busy monitoring for contamination should be
work areas, public corridors, secretarial started as soon as possible, so that
23  •  Radiation Safety and Health Physics 439

contaminated and uncontaminated into the environment—for example,


persons can be segregated. To prevent radioactive gases into the ventilation
the further spread of radioactivity, con- system or liquid wastes into the sink—
taminated individuals should not be provided that the concentrations do not
allowed to leave the area until they are exceed the values specified in 10CFR20
decontaminated, and uncontaminated (see Table 23-3). In keeping with the
individuals (with the exception of appro- ALARA concept, however, this tech-
priately protected emergency personnel nique should not be used if reasonable
and other designated personnel involved alternatives are available (e.g., steps 2
with the cleanup) should not be allowed and 3).
to enter the spill area. Contamination 2. Store and decay. For materials having
monitoring should be done using a sensi- reasonably short half-lives (e.g., a few
tive radiation monitoring instrument weeks or less), and if suitable storage
appropriate for the type of radioactivity space is available, this may be an eco-
involved. It is advisable that each  nomical and effective disposal tech-
laboratory have on hand a thin-window nique. After a decay period of 10
Geiger-Müller (GM) counter survey half-lives has elapsed, only 0.1% of the
meter (Section E.1) for handling such initial activity remains. It is advisable
situations. to separate waste materials into two
3. Personnel decontamination procedures categories: those having half-lives
should receive first priority, followed by shorter than 3 days and those having
decontamination of work areas, and so half-lives longer than 3 days, so that
on. Personnel involved in decontamina- long-term accumulation of large volumes
tion procedures should wear protective of waste material can be avoided. Dis-
clothing to avoid becoming contaminated posal by decay of materials with half-
themselves in the process. Contami- lives longer than approximately 1 month
nated skin should be flushed thoroughly is frequently impractical because of the
with water. Special attention should be long storage period required.
given to open wounds and contamination 3. Concentrate and bury. This is frequently
around the eyes, nose, and mouth. Con- the only effective means of disposal of
taminated clothing should be removed long-lived radioactivity, particularly if
and placed in plastic bags for storage. storage space is limited. A number of
After major localized areas of personnel commercial companies provide this type
contamination have been attended to, a of disposal service.
shower bath may be required to remove
more widely distributed contamination.
Decontamination of laboratory and work E.  RADIATION MONITORING
areas should not be attempted except under
the supervision of the radiation safety officer
or radiation health physicist. If the work sur-
1.  Survey Meters and Laboratory
faces and floors are constructed from a non� Monitors
absorbent material, soap and water is generally Survey meters are used to monitor radiation
all that is needed for decontamination. Con- levels in and near laboratories where radioac-
taminated areas should be cleaned “from tive materials or other radiation sources are
outside in” to minimize the spread of contami- present. Generally, they are battery operated
nation. Porous or cracked surfaces may create and portable. The radiation detector is usually
difficult problems. If complete decontamina- an ionization chamber or a GM tube (see Figs.
tion is not possible, it may be necessary to 7-3 and 7-11).
cover and shield the affected surfaces or Ionization chamber types are calibrated to
perhaps even to remove and replace them. read exposure levels. The full-scale reading
and range on the meter display is switch
selectable, typically from 0 to 3╯mR╛/╛hr up to
D.  DISPOSAL OF RADIOACTIVE WASTE 0 to 300╯mRâ•›/â•›hr. Many systems now also
provide readings in units of air kerma. Some
There are three general techniques for dispos- types have very thin mica or aluminum
ing of radioactive wastes. entrance windows for the ionization chamber
1. Dilute and disperse. Small quantities of and can be used to detect β particles as well
radioactive materials may be released as x rays or γ rays. Ionization chamber survey
440 Physics in Nuclear Medicine

meters give reasonably accurate estimates of clicking noise when radiation is detected in
exposure rates (±10%) over most of the nuclear addition to having a meter display of count-
medicine energy range. Most ionization ing rate. A laboratory monitor should be used
chamber survey meters do not have sealed in any area where large quantities of radio-
chambers. Thus for greatest accuracy their activity are handled (e.g., in a radio�pharmacy
readings should be corrected for ambient tem- laboratory) to warn of the presence of high
perature and pressure variations (see Chapter radiation levels. They also are useful for
7, Section A.2, Equation 7-1). These correc- monitoring hands after operations requiring
tions are small at sea-level pressures and the handling of radioactivity.
room temperatures; however, the pressure
correction factor may be significant at higher 2.  Personnel Dosimeters
elevations (~20% at 1600╯m). Personnel dosimeters are devices worn by
The accuracy of an ionization chamber laboratory personnel to monitor radiation
survey meter should be checked periodically doses from external sources. There are two
(e.g., annually, or following major repairs) general types: dosimeter badges, which are
using a radiation source producing a known used to measure cumulative doses over
radiation exposure level. Sealed sources used periods of weeks or months, and pocket dosim-
in radiation therapy departments are useful eters, which are generally used for monitoring
for this purpose. over a shorter term.
GM tube types of survey meters are more Dosimeter badges monitor radiation doses
sensitive than ionization chamber types using either a small piece of x-ray film, or
because they respond to individual ionizing much more commonly, thermoluminescent
radiation events. Most of these instruments dosimeter (TLD) chips (Fig. 23-3). TLDs gen-
have meters that display event counting rates erally use small “chips” of LiF, a material that
(cpm). Some types with thin mica or alumi- gives off light when heated after it has been
num entrance windows are suitable for detect- exposed to ionizing radiation. The amount of
ing α and β particles as well as γ rays and light given off is measured using a photoÂ�
x rays. Because of their relatively high sensi- multiplier tube while the chip is heated in an
tivity, GM-type survey meters are most useful oven inside a light-tight enclosure. The
for detecting small quantities of radioactivity amount of light given off is used to estimate
from minor spills, in waste receptacles, and the radiation dose received. There also are
so on. dosimeter badges based on optically stimu-
Laboratory monitors are very similar to lated (rather than heat-stimulated) lumines-
survey meters, but they are designed to be cence of materials such as Al2O3.
used at a fixed location rather than as por- Dosimeter badge services are provided by
table units. They are operated continuously; a number of commercial suppliers. New
thus they are generaÂ�lly plugged into the  badges are supplied at regular (e.g., monthly)
wall rather than battery operated. Most have intervals, and readings for the preceding
GM tube detectors and produce an audible period are reported back to the user, typically

FIGURE 23-3  Examples of personnel dosimeter badges. Left, Thermoluminescent dosimeter (TLD) badge, which
usually contains several TLD chips, with one chip being exposed through a thin Mylar window in the badge to permit
measurement of low-energy beta radiation. Right, Photograph of ring dosimeters that contain a single lithium fluoride
TLD chip and are useful for measuring the dose to the skin and hands from the handling of radionuclides. Bar codes
are used on most personnel monitors to permit easy identification and data logging when reading out the TLD chips.
(Courtesy Mirion Technologies, Irvine, CA.)
23  •  Radiation Safety and Health Physics 441

within about a month. The reports provided Turner JE: Atoms, Radiation, and Radiation Protection,
by most companies are satisfactory for NRC 2nd ed. New York, 1995, Wiley.
record-keeping purposes.
Pocket dosimeters were described in Regulatory documents can be found on the website
Chapter 7, Section A.2 (Fig. 7-5). They are of the Nuclear Regulatory Commission at http://
essentially ionization chamber devices that www.nrc.gov [accessed October 14, 2011]. Relevant
provide an immediate readout of radiation documents on this website include the following:
doses and thus are especially useful for mea- NRC Regulations:
suring over short periods or when a rapid 10CFR20: http://www.nrc.gov/reading-rm/doc-collections/
cfr/part020/index.html
indication of results is needed, such as during 10CFR35: http://www.nrc.gov/reading-rm/doc-collections/
complicated radiopharmaceutical prepara- cfr/part035/index.html
tion procedures. NRC Regulatory Guides (available at http://www.nrc.gov/
reading-rm/doc-collections/reg-guides/occupational-
3.  Wipe Testing health/rg/):
8.10: Operating Philosophy for Maintaining Exposures as
Wipe testing is used to detect small amounts Low as Reasonably Achievable
of radioactive contamination on bench-top sur- 8.18: Information Relevant to Ensuring that Occupa-
faces, on the outside of shipping packages, and tional Radiation Exposures at Medical Institutions
so on, or to detect small amounts of radioactive will be As Low As Reasonably Achievable
8.36: Radiation Dose to the Embryo/Fetus
leakage from sealed radioactive sources. The 8.39: Release of Patients Administered Radioactive
surface is wiped with an alcohol-soaked patch Materials
of gauze or cotton-tipped swab, which is then
counted in a well counter (for γ-emitting
nuclides) or a liquid scintillation counter (for The National Council on Radiation Protection and
Measurement website is at http://www.ncrp.com
β emitters). Contamination below the kBq [accessed October 14, 2011]. Important NCRP pub-
level can be detected by wipe testing. NRC lications in addition to those listed in the refer-
regulations require periodic wipe testing of ences are the following:
work areas and maintaining records of these Uncertainties in the Measurement and Dosimetry of
tests. External Radiation (NCRP Report No. 158), 2007.
Operational Radiation Safety Training (NCRP Report
No. 134), 2000.
REFERENCES Radionuclide Exposure of the Embryo/Fetus (NCRP
Report No. 128), 1998.
1. Evaluation of the Linear Nonthreshold Dose-Response
Operational Radiation Safety Program (NCRP Report
Model for Ionizing Radiation (NCRP Report No. 136).
No. 127), 1998.
Bethesda, MD, NCRP, 2001.
Limitation of Exposure to Ionizing Radiation (NCRP
2. Rossi HH: Sensible radiation protection. Health
Report No. 116), 1993.
Physics 70:394-395, 1996.
Implementation of the Principle of As Low as Reasonably
3. Simmons JA, Watt DE: Radiation Protection Dosime-
Achievable (ALARA) for Medical and Dental Personnel
try: A Radical Reappraisal. Madison, WI, 1999,
(NCRP Report No. 107), 1990.
Medical Physics Publishing Corp.
Radiation Protection for Medical and Allied Health Per-
4. Kondo S: Health Effects of Low-Level Radiation.
sonnel (NCRP Report No. 105), 1989.
Madison, WI, 1993, Medical Physics Publishing 
Protection in Nuclear Medicine and Ultrasound Diagnos-
Corp.
tic Procedures in Children (NCRP Report No. 73),
5. Source and Effects of Ionizing Radiation (United
1983.
Nations Scientific Committee on the Effects of Atomic
Management of Persons Accidentally Contaminated with
Radiation, 2008 Report to the General Assembly), New
Radionuclides (NCRP Report No. 65), 1980.
York, 2010, United Nations. Available at http://
Safe Handling of Radionuclides (NCRP Report No. 30), 
www.unscear.org/unscear/en/publications.html
1964.
[accessed October 14, 2011].
6. Sources and Magnitude of Occupational and Public
Exposures from Nuclear Medicine Procedures (NCRP
Report No. 124). Bethesda, MD, NCRP, 1996. The International Atomic Energy Agency website
7. Anger RT: Radiation protection in nuclear medicine. is at www.iaea.org [accessed October 14, 2011] and
In The Physics of Nuclear Medicine, Chicago, 1977, has several publications relevant to nuclear medi-
American Association of Physicists in Medicine. cine that can be downloaded from the website: For
example:
Nuclear Medicine Resources Manual, 2006.
BIBLIOGRAPHY Cyclotron Produced Radionuclides: Guidelines for 
Setting Up a Facility, Technical Reports Series No.
A detailed discussion of health physics and radia-
471, 2009.
tion protection techniques can be found in the fol-
Quality Assurance for Radioactivity Measurement in
lowing textbooks:
Nuclear Medicine, Technical Reports Series No. 454,
Shapiro J: Radiation Protection: A Guide for Scientists, 2006.
Regulators, and Physicians, 4th ed. Cambridge, MA, Applying Radiation Safety Standards in Nuclear Medi-
2002, Harvard University Press. cine, Safety Reports Series No. 40, 2005.
442 Physics in Nuclear Medicine

International bodies providing information or rec- The United Nations Scientific Committee on the
ommendations regarding radiation dose: Effects of Atomic Radiation website is at
www.unscear.org/ [accessed October 14, 2011). Two
The International Commission on Radiological
comprehensive publications of interest are:
Protection website is at http://www.icrp.org
[accessed October 14, 2011). An important ICRP UNSCEAR 2008 Report: “Sources and effects of ionizing
publication with recommendations regarding dose radiation.”
limits is the following: UNSCEAR 2006 Report: “Effects of ionizing radiation.”
Recommendations of the International Commission on
Radiological Protection (ICRP Publication No. 103),
Annals of the ICRP, Vol. 37, 2-4, 2007.
appendix
A
Unit Conversions

Quantity SI Units Traditional Units


Activity 1 becquerel (Bq) = 2.703 × 10−11 curies (Ci)
3.7 × 1010 Bq = 1 Ci
1 MBq = 27.03 µCi
37 MBq = 1 mCi
Absorbed Dose 1 gray (Gy) = 100 rads
1 × 10−2 Gy = 1 rad
1 mGy = 0.1 rad
Equivalent Dose, Effective Dose 1 sievert (Sv) = 100 rems
1 × 10−2 Sv = 1 rem
1 mSv = 0.1 rem
Exposure 1 C/kg air = 3876 roentgen (R)
2.58 × 10−4 C/kg air = 1 R
Energy 1 joule (J) = 6.242 × 1018 electron volts (eV)
1.602 × 10−19 J = 1 eV
Mass* 1 kilogram (kg) = 6.02214 × 1026 unified atomic mass
units (u)
1.66054 × 10−27 kg = 1 u
Pressure 1 pascal (Pa) = 7.501 × 10−3 mm Hg (torr)
1.333 × 102 pascals (Pa) = 1 mm Hg (torr)
1 Pa = 9.869 × 10−6 atmospheres (atm)
1.013 × 105 Pa = 1 atm
Area 1 square meter (m2) = 1 × 1028 barns
1 × 10−28 m2 = 1 barn
Temperature* x kelvin (K) = x − 273.15 degrees centigrade (°C)
x + 273.15 K = x °C
Magnetic Flux Density 1 tesla (T) = 1 × 104 gauss (G)
1 × 10−4 T = 1 G
*Note that mass and temperature are the only SI base units in this table. All others are derived from these and/or the
five other SI base units.
A useful source of further information on SI units and unit conversions is the National Institute of Standards and
Technology website, http://physics.nist.gov/cuu/Units/index.html. Accessed 4 November 2011.

443
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appendix
B
Properties of the
Naturally Occurring
Elements
Atomic Weight* Density† KB‡
Name Symbol Atomic Number (12C scale) (g/cm3) (keV)
Actinium Ac 89 (227) 10.0 106.756
Aluminum Al 13 26.982 2.70 1.560
Antimony Sb 51 121.760 6.68 30.491
Argon Ar 18 39.948 1.63 §
3.203
Arsenic As 33 74.922 5.75 11.867
Astatine At 85 (210) — 95.730
Barium Ba 56 137.327 3.62 37.440
Beryllium Be 4 9.012 1.85 0.111
Bismuth Bi 83 208.980 9.79 90.526
Boron B 5 10.811 2.34 0.188
Bromine Br 35 79.904 3.10 13.474
Cadmium Cd 48 112.411 8.69 26.711
Calcium Ca 20 40.078 1.54 4.038
Carbon C 6 12.011 2.2 (graphite) 0.284
3.51 (diamond)
Cerium Ce 58 140.116 6.77 40.443
Cesium Cs 55 132.905 1.87 35.985
§
Chlorine Cl 17 35.453 2.90 2.822
Chromium Cr 24 51.996 7.15 5.989
Cobalt Co 27 58.933 8.86 7.709
Copper Cu 29 63.546 8.96 8.979
Dysprosium Dy 66 162.500 8.55 53.789
Erbium Er 68 167.260 9.07 57.486
Europium Eu 63 151.964 5.24 48.519
§
Fluorine F 9 18.998 1.55 0.685
Francium Fr 87 (223) — 101.147
Gadolinium Gd 64 157.250 7.90 50.239
Gallium Ga 31 69.723 5.91 10.367
Germanium Ge 32 72.610 5.32 11.103
Continued
445
446 Physics in Nuclear Medicine

Atomic Weight* Density† KB‡


Name Symbol Atomic Number (12C scale) (g/cm3) (keV)
Gold Au 79 196.967 19.3 80.725
Hafnium Hf 72 178.490 13.3 65.351
§
Helium He 2 4.003 0.164 0.025
Holmium Ho 67 162.930 8.80 55.618
Hydrogen H 1 1.008 0.082§ 0.014
Indium In 49 114.818 7.31 27.940
Iodine I 53 126.904 4.93 33.169
Iridium Ir 77 192.217 22.6 76.111
Iron Fe 26 55.845 7.87 7.112
§
Krypton Kr 36 83.800 3.43 14.326
Lanthanum La 57 138.906 6.15 38.925
Lead Pb 82 207.200 11.3 88.005
Lithium Li 3 6.941 0.534 0.055
Lutetium Lu 71 174.967 9.84 63.314
Magnesium Mg 12 24.305 1.74 1.305
Manganese Mn 25 54.938 7.3 6.539
Mercury Hg 80 200.590 13.5 83.102
Molybdenum Mo 42 95.940 10.2 20.000
Neodymium Nd 60 144.240 7.01 43.569
§
Neon Ne 10 20.180 0.825 0.867
Nickel Ni 28 58.693 8.90 8.333
Niobium Nb 41 92.906 8.57 18.986
Nitrogen N 7 14.007 1.15§ 0.402
Osmium Os 76 190.230 22.59 73.871
Oxygen O 8 15.999 1.31§ 0.532
Palladium Pd 46 106.420 12.0 24.345
Phosphorus P 15 30.974 1.82 (white) 2.146
2.16 (red)
2.69 (black)
Platinum Pt 78 195.078 21.5 78.395
Polonium Po 84 (209) 9.2 93.105
Potassium K 19 39.098 0.89 3.607
Praseodymium Pr 59 140.908 6.77 41.991
Promethium Pm 61 (145) 7.26 45.184
Protactinium Pa 91 231.036 15.4 112.601
Radium Ra 88 (226) 5 103.922
Radon Rn 86 (222) 9.074§ 98.404
Rhenium Re 75 186.207 20.8 71.676
Rhodium Rh 45 102.906 12.4 23.220
Rubidium Rb 37 85.468 1.53 15.200
Ruthenium Ru 44 101.070 12.1 22.117
Samarium Sm 62 150.360 7.52 46.834
Scandium Sc 21 44.067 2.99 4.493
Appendix B╇ •â•‡ Properties of the Naturally Occurring Elements 447

Atomic Weight* Density† KB‡


Name Symbol Atomic Number (12C scale) (g/cm3) (keV)
Selenium Se 34 78.960 4.81 (gray) 12.658
4.39 (α form)
4.28 (vitreous)
Silicon Si 14 28.086 2.33 1.839
Silver Ag 47 107.868 10.5 25.514
Sodium Na 11 22.990 0.97 1.072
Strontium Sr 38 87.620 2.64 16.105
Sulfur S 16 32.066 2.07 (rhombic) 2.472
2.00 (monoclinic)
Tantalum Ta 73 180.948 16.4 67.416
Technetium Tc 43 (98) 11 21.044
Tellurium Te 52 127.600 6.23 31.814
Terbium Tb 65 158.925 8.23 51.996
Thallium Tl 81 204.383 11.8 85.530
Thorium Th 90 232.038 11.7 109.651
Thulium Tm 69 168.934 9.32 59.390
Tin Sn 50 118.710 5.77 (gray) 29.200
7.29 (white)
Titanium Ti 22 47.867 4.51 4.966
Tungsten W 74 183.840 19.3 69.525
Uranium U 92 238.029 19.1 115.606
Vanadium V 23 50.942 6.0 5.465
§
Xenon Xe 54 131.290 5.37 34.561
Ytterbium Yb 70 173.040 6.90 61.332
Yttrium Y 39 88.906 4.47 17.038
Zinc Zn 30 65.390 7.13 9.659
Zirconium Zr 40 91.224 6.52 17.998
*Values averaged for the elements in their natural abundance. For nuclides with no stable isotopes, value in parentheses
corresponds to mass number of most stable isotope. Values from http://physics.nist.gov/PhysRefData. Accessed 16 June
2011.

Values averaged for the elements in their natural abundance. Values from The Handbook of Chemistry and Physics,
91st ed., CRC Press, 2010-2011.

K-shell binding energies. Values from http://www.nist.gov/pml/data/xraytrans/index.cfm. Accessed 23 November 2011.
§
Densities for gases in g/liter at 0° C and pressure of 1╯atm.
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appendix
C
Decay Characteristics
of Some Medically
Important Radionuclides
The figures show nuclear decay scheme dia- Legend for radiation listed in decay tables:
grams using the conventions described in γ gamma ray
Chapter 3. In the tables accompanying the –
beta-minus particle
β
decay diagrams, the first column is the type
+
of radiation emitted, y(i) is the frequency β beta-plus particle
of the ith emission per nuclear decay in γâ•›± annihilation photons
(Bq•sec)–1, E(i) is the corresponding transi-
tion energy for the emission in MeV (given ce-K, ce-L, etc…. internal conversion electrons
as the average energy for beta decay), and ejected from the K, L, etc….
shell (Chapter 3, Section E)
y(i) × E(i) is the average energy emitted per
decay. [Figures from ICRP Publication No. Auger-XXX Auger electrons (see
38, Radionuclide Transformations: Energy Chapter 2, Section C.3 for
and Intensity of Emissions. In Annals of the explanation of notation)
ICRP (International Commission on Radio- Kα, Kβ etc, … X ray characteristic x rays (see
logical Protection). Oxford, Pergamon Press, Chapter 2, Table 2-1 for
1983.] notation)
ΔE residual low-energy radiation
(mainly Auger processes) not
easily described by individual
discrete transitions

HYDROGEN-3

3
1
H(12.35y)
0.0

0.0
β1 3


2He(stable)

Half Life = 12.35 Years


Decay Mode(s): β–
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
β 1

1.00E 00 5.683E-03* 5.68E-03
LISTED β, ce AND Auger RADIATIONS 5.68E-03
LISTED RADIATIONS 5.68E-03
*AVERAGE ENERGY (MeV)
HELIUM-3 DAUGHTER IS STABLE.

449
450 Physics in Nuclear Medicine

CARBON-11 NITROGEN-13
13
11 7N(9.965m)
6 C(20.38m) 0.0
0.0

0.0
0.0 13 EC1,β 1

+ 6C(stable)
11
B(stable) EC1,β1
5
Half Life = 9.965 Minutes
Half Life = 20.38 Minutes Decay Mode(s): EC, β+
Decay Mode(s): EC, β +
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i) β 1 9.98E-01 4.918E-01* 4.91E-01
β+ 1 9.98E-01 3.855E-01* 3.85E-01 γâ•›± 2.00E 00 5.110E-01 1.02E 00
γâ•›± 2.00E 00 5.110E-01 1.02E 00 Kα1 X ray 2.38E-06 2.774E-04 6.59E-10
Kα1 X ray 1.62E-06 1.833E-04 2.97E-10 Kα2 X ray 1.19E-06 2.774E-04 3.30E-10
Kα2 X ray 8.10E-07 1.833E-04 1.48E-10 Auger-KLL 1.80E-03 2.564E-04* 4.61E-07
LISTED X, γ AND γâ•›± RADIATIONS 1.02E 00 LISTED X, γ AND γâ•›± RADIATIONS 1.02E 00
LISTED β, ce AND Auger RADIATIONS 3.85E-01 LISTED β, ce AND Auger RADIATIONS 4.91E-01
LISTED RADIATIONS 1.40E 00 LISTED RADIATIONS 1.51E 00
*AVERAGE ENERGY (MeV) *AVERAGE ENERGY (MeV)
BORON-11 DAUGHTER IS STABLE. CARBON-13 DAUGHTER IS STABLE.

OXYGEN-15
15
8O(122.24s)
0.0

CARBON-14
0.0
15 EC1,β
7N(stable)
14 1
6C(5730y)
0.0
Half Life = 122.24 Seconds
Decay Mode(s): EC, β+

0.0 Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)


β 14 +
β 1 9.99E-01 7.353E-01* 7.34E-01
7 N(stable)
1

γâ•›± 2.00E 00 5.110E-01 1.02E 00


Half Life = 5730 Years Kα1 X ray 2.65E-06 3.924E-04 1.04E-09
Decay Mode(s): β– Kα2 X ray 1.32E-06 3.924E-04 5.19E-10
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i) Auger-KLL 1.13E-03 3.684E-04* 4.15E-07

β 1 1.00E 00 4.945E-02* 4.95E-02 LISTED X, γ AND γâ•›± RADIATIONS 1.02E 00
LISTED β, ce AND Auger RADIATIONS 4.95E-02 LISTED β, ce AND Auger RADIATIONS 7.34E-01
LISTED RADIATIONS 4.95E-02 LISTED RADIATIONS 1.76E 00
*AVERAGE ENERGY (MeV) *AVERAGE ENERGY (MeV)
NITROGEN-14 DAUGHTER IS STABLE. NITROGEN-15 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 451

FLUORINE-18
18
9F(109.77m)
0.0

0.0
18
8O(stable)
EC1,β1

Half Life = 109.77 Minutes


Decay Mode(s): EC, β+
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i)
+
β 1 9.67E-01 2.498E-01* 2.42E-01
γâ•›± 1.93E 00 5.110E-01 9.86E-01
LISTED X, γ AND γâ•›± RADIATIONS 1.02E 00
LISTED β, ce AND Auger RADIATIONS 2.50E-01
LISTED RADIATIONS 1.27E 00
*AVERAGE ENERGY (MeV)
OXYGEN-18 DAUGHTER IS STABLE.

SODIUM-22
22
11Na(2.602y)
0.0

1.2746
EC1,β
1
γ1
0.0
22 
Ne(stable) EC2,β2
10

Half Life = 2.602 Years


Decay Mode(s): EC, β+
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
β 1 8.98E-01 2.154E-01* 1.94E-01
+
β 2 6.00E-04 8.350E-01* 5.01E-04
γâ•›± 1.80E 00 5.110E-01 9.19E-01
γ1 9.99E-01 1.275E 00 1.27E 00
ce-K, γ 1 6.43E-06 1.274E 00 8.19E-06
ce-L1, γ 1 3.77E-07 1.274E 00 4.81E-07
ce-L2, γ 1 2.07E-10 1.275E 00 2.64E-10
ce-L3, γ 1 3.40E-10 1.275E 00 4.33E-10
Kα1 X ray 9.42E-04 8.486E-04 7.99E-07
Kα2 X ray 4.72E-04 8.486E-04 4.01E-07
Kα3 X ray 1.19E-12 8.219E-04 9.76E-16
Auger-KLL 9.96E-02 8.006E-04* 7.97E-05
LISTED X, γ AND γâ•›± RADIATIONS 2.19E 00
LISTED β, ce AND Auger RADIATIONS 1.94E-01
LISTED RADIATIONS 2.39E 00
*AVERAGE ENERGY (MeV)
NEON-22 DAUGHTER IS STABLE.
452 Physics in Nuclear Medicine

PHOSPHORUS-32 CHROMIUM-51
32
15 P(14.29d) 51
0.0 24
Cr(27.704d)
0.0

0.0
β 32 0.3201
1 16 S(stable)
EC1
γ1
Half Life = 14.29 Days
0.0
Decay Mode(s): β– 51 EC2
23V(stable)
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i)
β– 1 1.00E 00 6.947E-01* 6.95E-01 Half Life = 27.704 Days
LISTED β, ce AND Auger RADIATIONS 6.95E-01
Decay Mode(s): EC
LISTED RADIATIONS 6.95E-01
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
*AVERAGE ENERGY (MeV)
γ1 9.83E-02 3.201E-01 3.15E-02
SULFUR-32 DAUGHTER IS STABLE.
ce-K, γ 1 1.52E-04 3.146E-01 4.78E-05
ce-L1, γ 1 1.38E-05 3.194E-01 4.41E-06

SULFUR-35 Kα1 X-ray 1.33E-01 4.952E-03 6.59E-04


Kα2 X-ray 6.70E-02 4.945E-03 3.31E-04
35
16
S(87.44d)
Kβ1 X-ray 1.76E-02 5.427E-03 9.53E-05
0.0
Kβ3 X-ray 8.88E-03 5.427E-03 4.82E-05
Auger-KLL 5.58E-01 4.339E-03* 2.42E-03
0.0 Auger-KLX 1.13E-01 4.876E-03* 5.49E-04

β1 35 Auger-KXY 8.59E-03 5.386E-03* 4.63E-05
17 Cl(stable)
Auger-LMM 1.51E 00 4.859E-04* 7.34E-04
Half Life = 87.44 Days
Auger-LMX 1.05E-02 5.183E-04* 5.45E-06
Decay Mode(s): β–
Auger-MXY 3.19E 00 1.603E-05* 5.12E-05
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
LISTED X γ AND γâ•›± RADIATIONS 3.26E-02

β 1 1.00E 00 4.883E-02* 4.88E-02
OMITTED X γ AND γâ•›± RADIATIONS** 5.89E-07
LISTED β, ce AND Auger RADIATIONS 4.88E-02
LISTED β, ce AND Auger RADIATIONS 3.86E-03
LISTED RADIATIONS 4.88E-02
OMITTED β, ce AND Auger 8.33E-08
*AVERAGE ENERGY (MeV) RADIATIONS**
CHLORINE-35 DAUGHTER IS STABLE.
LISTED RADIATIONS 3.65E-02
OMITTED RADIATIONS** 6.72E-07
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES
<â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
VANADIUM-51 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 453

COBALT-57
57
27
Co(270.9d)
0.0

0.7064
EC1

γ9

0.1365 EC2
γ2
0.0144
γ3 γ1
0.0
57
26Fe(stable)

Half Life = 270.9 Days


Decay Mode(s): EC
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i)
γ1 9.19E-02 1.441E-02 1.32E-03
ce-K, γ 1 7.13E-01 7.301E-03 5.20E-03
ce-L1, γ 1 6.80E-02 1.357E-02 9.22E-04
ce-L2, γ 1 4.20E-03 1.369E-02 5.75E-05
ce-L3, γ 1 1.69E-03 1.370E-02 2.31E-05
γ2 8.56E-01 1.221E-01 1.04E-01
ce-K, γ 2 1.84E-02 1.150E-01 2.12E-03
ce-L1, γ 2 1.73E-03 1.212E-01 2.10E-04
γ3 1.06E-01 1.365E-01 1.45E-02
ce-K, γ 3 1.43E-02 1.294E-01 1.84E-03
ce-L1, γ 3 1.27E-03 1.356E-01 1.73E-04
γ9 1.60E-03 6.920E-01 1.11E-03
Kα1 X ray 3.34E-01 6.404E-03 2.14E-03
Kα2 X ray 1.69E-01 6.391E-03 1.08E-03
Kβ1 X ray 4.51E-02 7.058E-03 3.19E-04
Kβ3 X ray 2.29E-02 7.058E-03 1.61E-04
Auger-KLL 8.54E-01 5.574E-03* 4.76E-03
Auger-KLX 2.04E-01 6.302E-03* 1.29E-03
Auger-KXY 1.79E-02 7.000E-03* 1.25E-04
Auger-LMM 2.43E 00 6.703E-04* 1.63E-03
Auger-LMX 1.54E-01 7.067E-04* 1.09E-04
Auger-MXY 5.33E 00 2.232E-05* 1.19E-04
LISTED X, γ AND γâ•›± RADIATIONS 1.25E-01
OMITTED X, γ AND γâ•›± RADIATIONS** 1.57E-04
LISTED β, ce AND Auger RADIATIONS 1.86E-02
OMITTED β, ce AND Auger RADIATIONS** 4.08E-05
LISTED RADIATIONS 1.44E-01
OMITTED RADIATIONS** 1.98E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
IRON-57 DAUGHTER IS STABLE.
454 Physics in Nuclear Medicine

COBALT-60 COPPER-62
60
27Co(5.271y) 62
29Cu(9.74m)
0.0
0.0
2.5057
γ3
β
1
1.3325 2.0488
β 
3 EC8,β 2
γ4 γ3
0.0 1.1730
60 
28Ni(stable)
EC9,β 3
γ6
Half Life = 5.271 Years
Decay Mode(s): β– 0.0

62 EC10,β 4
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i) 28Ni(stable)

β– 1 9.99E-01 9.577E-02* 9.57E-02


Half Life = 9.74 Minutes

β 3 8.00E-04 6.258E-01* 5.01E-04
Decay Mode(s): EC, β+
γ3 9.99E-01 1.173E 00 1.17E 00
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
ce-K, γ 3 1.50E-04 1.165E 00 1.75E-04 +
β 4 9.76E-01 1.315E 00* 1.28E 00
γ4 1.00E 00 1.332E 00 1.33E 00
γâ•›± 1.96E 00 5.110E-01 1.00E 00
ce-K, γ 4 1.14E-04 1.324E 00 1.50E-04
γ3 1.47E-03 8.757E-01 1.29E-03
LISTED X, γ AND γâ•›± RADIATIONS 2.50E 00
γ6 3.35E-03 1.173E 00 3.93E-03
OMITTED X, γ AND γâ•›± RADIATIONS** 1.14E-04
LISTED X, γ AND γâ•›± RADIATIONS 1.00E 00
LISTED β, ce AND Auger RADIATIONS 9.65E-02
OMITTED X, γ AND γâ•›± RADIATIONS** 1.92E-03
OMITTED β, ce AND Auger 4.73E-05
LISTED β, ce AND Auger RADIATIONS 1.28E 00
RADIATIONS**
OMITTED β, ce AND Auger 1.48E-03
LISTED RADIATIONS 2.60E 00
RADIATIONS**
OMITTED RADIATIONS** 1.61E-04
LISTED RADIATIONS 2.29E 00
*AVERAGE ENERGY (MeV)
OMITTED RADIATIONS** 3.40E-03
**EACH OMITTED TRANSITION CONTRIBUTES
<â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY. *AVERAGE ENERGY (MeV)
NICKEL-60 DAUGHTER IS STABLE. **EACH OMITTED TRANSITION CONTRIBUTES
<â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
NICKEL-62 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 455

COPPER-64
64
29
Cu(12.701h)
0.0

1.3459
γ1
EC1 0.0
0.0 
β1 64
30Zn(stable)

64 EC2,β 1
28Ni(stable)

Half Life = 12.701 Hours


Decay Mode(s): β–, EC, β+
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)

β 1 3.72E-01 1.902E-01* 7.08E-02
+
β 1 1.79E-01 2.781E-01* 4.97E-02
γâ•›± 3.58E-01 5.110E-01 1.83E-01
γ1 4.90E-03 1.346E 00 6.59E-03
Kα1 X ray 9.78E-02 7.478E-03 7.31E-04
Kα2 X ray 4.97E-02 7.461E-03 3.71E-04
Auger-KLL 1.84E-01 6.489E-03* 1.20E-03
Auger-KLX 4.83E-02 7.356E-03* 3.55E-04
Auger-LMM 5.66E-01 8.103E-04* 4.59E-04
LISTED X, γ AND γâ•›± RADIATIONS 1.90E-01
OMITTED X, γ AND γâ•›± RADIATIONS** 1.68E-04
LISTED β, ce AND Auger RADIATIONS 1.23E-01
OMITTED β, ce AND Auger RADIATIONS** 1.06E-04
LISTED RADIATIONS 3.13E-01
OMITTED RADIATIONS** 2.74E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
ZINC-64 DAUGHTER, YIELD 3.72E-01, IS STABLE.
NICKEL-64 DAUGHTER, YIELD 6.28E-01, IS STABLE.
456 Physics in Nuclear Medicine

GALLIUM-67
67
31
Ga(78.26h)
0.0

0.8877
EC1

γ10 γ7

0.3935 EC2
γ9 γ6 γ5 γ4
0.1846 EC3
γ3 γ1
0.0933 EC4
γ2
0.0 EC5
67
30Zn(stable)

Half Life = 78.26 Hours Half Life = 78.26 Hours Half Life = 78.26 Hours
Decay Mode(S): EC Decay Mode(s): EC Decay Mode(S): EC
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i) Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ1 3.07E-02 9.127E-02 2.80E-03 γ 10 1.45E-03 8.877E-01 1.29E-03
ce-K, γ 1 2.23E-03 8.161E-02 1.82E-04 Kα1 X ray 3.28E-01 8.639E-03 2.83E-03
γ2 3.83E-01 9.331E-02 3.57E-02 Kα2 X ray 1.67E-01 8.616E-03 1.44E-03
ce-K, γ 2 2.87E-01 8.365E-02 2.40E-02 Kβ1 X ray 4.49E-02 9.572E-03 4.30E-04
ce-L1, γ 2 2.54E-02 9.212E-02 2.34E-03 Kβ3 X ray 2.30E-02 9.572E-03 2.20E-04
ce-L2, γ 2 3.98E-03 9.227E-02 3.67E-04 Auger-KLL 4.67E-01 7.466E-03* 3.49E-03
ce-L3, γ 2 5.81E-03 9.229E-02 5.36E-04 Auger-KLX 1.33E-01 8.482E-03* 1.12E-03
ce-M, γ 2 5.17E-03 9.322E-02* 4.82E-04 Auger-KXY 1.31E-02 9.473E-03* 1.24E-04
γ3 2.09E-01 1.846E-01 3.87E-02 Auger-LMM 1.55E 00 9.444E-04* 1.46E-03
ce-K, γ 3 4.07E-03 1.749E-01 7.11E-04 Auger-LMX 1.43E-01 1.020E-03* 1.46E-04
ce-L1, γ 3 3.87E-04 1.834E-01 7.11E-05 Auger-MXY 3.49E 00 4.566E-05* 1.60E-04
γ4 2.37E-02 2.090E-01 4.94E-03 LISTED X, γ AND γâ•›± RADIATIONS 1.58E-01
ce-K, γ 4 1.90E-04 1.993E-01 3.79E-05 OMITTED X, γ AND γâ•›± RADIATIONS** 8.52E-05
γ5 1.68E-01 3.002E-01 5.04E-02 LISTED β, ce AND Auger RADIATIONS 3.54E-02
ce-K, γ 5 5.83E-04 2.906E-01 1.69E-04 OMITTED β, ce AND Auger 1.04E-04
RADIATIONS**
γ6 4.70E-02 3.935E-01 1.85E-02
LISTED RADIATIONS 1.93E-01
γ7 6.86E-04 4.942E-01 3.39E-04
OMITTED RADIATIONS** 1.89E-04
γ9 5.13E-04 7.944E-01 4.08E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
ZINC-67 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 457

GALLIUM-68 GERMANIUM-68
68 68
31Ga(68.0m) 32
Ge(271d)
0.0 0.0

2.3387
EC2
1.8832 0.0
EC3
γ4
68
31Ga(68.0m)
EC1

1.0774  Half Life = 271 Days


EC5,β 1
Decay Mode(s): EC
γ6 γ3 Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
Kα1 X ray 2.55E-01 9.252E-03 2.36E-03
0.0 EC6,β 2

Kα2 X ray 1.31E-01 9.225E-03 1.20E-03
68
30Zn(stable) Kα3 X ray 3.93E-07 9.069E-03 3.56E-09
Kβ1 X ray 3.59E-02 1.026E-02 3.68E-04
Half Life = 68 Minutes
Kβ3 X ray 1.83E-02 1.026E-02 1.88E-04
Decay Mode(s): EC, β+
Kβ5 X ray 6.43E-05 1.035E-02 6.66E-07
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
Lα X ray 4.55E-03 1.098E-03* 5.00E-06
β+ 1 1.08E-02 3.526E-01* 3.80E-03
+ Lβ X ray 1.91E-03 1.131E-03* 2.16E-06
β 2 8.79E-01 8.358E-01* 7.35E-01
Lη X ray 1.13E-04 9.842E-04 1.11E-07
γâ•›± 1.78E 00 5.110E-01 9.10E-01
Ll X ray 2.29E-04 9.573E-04 2.20E-07
γ3 3.30E-02 1.077E 00 3.56E-02
Auger-KLL 3.19E-01 7.976E-03* 2.55E-03
γ4 9.90E-04 1.261E 00 1.25E-03
Auger-KLX 9.39E-02 9.074E-03* 8.52E-04
γ6 1.43E-03 1.883E 00 2.69E-03
Auger-KXY 9.49E-03 1.015E-02* 9.63E-05
LISTED X, γ AND γâ•›± RADIATIONS 9.49E-01
Auger-LMM 1.11E 00 1.017E-03* 1.13E-03
OMITTED X, γ AND γâ•›± RADIATIONS** 1.61E-03
Auger-LMX 1.18E-01 1.108E-03* 1.31E-04
LISTED β, ce AND Auger RADIATIONS 7.39E-01
Auger-MXY 2.53E 00 5.928E-05* 1.50E-04
OMITTED β, ce AND Auger 5.45E-04
RADIATIONS** LISTED X, γ AND γâ•›± RADIATIONS 4.13E-03

LISTED RADIATIONS 1.69E 00 LISTED β, ce AND Auger RADIATIONS 4.90E-03

OMITTED RADIATIONS** 2.15E-03 LISTED RADIATIONS 9.03E-03


*AVERAGE ENERGY (MeV) *AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES GALLIUM-68 DAUGHTER IS RADIOACTIVE.
<â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
ZINC-68 DAUGHTER IS STABLE.
458 Physics in Nuclear Medicine

RUBIDIUM-82 YTTRIUM-90
82 90
37
Rb(1.3m) 39Y(64.0h)
0.0 0.0

1.7607
β
1 γ1

0.0
β 90
40Zr(stable)
2

2.1718 
EC4,β 4 Half Life = 64 Hours
Decay Mode(s): β–
1.4748 
EC6,β 6 Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ5 β 2

1.00E 00 9.348E-01* 9.35E-01
0.7765 
EC7,β 7 Kα1 X ray 5.79E-05 1.578E-02 9.13E-07

γ6 γ4 Kα2 X ray 3.03E-05 1.569E-02 4.75E-07


0.0 
EC8,β 8 Kβ1 X ray 9.55E-06 1.767E-02 1.69E-07
82
36Kr(stable) Kβ2 X ray 2.14E-06 1.797E-02 3.85E-08
Kβ3 X ray 4.89E-06 1.765E-02 8.63E-08
Half Life = 1.3 Minutes
Lα X ray 2.29E-06 2.042E-03* 4.67E-09
Decay Mode(s): EC, β+
Lβ X ray 1.61E-06 2.130E-03* 3.43E-09
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
LISTED X, γ AND γâ•›± RADIATIONS 1.69E-06
+
β 4 2.76E-03 5.174E-01* 1.43E-03
OMITTED X, γ AND γâ•›± RADIATIONS** 1.25E-09
β+ 6 1.72E-03 8.325E-01* 1.44E-03
LISTED β, ce AND Auger RADIATIONS 9.35E-01
+
β 7 1.16E-01 1.157E 00* 1.34E-01
OMITTED β, ce AND Auger 3.10E-04
β+ 8 8.33E-01 1.523E 00* 1.27E 00 RADIATIONS**
γâ•›± 1.91E 00 5.110E-01 9.75E-01 LISTED RADIATIONS 9.35E-01
γ4 1.34E-01 7.765E-01 1.04E-01 OMITTED RADIATIONS** 3.10E-04
γ5 5.05E-03 1.395E 00 7.05E-03 *AVERAGE ENERGY (MeV)
γ6 9.38E-04 1.475E 00 1.38E-03 **EACH OMITTED TRANSITION CONTRIBUTES
<â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
LISTED X, γ AND γâ•›± RADIATIONS 1.09E 00 ZIRCONIUM-90 DAUGHTER IS STABLE.
OMITTED X, γ AND γâ•›± RADIATIONS** 5.36E-03
LISTED β, ce AND Auger RADIATIONS 1.41E 00
OMITTED β, ce AND Auger 7.03E-04
RADIATIONS**
LISTED RADIATIONS 2.49E 00
OMITTED RADIATIONS** 6.06E-03
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES
<â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
KRYPTON-82 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 459

ZIRCONIUM-89

89
40Zr(78.43h)
0.0

2.6221
EC1
2.5665 EC2

1.7445 EC4

4 3

0.9092 EC5, 
1

5 1

0.0
89
39Y(stable)

Half Life = 78.43 Hours


Decay Mode(s): EC, β+
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
β 1 2.26E-01 3.949E-01* 8.94E-02
γâ•›± 4.53E-01 5.110E-01 2.31E-01
γ1 9.99E-01 9.092E-01 9.08E-01
ce-K2, γ 1 7.44E-03 8.922E-01 6.63E-03
ce-L1, γ 1 8.26E-04 9.068E-01 7.49E-04
γ3 9.99E-04 1.657E 00 1.66E-03
γ4 7.69E-03 1.713E 00 1.32E-02
γ5 1.30E-03 1.744E 00 2.26E-03
Kα1 X ray 2.69E-01 1.496E-02 4.03E-03
Kα2 X ray 1.40E-01 1.488E-02 2.09E-03
Auger-KLL 1.40E-01 1.262E-02* 1.76E-03
Auger-KLX 5.14E-02 1.453E-02* 7.47E-04
Auger-LMM 5.58E-01 1.664E-03* 9.28E-04
Auger-LMX 2.21E-01 1.960E-03* 4.34E-04
Auger-MXY 1.50E 00 2.250E 04 3.38E-04
LISTED X, γ AND γâ•›± RADIATIONS 1.16E 00
OMITTED X, γ AND γâ•›± RADIATIONS** 2.45E-03
LISTED β, ce AND Auger RADIATIONS 1.01E-01
OMITTED β, ce AND Auger RADIATIONS** 3.45E-04
LISTED RADIATIONS 1.26E 00
OMITTED RADIATIONS** 2.79E-03
Yttrium-89 DAUGHTER IS STABLE.
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
460 Physics in Nuclear Medicine

MOLYBDENUM-99

99
42 Mo(66.0h)
0.0

1.1418
β
2
γ29
1.0040
β
4 γ28
0.9206
β
5

γ25

0.6715

γ19
0.5091
β
6

γ27 γ11

0.1811
γ2

0.1426
β
7
γ8 0.1405
γ4
0.0
99
43Tc(2.13E5y)
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 461

Half Life = 66 Hours


Decay Mode(s): β–
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)

β 5 1.66E-01 1.330E-01* 2.20E-02
β– 6 1.17E-02 2.895E-01* 3.39E-03

β 7 8.20E-01 4.426E-01* 3.63E-01
γ2 1.16E-02 4.059E-02 4.69E-04
ce-K, γ 2 3.77E-02 1.954E-02 7.38E-04
γ4 4.95E-02 1.405E-01 6.95E-03
ce-K, γ 4 4.89E-03 1.194E-01 5.84E-04
γ8 6.06E-02 1.811E-01 1.10E-02
ce-K, γ 8 7.62E-03 1.600E-01 1.22E-03
γ 11 1.19E-02 3.664E-01 4.37E-03
γ 19 5.45E-04 5.288E-01 2.88E-04
γ 24 2.60E-04 6.218E-01 1.61E-04
γ 25 1.22E-01 7.395E-01 9.02E-02
γ 27 4.32E-02 7.779E-01 3.36E-02
γ 28 1.33E-03 8.230E-01 1.09E-03
γ 29 9.76E-04 9.608E-01 9.37E-04
Kα1 X ray 2.15E-02 1.837E-02 3.95E-04
Kα2 X ray 1.13E-02 1.825E-02 2.06E-04
LISTED X, γ AND γ± RADIATIONS 1.50E-01
OMITTED X, γ AND γ± RADIATIONS** 4.87E-04
LISTED β, ce AND Auger RADIATIONS 3.91E-01
OMITTED β, ce AND Auger RADIATIONS** 1.33E-03
LISTED RADIATIONS 5.41E-01
OMITTED RADIATIONS** 1.82E-03
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
TECHNETIUM-99M DAUGHTER, YIELD 8.76E-01, IS RADIOACTIVE.
TECHNETIUM-99 DAUGHTER, YIELD 1.24E-01, IS RADIOACTIVE.
462 Physics in Nuclear Medicine

TECHNETIUM-99M

99m
43Tc(6.02h)
0.1426
γ1
0.1405

γ 3 γ2

0.0
99
43Tc(2.13E5y)

Half Life = 6.02 Hours


Decay Mode(s): IT
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i)
ce-M, γ 1 9.14E-01 1.749E-03* 1.60E-03
ce-N , γ 1
+
7.57E-02 2.174E-03* 1.65E-04
γ2 8.89E-01 1.405E-01 1.25E-01
ce-K, γ 2 8.79E-02 1.194E-01 1.05E-02
ce-L1, γ 2 9.67E-03 1.374E-01 1.33E-03
ce-L2, γ 2 6.10E-04 1.377E-01 8.40E-05
ce-L3, γ 2 3.01E-04 1.378E-01 4.15E-05
ce-M, γ 2 1.92E-03 1.400E-01* 2.70E-04
ce-N , γ 2
+
3.71E-04 1.405E-01* 5.21E-05
ce-K, γ 3 6.91E-03 1.216E-01 8.41E-04
ce-L1, γ 3 1.17E-03 1.396E-01 1.63E-04
ce-L2, γ 3 2.43E-04 1.399E-01 3.39E-05
ce-L3, γ 3 7.40E-04 1.400E-01 1.04E-04
ce-M, γ 3 4.19E-04 1.422E-01* 5.97E-05
Kα1 X ray 4.03E-02 1.837E-02 7.39E-04
Kα2 X ray 2.12E-02 1.825E-02 3.86E-04
Kβ1 X ray 6.88E-03 2.062E-02 1.42E-04
Auger-KLL 1.45E-02 1.535E-02* 2.23E-04
Auger-KLX 5.76E-03 1.777E-02* 1.02E-04
Auger-LMM 7.10E-02 2.053E-03* 1.46E-04
Auger-LMX 3.05E-02 2.468E-03* 7.53E-05
Auger-MXY 1.11E 00 4.090E-04* 4.54E-04
LISTED X, γ AND γâ•›± RADIATIONS 1.26E-01
OMITTED X, γ AND γâ•›± RADIATIONS** 1.58E-04
LISTED β, ce AND Auger RADIATIONS 1.62E-02
OMITTED β, ce AND Auger RADIATIONS** 3.88E-05
LISTED RADIATIONS 1.42E-01
OMITTED RADIATIONS** 1.96E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
TECHNETIUM-99 DAUGHTER IS RADIOACTIVE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 463

INDIUM-111
111
49 In(2.83d)
0.0

0.4167
γ1 EC1

0.2454

γ2

0.0
111
48 Cd(stable)

Half Life = 2.83 Days Half Life = 2.83 Days Half Life = 2.83 Days
Decay Mode(S): EC Decay Mode(s): EC Decay Mode(S): EC
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i) Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ1 9.05E-01 1.713E-01 1.55E-01 Kβ2 X ray 2.35E-02 2.664E-02 6.26E-04
ce-K, γ 1 8.27E-02 1.446E-01 1.19E-02 Kβ3 X ray 4.14E-02 2.606E-02 1.08E-03
ce-L1, γ 1 9.51E-03 1.673E-01 1.59E-03 Auger-KLL 1.06E-01 1.917E-02* 2.03E-03
ce-L2, γ 1 5.32E-04 1.676E-01 8.91E-05 Auger-KLX 4.55E-02 2.232E-02* 1.02E-03
ce-M, γ 1 1.95E-03 1.707E-01* 3.33E-04 Auger-KXY 5.85E-03 2.544E-02* 1.49E-04
ce-N+, γ 1 4.08E-04 1.713E-01* 6.99E-05 Auger-LMM 6.73E-01 2.590E-03* 1.74E-03
γ2 9.40E-01 2.454E-01 2.31E-01 Auger-LMX 3.06E-01 3.187E-03* 9.75E-04
ce-K, γ 2 5.03E-02 2.187E-01 1.10E-02 Auger-LXY 3.86E-02 3.583E-03* 1.38E-04
ce-L1, γ 2 5.15E-03 2.414E-01 1.24E-03 Auger-MXY 1.91E 00 5.104E-04* 9.75E-04
ce-L2, γ 2 1.38E-03 2.417E-01 3.32E-04 LISTED X, γ AND γâ•›± RADIATIONS 4.05E-01
ce-L3, γ 2 1.32E-03 2.419E-01 3.19E-04 OMITTED X, γ AND γâ•›± RADIATIONS** 2.00E-04
ce-M, γ 2 1.52E-03 2.448E-01* 3.71E-04 LISTED β, ce AND Auger RADIATIONS 3.44E-02
ce-N+, γ 2 3.01E-04 2.454E-01* 7.39E-05 OMITTED β, ce AND Auger 3.14E-05
RADIATIONS**
Kα1 X ray 4.43E-01 2.317E-02 1.03E-02
LISTED RADIATIONS 4.40E-01
Kα2 X ray 2.36E-01 2.298E-02 5.42E-03
OMITTED RADIATIONS** 2.31E-04
Kβ1 X ray 8.07E-02 2.609E-02 2.10E-03
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
CADMIUM-111 DAUGHTER IS STABLE.
464 Physics in Nuclear Medicine

IODINE-123
123
53I(13.2h)
0.0

0.8947
γ39 EC4
0.7836
EC5
γ36 0.6975
EC7
0.6879
γ29 γ12 EC8

0.5053
γ28 γ22 EC10
0.4400
EC12

γ30 γ16

0.1590
EC13
γ41 γ38 γ25 γ2

0.0
123
52Te(1E13y)
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 465

Half Life = 13.2 Hours


Decay Mode(s): EC
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ2 8.28E-01 1.590E-01 1.32E-01
ce-K, γ 2 1.35E-01 1.272E-01 1.72E-02
ce-L 1, γ 2 1.60E-02 1.540E-01 2.47E-03
ce-L2, γ 2 1.09E-03 1.544E-01 1.69E-04
ce-L3, γ 2 3.46E-04 1.546E-01 5.35E-05
ce-M, γ 2 3.46E-03 1.582E-01* 5.48E-04
ce-N+, γ 2 8.27E-04 1.590E-01* 1.32E-04
γ 12 7.07E-04 2.480E-01 1.75E-04
γ 16 7.86E-04 2.810E-01 2.21E-04
γ 22 1.25E-03 3.463E-01 4.33E-04
γ 25 4.25E-03 4.400E-01 1.87E-03
γ 28 3.14E-03 5.053E-01 1.59E-03
γ 29 1.38E-02 5.290E-01 7.31E-03
ce-K, γ 29 9.90E-05 4.971E-01 4.92E-05
γ 30 3.79E-03 5.385E-01 2.04E-03
γ 36 8.28E-04 6.246E-01 5.17E-04
γ 38 2.66E-04 6.879E-01 1.83E-04
γ 39 6.12E-04 7.358E-01 4.50E-04
γ 41 5.90E-04 7.836E-01 4.62E-04
Kα 1 X ray 4.58E-01 2.747E-02 1.26E-02
Kα2 X ray 2.46E-01 2.720E-02 6.70E-03
Kβ1 X ray 8.66E-02 3.100E-02 2.69E-03
Kβ2 X ray 2.66E-02 3.171E-02 8.43E-04
Kβ3 X ray 4.46E-02 3.094E-02 1.38E-03
Auger-KLL 8.15E-02 2.254E-02* 1.84E-03
Auger-KLX 3.69E-02 2.635E-02* 9.73E-04
Auger-KXY 4.92E-03 3.013E-02* 1.48E-04
Auger-LMM 6.06E-01 3.080E-03* 1.87E-03
Auger-LMX 3.11E-01 3.849E-03* 1.20E-03
Auger-LXY 4.40E-02 4.380E-03* 1.93E-04
Auger-MXY 1.80E 00 6.991E-04* 1.26E-03
LISTED X, γ AND γ â•›± RADIATIONS 1.71E-01
OMITTED X, γ AND γâ•›± RADIATIONS** 6.76E-04
LISTED β, ce AND Auger RADIATIONS 2.80E-02
OMITTED β, ce AND Auger RADIATIONS** 1.21E-04
LISTED RADIATIONS 1.99E-01
OMITTED RADIATIONS** 7.97E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
TELLURIUM-123M DAUGHTER, YIELD 5.00E-05, IS RADIOACTIVE.
TELLURIUM-123 DAUGHTER, YIELD 9.999E-01, IS RADIOACTIVE.
IODINE-124

466
124
53I(4.18d)
0.0

Physics in Nuclear Medicine


3.0010
EC1
2.9878
EC2
2.8860
EC3
2.8350
EC4
2.7469
EC5
2.7018
EC6
γ49 2.6937
EC7
2.6816
EC8
γ54 γ52 γ50 γ43 γ42 γ31 γ27 2.6410
EC9
2.5213
EC10
2.4540
EC12
2.3231
EC14
2.2937
EC15
2.0916
EC17
1.6567
EC20,β
1
γ75 γ69 γ67 γ66 γ65 γ64 γ62 γ61 γ60 γ59 γ58 γ56 γ55 γ48 γ32 γ17 γ11 1.3255
EC21,β
2
1.2485
EC22,β3
0.6027
EC24,β
5

γ70 γ68 γ40 γ9

0.0
124
52 Te(stable)
EC25,β
6
IODINE-124

Half Life = 4.18 Days Half Life = 4.18 Days Half Life = 4.18 Days

Decay Mode(S): EC, β + Decay Mode(s): EC, β+ Decay Mode(S): EC, β+

Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i) Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
β 2 2.92E-03 3.657E-01* 1.07E-03 γ 61 3.50E-03 2.079E 00 7.27E-03
+
β 5 1.12E-01 6.859E-01* 7.66E-02 γ 62 5.80E-03 2.091E 00 1.21E-02
+
β 6 1.12E-01 9.736E-01* 1.09E-01 γ 64 1.40E-03 2.099E 00 2.94E-03
γ± 4.53E-01 5.110E-01 2.31E-01 γ 65 1.10E-03 2.144E 00 2.36E-03

Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides


γ9 6.11E-01 6.027E-01 3.68E-01 γ 66 5.80E-03 2.232E 00 1.29E-02
ce-K, γ 9 2.57E-03 5.709E-01 1.47E-03 γ 67 6.70E-03 2.283E 00 1.53E-02
γ 11 9.56E-03 6.458E-01 6.17E-03 γ 68 1.00E-03 2.294E 00 2.29E-03
γ 17 1.01E-01 7.228E-01 7.27E-02 γ 69 2.00E-03 2.385E 00 4.77E-03
ce-K, γ 17 3.42E-04 6.910E-01 2.36E-04 γ 70 1.10E-03 2.454E 00 2.70E-03
γ 27 4.20E-03 9.682E-01 4.06E-03 γ 75 5.70E-03 2.747E 00 1.57E-02
γ 31 4.30E-03 1.045E 00 4.49E-03 Kα1 X ray 3.08E-01 2.747E-02 8.45E-03
γ 32 1.20E-03 1.054E 00 1.26E-03 Kα2 X ray 1.65E-01 2.720E-02 4.49E-03
γ 40 1.45E-02 1.325E 00 1.92E-02 Kβ1 X ray 5.81E-02 3.100E-02 1.80E-03
γ 42 2.90E-03 1.368E 00 3.97E-03 Auger-KLL 5.47E-02 2.254E-02* 1.23E-03
γ 43 1.69E-02 1.376E 00 2.32E-02 Auger-KLX 2.48E-02 2.635E-02* 6.53E-04
γ 48 1.80E-03 1.489E 00 2.68E-03 Auger-LMM 4.07E-01 3.080E-03* 1.25E-03
γ 49 3.03E-02 1.509E 00 4.57E-02 Auger-LMX 2.09E-01 3.849E-03* 8.03E-04
γ 50 1.70E-03 1.560E 00 2.65E-03 Auger-MXY 1.21E 00 6.991E-04* 8.44E-04
γ 52 2.00E-03 1.638E 00 3.27E-03 LISTED X, γ AND γâ•›± RADIATIONS 1.08E 00
γ 54 1.10E-03 1.676E 00 1.84E-03 OMITTED X, γ AND γâ•›± RADIATIONS** 1.82E-02
γ 55 1.06E-01 1.691E 00 1.79E-01 LISTED β, ce AND Auger RADIATIONS 1.93E-01
γ 56 1.70E-03 1.720E 00 2.92E-03 OMITTED β, ce AND Auger RADIATIONS** 7.71E-04
γ 58 2.10E-03 1.851E 00 3.89E-03 LISTED RADIATIONS 1.27E 00
γ 59 1.60E-03 1.919E 00 3.07E-03
OMITTED RADIATIONS** 1.90E-02
γ 60 3.40E-03 2.038E 00 6.93E-03
*AVERAGE ENERGY (MeV)

467
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
468 Physics in Nuclear Medicine

IODINE-125

125
53I(60.14d)
0.0

0.0355
γ1 EC1
0.0
125
52Te(stable)

Half Life = 60.14 Days


Decay Mode(s): EC
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ1 6.67E-02 3.549E-02 2.37E-03
ce-K, γ 1 8.03E-01 3.678E-03 2.95E-03
ce-L1, γ 1 9.52E-02 3.055E-02 2.91E-03
ce-L2, γ 1 7.64E-03 3.088E-02 2.36E-04
ce-L3, γ 1 1.91E-03 3.115E-02 5.96E-05
ce-M, γ 1 2.09E-02 3.467E-02* 7.25E-04
ce-N+, γ 1 4.96E-03 3.549E-02* 1.76E-04
Kα1 X ray 7.41E-01 2.747E-02 2.04E-02
Kα2 X ray 3.98E-01 2.720E-02 1.08E-02
Kβ1 X ray 1.40E-01 3.100E-02 4.34E-03
Kβ2 X ray 4.30E-02 3.171E-02 1.36E-03
Kβ3 X ray 7.20E-02 3.094E-02 2.23E-03
Kβ5 X ray 1.44E-03 3.124E-02 4.51E-05
Lα X ray 6.14E-02 3.768E-03* 2.31E-04
Lβ X ray 5.93E-02 4.092E-03* 2.43E-04
Auger-KLL 1.32E-01 2.254E-02* 2.97E-03
Auger-KLX 5.97E-02 2.635E-02* 1.57E-03
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 469

IODINE-125—cont'd

Half Life = 60.14 Days


Decay Mode(s): EC
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i)
Auger-KXY 7.95E-03 3.013E-02* 2.40E-04
Auger-LMM 1.01E 00 3.086E-03* 3.11E-03
Auger-LMX 5.17E-01 3.855E-03* 1.99E-03
Auger-LXY 7.33E-02 4.386E-03* 3.21E-04
Auger-MXY 2.99E 00 6.989E-04* 2.09E-03
ΔE 6.22E-01 5.577E-05* 3.47E-05
LISTED X, γ AND γ± RADIATIONS 4.20E-02
OMITTED X, γ AND γ± RADIATIONS** 4.58E-05
LISTED β, ce AND Auger RADIATIONS 1.94E-02
LISTED RADIATIONS 6.14E-02
OMITTED RADIATIONS** 4.58E-05
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
TELLURIUM-125 DAUGHTER IS STABLE.
470 Physics in Nuclear Medicine

IODINE-131
131
53 I(8.04d)
0.0

0.7229
β
1
γ18
0.6669
β
2
0.6370
β
3

γ16 γ12

0.3645
β
4

0.3411
β
5

γ4

0.1639
β
6 γ17 γ7
0.0802
γ19 γ14 γ1
0.0
131
54 Xe(stable)
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 471

Half Life = 8.04 Days


Decay Mode(s): β–
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)

β 1 2.13E-02 6.935E-02* 1.48E-03
β– 2 6.20E-03 8.693E-02* 5.39E-04

β 3 7.36E-02 9.660E-02* 7.11E-03

β 4 8.94E-01 1.915E-01* 1.71E-01

β 6 4.20E-03 2.832E-01* 1.19E-03
γ1 2.62E-02 8.018E-02 2.10E-03
ce-K, γ 1 3.63E-02 4.562E-02 1.66E-03
ce-L1, γ 1 4.30E-03 7.473E-02 3.21E-04
γ4 2.65E-03 1.772E-01 4.70E-04
γ7 6.06E-02 2.843E-01 1.72E-02
ce-K, γ 7 2.48E-03 2.497E-01 6.20E-04
γ 12 2.51E-03 3.258E-01 8.18E-04
γ 14 8.12E-01 3.645E-01 2.96E-01
ce-K, γ 14 1.55E-02 3.299E-01 5.10E-03
ce-L1, γ 14 1.71E-03 3.590E-01 6.13E-04
γ 16 3.61E-03 5.030E-01 1.82E-03
γ 17 7.27E-02 6.370E-01 4.63E-02
γ 18 2.20E-03 6.427E-01 1.41E-03
γ 19 1.80E-02 7.229E-01 1.30E-02
Kα1 X ray 2.59E-02 2.978E-02 7.72E-04
Kα2 X ray 1.40E-02 2.946E-02 4.12E-04
LISTED X, γ AND γâ•›± RADIATIONS 3.80E-01
OMITTED X, γ AND γâ•›± RADIATIONS** 1.09E-03
LISTED β, ce AND Auger RADIATIONS 1.90E-01
OMITTED β, ce AND Auger RADIATIONS** 1.86E-03
LISTED RADIATIONS 5.70E-01
OMITTED RADIATIONS** 2.95E-03
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
XENON-131M DAUGHTER, YIELD 1.11E-02, IS RADIOACTIVE.
XENON-131 DAUGHTER, YIELD 9.889E-01, IS STABLE.
XENON-133
133
54Xe(5.245d)
0.0

0.1606
β2
γ3 γ1

0.0810
β
3
γ2
0.0
133
55Cs(stable)

Half Life = 5.245 Days


Decay Mode(s): β–
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)

β 2 6.60E-03 7.502E-02* 4.95E-04
β– 3 9.93E-01 1.005E-01* 9.98E-02
γ1 2.11E-03 7.962E-02 1.68E-04
ce-K, γ 1 3.17E-03 4.364E-02 1.38E-04
γ2 3.74E-01 8.100E-02 3.03E-02
ce-K, γ 2 5.35E-01 4.501E-02 2.41E-02
ce-L1, γ 2 6.52E-02 7.528E-02 4.91E-03
ce-L2, γ 2 4.91E-03 7.564E-02 3.72E-04
ce-M, γ 2 1.45E-02 8.000E-02* 1.16E-03
ce-N+, γ 2 3.80E-03 8.100E-02* 3.08E-04
γ3 6.20E-04 1.606E-01 9.96E-05
Kα1 X ray 2.53E-01 3.097E-02 7.85E-03
Kα2 X ray 1.37E-01 3.063E-02 4.20E-03
Kβ1 X ray 4.89E-02 3.499E-02 1.71E-03
Kβ2 X ray 1.70E-02 3.584E-02 6.08E-04
Kβ3 X ray 2.52E-02 3.492E-02 8.80E-04
Lα X ray 2.44E-02 4.285E-03* 1.04E-04
Lα X ray 2.32E-02 4.694E-03* 1.09E-04
Auger-KLL 3.69E-02 2.524E-02* 9.31E-04
Auger-KLX 1.73E-02 2.961E-02* 5.12E-04
Auger-LMM 3.03E-01 3.441E-03* 1.04E-03
Auger-LMX 1.72E-01 4.344E-03* 7.45E-04
Auger-MXY 9.33E-01 8.695E-04* 8.11E-04
LISTED X, γ AND γâ•›± RADIATIONS 4.60E-02
OMITTED X, γ AND γâ•›± RADIATIONS** 6.66E-05
LISTED β, ce AND Auger RADIATIONS 1.35E-01
OMITTED β, ce AND Auger RADIATIONS** 3.82E-04
LISTED RADIATIONS 1.81E-01
OMITTED RADIATIONS** 4.49E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
CESIUM-133 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 473

CESIUM-137

137
55Cs(30.0y)
0.0

0.6616
β
1

0.0
β 137
56Ba(stable)
2

Half Life = 30 Years


Decay Mode(s): β–
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)

β 1 9.46E-01 1.734E-01* 1.64E-01

β 2 5.40E-02 4.246E-01* 2.29E-02
LISTED β, ce AND Auger RADIATIONS 1.87E-01
LISTED RADIATIONS 1.87E-01
*AVERAGE ENERGY (MeV)
BARIUM-137M DAUGHTER, YIELD 9.46E-01, IS RADIOACTIVE.
BARIUM-137 DAUGHTER, YIELD 5.40E-02, IS STABLE.
474 Physics in Nuclear Medicine

THALLIUM-201

201
81Tl(3.044d)
0.0

0.1675 EC1

γ5
γ7 γ6

0.0322 EC2
γ3
0.0016 EC4
γ4 γ1
0.0
201
80 Hg(stable)

Half Life = 3.044 Days


Decay Mode(s): EC
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
ce-N , γ 1 6.10E-01 1.570E-03* 9.58E-04
ce-L1, γ 3 7.30E-02 1.576E-02 1.15E-03
ce-L2, γ 3 7.55E-03 1.639E-02 1.24E-04
ce-M, γ 3 1.90E-02 2.775E-02* 5.27E-04
ce-N+, γ 3 6.78E-03 3.060E-02* 2.07E-04
ce-L1, γ 4 6.28E-02 1.735E-02 1.09E-03
ce-L2, γ 4 6.53E-03 1.798E-02 1.17E-04
ce-M, γ 4 1.63E-02 2.934E-02* 4.80E-04
ce-N , γ 4
+
5.74E-03 3.219E-02* 1.85E-04
γ5 2.65E-02 1.353E-01 3.59E-03
ce-K, γ 5 7.47E-02 5.224E-02 3.90E-03
ce-L1, γ5 1.14E-02 1.205E-01 1.37E-03
ce-L2, γ 5 1.20E-03 1.211E-01 1.45E-04
ce-M, γ 5 2.97E-03 1.325E-01* 3.93E-04
ce-N , γ 5
+
9.58E-04 1.353E-01* 1.30E-04
γ6 1.60E-03 1.659E-01 2.65E-04
ce-K, γ 6 2.26E-03 8.278E-02 1.87E-04
ce-L1, γ 6 3.42E-04 1.510E-01 5.16E-05
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 475

THALLIUM-201—cont'd

Half Life = 3.044 Days


Decay Mode(s): EC
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ7 1.00E-01 1.674E-01 1.67E-02
ce-K, γ 7 1.54E-01 8.433E-02 1.30E-02
ce-L1, γ 7 2.35E-02 1.526E-01 3.58E-03
ce-L2, γ 7 2.48E-03 1.532E-01 3.80E-04
ce-L3, γ 7 2.80E-04 1.551E-01 4.35E-05
ce-M, γ 7 6.10E-03 1.646E-01* 1.00E-03
ce-N+, γ 7 1.96E-03 1.674E-01* 3.29E-04
Kα1 X ray 4.62E-01 7.082E-02 3.27E-02
Kα2 X ray 2.72E-01 6.889E-02 1.87E-02
Kβ1 X ray 1.05E-01 8.026E-02 8.45E-03
Kβ2 X ray 4.43E-02 8.258E-02 3.66E-03
Kβ3 X ray 5.48E-02 7.982E-02 4.37E-03
Kβ5 X ray 2.88E-03 8.077E-02 2.33E-04
Lα X ray 1.90E-01 9.980E-03* 1.90E-03
Lβ X ray 1.82E-01 1.185E-02* 2.15E-03
Lγ X ray 3.40E-02 1.397E-02* 4.75E-04
Auger-KLL 2.01E-02 5.526E-02* 1.11E-03
Auger-KLX 1.12E-02 6.652E-02* 7.45E-04
Auger-KXY 1.80E-03 7.733E-02* 1.39E-04
Auger- 4.30E-01 7.753E-03* 3.34E-03
LMM
Auger-LMX 2.78E-01 1.022E-02* 2.84E-03
Auger-LXY 4.63E-02 1.214E-02* 5.62E-04
Auger-MXY 1.74E 00 2.673E-03* 4.66E-03
ΔE 1.05E 00 5.204E-04* 5.45E-04
LISTED X, γ AND γâ•›± RADIATIONS 9.32E-02
OMITTED X, γ AND γâ•›± RADIATIONS** 2.52E-04
LISTED β, ce AND Auger RADIATIONS 4.33E-02
OMITTED β, ce AND Auger RADIATIONS** 1.16E-04
LISTED RADIATIONS 1.37E-01
OMITTED RADIATIONS** 3.68E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
MERCURY-201 DAUGHTER IS STABLE.
appendix
D
Mass Attenuation Coefficients
for Water, NaI(Tl), Bi4Ge3O12,
Cd0.8Zn0.2Te, and Lead

Attenuation Coefficient, µ (cm2/g)*


Photon Energy
(MeV) H2O Nal(Tl) Bi4Ge3O12 Cd0.8Zn0.2Te Pb
      ρ (g/cm ) →
3
1.00 3.67 7.13 5.81 11.34
0.02 0.721 20.7 65.8 21.4 84.0
0.0267 — — — 9.5 —
0.0267 — — — 25.8 —
0.03 0.329 6.71 22.6 19.1 28.9
0.0318 — — — 16.3 —
0.0318 — — — 33.2 —
0.0332 — 5.08 — — —
0.0332 — 29.87 — — —
0.04 0.240 18.35 10.5 18.2 13.4
0.05 0.208 10.18 5.76 10.0 7.39
0.06 0.192 6.23 3.53 6.10 4.53
0.08 0.176 2.86 1.66 2.78 2.11
0.088 — — — — 1.65
0.088 — — — — 7.42
0.0905 — — 1.21 — —
0.0905 — — 4.92 — —
0.1 0.165 1.58 3.82 1.52 5.34
0.15 0.148 0.566 1.39 0.544 1.91
0.2 0.136 0.302 0.696 0.290 0.936
0.3 0.118 0.153 0.294 0.148 0.373
0.4 0.106 0.110 0.179 0.107 0.215
0.5 0.0967 0.0904 0.131 0.0877 0.150

476
Appendix D╇ •â•‡ Mass Attenuation Coefficients for Water, NaI(Tl), Bi4Ge3O12, Cd0.8Zn0.2Te, and Lead 477

Attenuation Coefficient, µ (cm2/g)*


Photon Energy
(MeV) H2O Nal(Tl) Bi4Ge3O12 Cd0.8Zn0.2Te Pb
      ρ (g/cm ) →
3
1.00 3.67 7.13 5.81 11.34
0.6 0.0894 0.0790 0.105 0.0769 0.117
0.8 0.0786 0.0657 0.0794 0.0641 0.0841
1.0 0.0707 0.0576 0.0661 0.0562 0.0680
1.022 0.0699 0.0569 0.0650 0.0556 0.0668
1.5 0.0575 0.0464 0.0506 0.0454 0.0509
2.0 0.0494 0.0412 0.0447 0.0404 0.0453
3.0 0.0397 0.0367 0.0402 0.0363 0.0420
4.0 0.0340 0.0351 0.0388 0.0350 0.0418
5.0 0.0303 0.0347 0.0387 0.0349 0.0426
6.0 0.0277 0.0348 0.0391 0.0352 0.0438
8.0 0.0243 0.0358 0.0406 0.0365 0.0467
10.0 0.0222 0.0372 0.0424 0.0382 0.0497
*Values without coherent scattering, obtained from reference 2 in Chapter 6.
H 2O, water; NaI(Tl), thallium-doped sodium iodide; Bi4Ge3O12, bismuth germanate; Cd0.8Zn0.2Te, cadmium zinc telluride;
Pb, lead.
appendix
E
Effective Dose
Equivalent (mSv/MBq)
and Radiation
Absorbed Dose
Estimates (mGy/MBq)
to Adult Subjects from
Selected Internally
Administered
Radiopharmaceuticals
Absorbed Dose for Selected
Effective Dose
Organs (mGy/MBq)†
Route of Equivalent*
Radiopharmaceutical Administration (mSv/MBq) Organ Dose
13
N-ammonia Intravenous 2.2 × 10−3 Bladder wall 6.9 × 10−3
Brain 4.7 × 10−3
Liver 3.8 × 10−3
Gonads 1.7 × 10−3
Red marrow 1.8 × 10−3
15
O-water Intravenous 1.1 × 10−3 Heart wall 2.2 × 10−3
Kidneys 1.9 × 10−3
Lungs 1.9 × 10−3
Gonads 6.7 × 10−4
Red marrow 9.0 × 10−4
18
F-fluorodeoxyglucose (FDG) Intravenous 3.0 × 10−2 Bladder wall 1.9 × 10−1
Heart wall 6.0 × 10−2
Spleen 3.7 × 10−2
Gonads 1.7 × 10−2
Red marrow 1.3 × 10−2
67
Ga-citrate Intravenous 1.1 × 10−1 Bone surfaces 3.2 × 10−1
LLI wall 2.6 × 10−1
ULI wall 1.5 × 10−1
Gonads 8.7 × 10−2
Red marrow 1.2 × 10−1

478
Appendix E╇ •â•‡ Selected Internally Administered Radiopharmaceuticals 479

Absorbed Dose for Selected


Effective Dose
Organs (mGy/MBq)†
Route of Equivalent*
Radiopharmaceutical Administration (mSv/MBq) Organ Dose
99m
Tc-pertechnetate Intravenous 1.1 × 10 −2
Bladder wall 3.6 × 10−2
ULI wall 2.8 × 10−2
LLI wall 2.7 × 10−2
Gonads 8.6 × 10−3
Red marrow 3.3 × 10−3
99m
Tc-MDP Intravenous 6.1 × 10−3 Bone surfaces 3.5 × 10−2
Bladder wall 3.3 × 10−2
Kidneys 8.6 × 10−3
Gonads 3.3 × 10−3
Red marrow 5.4 × 10−3
99m
Tc-sestamibi Intravenous 1.5 × 10−2 ULI wall 5.0 × 10−2
Bladder wall 3.7 × 10−2
LLI wall 3.7 × 10−2
Gonads 1.4 × 10−2
Red marrow 4.5 × 10−3
99m
Tc-DTPA Intravenous 8.2 × 10−3 Bladder wall 7.7 × 10−2
Uterus 1.0 × 10−2
Kidneys 5.7 × 10−3
Gonads 5.5 × 10−3
Red marrow 2.2 × 10−3
99m
Tc-mertiatide (MAG3) Intravenous 1.2 × 10−2 Bladder wall 1.4 × 10−1
Uterus 1.5 × 10−2
LLI wall 7.1 × 10−3
Gonads 6.6 × 10−3
Red marrow 1.1 × 10−3
99m
Tc-exametazime (HMPAO) Intravenous 1.4 × 10−2 Gallbladder 5.1 × 10−2
Kidneys 3.5 × 10−2
Bladder wall 2.8 × 10−2
Gonads 7.0 × 10−3
Red marrow 3.5 × 10−3
111
In-DTPA Intravenous 4.1 × 10−2 Bladder wall 4.3 × 10−1
Uterus 5.4 × 10−2
LLI wall 2.8 × 10−2
Gonads 2.5 × 10−2
Red marrow 8.2 × 10−3
123
I-sodium iodide Oral 1.2 × 10−1 Thyroid 3.4 × 100
Bladder wall 9.6 × 10−2
Stomach 5.5 × 10−2
Gonads 1.2 × 10−2
Red marrow 5.8 × 10−3
131
I-sodium iodide Oral 1.1 × 101 Thyroid 3.4 × 102
Bladder wall 6.2 × 10−1
Stomach 3.6 × 10−1
Gonads 4.7 × 10−3
Red marrow 8.3 × 10−2
201
Tl-thallium chloride Intravenous 1.6 × 10−1 Thyroid 6.2 × 10−1
Kidneys 4.6 × 10−1
Small intestine 4.5 × 10−1
Gonads 2.0 × 10−1
Red marrow 5.5 × 10−2
Data from Stabin MG, Stubbs JB, Toohey RE: Radiation Dose Estimates for Radiopharmaceuticals, Oak Ridge Institute
for Science and Education, NUREG/CR-6345, 1996. Available electronically at http://www.nrc.gov/reading-rm/doc-
collections/nuregs/contract/cr6345/. Accessed 5 November 2011.
DTPA, diethylenetriaminepenta acetic acid; HMPAO, hexamethylpropyleneamine oxime; LLI, lower large intestine;
MDP, methylene diphosphonate; ULI, upper large intestine.
*Effective dose equivalent has now been replaced by the quantity effective dose which uses somewhat different tissue
weighting factors (see Chapter 22, Section B.7).

Three organs with highest absorbed doses and the absorbed dose to red marrow and the gonads which are both
radiosensitive. Values given for gonads are the higher of the absorbed dose estimates for the testes and ovaries.
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appendix
F
The Fourier Transform

Fourier transforms (FTs) play an important The concept of spatial frequency is illus-
role in tomographic reconstruction (see trated in Figure F-1. Slow oscillations
Chapter 16) and in computer implementation represent low spatial frequencies and rapid
of convolutions (see Appendix G). As well, they oscillations represent high frequencies. If fâ•›(x)
are the basis for the modulation transfer func- represents an image profile, the former would
tion (MTF), one of the methods for evaluating represent primarily the coarse structures,
spatial resolution of imaging systems (see whereas the latter would represent fine
Chapter 15) and many other methods for details.
image analysis and image processing. This Thus F(k) is a representation of the image
appendix is intended to provide an intuitive profile in k-space, or spatial-frequency space,
description of what the FT is, how it is calcu- whereas fâ•›(x) is a representation of the profile
lated, and some of its properties. For simplicity, in object space (sometimes also called distance
the analysis is presented for one-dimensional space). Either fâ•›(x) or F(k) is a valid represen-
examples. The extension to higher dimensions tation of the image intensity profile and, as
is relatively straightforward. A detailed treat- shown subsequently, either one can be derived
ment is beyond the scope of this text. The from the other. Another notation for the FT is
interested reader is referred to the excellent
texts by Bracewell for further information.1,2 F (k) = F [ f ( x)] (F-1)

where the symbol F denotes the operation of


A.  THE FOURIER TRANSFORM:   computing an FT.
WHAT IT REPRESENTS FTs can be computed for functions in other
coordinate spaces as well. For example, in
The FT is an alternative manner for repre- audio technology, signal intensity varies as a
senting a mathematical function or mathe- function of time, t, and its FT describes the
matical data. For example, suppose that the function in terms of temporal frequencies, v,
function fâ•›(x) represents an image intensity expressed as cycles per second, or Hz (sec−1).
profile. It can be shown that, so long as fâ•›(x) Coordinate pairs that are represented by a
has “reasonable properties,” the profile can function and its FT, such as x and k, or t and
be represented as a sum of sine and cosine v, are referred to as conjugate variables.
functions of different frequencies extending
along the x-axis. The FT of fâ•›(x), denoted as
F(k), represents the amplitudes of the sine B.  CALCULATING FOURIER
and cosine functions for different spatial fre- TRANSFORMS
quencies, k. Spatial frequency reflects how
rapidly a sine or cosine function oscillates FTs can be calculated for continuous func-
along the x-axis and has units of “cycles per tions, which have values for all values of x, or
distance,” such as cycles per cm,* or cm−1. for discrete functions, which have values only
at discrete sampling intervals Δâ•›x. A discrete
function may be a sampled version of a con-
*As noted in Chapter 15, the notation k is used in physics tinuous function. Continuous FTs often are
to denote “spatial radians per distance” and the notation employed for theoretical modeling or analysis.

k , or “k-bar,” is used to denote “cycles per distance.”
Mathematically, − k = k/2π, because there are 2π radians However, because the signals of interest in
per cycle. However, for notational simplicity, we use k for nuclear medicine imaging always are sampled
“cycles per distance” in this text. (or “digitized”) in projection bins, image pixels,
481
482 Physics in Nuclear Medicine

High
frequency

Medium
frequency
FIGURE F-1â•… Sinusoidal functions representing
low, medium, and high spatial frequencies.

Low
frequency

and so on, we will restrict our analysis to the where i = −1 is a complex (“imaginary”)
discrete Fourier transform (DFT). number. Thus values for F are computed at N
In practice, a function representing a points at intervals Δâ•›k along the k-axis,
signal, such as an image intensity profile fâ•›(x), ranging from k = 0 to kmax = (N – 1)Δâ•›k. The
is sampled at a finite number of points, N, at “zero-frequency” term actually represents a
equally spaced intervals Δâ•›x. The range of x constant equal to the average value of fâ•›(x)
over which the function is sampled, NΔâ•›x, is within the digitized field of view, FOVx. We
the field-of-view along x, denoted by FOVx. For will designate the range of k-space over which
detectors with discrete detector elements, the the FT is computed, NΔâ•›k, as FOVk (i.e., the
sampling interval generally is the width of a “field of view” in k-space).
detector element and the number of samples The complex exponential term in Equation
is the number of elements across the detector F-3 represents Euler’s equation, which states
array. For gamma cameras, N and Δâ•›x (or that
FOVx) can be chosen somewhat arbitrarily
under computer control. In this case, FOVx
may or may not equal the physical field of view eiθ = cos θ + i sin θ (F-4)
of the detector. It simply refers to the distance
along the x-axis over which data are sampled, Thus in general, the values of Fm are complex
which may be smaller (or even larger) than numbers with “real” and “imaginary” parts.
the physical dimensions of the detector. This does not imply that the FT is some
Although N can be any integer, it usually is a sort of “imaginary” entity. Rather, the use
power of 2 (64, 128, 256, etc.). Using a power of complex numbers in Equation F-3 provides
of 2 allows one to use a very fast computa- a mathematically convenient way for com�
tional algorithm called the fast Fourier trans- puting the amplitudes of “cosine” functions
form (FFT). FFTs are provided in many versus “sine” functions in the representation
mathematical software packages. The basic of fâ•›(x).
algorithm is described in reference 3. Conversely, if one is provided with a set
Consider the case in which fâ•›(x) is sampled of N values for F, they can be used to compute
at N points over a range of x values from x = N values for f using the inverse discrete FT,
0 to (N – 1)Δâ•›x. The sampled data are repre- described by
sented as
N −1
f j = f ( j∆ x ) j = 0, 1, 2, .… N − 1 (F-2)
f ( j∆ x) = f j = ∑Fe κ
i 2 π jκ / N
(F-5)
Given N sampled points, the discrete FT of κ =0

f is calculated from the following equation


This equation differs from Equation F-3 only
N −1 in the sign of the exponent and the appear-
F (m∆ k) = Fm = (1 / N ) ∑ f j e− i2 πmj / N ance of the (1/Nâ•›) term in the former. (Some
j =0 (F-3) alternative formulations for Equations F-3
m = 0, 1, 2, .… N − 1 and F-5 show different placements for N.) To
Appendix F╇ •â•‡ The Fourier Transform 483

distinguish between the two, Equation F-3 interval in object space. The relationships
sometimes is referred to as the forward FT. between data ranges and intervals are com-
Finally, if the original data are properly pletely symmetrical between object space
sampled (e.g., if they meet the requirements and k-space. Figure F-2 illustrates these
of the sampling theorem discussed later), the relationships.
inverse FT of the forward FT returns an exact Equations F-7 and F-8 have important
replica of the original data. In other words, practical ramifications. Specifically, a funda-
mental assumption underlying the discrete
F −1
[ F [ f ( x)]] = f ( x) (F-6) FT algorithm is that the sampled function fâ•›(x)
actually extends indefinitely along the x-axis,
repeating itself at intervals NΔâ•›x = FOVx. In
other words, it assumes that the sampled
C.  SOME PROPERTIES OF FOURIER data simply repeat themselves to infinity in
TRANSFORMS both directions along the x-axis. Conversely,
it assumes as well that F(k) repeats itself at
Equations F-3 and F-5 are mathematically intervals NΔâ•›k, again to infinity, in both direc-
powerful, but not exactly transparent regard- tions along the k-axis. This means, for
ing how they operate. Therefore we will not example, that because of cyclic repetition,
attempt to analyze them in any detail. Rather, F(NΔâ•›k) = F(0). This result can be understood
we will focus only on some properties of the by observing that NΔâ•›k = FOVk and, according
discrete FT. to Equation F-8, FOVk = 1/Δâ•›x.
As noted previously, the FT of a function Thus if a sinusoidal oscillation with spatial
that is sampled at N points also has N values. frequency NΔâ•›k is present in the underlying
It can be shown that the following relation- sampled function, it would be sampled pre-
ships apply regarding data intervals and cisely once per cycle. Furthermore, with precise
range in k-space: timing, it would be sampled always at the
same point during the cycle. Thus the sampled
∆k = 1/FOVx (F-7) data for a spatial frequency k = NΔâ•›k would be
FOVk = 1/∆ x (F-8) indistinguishable from a “constant” signal
level (i.e., k = 0). Similarly, the next higher
Thus the data interval in k-space is inversely frequency, (N + 1)Δâ•›k, would be sampled less
proportional to the data range in object than once per cycle and would be indistin-
space, and conversely, the data range in guishable from a lower frequency, which turns
k-space is inversely proportional to the data out to be k1. This effect, in which a higher

FOVx1/k

x
x

k

FOVk1/x
FIGURE F-2â•… Illustration of the relationships between sampling ranges and sampling intervals in object space and
k-space.
484 Physics in Nuclear Medicine

frequency is falsely identified as a lower one, sampled function actually contained frequen-
is called aliasing.* cies out to ±10╯ cm−1. Because of underÂ�
From this illustration, it is apparent that sampling, frequencies between 8 and 10╯ cm−1
the highest spatial frequency that can be rep- are “wrapped around” and overlap the lower
resented accurately in a discrete FT is deter- end of the negative frequency portion of
mined by the sampling interval along the the spectrum. A similar wraparound of nega-
x-axis. However, there is yet another compli- tive frequencies occurs at the high end of
cation. Specifically, an image (or any object- the spectrum. When the FT is calculated,
space profile) can contain both positive and the overlapped portions are simply added
negative frequencies. For a cosine function, together in the aliased regions of the
there is no difference, because cos(–x) = cos(x). spectrum.
However, for a sine function, sin(–x) = –sin(x), This effect and its consequences for emis-
so the positive and negative oscillations are sion CT reconstruction are discussed in
reversed. In terms of the level of “detail” con- Chapter 16, Section C.1. Similar effects occur
tained in an image or profile, the difference in other applications of FTs [e.g., computa-
between positive and negative frequencies is tions of MTFs (see Chapter 15, Section B.2)].
unimportant. The practical importance is The sampling theorem also has practical ram-
that the use of “negative frequencies” allows ifications for data acquisition with arrays of
one to obtain consistent representations discrete detector elements. It can be shown
for the FT of a function fâ•›(x) that is shifted that a linear array of detector elements, each
along the x-axis, but otherwise unchanged. of width d, with negligibly small spacings
This is the basis of the “shift theorem,” which between elements, can detect spatial frequen-
is discussed in advanced texts.4 cies out to k = 1/d and even beyond. (See
The presence of negative frequencies means Figure F-5C, which is essentially the MTF for
that the highest spatial frequency that can an aperture of width d = 1.) However, with
be computed by a discrete FT is not NΔâ•›k, only one sample per distance d, the Nyquist
but only half this value. This frequency, called frequency is kNyquist = 1/(2d ) = (1/2) × (1/d ) (i.e.,
the Nyquist frequency, can be derived one half the frequency that would be desired
from Equations F-6 and F-7 and usually is for kmax = 1/d ). Thus spatial frequencies in the
expressed as range 1/(2d ) < k < 1/d are aliased back into
lower frequency portions of the spectrum,
kNyquist = 1/ (2 × ∆ x) (F-9) where they can cause distortions of the
recorded profile. One way to avoid this is to
This equation is the basis of the sampling acquire a second set of data with the detector
theorem,5 which states that, to accurately array “shifted” by one half the width of the
compute (or “recover”) a specified spatial fre- individual detector elements and to insert
quency requires a sampling rate of at least these data points between those for the
two samples per cycle at that frequency. Fre- “unshifted” data. This reduces the sampling
quencies higher than the Nyquist frequency interval from d to d/2, thereby suppressing
cannot be distinguished from lower frequen- the effects of aliasing.
cies. An example is illustrated in Figure F-3. This analysis applies when the spatial
Profiles (or signals) containing frequencies resolution of the individual detector elements
that are higher than the Nyquist frequency is essentially the width of the element. This
specified in Equation F-9 are said to be would apply, for example, to collimated linear
undersampled. arrays operating in single-photon counting
Undersampling and aliasing can lead to mode. The situation is yet more complicated
image distortions, errors in data analysis, in positron emission tomography (PET), for
and so forth. Figure F-4 illustrates their which the spatial resolution of a pair of detec-
effects in k-space. In this hypothetical tors of width d can be as small as d/2 (see
example, a sampling rate was used corre- Chapter 18, Section A.3). In this case, inter-
sponding to kNyquist = 8╯ cm−1; however, the leaving is essential to achieve the required
sampling frequency. Techniques for accom-
plishing this in PET imaging are described in
Chapter 18, Section A.6.
*Most readers will have seen examples of aliasing in It is important to realize that aliasing
motion pictures, in which undersampling in the frame
rate leads to the appearance of false and even backward
cannot be “undone” by postprocessing of
rotations of the spokes of wagon wheels, helicopter undersampled data. If one starts with an
blades, and so forth. undersampled data set, there is no way to
Appendix F╇ •â•‡ The Fourier Transform 485

Signal level
1

1
0 0.5 1 1.5 2
Distance (cm)
FIGURE F-3â•… Illustration of the effects of undersampling of a spatially varying source distribution. The red curve
represents the actual signal, which has a spatial frequency of 6 cycles per cm (6╯cm−1). Black dots represent sampled
points. The sampling distance is Δâ•›x = 0.1╯cm, for which the Nyquist frequency is 5╯cm−1. As a result of undersampling,
the sampled data for a spatial frequency of 6╯cm−1 cannot be distinguished from a signal corresponding to a spatial
frequency of 4╯cm−1 (╛╛green line). The false representation of higher frequencies as lower frequencies is called
aliasing.

Aliased regions
F (k)

Actual spectrum

Overlap

10 8 6 4 2 0 2 4 6 8 10
Spatial frequency, k (cm1)
FIGURE F-4â•… Illustration of the effects of aliasing in k-space. The graphs represent hypothetical Fourier transforms
(FTs). Data in object space were sampled at 16 points per cm (cm−1) for computing the FT. The Nyquist frequency for
this sampling rate is 8╯cm−1. However, the actual spatial-frequency spectrum (blue line) has significant frequency
content extending out to 10╯cm−1. As a result of undersampling, the replicated ends of the actual spectrum (orange line)
overlap and add to the calculated spectrum (heavy red line), creating an aliased region of the spectrum. The calculated
spectrum does not accurately represent the true FT for the object.

“unwrap” the spectral overlap illustrated in that is sufficiently small to meet the
Figure F-4. requirements of the sampling theorem
Aliasing can be avoided in a number of for all frequencies present in the data.
ways, including the following: One way to achieve this is to acquire
1. The most direct way is to use a sampling more data points along the sampled dis-
interval along the x-axis (or along what- tance. However, for applications involv-
ever object-space axis is being sampled) ing FFTs, this requires increasing the
486 Physics in Nuclear Medicine

number of samples (e.g., pixels) by a spatial frequency that has nonzero amplitude
power of 2, which could be impractical is k = 0, and that amplitude is equal to the
for reasons of dataset size, computation value of the constant.
time, and so on. Figure F-5B shows a cosine wave of spatial
2. If increasing the number of samples is frequency 1 cycle per cm and amplitude 1.0
not practical, one could use the same superimposed on a constant value of 1 unit.
number of samples but apply them over In this case, fâ•›(x) = 0.5 cos (2πâ•›x) + 1. The FT
a smaller field-of-view, thereby decreas- has an amplitude of 1 at k = 0, and amplitudes
ing the sampling interval Δâ•›x. This would of 0.5 each at ±1╯cm−1. This ambiguity arises
increase the Nyquist frequency (Equa- from the fact that the FT cannot distinguish
tion F-9); however, reducing FOVx also between positive versus negative cosine func-
has practical constraints. For example, tions at these frequencies. (They are in fact
the field-of-view must provide full cover- identical.) Thus it assigns half of the observed
age of the scanned portion of the body in amplitude to each value. (The FT of a sine
computed tomography. function is similar, except that the value for
3. A third alternative is to deliberately k = –1╯cm−1 is –0.5. This is because the FT
“blur” the input profile (or image) before cannot distinguish a positive sine wave of
it is recorded by the detectors so as negative frequency from a negative sine wave
to suppress the potentially undersam- of positive frequency.)
pled high-frequency components. In the Figure F-5C shows a “boxcar” function
context of image profiles, this means that (sometimes also called a “rect” function) for
the data projected onto the detector itself which fâ•›(x) = 1 when x is within the range –0.5
must be “blurred” (e.g., by using a coarser ≤ x ≤ +0.5 and fâ•›(x) = 0 outside this range. This
collimator). The obvious disadvantage of function crops up often in signal-processing
this approach is that the resulting image techniques that employ “windowing” filters to
also is blurred. eliminate portions of the spectrum outside a
If none of these options are practical, the windowed range in k-space. In this case, the
effects of undersampling can be minimized FT is a more complicated function (specifi-
(but not eliminated) by postprocessing steps. cally, a “sinc function”).
One approach for already undersampled data Figure F-5C illustrates that FTs can exist
is to simply “lop off ” or otherwise completely even for functions with unusual properties,
suppress portions of the frequency spectrum such as discontinuities. Also, although fâ•›(x)
that might be affected by aliasing. However, itself does not have apparent “high-frequency
as illustrated in Figure F-4, the potentially oscillations,” its FT has high-frequency com-
affected range is somewhat unpredictable and ponents. These components are necessary to
may be large. This also is a rather wasteful represent the sharp edges of the boxcar. Thus
approach, because one ends up throwing away the MTF of an imaging system must have a
not only frequencies above the Nyquist fre- good high-frequency response to faithfully
quency but any lower frequencies that they reproduce sharp edges and fine details. In
overlap after they are wrapped around in the addition, the figure indicates that windowing
spectrum. filters with sharp edges in k-space can create
“ringing artifacts” (sometimes called Gibbs
phenomenon) in object space. These features,
as well as illustrations of FTs of many other
D.  SOME EXAMPLES OF FOURIER mathematical functions, are presented and
TRANSFORMS discussed in reference 1.
Finally, Figure F-6 shows a brain image, an
Figure F-5 shows some one-dimensional intensity profile for a strip across the image,
examples of functions and their FTs. Note and the FT of that profile. Note that most of
that the functions are represented as continu- the “information” is contained in the low-fre-
ous functions. If DFTs were involved, the quency portion of the spectrum. This does not
underlying functions would be the same, but mean that the high-frequency response (MTF)
the data would be represented by “points” on of the imaging system is unimportant. Indeed,
the curves, following the rules outlined in the because the high-frequency components are
preceding section. relatively weak to begin with, it is important
In Figure F-5A, fâ•›(x) is a constant, as would that the imaging system be able to faithfully
be all sampled values of it. Therefore the only preserve them.
Appendix F╇ •â•‡ The Fourier Transform 487

2 1.5

1.5 1

Fourier

F(k)
f (x)

1 transform 0.5

0.5 0

0 0.5
2 1 0 1 2 2 1 0 1 2
A Spatial domain (cm) Frequency domain (cm1)

2 1.5

1.5 1

Fourier
F (k)
f (x)

1 transform 0.5

0.5 0

0 0.5
2 1 0 1 2 2 1 0 1 2
B Spatial domain (cm) Frequency domain (cm1)

2 1.5

1.5 1

Fourier
F(k)
f(x)

1 transform 0.5

0.5 0

0 0.5
2 1 0 1 2 4 2 0 2 4
C Spatial domain (cm) Frequency domain (cm1)

FIGURE F-5â•… Three functions and their Fourier transforms (FTs). A, fâ•›(x) = 1.0. Its FT has only one value, at k = 0.
B, f (x) = cos(2πâ•›x) + 1. Its FT has values at k = 0 and at k = ±1╯cm−1, corresponding to the spatial frequency of the cosine
function. C, A boxcar function, fâ•›(x) = 1 when –0.5 < x < 0.5, fâ•›(x) = 0 otherwise. Its FT is a sinc function, sinc(x) =
[sin(πâ•›x)]â•›/(πâ•›x). Note that this also is the modulation transfer function of an aperture or a detector element of unit width.
488 Physics in Nuclear Medicine

250

200

150

Counts
100

50

0
0 32 64 96 128

Pixel (x )

FT

250

200
Amplitude

150

100

50

0
64 32 0 32 64

Frequency (pixels1)
FIGURE F-6â•… Frequency spectrum for a profile recorded through a brain image. The box on the image indicates the
sampling line for the profile (i.e., the direction x is vertical).

REFERENCES 4. Bracewell RN: The Fourier Transform and Its


Applications, ed 3, New York, 2000, McGraw-Hill,
1. Bracewell RN: The Fourier Transform and Its Applica- pp 111-113.
tions, ed 3, New York, 2000, McGraw-Hill. 5. Bracewell RN: The Fourier Transform and Its Applica-
2. Bracewell RN: Fourier Analysis and Imaging, New tions, ed 3, New York, 2000, McGraw-Hill, Chapter 10.
York, 2004, Kluwer Academic Publishers.
3. Press WH, Teukolsky SA, Vetterling WT, Flannery BP:
Numerical Recipes in C, ed 2, Cambridge, 1992, United
Kingdom, Chapter 12.
appendix
G
Convolution

Convolution is a mathematical technique that functions represented by a series of n


is used in imaging to compute the effects of values is
two (or more) simultaneously operating “blur-
ring” functions. For example, the image pro- f = [ a0, a1, … , an −1 ] (G-4)
jected by a collimator onto an Anger camera
detector is blurred by the collimator holes (see
Chapter 14, Sections C and D). Suppose that g = [b0, b1, … , bn −1 ] (G-5)
the collimator point-spread function is
described by a one-dimensional function fâ•›(x). A more compact notation is fâ•›(xi). Here it is
That profile is projected onto the camera understood that xi = (i × Δâ•›x), in which Δâ•›x is
detector where it is blurred again by the the sampling interval along the x-axis and i
intrinsic resolution of the detector (see = 0, 1, 2, …, (n – 1).
Chapter 14, Section A.1). Suppose that the Using the notation of Equations G-4 and
detector point-spread function is described G-5, the convolution of two discrete functions
by a function gâ•›(x). Then the combined effects is described by
or the collimator and detector blurring j
are described by the convolution, h(x), sym- h j = ∑ ( ai × b j − i ) (G-6)
bolized as i=0

The subscript j runs from 0 to (2n – 1); in


h( x) = f ( x) ∗ g ( x) (G-1) other words, the convolution yields (2n – 1)
values for h.†
An alternative notation is Analogous expressions exist for two-
dimensional convolutions (i.e., functions of
h( x) = f ( x) 
* g ( x) (G-2) two variables, x and y). Convolutions fre-
quently are performed for two-dimensional
The function h(x) is thus the system point- image processing (e.g., image smoothing—
spread function that accounts for both colli- another form of “blurring”); however, the con-
mator and detector blurring. Mathematical cepts embodied in Equations G-3 and G-6 are
convolutions find use in other fields as well, most easily demonstrated using one-dimen-
including statistics, electrical engineering, sional graphical examples.
and general signal processing. Consider first the convolution of two con-
Mathematically, the convolution of two tinuous functions. In Figure G-1A, the func-
continuous functions is described by1 tion fâ•›(u) is plotted as a function of u. (Note
∞ that this is only a change of notation for
h( x) ∫ f (u) g ( x − u) du (G-3) mathematical representation. It is not a
−∞
Equation G-3 is useful for theoretical †Note that some of the values for a and b appearing in
development and analysis (e.g., for system Equation G–6 do not exist. Specifically, there are no
design). However, most practical uses of values of a or b when their subscripts exceed (n – 1), both
convolution in the nuclear medicine labora- of which occur in the equation as written. For computer
tory involve discrete, rather than continuous implementation, the practical solution is to increase the
length of the arrays for f and g by adding zeros to the list
functions (e.g., a projection profile for emis- of values in Equations G–4 and G–5. This is sometimes
sion computed tomography is a discrete series called “zero padding.” Additional values for h that are
of numbers). One representation for discrete generated by this step are discarded.
489
490 Physics in Nuclear Medicine

f (u) g(u)

A Input function B Convolving function

FIGURE G-1â•… Illustration of the steps


involved in determining the value of the con-
g(u) g(au) volution of two functions, f (x) and g(x), at
x = a. A and B, the variable x is replaced by
u. C, The convolving function, g, is reflected
through the origin, u = 0. D, The reflected
function is shifted by a distance, x = a, to the
right. E, The function f and the shifted func-
a tion, g, are overlapped. F, The product of f and
the shifted function g is taken at each value
of u. The area under the curve representing
C g(u) Reflected D g(u) Reflected and shifted this product is h(a), the value of the convolu-
tion at the value of x = a.

f (u) g(au) h(a)Area

E Functions superimposed F Product of functions

change of coordinate systems.) The convolv- but unshifted (a = 0) version of g and f is


ing function, g(u) is shown in Figure G-1B. formed and summed across both functions.
Figure G-1C shows g(–u), which is g(u) This is h(0), which happens to have a value
reflected through the origin. In Figure G-1D, of zero in this example. The reflected and
g is shifted by a distance a along the u-axis. shifted version of g then is shifted along the
This is g(a – u), or g(x – u) for x = a in Equa- horizontal axis and the process is repeated at
tion G-3. According to Equation G-3, the unit increments of a. In each successive illus-
integral of the product of f and the reflected tration for different values of a, the product
and shifted function g is the value of the is proportional to the shaded area. The process
convolution function, h at x = a; in other is repeated until g has passed completely over
words, h(a). This is proportional to the the function f and only values of zero are
shaded area in Figure G-1F. These steps obtained (bottom row, right). As indicated
(reflect, shift, take the product, and inte- earlier, this requires (2n – 1) steps, yielding
grate) are repeated for all values of x (i.e., a (2n – 1) values for h.
in Figure G-1D) to obtain the full functional Some important properties of convolutions,
representation of h(x). either continuous or discrete, are that they
Figure G-2 illustrates the convolution of are commutative, distributive over addition,
two discrete functions, f = [1,2,1] and g = and associative. These properties are respec-
[0,2,1]. As in Figure G-1, the convolving func- tively described by the following equations.
tion, g, first is reflected through the origin
(middle row, left). The product of the reflected f ( x) ∗ g ( x) = g ( x) ∗ f ( x) (G-7)
Appendix G╇ •â•‡ Convolution 491

5
4

2 2 2
1 1 1 1
0 0

f * g  h

h(0)(10)(20)0 h(1)(10)(21)2 h(2)(11)(22)5

h(3)(12)(21)4 h(4)(11)(20)1 h(5)(10)(20)0


FIGURE G-2â•… Top row, The convolution of two discrete functions, fâ•›(x) = [1,2,1] and g(x) = [0,2,1], is given by h(x) =
[0,2,5,4,1]. Bottom rows, The convolving function, g(x), is reflected and then progressively shifted (orange curves) in
unit increments of x across the stationary function, fâ•›(x) (blue curve). The product of the overlapping functions is formed
at each shift increment (shaded areas). The summation of the product (shaded yellow areas) is the value of the convo-
lution, h, for the value of x = to the shift distance. Where the reflected and shifted version of g does not overlap with
f (e.g., x = 0 and x = 5), the convolution h is zero.

f ( x) ∗ [ g ( x) + h( x)] = [ f ( x) ∗ g ( x)] + [ f ( x) ∗ h( x)] function, not the convolution of f and g as


(G-8) used in Equations G-1 to G-3.)
Convolutions have other useful properties.
f ( x) ∗ [ g ( x) ∗ h( x)] = [ f ( x) ∗ g ( x)] ∗ h( x) (G-9) For example, Figure G-3 illustrates the con-
volution of two Gaussian functions. Gaussian
Equation G-7 (commutative property) says functions often are used to approximate the
that the order of the convolution can be blurring caused by collimators, intrinsic reso-
reversed. Thus the result would be the same lution of the detector, and so on. These func-
for a gamma camera image if the intrinsic tions are characterized by a mean value, µ,
blurring occurred before or after collimator and variance, σ2, and are of the form
blurring.
Equation G-8 (distributive property) says 1 2 / 2 σ2
f ( x) = e− ( x − µ ) (G-10)
that the convolution of the sum is the same 2πσ 2
as the sum of the convolutions. Thus if two
images are projected simultaneously onto the It can be shown that the convolution of two
detector and then blurred, the same result is Gaussian functions, with means µ1 and µ2 and
obtained as if the two images were projected variances σ1 and σ2, is a third Gaussian func-
separately, blurred, and then added. tion with mean and variance given by
Finally, Equation G-9 (associative prop-
erty) says that the order of convolution does µ 3 = µ1 + µ 2 (G-11)
not affect the outcome. Thus if multiple blur-
ring effects are present, the order in which σ =σ +σ
2
3
2
1
2
2 (G-12)
they occur does not affect the outcome. This
property is useful for image processing opera- Equation G-12 applies as well to the full
tions that employ convolutions. (Note that width at half-maximum (FWHM) for the
h(x) in Equation G-9 refers to a third blurring Gaussian functions. Thus, if two Gaussian
492 Physics in Nuclear Medicine

0.8

0.6 f(x)
Function value

FIGURE G-3â•… The convolution of two Gaussian


0.4 g(x) functions, fâ•›(x) and g(x), each having a mean
value µ = 1.0 and variance σ2 = 0.25, is another
h(x) Gaussian, h(x), with µ = 2.0 and variance σ2 =
0.5.
0.2

0.0
3 2 1 0 1 2 3 4 5
x

functions, f and g, are characterized by Here, F represents the operation of comput-


FWHM( f ) and FWHM( g ), the full width ing the FT and F −1 represents the inverse
at half-maximum of their convolution, h, is FT, as described in Appendix F. Thus convolu-
given by tion of two functions in the spatial domain is
equivalent to point-by-point multiplication of
FWHM(h) = FWHM( f )2 + FWHM( g)2 their spectra in the spatial-frequency domain.
(G-13) One practical application of the convolu-
tion theorem is that the modulation transfer
This can be used to calculate the effect of function (MTF) of a system (see Chapter 15,
combining the spatial resolutions of two com- Section B.2) is equal to the product of the
ponents in an imaging system. For example, MTFs of its individual components. This can
if a scintillation camera has an intrinsic reso- be very helpful when the shapes of their
lution of 4╯mm FWHM and a collimator reso- point-spread functions are varied and non-
lution of 10╯mm FWHM, and both can be Gaussian. Another practical application is
reasonably approximated by a Gaussian that it provides a convenient alternative to
shape, then their combined blurring effect is Equation G-6 for computing the convolution
described by another Gaussian function with of two functions. That equation requires many
FWHM = (102 + 42)1/2 = 10.8╯mm. This would multiplications and data shifts, which can be
describe the system resolution for the detec- very time consuming and tedious to imple-
tor/collimator combination (see Chapter 14, ment in a computer. The convolution approach
Section C.4). Note that blurring effects are requires only the calculation of two FTs, a
not simply additive (i.e., 10╯mm + 4╯mm = single point-by-point multiplication of these
14╯mm) and that the combined effect is domi- FTs, and the calculation of an inverse FT, all
nated by the component that produces the which can be performed much more rapidly
greatest amount of blurring (the collimator, by a computer than the tedious process
in this example). described by Equation G-6. It should be noted
One final useful property of convolution is that the convolution theorem can be extended
given by the convolution theorem. If the to an arbitrary number of functions or
Fourier transforms (FTs) of two functions fâ•›(x) dimensions.2
and gâ•›(x) are F(k) and G(k), then the FT of
their convolution has the properties that REFERENCES
1. Bracewell RN: The Fourier Transform and Its Applica-
F [ f ( x) ∗ g ( x)] = F (k) × G(k) (G-14) tions, New York, 2000, McGraw-Hill, Chapter 3.
2. Bracewell RN: Fourier Analysis and Imaging. New
F −1
[ F (k) × G(k)] = f ( x) ∗ g ( x) (G-15) York, 2004, Kluwer Academic Publishers, Chapter 5.
Index

Note: Page numbers followed by f indicate figures; those followed by t indicate tables.

A Absorbers (Continued) Activity (Continued)


A (mass number), 13 photon attenuation in, 78-85 of mixture
Absolute activity, assay of, 177 broad-beam, 79-80, 81f, 83, parent-daughter, 39-42, 39f,
Absolute quantification of PET, 84t 40f, 41f, 42f
339-340 coefficients for, 78-79 of unrelated species, 38-39,
Absolute spatial linearity, of narrow-beam, 79-83, 81f, 82t 39f
gamma cameras, 229-230 with polyenergetic sources, product, buildup and decay of,
Absorbed dose, 407, 432-435, 84-85 56
433t. See also Radiation radiation dose in, 407 specific, 37-38
dose. thickness of. See also Range of carrier-free, 37-38
air kerma and, 428-430, 434 charged particles. in nuclear medicine, 38, 56
average, 408, 414, 417, 428, attenuation and, 78-85. product, 56
429t See also Attenuation. of radionuclides, 57-58
radiation safety and, 427, 428, detection efficiency and, of radiopharmaceuticals, 59
429-430, 435 160-162, 166f saturation level of, 56
scaling factor for, 430, 430f half-value, 82, 82t typical amounts of, 32
units for, 431-432 range and, 70-74. See also units of, 31-32
Absorbed dose constant, Range of charged for cumulated activity, 409
equilibrium, 412-413 particles. in voxel, 285, 339-340, 364,
Absorbed fraction, 413-414, 414f, tenth-value, 82, 82t 367
415t transmission factors for, 83 ADCs. See Analog-to-digital
specific absorbed fraction, Absorption, detection efficiency converters (ADCs).
414-415 and, 166, 173-175, 174f AES. See Automatic external
Absorbed fraction (MIRD) method, Absorption edges, 79, 80f standardization (AES)
407. See also Radiation Absorptive collimation, 201, 220, method.
dosimetry, internal. 312-321, 322 Agreement states, 431
absorbed fraction and, 413-414 electronic collimation vs., 308 Air kerma, 89, 428-431, 429t
anatomic models for, 409, 414, Accelerators, charged-particle, Airborne radioactive materials,
414f, 415t, 424 47-50, 48f-50f, 50t 432, 432t, 438
cumulated activity and, 409-410, Accidental coincidences. See ALARA concept, 433-434, 437-438,
424 Random coincidences. 439
dose reciprocity theorem and, ACD. See Annihilation coincidence Albumin, radiolabeled, 393, 394
415 detection (ACD). Aliasing, 263, 273, 484-485, 485f,
effective dose and, 417 ACF. See Attenuation correction 487
equilibrium absorbed dose factor (ACF). α (e/γ conversion ratio), 24
constant and, 412-413 Acquisition modes, 322, 329, Alpha (α) particles. See also
limitations of, 424-425 332-333, 334, 369 Charged particles.
mean dose per cumulated Activation cross section, 53-54, acceleration of, in cyclotron, 47
activity and, 415-416 54f Cerenkov effect and, 68-70
specific absorbed fraction and, Activation rates, 54-56 decay of, 26-28
414-415 Activation thresholds, 50t, 54 detection of, with survey meter,
steps in, 408-409 Active transport, 389 440
surface dose and, 409 Activity, 31-32 emission of, 12, 15, 26, 27, 28
time-activity curves and, absolute, assay of, 177 energy losses by, 63-65. See also
409-410, 410f-411f cumulated. See Cumulated Energy losses.
tissue weighting factors for, 417, activity. equivalent dose of, 408t
425t decay constant and, 31 interactions with matter, 63-70
whole-body dose and, 417, 425t definition of, 31-32 Cerenkov effect in, 68-70
Absorbers. See also Attenuation. equivalent, 177 energy losses in, 66, 70
atomic number of, 75, 79, 81f measurement of ranges in, 70-71, 82-83, 83t
buildup factors for, 83, 84t with dose calibrator, 89, 89f, specific ionization in, 68, 69f,
charged particle interactions in. 189-190 71
See Charged particles. with NaI(Tl) well counter, tracks in, 66, 67, 67f, 68, 70
density of, 71, 72, 73, 73f, 75, 177 range of, 65, 70, 70f, 72f-73f,
78-79 of mixed samples, 38-39, 39f 82t
493
494 Index

Alpha (α) particles (Continued) Annihilation coincidence detection Artifacts (Continued)


shielding of, 71 (ACD) (Continued) motion, 234, 266, 359
tracks of, 66-67, 67f scatter coincidences, 322f, attenuation correction artifacts
energy deposition along, 323-324, 329-330 and, 359
67-68 true coincidences, 322-324, breath-holding and, 359
length of, 70, 70f, 72f-73f 322f image quality and, 234, 266,
Alumina, in 99Mo-99mTc generators, geometric efficiency for, 359
51, 51f, 53 319-322 pincushion, 199-200, 215f-216f,
Aluminum ion in 99mTc, 53 noncolinearity in, 314, 315f, 216-217
Alzheimer’s disease, FDG-PET in, 316 in SPECT, 302
341-342, 342f root mean square effective range structured noise from, 243
Amplification factor, gas and, 314 truncation, 359, 359f
in Geiger-Müller counters, 92-93, scintillators for, 309-310 Atomic emissions, 10-13, 11f-12f
94f sensitivity in, 308, 312, 319-320, from radionuclides, 57, 58t
in proportional counter, 91, 92f 321, 322 Atomic mass, isotope effect and, 20
Amplifiers, 110-113, 110f, 111f, spatial resolution in Atomic mass unit, 7
114f depth-of-interaction effect in, Atomic number (Z), 9, 13-14
baseline shift in, 112-113, 112f 316-318, 317f binding energy and, 10
bipolar output of, 113 detectors and, 310, 311f, 312 collisional losses and, 64-65
dead time and, 168 with gamma cameras, 209-211, definition of, 9, 13
in nuclear instrument module, 210f, 211f effective, 65, 101t, 103-104
122-123 geometric efficiency and, fluorescent yield and, 12, 13f
pulse pileup in, 112-113, 112f 319-321 of naturally occurring elements,
pulse shaping by, 110-113, 110f with PET scanner, 323 445-447
in rate meter, 120-121 positron physics and, 312-316, photon attenuation and, 78-79,
resistor-capacitor, 110f, 111-112, 313f-315f, 313t 81f
112f reconstruction filters and, radiation losses and, 64-65
Analog buffers, 213-214 319 of scintillators, 101t, 102,
Analog radiopharmaceuticals, 60, sampling and, 318-319, 318f 103-104
61, 382 system resolution in, 314-315 Atomic physics, basic concepts of,
Analog rate meters, 120-121, in time-of-flight PET, 309-310, 7-18
120f 310f Atomic weight, 13
Analog signals, digitization of, 363, time-to-amplitude converter in, Atoms, 9-13, 10f, 11f
364, 365f 118, 118f binding energy of, 15
Analog tracers, 382 Annihilation photons, 25, 25f Bohr, 9, 10f
Analog-to-digital converters after pair production, 77, 77f characteristic x rays of.
(ADCs), 116-118, 116f, 120, in annihilation coincidence See Characteristic x rays.
124, 363 detection, 307-308, composition and structure of, 9
of gamma camera, 196-197, 196f, 308f-309f notation for, 12-15
198, 365f interactions with matter, nuclear, 9
Anatomic models for radiation 74-78 nucleus of. See Nucleus.
dosimetry, 409, 414, 414f, 415t, in radiation detectors, 142, 144, Attenuation, 78-85, 160-162.
424. See also Phantoms. 145-146, 145f, 149, 150, 151, See also Absorbers.
Anger, Hal, 2, 4f, 95-196 159 broad-beam, 79-80, 81f, 83, 84t
Anger cameras. See Gamma shielding for, 437 coefficients for, 78-79
cameras. Annihilation reaction, 25, 25f conjugate counting and, 287-291,
Angular sampling intervals, Anode 287f, 288f, 289f, 290f, 291t,
263-265, 266, 266f, 301 in cathode ray tubes, 123, 292f, 292t, 293
Angular sampling range, 266, 123f contrast-media-related, 359-360
266f in ionization detectors, 87, 88f correction factors for, 293-294,
in SPECT, 281, 301 in photomultiplier tubes, 98-99, 294f
Annihilation coincidence detection 98f detection efficiency and,
(ACD), 307-308. See also Anthracene, 188 160-164
Positron emission tomography Anticoincidence circuits, 113, narrow-beam, 79-83, 81f, 82t
(PET). 114f in PET, correction of, 338-339,
basic principles of, 307-308, 308f, Antineutrino, 20 338f
309f Application-specific integrated in PET/CT and SPECT/CT,
coincidence unit in, 121-122, circuits (ASICs), 363 correction of, 356-360
121f Archival systems for digital artifacts in, 358-360, 359f
counting rates in, 321 images, 378 image segmentation in, 357
effective positron range and, 313, Arithmetic mean in conjugate mapping in, 357-358, 358f
313f counting, 287-293, 289f of photons, 78-85, 78f, 80f
electronic collimation and, 308 Artifacts broad-beam, 79-80, 81f, 83,
energy resolution in, 150 aliasing, 263 84t
event types in barrel, 216-217, 216f coefficients for, 78-79
prompt coincidences, 322-324, from breath-holding, 359 narrow-beam, 79-83, 81f, 82t
322f, 340 from contrast agents, artifacts with polyenergetic sources,
random coincidences, 322-332, from, 359-360 84-85
322f in CT-based attenuation quality assurance and, 302
corrections for, 336-337 correction, 358-360, 359f scattering and, 286, 294f, 302
estimation of, 336, 340 from dental implants, 360 in SPECT, 287-293, 291t-292t
Index 495

Attenuation (Continued) Background counting rates (β+, γ) decay, 25-26


conjugate counting and, 287 (Continued) (β−, γ) decay, 21-22, 22f
correction of, 293-294 of NaI(Tl) conventional detector, (β−, γ) emission, 21-22, 22f
Chang multiplicative 190 in medical applications, 46t, 57
method for, 294, 294f, of NaI(Tl) well counter, 173, 174, metastable nuclide vs., 24
296, 297f 177-178, 180, 181 Beta (β) particles, 20-21. See also
scatter correction and, pulse-height analysis and, 132, Charged particles; Electrons.
296-299, 298f 184-185 backscattering of, 166-167,
transmission scans and, random coincidences causing, 167f
294-296, 295f-297f 336 Cerenkov effect and, 68-70
transmission scans and, 294-295, scattered radiation and, 240-241, detection and measurement of,
295f, 296f, 297f 241f 21
in vivo probe measurements and, of semiconductor detector, 190 with Bremsstrahlung counting,
192 sources of, 240-242 168
Attenuation coefficients, 78-79, 78f, statistics of, 131, 132-133 with Geiger-Müller counters,
80f, 81f. See also Linear Background information density, 166-167, 167f
attenuation coefficients; Mass 244 problems in, 166-168
attenuation coefficients. Background radiation with proportional counters,
scatter corrections and, in effective dose from, 427 166-167, 167f
SPECT, 297, 297f sources of, 177-178, 427 with survey meters, 166-167,
Attenuation correction factor Background subtraction, 242-243 166f
(ACF) Backprojection. See also energy losses by, 63-65. See also
for PET, 338 Reconstruction tomography. Energy losses.
for SPECT, 293 definition of, 257 energy spectrum for, 21, 21f
Attenuation maps filtered. See Filtered interactions with matter, 63-70
in SPECT, 294-296, 296f, backprojection (FBP). Cerenkov effect and, 68-70
298-299 simple, 256-258, 266f radiation losses in, 64-65, 67f
in SPECT/CT and PET/CT, in SPECT, 294, 296 range of, 71-72, 72f, 73t
357-358 Backscatter peak, 143f, 144, 151 self-absorption of, 166-167,
Audio systems, frequency response Backscattered photons, 75, 167f
curves for, 236-237, 236f 166-167, 167f tracks of, 66-67, 67f
Auger effect, 10-13, 12f Backscattering, 75 energy deposition along,
Auger electrons, 10-13, 12f detection efficiency and, 163, 167, 67-68
after electron capture, 24 167f length of, 71, 73t
after internal conversion, 23 Badge dosimeters, 440-441, 440f Beta-particle emitters, ranges for,
after ionization, 63 BaF2, 102-103, 310, 322t 73, 73t
after photoelectron ejection, 74, Bar phantoms, 235, 235f Beta-particle probes, miniature,
78t modular transfer functions and, 194
photoelectric effect and, 74 237-238 BGO. See Bismuth germanate
Automatic external Barn, 53-54 (BGO).
standardization (AES) Barrel distortion, 216-217, 216f Binary numbers, 364-365
method, 186-187, 187f Baseline restoration, 112-113 Binding affinity, 403
Autoradiography, deoxyglucose Baseline shift, 112-113, 112f Binding energy
method and, 401 dead time losses and, 168 of atoms, 15
Avalanche ionization in gamma camera, 220 of electrons, 9-10, 11f
in Geiger-Müller counters, 92-93, in pulse-height spectrometry, photoelectric effect and, 74
94f 146, 147 nuclear, 15-16
in ionization chambers, 91, 92f Bateman equations, 39-40, 39f nuclide stability and, 17-18,
in proportional counters, 91, 92f Beam hardening, 84 17f
Avalanche photodiode detectors, Becquerel (Bq), 31 Binding potential, 402-403
99-100, 332 Becquerel, Henry, 2, 9 Biologic excretion curve, 410-412
Average absorbed dose, 408, 414, Becquerels per gram, 37 Biologic half-life, 59
417, 424, 428, 429t β+ decay, 25-26, 26f Bipolar pulse, 112, 115
Average lifetime, 34, 82 β− decay, 20-21 Bis-MSB [p-bis-(omethylstyryl)
cumulated activity and, 410, inverse, 24-25 benzene], 105, 187
411f (β+, EC) decay, competitive, 26 Bismuth germanate (BGO), 101t,
Average range for electrons, 73 β+ emission. See Positron (β+, 102-103
Averaging, effects of, 130 γ) emission; Positron (β+) detection efficiency of, 161, 161f,
Axial deviation of detector heads, emission; Positrons. 162
303 β− emission, 20-21, 20f, 21f mass attenuation coefficients of,
Axial resolution, 301 in decay series, 21-22, 22f 477-478
by fission products, 44, 45 in PET systems, 316, 324, 324f,
by neutron-activated 325, 325f, 328, 328f, 334
B radionuclides, 46 energy resolution and, 337
Background counting rates, 131 β− emitters sensitivity and, 321, 322t
contrast and, 239-240 in cancer therapy, 61 Bits, 364-365
daily measurement of, 172 detection and measurement of, 21 Bladder, surface dose to, 409
detectability and, 240 with gas flow counter, 183 Blank scans, 338
image noise and, 240 with LS system, 183, 183t Block detectors, 324-325, 325f,
of liquid scintillation counter, problems in, 166-167, 167f 327f
184 shielding of, 65, 66f modified, 325-326, 326f-327f
496 Index

Blood flow Brain imaging (Continued) Cadmium telluride (CdTe) detectors


measurement of with gamma camera, 4f (Continued)
area-height method for, 396, parametric, for glucose for intraoperative probe, 193,
396f metabolism, 400, 401f 193f
central volume principle and, with PET, 330-331, 330f intrinsic efficiency of, 158
380, 394 3-D acquisition in, 332, 333f, Cadmium zinc telluride (CZT)
clearance methods for, 394-396, 334 detectors, 89t, 96-97, 151-152,
396f FDG for, 342, 342f, 397-398, 153f. See also Radiation
diffusible tracers for, 394-395 398f, 400, 401f detectors; Semiconductor
equilibrium methods for, 393 perfusion studies in, 388, detectors.
Kety-Schmidt method for, 395 394 for cardiac SPECT, 281, 283f
labeled microsphere technique random coincidences in, 323 detection efficiency of, 164
for, 393-394 resolution of, 330-331, 330f energy resolution of, 190, 191
modeling for, 383, 386-388, scatter in, 323, 332, 338 for gamma-ray probes, 293
388f systems for, 330, 330f for intraoperative probe, 193-194,
nondiffusible tracers for, 394 time-activity curves and, 373, 193f
reference sample technique for, 374f intrinsic efficiency of, 158
393-394 during visual stimulation, 371, mass attenuation coefficients of,
tracers for, 380, 381, 381t, 372f 477-478
383-384, 386, 387-388, region of interest in, 372, 372f Calibration
390f, 393-396 with SPECT, 280-281, 282f, of liquid scintillation counter,
labeled ammonia as, 304-305, 304f 185
341-342, 479 attenuation corrections in, of NaI(Tl) detector, 147-148,
trapping methods for, 294 148f
393-394 in cerebral perfusion studies, of NaI(Tl) well counter, 178
tracer delivery and, 387 304-305, 304f precalibrated radionuclides and,
Blood samples, counting systems perfusion studies in, 304-305, 35
for, 105, 173, 182 304f quality assurance procedures for,
Blood volume, tracers for, 381t, systems for, 301, 302-303 172
383 Brain phantom Calibration factor, 339-340
Blumgart, H.L., 2 image contrast in, 240, 241f Calibration sources, 164, 165f,
Blunders, 125 motion blurring in, 234, 234f 165t, 166
Blurring. See also Artifacts; Branching decay, 27-28, 31 absolute activity assays and,
Image quality; Spatial Branching ratio, 31, 40 177
resolution. Breast imaging americium-241 as, 28
convolution and, 489, 491, 492 gamma camera for, 207, 208f detection efficiency and, 164-166,
motion, 234, 266 PET systems for, 330-331, 165f, 165t
attenuation correction artifacts 331f mock, 177
and, 359 sentinel-node, gamma-ray probes Calibrators, dose, 89, 89f, 189-190,
breath-holding and, 359 for, 192-193 189f
image quality and, 234, 266, Bremsstrahlung, 64, 64f-66f shielding of, 189-190, 189f
359 charged-particle tracks and, 66, Cancer
noncolinearity, 314, 315f, 316 67f, 68 bone scan of, 5t, 197
1/r blurring, 258, 260-261 electron transmission curve and, coregistered images of, 375
spectral, 144, 148-151. See also 71 FDG-PET imaging of, 50, 60, 61,
Energy resolution. interactions with matter, 74-78 341-342, 341f, 354, 355
Blurring tomography, 257 penetrating ability of, 195 gamma-ray probes in,
Bohr atom, 9, 10f radiation losses and, 64, 65, 65f, 192-193
Bone 66f PET/CT in, 355-356, 356f
attenuation by, 287, 294, 338 shielding and, 65, 67f, 437 probe systems and, 192-193
energy absorption in, 430 in x-ray tubes, 346 radiation exposure and, 427
f factor for, 430, 430f Bremsstrahlung counting, of SPECT in, 305-306
positron ranges in, 314 β particles, 168 therapy for
Bone marrow. See also Organs. Broad-beam attenuation coefficient, dose in, 417, 424
absorbed fraction in, 413 297, 297f β− emitters in, 61
Bone scan, 1, 5t, 60t, 197, 207f Broad-beam geometry, 79-80, 81f, Capillary extraction. See
Bq (becquerel), 31 83, 84t Extraction.
Bragg ionization peak, 68, 69f Broad-scope licenses, 435 Carbon-11, 450t
Brain Buildup factors, 83, 84t production of, 49
blood flow in Bulk flow across capillaries, 389 properties of, 58t
imaging of, 323, 330, 330f, Byte, 365 Carbon-14, 450. See also
375-376, 377f, 394, 395 Liquid scintillation counters
during visual stimulation, (LSCs).
371-372, 372f C Cardiac ejection fraction
tracer measurements of, Cadmium telluride (CdTe) calculation, with 99mTc-labeled
394-395 detectors, 89t, 96-97, 158, 164. red cells, 392, 392f
receptor studies of, 304-305, 380, See also Radiation detectors; Cardiac imaging
381t, 402, 403 Semiconductor detectors. with 99mTc-labeled red cells, 392,
Brain imaging detection efficiency of, 164 392f
co-registration of images in, energy resolution of, 190, 191 SPECT in, 281-283, 303, 305f,
375-376, 377f for gamma-ray probes, 193 306
Index 497

Cardiac output, 393, 394 Chang multiplicative method, 294, Coincidence counting rates,
Cardiac studies 294f, 296, 297f 162-163, 322-324, 322f,
first-pass Channels of multichannel analyzer, 329-330
gamma camera for, 213, 214, 116-118, 116f in PET, 322-324, 322f, 329-330
392 Characteristic x rays, 10-13, 11f, random, 322-323, 322f, 329-330
labeled RBCs for, 392, 392f 12t correction for, 336-337
PET for, 339 after electron capture, 24-25 estimation of, 336, 340
SPECT system for, 81 after internal conversion, 23 scatter, 322-324, 322f, 329-330
frame rates in, 368 after ionization, 63 correction for, 337-338
gated, 234, 303, 304, 304f, 392, after photoelectron ejection, 74 true, 322-323, 322f
392f in radiation detector, 151 uncertainty in, 336, 337
motion blurring in, 234, 369 Charged particles. See also Alpha Coincidence detection. See also
with PET, 339 particles; Beta particles; Annihilation coincidence
short axis views in, 369 Electrons; Positrons. detection (ACD).
with SPECT, 281-283, 303, 305f, Cerenkov effect and, 68-70 of cascaded emissions, 162-163
306 definition of, 63 efficiency of, 162-163
Carrier-free samples, 37-38 energy losses and, 63-66, 67, 67f, for liquid scintillation counters,
production of, 46 68, 70. See also Energy 183f, 184
Carrier-free specific activity losses. spatial resolution for, 310,
(CFSA), 37-38, 56 interactions with matter, 63-68, 311f-312f
Carrier-mediated diffusion, 64f, 65f, 66f, 67f, 69f, 70 Coincidence rate, 319
389-390, 397 ranges of, 70-74, 70f, 72f-73f, Coincidence summing, 145,
Cassen, Benedict, 2, 3f, 195 73t 146f
Cathode ray tubes (CRTs), 123-124, ACD and, 312-314, 313f, Coincidence timing windows, 121,
123f, 367 314f 307
digital image and, 367 detector types and, 141 definition of, 121
hard copy derived from, 367 tracks of, 66-68, 67f in PET systems, 307, 322, 323,
Cathodes in ionization detectors, energy deposition along, 67-68, 329, 337
87, 88f, 99 67f Coincidence units (logic), 121-122,
Cd-109, 165t length of, 70-74, 70f, 72f-73f, 184
C-D studies. See Contrast-detail 73t in PET, 307
(C-D) studies. Charged-particle accelerators, Cold lesions, 246, 248, 269
CdTe detectors. See Cadmium 47-50, 48f-50f, 50t Coldfinger, 97, 97f
telluride (CdTe) detectors. Charge-sensitive preamplifiers, Collimation
Center of field-of-view (CFOV), 107-108, 109f absorptive, 201, 220, 312-321,
229-230 Chelation, 58 322
Center of rotation (COR) in SPECT, Chemical elements, 9. See also electronic, 308
302-303 Nuclides. Collimator efficiency
Central processing units (CPUs), properties of, 445 of converging collimators,
363 transmutation of, 20, 21, 24, 25, 225-228, 226f-227f
Central volume principle, 380, 27 definition of, 220, 223
394 Chemical properties, radioactive of diverging collimators, 225-228,
Kety-Schmidt method and, 395 decay and, 19-20 226f-227f
CERASPECT system, 280-281, Chemical purity, 59 of parallel-hole collimators, 222,
282f Chemical quenching, 106, 188 224f, 225t
Cerebral imaging Chi square test, 133-134, 134f of pinhole collimators, 225-228,
image co-registration and, in quality assurance, 172 226f-227f
375-376 Chromatography volume sensitivity and, 301
parametric, for glucose liquid scintillation counting with, Collimator resolution. See also
metabolism, 400, 401f 188 Spatial resolution.
PET in, 330-331, 330f NaI(Tl) detector with, 182, 183f of converging collimators,
SPECT in, 280-281, 282f, Chromium-51, 452 225-228, 226f-227f
304-305, 304f Ci. See Curie (Ci). definition of, 220, 222
Cerenkov counting, 188 Cine mode, 371 of diverging collimators, 225-228,
Cerenkov effect, 68-70 Classic method in internal 226f-227f
Cesium-137, 165t, 473 radiation dosimetry, 407 of parallel-hole collimators, 220,
Cesium antimony (CsSb), 98 Clearance, tracer, 388 222, 222f, 225t
Cesium fluoride (CsF), 102-103 Clearance methods for blood system resolution and, 225. See
Cesium iodide [CsI(Tl)], 100, 101t flow measurement, 394-396, also Parallel-hole
in compact gamma camera, 207 396f collimators: collimator
in intraoperative gamma probe, Cloud chambers, 66 resolution and.
193, 193f CNR. See Contrast-to-noise ratio of pinhole collimators, 225-228,
Cesium iodide [CsI(Tl)] detectors, (CNR). 226f
101t Cobalt-57, 165t source-to-collimator distance
for cardiac SPECT, 281, 296-299 Cobalt-60, 165t and, 223, 224f, 227-228,
in gamma-ray probes, 193 Cocktails, liquid scintillation, 105, 227f-228f
CFOV. See Center of field-of-view 187 system resolution and, 225, 227
(CFOV). Code of Federal Regulations, 431 Collimators, 196, 196f, 201-203. See
CFSA. See Carrier-free specific Coherent scattering, 77 also specific types.
activity (CFSA). in SPECT, 297 absorptive, 201
Chain reaction, nuclear, 43 Coincidence circuits, 184 cone-beam, 274-275, 274f
498 Index

Collimators (Continued) Compton scattering (Continued) Contrast (Continued)


converging. See Converging in tissue information density and,
collimators. detection efficiency and, 243-244
diverging. See Diverging 163-164, 164f lesion size and, 243-244, 245
collimators. downscatter derived from, modulation transfer function
fan-beam, 273-274, 274f-275f, 296-297, 297f and, 236, 237f
294, 295f, 304f probe measurements and, 192 in PET, 241-242, 253, 336, 337,
for gamma cameras. See Gamma in x-ray CT, 349 346
cameras: collimators for. Computed tomography (CT), 253. Rose criterion for, 244, 269
multi-pinhole, 202f, 203 See also Hybrid imaging scattered radiation and, 240-241,
parallel-hole. See Parallel-hole systems; Positron emission 242f
collimators. tomography (PET); Single septal penetration and, 240-241,
pinhole. See Pinhole collimators. photon emission computed 242f
response characteristics of, 254, tomography (SPECT); X-ray spatial resolution and, 243, 246,
254f computed tomography. 247f, 249f
sensitivity of, 231 emission, 253. See also in SPECT, 241-242, 243f, 253
in gamma camera, 223, 224f, Reconstruction tomography; Contrast agents
225t, 227, 231 Tomographic imaging. artifacts from, in PET/CT and
lesion detectability and, 246, advantages of, 269-270 SPECT/CT attenuation
247f image quality in, 263-270 correction, 359-360
septal thickness in, 203, 203f, for low-contrast lesions, for x-ray CT, 349-350
211, 220-221, 220f-221f 269-270 artifacts from, 359-360
slant-hole, 203 noise in, 266-268 Contrast enhancement, 242-243
Collisional energy losses, 64-65, in multimodality Contrast-detail (C-D) studies,
66f-67f instrumentation, 4-5 247-249, 248f-249f
rate of, 66-68, 69f transmission, 253 Contrast-to-noise ratio (CNR),
Collisions of charged particles with Computer networks, 367, 378 243-247. See also Noise.
matter, 63-64, 64f Computer observer performance in reconstruction tomography,
Colloids, 99mTc-labeled, 192-193 studies, 233 266-268
Color displays, 367, 368f Computers, 363. See also Digital in tomographic imaging, 253,
Color quenching, 106 image processing; Digital 266, 269-270
Combined-modality imaging. See images; Tomographic imaging. Control rods, 43-44
Hybrid imaging systems. contrast enhancement algorithms Converging collimators, 204, 204f
Comparators, 113 of, 242 advantages and limitations of,
Compartmental models, 390-392, dead time losses in, 168 228
390f-391f. See also Tracer in gamma camera SPECT efficiency of, 225-228, 226f-227f
kinetic modeling: system, 280 performance characteristics of,
compartments in. in liquid scintillation counting 225-228, 226f-227f
basic concepts of, 380, 382, 384f systems, 183f, 184, 189 resolution of, 225-228, 226f-227f
for FDG, 396, 397 pixelation effects caused by, 234 source-to-collimator distance
formulation of, 390-392, 390f, in well-counter systems, 178, and, 228, 228f
391f 181 in SPECT, 279-280
Renkin-Crone model vs., 389f, Concrete shielding, 437 Conversion electrons, 22-24, 23f
390-391 Cone-beam collimators, 274-275, Converter for proportional counter,
Competitive (β+, EC) decay, 26 274f 159
Compton edge, 143, 143f, 144, 146, Cone-beam reconstruction, 273-275, Convolution, 489-492, 490f, 491f,
151 274f 492f
Compton region, 143, 143f, 145, Confidence intervals, 127, 127t backprojection and, 258
147 Conjugate counting, 287-291, 287f, smoothing filter and, 373
Compton scattering, 74-78, 75f-77f, 288f, 289f, 290f, 291t, 292f, Convolution theorem, 492
75t, 78t, 104. See also 292t, 293 Copper-62, 454
Scattered radiation. Conjugate variables, 481 Copper-64, 455
in gamma camera studies Consistency requirements in COR (center of rotation) of SPECT
energy resolution and, 209, reconstruction tomography, system. See Center of rotation
211-212 266, 266f-267f (COR) in SPECT.
spatial resolution and, 209, Constant fraction timing, 115-116 Co-registration, 375-376, 377f
210 Contaminants Coronal sections, orientation of,
intrinsic spatial resolution and, detection of, by curve stripping, 369, 370f
209-211, 210f-211f 39 Correlation coefficient, 139-140
in PET, 322-323, 322f, 329-330 effects of, 58 Cosmic rays, 177-178, 432
correction for, 337-338 in 99mTc, 53, 58 Cost function, 271
photon attenuation and, 79, Contrast, 233, 239-240, 243-247 Coulombic forces, 14
80f-81f background counting rates and, Count skimming, 218
in radiation detectors, 141-143, 239-240 Counter paralysis, 169. See also
142f-143f definition of, 233, 239 Paralyzable counting
gamma-ray energy and, with gamma camera systems.
146-147, 147f energy resolution and, 214 Counters, digital, 119-121, 120f
nonlinearity and, 148 pulse pile-up and, 213, 214, Counting, energy-selective. See
scintillator materials and, 102, 214f Energy-selective counting.
103, 104 of hot vs. cold lesions, 246, 248 Counting curves for Geiger-Müller
in SPECT, 296-299 in image display, 369, 370f counters, 94, 95f
Index 499

Counting losses in gamma camera, Counting systems (Continued) Dead time/dead time losses,
213-214, 213f, 215f, 230 in vivo, 173, 192-194 168-171, 168f, 169f, 171f
Counting rates, 130 whole-body, 194 apparent, 213, 213f, 214
in annihilation coincidence Counting time, statistical determination of
detection, 321 reliability and, 132-133 fixed-rate pulser method for,
background, 131 Counting vials, 184-185 171, 171f
for calibration sources Count-rate performance in SPECT, two-source method for, 171,
absolute activity assays and, 302 171f
177 Coverage requirements in in gamma cameras, 213-214,
detection efficiency and, 164 reconstruction tomography, 213f, 230
mock sources and, 177 266, 266f-267f correction methods for,
coincidence. See Coincidence CPUs. See Central processing units 213-214
counting rates. (CPUs). in Geiger-Müller counters, 188
crosstalk and, 178-179 CR differentiation circuit, 111-112, in liquid scintillation counters,
dead time losses and, 168-171 111f-112f 168
detection efficiency and, 155 Cristy-Eckerman phantoms, 414, mathematical models of,
with absorbing medium, 163 414f, 415t 168-169
with cascaded emissions, Cross section in NaI(Tl) well counters, 179
162-163 activation, 53-54, 54f in paralyzable vs.
with full-spectrum counting, neutron-capture, 45-47, 46t nonparalyzable systems,
159, 163 Cross-plane data acquisition, 332, 168-169, 168f-169f
with scattering medium, 163 333f percentage, 169
differences between, 130-131 Crosstalk in PET, 326, 330, 332, 339,
with energy-selective counting, in liquid scintillation counting, 340
159 184, 185, 187, 187f in SPECT, 302
estimation of, 132 between projection elements, 286 window fractions and, 170, 213,
of gamma camera, 213-216, 230 in well-counter measurements, 213f
with multiple radionuclide 178, 178f, 179, 181-182 Decay. See Radioactive decay.
sources, 178-179 CRTs. See Cathode ray tubes Decay constant, 31, 32
noise equivalent, 340-341, 341f (CRTs). average lifetime and, 34
observed vs. true, 168-169, CsF. See Cesium fluoride (CsF). definition of, 31
168f-169f CsI(Tl). See Cesium iodide [CsI(Tl)] half-life and, 33-34
optimal division of, 133 detectors. Decay curve, universal, 35, 35f
for paralyzable vs. CsSb. See Cesium antimony (CsSb). Decay factors, 32-33, 33f
nonparalyzable counting CT. See Computed tomography approximation to, 32, 32f, 33
systems, 168-169, 168f-169f (CT). determination of, 34-35
in pulse-height spectrometry, Cumulated activity, 409-412, 410f, effective, 35-37, 36f
146, 147f 411f tables of, 34, 34t
of SPECT system, 302 average absorbed dose and, 408, Decay rate. See Activity.
statistical significance of, 414, 417, 424 Decay scheme diagrams, 20-21,
130-131 calculation of, 424 20f
total-spectrum, 170 mean dose per, 411f, 414f, of important radionuclides, 449,
uncertainty in, 130, 131, 132, 415-416, 418t-423t 449f-475f
133 for 18F, 415-416, 422t-423t Decay series, 27-28, 27f
Counting statistics. See Statistical for 131I, 415-416, 420t-421t Decay time of scintillators, 101t,
analysis. for 99mTc, 415-416, 418t-419t 104
Counting systems, 173-194 problems in determination of, Decontamination measures, 439
for Cerenkov counting, 188 424 Deep-dose equivalent, 431-432
comparison of, 132 in source organ, 409-410, 424 Degrees of freedom, 136, 136f,
components of, 107, 108f, 173 Curie (Ci), 32 140
dead times of, 168-171 Curie, Marie, 2 Delayed window method, 336-337
detectors for, 173 Curve stripping, 39 Delay-line methods, 111, 113
conventional NaI(Tl), 182 Cut-off frequency in PET, 319 Delta (δ) rays, 63, 66, 67f
gas-filled, 189-190 Cyclotrons, 47-49, 48f-49f, 50t Density of absorbers
gas-flow counters in, 190 negative-ion, 48-49, 49f attenuation coefficient and,
liquid scintillation, 182-189. See principles and design of, 47-49, 78-79
also Liquid scintillation 48f-49f energy losses and, 65
counters (LSCs). radionuclides produced in, 49-50, range of alpha particles and,
NaI(Tl) well counters in, 50t 71
173-182, 174f, 174t. See also in cyclotrons, 47-50, 50t range of electrons and, 72, 73,
NaI(Tl) well counters. CZT detectors. See Cadmium zinc 73f
paralyzable vs. nonparalyzable, telluride (CZT) detectors. range of positrons and, 314
168-169 Dental implants, artifacts from,
probe 360
miniature beta particle, 194 D Deoxyglucose method, 397, 400
miniature gamma-ray, 192-194, (d, n) reaction, 47, 50t Depreotide, 99mTc-labeled, 305
193f Dalton (Da), 8 Depth-of-interaction (DOI) effect,
NaI(Tl), 192, 192f Dalton, John, 9 316-318, 317f, 326, 329, 330,
quality assurance for, 171-172 Dark adaptation of samples, 185 331
semiconductor, 190-192, 191f Daughter nucleus, 19 Derandomizers, 213-214
in vitro, 173 De Hevesy, Georg, 2 Derived quantities, 7
500 Index

Detectability. See also Phantoms. Detection efficiency (Continued) Digital image processing
of cold vs. hot lesions, 246, 248, of liquid scintillation counter, (Continued)
248f, 297 157, 185 image display in, 367
contrast-to-noise ratio and, of NaI(Tl) conventional detector, color, 367, 368f
243-244 156, 182 grayscale, 367, 370f
in emission computed of NaI(Tl) well counter, 157, 174, image segmentation in, 373-375,
tomography, 269-270 175, 175f-176f, 179 377f
information density and, nonuniform, 160-162, 160f-161f in CT-based attenuation
244-245, 246 of PET systems, 324 correction, 357
observer performance studies Compton scattering and, image smoothing in, 373, 375f
of, 247, 248, 249f, 250-251, 337 image visualization in
250f normalization corrections to, orientation of sections in, 369,
Rose criterion for, 244, 269 335-336 370f
size and, 244, 245, 246, 247 in phantoms, 166 parametric images and, 372
spatial resolution and, 246-247, photofraction and, 159, 160f projection tool for, 369-371,
247f photopeak and, 163 371f
Detection efficiency, 155-166 radiation absorption and, 156 surface rendering in, 369-371
attenuation and, 156, 160-164 radiation scatter and, 156, windowing in, 369, 370f
calibration sources and, 164-166, 163-164 Laplacian technique in,
165f, 165t scatter outside of detector and, 373-375
cascaded gamma emissions and, 144, 163-164, 164f linear sampling distance and,
162, 163 of semiconductor detectors, 151, 365-366
in coincidence detection, 158, 164, 190 matrix size in, 365
162-163 total, 160-161, 160f microprocessors for, 363
complicating factors in, 160-164, Detector scatter events, 204-205 for multislice tomographic
160f, 161f, 164f Detectors. See Radiation images, 364
components of, 155-156 detectors. networks for, 378
definition of, 156 Detergents for LS sample overview of, 363
edge effects and, 160 preparation, 187 pixel depth in, 365
emission rates and, 155 Deuterons in cyclotron, 47, 48 pixels in, 364, 364f. See also
energy-selective counting and, DF. See Decay factors. Pixels.
156, 159 DFT. See Discrete Fourier regions of interest in, 372-373,
factors affecting, 155-156 transform (DFT). 372f
of gamma camera, 211, 212f DICOM. See Digital Imaging and spatial resolution and, 365-367,
detector thickness and, 211, Communications in Medicine 366f. See also Spatial
212f (DICOM). resolution.
nonuniformity and, 217 Diethylenetriamine penta-acetic steps in, 376-378
used for PET, 329-330 acid (DTPA), 5t, 60t, 381t, techniques of, 369-376
of gamma cameras 479 co-registration in, 375-376,
detector thickness and, 211, Differential spatial linearity, 377f
212f 229-230 edge detection in, 373, 375,
nonuniform, 217 Differential uniformity, 229-230 376f
of gas flow counter, 190 Differentiation circuits, 111-112, image smoothing in, 373, 375f
geometric, 156, 157f-158f 111f-112f regions of interest in, 372-373,
of absorptive collimators, 321 Diffusion, carrier-mediated, 389, 372f
edge effects on, 160 390, 395, 397 segmentation in, 373, 375,
of gas flow counter, 190 Diffusion constant, 389 377f
of liquid scintillation counters, Digital counters, 119-121, 120f time-activity curves in, 373,
157 Digital image processing, 363-378. 374f
of NaI(Tl) detectors, 156, 182 See also Digital images. visualization tools in, 369,
in whole-body counter, 194 acquisition modes in, 367-369 370f, 371-372, 371f, 372f
of NaI(Tl) well counters, 157, frame-mode, 367-368 terminology for, 364-365
174, 175 gated imaging, 245, 369 time-activity curves and, 365,
of PET systems, 319-322, 330, list-mode, 368-369 374f
331, 334 archival systems for, 378 visualization tools for, 369-372,
of semiconductor detector, binary numbers in, 364-365 370f-372f
190-191 computer processors for, 363 volume of interest in, 373
housing of detector and, 164 definition of, 363 voxels in, 364
intrinsic, 156, 158-159, 159f display in Digital images, 364-369. See also
calibration and, 164 cathode ray tube, 367 Image quality.
of coincidence detector, 310, hard copy, 367 acquisition modes of, 367-369
311f, 312, 315, 319 liquid crystal, 367 archiving of, 378
definition of, 156 edge detection in, 373-375 basic characteristics of, 364-365,
of gas-filled detectors, 158-159 equipment for, 376-378 364f, 365f
of NaI(Tl) detectors, 158-159 file format standards for, 378 computer networks for
nonuniform attenuation and, for gamma camera images, management of, 378
160-162, 161f, 162f 364 display of
of semiconductor detectors, detector area and, 364, 365f image structure and, 367,
158 image arithmetic in, 371 368f
of well-counter detector, 174, image co-registration in, 375-376, spatial resolution and,
175f 377f 365-367, 366f
Index 501

Digital images (Continued) Dose reciprocity theorem, 415 Effective positron range, 313, 313f
technologies for, 119-121, 119f, Dose-equivalent rate, 435 Efficacy studies, 250-251
120f, 121 Dose-modifying factors, 428 Efficiency. See Collimator efficiency;
visualization tools for, 367, Dose-rate constant, 434-435, 435t Detection efficiency.
368f Dosimeters e/γ conversion ratio, 24
file formats for, 378 badge, 440, 440f Ejection fraction, 392, 392f
gamma camera and, 197, 364, pocket, 89-90, 90f, 440 Electrical forces, 14
365f, 482 ring, 440, 440f Electromagnetic radiation, 8-9, 66.
hard copy of, 367 Dosimetry, internal radiation. See See also Gamma rays; Photons;
parametric, 372 Radiation dosimetry, internal. X rays.
retrieval of, 376, 378 Double differential shaping, 112, Electromagnetic spectrum, 8-9, 8f
spatial resolution of, 365-367, 112f Electrometers, 89
366f Double escape peaks, 144, 145f in dose calibrators, 89, 89f
terminology of, 364-365, 364f, Downscatter during transmission in survey meters, 89-91, 89f
365f scan, 296, 297f Electron capture (EC), 24-25
Digital Imaging and Dps. See Disintegrations per second competitive with positron
Communications in Medicine (dps). emission, 27, 27f, 26, 26f
(DICOM), 378 DTPA (diethylenetriamine penta- by cyclotron-produced
Digital signal processors, 363 acetic acid), 5t, 60t, 381t, 480 radionuclides, 49, 50t
Digitization, 117-118, 363 Dynamic imaging, 392-403. See in (EC, γ) decay, 24-25, 24f
Di-isopropylnaphthalene (DIN), also Cardiac studies; Tracer line of stability and, 28
105, 187 kinetic modeling. by reactor-produced
Dilution principle, 382-383 in blood flow measurement, radionuclides, 49, 46, 46t
Dilution quenching, 106 379-386, 394-396. See also Electron gun, 123
DIN. See Di-isopropylnaphthalene Blood flow: measurement of. Electron multiplication factor,
(DIN). in cardiac imaging, 392. See also 148-149
Direct Fourier transform Cardiac imaging. Electron shells, 9, 14
reconstruction, 258-260, in enzyme kinetic studies, Electron volt (eV), 8
259f-260f. See also 396-401 Electronic collimation, 308
Reconstruction tomography. with gamma camera, 197, Electronic instrumentation,
image quality in, 263-270 206-207, 207f 107-124
sampling in, 263-265 in glucose metabolism studies, amplifiers in, 110-113, 110f, 111f,
Direct substitution, 59-60 396-401 112f
Discrete Fourier transform (DFT), with PET, 335 dead time and, 168, 170
482 in receptor binding studies, in nuclear instrument module,
Discriminators, 114, 115f, 118, 121, 402 122-123
121f in receptor ligand assays, in rate meter, 120
of gamma camera, 201, 205 401-403, 402f, 404f coincidence units in, 121-122,
lower-level, 113, 114f with SPECT, 279-278, 284, 286f, 121f
upper-level, 113, 114f 305f, 306 for PET scanner, 307-308
Disintegrations per second (dps), in receptor binding studies, counters and rate meters in,
31 402 119-121, 119f, 120f, 121f
Disposal of radioactive waste, Dynodes, 98-99, 98f detectors in. See Radiation
439 detectors.
Distribution volume, 382-383, display technologies in, 123-124,
384f E 123f
blood flow measurement and, EC. See Electron capture (EC). high-voltage power supplies in,
393 (EC, γ) decay, 24-25 122
Diverging collimators, 202f, 203 competitive, 26 NIM (modular) systems in,
advantages and limitations of, ECD. See Ethyl-cysteine-dimer 122-123
228 (ECD). preamplifiers in, 107-110, 108t,
efficiency of, 225-228, 226f-227f ECT. See Emission computed 109f
performance characteristics of, tomography (ECT). of gamma camera, 219
225-228, 226f-227f Edge detection, 373, 375, 376f pulse-height analyzers in. See
resolution of, 225-228, 226f-227f Edge effects, 160 Pulse-height analyzers
source-to-collimator distance Edge packing, 217, 229 (PHAs).
and, 228, 228f Edge sharpness, 237, 260-261 time-to-amplitude converters in,
DMSA (2,3-dimercaptosuccinic Effective atomic number, 65, 101t, 118-119, 119f
acid), 60t 103-104 Electronic noise. See also Noise;
DOI. See Depth-of-interaction Effective decay factors, 35-37, 36f Signal-to-noise ratio (SNR).
(DOI) effect. Effective dose, 417, 425t, 429t counting uncertainty and, 131
DOPA, 18F-Fluoro, 372f, 373, 374f, from background radiation, 427 energy resolution and
381t recommended limits for, 434t with scintillation detectors,
Dose. See Radiation dose; Effective dose equivalent, 417, 428, 148, 149, 150, 150f
Radiation dosimetry, internal. 429t, 432, 434t, 435. See also with semiconductor detectors,
Dose calibrators, 89, 89f, 189-190, Equivalent dose. 152, 152f
189f regulatory limits for, 431-432 in liquid scintillation counters,
shielding of, 189-190, 189f, 437 for selected 184, 185, 186
Dose equivalent. See Effective dose radiopharmaceuticals, power supply and, 122
equivalent; Equivalent dose. 478-479 pulse shaping and, 110-111,
Dose limits, 431-432 Effective half-life, 411-412 111f
502 Index

Electronic noise (Continued) Emissions Energy response curve for survey


reduction by coincidence cascaded, coincidence detection meters, 90-91, 91f
detection, 184 of, 162-163 Energy spectrometry. See Pulse-
spectral blurring and, 148 inverse-square law and, 156, height spectrometry.
Electrons. See also Beta particles; 157f Energy window
Charged particles. isotropic, 156 of gamma camera, 212, 212f, 213,
annihilation of, after pair Emission/transmission scans, 218, 218f
production, 78, 78t simultaneous, in PET for PET, 336, 337
Auger, 10-13, 12f, 23, 24, 63, 74, attenuation correction, image contrast and, 240, 241f
78t 338-339 with NaI(Tl) detectors, 240
binding energy of, 9-10, 11f Energy volume sensitivity and,
in Bohr atom, 9, 10f binding 301-302
Cerenkov effect and, 68-70 electron, 9-12 Energy-mass conversion in
conversion, 22-24, 23f nuclear, 15-18, 17f radioactive decay, 19
decay modes involving, 20-22, mass and, 8, 15-16, 19 Energy-selective counting, 156,
20f, 21f, 22f, 23f of photon, 8 159, 160f
energy losses by, 63-70. See also transition, 19 cascaded gamma emissions in,
Energy losses. units of, 7-8 164
rate of, 66-68, 69f Energy corrections for gamma detection efficiency and, 156,
energy-level diagram of, 10, 11f camera, 217-218 159
Exclusion Principle for, 9 Energy deposition in gamma camera, 200, 201f
interactions with matter, 63-70 by charged particles, 63-66, 67, scattering medium in, 163
Cerenkov effect in, 70 67f, 68, 70 window fraction effect in,
energy deposition in, 67-68, dose and. See Radiation dose; 170-171
67f, 77-78, 77f, 78t Radiation dosimetry, Energy-sensitive detectors, 107,
by photoelectrons, 74, 74f internal. 108, 109, 111, 113. See also
ranges in, 74, 75 by photons, 64, 77-78, 77f, 78t Proportional counters;
photon MFP vs, 82t in radiation detectors, 91 Scintillation detectors;
tracks in, 66-67, 67f Energy levels Semiconductor detectors.
mass-energy equivalence and, 8, of electrons, 10, 10f Entrance windows, 98, 98f,
16 of nucleus, 13, 13t, 15-16 101-102, 104
notation for, 12-13 Energy linearity, 147-148, 148f thickness of, 166-167
orbits of, 9, 10f calibration for, 147-148, 148f Enzyme kinetics, 396-401
pair production and, 76-77, 77f. with well counter, 178 in carrier-mediated diffusion,
See also Pair production. energy resolution and, 148-151 390
as particulate radiation, 8 Energy losses, 63-64, 66 glucose metabolism and, 396-401,
photoelectron as, 74, 74f. collisional vs. radiation, 64-65, 397f, 398f, 401f
See also Photoelectric 66f-67f Michaelis-Menten hypothesis
effect. linear energy transfer and, 68 and, 396-397, 397f
properties of, 13t linear stopping power and, 68 Enzyme-substrate complex, 385,
radiation from, 10-13, 11f-12f, rate of, 66-68, 69f 385f, 397
12t specific ionization and, 68 Equilibrium absorbed dose
range of, 71-72, 82t Energy resolution. constant, 412-413
recoil, 74-76, 75f, 75t, 78t, 144 of crystal scintillation detectors, Equilibrium dissociation constant,
pulse-height spectrum and, 148-151, 149f, 150f 401
142, 144 definition of, 148-149 Equilibrium methods for blood flow
in Rutherford atomic model, 9 electronic noise and, 148, 149, measurement, 393
secondary, 63, 64f, 66, 67f, 78t 150, 150f Equilibrium models, 386
in photomultiplier tubes, energy linearity and, 147-148 Equivalent dose, 407-408, 429t.
98-99, 100f factors affecting, 148-151 See also Effective dose
substates of, 9 of gamma cameras, 150, 201, equivalent.
tracks of, 66-67, 67f 211-213, 212f, 231 air kerma and, 435-436
energy deposition along, measurement of, 231 distance from source and,
67-68 integration time and, 150 435-436
length of, 70, 70f, 72f-73f of liquid scintillation detectors, dose-equivalent rate and, 435
x-ray emission and. See 153, 153f recommended limits for, 431-432,
Characteristic x rays. of NaI(Tl) detectors, 148-151 434t
Elements, 9 of PET detectors, 337 units of, 407-408, 428
EM (expectation-maximization) photoelectron production and, Error. See also Statistical
algorithm, 272 149-150 analysis.
Embryo, dose limits for, 432 of proportional counters, 151, propagation of, 128-130
Emission computed tomography 153 types of, 125-126
(ECT), 253. See also quality assurance and, 172 Escape peaks, 144, 145f
Reconstruction tomography; of semiconductor detectors, iodine, 144, 144f
Tomographic imaging. 151-152, 152f, 190-192, 191f, Ethyl-cysteine-dimer (ECD), 5t,
advantages of, 269-270 240 60t, 304
image quality in, 263-270 in SPECT, 302 Euler’s equation, 482
for low-contrast lesions, 269-270 spectral blurring and, 144, eV. See Electron volt (eV).
noise in, 266-268 148-151 Event detection in gamma
Emission rates, 155 statistical variations and, cameras, 204-206, 205f
Emission scans with SPECT, 296 148-150 Exchange forces, 14-15
Index 503

Excitation, 63-64, 87 Fick principle, 387, 395 Flood-field images (Continued)


by charged particles, 63, 64, 64f Field-effect transistors, 109 corrected, 217-218, 218f, 219f
after photon interactions, 78 Field-of-view (FOV) in SPECT, 302
in radiation detection, 87 Fourier transform and, 482, 483, Flow counting
by Geiger-Müller counter, 92 483f, 487 with liquid scintillation counters,
by organic scintillator, 105 image quality and, 262, 263, 265, 188
Excited states 266 with NaI(Tl) detectors, 182
See Excitation. in PET, 318, 319, 321, 323, 329, Flow rate, tracer measurement of,
nuclear, 14, 15 335 380, 380f
in (β−, γ) decay, 21, 22, 22f axial, 326, 328, 332, 335 Fluor, 105, 106
in in (β+, γ) decay, 25 with gamma camera, 332 Fluorescent yield, 12, 13f
in (EC, γ) decay, 24 with three-D acquisition, 332, Fluorine-18
Exclusion Principle, 9 334 characteristics of, 451
Excretion pixel size and, 364, 365 decay of, 26, 27, 451
of accidentally ingested in SPECT, 279, 280, 281 detection of, with CZT
radioactive material, 437 for performance spectrometer, 151, 153f
cumulated activity and, 409, 410, measurements, 301, 302 in FDG labeling, 49-50
411, 411f, 412 for transmission scan, 295 labeling with, 60-61
Expectation-maximization useful, 217, 229, 230, 231 mean dose per cumulated
reconstruction, 272-273 in PET, 319, 321 activity for, 415-416,
Exponential decay, 32-34, 32f-33f File format standards, 378 422t-423t
Exponential functions, properties Film positron range of, 314, 314f, 315
of, 33, 34, 35 analog images on, 364 production of, 46-47, 49-50
Exposure, radiation, 428-431, 429t spatial resolution on, 233-234 properties of, 58t
air kerma and, 428-431, 429t, transparency, hard-copy images Fluorodeoxyglucose (FDG), 61
438-439 on, 367 advantages of, 60
definition of, 429-430 Film badge, 440 as analog tracer, 382
minimizing duration of, 436 Filtered backprojection (FBP), clinical uses of, 5, 5t, 60, 61,
TDS rules and, 436 260-262, 260f, 261f, 262f. See 341-342, 342f
units of, 428-431, 429t also Reconstruction co-registered images with, 377f
Exposure rate, 89, 428-431 tomography. 18
F labeling of, 49-50
External beam radiation, 48 attenuation correction to, 293 kinetics in metabolism of, 396,
Extraction, 386-388, 387f, 388f, for fan-beam data, 274 397-400, 398f
389f, 390-391, 390f image quality in, 263, 264f, production of, 50
Extraction coefficient, 388 265-270, 265f, 266f, 267f radiation dose estimates for,
Extrapolated range, 71-74, 72f-73f iterative reconstruction vs., 425t, 427, 478, 479
of electrons, 71-73, 72f, 73f, 74 270-271 Flux, 383-384
of positrons, 312-314 limitations of, 262 steady state and, 385-386, 386f
Extrinsic uniformity for gamma noise in, 260-261, 263, 264f, 293f Flux density, 54, 55f
cameras, 229-230 for PET data, 332 Focal spot, 347
sampling in, 263-265 Forward projection, 270-272, 270f,
simple backprojection vs., 276
F 260-261 Fourier slice theorem. See
f factor, 430, 430f steps in, 260, 261f Projection slice theorem.
False-positive fraction (FPF), 249, Filters Fourier transform (FT), 258
250f reconstruction, 260-261, 263, basic concept of, 481, 482f
Families, nuclear, 14, 14f 264f calculation of, 258
Fan-beam collimators, 273-274, Hann, 261, 262f of convolution, 492
274f-275f, 294, 295f, 304f in PET, 319 definition of, 258
Fan-beam projections in PET, 320f, ramp, 260-261, 261f-262f direct, 258-260. See also Direct
321 in SPECT, 301 Fourier transform
Fan-beam reconstruction, 273-276, Shepp-Logan, 261, 262f, reconstruction.
274f-275f 263-265, 264f examples of, 487f, 487, 488f
Fast Fourier transform (FFT), 482, smoothing, 373 inverse, 258
485 First-order kinetics, 384, 390 modulation transfer function
FBP. See Filtered backprojection First-order rate constants, 384-385, and, 238, 481, 485f, 492
(FBP). 385f properties of, 483-485, 483f,
FDG. See Fluorodeoxyglucose Fission 487
(FDG). radioactive decay by, 28 in tomographic reconstruction
FDG model for glucose metabolism, radionuclide production by, for 3-D PET data, 334
397-401, 398f 43-47 direct, 258-260, 259f
FDG-PET, 341-342, 342f in reactors, 43-44 FOV. See Field-of-view (FOV).
with CT, 355-356, 356f Fission fragments, 28, 44-45, 45f FPF. See False-positive fraction
with MRI, 360-361, 361f Fission moly generators, 53 (FPF).
Feldkamp algorithm, 275 Fission neutrons, 28, 43, 53 Frame-mode acquisition, 367-368
Fetus, dose limits for, 432, 433, Flat-panel display, 124 Free-response operating
434t Floating point numbers, 365 characteristics (FROC), 250
18F-2-fluoro-2-deoxy-D-glucose. See Flood source, 294, 295f Frequency, 8
Fluorodeoxyglucose (FDG). Flood-field images, 216f, 217 Frequency distributions, 126, 127f
FFT. See Fast Fourier transform from block detector, 324, 325f Gaussian, 127f, 128
(FFT). checks of, 229, 230 Poisson, 126, 127f, 128
504 Index

Frequency response curves, Gamma cameras (Continued) Gamma cameras (Continued)


236-237, 236f collimator efficiency and, 220 intrinsic spatial resolution of,
FT. See Fourier transform (FT). collimator resolution and, 220, 209-211, 210f-211f. See also
Full width at half maximum 222, 225t Spatial resolution: intrinsic.
(FWHM). collimators for, 196, 196f, Compton scattering and, 209
computation of, 149, 149f 201-204, 202f, 203f, 204f detection efficiency vs., 211,
definition of, 148-149 absorptive, 201 212f
of gamma camera image converging, 204, 204f detector thickness and, 210,
collimator resolution and, 222, design and performance of, 211f
222f, 227 220-223, 221f, 222f, 224f, full width at half maximum
intrinsic resolution and, 225, 225t, 226f, 230 and, 210-211, 225
210-211, 221, 225t, 229 diverging, 202f, 203 gamma ray energy and, 210,
system resolution and, 225, modulation transfer functions 210f
229, 235-236 of, 236, 237f, 238f, 239f improvement of, 219
of Gaussian function, 491-492 multi-pinhole, 202f, 203 limits on, 209-210
linear sampling distance and, parallel-hole, 202f, 203, measurement of, 210, 229
263, 265 220-225, 221f-222f, 224f, optimum, 210-211
in PET 226f. See also Parallel-hole mobile, 207, 208f
of angular distribution, 319 collimators. modulation transfer functions for,
partial-volume effects and, 340 penetration of. See Septal 237, 238f
of positron range, 312f, 314, penetration. NaI(Tl) crystal in, 196-198, 196f
314f, 316 pinhole, 202-203, 202f performance of, 209-231
of spatial resolution, 310, 311f, scatter from, 204-205 collimators in, 220-223, 221f,
317, 318 sensitivity of, 223, 224f, 225t, 222f, 224f, 225, 225t, 226f,
pixel size and, 234, 366 227, 231 230
in reconstruction tomography, septal thickness in, 203, 203f dead time in, 213-214, 230
263 slant-hole, 203 detection efficiency in, 211,
in resolution evaluation, 235-236 for small animal imaging, 212f
in SPECT 207-208 detector thickness and, 211,
partial-volume effects and, 299, compact, 207, 208f 212f
300f components of, 196-206, 196f nonuniform, 217
reconstruction tomography counting rates for energy resolution in, 150, 201,
and, 301-302 high, 213-216 211-213, 212f
of spatial resolution, 301 measurement of, 230 measurement of, 231
Full width at tenth maximum current availability of, 4 at high counting rates, 213-216
(FWTM) definition of, 195 image nonlinearity in, 216-217,
of gamma camera image, 229 derandomizers for, 213-214 216f, 218, 218f-219f
Fundamental quantities, 7 detectors in, 197-201, 207 image nonuniformity in,
FWHM. See Full width at half thickness of 217-219, 218f-219f, 243
maximum (FWHM). detection efficiency and, 211, measurements of, 228-231
FWTM. See Full width at tenth 212f pulse pile-up in, 213-216, 213f,
maximum (FWTM) intrinsic spatial resolution 214f-215f
and, 210, 211f spatial resolution in. See
development of, 196 Spatial resolution.
G digital image processing for, tuning methods and, 219-220,
Gadolinium-153, transmission scan 197, 200, 364, 365f, 482. 220f
with, 295, 296, 297f See also Digital image in PET, 327f, 329-330
Gadolinium oxyorthosilicate (GSO) processing. photomultiplier tubes of, 196,
in PET detectors, 322t, 326 dual-headed, 206-207, 206f 196f
properties of, 101t dynamic imaging with, 197, arrangement of, 196-198, 196f,
Gain factor 206-207 216
for amplifiers, 110 edge packing and, 217 charge integration time for,
drift in, in gamma camera, electronics of, 197-201, 197f, 214
219-220, 220f 198f, 199f, 200f, 201f dead time and, 214
for preamplifiers, 108-109 energy corrections and, 217-218 energy resolution and, 149-150
Gallbladder, gamma camera energy selection for, 200, 201f image nonlinearity and, 216,
imaging of, 207f energy window for, 212, 212f, 216f
Gallbladder dynamics, tracers for, 213, 218, 218f, 336, 337 image nonuniformity and, 217
381t event detection in, 204-206, intrinsic resolution and, 209,
Gallium-67, 5t, 58t, 243, 305, 478 205f 210, 234
Gallium-68, 313t, 315f, 316, 328, event localization in, 197, 198, light sharing between, 198,
457 200f, 219 199f
Gamma cameras, 195-208 film recorders for, 196 pulse pile-up and, 214
acceptance testing for, 228-231 flood-field images from, 216f, 217 in scintillation event
analog, 197-200 gallbladder imaging with, 207f localization, 198-200
analog buffers for, 213-214 gamma-ray energy in, 211 statistical fluctuations in,
in annihilation coincidence historical development of, 4, 4f, 209-210
detection, 310-312, 311f 196 tuning of, 219-220, 220f
calibration of, 147-148 image display for, 197 photopeak selection for, 200, 201f
clinical uses of, 1, 206-208, 206f, image formation in, 196-197 pincushion artifacts and,
207f, 208f imaging modes with, 196-197 199-200, 215f, 216
Index 505

Gamma cameras (Continued) Gamma rays (Continued) Gaussian spectral curve, 149
quality assurance for, 228-231 penetration by, 195 Geiger-Müller (GM) counters,
response characteristics of, 254, septal, 205, 220-221 92-96, 93f, 94f, 95f
254f prompt, 45-46 avalanche ionization in, 92-93,
scintillation event localization in pulse-height spectrum of, 94f
in analog camera, 198-200 142-147, 143f, 145f, 146f, backscatter and, 166-167, 167f
in digital camera, 200 147f, 151 for β-emitting radionuclides,
sensitivity of, measurement of, radiation safety and, 434, 435, 167
231 437 as gas flow counters, 190
single-headed, 206-207, 206f Gamma-ray converters, 158-159 counting curves for, 94, 95f
for small animal imaging, Gamma-ray probes dead time in, 168, 188
207-208 miniature, 192-194, 193f intrinsic efficiency of, 158-159
spatial linearity and, in oncology, 192-193 limitations of, 93, 95, 166-167
measurement of, 229-230 radiation detectors for, 193 pancake, 95-96, 95f
in SPECT, 279-280 Gas amplification power supply for, 122
in SPECT/CT, 350f, 351, 352f in Geiger-Müller counters, 92-93, principles and design of, 92, 93f,
static imaging with, 197 94f 95-96, 95f
system resolution of, 210-211, in ionization chambers, 91, 92f pulse signals of, 107, 107t
214, 225, 227-228 in proportional counters, 91, self-absorption and, 166-167,
measurement of, 229 92f 167f
technical advances in, 207 Gas chromatograph self-quenched, 93-94
in tomographic imaging, 254, with gas-filled detector, 190 as survey meter, 95-96, 95f,
254f, 255, 255f, 256f with liquid scintillation counter, 439
for PET, 4, 325-326, 327f, 188 Generators, 24, 50-53, 51f, 51t
329-330, 332, 334 with NaI(Tl) detector, 182, 183f contaminants in, 50-53, 58
for SPECT, 279-280, 280f, 281, Gas flow counters, 190 fission moly, 53
283, 301-303 Gas flow counting with LS systems, historical development of, 2
triple-headed, 206-207 188 radionuclide, 50-53, 51f-52f,
types of, 206-208, 206f, 207f, 208f Gas proportional counters. See 51t
uniformity measures for, 230 Proportional counters. safe handling of, 436
whole-body imaging with, 207f Gases, radioactive Geometric detection efficiency.
X- and Y-position signals in, dose limits for, 431-432 See Detection efficiency:
199-200 safe handling of, 437, 438 geometric.
Gamma probes, intraoperative, Gas-filled detectors, 87-96, Geometric mean, in conjugate
193f, 194 189-190. See also Geiger- counting, 287-293
Gamma rays. See also Photons. Müller (GM) counters; correction for, 293-294, 294f
annihilation, 25 Ionization chambers; Germanium-68, 165t
biologic effects of, 78, 428 Proportional counters. characteristics of, 457
in collimators, 201-203 advantages and limitations of, as rod source, in PET scanner,
Compton scattering of. See 102 328f, 329, 338
Compton scattering. applications of, 189-190 Germanium detectors, 89t, 96-97.
detection of. See Radiation in dose calibrators, 189-190 See also Radiation detectors;
detectors. energy deposition in, 141 Semiconductor detectors.
in electromagnetic spectrum, 8, in gas flow counters, 190 detection efficiency of, 158
8f Geiger-Müller counters, 92-96, intrinsic, 96, 158
energy of 93f-95f lithium-drifted, 89t, 96-97, 97f
attenuation and, 163-164, 164f intrinsic efficiency of, 158-159 spectrometry with, 151, 152f
in SPECT, 287-294 ionization chamber, 87-91, GFR. See Glomerular filtration
gamma camera resolution and, 89f-91f. See also Ionization rates (GFR).
211-213, 234 chambers. Gibbs phenomenon, 486
intrinsic efficiency and, 158, principles and design of, 87, 88f Glass, leaded, 436-437, 436f
159f, 174, 175f proportional counters, 91-92, Glass vials for liquid scintillation
nuclear transitions and, 15 92f counting, 184-185
photofraction and, 159, 160f, semiconductor, 96-97, 97f Glomerular filtration rate (GFR),
174, 174f Gated imaging, 369 379
pulse-height spectrum and, in cardiac studies, 234, 303, 304, Glucose. See also
142-147, 143f, 145f, 146f, 304f, 392, 392f Fluorodeoxyglucose (FDG).
147f, 151 with gamma camera, 197 metabolism of, 396-401
scatter and, 163-164, 164f motion blurring and, 245 FDG model of, 397-401, 398f
in vivo measurements and, 163 Gaussian blurring function, Michaelis-Menten hypothesis
interactions with matter, 74-78 235-236, 491 and, 396-397, 397f
in nuclear medicine, 1 Gaussian distribution, 127f, 128 parametric brain imaging and,
from nuclear transitions, 8-9, 8f, statistical tests and, 133, 135, 400, 401f
15 138 Sokoloff deoxyglucose method
in (α, γ) decay, 28 Gaussian function, convolution of, and, 397, 400
in (β+, γ) emission, 26 491 transport of, 389
in (β−, γ) emission, 21-22, 22f, Gaussian response profile of GM counters. See Geiger-Müller
23f annihilation coincidence (GM) counters.
in (EC, γ) decay, 24, 24f detector, 308, 310f Graphics processing units, 363
isomeric, 22-23, 23f, 24 Gaussian smoothing filters, 373, Gray (Gy), 89, 407, 433-434
in (n, γ) reaction, 46 375f Grayscale images, 367, 370f
506 Index

Ground state of nucleus, 14, 15, I Image quality (Continued)


15f, 16 ICRP. See International in iterative reconstruction, 273
GSO. See Gadolinium Commission on Radiological Nyquist frequency and, 263
oxyorthosilicate (GSO). Protection (ICRP). sampling and, 263-265
ICRU. See International spatial resolution and, 233-239.
Commission on Radiological See also Spatial resolution.
H Units (ICRU). in SPECT, 302-303
Half-life, 33-34 Image arithmetic, 371, 371f system resolution and, 265-266
biologic, 59, 410-411, 411f, 412 Image contrast. See Contrast. tomographic reconstruction and
effective, 411-412 Image intensity, Fourier transform with FT and FBP, 263, 264f,
physical, 33-34 of, 481, 482 265-270, 265f, 266f, 267f
average lifetime and, 34 Image noise, 243-247, 247f. See with iterative methods,
for clinical applications, 59, also Contrast-to-noise ratio 275-276
60-61 (CNR); Statistical noise. in x-ray computed tomography,
cumulated activity and, in digital image, 366, 367 263-270
410-412 in tomographic image, Image reconstruction. See
of radiopharmaceuticals, 59 266-270 Reconstruction tomography.
Half-time of turnover, 384, 480 filtered backprojection and, Image registration. See
Half-time of uptake, 410 261-262 Co-registration.
Half-value layer (HVL). See in PET, 319 Image segmentation, 375, 377f
Half-value thickness (HVT). ramp filter and, 268, 301 in CT-based attenuation
Half-value thickness (HVT), 82, Image processing. See Digital correction, 357
82t, 83, 84 image processing. Image smoothing, 373, 375f, 489
Hann filter, 261, 262f Image quality, 233-251. See also Image space, 258
Harper, Paul, 2-4 Detectability. Image visualization, 369-372,
Hasegawa, Bruce, 350 basic methods for 370f-372f
Health care workers, occupational characterization of, 233 Image-frame decay corrections,
exposure of. See Radiation contrast and, 233, 239-240 35-36, 36f
safety. coverage and, 266, 266f-267f Images. See Digital images.
Health physics, 427-428. See also definition of, 233 Imaging, radionuclide. See
Radiation safety. in direct Fourier transform Gamma cameras; Tomographic
air kerma and, 428-431, 434-435 reconstruction, 263-270 imaging.
dose-modifying factors and, 428 edge sharpness and, 237 Impedance matching, 107
exposure rate and, 89, 428-431 in emission CT, 263-270 Impulse response, 391-392
quantities and units in, 428-431, evaluation of, 233 In vitro counting systems, 173
429t contrast-detail studies for, In vivo counting systems, 173,
Heart. See Cardiac studies; 247-249, 248f-249f 192-194, 192f, 193f
Organs. observer performance studies detection efficiency in, 156, 166
Heat scale, 367 for, 247-251 Index of refraction of scintillators,
Hevesy, Georg de, 2 receiver-operating 101t, 104
Hexokinase, 396, 397, 398f, 399 characteristic studies in, Indium-111, 58t
HIDA, 99mTc-labeled, 60t, 207f 248-251, 250f characteristics of, 463
High-voltage power supplies, 122 filtered backprojection and, pentetreotide labeled with, 305
HMPAO 263-270 in radioimmunoguided surgery,
(hexamethylpropyleneamine with gamma (Anger) camera, 193
oxime), 304, 304f 233 white blood cells labeled with,
Hormesis, 427 nonlinearity and, 216-217, 5t
Hot lesions, 246 216f, 218 Infection, tracers for, 5t, 381t
Hot-body scale, 367 in PET, 335 Information density, 244, 245, 247,
Hounsfield units, 349 nonuniformity and, 217-220, 247f
HPGe (high purity germanium), 97 218f, 219f, 220f, 243 Inorganic scintillators, 100-103,
Human observer performance in PET, 335 101f, 101t, 102f, 103f
studies, 233 pulse pileup and, 213, 214, NaI(Tl), 100-103, 101f-103f,
contrast-detail studies, 247-248, 214f 101t. See also NaI(Tl)
248f-249f information density and, 244, detectors.
receiver operating characteristic 245, 246-247, 247f for PET, 316, 322t, 324, 326
studies, 248-251, 250f noise and, 233, 243-247 properties of, 101t, 103, 103f
HVT. See Half-value thickness observer performance studies of, selection of, 103
(HVT). 233, 247-251, 248f, 249f, In-plane resolution, 301
Hybrid imaging systems 250f Input function, 390, 391, 391f
CT-based, 346-354, 356-360. See patient motion and, 234, 266, Instrumentation. See Counting
also PET/CT; SPECT/CT; 359 systems; Electronic
X-ray computed tomography. in PET, 335 instrumentation; Radiation
advantages of, 332-334 processing and. See Digital image detectors.
future directions for, 345-346 processing. Integral uniformity, for gamma
image co-registration and, 376 quality assurance and. cameras, 229-230
MRI-based, 360-361 See Quality assurance. Integration circuits, 111, 112f
Hydrogen-3 (tritium), 449. See also in reconstruction tomography, Integration time
Liquid scintillation counters 263-270, 266f-267f energy resolution and, 150
(LSCs). coverage and consistency in gamma camera, 214
Hypoxia, tracers for, 381t requirements and, 266 Internal conversion, 15, 22-23, 23f
Index 507

Internal dosimetry. See Radiation Ionization (Continued) J


dosimetry, internal. tracks associated with, 66, 67, Joule, 407
Internal standardization method, 67f, 68, 70
186, 186f units of radiation and, 428-429
International Commission on Ionization chambers, 87-91, 88f, K
Radiological Protection (ICRP), 89f, 90f, 91f K absorption edges, 79, 80f
417, 431, 433, 434t. See also detector materials for, 89t K shells, 65f-67f, 67-70, 73t
Radiation safety. in dose calibrators, 89, 89f, Kerma, air, 89, 428-431, 429t
International Commission on 189-190 Kety-Schmidt method, 387, 395
Radiological Units (ICRU), efficiency of, 90-91, 158-159 keV. See Kiloelectron volt (keV).
437 energy response curve for, 90-91, Kidney, functional evaluation of,
Intersubject image co-registration, 91f 379
375-376 gas amplification in, 91, 92f Kilocurie, 32
Intrasubject intramodality image gas-filled, 87-96 Kiloelectron volt (keV), 8
co-registration, 375-376 limitations of, 90-91 Kinetic energy
Intrinsic detection efficiency. See in pocket dosimeters, 89-90, kerma and, 429, 429t
Detection efficiency: intrinsic. 90f in radioactive decay, 19, 20
Intrinsic germanium detectors, principles and design of, 87-91, Kinetic modeling. See Tracer
96 88f kinetic modeling.
Intrinsic photopeak efficiency in survey meters, 89, 89f k-space, 258-259, 260f, 481, 482,
for NaI(Tl) well counters, 174, voltage response curve for, 87-88, 483, 483f, 484, 485f, 487
176f 88f, 91, 92f Nyquist frequency and, 263, 484,
of semiconductor detector, 191 vs. proportional counters, 485f, 487
Intrinsic spatial resolution. See 91-92 Kuhl, D.E., 4
Spatial resolution: intrinsic. Ionization detectors, 87. See also
Intrinsic uniformity, 229-230 Gas-filled detectors;
Inverse β− decay, 24-25 Semiconductor detectors. L
Inverse Fourier transform, 258 gas-filled, 87, 88f L (linear energy transfer), 68
Inverse-square law, 156, 157f, 435 semiconductor, 96-97, 97f L shells, 65f, 67-70, 72f-73f, 73t
Iodine-123, 464-465 Ionization events Labeled microsphere technique,
Iodine-124, 466-467 primary, 141, 142f 393-394
Iodine-125, 24-25, 24f, 58t, secondary, 141, 142f Labels/labeling. See also
468-469 Ionization potential, 68 Radiopharmaceuticals.
Iodine-129, as calibration standard, Ionizing radiation, 63 by analog creation, 60
165t biologic effects of, 427-428 by direct substitution, 59-60
Iodine-131 definition of, 8, 63 with 99mTc, 60, 60t
characteristics of, 470-471 secondary, 74 with positron emitters, 60-61
dosimetry of, internal, 416, 420t Isobaric decay modes, 20, 24, of radiopharmaceuticals, 59-60
as iodide ion, 57 25-26, 27 requirements for, 381-382
mean dose per cumulated Isobars, 14, 14f Laboratory design, 438
activity of, 415-416, stability of, 17 Laboratory monitors, 436
420t-421t Isomeric state, 14-15 L absorption edges, 79, 80f
mock calibration source for, 177 decay of, 19-20 Lanthanum bromide, 101t, 103
notation for, 14 Isomeric transition, 22 Lanthanum chloride, 103
properties of, 58t Isomers, 14 Laplacian technique, 373, 375,
in radioimmunoguided surgery, Isotones, 14, 14f, 16f, 17, 28 376f
193 Isotope effect, 20, 380 Lawrence, Ernest O., 2, 3f
safe handling of, 432 Isotopes, 14, 14f LC. See Lumped constant (LC).
in thyroid imaging, 2, 3f, 5t on chart of nuclides, 28 LCD. See Liquid crystal display
Iodine escape peak, 144, 144f definition of, 14 (LCD).
Ionization, 87, 87f radioactive. See Radionuclides. Lead
avalanche stable, 16f, 17 in bar phantom, 235
in Geiger-Müller counters, Isotropic emission, 156 in collimator
92-93, 94f Iterative reconstruction, 262, of gamma camera, 195, 196,
in ionization chambers, 91, 92f 270-273 203, 221
in proportional counters, 91, for coded aperture imaging, 285 of SPECT system, 281, 283
92f cone-beam data in, 275 mass attenuation coefficients of,
Bragg peak in, 68, 69f 3-D, 276 476-477
collisional energy losses in, expectation-maximization, Lead shielding, 436-437, 436f. See
64-65, 66f-67f 272-273 also Shielding.
pair production and, 76-77, 87. filtered backprojection vs., for dose calibrator, 189, 437
See also Pair production. 271-272 natural radioactivity in, 178
radiation detection and, 87, forward projection and, 270-272 in PET systems, 323
141-142, 142f image quality in, 273 for well counter, 178, 180f, 181,
secondary, 63, 64f overview of, 258 183f
to charged-particle for PET data, 331, 332, 334 x-ray peaks from, 144, 151
interactions, 63, 64, sampling in, 273 Lead x-ray peaks, 144
141-142, 142f scatter corrections in, 298, 299 Leaded glass, 436-437, 436f
to photon interactions, 74, steps in, 270-271, 270f-271f Leading-edge timing, 115, 115f
76-77, 78, 141, 142f tissue attenuation information LEDs. See Light-emitting diodes
specific, 68, 69f, 71 in, 296, 298 (LEDs).
508 Index

Left ventricular ejection fraction, Liquid chromatography, with Lutetium yttrium orthosilicate
392, 392f NaI(Tl) detectors, 182, 183f (LYSO), 101t, 102-103
Lesion detectability. See Liquid crystal display (LCD), 124, Lymph nodes, sentinel, gamma-ray
Detectability. 367 probes for, 192-193
Lesions. See Detectability. Liquid nitrogen in semiconductor
LET. See Linear energy transfer detectors, 97, 97f
(LET). Liquid scintillation (LS), 104-106, M
Licensing for use of radionuclides, 105f, 187-188 MAG3 (mercapto-acetyl-triglycine),
431, 432, 433 Liquid scintillation (LS) cocktails, 5t
Ligand, 60 105, 187 Magnetic resonance imaging
Light coupling. See Optical Liquid scintillation counters (MRI)
coupling. (LSCs), 184-185 combined with nuclear medicine
Light guide of gamma camera, 196, applications of, 105, 183-184, imaging, 376, 377f
196f, 198, 219 189 image reconstruction in, 4, 259
Light-emitting diodes (LEDs), automated multi-sample, in k-space, 259
219 188-189, 188f limitations of, 1
Limited-angle tomography, 266 calibration of, 185 with PET, 345-346, 360-361,
Limited-scope licenses, 431 Cerenkov counting with, 188 361f
Line broadening, 148. See also coincidence detection by, 184 with SPECT, 360
Energy resolution. components of, 105f, 182-184, stray fields from, gamma camera
Line integrals, 254, 254f 183f and, 197
Line of response, 254, 254f dark adaptation of samples and, Malignant melanoma, sentinel
actual vs. idealized, 285-286 185 nodes in, gamma-ray probes
conjugate counting and, 287 dead time in, 168 for, 193-193
scattering into, 296 efficiency of, 157, 185 Mass
in transmission scan, 295-296 flow counting with, 188 equivalence to energy, 8, 15-16,
Line of stability, 16, 16f gas/liquid chromatography with, 19
decay modes and, 28 188 units of, 7-8
Linear accelerators, 47 limitations of, 106 Mass attenuation coefficients, 79,
Linear attenuation coefficients, 78, mixtures of radionuclides in, 185, 158
81, 82, 83, 158 188-189 absorbed dose and, 430
of bone, 287, 294, 338 noise in, 184, 185, 186 table of, 476-477
coincidence rate and, 319 organic scintillators for, 104-106 Mass deficiency, 15
of collimator material, 221, 222 principles and design of, 182-184, Mass number (A), 13
detection efficiency and, 158, 183f Mass-energy conversion in
159 pulse signals of, 108t radioactive decay, 19
in PET, 321 pulse-height spectrometry with, Matrix of pixels, 365, 365f
of tissue, 192, 296 141, 153, 153f, 184, 185f Matrix size, 365-366, 366f
transmission scan and, 294, quenching in, 106, 188 Maximum intensity projection,
338 correction methods for, 369-371
Linear energy transfer (LET) 185-187, 186f-187f Maximum-likelihood (ML)
of charged particles, 68, 71 radionuclides counted with, 105, reconstruction, 272-273
of photons, 78 166, 182-184, 183t MCAs. See Multichannel analyzers
Linear nonthreshold (LNT) model, refrigeration of, 184 (MCAs).
427 sample preparation for, 106, MDA. See Minimum detectable
Linear regression, 139-140 187-188 activity (MDA).
Linear sampling distance, 263, 265 scintillator solutions in, 104-106, MDP. See Methylene diphosphonate
in annihilation coincidence 187 (MDP).
detection, 318, 318f vials for, 184-185 Mean dose per cumulated activity,
in imaging processing, 365-366 List-mode acquisition, 335, 411f, 414f, 415-416, 418t-419t
with iterative algorithms, 368-369 for 18F, 415-416,
273 Lithium fluoride, 422t-423t
performance measurement and, thermoluminescent, 440f for 131I, 415-416, 420t-421t
301 Logarithmic rate meters, 121, for 99mTc, 415-416, 418t-419t
pixel size and, 366 121f Mean free path, photon, 82, 82t
SNR and, 267 Logic pulses, 118-119 Mean transit time, 380, 380f,
Linear stopping power, 68 Lower-level discriminator, 113, 384
Line-spread function (LSF) 114f Mean value, 126, 127
distance from source vs., 288f LS. See Liquid scintillation (LS). arithmetic vs. geometric,
FWHM and, 235 LSCs. See Liquid scintillation 287-288, 288f
of gamma-camera collimators, counters (LSCs). confidence interval for, 127,
222-223, 222f, 224f, 225 LSF. See Line-spread function (LSF). 127t
modular transfer function and, LuAP, 101t, 103 t-test and, 135-137
238, 240-241, 242f Lumped constant (LC), 399, 400 uncertainty in, 128
pixel size and, 366 Lung perfusion, 393 Measurement errors, 125-126
in resolution evaluation, 235 Lung ventilation, 381t blunders, 125
scattered radiation and, 240-241, Lutetium oxyorthosilicate (LSO), propagation of, 128-130
242f 101t, 102-103 random, 125-126
septal penetration and, 240-241, in PET systems, 321, 322t, 324, systematic, 125
242f 325, 325f, 326 types of, 125-126
in SPECT imaging, 288f, 298 energy resolution and, 337 Measurement standards, 125
Index 509

Measurements. See also Statistical Modulation transfer function (MTF) NaI(Tl) detectors (Continued)
analysis. (Continued) counting applications of
constant multipliers and, 129 of SPECT system, 301 with gas/liquid
frequency distribution of, 126, system effects and, 238 chromatographs, 179
127f Moly shield, 53 with large sample volumes,
inaccurate, 125 Molybdenum-99, 45, 51f, 51t, 53 182
reproducible, 126 breakthrough of, 50-53, 84 with NaI(Tl) well counters,
sums and differences of, 129 characteristics of, 460 173, 174f, 174t
true value of, 126 detection of, with dose calibrator, cracked crystal in, 104, 150, 217
uncertainty in, 126-127, 129 189 dead times of systems with, 179
Medical Internal Radiation Dose production of, 44-45 detection efficiency of, 157, 174,
(MIRD) Committee, 28, 407, Molybdenum-99—technetium-99 175, 175f-176f, 179
414 generators, 50-53, 51f, 51t, intrinsic, 158-159
Medical Internal Radiation 60 with source in tissue, 163, 164f
Dosimetry (MIRD) method. See Monitoring of radiation. See total, 160-161, 161f
Absorbed fraction (MIRD) Radiation monitoring; digitization of signals from,
method. Radiation safety; Survey 117-118
Medical Internal Radiation meters. disadvantages of, 102
Dosimetry (MIRD) Motion, patient, 234, 234f energy linearity and, 147-148
publications, 28 attenuation correction artifacts energy resolution and, 148-151
Megaelectron volt (MeV), 8 and, 359 in gamma cameras, 196-198,
Melanoma, sentinel nodes in, breath-holding and, 359 196f
gamma-ray probes for, gated imaging and, 234, 368 crystal thickness in, 210, 210f,
192-193 in SPECT, 303, 304f 211, 211f
Metabolic tracers. See image quality and, 234, 266, limitations of, 216
Fluorodeoxyglucose (FDG); 359 limitations of, 182
Methylene diphosphonate in PET, 308, 339 linear attenuation coefficient of,
(MDP); Oxygen-15. Motion blurring, 234, 266 321, 322t
Metastable radionuclides, attenuation correction artifacts mass attenuation coefficients of,
generators of, 24, 50-53, 51t, and, 359 476-477
52f breath-holding and, 359 minimum detectable activity
Metastable state, 10f, 14-15 image quality and, 234, 266, with, 191
decay of, 22 359 in PET scanners, 321, 322t, 324,
Methylene diphosphonate (MDP), MRI. See Magnetic resonance 327f, 330, 337
5t, 60t, 207f, 479 imaging (MRI). photofraction with, 159, 160f
Metric units, 7 MTF. See Modulation transfer power supply for, 122
MeV. See Megaelectron volt (MeV). function (MTF). preamplifiers for, 108-109
Michaelis-Menten kinetics, Multichannel analyzers (MCAs), principles and design of, 91,
396-397, 397f 113, 116-118, 116f 100-102, 101f
Microcurie, 32 dead time of, 168 pulse-height spectrometry with,
Microdosimetry, 425 of liquid scintillation counters, 142-151. See also Pulse-
Microprocessors, 363 184 height spectrometry: with
Microsphere technique, 393 of NaI(Tl) well counters, 173, NaI(Tl) detectors.
Millibarn, 53-54 180f, 181 advantages of, 151
Miniature probes for surgery, for radiochemical identification, calibration for, 147-148
192-194 182 counting rate and, 146, 147f
Minimum detectable activity of semiconductor detectors, 190 crystal size and, 145-146, 146f,
(MDA), 131 Multi-pinhole collimators, 202f, 158, 159, 160f
with semiconductor detectors, 203 energy linearity in, 148-149,
191 Multiple scattering, intrinsic 148f
MIRD Committee. See Medical resolution and, 209, 210 energy resolution in, 148-151,
Internal Radiation Dose Multiprobe systems, 192 149f, 150f
(MIRD) Committee. Multi-slice imaging, 262-263 vs. semiconductor detectors,
MIRD method. See Absorbed Mu-metal shielding, 99, 101f 151, 152, 152f
fraction (MIRD) method; Muscle, f factor for, 430, 430f gamma-ray energy and, 147,
Radiation dosimetry, internal. Myocardial imaging 147f
MIRD publications. See Medical with 99mTc-labeled red cells, 392, scatter rejection in, 240
Internal Radiation Dosimetry 392f spectral structure in, 142-145,
(MIRD) publications. SPECT in, 281-283, 303, 305f, 143f, 144f, 145f, 146f
ML reconstruction. See Maximum- 306 timing methods in, 114-115
likelihood (ML) reconstruction. Myocardial perfusion. See Cardiac in SPECT
ML-EM method, 272-273 studies. in brain imaging, 280-281, 282f
Mn-54, 165t in cardiac imaging, 281-283
Mock calibration sources, 177 in CERASPECT system, 281,
Modulation transfer function N 282f
(MTF), 236-237, 487, 492 (n, γ) reaction, 45, 46 in small-animal imaging,
3-D representation of, 238 (n, p) reaction, 46, 47 281-283, 282f
derivation of, 238 NaI(Tl) detectors, 100-103, 182 in SPRINT II system, 280-281,
line-spread function and, 238, advantages of, 102, 190-191 282f
240-241, 242f amplifiers for, 113 through-hole, 180, 180f-181f
scatter and, 241, 242f for cardiac SPECT, 281-283 timing methods for, 114-116
510 Index

NaI(Tl) detectors (Continued) Neutrons (Continued) Nuclear counting systems,


in whole-body counters, 194 fission as, 26 comparison of, 132
window fractions and, 170-171 positron emission and, 25 Nuclear emissions, 15. See also
in well counters. See NaI(Tl) well energy levels of, 10f, 14-15 Radioactive decay.
counters. equivalent dose of, 408t Nuclear energy-level diagrams, 15,
NaI(Tl) probe systems, 207, 208f fission, 28, 43 15f
NaI(Tl) well counters, 173-182 forces on, 14-15 Nuclear families, 14, 14f
absolute activity assays and, 177 nuclear stability and, 14-18, Nuclear fission, 26, 28
applications of, 182 16f-17f radioactive decay by, 28
automated multiple-sample, number of, 13-14 radionuclide production by, 43-47
179-182, 180f properties of, 13, 14t in reactors, 43-44
background in, 179, 180, 181 in shell model, 14 Nuclear forces, 14-15
background radiation and, slow (thermal), 43-44 Nuclear fragments, 43
177-178, 179, 180, 181 Neutron-to-proton ratio, 16 Nuclear instrument modules
calibration of, 178 NIM. See Nuclear instrument (NIM), 122-123
coincidence detection and, 163 modules (NIM). Nuclear medicine, 1-6
coincidence summing in, 145, Nitrogen-13, 58t, 60-61, 382, 450 advantages of, 1-2
146f, 163 Noise, 233, 239-240, 243-247 applications of, 1-2, 12t
dead time of, 179, 182 contrast-to-noise ratio and, current practice of, 4-5
detection efficiency of, 157, 174, 243-244 fundamental concepts of, 1
175, 175f-176f, 179 in reconstruction tomography, historical perspective on, 2-4,
detector characteristics in, 173, 266-268 3f-4f
174f definition of, 233 risks of procedures in, 424, 427
detectors in, 173, 174f, 174t in filtered backprojection, role of physics in, 6
through-hole, 180, 180f 260-263, 293f safety of, 2
efficiency of, 174, 175, 175f-176f, image quality and, 233, 243-247 selected procedures in, 5t
179 image smoothing and, 373, 375f Nuclear physics
geometric, 157 in iterative reconstruction, 273 basic concepts of, 7-18
energy calibration of, 178 in liquid scintillation counters, in medicine, 6
energy resolution of, 173 184 Nuclear reactors, 43-44, 44f
multichannel analyzers for, 173, random, 243 neutron-capture cross sections in,
180f, 181 contrast-to-noise ratio and, 54
multiple radionuclides in, 243-244 principles and design of, 43-44,
178-179, 178f, 181, 182 in reconstruction tomography, 44f
rod standards for, 164, 165f 266-268 radionuclide production in, 43-47,
sample volume effects and, reduction of, by coincidence 46t
175-177, 177f detection, 184 Nuclear Regulatory Commission
shielding for, 177-178 sampling requirements and, (NRC), 431, 432, 433
volume effects in, 174, 175-177, 366 Nuclear-binding energy, 15-18
177f signal-to-noise ratio and, 110 per nucleon, 17, 17f
with through-hole detector, in filtered backprojection, Nucleons, 13-14, 13t. See also
180, 180f-181f 260-261, 263, 264f Neutrons; Protons.
Nanocurie, 32 image smoothing and, 373, arrangement of, 14-15
Narrow-beam attenuation 375f basic properties of, 13t
coefficient, 297 in reconstruction tomography, binding energy per, 17, 17f
Narrow-beam geometry, 79-83, 81f, 266-268 energy levels of, 10f, 14-15
82t spectral blurring and, 148 forces on, 14-15
National Council on Radiation structured, 243 nuclear stability and, 14-18,
Protection and Measurement Noise equivalent counting rates, 16f-17f
(NCRP), 431, 433, 434t 340-341, 341f in shell model, 14
NCRP. See National Council on Noncolinearity, 314, 315f, 316 Nucleus, 9, 13-18. See also Atomic
Radiation Protection and Nondisplaceable compartments, number (Z).
Measurement (NCRP). 384, 402f binding energy of, 15-16, 17-18,
Negative-ion cyclotrons, 48-49, Nonlinear energy response of 17f
49f NaI(Tl) detectors, 148, composition of, 13, 13t
Net extraction fraction, 387 149-150, 178 daughter, 19
Neurodegenerative diseases, Nonparalyzable counting systems, decay of. See Radioactive decay.
341-342 168-169, 168f-169f in excitable state, 10f, 14-15
Neutrinos, 20-21, 24, 25 Normal distribution, 127f, 128, excited states of, 14, 15, 21, 22,
Neutron activation, 45-47, 46t 133 22f, 24, 25
Neutron activation analysis, 190, NRC. See Nuclear Regulatory forces and energy levels in,
192 Commission (NRC). 14-15, 15f
Neutron deficient nuclides, 17, 28 Nuclear atom, 9 in ground state, 14
Neutron number, 13 Nuclear binding energy, 15-16 mass number of, 13
Neutron-capture cross-sections, 54 nuclide stability and, 17-18, 17f in metastable state, 10f, 14-15
Neutrons, 13-14, 13t Nuclear chain reactions, 43. See metastable states of, 14-15, 22,
arrangement of, 14-15 also Fission. 24
decay modes involving. See also Nuclear counting statistics, neutron number of, 13
specific modes. 125-140. See also notation for, 13-15, 14f
β− decay as, 20-21 Measurements; Statistical parent, 19
electron capture as, 24, 28 analysis. of Rutherford atomic model, 9
Index 511

Nucleus (Continued) Organs (Continued) Parallel-hole collimators


shell model of, 14 source and target, 408, 413-414, (Continued)
stability of, 14-18, 16f-17f 415, 416, 418t-424t septal thickness in, 203, 203f,
radioactive decay and, 19 weighting factors for, 424, 428, 211, 220f-221f
Nuclides, 14, 14f. See also 429t, 435 efficiency and, 223
Radionuclides. Oscilloscopes system resolution of, 225, 227
chart of, 29f analog, 124 in tomographic imaging, 254-256,
definition of, 14 cathode ray tubes for, 123-124, 254f, 255f, 256f
energy-level diagram for, 15, 123f with SPECT, 279-281, 285,
15f digital, 124 288, 288f, 291, 293, 294
isomers of, 14-15 Outliers, 138, 138t, 139f Paralyzable counting systems,
metastable, separation of, 24 Oxygen-15, 60-61 168-169, 168f-169f
stable, 14-18, 16f-17f, 27, 28 blood flow measurement with, gamma camera as, 213, 230
Nutt, Ron, 354 393, 395 Parametric imaging, 372
Nyquist frequency, 263, 484, 485f, decay of, 25-26, 26f of glucose metabolism in brain,
487 in PET 400, 401f
for cerebral perfusion studies, Parent nucleus, 19
371, 372f Parent-daughter decay, 39-42
O dead time losses with, 339 activity relationships in, 39-42,
Object detectability. See positron range of, 113t, 314, 39f, 40f, 41f, 42f
Detectability. 314f Bateman equations for, 39-40,
Object scatter, 144-145, 205 production of, 49 39f
with gamma camera, 205, 205f properties of, 58, 58t, 381t, 382, definition of, 19
with NaI(Tl) detector, 144, 145, 450 in generator, 50, 51, 51t, 52
147, 147f, 152f Oxygen utilization rate, 387 in no equilibrium, 42
Object space, 258, 481, 483, 483f, product activity and, 56
485, 485f, 487 in secular equilibrium, 40-41,
Observer performance studies, P 40f
247-251 (p, n) reaction, 47, 50t in transient equilibrium, 41-42
computer, 233 P value, 134, 134f, 135, 136-137, Partial-volume effects
human, 233 136f, 172 in PET, 340, 373
contrast-detail studies, PACs. See Picture archival in SPECT, 299, 300f, 373
247-248, 248f-249f communications systems Particulate radiation, 8. See also
receiver operating (PACs). Charged particles.
characteristic studies, Pair production, 76-77, 77f, 78t Partition coefficient, 383, 383f, 395,
248-251, 250f photon attenuation and, 79, 396, 399
Occupational dose limits, 432, 80f-81f Passive transport, 389-390
434t in radiation detectors, 141-142, carrier-mediated diffusion and,
Occupational exposure. See also 142f 389
Radiation safety. Paired data, 135, 137 Patient motion
definition of, 431 Pancake Geiger-Müller counters, attenuation correction artifacts
dose limits for, 431-432, 434t 95-96, 95f and, 359
in pregnancy, 433 Parallel-hole collimators, 202f, 203, breath-holding and, 359
Oncology 220 image quality and, 234, 266,
FDG-PET in, 341 collimator resolution and, 222, 359
gamma-ray probes in, 192-193 222f, 225t Pauli Exclusion Principle, 9
PET/CT in, 355-356, 356f efficiency and, 223 Peak detection timing, 115-116
SPECT in, 305-306 FWHM and, 222, 222f, 227 Penetrating radiation, 82-83. See
1/r blurring, 258, 260-261 hole geometry and, 222 also Photons.
One-sided t test, 136, 137 source-to-collimator distance absorbed fraction for, 414
Optical coupling, 149, 150, 151 and, 223, 224f, 228, 228f definition of, 83
Optical windows, 101-102 system resolution and, 225 GM counters for, 95
Orbits, electron, 9, 10f design and performance of, Penetration, septal, 205, 220-221
Order of reaction, 385 220-223, 221f, 222f, 224f, Pentetreotide, 111In-labeled, 305
Ordered subsets, 272 225, 225t, 226f Percentage uncertainty, 127, 129
Organic scintillators, 104-106 efficiency of, 222, 224f, 225t in counting rate, 130, 131, 132,
in liquid solution, 97, 104-106, collimator resolution and, 223 133
106f, 185, 187, 188 hole geometry and, 222 Performance studies
plastic, 105, 105f septal thickness and, 223 computer, 233
solid, for flow counter, 187 gamma-ray energy and, 221-222, human, 233, 247-251
Organs. See also Radiation 225t Perfusion. See also Blood flow.
dosimetry, internal; Tissue. hole geometry in, 222, 222f, definition of, 386
dose estimates for 224f measurement of, 393, 394, 395
with FDG, 424, 425t line-spread function for, 222-223, uptake and, 387
phantom models and, 414, 222f, 224f, 225 Periodic table, 9
414f, 415 modulation transfer functions for, Permeability, membrane
for selected 237, 238f diffusion constant and, 389
radiopharmaceuticals, point-spread function for, extraction and, 387, 387f, 389,
478-479t 222-223, 222f, 224f, 225 389f
dose limits for, 432, 432t in reconstruction tomography, Persistence time of phosphor in
radiation damage to, 427, 428 273 CRT, 124
512 Index

Personal computers, 363 Photoelectric effect (Continued) Photons (Continued)


MCA boards for, 117 in radiation detectors, 141-142, photoelectric effect and, 74, 74f,
Personnel dosimeters, 440-441, 142f 77-78, 78t
440f gamma-ray energy and, 147 secondary, 77, 78t, 141-142
badge, 440-441, 440f iodine escape peak and, 144 transmission measurements for,
pocket, 89-90, 90f, 440-441 nonlinearity and, 148 78-79, 78f
ring, 440-441, 440f photon attenuation and, 79, ultraviolet
Pertechnetate, 99mTc-labeled, 4f, 51, 80f-81f in Geiger-Müller counter, 92,
60, 480 in scintillation detectors, 102, 94
PET. See Positron emission 103 in scintillation detector,
tomography (PET). Photoelectrons, 74 99-100
PET/CT, 4-5, 330, 354-356 in photomultiplier tubes, 98, of visible light. See also
advantages of, 332-334, 356-357 100f Scintillation detectors.
applications of energy resolution and, 149-150 in Geiger-Müller counter, 92
clinical, 355-356, 356f Photoemissive substance, 98 spectrum of, 8, 8f
small-animal, 356, 356f Photofraction Photopeak, 142, 143, 143f, 144,
attenuation correction in, 348, definition of, 159 144f, 145-146, 145f, 146f
356-360 for NaI(Tl) detectors, 159, 160f baseline shift and, 146, 147r
image segmentation in, 357 in NaI(Tl) well counters, 174, cascaded gamma emissions and,
scanners in 175f 162, 163
clinical, 354-356, 354f-355f Photomultiplier (PM) tubes, 98-99, coincidence detection and, 163
small animal, 356, 356f 98f, 100f Compton-scattered gamma rays
scatter correction in, 337, of gamma cameras. See Gamma in, 163-164, 164f
356-360 cameras: photomultiplier crystal size and, 145, 146f
PET/MRI, 345-346, 360-361, 361f tubes of. definition of, 142
Phantoms of liquid scintillation counters, gamma-ray energy and, 147
for absorbed fraction method, 104, 153, 182-183, 206f photofraction in, 159, 160f
409, 414, 414f, 415t noise reduction and, 184 for NaI(Tl) well counter, 174,
bar, 235, 235f magnetic fields and, 197 175f
modular transfer functions of NaI(Tl) detectors, 101-102, pulse pile-up and, 146, 147f
and, 237-238 101f-102f selection of, for gamma cameras,
computer-simulation, 258f, 263, energy resolution and, 148, 200, 201f
264f, 265, 265f, 266f, 267f 149, 150 tail of, with CZT detector, 151
in contrast-detail studies, of NaI(Tl) well detectors, 173, width of, 149
247-248, 248f, 249f 174f, 178, 180 window fraction for, 170
Cristy-Eckerman, 414, 414f, of PET detectors, 324, 325-326, Photopeak detection efficiency
415t 325f, 326f, 330, 331, 332 of gamma camera, 211, 212f
dosimetry calculations based on, data corrections and, 335 intrinsic, of NaI(Tl) well counter,
414, 414f, 415, 415t in PET/MRI, 360 174, 176f
in ROC studies, 248 power supply for, 122 Picture archival communications
Rollo, 247-248, 248f in SPECT/CT, 351 systems (PACs), 367, 378
scatter correction based on, 298 in SPECT/MRI, 360 Pile-up. See Pulse pile-up.
spatial resolution and, 234-235, Photons, 8. See also Annihilation Pincushion distortion, 199-200,
234f-235f photons; Bremsstrahlung; 215f-216f, 216-217
with bar phantom, 235, 235f, Gamma rays; X rays. Pinhole collimators, 202-203, 202f,
237-238 annihilation, 25, 25f 225-228
detection efficiency in, 166 after pair production, 77, 77f advantages and limitations of,
SPECT images of, 289-290, 291, in annihilation coincidence 228
298, 298f, 299 detection, 307-308, collimator resolution of, 225-228,
volume sensitivity measurement 308f-309f 226f-227f
with, 301-302 interactions with matter, 74-78 source-to-collimator distance
PHAs. See Pulse-height analyzers in radiation detectors, 142, and, 228, 228f
(PHAs). 144, 145-146, 145f, 149, efficiency of, 225-228,
Phelps, M.E., 4 150, 151, 159 226f-227f
Phosphorescence of scintillator shielding for, 437 performance characteristics of,
solution, 184, 185 attenuation of. See Attenuation. 225-228, 226f-227f
Phosphorus-32, 58t, 452 backscattered, 75, 166-167, 167f in reconstruction tomography,
Phoswich detectors, 326, 327f bremsstrahlung. See 274-275
Photocathodes, 98-99, 98f Bremsstrahlung. in small-animal SPECT, 284-285,
temperature and, 184 coherent scattering of, 77 284f-286f, 302
Photodiodes, silicon, 99-100 Compton scattering of. See Pixel depth, 365
avalanche, 100 Compton scattering. Pixelation effects, 234
in PET systems, 332 energies of, 8 Pixels, 196-197
in compact gamma camera, 207 energy deposition by, 64, 77-78, addresses of, 364, 364f
in intraoperative gamma probe, 77f, 78t definition of, 364
193, 193f in radiation detectors, 141, display of
Photoelectric effect, 74, 74f, 77-78, 142f brightness levels in, 364
78t interactions with matter, 74-78, colors in, 367
in lead shielding, 144 78t on flat-panel display, 124
in photomultiplier tube, 98, 98f, pair production and. See Pair of gamma camera image,
148 production. 196-197, 218
Index 513

Pixels (Continued) Positron emission tomography Positron emission tomography


in grayscale displays, 367, (PET) (Continued) (PET) (Continued)
368f advantages of, 253 point source response profile in,
in image smoothing, 373, 375f annihilation coincidence 319
number of, matrix size and, detection in. See Annihilation principles of, 307-324
365-366, 366f coincidence detection (ACD). quantification of, 337, 340, 371f,
of parametric image, 372 applications of 372
size of clinical, 5t, 341-342, 341f-342f radiopharmaceuticals for, 60
full width at half maximum research, 342, 342f receptor binding and, 402-403,
and, 234 attenuation correction in, 402f
spatial resolution and, 365-366 338-339, 338f regions of interest in, 372-373,
of tomographic image, 257 binding potential and, 403 372f, 374f
in iterative reconstruction, 273, in brain imaging, 330-331, 330f research applications of, 5
275 in breast imaging, 330-331, scintillation detectors for, 104,
SNR of, 267, 268, 269 331f 316, 324-326, 325f, 326f,
in SPECT, 279, 281, 284, 286f, calibration factor for, 339-340 327f, 328, 330-332, 337
289f, 293-294, 296, 297, coincidence counting rates in, spatial resolution and,
299, 301 322-324, 322f, 329-330 314-315, 314f
voxels vs., 364 random, 322-323, 322f, sensitivity of, 308, 319-322
Planar single-photon imaging, 1. 329-330 for 2-D systems, 321-322, 332
See also Gamma cameras. correction for, 336-337 for 3-D systems, 321-322,
contrast in, 241, 243f estimation of, 336, 340 332-334
selected procedures with, 5t scattered, 322-324, 322f, in small animal imaging,
structured noise in, 243 329-330 331-332, 331f, 342, 342f
Plastic scintillators, 101, 101t correction for, 337-338 spatial resolution in, 310, 311f,
pulse signals of, 105, 105f true, 322-323, 322f 312-319, 312f, 313f, 313t,
Plateau curves, for Geiger-Müller coincidence logic in, 307 314f, 315f, 317f, 318f
counters, 94, 95f combined with CT scanner, 330 with block detector, 324-325
PM tubes. See Photomultiplier contrast in, 241-242, 253, 336, with cross-plane data, 332
(PM) tubes. 337, 346 cut-off frequency and, 319
Pocket dosimeters, 89-90, 90f, co-registered images in, 375-376, depth-of-interaction effect in,
440-441 377f 316-318
Point-spread function (PSF), 224f, current practice of, 4-5 detectors and, 310-312,
235, 263 data acquisition for, 332-335 311f-312f
collimator, 222-223, 222f, 224f, cross-plane, 332, 333f with gamma camera, 329-330
225 2-D, 321-322, 332, 333f geometric efficiency and, 321
convolution as, 489, 492 3-D, 321-322, 332-334, 333f positron physics and, 312-316,
modular transfer function and, for dynamic studies, 335 313f-315f, 313t
238 list-mode, 335 protocols for, 340-341
in resolution evaluation, 235 for whole-body scans, 335 reconstruction filters and, 319
scattering and, 297 data correction for, 335-340 sampling and, 318-319, 318f
in SPECT, 301 for attenuation, 338-339, 338f with specialized systems,
Poisson distribution, 126-128, for dead time, 339 330
127f normalization in, 335-336 system resolution in, 314-315
statistical tests and, 133, 134, for random coincidences, systems for, 324-332
135, 149 336-337 detectors
Pole zero cancellation, 112-113 for scattered radiation, arrays of, 326-328
POPOP [1,4-di-(2,5-phenyloxazole) 337-338 block, 324-325, 325f, 327f
benzene], 105 dead time in, 339 detection efficiency of, 321,
Position logic circuits, 196 dynamic studies with, 335 322t
Positive ion cyclotron, 48, 48f, 49 of receptor binding, 402 geometric efficiency of,
Positron (β+, γ) emission, 25, 26 with FDG, 341-342, 342f 319-322
Positron (β+) emission, 25, 25f, 26 Ge-68 rod source in, 328f, 329, modified block, 325-326,
competitive with EC, 26, 26f 338 326f-327f
line of stability and, 28 historical development of, 4 multicoincidence operation
Positron (β+) emitters image reconstruction protocols of, 320-321
cyclotron-produced, 49, 50, 50t for, 340-341 phoswich, 326, 327f
historical use of, 2, 313t for low-contrast imaging, quadrant-sharing, 325-326,
particle ranges of, 73-74, 73t 241-242 326f
properties of, 313t multi-slice images in, 262-263, types of, 324-332
radiopharmaceuticals labeled 321-322, 332-334 in whole-body systems,
with, 60-61 in neurodegenerative diseases, 326-330, 327f
safe handling of, 437, 441 341-342, 342f gamma cameras, 327f,
scintillation detectors for, 105, noise equivalent counting rates 329-330
182-183 and, 340-341, 341f performance characteristics of,
Positron decay, 25-26, 25f noncolinearity in, 314, 315f, 316 340-341
Positron emission tomography in oncology, 341 scanners, 314, 326-330, 327f
(PET), 253, 307-343. See also overview of, 1 multi-ring, 321-322, 332-334,
Tomographic imaging. parametric imaging with, 400, 333f
absolute quantification in, 401f septa of, 323, 324, 328f, 329,
339-340 partial-volume effects in, 340 332, 334
514 Index

Positron emission tomography Probes (Continued) PTSM [pyruvaldehyde bis(N-methy


(PET) (Continued) in oncology, 192-193 lthiosemithiocarbazone)], 381t,
specialized, 330-332, radiation detectors for, 193 394
330f-331f Production rate, 56 Pulse mode, 107
SPECT systems as, 307, 324 Projection profiles, 254, 254f, 255, Pulse pile-up, 112-113, 112f, 146,
in whole-body systems, 255f, 256f 147f
326-330, 327f-328f attenuation correction for, 293, dead time losses and, 168
3-D reconstruction, 275-276, 294 with gamma cameras, 213-216
276f backprojection and, 256, 257, correction of, 214-216
time-of-flight, 309-310, 310f 257f, 259, 259f, 260, 261f, counting losses and, 213-214,
timing resolution in, 307-308 263, 267 213f
tomographic reconstruction in, cone-beam data and, 274 dead time losses and, 213-214
253, 254, 256. See also fan-beam data and, 273 image distortion and, 214-216,
Tomographic imaging. iterative reconstruction 214f-215f
three-dimensional, 334 algorithms and, 270f, 272 in PET, 339
whole-body studies with, 335, scatter component in, 298 in pulse-height spectrometry,
340, 340f from transmission scan, 296 146, 147f
with x-ray CT. See PET/CT. Projection slice theorem pulse-tail extrapolation for,
Positron probes, 194 definition of, 259 214-216, 215f
Positronium, 25 in direct Fourier transform Pulse resolving time. See Dead
Positron-labeled reconstruction, 258-260 time/dead time losses.
radiopharmaceuticals, 60-61 in filtered backprojection, Pulse shaping
Positrons. See also Charged 260-262 by amplifier, 111-112, 112f
particles; Pair production. Projection tools, 369-371, 371f by preamplifier, 107-108, 108t
in annihilation coincidence Projections, 254, 254f in rate meter, 120
detection Proliferation, tracers for, 381t Pulse signal of various radiation
non-colinearity of, 314, 315f, Prompt coincidences, 322-324, 322f, detectors, 107, 108t
316 340 Pulse-height analyzers (PHAs),
ranges of, 307, 312-315, 313f, Prompt gamma rays, 45-46 113-118, 114f, 115f, 116f, 117f
314f, 315f, 316 Propagation of errors, 128-130 dead time losses and, 168
spatial resolution and, Proportional counters, 91-92, 92f energy-selective counting with,
312-316, 313f-315f, 313t backscatter and, 166-167, 167f 156, 158, 159, 160f
definition of, 25 dead times of, 168 of gamma camera, 142-147, 143f,
interactions with matter, 63 intrinsic efficiency of, 158-159 145f, 146f, 147f, 151
radionuclides emitting, 312, limitations of, 166-167 energy resolution and, 212,
313t in PET systems, 332 212f, 213
labeling with, 60-61 power supply for, 122 image corrections with, 218
ranges of pulse signals of, 108t image contrast and, 240, 241f
in ACD, 307, 312-315, 313f, pulse-height spectrometry with, multichannel, 113, 116-118, 116f
314f, 315f, 316 153-154 of liquid scintillation counters,
average, 73 self-absorption and, 166-167, 184
effective, 313, 313f 167f of NaI(Tl) well counters, 173,
Postinjection transmission scans, for β-emitting radionuclides, 180f, 181
338-339 167 of semiconductor detectors,
Potassium-40 as gas flow counters, 190 190
background radiation from, Protein synthesis, tracers for, as nonparalyzable systems, 168
184-185 381t object scatter and, 144, 145, 147
total-body potassium and, 194 Protein-binding assays, 173, in PET, 337
Power supplies, high-voltage, 189 principles and design of, 113,
122 Proton deficient nuclides, 17, 28 114f
PPO (2,5-diphenyloxazole), 105, Protons, 13-14, 13t. See also processor chip for, 363
187 Charged particles. single-channel, 113-116, 114f
Preamplifiers, 107-110, 108f arrangement of, 14-15 dead times of, 168
of gamma camera, 219 in cyclotron, 48, 49f NaI(Tl) well counters and, 173,
Precalibrated radionuclides, 35 decay modes involving. See also 178, 181
Precise measurement, 126 specific modes. timing methods for, 114-116,
Precursors, radionuclide, 58 β+ emission as, 25 115f
Pregnancy β− emission as, 20 spectral blurring in, 144,
dose limits and, 433, 434t electron capture as, 24 148-151
internal dosimetry and, 414 energy levels of, 10f, 14-15 window fractions and, 170-171
occupational exposure in, 437 equivalent dose of, 408t Pulse-height spectrometry, 116f,
Primary ionization events, 141, forces on, 14-15 117, 141-154
142f. See also Ionization. nuclear stability and, 14-18, dead time losses in, 168, 170
Primary solute, 105, 106 16f-17f with liquid scintillation counters,
Primary spectrum, 147f, 152f number of, 13 141, 153, 153f, 184, 185f
Probability matrix, 286, 296 as particulate radiation, 8 multichannel analyzer in, 113,
Probable error, 127 properties of, 13, 13t 116-118, 116f, 141
Probes in shell model, 14 with NaI(Tl) detectors, 142-151
β-particle, 194 Pseudocolor scale, 367, 368f actual spectrum for, 143-145,
γ-ray PSF. See Point-spread function 143f-147f
miniature, 192-194, 193f (PSF). counting rate and, 146, 147f
Index 515

Pulse-height spectrometry Radiation (Continued) Radiation dose (Continued)


(Continued) Cerenkov, 68-70 average, 414, 424, 427,
detector size and, 145-146, characteristic, 10-13, 11f, 12t 428
146f definition of, 8 estimation of, 434
energy linearity and, 147-148, GM counters for, 92 radiation safety and, 427, 428,
148f electromagnetic, 8-9, 66 429t, 434t
energy resolution and, 148-151, emission of. See Emissions. scaling factor for, 430, 430f
149f. See also Energy forms of, 8, 8f units for, 428-431
resolution. ionizing, 63 air kerma and, 434-436.
gamma-ray energy effects in, biologic effects of, 78, 427-428 See also Air kerma.
146-147, 147f definition of, 63, 87 in bone, 434
ideal spectrum for, 142-143, secondary, 74 calculation of. See Absorbed
143f long-term health effects of, 427 fraction (MIRD) method;
primary spectrum for, 147f particulate, 8 Radiation dosimetry,
scatter spectrum for, 147f penetrating, 82-83 internal.
principles of, 141-142 scattered. See Scattered choice of radionuclide and, 57
with proportional counters, radiation. contaminants and, 58
153-154 Radiation biology, 407 cumulated activity and, 409-410,
quality assurance checks of, 172 Radiation counting rate. See 424
with semiconductor detectors, Counting rates. definition of, 407
151-153, 151f-152f Radiation counting systems. See distance from source and,
two-energy window analysis and, Counting systems. 435-436
184 Radiation detectors, 87-106, 122. dose calibrators for, 89, 89f,
Pulse-resolving time. See Dead See also Gas-filled detectors; 189-190, 437
time/dead time losses. Scintillation detectors; effective, 417, 425t, 429t
Pulse-tail extrapolation, 214-216, Semiconductor detectors; from background radiation,
215f specific types. 427
Purity amplifiers for, 110-113 equivalent, 407-408, 429t
chemical, 59 for annihilation coincidence air kerma and, 434-436
radiochemical, 59 detection, 309-310 distance from source and,
radionuclidic, 58 coincidence detection and, 435-436
semiconductor detectors of, 162-163 half-life and, 57, 58
190, 191 coincidence units and, 121-122 information sources for, 422
PXE (phenylxylethane), 105, 187 dead areas of, 267f. See also internal. See also Radiation
Dead time/dead time losses. dosimetry, internal.
digital counters and, 119-121 avoidance of, 440-441
Q efficiency of, 155-166. See also limits on, 431-432, 432t, 433,
Q. See Transition energy (Q). Detection efficiency. 434t
Quadrant sharing, 325-326, 326f energy deposition in, 91, 141, mean, per unit cumulated
Quality assurance, 171-172. See 142 activity, 415-417
also Image quality. high-voltage power supplies for, for F-18, 422t-423t
for gamma cameras, 228-231 122 for I-131, 420t-421t
for Nal(Tl) well counters, 178 instrumentation for, 107-124 for Tc-99m, 418t-419t
for radiopharmaceuticals, 182 nuclear instrument modules and, occupational limits for, 431-433,
for SPECT, 302-303 122-123 434t. See also Radiation
Quanta, 8 as paralyzable systems, 168-169, safety.
Quantities, physical, 7-8 168f-169f scaling factor for, 430, 430f
Quantum efficiency, 98, 99f phoswich, 326, 327f surface, 409
Quantum mottle, 243 preamplifiers in, 107-110, 108f tissue weighting factors for, 417,
Quantum numbers, 9, 10f, 14 in pulse mode, 107 425t
Quench correction, 106 pulse output of, 107, 108t units of, 407-408, 408t, 428,
automatic external pulse-height analyzers and, 429-430
standardization method for, 113-118, 114f whole-body (total-body), 417,
186-187, 187f quadrant-sharing, 325-326, 425t
channel ratio method for, 186 326f Radiation dose-modifying factors,
internal standardization method quality assurance for, 171-172 428
for, 186, 186f rate meters and, 119-121 Radiation dosimetry, internal, 2,
for liquid scintillation counters, signal output of, 108t 407-425. See also Organs.
185-187, 186f-187f spectral blurring with, 144, absorbed fraction in, 413-414,
Quenching, 106 148-151 414f
Quenching gases, 93-94 thickness of specific, 414-415
depth of interaction and, anatomic models for, 409, 414,
316-317, 317f 414f, 415t, 424. See also
R intrinsic spatial resolution and, Phantoms.
Rad, 407 210, 211f basic procedure in, 408-409,
Radiation, 8-9. See also Charged time-to-amplitude converters 409f
particles; Photons. and, 118-119, 119f classic method in, 407
accidental ingestion of, 437-438 Radiation dose, 407-408. See also cumulated activity in, 409-412,
background Radiation safety. 410f, 411f
effective dose from, 431 absorbed, 432-435, 433t average absorbed dose and,
sources of, 177-178, 431 air kerma and, 434, 438-439 414, 424, 427, 428
516 Index

Radiation dosimetry, internal Radiation safety (Continued) Radioactive disintegration, 16


(Continued) material handling and, 433-439 Radioactive gases, safety measures
mean dose per unit of, 415-417 ALARA concept and, 433-434 for, 438
for F-18, 422t-423t dose reduction from external Radioactive spills, handling of,
for I-131, 420t-421t sources, 434-435 438
for Tc-99m, 418t-419t monitoring and. See Radiation Radioactive tracers, stability of,
problems in determination of, monitoring. 19-20
424 NCRP recommendations for, 431, Radioactive waste disposal, 439
dose in. See Radiation dose. 433, 434t Radioactivity. See also Radioactive
effective dose equivalent in, 417, quantities and units in, 428-431, decay.
425t, 427, 429t, 478-479 429t, 430f discovery of, 2, 9
effective dose in, 417, 425t, 427, for radioactive gases, 438 natural, as background, 177, 427,
429t, 433t shielding and. See Shielding. 432
equilibrium absorbed dose sources of exposure and, 427 Radioactivity, from internal
constant in, 412-413 spills and, 437 sources, 437-438. See also
future directions for, 424-425 TDS rules and, 436-437 Radiation dosimetry, internal.
information sources for, 422 waste disposal and, 439 Radiobiology, 407
limitations of MIRD method in, Radioactive decay, 19-29. See also Radiochemical purity, 59
424-425 Activity; Radionuclides. Radioimmunoassays, 173, 182, 189
MIRD Committee and, 407, 414 by alpha emission, 26-28 Radioisotope, 19. See also Isotopes;
quantities and units in, 407-408, average lifetime and, 34 Radionuclides.
408t chemical properties and, 19-20 Radioligands, 401
reciprocity theorem in, 414-415 decay constant in, 31, 32, 33, 34 Radionuclide imaging, 195-196. See
therapeutic applications of, decay factors in, 32-33, 33f also Gamma cameras;
416-417, 428 approximation to, 32, 32f, 33 Tomographic imaging.
Radiation energy losses, 64-65, determination of, 34-35 Radionuclides, 19
66f-67f effective, 35-37, 36f Radionuclides. See also
Radiation hormesis, 431 tables of, 34, 34t Radiopharmaceuticals.
Radiation losses, 64-66, 67, 67f, 68 decay scheme diagrams for, activity of. See Activity.
Radiation monitoring, 439-441, 20-21, 20f average lifetime of, 34, 82
440f. See also Radiation safety; of important radionuclides, cumulated activity and, 410,
Survey meters. 449-475 411f
laboratory monitors for, 440 decay series and, 27-28, 27f as calibration standards,
personnel dosimeters for, 89-90, definition of, 19 164-166, 165t
90f, 440-441, 440f general concepts of, 19 carrier-free, 37-38
survey meters for, 89, 89f, half-life and, 33-34 chemical properties of, 58
439-440 image-free decay corrections and, Compton-scattered photons from,
wipe testing for, 441 35-36, 36f 75-76, 75t
Radiation safety, 2, 427-442. by internal conversion, 22-24 contaminants in
See also Health physics. isobaric, 20 detection of, 39
air kerma and, 428-431, isotope effect and, 20 effects of, 58
434-435 line of stability and, 16, 16f, 28 in generator systems, 53, 58
airborne materials and, 432, mass-energy conversion in, 19 decay of. See Radioactive decay.
432t, 438 transition energy and, 19, 20, definition of, 19
background radiation and, 427 20f, 21, 21f, 24 dose calculations for, 424-425
biologic effects and, 427-428 of mixed samples, 38-42, 39f dose-rate constants of, 434, 435t
decontamination in, 439 parent-daughter, 39-42. See also emissions from, 57, 58t
distance from source and, Parent-daughter decay. fission fragments of, 28, 44-45,
435-436 of unrelated species, 38-39, 45f
dose-modifying factors and, 428 39f half-life of, 33-35, 57, 58t
exposure and, 428-431 modes of, 20-28. See also specific cumulated activity and,
general public and, 431, 432, modes. 410-412
433t, 434t alpha-particle emission as, information sources for, 28, 29f
government regulations for, 26-28 line of stability and, 16, 16f, 28
431-433 by β+, γ emission, 25-26 medically important, 57-59, 58t
advisory boards and, 433 by β , γ emission, 21-22, 22f

characteristics of, 57-59, 58t,
for airborne radioactivity, 432, by β+ emission, 26-28 449-475
432t-433t by β− emission, 20-21f cyclotron-produced, 49-50, 50t
for dose limits, 431-432, competitive β+ and EC as, 26 generator-produced, 3, 24,
435-436 EC, 24-25 50-53, 51f-52f, 51t
Nuclear Regulatory (EC, γ), 24-25 neutron-activated, 45-47, 46t
Commission (NRC) and, internal conversion as, 22-23, metastable, separation of, 24
431, 432, 433 23f naturally occurring, 427
for record keeping, 432-433 by isomeric transition, 22-24 neutron-activated, 45-47, 46t
for restricted and unrestricted nuclear fission, 28 positron-emitting, 312, 313t
areas, 431 overview of, 19 labeling with, 60-61
for sewage disposal, 432, positron emission, 25-26, 25f precalibrated, 35
433t rate of, 31 production of, 43-61
information sources for, 427-428 series, 27-28, 27f in accelerators, 47-50, 49f-51f,
for internal sources, 437-438 transition energy in, 19, 20, 20f, 50t
laboratory design and, 438 21, 21f, 22, 24 charged-particle, 47, 50t
Index 517

Radionuclides (Continued) Radiotracer(s). See Radionuclides; Reconstruction filters (Continued)


activity buildup and decay in, Radiopharmaceuticals; Tracer Shepp-Logan, 261, 262f, 263-265,
56 kinetic modeling. 264f
in cyclotrons, 47-50, 50t Radium-226, 27-28 spatial resolution and, 267, 269
equations for, 53-57 curies and, 32 in PET systems, 319
in generators, 3, 24, 50-53, Rainbow scale, 367, 368f in SPECT systems, 302,
51f-52f, 51t Ramp converters, 117-118, 117f 303f
contaminants and, 53, 58 Ramp filter, 260-261, 261f-262f Reconstruction tomography
safe handling of, 433-434 image quality and, 268, 269, backprojection in, 256-258,
historical perspective on, 2 301 266f
in reactors, 43-47, 46t in SPECT, 301 collimators in
properties of, 19, 57-59, 58t Random coincidences, 322-323, cone-beam, 274-275, 274f
purity of, 58 322f, 329-330 fan-beam, 273-274, 274f-275f
specific activity of, 57-58 corrections for, 336-337 parallel-hole, 273
for transmission scans estimation of, 336, 340 cone-beam, 273-275, 274f
in PET, 338, 339, 342 with gamma camera, 332 coordinate systems for, 255,
in SPECT, 294-295, 296, 300f septa and, 332 256f
Radionuclidic purity, 58 Random error, 125-126, 128 direct Fourier transform,
semiconductor detectors of, statistical significance and, 130, 258-260, 259f-260f
190-191 131, 134 emission CT in, 253
Radiopharmaceuticals, 1, 2, 5t, Random noise. See Statistical expectation-maximization
59-61, 379, 380 noise. reconstruction in, 272-273
analog, 60, 61, 382 Range of charged particles, 70-74, fan-beam, 273-276, 274f-275f
applications of, 5t, 60t 70f, 72f-73f, 73t Feldkamp algorithm in, 275
therapeutic, 61 average, 73-74 filtered backprojection in,
approval process for, 2, 424 effective, 313, 313f 260-262
assays of extrapolated, 71-74, 72f-73f image quality in, 263-270
semiconductor detectors for, mean, 70 coverage and consistency
191 Range straggling, 70, 70f requirements and, 266
well counters for, 182 Rate constants, 384-385, 384f, 385f, Nyquist frequency and, 263
biologic half-life of, 59, 417 390-391, 390f sampling and, 263-265
chemical properties of, 19-20 of enzymatic reaction, 396 iterative reconstruction
in clinical nuclear medicine, 61 Rate detectors, coincidence units algorithms in, 262, 270-273.
commonly used, 5t, 60t, 381t and, 121-122 See also Iterative
cumulated activity of. Rate meter time constant, 120 reconstruction.
See Cumulated activity. Rate meters, 119-121 multi-slice imaging in, 262-263
definition of, 57 analog, 120-121, 120f noise in, 266-268
diffusible, 394-395 logarithmic, 121, 121f overview of, 254-256
distribution of, 409 Rayleigh scattering, 77 in PET, 319, 340-341
dose estimates for, 425, RBCs. See Red blood cells 3-D, 275-276, 276f
478-479 (RBCs). projection profiles for, 254-256,
dosimetry for, 2 RC pulse shaping, 111-112, 112f 254f-256f
examples of, 5t, 60t, 381t RCs. See Recovery coefficients sinograms and, 255-256, 256f
for FDG-PET, 341-342 (RCs). ramp, 260-261, 262f
ideal, 380 Reaction rate, of enzymatic in SPECT, 301
impurities in, 59 reaction, 396, 398f response characteristics and,
assay of, 191 Reactors, nuclear, 43-44, 44f 254-256, 254f
in 99mTc, 51-53, 58, 85 neutron-capture cross sections in, Shepp-Logan, 261, 262f, 263-265,
labeling strategies for, 59-60 54 264f
as metabolic tracers, 380. principles and design of, 43-44, in SPECT, 301-303
See also Fluorodeoxyglucose 44f transmission CT in, 253
(FDG); Methylene radionuclide production in, 43-44, in x-ray CT, 348-350, 349f
diphosphonate (MDP); 46t Record-keeping regulations,
Oxygen-15. Receiver operating characteristic 432-433
microdosimetry of, 425 (ROC) studies, 248-251, 250f Recovery coefficients (RCs), 299,
nondiffusible, 394 Receptor ligand assays, 401-403, 300f
positron-labeled, 60-61 402f, 404f Rectilinear scanner, 195-196
production of, 57-61 tracers for, 381t Red blood cells (RBCs)
properties of, 59-61 Recoil electrons, 74-76, 75f, 75t, in cardiac studies, 392, 392f
purity of, 59 78t, 144 clumping of, by aluminum ion,
radionuclides for. See pulse-height spectrum and, 142, 53
Radionuclides: medically 144 distribution volume of, 383
important. Reconstruction algorithms. Reference sample technique, 393
safety of, 59 See Tomographic imaging: Reference scan, 295
specific activity of, 59 mathematical techniques in. Regions of interest (ROI), 372-373,
for SPECT, 304-306 Reconstruction filters, 260-261, 372f
99m
Tc-labeled, 60, 60t. 263, 264f kinetic modeling and, 379, 391,
See also Technetium-99m. Hann, 261, 262f 400, 404
therapy applications of, 61, 425 in PET, 319 time-activity curves and, 373,
in tracer kinetic modeling, ramp, 260-261, 261f-262f 374f
380-382, 381t in SPECT, 301 Registration algorithm, 296
518 Index

Regression analysis, 390 Sampling interval. See Angular Scattered radiation (Continued)
linear, 139-140 sampling intervals; Linear in vivo probe measurements
in tracer kinetic modeling, 390 sampling distance. and, 192
Regulations, U.S. government, 431, Sampling theorem, 263, 366, 483, window fraction and, 170
432, 433, 435-437, 436t-437t 484, 485 in SPECT/CT, correction of,
Rem, 408, 430 Saturation region, 87-88, 88f 356-360
Renal function, evaluation of, 379 Saturation specific activity, 56 in x-ray computed tomography
Renkin-Crone model, 387-388, Saturation voltage, 87-88, 88f (CT), 349
388f-389f, 390-391 Scalers, 119-120 Scintillation cameras, timing
Reproducibility of measurements, dead times of, 168 methods for, 114-115
126 Scaler-timers, 119-120, 119f Scintillation detectors, 97-106.
Resistor-capacitor pulse shaping, dead time losses in, 168 See also Radiation
111-112, 112f Scaling factor, for absorbed dose, detectors.
Resolution. See Energy resolution; 427, 430 amplifiers for, 111
Spatial resolution; Timing Scanner, rectilinear, 195-196 for intraoperative gamma probes,
resolution. SCAs. See Single-channel analyzers 194
Resolution volume of SPECT (SCAs). NaI(Tl), 100-103, 101f-103f,
system, 301-302 Scatter coincidences, 322-324, 101t. See also NaI(Tl)
Respiratory motion. See Motion 322f detectors.
blurring. with 3-D data acquisition, 332, for PET systems, 104, 316,
Restricted areas, 431 334 324-326, 325f, 326f, 327f,
radiation levels in, 431-432 with gamma camera, 329-330 328, 330-332, 337
Rest/stress studies, 303 septa and, 329 spatial resolution and,
Ring dosimeters, 440-441, 440f transmission scanning and, 339 314-315, 314f
Ringing artifacts, 486 uncertainty in, 336, 337 photodiodes in, 99-100
Ripple in HV power supply, 122 Scatter correction photomultiplier tubes for, 98-99,
Rise time in PET, 337-338 100f-101f, 101-102
of electronic signal, 111, 112 in SPECT, 296-299, 297f, 298f, with inorganic scintillators,
of scintillator light output, 309 302 100-103, 101f-103f
ROC studies. See Receiver- Scatter window, 298, 298f with organic scintillators,
operating characteristic (ROC) Scattered radiation, 166-167, 167f 105f
studies. background counting rates and, power supplies for, 122
Rod standards, 164, 165f 240-241, 241f preamplifiers for, 109, 110
Roentgen, Wilhelm, 2 backscattered, 75, 143f, 144, principles and design of, 97-98,
Roentgens, 89, 90, 429-430 166-167, 167f 98f
ROI. See Regions of interest beam geometry and, 80, 81, 81f, spectral blurring with, 148
(ROI). 84 time-to-amplitude converters for,
Rollo phantom, 247-248, 248f coherent, 77 118
Root mean square effective range, in SPECT, 297 Scintillators, 97
314 Compton-scattered. See Compton background noise associated
Rose criterion, 244, 269 scattering. with, 184
Rubidium-82, properties of, 58t detection efficiency and, 156, effective atomic number of,
Rutherford, Ernest, 9 163-164 103
Rutherford atomic model, 9 downscattered, 296 energy response of, nonlinear,
in gamma camera, 200, 204, 205, 148, 149-150
209 inorganic, 100-103, 101f, 101t,
S counting losses and, 213-214, 102f, 103f
Safety. See Radiation safety. 213f NaI(Tl), 100-103, 101f-103f,
Safety concerns. See Radiation energy resolution and, 212 101t. See also NaI(Tl)
safety. as multiple scattering, 209, detectors.
Sagittal sections, orientation of, 210 for PET, 316, 322t, 324, 326
369, 370f image contrast and, 240-241, properties of, 101t, 103, 103f
Sample volume 242f selection of, 103
with dose calibrator, 189-190 object scattered, 144-145, 205 organic, 104-106
with NaI(Tl) conventional in PET, 322-323, 322f, 329-330 in liquid solution, 97, 104-106,
detector, 182 correction for, 337-338 106f, 185, 187, 188
with NaI(Tl) well counter, 174, in PET/CT, correction of, 337, plastic, 105, 105f
175-177, 177f 356-360 solid, for flow counter, 187
Samples, dark adaptation of, in pulse-height spectrometry, SD. See Standard deviation (SD).
185 141, 212-213 Secondary electrons, 63, 64f, 66,
Sampling, 263, 264f, 265-266, 265f, Rayleigh scattering and, 77 67f, 78t
481, 482, 484, 487 scatter windows and, 298, 298f in photomultiplier tubes, 98-99,
in annihilation coincidence in SPECT, 286, 296, 299, 302 100f
detection, 318-319, 318f correction of, 296-299 Secondary emission in
performance measurement and, object scatter as photomultiplier tube, 98
301 with gamma camera, 205, Secondary ionization, 63, 64f,
pixel size and, 366 205f 141-142, 142f
preparation for liquid with Ge(Li) detector, 152f charged-particle interactions and,
scintillation counters, 106, with NaI(Tl) detector, 63, 68
187-188 144, 145, 147, 147f, photon interactions and, 77, 78t,
SNR and, 268 152f 141-142
Index 519

Secondary ionizing radiation, Sestamibi, 99mTc-labeled, 5t, 60t Silicon photodiodes, 99-100
74 blood flow measurement with, avalanche, 100, 332
Secondary photons, 77, 78t, 381t in compact gamma camera, 207
141-142 dose estimates for, 480 in gamma-ray probes, 193, 193f
Secondary solute, 105, 106 SPECT imaging with, 5t, 303f, Simple backprojection, 256-258,
Secular equilibrium, 40-41, 40f 304, 304f, 305 266f. See also Reconstruction
Segmentation, image, 357, 375, Sewage, dose limits and, 432, tomography.
377f 433t filtered backprojection vs.,
Self-absorption, 167, 167f Shallow-dose equivalent, 432 260-261
quench correction and, 187 Shell model of nucleus, 14 Simultaneous emission/
Semiconductor detectors, 96-97, Shells, electron, 9-13 transmission scans in PET
97f, 190-192, 191f. See also Shepp-Logan filter, 261, 262f, attenuation correction, 338-339
Radiation detectors. 263-265, 264f Single escape peaks, 144, 145f
advantages of, 96, 190-191, Shielding, 82t, 436-437, 436f Single photon emission computed
240 of α particles, 71 tomography (SPECT), 253,
amplifiers for, 111, 112, 113 background counting rates and, 279-306. See also Tomographic
applications of, 190-192 240 imaging.
cadmium telluride, 96-97 backscatter from, 144 advantages of, 253
cadmium zinc telluride, 96-97 beam geometry and, 82, 83 artifacts in, 286, 302
dead times of, 168 of β emitter, 65, 66f, 437 attenuation in, 285-293,
design of, 97, 97f Bremsstrahlung, 65, 67f 291t-292t
detection efficiency of, 151, 158, of dose calibrators, 189-190, 189f, conjugate counting and, 287
164, 190 437 correction of, 293-294
efficiency of, 158, 190-191 effectiveness of, 437 Chang multiplicative
energy resolution of, 151-152, lead. See Lead shielding. method, 294, 294f, 296,
152f, 190-192, 191f, 240 methods of, 436-437, 436f 297f
for gamma-ray probes, 193 Mu-metal, 99, 101f scatter correction and,
germanium, 96-97 for NaI(Tl) well counters, 296-299, 298f
intraoperative gamma probe as, 177-178 transmission scans and,
193f, 194 natural radioactivity in, 294-296, 295f-297f
limitations of, 96, 102, 190 177-178 attenuation maps for, 294-296,
lithium-drifted, 96-97, 97f pulse pile-up and, 214, 215f 296f
power supplies for, 122 for radiation safety, 436-437, binding potential and, 403
preamplifiers for, 107-110, 436f blank scans in, 295
108f TDS rules and, 436 blood flow measurements with,
pulse signals of, 108t tenth-value thickness and, 82, 393, 395
pulse-height spectrometry with, 82t, 437 in brain imaging, 280-281, 282f,
151-153, 151f-152f of whole-body counting chambers, 304-305, 304f
silicon, 96-97 194 in cancer, 305-306
applications of, 190 x-ray peaks caused by, 144, in cardiac imaging, 281-283, 303,
in scintillation detectors, 151 305f, 306
99-100 Shunt, intracardiac, detection of center of rotation in, 302-303
Semiconductor photodiodes. with labeled microspheres, CERASPECT system for,
See Silicon photodiodes. 394 280-281, 282f
Sensitivity with labeled RBCs, 392 clinical applications of, 303-306,
of collimator SI. See specific ionization (SI). 303f-305f
in gamma camera, 223, 224f, SI units. See Systeme International collimators in
225t, 227, 231 (SI) units. converging, 279-280
lesion detectability and, 246, Sievert (Sv), 408, 417, 428, 430 parallel-hole, 279-281
247f Signal amplification. See combined with x-ray CT. See
of PET, 308, 319-322 Amplifiers; Preamplifiers. SPECT/CT.
with 2-D data acquisition, Signal-to-noise ratio (SNR), 110. contrast in, 241-242, 243f, 297,
321-322, 332 See also Noise. 299
with 3-D data acquisition, amplifier time constant and, co-registered images in, 376
321-322, 332-334 110 current practice of, 4-5
of receiver operating in filtered backprojection, 3-D, 364
characteristic, 249 260-261, 263, 264f detector head orbits in, 280, 280f
Sentinel nodes, gamma-ray probes image smoothing and, 373, distortion sources and, 286
for, 192-193 375f downscatter in, 296
Septal penetration, 205, 220-221 preamplifier location and, 110 dynamic
background counting rates and, in time-of-flight PET, 309, 310 FASTSPECT system for,
240 in tomographic reconstruction, 279-278, 284, 286f
image contrast and, 240-241, 261, 263, 266-268 for receptor binding studies,
242f Silicon detectors, 96-97. See also 402
line-spread function and, Radiation detectors; flood-field uniformity in, 302
240-241, 242f Semiconductor detectors. gamma cameras for, 279-280
pinhole collimators and, 227 energy resolution of, 190 historical development of, 4
Septal thickness in collimators, instrinsic efficiency of, 158 image quality in, 302-303
203, 203f, 211, 220-221, lithium-drifted, 89t, 96-97, image reconstruction in, 301-303
220f-221f 97f imaging speed in, 280-281
Series decay, 27-28, 27f in scintillation detectors, 99 limitations of, 280
520 Index

Single photon emission computed Sinograms, 255-256, 256f, 270f, Spatial resolution (Continued)
tomography (SPECT) 271, 276 phantoms in, 234-235,
(Continued) Skin. See also Organs. 234f-235f
for low-contrast imaging, 241-242 contaminated, 439 point-spread function in, 235
multihead systems for, 280f, dose to, 428, 432, 434, 434t spatial frequency in, 245
281-299 Slant-hole collimators, 203 subjective, 234
multiple detector heads in, 279 Slice thickness, 301 factors affecting, 233-234, 235f
multislice images in, 262-263 in PET, 329 in-plane, 301
performance characteristics of, in SPECT, 301 intrinsic, 234
299-303 Slow neutrons, 43-44 Compton scattering and,
count-rate performance, 302 Small-animal imaging 209-211, 210f-211f
dead time, 302 3-D iterative reconstruction in, detector thickness and, 210,
energy resolution, 302 276 211f
spatial resolution, 301 gamma cameras for, 207-208 full width at half maximum
volume sensitivity, 301-302 PET in, 331-332, 331f, 342, and, 210-211, 221, 225t,
practical implementation of, 342f 229
285-299 PET/CT in, 356, 356f of gamma cameras, 209-211,
attenuation corrections in, SPECT in, 283-285, 286f, 305f, 210f-211f, 219, 234
293-294, 294f 306 bar phantom and, 235, 235f
conjugate counting in, 287, SPECT/CT in, 352-354, 353f in coincidence detection, 310,
288f Smoothing, image, 373, 375f 311f-312f
idealized assumptions and, Sn-113, as calibration standard, measurement of, 229
285-286 165t MTF for, 238
partial-volume effects in, 299, SNR. See Signal-to-noise ratio in PET systems, 329
300f, 373 (SNR). in SPECT systems, 299,
scatter corrections in, 296-299, Sodium-22, 165t 300f
297f, 298f, 302 Sodium iodide, 479t system resolution and, 229
transmission scans in, 294-296, Sodium iodide detectors. See γ-ray energy and, 210, 210f
295f-297f NaI(Tl) detectors. limits on, 209-210
vs. idealized assumptions, 286 Sokoloff deoxyglucose method, 397, measurement of, 210, 229
quality assurance for, 302-303 400 optimum, 210-211
quantitative images in, 372 Somatostatin receptors, 2, 305 system resolution and,
radiopharmaceuticals for, Source organs, 408, 413-414, 415, 210-211, 225, 227
304-306 416, 418t-424t lesion detectability and, 248,
recovery coefficients for, 299, Source-to-collimator distance 249f
300f collimator resolution and, 223, linear sampling distance and,
reference scans in, 295 224f, 227-228, 227f-228f 263, 365-366, 373
regions of interest in, 372-373 modulation transfer function matrix size and, 365-366, 366f
research applications of, 3, 403 and, 238, 238f patient motion and, 234
sensitivity of, 308, 321-322 in SPECT, 284 in PET. See Positron emission
in small-animal imaging, Spatial frequency, 236 tomography (PET): spatial
283-285, 286f, 305f, 306 Fourier transform and, 260f, 263, resolution in.
spatial resolution in, 280, 280f, 481, 483, 484, 485f, 486f, pixel size and, 365-366
281, 283, 284, 288, 289, 298, 487, 492 pixelation effects and, 234
299, 300f, 301 pixel size and, 366 reconstructed, measurement of,
SPECT/CT vs., 351-352 resolution and, 236, 237-238, 301. See also Reconstruction
spillover in, 299 237f, 238, 239f tomography.
SPRINT II system for, 280-281, Spatial frequency space. smoothing filter and, 375f
282f See k-space. in SPECT, 280, 280f, 281, 283,
system alignment in, 302-303 Spatial linearity of gamma 284, 288, 289, 298, 299, 300f,
systems for, 279-281, 280f, 282f, cameras, 229-230 301
283-285, 283f, 284f, 285f, Spatial resolution, 233-239. system resolution as. See System
286f See also Image quality. resolution.
used for PET, 307, 324 axial, 301 tomographic reconstruction and
tomographic reconstruction in, background subtraction and, collimator types and, 273, 279
253, 254, 255, 256 242-243 cutoff frequency and, 263, 264f,
volume sensitivity in, 301-302 collimator, 234. See also 301, 319
Single photon planar imaging, 1, Collimator resolution. with iterative algorithms,
5t, 241, 243, 243f. See also contrast enhancement and, 273-274
Gamma cameras. 242-243 sampling and, 265, 266, 267
Single-channel analyzers (SCAs), cut-off frequency and, 319 transaxial, 301
113-116, 114f, 118, 122 definition of, 209-211, 233-234 in x-ray CT, 349
counting rate and, 146-147 detectability and, 246-247 Specific absorbed fraction,
dead times of, 168 evaluation of, 234 414-415
of NaI(Tl) probe system, 207 full width at half maximum Specific activity, 37-38
NaI(Tl) well counters and, 173, and, 235-236 carrier-free, 37-38
178, 181 line-spread function in, 235 in nuclear medicine, 38, 56
for radiochemical identification, modulation transfer function of radionuclides, 57-58
181 in, 233, 236-237, of radiopharmaceuticals, 59
Singles method for random 237f-238f saturation level of, 56
coincidences, 337 objective, 234-239 Specific ionization (SI), 68, 69f, 71
Index 521

Specificity of receiver operating Statistical analysis (Continued) Survey meters (Continued)


characteristic, 249 Gaussian distribution in, 127f, surface contamination and,
SPECT. See Single photon emission 128 166
computed tomography linear regression in, 139-140 windows of, 166
(SPECT). mean value in, 126, 127, 127t, Sv. See Sievert (Sv).
SPECT/CT, 4-5 128, 135-137 S-value tables
advantages of, 332-334, 356-357 measurement errors and for F-18, 422t-423t
applications of propagation of, 128-130 for I-131, 420t-421t
clinical, 351-352, 353f types of, 125-126 for Tc-99m, 418t-419t
research, 353f, 354 minimum detectable activity in, Synchrocyclotron, 48
attenuation correction in, 131 Syringes
356-360 nuclear counting statistics in, dose rates in contact with,
image segmentation in, 357 126-128 431-432
detectors in outliers in, 138, 138t, 139f shielding for, 436-437, 436f
clinical, 350-352 percentage uncertainty in, 127, System alignment, in SPECT,
small-animal, 352-354 129 302-303
gamma cameras in, 350f, 351, Poisson distribution in, 126-128, System resolution, 265-266
352f 127f of gamma camera, 210-211, 225,
sampling in, 349 products and ratios in, 129 227
scanners for standard deviation in, 128, 134, measurement of, 229
clinical, 350-352, 350f, 135-136 in PET, 314-315
352f-353f of gaussian spectral curve, System sensitivity, for gamma
small-animal, 352-354, 353f 149 cameras, 231
scatter correction in, 356-360 statistical significance in, System volume sensitivity,
vs. SPECT, 351-352 130-131 301-302
SPECT/MRI, 360-361 sums and differences in, 129 Systematic errors, 125
Spectral blurring, 144, 148-151. See tests of significance in, 130-131, Systeme International (SI) units, 7,
also Energy resolution. 133, 135, 136f, 140 32, 407, 408, 409, 429, 443
Spectrometry. See Pulse-height t-test in, 135-137
spectrometry. Statistical errors. See Measurement
Spillover, 299 errors. T
Spills, safety measures for, 438 Statistical noise, 243-247. TAC (time-activity curve). See
Spontaneous fission, 43 See also Contrast-to-noise Time-activity curve (TAC).
Spontaneous radioactive decay, 19 ratio (CNR); Signal-to-noise Target nucleus, in neutron
SPRINT II system, 280-281, 282f ratio (SNR). activation, 46, 47
Sr-85, as calibration standard, in PET image, data corrections Target organs, 408, 409, 409f,
165t and, 340, 341 413-414, 415, 418t-423t
Stable nuclides, 14-18, 16f-17f, 27, in reconstructed image, 261, 263, TCT. See Transmission computed
28 271, 273 tomography (TCT).
Standard deviation (SD), 128, 134, scatter corrections and, TDS rules. See Time, distance,
135-136 298 shielding (TDS) rules.
of gaussian spectral curve, 149 Statistical (random) noise, 243 Technetium-99m
Standards, measurement, 125. See contrast-to-noise ratio and, advantages of, 50-51
also Calibration sources. 243-244 calibration standard for, 164,
Statistical analysis, 125-140. See Statistical tests, 133-140 166, 189
also Measurements. chi square test, 133-134, 134f carrier in sample of, 38
applications of, 130-133 outliers in, 138, 138t, 139f carrier-free, 38
background effects, 131 t-test, 135-137 characteristics of, 462
counting measurement Steady state, 385-386, 386f contaminants in, 53, 58, 190
differences, 130-131 Stopping power, linear, 68 decay factors for, 34, 34t
counting rates, 130-133. See Streak artifacts, 262, 265f, 273 dosimetry of, internal, 416
also Counting rates. Structured noise, 243 energy resolution in detection of,
counting system comparisons, Student t-test, 135-137 150, 151, 152f, 153f, 210,
132 Substates of atom, 9, 9f, 10, 12 211, 212, 231
effects of averaging, 130 Substrates of enzymatic reactions, gamma camera imaging with
estimating counting times, 385, 385f, 387 collimator sensitivity in, 231
132 Subtraction, image, 371, 372f counting rate in, 230
minimum detectable activity, Sulfur-35, 452 energy resolution in, 150, 151,
131 Summation circuits, 184 152f, 153f, 210, 211, 212,
optimal division of counting Surface dose, 409 231
times, 133 Surface rendering, 369-371 image distortion in, 217
chi square test in, 133-134, 134f Surgery, gamma probes for, 193f, intrinsic resolution in, 210,
confidence intervals in, 127, 194 211
127t Survey meters, 439-440 spatial resolution in, 235
constant multipliers in, 129 for β particles, 166-167, 166f historical development of, 2, 4
correlation coefficient in, 139-140 Geiger-Müller counters in, 95-96, mean dose per cumulated
counting system comparison and, 95f, 439 activity for, 415-416,
132 ionization chamber, 89, 89f 418t-419t
dead time losses and, 171 energy response curve for, as metastable state, 15, 24
frequency distributions in, 126, 90-91, 91f production of, 50-53, 51f, 51t
127f, 128 quality checks of, 172 properties of, 58t
522 Index

Technetium-99m (Continued) Time-to-amplitude converters, Tomographic imaging (Continued)


radiopharmaceuticals labeled 118-119, 119f with pinhole collimator,
with Timing resolution, 307-308 274-275
dose estimates for, 479t Timing walks, 115 simple backprojection as,
examples of, 5t, 379, 381t Tissue. See also Organs. 256-258, 257f, 258f
from kits, 60, 60t attenuation coefficient in, 287, in multimodality
RBCs labeled with, 392 287f, 293 instrumentation, 4-5
renal studies with, 379 transmission scan and, 294, overview of, 254-256
for sentinel node detection, 337 terminology of, 254-256
192-193 extraction of tracer by, 386-390, transmission, 253
SPECT imaging with 387f, 388f, 389f types of, 253
attenuation in, 287, 287f, 288f, f factor for, 430, 430f Total-body dose, 417. See also
289f, 290, 290f, 291t positron ranges in, 314 Whole-body imaging.
clinical applications of, 303f, Tissue compartments. See Total-spectrum counting rate,
304, 304f, 305, 305f, 306 Compartmental models. 170
performance measurement in, Tissue response curves, 391 Townsend, David, 354
301 Tissue weighting factors, 417, Townsend avalanche, 91
scattering in, 297, 298, 298f 425t TPF. See True-positive fraction
transmission scan and, 294, TLDs. See Thermoluminescent (TPF).
296, 296f dosimeters (TLDs). Tracer kinetic modeling, 379-405
in syringes, dose rates with, Tomographic imaging, 253-278. See basic concepts of, 379-380,
431-432 also Positron emission 380f
Tenth-value thickness (TVT), 82, tomography (PET); Single blood flow measurement and,
82t, 437 photon emission computed 392-396. See also Blood flow:
Tetrofosmin, 99mTc-labeled, 5t, 304 tomography (SPECT). measurement of.
Thallium-201, 58t, 303, 304, advantages of, 253, 269 cardiac imaging and, 392
474-475 basic concepts of, 254-256, 254f, compartment models for,
Thallium-201 chloride, 5t, 394, 255f, 256f 390-392, 390f-391f
479t contrast in, 241-242, 243f, 269 compartments in, 380-386
Thallium-activated cesium iodide in PET, 241-242, 253, 336, 337, dilution principle and,
[CsI(Tl)], 100, 101t 346 382-383
in compact gamma camera, 207 in SPECT, 241-242, 243f, 297, distribution volume of,
in intraoperative gamma probe, 299 382-383, 384f
193, 193f coordinate systems in, 255-256, flux between, 383-384
Thallium-activated sodium iodide 256f nondisplaceable, 384, 402f
[NaI(Tl)]. See NaI(Tl) digital image format for, 364. See open vs. closed, 382-383
detectors. also Digital image partition coefficient and, 383
Thermal emission noise, 184 processing. of complex systems, 402
Thermal neutrons, 43-44 emission, 253 distribution volume in, 382-383
Thermoluminescent dosimeters historical development of, 4, 253 dynamic imaging and, 392-403
(TLDs), 440, 440f image processing in. See Digital enzyme kinetics and, 396-401
Thompson criteria, 138 image processing. equilibrium models in, 386
Three-dimensional data image quality in. See also extraction in, 386-388, 387f, 388f,
acquisition Sampling; Spatial resolution: 389f, 390-391, 390f
in PET, 332, 333f, 334-335 tomographic reconstruction first-order kinetics in, 384-385
voxels in, 285, 339-340, 364, 367 and. glucose metabolism and,
Three-dimensional iterative consistency requirements and, 396-401
reconstruction, 276 266, 266f rate constants in, 384-385, 384f,
Three-dimensional PET with FT and FBP, 263, 264f, 385f, 390-391, 390f, 396
reconstruction, 275-276, 276f 265-270, 265f, 266f, 267f receptor ligand assays and,
Threshold dose, 427 noise and, 253, 266-270, 267f 401-403, 402f, 404f
Through-hole detectors, 180, image reconstruction in. See steady state in, 385-386, 386f
180f-181f Reconstruction tomography. time-activity curves in, 373, 374f,
Thyroid, uptake of iodine in, 192, limited-angle, 266 379-380, 410, 410f
192f for low-contrast imaging, tracer characteristics in,
Time, distance, shielding (TDS) 241-242 380-382
rules, 436-437 mathematical techniques in. See tracer delivery and, 386-390
Time constants also Fourier transform (FT). blood flow and, 386-387
amplifier, 110-113, 110f, 111f, with cone-beam collimator, clearance and, 388, 389f
114f 274-275, 274f extraction and, 386-388
preamplifier, 107-110, 108f direct Fourier transform as, Fick principle and, 387
rate meter, 120 258-260, 259f Renkin-Crone model for,
Time stamp, 307 with fan-beam collimator, 387-388, 388f-389f,
Time-activity curve (TAC) 273-274, 274f-275f 390-391
cumulated activity and, 409, 410, filtered backprojection as. See transport and, 389-390
410f Filtered backprojection Tracer studies. See also
image processing and, 373, 374f (FBP). Radiopharmaceuticals; Tracer
kinetic modeling and, 379-380, iterative reconstruction as. See kinetic modeling.
385f, 392, 396f, 401 Iterative reconstruction. of blood flow. See Blood flow.
Time-of-flight PET, 309-310, 310f for multiple slices, 262-263 of cardiac function. See Cardiac
Timers, 119-120, 119f for PET, 253, 336, 337 studies.
Index 523

Tracer studies (Continued) Undersampling, 263, 264f, 484, Whole-body imaging


of enzyme kinetics, 396-401, 485f, 486 with gamma camera, 207f
397f, 398f, 401f in annihilation coincidence with PET, 335, 340, 340f
gamma camera for, 197 detection, 318 Wilkinson converters, 117-118,
historical, 2 with iterative algorithms, 273 117f
of receptors, 401-402, 402f pixel size and, 366 Window fractions, dead times and,
Tracers. See Radionuclides; Unidirectional extraction fraction, 170-171, 213, 213f
Radiopharmaceuticals; Tracer 387, 388, 388f, 389f Window width, 113
kinetic modeling. Unified atomic mass unit (u), 7 Windowing, 369
Transaxial direction, 254-255 Uniformity measurements for Windows
Transaxial resolution, 301 gamma cameras, 229-230 coincidence timing, 121, 307
Transaxial sections, orientation of, Unipolar pulse, 112, 113 entrance, 98, 98f, 101-102, 104
369, 370f Units of measure, 7-8 thickness of, 166-167
Transient equilibrium, 41, 41f for radiation, advisory body for, for gamma cameras, 201
Transistors, field-effect, 109 433 optical, 101-102
Transit time, mean, 380, 380f, for radiation dose, 407 scatter, 298, 298f
384 SI, 7, 32 of survey meters, 166
Transition energy (Q), 19, 20, 20f, Universal decay curve, 35, 35f Wipe testing, 441
21, 21f, 22 Unrestricted areas, 431-432 Wrenn, F.R., 2
Transmission computed Upper-level discriminator, 113,
tomography (TCT), 253. See 114f
also Tomographic imaging. Uptake half-time, 410-411 X
Transmission curves Uptake of tracer, 59, 387, 410-411. X rays, 8-9, 8f. See also Photons.
for α particles, 70, 70f See also Extraction. characteristic. See Characteristic
for β particles and electrons, Uranium, in nuclear reactors, x rays.
71-72, 73f 43-44 Compton scattering of, 75, 75t
for photons, 84 Urine samples, counting systems detection of. See Radiation
Transmission factors, 83 for, 105, 173, 182 detectors.
Transmission scans Useful field-of-view (UFOV), 217, discovery of, 2
in PET attenuation correction 229, 230, 231 in electromagnetic spectrum, 8,
postinjection, 338-339 in PET, 319, 320, 320f, 321, 323 8f
with SPECT, 294-296, health physics and, 429, 434-435
295f-297f interactions with matter, 74-78
Transmutation of elements, 20, 21, V passage through matter, 74-78
24, 25, 27 Valid events, 204 pulse-height spectrum and,
Transport Variance, 126-127 142-145
active, 389 Ventricular ejection fraction, radiobiologic effects of, 78
passive, 389-390 calculation of, 99mTc-labeled red scattering of. See Scattered
carrier-mediated diffusion and, cells for, 392, 392f radiation.
389 Vials, counting, 184-185 Xenon-133
Transverse direction, 254-255 Voltage, saturation, 87-88, 88f blood flow measurement with,
Transverse sections, orientation of, Voltage response curve, for 395, 396
369, 370f ionization chambers, 87-88, characteristics of, 472
Trapping methods for blood flow 88f, 91, 92f decay scheme of, 21, 22, 22f, 472
measurement, 393-394 in Geiger-Müller counters, 94f safe handling of, 433t, 433
Triple-head gamma camera, in proportional counters, 92f Xenon, nuclear energy-level
206-207 Voltage-sensitive preamplifiers, diagram for, 15, 15f
True coincidences, 322-323, 322f 107-108, 109f X-ray computed tomography, 253,
True color display, 367 Volume, sample. See Sample 346-350. See also Hybrid
True-positive fraction (TPF), 249, volume. imaging systems.
250f Volume of interest, 373 coherent scattering in, 77
Truncation artifacts, 359, 359f Volume sensitivity in SPECT, in co-registered imaging,
t-test, 135-137 301-302 375-376, 377f
Tumor imaging Voxels, 285, 339-340, 364, 367 image quality in, 263-270
FDG-PET in, 341 with PET. See PET/CT.
gamma-ray probes in, 192-193 reconstruction in, 348-350, 349f
PET/CT in, 355-356, 356f W scanners in, 348, 348f
SPECT in, 305-306 Waste disposal, 439 scattered radiation in, 349
Tungsten septa, 323 Water, radioactivity in, regulation spatial resolution in, 349
Turnover time, 384 of, 431, 432 with SPECT. See SPECT/CT.
TVT. See Tenth-value thickness Wavelength, 8 x-ray detectors in, 347-348, 348f
(TVT). Waveshifters, 89-90 x-ray tubes in, 346-347, 346f-347f
Two-energy window analysis, Weight, atomic, 13 X-ray detectors, 347-348, 348f
184 Weighting factors, 408, 408t, 417, X-ray tubes, 346-347, 346f-347f,
Two-source method, 171, 171f 424, 428, 429t, 435 355
Weiss, S., 2
Well counters. See NaI(Tl) well
U counters. Z
Ultraviolet (UV) photons White blood cells, labeling of, 5t Z. See Atomic number (Z).
in Geiger-Müller counter, 92, 94 Whole-body counters, 194 Zero padding, 489
in scintillation detector, 99-100 Whole-body dose, 417 Zero-crossover timing, 115-116
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