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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. ana