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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
Last digit is the print number:â•… 9â•… 8â•… 7â•… 6â•… 5â•… 4â•… 3â•… 2â•… 1
Preface
vii
viii 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
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 1-2 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
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
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
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
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
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
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)
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
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
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
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
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
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
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)
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
E max
β
= 1.7 MeV
15
7N
3 • Modes of Radioactive Decay 27
18
9F
EC
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
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
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:
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
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
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
0.0
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:
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
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
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)
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
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
Coolant in
Pressure
vessel
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
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
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.)
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
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
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
Particle beam,
flux density
x
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
TABLE 5-4â•…
PHYSICAL PROPERTIES OF RADIONUCLIDES USED IN NUCLEAR MEDICINE STUDIES
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
TABLE 5-5â•…
SOME 99mTc-LABELED RADIOPHARMACEUTICALS PREPARED FROM KITS
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
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
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
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
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
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*
TABLE 6-2â•…
SCATTERED PHOTON AND RECOIL ELECTRON ENERGIES FOR 180-DEGREE COMPTON
SCATTERING INTERACTIONS
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
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
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.
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.
Radiation source
Source
collimator
Absorber
Detector
collimator
Detector
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)
TABLE 6-5â•…
COMPARISON OF PHOTON MEAN FREE PATHS AND MAXIMUM ELECTRON AND
α-PARTICLE RANGES
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
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.
Outside
case
C
Charging
electrode
Insulator
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
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
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
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.
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
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
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
UV
1.00
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
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.
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
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
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
Input Cd Output
Ri
A
Voltage
Rd Ci
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.
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
TD
0 Discriminator output for (2)
t
Time
A
E E (ULD)
(1)
(2) E
E (LLD)
0
Voltage
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),
Memory
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
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
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
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
beam
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 mea�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
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
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
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.
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%)
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
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 dis�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
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
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
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)
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)
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
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
Compton region
Multiple Compton
scattering
Single
Compton
scattering
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
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-
(1600 keV)
Photopeak
Single escape peak
100
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.
80-keV
4
284-keV
in well counter
247 keV
recorded for 111In with a NaI(Tl)
111Cd
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
10
Pulse
pileup 99mTc
5
0
0 40 80 120 160
Window 10
B 20% 203Hg
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
8 Object scatter
2
Relative number of counts
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
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
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
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.
gp 1/2 (1-cos )
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.
10 511/NaI, 0.3
8
511/BGO, 0.6
Minimum distance (cm)
6 140/NaI, 0.9
140/BGO, 1.0
2
0
0.1 1 5
Detector diameter (cm)
FIGURE 11-8 Minimum distance at which simplified equations for detection efficiency (Equations 11-7, 11-9, and
11-10) can be used with errors of less than 10% for 1-cm–thick detectors of different diameters and different combina-
tions of photon energy-detector material. The graph assumes a point source of radiation is placed on the central axis
of the detector. Photon energies are measured in keV. At closer distances, total detection efficiency must be computed
from more-complicated mathematical models (see reference 2).
162 Physics in Nuclear Medicine
efficiency computed using Equations 11-7 and counting is used, such as with the photopeak
11-9 in Equation 11-10 is accurate to within of one or the other γ ray, the pulse from the
10%. At distances closer than the minimum resulting event could be moved out of the
distance, the simplified calculations are inac- selected analyzer window, thereby decreasing
curate by more than 10%, and the more com- the counting rate for that γ ray (see Fig. 10-7).
plicated methods of integral calculus should Note, however, that simultaneous detection
be used to compute the total detection effi- does not occur when there is a significant
ciency, εt.2 delay before the emission of the second γ ray,
Figure 11-8 shows that for detectors having such as in metastable states (see Chapter 3,
a high value of intrinsic efficiency (e.g., BGO Section E).
detector for 140-keV photons, ε ≈ 1), the sim- A full treatment of the problem of coinci-
plified equations can be used with less than dence detection of cascaded emissions is
10% error at relatively close distances. Even beyond the scope of this text. However, the
for the “narrow” detector profile shown in following discussion provides a first-level
Figure 11-7, they can be used within 2╯cm of analysis and an indication of when it must be
the detector. At the other extreme, for a detec- taken into conÂ�sideration. Suppose that two γ
tor having a low value of intrinsic efficiency rays, which we denote as γ1 and γ2, are emitted
[e.g., NaI(Tl) for 511-keV positron annihila- simultaneously, in cascaded fashion, with
tion photons, ε ≈ 0.3], the simplified equations relative frequencies per disintegration η1 and
fail within approximately 10╯cm from a η2. (Note that it is not necessary that η1 = η2;
“narrow” detector and within about 5╯cm from e.g., η2 could be reduced by alternative decay
a “wide” one. pathways that result in nonÂ�detectable emis-
Figure 11-8 provides general guidance as sions, such as internal conversion.) Suppose
to when the simplified equations can be used further that the total (full-spectrum) detec-
for estimating relative detection efficiencies tion efficiencies for the two γ rays are D1 and
on existing systems in a laboratory or for D2, respectively. The probability that a single
preliminary design work for a new detector nuclear disintegration will result in the detec-
system. It also can be used for guidance tion of γ1 is
with other combinations of photon energy
and detector material having dimensions and p1 = η1 D1 (11-11)
values of ε similar to those indicated on the
graph. For more precise design work, it gener- In the absence of coincidence detection, the
ally is preferable to go directly to the methods counting rate recorded for γ1 would be
of integral calculus. Alternatively, Monte
Carlo techniques, using a computer to simu- R1 = p1 × A (11-12)
late photon trajectories and interactions for a
large number of individual photons originat- where A is the source activity in Bq. Simi-
ing from a radioactive source, can be used to larly, in the absence of coincidence detection,
estimate detection efficiency. the counting rate resulting from detection of
γ2 events would be
b. Detection of Simultaneously Emitted
Radiations in Coincidence R2 = p2 × A (11-13)
Yet another complicating factor is that some
radionuclides emit multiple γ rays in cascaded Thus, if one did not account for the possibility
fashion from a single nuclear disintegration. of coincidence detection, the predicted full-
In Figure 3-3, for example, β1 may be followed spectrum counting rate for the source would
by the emission of multiple γ rays (e.g., γ5 and be (R1 + R2).
γ2). In this example and in most other cases Taking into account the possibility of coin-
of cascaded γ emissions, the γ rays are emitted cidence detection, the probability that γ1 and
within a few nanoseconds of each other, which γ2 will be detected simultaneously is
is well within the resolving time of most
detectors (see Section C). If the two γ rays are p12 = η1 D1 × η2 D2 (11-14)
detected simultaneously (coincidence detec-
tion), they are recorded as a single event and the counting rate for simultaneously
having an apparent energy equal to the sum detected events is
of the energies deposited in the detector by
the individual γ rays. If energy-selective R12 = p12 × A (11-15)
11 • Problems in Radiation Detection and Measurement 163
40
20
0
0.02 0.04 0.1 0.2 0.4 1
-ray energy (MeV)
FIGURE 11-9 General effects of γ↜-↜ray energy on the fraction of γ rays scattered or absorbed from a point source 7.5╯cm
deep in tissue and on the fraction of unscattered γ rays and scattered γ rays having sufficient energy to be recorded
with a photopeak window and NaI(Tl) detector. (From Anger HO: Radioisotope cameras. In Hine GJ, editor: Instru-
mentation in Nuclear Medicine, Vol 1. New York, 1967, Academic Press, p 514.)
increasing energy separation between scat- determination usually is made by the com-
tered γ rays and the photopeak (see Fig. mercial supplier of the source.
10-10). With semiconductor detectors (Ge, Si, Detection efficiency can be determined by
CdTe, or CZT), this fraction is much smaller measuring the counting rate recorded from
because of their ability to clearly resolve scat- the calibration source and applying Equation
tered γ rays from the photopeak (see Figs. 11-2. This method generally is satisfactory for
10-14 and 10-15). systems in which a standard measuring con-
Another factor affecting detection efficiency figuration is used and for which the calibra-
is attenuation by the housing material of the tion source accurately simulates the shape
detector. Most γ-ray detectors are fabricated and distribution of the sources usually mea-
with relatively thin entrance windows, such sured with the system. For example, “rod
as thin layers of aluminum, so that their standards” (Fig. 11-10) are used for determin-
attenuation is negligible. Detectors designed ing detection efficiencies of well counters for
for applications involving very-low-energy γ test-tube samples.
rays sometimes are constructed with ultra- Some γ-ray-emitting source materials that
thin (and fragile) entrance windows of alter- are available as calibration standards are
native materials, such as beryllium. However, listed in Table 11-1. Most are quite long-lived.
attenuation can become significant if the Detection efficiencies for short-lived radionu-
detector is used outside the range of its clides can be estimated from measurements
intended applications. Information provided made on a calibration standard having similar
by the manufacturer can be used to estimate emission characteristics. For example, 57Co
this effect in questionable situations. (Eγ = 122╯keV and 136╯keV) frequently is used
Attenuation by the detector housing can be to simulate 99mTc (Eγ = 140╯keV). (Cobalt-57
severe in β-particle counting. This is dis- is sometimes called “mock 99mTc.”) For most
cussed separately in Section B. detection systems, intrinsic efficiencies at
these three energies are virtually identical.
6. Calibration Sources Therefore the detection efficiency per emitted
Detection efficiencies can be determined γ ray as calculated from Equation 11-2 would
experimentally using calibration sources. A be the same for 99mTc and 57Co (assuming the
calibration source is one for which the activity same energy-selective counting conditions
or emission rate is known accurately. This were used, e.g., photopeak counting for both).
FIGURE 11-10 “Rod standards” containing accu-
rately known quantities of different radionuclides
used for determining the detection efficiencies of well
counters. The sources are meant to simulate radioac-
tivity in test tubes.
TABLE 11-1â•…
PROPERTIES OF SOME γ â•›-↜RAY SOURCES USED AS CALIBRATION STANDARDS
Emission
γ -Ray or x-Ray Energy Frequency
Radionuclide Half-Life (keV)* (γ or x raysâ•›/dis)
22
Na 2.60╯yr 511 1.798
1274 0.999
54
Mn 312 d 834.8 1.000
57
Co 272 d 14.4 0.095
122.1 0.856
136.5 0.105
60
Co 5.27╯yr 1173 0.999
1333 1.000
68
Ge 271 d 511 1.780
85
Sr 64.9 d 514 0.980
109
Cd 463 d 22.0 (Kα x ray) 0.842
24.9 (Kβ x ray) 0.178
88.0 0.037
113
Sn 115 d 24.1 (Kα x ray) 0.794
27.3 (Kβ x ray) 0.172
391.7 0.649
129
I 15.7 × 10 ╯yr
6
29.7 (Kα x ray) 0.571
33.6 (Kβ x ray) 0.132
39.6 0.075
137
Cs 30╯yr 32.0 (Kα x ray) 0.057
36.4 (Kβ x ray) 0.013
661.7 0.851
Data adapted from NCRP Report No. 58: A Handbook of Radioactivity Measurements Procedures, ed 2, Bethesda, MD,
1985, National Council on Radiation protection and Measurements.
*Only predominant photon emissions are listed.
166 Physics in Nuclear Medicine
If the detection efficiency is determined on the problems are especially severe with low-
basis of cps/Bq, one must take into account energy β-particle emitters, such as 3H and 14C.
the differing emission frequencies of the two The preferred method for assay of these radio-
radionuclides. Cobalt-57 emits 0.96 γâ•›/dis (γ nuclides is by liquid scintillation counting
rays per disintegration), whereas 99mTc emits techniques (Chapters 7 and 12); however,
0.89 γâ•›/dis (see Appendix C). Therefore the these techniques are not applicable in all situ-
counting rate per Bq of 99mTc would be a factor ations, such as when surveying a bench top
of 0.89/0.96 = 0.93 smaller than that mea- with a survey meter to detect 14C contamina-
sured per Bq of 57Co. This should be applied tion (Chapter 23). A complete discussion of
as a correction factor to the counting rate per the problems arising in detection and assay
Bq determined for 57Co to obtain the counting of β-particle emitters is beyond the scope of
rate per Bq for 99mTc. this book; however, a few of the practical
Calibration sources also are used in phan- problems are described briefly.
toms simulating the human anatomy for esti- A survey meter can be used to detect
mating the detection efficiency for in vivo surface contamination by β-particle emitters
measurement systems; however, the result is provided it has an entrance window suffi-
only as accurate as the phantom and source ciently thin to permit the β particles to enter
distribution are accurate for simulating the the sensitive volume of the detector. Figure
human subject. For example, a 1-cm discrep- 11-11 shows relative counting rate versus
ancy between source depths in the phantom entrance window thickness for two β-emitting
and in the human subject may result in a 10% radionuclides. Efficient detection of low-
to 20% difference in counting rate (see Chapter energy β emitters requires a very thin
12, Section F.1). entrance window, preferably fabricated from
a low-density material. A typical entrance
window for a survey meter designed for 3H
and 14C detection is 0.03-mm-thick Mylar
B. PROBLEMS IN THE DETECTION (~1.3╯mg/cm2 thick).* Mica and beryllium also
AND MEASUREMENT OF β PARTICLES
*Thicknesses of detector windows often are specified in
Because of their relatively short ranges in units of mass/area, for example, mg/cm2. To obtain the
solid materials, β particles create special window thickness, divide by the material density using
detection and measurement problems. These the same units (e.g., mg/cm3).
100
32 max
P (E = 1.7 MeV)
80
Relative counting rate
60
40
20 14C max
(E = 0.156 MeV)
0
0 1 2 3 4 5 6 7 8
2
Detector window thickness (mg/cm )
FIGURE 11-11 Relative counting rate versus detector window thickness for some β-emitting radionuclides. (Adapted
from Quimby EH, Feitelberg S, Gross W: Radioactive Nuclides in Medicine and Biology. Philadelphia, 1970, Lea &
Febiger.)
11 • Problems in Radiation Detection and Measurement 167
100
32 max
Relative counting rate (%)
60
40
20
14C max
(Eβ = 0.156 MeV)
0
1 10 100 1000
Sample thickness (mg/cm2)
FIGURE 11-13 Effect of sample self-absorption on counting rate for two β emitters. (Adapted from Quimby EH,
Feitelberg S, Gross W: Radioactive Nuclides in Medicine and Biology. Philadelphia, 1970, Lea & Febiger.)
168 Physics in Nuclear Medicine
are important, then it is necessary to have liquid scintillation systems have dead times of
sample volumes and sample holders as nearly 0.1–1 µsec.
identical as possible. Other techniques for Dead time losses also occur in pulse-height
dealing with these difficult problems are dis- analyzers, scalers, computer interfaces, and
cussed in reference 3. other components that process pulse signals.
Bremsstrahlung counting can be employed Generally scalers and single-channel analyz-
as an indirect method for detecting β parti- ers have dead times of much less than 1 µsec,
cles using detectors that normally are sensi- whereas multichannel analyzer and computer
tive only to more penetrating radiations such interface dead times are on the order of a few
as x rays and γ rays, for example a NaI(Tl) microseconds. Usually the dead time is given
well counter (Chapter 12). Bremsstrahlung for the counting system as whole; however, if
counting also was employed in some early one of the components has a dead time that
studies using 32P for the detection of brain is long in comparison to the other compo-
tumors and still is used occasionally to map nents, then system dead time is determined
the distribution of 32P-labeled materials by that component.
administered for therapeutic purposes. Brems-
strahlung counting is effective only for rela- 2. Mathematical Models
tively energetic β particles (e.g., 32P, Eβmax = Counting systems usually are classified as
1.7 MeV, but not 14C, Eβmax = 0.156╯MeV) and being of the paralyzable or nonparalyzable
requires perhaps 1000 times greater activity type. A nonparalyzable system is one for
than a γ-ray emitter because of the very low which, if an event occurs during the dead time
efficiency of bremsstrahlung production. τ of a preceding event, then the second event
is simply ignored, with no effect on subse-
quently occurring events (Fig. 11-14). Digital
counters, pulse-height analyzers, and com-
C. DEAD TIME
puter interfaces frequently behave as non-
paralyzable systems. A paralyzable system is
1. Causes of Dead Time one for which each event introduces a dead
Every radiation counting system exhibits a time τ whether or not that event actually is
characteristic dead time or pulse resolving counted. Thus an event occurring during the
time τ that is related to the time required to dead time of a preceding event would not be
process individual detected events. The pulses counted but still would introduce its own dead
produced by a radiation detector have a finite time during which subsequent events could
time duration, such that if a second pulse not be recorded. A paralyzable system may be
occurs before the first has disappeared, the thought of as one with an “extendable” dead
two pulses will overlap to form a single dis- time. Most radiation detectors behave as par-
torted pulse. With GM detectors, the overlap alyzable systems.
may occur in the detector itself, during the Because of dead time losses, the observed
time that the “avalanche charge” is being col- counting rate Ro (cps) is less than the true
lected from a previous pulse, so that the
second pulse does not produce a detectable
output signal and is lost (see Chapter 7, Dead time
counting rate Rt (cps), where the latter is the For a paralyzable system, the observed
counting rate that would be recorded if τ = 0. counting rate rises to a maximum value given
The relationship among Ro, Rt, and τ depends by
on the type of dead time. For nonparalyzable
Romax = 1 / eτ (11-20)
systems,
where e (= 2.718 …) is the base of natural
Ro = Rt /(1 + Rt τ) (11-16) logarithms. Then the observed counting rate
actually decreases with a further increase in
Rt = Ro /(1 − Ro τ) (11-17) true counting rate. This is because additional
events serve only to extend the already long
where τ is given in seconds. If the system has dead time intervals without contributing to
a paralyzable dead time, then additional events in the observed counting
rate. At very high true counting rates, the
Ro = Rt e− Rt τ (11-18) observed counting rate actually approaches
zero. This is called counter paralysis.
There is no analytic equation for Rt as a func- Dead time losses are given by the differ-
tion of Ro for the paralyzable case. ence between observed and true counting
Figure 11-15 shows Ro versus Rt for the rates, Rt – Ro, and percentage losses are given
two types of systems. For a nonparalyzable by
system, the observed counting rate increases
asymptotically toward a maximum value percentage losses = [( Rt − Ro ) / Rt ] × 100%
(11-21)
Romax = 1/τ (11-19)
When the product Rtτ is “small” (0.1), the
At very high true counting rates, greater than percentage losses are “small” (i.e., 10%),
one count per dead time interval, the system and they can be described by the same equa-
simply records one event per dead time inter- tion for both paralyzable and nonparalyzable
val, ignoring all the others that occur during systems
the dead time interval between counted
events. percentage losses ≈ ( Rt τ) × 100% (11-22)
es
ss
lo
Observed counting rate, Ro
No
R omax 1/τ
Nonparalyzable
R omax 1/eτ
Paralyzable
FIGURE 11-15 Observed (Ro) versus true (Rt ) counting rate curves for paralyzable and nonparalyzable systems having
the same dead time value, τ.
170 Physics in Nuclear Medicine
methods (Equation 11-18 and Fig. 11-15) if it fixed-rate pulser connected to the preampli-
is paralyzable. fier of the radiation detector. The pulser
Dead time τ can be determined using the injects pulses of fixed amplitude (usually
two-source method. Two radioactive sources of larger than the photopeak pulses of interest)
similar activities, for which the dead time into the circuitry, and the counting rate for
losses are expected to be 10% to 20%, are these events is monitored using a separate
needed (Fig. 11-16). The counting rate for single-channel analyzer window (Fig. 11-17).
source 1 is determined, R1 (cps). Without dis- The fractional loss of pulser events is equal to
turbing the position of source 1 (so as not to the fractional loss of radiation events because
change the detection efficiency for source 1), both are subject to the same loss mechanisms.
source 2 is placed in position for counting and The observed counting rate Ro from the γ-ray
the counting rate for the two sources together source is corrected by the ratio of true-to-
is determined, R12 (cps). Then source 1 is observed pulser counting rates, Pt╛/↜Po, to
removed (again, without disturbing source 2), obtain the true γ-ray counting rate,
and the counting rate for source 2 alone is
Rt = Ro ( Pt /Po ) (11-26)
determined, R2 (cps). If the system is non-
paralyzable, the dead time τn in seconds is Dead time losses also affect counting sta-
given by tistics. For example, the standard deviation
in observed counts, No, is not given by No if
τ n ≈ ( R1 + R2 − R12 ) /( R12
2
− R12 − R22 ) (11-24)
there are substantial dead time losses.
If the system is paralyzable, then Detailed discussions of counting statistics
with dead time losses are presented in refer-
τ p ≈ [2 R12 /( R1 + R2 )2 ] ln[( R1 + R2 ) / R12 ] ence 7.
(11-25)
R1 R 12 R2
Source
Source
holder Energy or pulse amplitude
FIGURE 11-17 Principles of dead time correction using
Steps 1 2 3 the fixed-rate pulser method. The fractional loss of events
in the pulse peak (from the fixed-rate pulser) is assumed
FIGURE 11-16 Illustration of the steps followed in to equal the fractional losses of radiation events in the
determining dead time by the two-source method. γ -ray photopeak window. SCA, Single-channel analyzer.
172 Physics in Nuclear Medicine
Radiation counting systems are used for a for β particles and low-energy x rays or γ
variety of purposes in nuclear medicine. In rays are presented in Section C later in this
vitro (from Latin, meaning “in glass”) counting chapter. Counting systems based on gas
systems are employed to measure radioactivity detectors and semiconductor detectors are
in tissue, blood, and urine samples; for radio- discussed in Sections D and E, respectively.
immunoassay and competitive protein binding Section F deals with counting systems for in
assay of drugs, hormones, and other biologi- vivo applications, including thyroid uptake,
cally active compounds; and for radionuclide sentinel node detection, and intraoperative
identification, quality control, and radioactiv- probes.
ity assays in radiopharmacy and radiochem-
istry. In vitro counting systems range from
relatively simple, manually operated, single- A. NaI(Tl) WELL COUNTER
sample, single-detector instruments to auto-
mated systems capable of processing hundreds
of samples in a batch with computer process- 1. Detector Characteristics
ing of the resulting data. The detector for a NaI(Tl) well counter is a
In vivo (from Latin, meaning “in the living single crystal of NaI(Tl) with a hole in one
subject”) counting systems are employed for end of the crystal for the insertion of the
measuring radioactivity in human subjects or sample (Fig. 12-1A). Dimensions of some
experimentally in animals. Different in vivo commonly used well detectors are given in
systems are designed for measuring localized Table 12-1. The 4.5-cm diameter × 5-cm long
concenÂ�trations in single organs (e.g., thyroid, crystal with 1.6-cm diameter × 3.8-cm deep
kidney) and for measurements of whole-body well, the standard well-counter detector, is
content of radioactivity. the most frequently used in nuclear medi-
Most nuclear medicine counting systems cine. It is designed for counting of samples in
consist of the following basic components: a standard-size test tubes. Very large well-
detector and high voltage supply, preampli- counter detectors, up to 13-cm diameter ×
fier, amplifier, one or more single-channel 25-cm length, have been employed for count-
analyzers (SCAs) or a multichannel analyzer ing very small quantities of high-energy γ-ray
(MCA) (“data analysis”), and a digital or emitters (e.g., 40K and 137Cs). Most well-
analog scaler-timer, rate meter, or other data counter systems employ 5╯cm or greater
readout device. The majority of systems thickness of lead around the detector to
employ a computer or microprocessor for data reduce background counting levels. A typical
analysis and readout. manually loaded well-counter system is
At present, the most efficient and econom- shown in Figure 12-1B.
ical detector for counting γ-ray emissions* is Light transfer between the NaI(Tl) crystal
a sodium iodide [NaI(Tl)] scintillation detec- and the photomultiplier (PM) tube is less
tor. The characteristics of various NaI(Tl) than optimal with well-type detectors because
counting systems are discussed in Sections A of reflection and scattering of light by the well
and B in this chapter. Scintillation counters surface inside the detector crystal. Energy
resolution is therefore poorer [10% to 15% full
width at half maximum (FWHM) for 137Cs]
*In this chapter the term γâ•›-ray emission also includes
than obtained with optimized NaI(Tl) detec-
other forms of ionizing electromagnetic radiation (e.g., x tor designs (approximately 6% FWHM) (see
rays, bremsstrahlung, and annihilation radiation). Chapter 10, Section B.7).
173
174 Physics in Nuclear Medicine
TABLE 12-1â•…
DIMENSIONS OF TYPICAL NaI(Tl)
WELL-COUNTER DETECTORS
Test tube Crystal Dimensions Well Dimensions
containing (cm) (cm)
sample
Diameter Length Diameter Depth
4.5* 5.0* 1.6* 3.8*
NaI(Tl)
crystal 5.0 5.0 1.6 3.8
7.6 7.6 1.7 5.2
10.0 10.0 3.8 7.0
12.7 12.7 3.8 7.0
*“Standard” well-counter detector.
Lead
shielding
100
0
0.1 1 10
-ray energy (MeV)
FIGURE 12-2 Intrinsic efficiency (γ -ray absorption efficiency, Equation 11-9) vs. γ -ray energy for different NaI(Tl)
well-counter detectors.
100
Wall
thickness
80
Photofraction, fp (%)
(cm)
4.5
60 Crystal size
Diam. Length
2.6 (cm) (cm)
40
12.7 12.7
7.6 7.6
20
1.3 4.5 5.0
0
0.1 1 10
-ray energy (MeV)
FIGURE 12-3 Photofraction versus γ -ray energy for different NaI(Tl) well-counter detectors.
radionuclides in the standard well counter. geometric efficiency of a well counter depends
These values apply to 1-mL samples in stan- on sample positioning. If a small volume of
dard test tubes. radioactive solution of constant activity in a
test tube is diluted progressively by adding
3. Sample Volume Effects water to it, the counting rate recorded from
The fraction of γ rays escaping through the the sample in a standard well detector pro-
hole at the end of the well depends on the gressively decreases, even though total activ-
position of the source in the well. The fraction ity in the sample remains constant (Fig. 12-5).
is only about 7% near the bottom of the well In essence, the geometric efficiency for the
but increases to 50% near the top and is even sample decreases as portions of the activity
larger for sources outside the well. Thus the are displaced to the top of the well.
176 Physics in Nuclear Medicine
100
40 Crystal size
Diam. Length
2.6
(cm) (cm)
20 12.7 12.7
1.3
7.6 7.6
4.5 5.0
0
0.1 1 10
-ray energy (MeV)
FIGURE 12-4 Intrinsic photopeak efficiency vs. γ -ray energy for different NaI(Tl) well-counter detectors.
TABLE 12-2â•…
COUNTING EFFICIENCY FOR 1-mL SAMPLES IN A STANDARD SODIUM IODIDE WELL COUNTER
(ASSUMING ALL PULSES COUNTED)
If the volume of a sample is increased by increase in volume, increases the counting
adding radioactive solution at a constant con� rate by only about 1%.
centration, the counting rate first increases Thus sample volume has significant effects
linearly with sample volume (or activity) but on counting rate with well counters. Sample
the proportionality is lost as the volume volumes should be the same when comparing
approaches and then exceeds the top of the two samples. One technique that is used when
well. Eventually there is little change with adequate sample volumes are available is to
increasing sample volume, although the total fill the test tubes to capacity because with full
activity is increasing (see Fig. 12-5). For test tubes, small differences in total volume
example, an increase of sample volume in a have only minor effects on counting rate
standard test tube from 7 to 8╯mL, a 14% (curve B in Fig. 12-5); however, this requires
12 • Counting Systems 177
5.0
B
4.0
3.0 Constant
concentration
Relative counting rate
2.0
1.0
0.9
0.8 Constant
0.7 total activity
A
0.6
0.5
0 2 4 6 8
Sample volume (mL)
FIGURE 12-5 A, Change in counting rate in a standard NaI(Tl) well counter for a sample of constant activity but
diluted to increasing sample volume in a test tube. B, Change in counting rate with volume for constant
concentration.
that identical test tubes be used for all where R(131I) and R(mock 131I) are the count-
samples, so that the volume of activity inside ing rates recorded in the well counter for
the well itself does not differ between samples. the sample and the calibration standard,
Absorption of γ rays within the sample respectively.
volume or by the walls of the test tube is not Another commonly used mock standard is
57
a major factor except when low-energy Co (129 and 137╯keV) for 99mTc (140╯keV). If
sources, such as 125I (27-35╯keV) are counted. the 57Co is calibrated in “equivalent Bq of
99m
Identical test tubes and carefully prepared Tc,” then Equation 12-2 can be used for
99m
samples of equal volume should be used when Tc calibrations also. If it is calibrated in
comparing samples of these radionuclides. becquerels of 57Co, however, one must correct
for the differing emission frequencies between
4. Assay of Absolute Activity 57
Co and 99mTc (0.962 γ rays/disintegration vs.
A standard NaI(Tl) well counter can be used 0.889 γ rays/disintegration, respectively). The
for assay of absolute activity (Bq or Bq/mL) activity X of a sample of 99mTc of unknown
in samples of unknown activity using the cali- activity would then be given by
bration data given in Table 12-2. Alterna- X (Bq) = A(Bq) × [ R( 99 m Tc) /R( 57 Co)]
tively, one can compare the counting rate of
the unknown sample to that of a calibration × (0.962 / 0.889)
source (see Chapter 11, Section A.6). “Mock” (12-3)
sources containing long-lived radionuclides where A is the calibrated activity of the 57Co
are used to simulate short-lived radio�nuclides, standard and R(99mTc) and R(57Co) are the
for example, a mixture of 133Ba (356- and counting rates recorded from the 99mTc sample
384-keV γ rays) and 137Cs (662-keV γ rays) for and the 57Co standard, respectively.
“mock 131I.” Frequently, such standards are
calibrated in terms of “equivalent activity” of 5. Shielding and Background
the radionuclide they are meant to simulate. It is desirable to keep counting rates from
Thus if the activity of a mock 131I standard is background radiation as low as possible with
given as “A(Bq) of 131I,” then the activity of a the well counter to minimize statistical uncer-
sample of 131I of unknown activity X would be tainties in counting measurements (see
obtained from Chapter 9, Section D.4). Sources of background
include cosmic rays, natural radio�activity in
X (Bq) = A(Bq) × [ R( 131 I) /R(mock 131 I)] (12-2) the detector (e.g., 40K) and surrounding
178 Physics in Nuclear Medicine
99mTc
140 keV
51Cr
320 keV
Relative number of counts
Window 1
Window 2
Energy
FIGURE 12-6 Window settings used for simultaneous measurement of 99mTc and 51Cr in a mixed sample. Crosstalk
from 51Cr into the 99mTc window must be corrected for, using methods described in the text.
12 • Counting Systems 179
and the number of counts from 51Cr in window N2 ( 51 Cr) = (8000 − 0.05 × 18, 000) / (1 − 0.6 × 0.05)
2 [N2(51Cr)] from
= 7100 / 0.97
N2 ( 51 Cr) = ( N2 − R 21 N1 ) / (1 − R12 R 21 ) (12-5) ≈ 7320 counts
Test tube
containing sample
Photomultiplier tube
Lead shielding
NaI(Tl) crystal
Sample changer
FIGURE 12-8 Schematic cross-sectional drawing of through-hole detector and sample-changing system. Placement of
the sample can be automatically adjusted to center the sample volume in the detector.
12 • Counting Systems 181
1.05
1
Through-hole
Relative efficiency
0.95
Well-type
0.9
0.85
0 0.5 1 1.5 2
Sample volume (mL)
FIGURE 12-9 Efficiency of a well counter versus a through-hole counter for a constant total activity of 59Fe. The
efficiency of the through-hole detector shows less variation with sample volume because the sample can be centered
in the detector. (Adapted from Guide to Modern Gamma Counting. Packard Instrument Company, Meriden, CT, 1993.)
systems, counting vials loaded into a tray or spectrum from background sources, which
carriage are selected automatically and placed could indicate a radioactive spill or contami-
sequentially in the NaI(Tl) well counter. Mea- nation, or for checking the general condition
surements are taken for a preset time or a of the NaI(Tl) detector.
preset number of counts selected by the user. Modern well-counter systems are inter-
The well counter usually is shielded with 5 to faced to computers or have dedicated circuits
7.5╯cm of lead, with a small hole in the lead that control sample changing, placement and
shielding above and beneath the detector for counting time, and perform corrections for
insertion of the sample. One disadvantage of radionuclide decay and background. Pro-
automated systems is that there is no lead grams for spectral analysis and correction of
shielding directly above or below the sample multiple isotope samples are also generally
being counted. Therefore the system is not as available. All interactions with the well-
well shielded as a manual well counter, which counter system generally are through the
can cause an increase in background counting keyboard, where the user selects from a range
rates, particularly from other samples in the of predefined protocols and provides informa-
carriage. This can be a problem when low- tion regarding the radionuclide, desired
activity samples are counted with high- counting time, and sample volume.
activity samples in the carriage. For very high throughput, there are even
Commercial systems usually have MCAs or multidetector systems that may contain as
multiple SCAs to allow the selection of many many as 10 NaI(Tl) scintillation detectors.
different counting windows. The MCA also This permits 10 samples to be counted simul-
can be used to display the entire spectrum taneously and many hundreds or even thou-
recorded by the NaI(Tl) detector on a com- sands of samples to be counted per hour. The
puter. The displayed spectrum allows the individual detectors are carefully separated
user to inspect visually and select the posi- and shielded from each other by lead to
tions of the single-channel windows for count- prevent crosstalk; however, when counting
ing and to examine crosstalk interference high-energy γ rays (300╯keV) some crosstalk
when multiple radionuclides are counted may occur. This is in addition to the source of
simultaneously. It is also very useful for crosstalk described in Section A.7, which
quickly and reliably checking to see if there occurs from the samples waiting to be counted
are any significant photopeaks in the in the sample changer system. Background
182 Physics in Nuclear Medicine
Labeled
compounds
Gas or liquid
chromatograph Dual recorder
Mass
Mass detector signal
Effluent
collection
vial
FIGURE 12-10 NaI(Tl) detector system used in conjunction with a gas or liquid chromatograph. The “mass detector”
is used to detect chemical species, and the radiation detector is used to detect the radioactivity associated with these
species for radiochemical identification.
Pulse summation
TABLE 12-3â•…
RADIONUCLIDES COMMONLY COUNTED
Amplifier
WITH LIQUID SCINTILLATION DETECTORS
MCA Maximum β
Trigger Energy
Radionuclide Half-Life (MeV)
Computer 3
H 12.3╯yr 0.019
14
C 5700╯yr 0.156
FIGURE 12-11 Basic components of a liquid scintillation
counter. 35
S 87.5╯d 0.167
45
Ca 163╯d 0.257
65
Zn 243╯d 0.325
or plastic of the test tube used to contain the
59
sample in a standard well counter. They are Fe 45╯d 0.467
also used for counting emitters of low-energy 22
Na 2.6╯yr 0.546
x rays and γ rays, which cannot be detected 131
I 8.06╯d 0.606
efficiently with NaI(Tl) detectors because of
the thickness of canning material required
36
Cl 3 × 10 ╯d5
0.714
around the detector. 40
K 1.3 × 109╯yr 1.300
The LS solution has a low atomic number 24
Na 15.0╯hr 1.392
(Z ~ 6 to 8) and density (ρ ~ 1) in comparison 32
P 14.3╯d 1.711
with other scintillators, such as NaI(Tl).
184 Physics in Nuclear Medicine
counted in a standard well counter, because small. Random coincidence rates Rr (cps) can
of the penetrating 511-keV γ rays produced be determined from
from the annihilation (see Chapter 3, Section
G) of positrons with electrons in the sample,
or in the walls of the tube containing the Rr = (2τ) Rn2 (12-6)
sample.
Because LSC systems are used primarily where 2τ is the resolving time of the coinci-
to count very low-energy particles, the system dence circuit and Rn is the noise pulse rate for
must have very low electronic noise levels. each PM tube (assumed to be equal) caused
For example, with 3H, the energy range of the by PM tube noise and phosphorescence in the
β particle is 0-18╯keV. Under optimal condi- sample. For 2τ = 0.03 µsec and Rn = 1000╯cps,
tions, β particles from 3H decay produce only one obtains Rr = 3 × 10−8 × (103)2 = 0.03╯cps.
0 to 25 photoelectrons at the PM tube photo- Thus most of the noise pulses are rejected by
cathode, with an average of only about eight the coincidence circuit.
( Eβ ≈ 1/ 3 Eβmax ). Background electronic noise is The output signals from the two PM tubes
due mainly to spontaneous thermal emission and preamplifiers are fed into the coincidence
of electrons from the photocathode of the PM circuit as described earlier and also into a
tube. Background noise also is present from summation circuit, which adds the two signals
exposure to light of the scintillator solution together to produce an output signal propor-
during sample preparation. This exposure tional to the total energy of the detected event
can produce light emission (phosphorescence), (see Fig. 12-11). The output signals from the
which persists for long periods (i.e., hours). summing circuit are sent to an amplifier to
Several methods are employed in LS detec- boost the signal, which is then digitized in an
tors to reduce this noise or background count MCA. The output from the coincidence circuit
rate. Thermal emission is reduced by refrig- is fed to the MCA to enable data collection
eration of the counting chamber to maintain only when both PM tubes have registered a
the PM tubes at a constant low temperature pulse, thus rejecting noise. The MCA provides
(typically about −10° C). Constant PM tube a spectrum of the energies of the detected
temperature is important because the photo- events, which can be further processed by a
cathode efficiency and electronic gain of the computer, including routines for separating
PM tube are temperature dependent, and the counts from two radionuclides that are
variations in temperature produce variation being counted simultaneously and for per-
in the amplitude of the output signal. forming quench corrections as discussed in
Pulse-height analysis also may be used to Section C.5.
discriminate against noise because true radi-
ation events usually produce larger signals 2. Pulse-Height Spectrometry
than thermal emission noise; however, Pulse-height analysis is used with LS count-
thermal emission noise still is superimposed ing to further reduce the background count-
on the radiation signals, which can cause ing rate by selecting only the energy region
deterioration of the energy resolution and lin- corresponding to the radiation of interest or
earity of the system. to select different energy regions when simul-
The most effective reduction of noise is taneous sources are being counted. An
achieved by coincidence detection techniques example of two-energy window analysis for a
(see Fig. 12-11). When a scintillation event source containing 3H and 14C is shown in
occurs in the scintillator, light is emitted in all Figure 12-12. Because of the continuous
directions. Optical reflectors placed around energy distribution in β decay, pulse-height
the counting vial reflect the light into two analysis cannot separate completely the two
opposing PM tubes to maximize light collec- spectra, and there is crosstalk interference.
tion efficiency. Pulses from each of the PM Methods to correct for this situation are dis-
tubes are routed to separate preamplifiers cussed in Section C.4.
and a coincidence circuit (see Chapter 8,
Section F). The coincidence circuit rejects any 3. Counting Vials
pulse that does not arrive simultaneously Counting vials containing the radioactivity
with a pulse from the other PM tube (i.e., and the liquid scintillator solution usually are
within approximately 0.03 µsec). Noise pulses made of polyethylene or low-potassium-con-
are distributed randomly in time; therefore tent glass. The low-potassium-content glass is
the probability of two noise pulses occurring used to avoid the natural background of 40K.
simultaneously in the two PM tubes is very When standard laboratory glass vials (lime
12 • Counting Systems 185
3H
composition and thickness of the sample vial
and on the effects of quenching, which are
discussed in Section C.5).
Frequently, samples containing a mixture
of two radionuclides (e.g., 3H and 14C) are
14C
counted. By selecting separate energy windows
on each of the β spectra (see Fig. 12-12), the
activities of each of the radionuclides can be
determined. The optimal window for each
radionuclide is determined individually by
using separate 3H and 14C sources. If possible,
the energy windows should be adjusted so
Energy that counts from the lower-energy emitter are
FIGURE 12-12 Example of pulse-height spectra obtained not included in the window used for the higher-
from 3H and 14C by liquid scintillation counting. energy emitter. The method and equations
used to correct for crosstalk interference—
described in Section A.7 for well-counter
glass) are used, the background for 3H and 14C applications—can be also used on the LS
is increased by 30-40╯cpm because of 40K in counter. There are also a number of increas-
the glass. Polyethylene vials frequently are ingly sophisticated methods for dealing with
used to avoid this problem and also to increase samples containing radionuclides with very
light transmission from the liquid scintillator similar spectra. These methods are described
to the PM tubes. Polyethylene vials are excel- in detail in reference 1.
lent for dioxane solvents but should not be
used with toluene as the scintillator solvent 5. Quench Corrections
because toluene will cause the vials to distort Quenching refers to any process that reduces
and swell, which may jam the sample changer. the amount of scintillation light produced by
Materials such as quartz, Vicor, and others the sample or detected by the PM tubes. The
also are used for counting vials. causes of quenching in LS counting were
Exposure of the vial and liquid scintillator described in Chapter 7, Section C.6. The
solution to strong sunlight produces a back- principal effect of quenching is to cause an
ground of phosphorescence that may take apparent shift of the energy spectrum to
hours to decay; therefore samples frequently lower energies (Fig. 12-13). This results in a
are stored temporarily in a darkened con-
tainer before counting. This is referred to as
dark adaptation of samples.
4. Energy and Efficiency Calibration
Relative number of counts
80
60
Detection efficiency (%)
14C, 47.8%
40
3H efficiency
3H, 23.1%
20
14C in 3H, 11.3%
14C counts in
3H Channel
0
0.0 0.2 0.4 0.6 0.8 1.0
AES ratio
FIGURE 12-15 Representative quench correction curves based on the automatic external standardization (AES)
method for counting mixed 14C-3H samples. For example, with an AES ratio of 0.7 (vertical dashed line) counts in the
3
H channel must first be corrected for 14C crosstalk by 11.3% of the counts in the 14C channel. The counting efficiency
for the corrected 3H counts is 23.1% and for the 14C counts is 47.8% relative to an unquenched sample. Note that the
AES ratio decreases with increasing quenching.
188 Physics in Nuclear Medicine
detergents include the alkyl phenol ethoxyl- solid scintillator crystals through which the
ates, alkyl and alkylaryl sulfonates, alcohol radioactively labeled gas or liquid is allowed
sulfates, and phosphate esters. Polar com- to flow. The most common scintillator mate-
pounds also can be used by forming insoluble rial for this purpose is the organic scintillator
suspensions. For example, 14CO2 can be pre- anthracene. This technique is used primarily
cipitated as barium carbonate and then sus- for β-emitting radionuclides, typically 14C and
pended in the scintillator solution with the 3
H. The β particles interact with the anthra-
addition of thixatropic jelling agents. Silica cene crystals, and the resulting scintillation
gels from thin-layer chromatography also can is detected in the same manner as from the
be counted in this manner. Samples deposited LS vial.
on filter paper such as from paper chromatog- These systems have been used for monitor-
raphy frequently are counted by placing the ing the effluent from amino acid analyzers,
paper strip in the liquid scintillator. The scin- liquid chromatographs, and gas chromato-
tillator solution also can be dissolved or sus- graphs. To monitor the effluent from gas
pended in the sample itself. chromatographs, the compounds usually are
Another straightforward approach to count- passed through a gas combustion furnace to
ing complicated organic compounds such as convert them into 14CO2 or 3H2O (vapor).
proteins or sections of acrylamide gel columns Carrier gas from the gas chromatograph (e.g.,
with high efficiency is to combust the sample. He) is used to sweep the 14CO2 or 3H2O through
The 14CO2 and 3H2O released may be collected, the counting cell.
dissolved in scintillator solution, and then Counting rates in these systems depend on
counted. the activity concentration and the flow rate.
Numerous other techniques have been If fast flow rates and low-activity concentra-
developed for LS sample preparation. More tions are required, the result may be data of
discussion of these techniques is presented in poor statistical quality. Data from flow count-
reference 1. Careful sample preparation is ing represent the time course of some process
critical for accurate application of the LS and usually are displayed as time-activity
technique. curves.
7. Cerenkov Counting 9. Automated Multiple-Sample LS
High-energy beta emitters may also be Counters
assayed in LSC systems without the use of a LSC may be used for counting large numbers
liquid scintillator solution by detecting optical of samples or for counting low-level samples
Cerenkov radiation (see Chapter 6, Section for long counting times. To expedite this and
A.5). Beta particles with an energy in excess to remove the tedious job of manually count-
of 263╯keV will produce Cerenkov light in a ing multiple samples, automated multiple-
water solution, which can be detected by the sample LSC systems have been developed.
PM tubes in a LSC system. The calibration of These systems have automated sample chang-
the LSC system for measuring activity from ers that frequently can handle 100 or more
the detected Cerenkov light must account for counting vials (Fig. 12-16). A number of
the directionality of the light cone produced
and the spectral characteristics of the Ceren-
kov light, which is weighted toward the blue
end of the visible spectrum. Because the pro-
duction of Cerenkov light is a physical phe-
nomenon, there is no chemical quenching of
the signal. However, color quenching still
must be accounted for. Cerenkov counting is
used primarily to measure samples contain-
ing 32P ( Eβmax = 1710╯keV) in which the count-
ing efficiency can be in excess of 50%.
8. Liquid and Gas Flow Counting
In addition to counting individual samples,
LSC systems also can be used for continuous
FIGURE 12-16 A liquid scintillation counter with auto-
monitoring of gas streams or flowing liquids. mated sample loading can efficiently count and analyze
In these systems, the vial of LS solution is hundreds of samples. (Courtesy Beckman Coulter, Inc.,
replaced with a cell filled with finely dispersed Brea, CA.)
12 • Counting Systems 189
instrument reading changes with sample and other fields. To date, however, they have
volume. had limited effect on nuclear medicine. Their
Another parameter worth evaluating is lin- disadvantages of small size and high cost out-
earity of response versus sample activity. This weigh their advantage of superior energy
may be determined conveniently by recording resolution in comparison with other detection
the reading for a 99mTc source of moderately systems [e.g., NaI(Tl)] for general-purpose
high activity (e.g., 1╯GBq, or whatever the applications; however, the energy resolution
approximate maximum amount of activity of semiconductor detectors allows the separa-
the dose calibrator will be used to assay), then tion of γ rays differing in energy by only a few
recording the readings during a 24- to 48-hour keV as opposed to 20-80╯keV with NaI(Tl)
period (4-8 half-lives) to determine whether (Fig. 12-18; see also Fig. 10-14). Therefore in
they follow the expected decay curve for 99mTc. applications in which energy resolution is the
Deviations from the expected decay curve critical factor and the relatively small size of
may indicate instrument electronic non� the semiconductor detector is not completely
linearities requiring adjustment or correction restrictive, Ge or Si detectors are the system
of readings. In applying this technique, it is of choice.
necessary to correct for 99Mo contamination Semiconductor detectors are used exten-
using the shielding technique described sively as charged-particle and γ-ray spectrom-
earlier, especially after several 99mTc half-lives eters in physics. Their principal application
have elapsed. in nuclear medicine is for assessment of
radionuclide purity. Si has a lower atomic
2. Gas Flow Counters number and density than Ge and therefore a
Gas-filled detectors also are used in gas flow lower intrinsic detection efficiency for γ rays
counters, primarily for measurement of with energies ╛40╯keV (see Chapter 11,
β-emitting activity. The detector in these Section A.3). Thus Si detectors are used pri-
systems usually can be operated in either pro- marily for detection of low-energy x rays and
portional counter or Geiger-Müller mode. The Ge, cadmium telluride (CdTe), and cadmium
most frequent application for these systems zinc telluride (CZT) are used for γ rays.
in nuclear medicine is for monitoring the The basic configuration of a semiconductor
effluent from gas chromatographs. Gases system for in vitro analysis is shown in Figure
labeled with 3H or 14C in helium carrier gas 7-12. Except for a special low-noise high-
from the chromatograph are passed through voltage supply, preamplifier, and amplifier,
a combustion furnace to convert them to 3H2O the system components are the same as those
or 14CO2, which then is allowed to flow through of NaI(Tl) counting systems. Usually an MCA
the counter gas volume itself with the count- is employed rather than an SCA with semi-
ing gas (usually 90% He plus 10% methane). conductor detectors because the detectors
This permits a time-course analysis of the most commonly are used to resolve complex
outflow from the chromatograph. These spectra of multiple emissions and multiple
systems have good geometric and intrinsic radionuclides (see Fig. 12-18).
detection efficiencies for low-energy β emit- The superior energy resolution of semiÂ�
ters, such as 3H and 14C; however, their intrin- conductor detectors may result in a signifi-
sic efficiency for γ-ray detection is only cant advantage in sensitivity [i.e., minimum
approximately 1%. Gases labeled with β emit- detectable activity (MDA)] (see Chapter 9,
ters are therefore analyzed using NaI(Tl) Section D.5) in comparison with NaI(Tl)
detectors. detectors for some applications. MDA depends
on the ratio S/ B , in which S is the net
sample counting rate and B is the background
E. SEMICONDUCTOR DETECTOR counting rate. Because the energy resolution
of a semiconductor detector is 20 to 80 times
SYSTEMS
better than NaI(Tl), a photopeak window 20
to 80 times narrower can be used, resulting
1. System Components in typically 20 to 80 times smaller background
Semiconductor detectors [germanium (Ge) counting rate. Considering background alone,
and silicon (Si)] (see Chapter 7, Section B) then, the MDA for a semiconductor detector
created revolutionary advances in nuclear could be a factor 20 to 80 smaller than a
physics, nuclear chemistry, radiation chemis- NaI(Tl) detector of comparable size. This
try, nondestructive materials analysis (e.g., advantage is partially offset by the larger
x-ray fluorescence and neutron activation), available detector sizes with NaI(Tl) and,
12 • Counting Systems 191
NaI(Tl) detector
(122, 136)
(140)
57Co
99mTc
Relative number of counts 8
(392)
Pb x rays
(365)
131I (80)
x rays
6
113mIn
(514)
131I
(662)
4
85Sr
(284)
(637)
137Cs
(723)
131I
2
131I
131I
0
0 200 400 600 800
A Energy (keV)
Ge(Li) detector
x ray
Xe x rays
Rb x rays
(14.4)
In x rays
Ba x rays
spectrum
Tc x rays
Xe x rays
4
Ba x rays
In x rays
(140)
57Co
2
137Cs (662)
99mTc
Relative number of counts
0
Pb x rays
6
57Co (136)
0 15 30
131I (85)
(365)
(392)
(637)
4
×20
131I
(122)
131mIn
(514)
(284)
(723)
131I
57Co
2
85Sr
131I
131I
0
0 200 400 600 800
B Energy (keV)
FIGURE 12-18 Comparative pulse-height spectra of a mixed radionuclide sample recorded with NaI(Tl) (A) and Ge(Li)
(B) detectors. Because of its superior energy resolution, the Ge(Li) detector clearly resolves multiple γ rays and x rays
of similar energies that appear as single peaks with NaI(Tl).
above approximately 200╯keV, by the greater than NaI(Tl), limiting them to situations in
intrinsic photopeak efficiency of NaI(Tl) for which small detector sizes are acceptable.
comparable detector thicknesses (see Chapter
11, Section A.3); however, for lower-energy γ 2. Applications
rays, measured in a configuration having a The major in vitro applications of semicon-
high geometric efficiency (e.g., sample placed ductor detectors in nuclear medicine have
directly against the detector), there is usually been for tracer studies employing many radio-
an advantage in MDA favoring the semicon- nuclides simultaneously and for the assay of
ductor detector. For higher-energy γ rays, radionuclidic purity of radiopharmaceuticals.
CdTe or CZT semiconductors provide the In both of these applications the superior
advantage of both excellent energy resolution energy resolution of semiconductor detectors,
and good photopeak efficiency, although the illustrated by Figure 12-18, offers a distinct
cost per unit detector volume is much higher advantage. The energy resolution of the Ge
192 Physics in Nuclear Medicine
breast cancer and melanoma. The sentinel better for this application than Si or Ge
node is the most likely initial site for meta- because they have higher stopping power for
static spread of the cancer; thus biopsy of the γ rays and can be operated at room tempera-
sentinel node is important for patient man- ture. A small collimator is used in front of the
agement. The sentinel node is identified by probe to provide directionality.
direct injection of a 99mTc-labeled colloid (a Figure 12-20 shows the components of a
suspension of fine particles labeled with 99mTc) typical γ-ray probe system. The output signals
into the tumor. This colloid is trapped in the from the probes are amplified and sent to an
first lymph node draining the tumor. During MCA. Discriminator levels are set automati-
surgery, the γ-ray probe is used to identify the cally for each different radionuclide. The
sentinel node, from which a biopsy sample is counting rate is presented on a digital display.
taken and sent to a pathology laboratory for Many systems also have an audible output
analysis. proportional to the counting rate. The whole
The second broad class of applications is in unit is battery powered and can run for many
radioguided surgery. Here, tumor-seeking hours on a single charge, eliminating the need
radiopharmaceuticals are injected into the for power cords. Wireless probes also are
patient. The radiopharmaceutical agent is
designed to target and bind to cancer cells
with high selectivity. After waiting for an Collimator
appropriate length of time for selective uptake Si photodiode
CsI(Tl)
of the radiopharmaceutical agent into the
tumor, the patient goes to surgery and the Preamp
surgeon uses the γ-ray probe to assist in locat-
ing and removing the cancerous tissue, while High energy -ray probe
sparing as much healthy tissue as possible. Collimator
This procedure has been applied in para� CZT or CdTe
thyroid surgery and colorectal cancer, and in
detecting lymph node involvement for a range Preamp
of other cancers. Low energy -ray probe
The requirements for γ-ray probes for intraÂ�
operative use are that they have high effi-
ciency (so that radiolabeled tissue can be Amplifier
0000
found quickly in the surgical environment), cpm
that they be lightweight and easy to use, and MCA
that they pose no hazard to the patient. The
probe of choice for high-energy γ emitters, Processing
such as 111In, 131I, and 18F, is a scintillation
detector. A typical probe consists of a 5-mm
diameter × 10-mm high cesium iodide [CsI(Tl)] A
scintillator crystal, coupled to a Si photodiode.
The Si photodiode is a light-sensing semi�
conductor detector that replaces the PM tube
found in conventional scintillation detectors
and converts the scintillation light into an
electrical signal (see Chapter 7, Section C.3).
It is preferred in this application because of
its compact size and low weight compared
with a PM tube. CsI(Tl) is used in place of
NaI(Tl) as the scintillator because its emis-
sion wavelengths are better matched to the
spectral response of the Si photodiode. For
lower-energy γ emitters, such as 99mTc, a semi-
conductor detector made from CZT or CdTe B
(see Chapter 7, Section B) that directly con-
verts the γ rays to electric charge is typically FIGURE 12-20 A, Schematic representation of γ -ray
probes for intraoperative use. B, Four different wireless
used. This is an ideal application for these gamma probes shown with control unit. The geometry of
semiconductor detectors, because the required the probes are tailored to suit specific clinical applications.
detector area is small. CZT and CdTe are (Figure B courtesy IntraMedical Imaging, Los Angeles, CA.)
194 Physics in Nuclear Medicine
available, further facilitating their use in the Another application for whole-body count-
sur�gical environment. References 2 and 3 ing is the measurement of naturally occurring
40
provide a detailed review of counting probe K, which can be used to estimate total-body
systems for intraoperative use. potassium content. This is another high-
Probes for β-particle detection also have energy γ emitter present in very small quanti-
been developed. These are typically used in ties, requiring good detection efficiency for
conjunction with tumor-seeking, positron- accurate measurement. Whole-body counters
emitting radiopharmaceuticals to aid in locat- also are used for detecting and monitoring
ing tumors during surgery or to map tumor possible accidental ingestion of radioactive
margins during surgical resection, helping to materials.
ensure that the tumor is completely removed Most whole-body counters employ rela-
while sparing normal tissue. They differ from tively large NaI(Tl) detectors, 15 to 30╯cm in
the γ-ray probes described previously in that diameter × 5 to 10╯cm thick, to obtain good
these probes directly detect β+ particles (posi- geometric efficiency as well as good intrinsic
trons) rather than the 511-keV annihilation efficiency for high-energy γ rays. Several such
photons. Because of the short range of posi- detectors may be employed. Also the “count-
trons in tissue (see Chapter 6, Section B.2), ing chamber” is well shielded with lead, con-
they can only detect radioactivity that is crete, steel, and other materials to obtain
very superficial (1-2╯mm) at the surgical site, minimal background levels, thus ensuring
but have the advantage over γ-ray probes of minimum statistical error caused by back-
being very insensitive to radioactivity that ground counting rates (see Chapter 9, Section
may be contained in adjacent tissues and D.4). Shielding materials are selected care-
organs and that could interfere with the local fully for minimum contamination with back-
measurement. ground radioactivity.
3. Whole-Body Counters
Another class of in vivo measurement systems
are whole-body counters, which are designed REFERENCES
to measure the total amount of radioactivity A detailed reference on in vitro counting systems
in the body, with no attempt at localization of is the following:
the activity distribution. Many (but not all) of 1. L’Annunciata MF: Handbook of Radioactivity Analy-
these systems employ NaI(Tl) detectors. They sis, ed 2, San Diego, 2003, Academic Press.
are used for studying retention, turnover, and The design and application of miniature γ probes
clearance rates with nuclides such as 60Co and for surgical use are reviewed in detail in the
57
Co (labeled vitamin B12), 24Na, 42K, 47Ca, and following:
59
Fe. Most of these radionuclides emit high- 2. Hoffman EJ, Tornai MP, Janacek M, et al: Intraopera-
energy γ rays, and several have quite long tive probes and imaging probes. Eur J Nucl Med
half-lives. Thus it is important that a whole- 26:913-935, 1999.
3. Povoski SP, Neff RL, Mojzisik CM, et al: A comprehen-
body counter have good detection efficiency, so sive overview of radioguided surgery using gamma
that very small amounts of activity (╛50╯kBq) detection probe technology. World J Surg Oncol 7:11,
can be detected and measured accurately. 2009.
chapter
13
The Gamma Camera:
Basic Principles
Radionuclide imaging is the most important little use for imaging because they cannot
application of radioactivity in nuclear medi- penetrate more than a few millimeters of
cine. Radionuclide imaging laboratories are tissue. Therefore they cannot escape from
found in almost every hospital, performing within the body and reach an external radia-
hundreds and even thousands of imaging pro- tion detector, except from very superficial
cedures per month in larger institutions. tissues. Bremsstrahlung (see Fig. 6-1) gener-
In this chapter, we discuss briefly some ated by electron emissions is more penetrat-
general aspects of radionuclide imaging, and ing, but the intensity of this radiation
we describe the basic principles of the most generally is very weak.
widely used imaging device, the gamma Imaging system detectors must therefore
camera, also known as the Anger scintillation have good detection efficiency for γ rays. It is
camera, named after its inventor, Hal Anger also desirable that they have energy discrimi-
(see Chapter 1, Section C and Fig. 1-3). The nation capability, so that γ rays that have lost
performance characteristics of this instru- positional information by Compton scattering
ment are discussed in Chapter 14. The use of within the body can be rejected based on
the gamma camera for tomographic imaging their reduced energy (see Chapter 6, Section
is described in Chapter 17. C.3). A sodium iodide [NaI(Tl)] scintillation
detector (see Chapter 7, Section C) provides
both of these features at a reasonable cost;
A. GENERAL CONCEPTS OF for this reason it is currently the detector of
RADIONUCLIDE IMAGING choice for radionuclides with γ-ray emissions
in the range of 80-300╯keV.
The purpose of radionuclide imaging is to The first attempts at radionuclide “imaging”
obtain a picture of the distribution of a radio- occurred in the late 1940s. An array of radia-
actively labeled substance within the body tion detectors was positioned on a matrix of
after it has been administered (e.g., by intra- measuring points around the head. Alterna-
venous injection) to a patient. This is accom- tively, a single detector was positioned manu-
plished by recording the emissions from the ally for separate measurements at each point
radioactivity with external radiation detec- in the matrix. These devices were tedious to
tors placed at different locations outside the use and provided only very crude mappings of
patient. The preferred emissions for this the distribution of radioactivity in the head
application are γ rays in the approximate (e.g., left-side versus right-side asymmetries).
energy range of 80 to 500╯keV (or annihilation A significant advance occurred in the early
photons, 511╯keV). Gamma rays of these 1950s with the introduction of the rectilinear
energies are sufficiently penetrating in body scanner by Benedict Cassen (see Fig. 1-2).
tissues to be detected from deep-lying organs, With this instrument, the detector was
can be stopped efficiently by dense scintilla- scanned mechanically in a raster-like pattern
tors, and are shielded adequately with rea- over the area of interest. The image was a
sonable thicknesses of lead (see Fig. 6-17—soft pattern of dots imprinted on a sheet of paper
tissue has attenuation properties similar to by a mechanical printer that followed the
water). Alpha particles and electrons (β par- scanning motion of the detector, printing the
ticles, Auger and conversion electrons) are of dots as the γ rays were detected.
195
196 Physics in Nuclear Medicine
Amp/ADC
Amp/ADC
Amp/ADC
Amp/ADC
Amp/ADC
Amp/ADC
described by Hal Anger in 1953. He used a
pinhole aperture in a sheet of lead to project
a γ-ray image of the radionuclide distribution
onto a radiation detector composed of a
NaI(Tl) screen and a sheet of x-ray film. The
film was exposed by the scintillation light
PM tube array
flashes generated by the γ rays in the NaI(Tl)
screen. Unfortunately, this detection system Light guide
(especially the film component) was so ineffi- NaI(Tl) crystal
cient that hour-long exposures and therapeu-
tic levels of administered radioactivity were Collimator
needed to obtain satisfactory images.
In the late 1950s, Anger replaced the film-
screen combination with a single, large-area,
NaI(Tl) crystal and a photomultiplier (PM)
tube assembly to greatly increase the detec- Patient
tion efficiency of his “camera” concept. This
instrument, the Anger scintillation camera,1
or gamma camera, has been substantially FIGURE 13-1 Basic principles and components of a
refined and improved since that time. modern gamma camera. The outputs of each photo�
Although other ideas for nuclear-imaging multiplier (PM) tube are amplified and digitized using an
instruments have come along since then, analog-to-digital converter (ADC). The X-Y locations for
none, with the exception of modern positron each gamma ray that interacts in the NaI(Tl) crystal are
computed from the digitized signals. The energy depos-
emission tomography systems (see Chapter ited by the gamma ray, E, which is proportional to the
18), has matched the gamma camera for a total measured pulse amplitude, also is computed by
balance of image quality, detection efficiency, summing the individual PM tube signals. If E falls within
and ease of use in a hospital environment. the selected energy window, the event is accepted and
placed at the appropriate X-Y location in the image.
The gamma camera has thus become the
most widely used nuclear-imaging instru-
ment for clinical applications.
image of the γ-ray distribution on the surface
of the NaI(Tl) crystal (see Section B.3). The
B. BASIC PRINCIPLES OF THE GAMMA second is that the NaI(Tl) crystal is viewed
by an array of PM tubes, rather than a
CAMERA
single PM tube. Signals from the PM tubes
are fed to electronic or digital position logic
1. System Components circuits, which determine the X-Y location of
Figure 13-1 illustrates the basic principles of each scintillation event, as it occurs, by
image formation with the gamma camera. using the weighted average of the PM tube
The major components are a collimator, a signals (see Section B.2).
large-area NaI(Tl) scintillation crystal, a Individual events also are analyzed for
light guide, and an array of PM tubes. Two energy, E, by summing the signals from all
features that differ from the conventional PM tubes. When the pulse amplitude of an
NaI(Tl) counting detectors described in event falls within the selected energy window,
Chapter 12 are crucial to image formation. it is accepted and the X and Y values are
The first is that an imaging collimator is binned into a discrete two-dimensional array
used to define the direction of the detected γ of image elements, or pixels. An image is
rays. The collimator most commonly consists formed from a histogram of the number of
of a lead plate containing a large number of events at each possible X-Y location. Large
holes. By controlling which γ rays are numbers of events are required to form an
accepted, the collimator forms a projected interpretable image because each pixel must
13 • The Gamma Camera: Basic Principles 197
have a sufficient number of counts to achieve reflective material such as TiO2 to maximize
an acceptable signal-to-noise level. Because light output and hermetically sealed inside a
images often are formed in 64- × 64-pixel or thin aluminum casing to protect it from mois-
128- × 128-pixel arrays, the counting require- ture. An optical glass window on the back
ments are some 103 to 104 times higher than surface of the casing permits the scintillation
for a simple counting detector. light to reach the PM tubes. A cross section of
Images are displayed on a computer a typical gamma camera crystal assembly is
monitor, where image brightness and con- shown in Figure 13-2. The choice of thickness
trast may be manipulated and different color of the NaI(Tl) crystal is a trade-off between
tables may be employed. More sophisticated its detection efficiency (which increases with
digital image processing is discussed in increasing thickness) and, as shown in
Chapter 20. Chapter 14, Section A.1, its intrinsic spatial
Most modern gamma cameras are com- resolution (which deteriorates with increas-
pletely digital, in the sense that the output of ing thickness). Most general-purpose gamma
each PM tube is directly digitized by an analog- cameras have crystal thicknesses of approxi-
to-digital converter (ADC). The calculation of mately 9.5╯mm. For lower-energy γ emitters,
X-Y position and pulse-height are performed such as 99mTc and 201Tl, however, detection
in software based on the digitized PM tube efficiency is adequate even with 6-mm-thick
signals, and errors in energy and positioning detector crystals.
caused by noise and pulse distortions caused An array of PM tubes is coupled optically
by the analog positioning circuitry are elimi- to the back face of the crystal with a silicone-
nated. This approach also permits improved based adhesive or grease. Round PM tubes
handling of pulse pile-up at high counting are arranged in a hexagonal pattern to maxi-
rates, as described in Section B.2. mize the area of the NaI(Tl) crystal that is
The gamma camera can be used for static covered. Some cameras use hexagonal (or
imaging studies, in which an image of an rarely, square) cross-section PM tubes for
unchanging radionuclide distribution can be better coverage of the NaI(Tl) crystal. Typical
recorded over an extended imaging time (e.g., PM tube sizes are 5╯cm in diameter. Most
minutes). Single contiguous images of the modern cameras employ between 30 and 100
whole body can be obtained by scanning PM tubes. Figure 13-3 shows a photograph of
the gamma camera across the entire length of a 30-tube model. The PM tubes are encased
the patient. This can be achieved by moving in a thin magnetic shield (Chapter 7, Section
either the bed or the gamma camera while C.2) to prevent changes in the gain caused by
adjusting the event positioning computation changes in the orientation of the gamma
to account for this movement. Clinically camera relative to the earth’s magnetic field.
important whole-body studies include bone The ultrasensitivity of PM tubes to magnetic
scans of the skeleton, and the localization of fields also makes gamma cameras susceptible
tumors or their metastases in the body. to the stray fields from magnetic resonance
The gamma camera also can be used for imaging systems.
dynamic imaging studies, in which changes
in the radionuclide distribution can be
observed, as rapidly as several images per
second. This allows physiologic information to
be obtained, such as the rate of tracer uptake Scintillation
or clearance from an organ of interest. Images NaI(Tl) crystal light exits to Glass
(typically 6- to PM tubes entrance
also can be synchronized to electrocardiogram 12.5-mm thick) window
signals, permitting images of the heart in dif-
ferent phases of the cardiac cycle to be formed.
These gated images can provide important
information on cardiac function.
2. Detector System and Electronics
Gamma rays
The gamma camera employs a single, large- enter from
area, rectangular NaI(Tl) detector crystal, Thin aluminum casing this side Reflector
usually 6- to 12.5-mm thick with sizes of up to hermetically seal material
to 60 × 40╯cm. Round crystals of 25 to 50╯cm crystal
in diameter were used in many older systems. FIGURE 13-2 Schematic cross-section of a NaI(Tl)
The NaI(Tl) crystal is surrounded by a highly crystal assembly for a gamma camera.
198 Physics in Nuclear Medicine
FIGURE 13-3 A rectangular gamma camera detector with the cover removed showing the photomultiplier (PM) tubes
mounted on the NaI(Tl) crystal. In this example, the gamma camera detector measures 50 × 15╯cm and is read out by
30 PM tubes 5╯cm in diameter. This is a digital camera in which each of the PM tube outputs is individually digitized.
(Courtesy Dr. Joel Karp, University of Pennsylvania, Philadelphia, PA.)
Many manufacturers employ plastic light The amount of light detected by a particu-
guides between the detector crystal and PM lar PM tube is inversely related to the lateral
tubes, whereas others couple the PM tubes distance between the interaction site and the
directly to the crystal. The functions of the center of that PM tube. This is illustrated in
light guide are to increase the light collection one dimension in Figure 13-4. Ideally, the
efficiency, by channeling scintillation light relationship between signal amplitude and
away from the gaps between the PM tubes, location with respect to the center of a PM
and to improve the uniformity of light collec- tube would be linear. This would enable the
tion as a function of position. The latter effect position of an event to be determined by
is achieved by painting or etching a carefully taking a weighted average or centroid of the
designed pattern onto the entrance face of the PM tube signals using the simple relation-
light guide. The use of the PM tubes with ships shown in Figure 13-4. In practice,
hexagonal or square cross-sections that can however, the response is more complex, with
be tiled without gaps on the NaI(Tl) crystal a plateau directly beneath the PM tube
may in some cases allow elimination of the (because the PM tube is not a “point” detector)
light guide, assuming there is sufficient and long, flat tails caused by reflections of
spreading of the scintillation light in the glass light from the back and side surfaces of the
entrance window of the PM tube for accurate NaI(Tl) crystal. Therefore a calibration for
positioning. spatial nonlinearity is required (see Chapter
The detector crystal and PM tube array are 14, Section B).
enclosed in a light-tight, lead-lined protective Figure 13-5A shows a schematic drawing
housing. In most modern cameras, most of for an eight-PM tube version of the gamma
the electronics (such as preamplifiers, pulse- camera and is used to illustrate the principles
height analyzers, automatic gain control, of scintillation event localization in an analog
pulse pile-up rejection circuits and ADCs) are detector. The position is determined by split-
mounted directly on the individual PM tube ting the signal from each PM tube onto four
bases within the detector housing to minimize output lines, whose signals are denoted X +,
signal distortions that can occur in long cable X −, Y↜↜+, and Y − (Fig. 13-5B). The fraction of
runs between the detector head and control the PM tube current that goes to each output
console. line is determined by the value of the resistors
13 • The Gamma Camera: Basic Principles 199
S2
S1
If linear, then:
D1 (S2 D) / (S1 S2)
D2 (S1 D) / (S1 S2)
where D D1 D2
PM tube array
NaI(Tl) crystal
D1 D2
Collimator
Gamma ray
FIGURE 13-4 Illustration of light sharing between photomultiplier (PM) tubes. The PM-tube signal, S, is inversely
related to the distance of the interaction site, D, from the center of the PM tube. Equations for a linear relationship
are shown.
(R) that are used. By Ohm’s law, this current on the pulse height. Note that the possible
is proÂ�portional to 1/R. A separate circuit sums range of X and Y values is from −1 to +1. The
the outputs of all the PM tubes to form the resistor values shown in Figure 13-5C were
Z-signal. The Z-signal is proportional to the chosen such that the calculated X- and
total amount of light produced by a scintilla- Y-position signals vary linearly with distance
tion event in the crystal, and therefore the in the X and Y directions. In a perfect gamma
total energy deposited by the gamma ray, and camera, measured (X, Yâ•›) values would change
is used for pulse-height analysis. linearly from (−1, −1) in the bottom left-hand
The X +, X −, Y +, and Y − signals are com- corner to (+1, +1) at the top right-hand corner
bined to obtain X-position and Y-position of the camera face. The X and Y values can
signals. The X-position of the scintillation be scaled by the detector size to determine the
event is given by the difference in the X + and absolute position of an event on the gamma
X − signals, divided by the total X signal (X + camera face.
+ X −) However, Equations 13-1 and 13-2 do not
give a perfect mapping of source position
X = ( X + − X − )/( X + + X − ) (13-1) because, as was discussed previously, the PM
tubes signal does not actually vary linearly
Similarly, for the Y-position with interaction position. This gives rise to a
“pincushion” artifact, which is illustrated in
Y = (Y + − Y − ) / (Y + + Y − ) (13-2) Figure 14-9. There are also effects caused
by nonuniformities in the crystal, light
The X- and Y-position signals are normalized reflections at the edge of the crystal, and non-
to the total X and Y signals, so that the cal- uniform response across the face of the PM
culated position of interaction does not depend tubes that can cause further nonlinearities in
200 Physics in Nuclear Medicine
1 2 3 3 12.5 12.5
X
4 5 4 50 16.7 25 25
PM tube 6 7 8 5 16.7 50 25 25
6 12.5 12.5
A
7 25 25 12.5
Y 8 12.5 12.5
C
RY
RX RX
X X
RY
Y
B
FIGURE 13-5 Illustration of analog positioning in a gamma camera. A, Schematic representation of an eight-
photomultiplier (PM) tube camera. B, Signals from individual PM tubes are split using resistors onto four output
lines, designated X +, X −, Y +, and Y −. C, Representative resistor values (in kΩ) for the eight PM tubes. Resistor
values are chosen such that the X and Y positions computed from Equations 13-1 and 13-2 vary linearly with inter-
action position in the detector, ranging from a value of −1 in the bottom left hand corner to +1 in the top right corner.
position determination. These effects and cor- significant pulse amplitude, the noise from
rection techniques for them are discussed in the PM tubes that produce negligible signal
Chapter 14, Section B. amplitude (and that therefore contribute
In digital cameras, the output signal from little to position information) is not included
each PM tube is digitized and the event posi- in the position calculation. Second, with
tion is calculated in software. Often, this is signal thresholding, only a small number of
simply analogous to the resistor readout PM tubes surrounding the interaction loca-
described earlier; the inverse of the resistor tion are used for position determination. This
values are used as weighting factors for the allows a gamma camera to detect multiple
individual PM tube signals, and Equations events simultaneously when they occur in dif-
13-1 and 13-2 are used to determine the X ferent portions of the gamma camera and
and Y values. However, digital cameras also their light cones (the projection of the scintil-
can use more sophisticated algorithms that lation light on the PM tube array) do not
incorporate information regarding the non- significantly overlap. This improves the
linearity of PM tube response with position counting rate performance of the gamma
into the weighting factors to provide better camera, reducing dead time losses.
positioning accuracy. Energy selection is important for imaging
A commonly used tactic that is employed in because it provides a means to discriminate
both digital and analog cameras to improve against γ rays that been scattered within the
the positioning accuracy is to include in the body and therefore lost their positional infor-
position calculation only PM tubes with mation. By choosing a relatively narrow pulse-
signals above a certain threshold. This has height analyzer window that is centered on
two important benefits. By using the signal the photopeak, only γ rays that undergo no
only from those PM tubes that produce a scatter or small-angle scatter will be accepted.
13 • The Gamma Camera: Basic Principles 201
Number of counts
efficiency and in PM tube gains, the position
of the photopeak varies somewhat from posi-
tion to position in the detector. If a single
discriminator level is applied across the whole
detector, the window must be widened to
accommodate the fluctuations in photopeak
position, thus accepting more scatter (Fig.
13-6, top).
In the second method, suitable only for
digital cameras, the photopeak positions and
appropriate discriminator level settings are Pulse height, Z
computed and stored for many different loca-
tions across the detector face (Fig. 13-6,
bottom). When an event is detected, the X, Y Z1
values are calculated based on Equations Z2
13-1 and 13-2, and a look-up table is used to Z3
find the appropriate discriminator levels for
that location. If the event amplitude Z falls
Number of counts
diverging, and converging. The different smaller than the collimator cone length f; it
types of collimator are introduced subse- is minified when the source distribution is
quently. Their effects on the spatial resolu- farther away. The image size I and object
tion and sensitivity of the gamma camera are (source) size O are related according to
discussed in Chapter 14 , Sections C and D.
A pinhole collimator (Fig. 13-7A) consists I/O = f / b (13-3)
of a small pinhole aperture in a piece of lead,
tungsten, platinum, or other heavy metal The size of the imaged area also changes with
absorber. The pinhole aperture is located at distance from the pinhole collimator. If the
the end of a lead cone, typically 20 to 25╯cm detector diameter is D and the magnification
from the detector. The size of the pinhole can (or minification) factor is I/O (Equation 13-3),
be varied by using removable inserts and is the diameter of the image area projected onto
typically a few millimeters in diameter. the detector, D′, is
The imaging principle of a pinhole collima-
tor is the same as that employed with inex- D
D′ = (13-4)
pensive “box cameras.” Gamma rays passing I/O
through the pinhole project an inverted image
of the source distribution onto the detector Thus a large magnification factor, obtained at
crystal. The image is magnified when the dis- close source-to-collimator distances, results in
tance b from the source to the pinhole is a small imaged area.
I I
f
O
b
O
Pinhole Parallel hole
A B
f
b
O f
I
Diverging Converging
C D
FIGURE 13-7 A-D, Four types of collimators used to project “γ -ray images” onto the detector of a gamma camera.
O, Radioactive object; I, its projected image.
13 • The Gamma Camera: Basic Principles 203
Image size changes with object-to-pinhole directly “head-on,” it can be positioned closer
distance b. Therefore the pinhole collimator to the patient for better image detail in some
provides a somewhat distorted image of three- imaging studies (e.g., left anterior oblique
dimensional objects because source planes at cardiac views).
different distances from the collimator are A diverging collimator (Fig. 13-7C↜) has
magnified by different amounts. Pinhole col- holes that diverge from the detector face. The
limators are used primarily for magnification holes diverge from a point typically 40-50╯cm
imaging of small organs (e.g., thyroid and behind the collimator, projecting a minified,
heart) and for small-animal imaging. noninverted image of the source distribution
Another type of pinhole collimator, the onto the detector. The degree of minification
multi-pinhole collimator, has an array of mul- depends on the distance f from the front of the
tiple pinholes, typically seven, arranged in collimator to the convergence point, the dis-
a hexagonal pattern. This collimator was tance b from the front of the collimator to the
employed in the past for tomographic imaging. object (source), and the collimator thickness t
This type of tomography now is seldom used
clinically; however, multi-pinhole approaches I/O = ( f − t) / ( f + b) (13-5)
are being widely employed for some small-
animal imaging applications. where I and O are image and object size,
The parallel-hole collimator (Fig. 13-7B) is respectively. The useful image area becomes
the “workhorse” collimator in most imaging larger as the image becomes more minified
laboratories. Parallel holes are drilled or cast (Equation 13-4).
in lead or are shaped from lead foils. The lead
EXAMPLE 13-1
walls between the holes are called collimator
septa. Septal thickness is chosen to prevent γ What is the minification factor for a diverging
rays from crossing from one hole to the next collimator 5-cm thick, with f = 45╯cm, and a
(see Chapter 14, Section C.2). A magnified source distribution 15╯cm from the collima-
view of a parallel-hole collimator is shown in tor? If the detector diameter is 30╯cm, what is
Figure 13-8. The parallel-hole collimator proj- the imaged area at this distance?
ects a γ-ray image of the same size as the
source distribution onto the detector. A varia- Answer
tion of the parallel-hole collimator is the From Equation 13-5,
slant-hole collimator, in which all of the holes I/O(minification factor)
are parallel to each other but angled, typically
= (45 − 5) / (45 + 15) = 0.67
by approximately 25 degrees, from the per-
pendicular direction. This type of collimator From Equation 13-4,
has characteristics that are similar to those Diameter of imaged area
of the parallel-hole type. Because it views the
= 30 cm/0.67 = 44.8 cm
source distribution from an angle rather than
PM tubes
Light guide
NaI(Tl) crystal
Collimator
C B A D
Patient with
-emitting
radionuclide
Liver concentrated in
liver
FIGURE 13-10 Illustration of different types of events that may be detected by a gamma camera. Red circles indi-
cate locations of γ ray interactions. A, Valid event. B, Detector scatter event. C, Object scatter event. D, Septal
penetration.
second time in the detector (as illus- the event is mispositioned, often many
trated in Fig. 13-10), in which case the centimeters from the original site of
full energy of the γ ray is deposited, or emission. These events lead to a low-
it may escape the detector, in which case spatial-frequency background in the
only part of the γ-ray energy is depos- images that results in a loss of contrast.
ited. In the former case, energy discrim- (See Chapter 15, Section C.). In clinical
ination cannot be used to reject the imaging situations, a large fraction of
event, and the event will be misposi- the detected events can be due to object
tioned between the two interaction loca- scatter, and good energy resolution in
tions. In the latter case, it is likely that the gamma camera is extremely impor-
the event will be rejected because it does tant (see Chapter 14, Section A.3). The
not satisfy the event energy criteria collimator itself can also be a cause of
established by the upper- and lower- scatter leading to similar effects.
level discriminators. As discussed in D: septal penetration—in this case a γ ray
Chapter 14, Section A.1, these events is emitted toward the collimator, but not
are relatively rare. parallel to it. Because of incomplete
C: object scatter event—the γ ray is not attenuation by the thin collimator walls
emitted toward the collimator holes but (septal penetration), there is a finite
is scattered within the body, then passes chance that the γ ray will reach the
through a collimator hole and subse- NaI(Tl) crystal and interact with it. This
quently is detected. The γ ray loses again leads to blurring of the image,
energy during scattering and will there- because all events are con�sidered to
fore produce a smaller signal in the have come from a direction perpendicu-
detector. Some of these events will be lar to the collimator face (for parallel-
rejected by energy discrimination, but if hole collimators). This effect becomes
the angle of scatter is small (â•›45 increasingly important when using
degrees), the energy loss is small and high-energy γ emitters or high-resolution
the event may be accepted. In this case collimators with thin septa.
206 Physics in Nuclear Medicine
Gallbladder
1st minute 2nd minute 3rd minute 4th minute 5th minute
6th minute 7th minute 8th minute 9th minute 10th minute
FIGURE 13-14 Planar gamma camera images over the region of the gallbladder following injection of 99mTc-HIDA. At
approximately 7 minutes, cholecystokinin was given to the patient to stimulate emptying of the gallbladder. The rate
and extent of emptying can be measured from this dynamic sequence of planar images. (Courtesy GE Medical Systems,
Milwaukee, WI.)
208 Physics in Nuclear Medicine
The performance of a gamma camera system blurring caused by the collimator, is called the
is defined by the sharpness and detail of the intrinsic spatial resolution of the camera.
images it produces, the efficiency with which Intrinsic resolution is limited primarily by
it detects incident radiation, its ability to two factors. The first is multiple scattering of
measure the energy of the incident γ rays (to γ-ray photons within the detector. If a photon
minimize scatter), and the counting rate it can undergoes Compton scattering within the
handle without significant dead time losses. A detector crystal and the residual scattered
gamma camera is not capable of producing photon also is detected, but at some distance
“perfect” images of the radionuclide distribu- away, the two events are recorded as a single
tion. Certain inherent imperfections arise event occurring at a location along the line
from the performance characteristics of the joining the two interaction sites. This is not
detector, its associated electronic circuitry, a serious cause of degraded resolution for
and the collimator. Image artifacts also can be photon energies 300╯keV in which multiple
caused by malfunctions of various camera scatter Compton interactions in NaI(Tl) are
components. In this chapter, we describe the almost negligible. Even at 662╯keV, Anger
major factors that determine gamma camera calculated that for a detector thickness of
performance and examine the limitations that 6.4╯mm, less than 10% of photons are mis-
can lead to artifacts in gamma camera images placed by more than 2.5╯mm as a result of
and their correction. Standard tests of gamma multiple scattering events.1
camera performance also are summarized. The second, and primary, cause of limited
intrinsic resolution is statistical fluctuation
in the distribution of light photons among
A. BASIC PERFORMANCE photomultiplier (PM) tubes from one scintil-
lation event to the next. The problem is
CHARACTERISTICS
exactly analogous to the statistical fluctua-
tions observed in radioactive decay, discussed
1. Intrinsic Spatial Resolution in Chapter 9. If a certain PM tube records, on
Spatial resolution is a measure of the sharp- average, N light photons from scintillation
ness and detail of a gamma camera image. events occurring at a certain location in the
Sharp edges or small, pointed objects produce detector crystal, the actual number recorded
blurred rather than sharply defined images. from one event to the next varies with a stan-
Part of the blurring arises from collimator dard deviation given by N . Thus if a very
characteristics discussed in Sections C and D narrow beam of γ rays is directed at a point
and part arises in the sodium iodide [NaI(Tl)] on the detector, the position of each event as
detector and positioning electronics. The limit determined by the positioning circuitry or
of spatial resolution achievable by the detec- computer algorithm is not precisely the same.
tor and the electronics, ignoring additional Rather, they are distributed over a certain
209
210 Physics in Nuclear Medicine
area, the size of which depends on the mag- their distribution are therefore proportional
nitude of these statistical fluctuations. to 1/ N . This causes noticeably greater blur-
A detailed method for measuring and char- ring at lower γ-ray energies. An example of
acterizing intrinsic spatial resolution is dis- the change of intrinsic spatial resolution as
cussed in Section E.1. Typically, a lead mask a function of γ-ray energy is shown in Figure
containing a number of narrow (~1╯mm) slits 14-1.
is placed on the face of the gamma camera Intrinsic resolution also depends on detec-
(without the collimator) and the camera is tor crystal thickness. Thicker detectors result
irradiated using a 99mTc (140-keV) point in greater spreading of scintillation light
source. The resulting image is a series of lines before it reaches the PM tubes. Furthermore,
corresponding to the locations of the slits there is a greater likelihood of detecting
(e.g., see Fig. 14-10A). The resolution is cal- multiple Compton-scattered events in thicker
culated as the full width at half maximum detectors, particularly with higher-energy
(FWHM) of a profile drawn perpendicular to radionuclides. These are the primary reasons
the image of the lines at various locations in why gamma cameras use relatively thin
the field of view. The intrinsic spatial resolu- detectors in comparison with NaI(Tl) systems
tion of modern large field-of-view gamma that are used for counting applications.
cameras measured with 99mTc in this manner Figure 14-2 shows an example of the intrin-
is in the range of 2.9- to 4.5-mm FWHM. sic spatial resolution versus crystal thickness
Because the resolution is considerably worse for 140-keV γ rays.
than the width of the slits, the contribution of Intrinsic resolution improves with increased
the slits themselves to the measured resolu- efficiency of collection of scintillation photons.
tion is very small (10% for measured resolu- Modern cameras are substantially improved
tion 2.5╯mm). over earlier versions in this regard because of
Intrinsic resolution becomes worse with the use of more efficient PM tubes and of
decreasing γ-ray energy because lower-energy better techniques for optical coupling between
γ rays produce fewer light photons per scinÂ� the detector crystal and the PM tubes. The
tillation event, and smaller numbers of light use of greater numbers of smaller PM tubes
photons result in larger relative statistical (5-cm-diameter tubes have become the stan-
fluctuations in their distribution (Chapter 9, dard, and some gamma cameras have as
Section B.1). As a rule of thumb, intrinsic many as 110 PM tubes per head) and improved
resolution is proportional to 1/ E, in which electronics also have contributed to this
E is the γ-ray energy. This follows because improvement. Accurate corrections for non-
the number of scintillation light photons linearity (see Section B.1) and nonuniformity
produced, N, is roughly proportional to E (see Section B.2) have also resulted directly
and the relative statistical fluctuations in in improvements in intrinsic resolution, as
4.5
Intrinsic resolution (mm FWHM)
4
FIGURE 14-1 Intrinsic spatial resolution
of a gamma camera as a function of γ-ray
energy for a 6.3-mm-thick NaI(Tl) crystal.
(Compiled with data from Sano RM,
3.5 Tinkel JB, LaVallee CA, Freedman GS:
Consequences of crystal thickness reduc-
tion on gamma camera resolution and sen-
sitivity. J Nucl Med 19:712-713, 1978; and
Muehllehner G: Effect of crystal thickness
3 on scintillation camera performance. J
Nucl Med 20:992-993, 1979.)
2.5
0 50 100 150 200 250 300 350 400
-ray energy (keV)
14 • The Gamma Camera: Performance Characteristics 211
5.5
FIGURE 14-2 Intrinsic spatial resolution
of a gamma camera at 140╯keV as a function
of crystal thickness. (Compiled with data 5
discussed in the following sections. The best 100% efficient for energies up to approxi-
reported intrinsic resolution for a large field- mately 100╯keV for all crystal thicknesses,
of-view gamma camera is just below 3╯mm but then shows a rather marked decrease in
FWHM at 140╯keV ( 99mTc). Significant efficiency at higher energies, depending on
improvements beyond approximately 2╯mm crystal thickness. At 140╯keV (γ-ray energy of
99m
FWHM will be difficult to achieve, owing to Tc), the difference in efficiency between
the ultimate limitation of the light photon 6.4-mm and 12.7-mm-thick crystals is approx-
yield of NaI(Tl). In most practical situations, imately 20% and the photopeak detection
however, the intrinsic spatial resolution efficiency is in the 70% to 90% range. At
makes a negligible contribution to the overall approximately 500╯keV, the standard gamma
system resolution of the gamma camera, camera (detectors 0.64-0.95-cm-thick) is less
which is largely determined by the resolution than 20% efficient at converting incident γ
of the collimator (see Sections C and D). rays into photopeak pulses.
At high energies, the performance of gamma
2. Detection Efficiency cameras with 0.64- to 1.27-cm-thick crystals
The gamma camera employs a sodium iodide is limited by decreasing detection efficiency
crystal that is relatively thin in comparison (as well as increasing collimator septal
with most other sodium iodide detectors used penetration—see Section C.2). Deteriorating
in nuclear medicine: 6.4 to 12.7╯mm versus 2 intrinsic spatial resolution becomes the limit-
to 5╯cm for probe counting systems, scanners, ing factor at lower energies. Because of these
and so on. The trade-off in gamma cameras is tradeoffs, the optimal γ-ray energy range is
between detection efficiency (which improves approximately 100 to 200╯keV for most gamma
with thicker crystals) and intrinsic spatial cameras. Some gamma cameras are now fitted
resolution (which improves with thinner with thicker crystals (12.7-25.4╯mm), enabling
crystals—see Fig. 14-2). The gamma camera is them to achieve improved efficiency for
designed to provide acceptable detection effi- imaging positron-emitting radionuclides at
ciency while maintaining high intrinsic spatial 511╯keV (Chapter 18, Section B.4). This comes
resolution in the energy range of 100-200╯keV. at the expense of some loss of intrinsic spatial
As a result, the detection efficiency of the resolution (see Fig. 14-2) when these systems
gamma camera detector is somewhat less than are used in the 100-200-keV energy range.
would be desirable at higher γ-ray energies.
Figure 14-3 shows photopeak detection 3. Energy Resolution
efficiency versus γ-ray energy for the gamma It is not unusual in a typical patient study for
camera detector for a range of NaI(Tl) crystal there to be more Compton-scattered than
thicknesses. The gamma camera is nearly unscattered γ rays striking the detector (see
212 Physics in Nuclear Medicine
5.08
2.54
10 1.27
0.64
1
0 100 200 300 400 500 600 700
-ray energy (keV)
FIGURE 14-3 Photopeak detection efficiency versus γ -ray energy for NaI(Tl) detectors of different thicknesses.
(Adapted from Anger HO: Radioisotope cameras. In Hine GJ [ed]: Instrumentation in Nuclear Medicine, Vol 1. New
York, 1967, Academic Press, p 506.)
and those scattered through smaller angles cardiac studies. Dead time corrections can be
are rejected less efficiently. applied; however, these corrections generally
Two advantages are obtained with improved become increasingly inaccurate as counting
energy resolution. First, the photopeak losses increase.
becomes narrower, resulting in more efficient Because pulse pile-up can occur between
detection of unscattered photons within the any two events in the pulse-height spectrum,
chosen energy window. This increases the system counting losses are determined by
number of valid events recorded and improves total-spectrum counting rates. Most gamma
the statistical quality of the image. Second, cameras behave as paralyzable systems. The
γ rays scattered through large angles are apparent dead time for a selected energy
rejected more efficiently, because their energy window depends on the window fraction, that
spread within the pulse-height spectrum is is, the fraction of the total spectrum counting
also smaller. Thus image contrast is improved. rate occurring within that window. The smaller
It also is true that γ rays scattered through the window fraction, the larger the apparent
smaller angles are detected somewhat more dead time. Thus the apparent dead time is
efficiently, because of the narrowing of their longer when a photopeak window is used than
distribution as well. However, the increased when a full-spectrum window is used. The
efficiency for recording photopeak events apparent dead time also is longer when
more than offsets this effect, in terms of scattered radiation is present, because this
contrast-to-noise ratio (Chapter 15, Section also adds to the counting rate outside the
D.2). Alternatively, one can take advantage of photopeak window (Fig. 14-5). Therefore,
the improved energy resolution to use a nar- when specifying gamma camera dead time, it
rower PHA window, trading back some of the is important to note the conditions of mea�
increased efficiency for recording photopeak surement. Dead time values as short as 1 to 2
events for improved rejection of small-angle µsec can be obtained in the absence of scatter-
scatter. Either way, improved energy resolu- ing material with a full-spectrum window;
tion results in better image quality. however, under clinically realistic conditions
(99mTc source in scattering material, 15% pho-
4. Performance at High topeak window), system dead times of 4 to 8
Counting Rates µsec are more typical. For a dead time of 5 µsec,
At high counting rates, there is increased like- counting losses are approximately 20% for a
lihood of recording two events at the same counting rate of 4 × 104 counts per second (cps).
time. The most troublesome effect is known as Dead time losses are not serious in most
pulse pile-up (Chapter 8, Section B.3). Pulse static imaging studies, but they can be impor-
pile-up has two undesirable effects on gamma tant in certain high-counting-rate applica-
camera performance: counting losses and tions (e.g., first-pass cardiac studies) in which
image distortion. counting rates as high as 105 cps may occur.
Counting losses cause inaccurate counting Pile-up rejection circuitry (see Chapter 8,
rates to be recorded at higher counting rates. Section B.3) is used to achieve higher usable
The inaccuracies are described by conven- counting rates in such situations. Another
tional dead time models (Chapter 11, Section approach for shortening camera dead time is
C) and may be significant in some high-count- by the use of analog buffers, or derandomiz-
rate quantitative studies, such as first-pass ers. These are electronic circuits that “hold” a
Observed counting rate
Source Source
Source behind in air No losses in air
Counts
10 cm water
voltage level or pulse from one circuit compo- (see Chapter 13, Section B.2), two events
nent (e.g., an amplifier) until the next circuit detected simultaneously at different locations
in the pulse-processing sequence (e.g., the in the detector are recorded as a single event
PHA) is ready to receive it. with energy equal to the sum of the two
Similarly, in digital gamma cameras, data events, at a location somewhere between
can be buffered in memory until the computer them (Fig. 14-6). If both are valid photopeak
is ready to process them. Both these approaches events, their total energy exceeds the value
result in a decrease in the “apparent” dead that would be accepted by the PHA window
time of the camera by effectively changing the and both events are rejected, resulting in
arrival times of the pulses. This, however, counting losses. On the other hand, it is pos-
means that the simple dead time models and sible for two Compton-scattered γ rays to
corrections presented in Chapter 11, Section have a total energy that falls within the
C can no longer be used, and more complex selected energy window, so that two invalid
modeling of system dead time must be carried events are accepted as a single valid event.
out to produce accurate correction at high The visible result at very high counting rates
counting rates. is to add a diffuse background to the image,
It also is possible to physically shorten the as illustrated in Figure 14-7. Note as well the
dead time of a camera by shortening the image in the upper right-hand corner of this
charge integration time from the PM tubes figure, showing how contrast can be restored
and using electronic circuitry that returns the by shielding high-activity areas outside the
signal to baseline after the chosen integration imaging area of interest (e.g., with a thin
time.2 Clearly, this also decreases the amount sheet of lead).
of signal used for determining event location. Early pile-up rejection methods were based
For example, with a charge integration time on measuring the length of a pulse. If the
of 0.4 µsec, only 81% of the scintillation light pulse did not return close to baseline level
is collected, compared with 98% for a 1-µsec within the time expected given the decay time
integration time. This causes a degradation of of NaI(Tl), it was assumed that pile-up of
intrinsic spatial resolution and energy resolu- two pulses had occurred and the event was
tion. Some gamma cameras have a variable rejected, resulting in the loss of both γ rays.
integration time, in which the charge integra- This improved image quality but resulted in
tion is automatically shortened as the count- an effective increase in system dead time,
ing rate increases. because many events were rejected at high
Other means for shortening dead time are counting rates.
to bypass altogether the pile-up rejection cir- Many gamma cameras now incorporate cir-
cuits and nonuniformity correction circuitry cuits that continuously monitor the decay of
(see discussion on pile-up correction later in a pulse and use a method based on pulse-tail
this section and on nonuniformity and its cor- extrapolation for pile-up correction. Consider
rection in Section B.3). The signal processing two γ-ray interactions that occur close together
that occurs in these circuits slows down the in time and create overlapping pulses. When
rate at which the camera can handle indi- the second γ ray arrives, the decay of the
vidual events, and bypassing them can pulse created by the first γ ray immediately
shorten system dead time from typical values
of 4 to 8 µsec down to 1 to 3 µsec. Some
cameras provide an optional “high count rate”
mode of operation in which some or all of
these corrections are turned off by software Source
control. This mode is intended specifically for Pile-up
applications requiring high counting rates, Source
such as first-pass cardiac studies. “Normal
mode,” in which all corrections are employed,
is used for routine imaging to obtain the
desired high-quality images. Obviously speci-
fications for gamma camera dead time should
indicate whether any circuits were bypassed
to achieve the reported value.
FIGURE 14-6 Images of two 99mTc point sources of rela-
The second undesirable effect of pulse tively high activities (~370 MBq each). Events appearing
pile-up is image distortion. Using standard in the band between the two point-source locations are
pulse-positioning logic for gamma cameras mispositioned events caused by pulse pile-up.
14 • The Gamma Camera: Performance Characteristics 215
105
3.2 min
103
1.0 10 100
Activity in phantom (mCi)
deviates from the expected exponential decay of NaI(Tl). At the same time, this extrapo-
and the gamma camera signal is switched to lated tail is also sent to the second amplifier
a second amplifier circuit. Estimator circuitry circuit and subtracted from the second pulse.
in the first amplifier circuit completes the This removes the contribution of the pulse
signal from the first γ ray by extrapolating the generated by the first γ ray from that of the
remainder of the tail of the pulse with an second γ ray. This process is summarized
exponential function based on the decay time in Figure 14-8. The pulse-tail extrapolation
P2 P1 + P2
P1
Amplifier
Estimator
P2
Subtractor
Amplifier 2
P2 + P1 Tail
216 Physics in Nuclear Medicine
A B
FIGURE 14-10 A, Illustration of nonlinearities in images of a straight-line test pattern obtained with a gamma camera.
Image demonstrates subtle waviness in the lines. B, Flood-field image obtained by exposing the same camera to a
uniform radiation field. This is the image obtained in the absence of any corrections for nonuniformity. Notice that the
photomultiplier tube pattern can be seen. The gray levels in this image are confined to a narrow display window to
improve visualization of the artifacts. (Images courtesy Dr. Magnus Dahlbom, UCLA School of Medicine, Los Angeles,
CA.)
14 • The Gamma Camera: Performance Characteristics 217
modern gamma camera to demonstrate the in areas of barrel distortion events are pushed
general appearance of nonlinearities. On outward from the center, causing an apparent
close inspection, some waviness of the lines is “cold spot.” Because of the characteristic pin-
apparent. On properly functioning cameras, cushion distortions occurring in front of PM
including the one illustrated, the nonlineari- tubes, it is common to see a pattern of hot
ties themselves (including the pincushion spots at the locations of the PM tubes on an
distortions in front of PM tubes) are barely otherwise uniform gamma camera image.
perceptible and rarely interfere directly with Other causes of nonlinearities (e.g., PM tube
image interpretation; however, they can have failure, crystal cracking, and collimator
significant effects on image nonuniformities, defects) also can result in nonuniformities.
as discussed in the following section. Another characteristic nonuniformity is a
bright ring around the edge of the image. This
2. Image Nonuniformity artifact, called edge packing, results from a
A more noticeable problem is image non� somewhat greater light collection efficiency
uniformity. Exposing the detector crystal to a for events near the edge versus central regions
uniform flux of radiation produces a flood- of the detector crystal. This is the result of
field image with small but noticeable nonuni- internal reflections of scintillation light from
formities in intensity, even with a properly the sides of the detector crystal back into the
functioning camera. These variations may be PM tubes near the edge. Also, for events
equivalent to counting rate variations of ±10% occurring toward the center of the crystal,
or more. A flood-field image from a gamma there are always PM tubes on either side of
camera demonstrating image nonuniformity the event location, whereas at the edges of the
is shown in Figure 14-10B. Intrinsic flood- crystal there are PM tubes only to one side.
field images are acquired with the colli�mator Thus events at the very edges are not distrib-
removed, using a point source placed far uted uniformly across the edge, but are
enough from the surface of the gamma camera “pulled” toward the center, compounding the
to give uniform irradiation of the surface (dis- edge-packing artifact. The portion of the
tance equal to 4-5 times the camera diame- image demonstrating this artifact usually is
ter). Extrinsic flood-field images are acquired masked on the image display and therefore is
with the collimator in place using a disk or not a part of the useful field of view (UFOV ).
thin flood phantom that covers the area of the Typically, 5╯cm or more of the detector width
detector. 99mTc or 57Co are the two most is eliminated by the mask. When specifying
commonly used radionuclides for flood-field gamma camera detector dimensions, it is
measurements. important to distinguish between the physi-
There are two primary causes of gamma cal dimensions of the crystal and the dimen-
camera nonuniformities. The first is non- sions of the useful imaging area.
uniform detection efficiency arising from (1) Both nonuniformity and edge-packing
small differences in the pulse-height spec- artifacts are related to the pattern of the
trum for different PM tubes and (2) position- distribution of scintillation light falling on
dependent collection efficiency of scintillation the PM tubes. For this reason, they also have
light, particularly for events located over the an energy-dependent component. When the
gaps and dead areas between the PM tubes gamma camera is used to image higher-
compared with events located directly over energy radionuclides, interactions, on average,
the center of a PM tube. The differences in occur deeper in the crystal, closer to the PM
PM tube response can be minimized by careful tubes. This produces a more narrow light
selection and tuning of all of the PM tubes of spread distribution on the PM tubes and gen-
a gamma camera; however, position-dependent erally results in a worsening of detector
effects on the pulse-height spectrum remain. nonuniformity.
If a fixed pulse-height window is used for all
output pulses, the result is an apparent dif- 3. Nonuniformity Correction
ference in detection efficiency owing to differ- Techniques
ences in the “window fraction” for different All modern gamma cameras incorporate tech-
areas of the crystal (see Fig. 13-6, top). niques that attempt to correct the causes of
The second cause of nonuniformities is nonuniformity described in the preceding
image nonlinearities described in Section section. All of these techniques begin with
B.1. In areas of pincushion distortion events spatially varying energy corrections, normally
are crowded toward the center of the distor- derived from an intrinsic flood-field image.
tion, causing an apparent “hot spot,” whereas The flood-field image is divided into a matrix
218 Physics in Nuclear Medicine
of small, square elements, typically 128 × 128 counts recorded in each pixel are thrown out,
elements (or pixels). Using the PHA, the depending on the relative value for that pixel
channel number (pulse amplitude) of the photo� in the energy-corrected flood-field image.
peak in the pulse-height spectrum is deter- For example, if the value in the normalized
mined for each element. This information is intensity-correction matrix is 110, then 1 of
stored in a 128 × 128 look-up table and used every 11 counts is subtracted from the patient
to set regionally varying PHA windows for image at that location. This process is some-
subsequent studies on patients. For example, times called count skimming.
if a 20% window is chosen for a patient study, Most modern digital gamma cameras
and the center of the photopeak is found in replace the second step described in the pre-
PHA channel 100 in a particular pixel in ceding paragraph with a correction for image
the flood-field image, then events at that nonlinearity, which more directly attacks the
location having Z-signal amplitudes between major underlying cause of image nonunifor-
PHA channels 90 and 110 are accepted in mity. For nonlinearity corrections, another
patient imaging studies. If the center of the flood-field image is obtained, this time with a
photo�peak is in channel 110 at another loca- sheet of lead having a uniformly spaced array
tion, events for which the Z-signal falls within of small holes (~1-mm diameter, ~â•›4-mm sepa-
the range of 99 to 121 are accepted at that ration) placed directly on the gamma camera
location. The position-dependent PHA window face (no collimator). The locations of the images
corrects for variations in the pulse-height of these holes are compared with their known
spectrum across the face of the camera detec- locations in the lead sheet to derive a matrix
tor. It also provides a partial correction for of offsets, Δâ•›x and Δâ•›y, for each (X,Y ) location on
image nonuniformity. the detectors, which is stored as another
The second step in the nonuniformity cor- look-up table. When an event is detected, its X
rection is to account for the remaining regional and Y coordinates are computed using conven-
variations in image intensity, largely caused tional positional circuitry or algorithms. These
by detector nonlinearity. In one older method, values then are corrected using the positional
the correction is based directly on variations offsets for that location stored in the look-up
in intensity of the energy-corrected flood-field table. The offsets and the corresponding
image. The number of counts recorded within look-up table usually are measured and gener-
each pixel in that image is stored in a matrix ated at the factory prior to shipment.
and compared to the smallest number Figure 14-11 shows the same data as Figure
recorded in the pixel array. This is used to 14-10, after the corrections for nonuniformity
derive a matrix of normalized intensity values, and nonlinearity described in the preceding
which range from 100 for the “coldest” pixel paragraphs have been applied. Figure 14-12,
to higher values for other pixels. In subse- showing intensity profiles across the flood-
quent patient studies, a certain fraction of the field images in Figures 14-10 and 14-11,
A B
FIGURE 14-11 Straight-line test pattern (A) and uniform flood-field (B) images after nonuniformity corrections are
applied. Compare with Figure 14-10. (Images courtesy Dr. Magnus Dahlbom, UCLA School of Medicine, Los Angeles,
CA.)
14 • The Gamma Camera: Performance Characteristics 219
1.2 1.2
0.6 0.6
0.4 0.4
0.2 0.2
0 0
0 50 100 150 200 250 0 50 100 150 200 250
Pixel Pixel
No correction Corrected
FIGURE 14-12 Profiles through the uniform flood-field images in Figures 14-10 and 14-11 showing relative uniformity
of flood-field image with and without nonuniformity correction. The standard deviation is improved from 3.4% to 1.9%
after correction.
clearly illustrates the improvements. The the tube output has changed by more than 1%
examples in these figures are for 99mTc. Note from the original reference value.
that different correction matrices must be In newer gamma cameras, the large
obtained for each radionuclide used, because number of PM tubes makes the manual
the effects corrected for generally vary with method impractical. Many digital gamma
γ-ray energy, for example, because of different cameras therefore contain tuning circuitry
average depths of interaction in the NaI(Tl) that allows the output of each individual PM
crystal. tube to be automatically adjusted to a set of
Improvements in camera uniformity also reference outputs. One automated approach
have contributed to improvements in intrinsic involves the use of light-emitting diodes
resolution. Earlier cameras used thicker light (LEDs) that are coupled to the neck of each
guides and large-diameter PM tubes, in part PM tube. These LEDs are pulsed to produce
to achieve satisfactory uniformity, at the a light signal on the photocathode of the PM
expense of somewhat degraded spatial resolu- tube that does not vary with time. The PM
tion. Because of effective uniformity correc- tube signals are then monitored and the pre-
tions, newer gamma cameras can use thinner amplifier adjusted electronically if the PM
light guides (or eliminate the light guide tube signal has drifted.
entirely) and smaller PM tubes, both of which A second approach uses two narrow energy
contribute to more accurate event localization windows, placed just above the photopeak
and improved intrinsic spatial resolution. position to minimize the influence of scatter
(Fig. 14-13). The count ratio between the two
4. Gamma Camera Tuning energy windows during flood-field irradiation
The nonuniformity corrections described pre- by the radionuclide of interest is measured for
viously require that the gamma camera each PM tube. This ratio remains constant,
remain very stable over time. However, the unless the PM tube signal drifts over time. If
gain of PM tubes invariably changes as the the count ratio changes, the PM tube pream-
tubes age. The high-voltage supply and ampli- plifier is adjusted electronically to restore the
fier gain can also drift over time. A method to ratio to its original value.
“tune” the PM tubes to ensure consistent per- Some of these tuning methods also can be
formance over time is therefore necessary. adapted so that they are continuous, in the
On many older systems, the tuning is done sense that the camera is tuned dynamically
manually. One method involves irradiation of every few seconds during a patient study.
the gamma camera detector through a lead This can be used to adjust the energy
mask with holes centered over each of the PM windows in real time, compensating for any
tubes. The output of each PM tube is exam- drift that occurs during the course of a study.
ined and the preamplifier gain is adjusted if The major cause of drift on such short
220 Physics in Nuclear Medicine
500 Window 1
400
Window 2
Counts
300
200
100
0 50 100 150
Energy (keV)
FIGURE 14-13 The ratio of counts detected in two narrow energy windows can be used to determine whether a pho-
tomultiplier tube is drifting. The windows are defined on the high side of the photopeak to avoid any contribution from
scatter. The ratio is virtually independent of source distribution and the amount of scattering material present.
Collimator efficiency g, defined as the frac- camera systems also provide a selection of col-
tion of γ rays passing through the collimator limators with different combinations of resolu-
per γ ray emitted by the source is given by tion and efficiency. Those with good resolution
but poor efficiency generally are described as
g ≈ K 2 (d/leff )2 [ d2 / (d + t)2 ] (14-7) “high-resolution” collimators, whereas those
with the opposite chara�cteristics are described
where t is septal thickness and K is a constant as “high-sensitivity” collimators. Those with
that depends on hole shape (~0.24 for round characteristics intermediate to the extremes
holes in a hexagonal array, ~0.26 for hexago- are referred to as “general purpose,” “all
nal holes in a hexagonal array, ~0.28 for purpose,” or by other similar names.
square holes in a square array1). Equation Equation 14-6 indicates that collimator
14-7 applies to a source in air and assumes resolution becomes poorer as source-to-
no attenuation of radiation by intervening collimator distance b increases. Thus struc-
body tissues. tures closest to the collimator are imaged
Several aspects of Equations 14-6 and 14-7 with sharpest detail. Figure 14-16 shows
should be noted. First, resolution improves as graphically the relationship between colli-
the ratio of hole diameter to effective length mator resolution and source-to-collimator
(d/leff) is made smaller. Long, narrow holes distance for three different collimators pro-
provide images with the best resolution; vided by one commercial manufacturer. Typi-
however, collimator efficiency decreases cally, collimator resolution deteriorates by a
approximately as the square of the ratio of factor of 2 at a distance of 4-6╯cm from the
hole diameter to length (d/leff)2. Thus an collimator.
approximate relationship between collimator On the other hand, according to Equation
efficiency, g, and spatial resolution, Rcoll, is 14-7, collimator efficiency for a source in air
is independent of source-to-collimator dis-
g ∝ ( Rcoll )2 (14-8) tance b. This rather surprising result is
obtained provided the counting rate for the
Therefore for a given septal thickness, colli- entire detector area is measured. The reason
mator resolution is improved only at the for this is illustrated by Figure 14-17. As the
expense of decreased collimator efficiency, source is moved farther away from the colli-
and vice versa. mator, the efficiency with which radiation is
transmitted through any one collimator hole
EXAMPLE 14-3 decreases in proportion to 1/b2 (inverse-square
Calculate the efficiency g of the collimator law), but the number of holes through which
described in Examples 14-1 and 14-2, assum- radiation can pass to reach the detector
ing it has hexagonal holes in a hexagonal increases in proportion to b2. The two effects
array. cancel each other, with the result that total
counting rate—and thus collimator efficiency—
Answer does not change with source-to-collimator dis-
For hexagonal holes in a hexagonal array, tance. Another illustration of this effect is
K = 0.26. Thus, shown in Figure 14-18. As source-to-collima-
tor distance increases, the maximum height
g ≈ (0.26)2 (0.25 / 2.4)2 × [(0.25)2 / (0.25 + 0.03)2 ] of the PSF or LSF decreases, but the width
≈ (0.0676) × (0.0109) × (0.797) increases (and resolution becomes poorer), so
that the total area under the curve (total
≈ 5.85 × 10−4
detector counting rate) does not change.
(photons transmitted/photons emitted))
Invariance of collimator efficiency with
This example illustrates the relatively small source-to-collimator distance applies to point
fraction of emitted γ rays that are transmitted sources, line sources, and uniform sheet
by a typical gamma camera collimator. sources in air with parallel-hole collimators;
however, it applies only to uniform sheet
Equation 14-7 also demonstrates the effect sources with converging, diverging, or pinhole
of septal thickness on efficiency. Medium- collimators (Section D). When the source is
energy collimators have lower efficiencies embedded at different depths in the patient,
than low-energy collimators because of their attenuation effects also must be considered.
greater septal thicknesses. Septal penetration and scatter of photons
In addition to providing low- and medium- from the walls of the collimator holes also are
energy collimators, manufacturers of gamma not considered in the earlier analysis.
224 Physics in Nuclear Medicine
2.0
1.8
1.6
Collimator resolution FWHM (cm)
1.4
ity
1.2 itiv
ens
hs
1.0 Hig e
pos
al pur
ner
0.8 Ge
0.6 tion
solu
igh re
H
0.4
0.2
0.0
0 2 4 6 8 10 12 14 16
Source-to-collimator distance (cm)
FIGURE 14-16 Collimator resolution versus source-to-collimator distance for three different collimators. (Adapted
from Hine GJ, Paras D, Warr CP: Recent advances in gamma-camera imaging. Proc SPIE 152:123, 1978.)
Single-hole
efficiency 1/b2
Collimator
Detector
Counting rate
Distance
14 • The Gamma Camera: Performance Characteristics 225
TABLE 14-1â•…
PERFORMANCE CHARACTERISTICS OF SOME TYPICAL COMMERCIALLY MANUFACTURED
PARALLEL-HOLE COLLIMATORS
Resolution Rcoll
Recommended Max. (FWHM at
Collimator Type Energy (keV) Efficiency, g 10╯cm)
Low-energy, high-resolution 150 1.84 × 10−4 7.4╯mm
Low-energy, general-purpose 150 2.68 × 10 −4
9.1╯mm
Low-energy, high-sensitivity 150 5.74 × 10 −4
13.2╯mm
Medium-energy, high-sensitivity 400 1.72 × 10−4 13.4╯mm
Adapted from Hine GJ, Erickson JJ: Advances in scintigraphic instruments. In Hine GJ, Sorenson JA (eds):
Instrumentation in Nuclear Medicine, Vol 2. New York, 1974, Academic Press.
FWHM, full width at half maximum.
Table 14-1 summarizes the physical con- differences between system resolutions for
struction and typical performance character- cameras having substantially different intrin-
istics of a number of collimators. Collimator sic resolutions (e.g., 4╯mm vs. 8╯mm), but the
resolution is the FWHM for a source at 10╯cm difference in system resolutions for cameras
from the face of the collimator. Collimator effi- having small differences in intrinsic resolu-
ciency g refers to the relative number of γ rays tions (e.g., 4╯mm vs. 5╯mm) is minor and not
transmitted by the collimator and reaching clinically significant. Small differences in
the detector per γ ray emitted by the source. intrinsic resolution may be apparent on bar-
Note that the approximate relationship pattern images or on images of very superfi-
between collimator efficiency and resolution cial structures in the patient, but they usually
given by Equation 14-8 is verified by these are not apparent on images of deeper-lying
data. Note also the relatively small values for structures.
collimator efficiency. System resolution also is degraded by scat-
tered radiation. This is discussed in Chapter
4. System Resolution 15, Section C. The method for combining com-
The sharpness of images recorded with a ponent resolutions to determine system reso-
gamma camera is limited by several factors, lution also is discussed in Appendix G.
including intrinsic resolution, collimator reso-
lution, scattered radiation, and septal pene-
tration. In terms of the FWHM of a PSF or D. PERFORMANCE CHARACTERISTICS
LSF, the most important factors are the OF CONVERGING, DIVERGING, AND
intrinsic resolution Rint of the detector and PINHOLE COLLIMATORS
electronics, and the collimator resolution Rcoll.
The combined effect of these two factors is to Figure 14-20 illustrates the important design
produce a system resolution Rsys that is some- parameters for converging, diverging, and
what worse than either one alone. System pinhole collimators. Equations for collimator
resolution Rsys (FWHM) is given by resolution, Rcoll, and efficiency, g, for these col-
limators are as follows:
Rsys = 2
Rint + Rcoll
2 (14-9)
Converging Collimator:
Because collimator resolution depends on
source-to-collimator distance, system resolu- Rcoll ≈ [ d(leff
′ + b) / leff
′ ][1 / cos θ]
tion also depends on this parameter. Figure (14-10)
× [1 − (leff
′ / 2) /( f + leff
′ )]
14-19 shows system resolution versus source-
to-collimator distance for a typical parallel-
hole collimator and different values of intrinsic g ≈ K 2 (d / leff
′ )2 [ d2 /(d + t)2 ][ f 2 /( f − b)2 ]
resolution. At a distance of 5-10╯cm (typical (14-11)
depth of organs inside the body), system
resolution is much poorer than intrinsic where
resolution and is determined primarily by
collimator resolution. There are significant ′ ≈ (l − 2µ −1 ) / cos θ ≈ leff / cos θ (14-12)
leff
226 Physics in Nuclear Medicine
1.8
m
1.6 8m
t
R in m
4m
1.4 t
R in
0
System resolution, FWHM (cm)
t
1.2 R in
0.4 Typical
organ
depths
0.2
0.0
0 2 4 6 8 10 12 14 16
Source-to-collimator distance (cm)
f
d d detector
α
l l l
d
b b
b
f
Rcoll ≈ [ d(leff
′ + b) / leff
′ ][1 / cos θ][1 + (leff
′ / 2 f )] Rcoll ≈ deff ,R (l + b) /l (14-15)
(14-13)
g ≈ K 2 (d / leff
′ )2 [ d2 /(d + t)2 ][( f + l) /( f + l + b)]
(14-14) g ≈ deff ,g 2 cos3 θ/ (16b2 ) (14-16)
14 • The Gamma Camera: Performance Characteristics 227
20 250
Diverging
16 200 Converging
Relative geometric efficiency
System resolution (mm)
Parallel-hole
12 150
Parallel-hole
8 100
Pinhole
4 Converging
50
Diverging
Pinhole
0 0
0 5 10 15 20 0 5 10 15 20
A B
Source-to-collimator distance (cm)
FIGURE 14-21 Performance characteristics ( A, system resolution; B, point-source geometric efficiency in air) versus
source-to-collimator distance for four different types of gamma camera collimators. (Adapted with permission from
Society of Nuclear Medicine from Moyer RA: A low-energy multihole converging collimator compared with a pinhole
collimator. J Nucl Med 15:59-64, 1974.)
228 Physics in Nuclear Medicine
(~35╯cm), where γ rays are transmitted distance; they also have a quite limited field
through all of the collimator holes, and then of view because of magnification effects at
decreases beyond that point. Point-source typical imaging distances (Equation 13-3).
collimator efficiency decreases with distance Generally they are used for imaging smaller
for the diverging and pinhole collimators, organs, such as the thyroid and heart, which
more severely for the latter. For an extended, can be positioned close to the collimator. They
large-area sheet source, sufficiently large to also are useful with high-energy γ-ray emit-
cover the entire field of view of the collimator, ters because they can be designed to reduce
efficiency does not change with source-to- septal penetration problems.
collimator distance for all of these collima- Differences between the resolution and
tors. Again, for sources embedded within a field-of-view obtained at different source-to-
patient, attenuation effects also must be collimator distances with parallel-hole, con-
accounted for. verging, diverging, and pinhole collimators are
Figure 14-21 illustrates that the converg- further illustrated by Figure 14-22. The distor-
ing collimator offers the best combination of tions caused by changing magnification with
resolution and efficiency at typical imaging depth for different structures inside the body
distances (5 to 10╯cm); however, the field-of- sometimes make images obtained with the
view is also somewhat limited at these dis- converging, diverging, and pinhole collimators
tances (Equation 13-6 and Example 13-2), difficult to interpret (see Fig. 13-9).
and for this reason converging collimators are
most useful with cameras having relatively
large-area detectors. Diverging collimators E. MEASUREMENTS OF GAMMA
offer a larger imaging area (Example 13-1) CAMERA PERFORMANCE
but at the cost of both resolution and effi-
ciency. Pinhole collimators offer very good It is important to define standardized experi-
resolution and reasonable efficiency at close mental protocols for measuring gamma
distances but lose efficiency very rapidly with camera performance that produce consistent
At
collimator
face
10 cm
distance
20 cm
distance
results, are easily reproducible, and that do (<10,000 cps for a small field-of-view gamma
not require specialized equipment. Such pro- camera) to avoid pile-up-related mis�
tocols can then be used in comparing one positioning. Two sets of images are taken,
gamma camera with another, in performing with a 90-degree rotation of the test pattern
acceptance testing on a newly installed between acquisitions so that both X and Y
gamma camera, and as part of a quality resolution are measured. Data are acquired
assurance program to ensure that the camera until the peak channel has at least 1000
is always performing to its specifications. counts. Images are acquired in a matrix with
The exact regulations for gamma camera pixel sizes less than 1 10 of the expected reso-
quality assurance and the guidelines for lution (typically <╛0.35╯mm). Profiles through
acceptance testing vary with locality. For the images of the line sources are taken at
example, in the United States, the Joint different locations across the gamma camera
Commission requires that instruments be face and fitted to a Gaussian function
tested prior to initial use and that the per� (Chapter 9, Section B.3). The FWHM (Fig.
formance of a gamma camera be tested at 14-15) and full width at tenth maximum
least once a year. Because of the rapidly (FWTM) of the profiles are measured in both
changing regulatory environment, and differ- X and Y directions. The reported measure-
ences between states and countries, a detailed ments usually are average measurements
review of the requirements of regulatory across the UFOV, and the average across the
agencies is beyond the scope of this book. In central field-of-view (CFOV ) that has linear
this section, we therefore briefly summarize dimensions scaled by 75% with respect to the
the more common measurements that are dimensions of the UFOV. Typical values of
performed to assess gamma camera perfor- intrinsic spatial resolution are 2.5 to 3.5╯mm.
mance (whether they be for acceptance
testing or for quality assurance). The proto- 2. System Resolution
cols presented here are largely based on the This measurement is made with the collima-
recommendations of the National Electrical tor in place and should be repeated for each
Manufacturers Association.6 A typical quality collimator of interest. The source consists of
assurance program might involve daily mea- two 1-mm-diameter line sources, placed 5╯cm
sures of flood-field uniformity, weekly checks apart at a distance of 10╯cm from the front
of spatial resolution and spatial linearity, face of the collimator. The measurement also
and semiannual checks of other performance can be performed with the addition of a scat-
parameters. It is important that all measure- tering medium by placing 10╯cm of plastic
ments be taken under the same conditions between the sources and the collimator, and
(pulse-height window width, correction algo- 5╯cm of the same material behind the sources.
rithms, and correction circuitry on or off ) as Images are acquired (typically several million
are used for routine clinical studies. More events, at a rate of <â•›30,000 cps to avoid pile-
detailed information on performance mea- up) and profiles taken through the image of
surements, quality assurance, and accep- the line sources are fitted to Gaussian func-
tance testing can be found in references tions to determine FWHM and FWTM as
7 to 9. described for intrinsic resolution. The results
vary widely depending on the exact type of
1. Intrinsic Resolution collimator used but are typically in the range
Intrinsic resolution is determined without a of 8 to 14╯mm for 99mTc.
collimator using a linearity test pattern, such
as the one shown in Figure 14-10 (left), placed 3. Spatial Linearity
directly on the surface of the NaI(Tl) crystal This measurement uses the same slit pattern
housing. The width of the strips in the pattern (Fig. 14-10A) and conditions as for the intrin-
is approximately 1╯mm, which is significantly sic resolution measurement. Once again,
smaller than the resolution expected in the measurements are taken with two orienta-
measurement. A point source (usually 99mTc tions of the test pattern, rotated by 90 degrees,
or 57Co) is placed at a distance equal to five to provide linearity measurements in both X
times the UFOV from the gamma camera and Y directions. Two measurements can be
face. The UFOV corresponds to the field of made from the resulting images. The differ-
view of the gamma camera after masking off ential spatial linearity is the deviation of the
the portion of the camera face affected by measured distance di between two slits from
edge-packing effects. Data are acquired with the actual distance D between them calcu-
the system count rate below 30,000 cps lated for each row i in the image. The means
230 Physics in Nuclear Medicine
and the standard deviations are reported for across all rows and columns of the image. It
the X and Y directions across the UFOV and is defined as
the CFOV and are defined as:
( high − low )
Differential Uniformity (%) = 100 ×
n ( high + low )
∑ (d i − D)
(14-19) (14-22)
i =1
Mean =
n where “high” refers to the maximum count
n difference for any five consecutive pixels (row
∑ (d i − D)2 (14-20) or column) in the image and “low” refers to
Standard Deviation = i =1 the minimum count different for any five con-
n −1 secutive pixels. This usually is reported for
the UFOV.
In addition, the absolute spatial linearity is For convenience, uniformity measurements
defined as the maximum deviation of the often are made with the collimator in place
location of the slits from their true location. (extrinsic uniformity). A thin flood-field source
Once again this is assessed for the UFOV of 99mTc or a disk source of 57Co that covers the
and the CFOV. It is not easy to detect small active area of the gamma camera is placed on
nonlinearities using these techniques, and top of the collimator to provide uniform irra-
tests of uniformity (discussed in the next diation. This protocol is more practical for
section) usually are better at revealing the routine quality assurance because the mea-
effects of small nonlinearities. surement can be done without removing the
collimator. Extrinsic uniformity measure-
4. Uniformity ments also have the advantage that they
Intrinsic uniformity is determined from flood- reveal any defects or problems caused by the
field images acquired without a collimator. A collimator itself.
99m
Tc source is placed at a distance of approxi-
mately 5 × the UFOV from the front face of 5. Counting Rate Performance
the gamma camera. The source activity is As described in Section A.4, most gamma
such that the counting rate on the gamma cameras behave as paralyzable counting
camera is less than approximately 30,000 cps. systems with the observed count rate described
Flood-field images are acquired so that there as a function of the true count rate by Equa-
are a minimum of 4000 counts in each pixel tion 11-18. The basis for measurement of the
of the image and then smoothed with a 9-point dead time, τ, is the two-source method
(3 × 3) smoothing filter with the following described in Chapter 11, Section C.4. Two
99m
weightings: Tc sources are placed approximately 1.5╯m
away from the camera face. The total activity
1 2 1 should be sufficient to cause approximately a
2 4 2 20% loss in the observed counting rate rela-
tive to the true counting rate. Counting rates
1 2 1 then are measured with both sources present,
and then with each individual source present.
Integral uniformity is based on the Care must be taken that all measurements
maximum and minimum pixel counts in the are performed with exactly the same source
image and is defined as geometry, that pile-up rejection electronics or
any other high counting rate correction cir-
Integral Uniformity (%) cuitry is turned on, and that source decay is
negligible (<1%) during the course of the mea-
max. pixel count − min. pixel count
= 100 × surement. The dead time can then be calcu-
max. pixel count + min. pixel count lated from Equation 11-25. The observed
(14-21) count rate at which a 20% counting rate loss
occurs, R20%, is also often quoted, and this can
This is calculated for the UFOV and CFOV. be computed from Equation 11-18 using the
Integral uniformity values are typically 2% fact that Ro = 0.8Rt as
to 4%.
Differential uniformity is based on the 0. 8
R20% = − ln(0.8) (14-23)
change in counts of five consecutive pixels τ
14 • The Gamma Camera: Performance Characteristics 231
A phantom that can be used for more objec- A still more quantitative approach to eval-
tive testing of spatial resolution is shown in uating spatial resolution is by means of the
Figure 15-2. Bar phantoms are constructed of point-spread function (PSF) or line-spread
lead or tungsten strips, generally encased in function (LSF). General methods for record-
a plastic holder. Strips having widths equal ing these functions were described in Chapter
to the spaces between them are used. For 14, Section E.2. Examples of LSFs are shown
example, a “5-mm bar pattern” consists of in Figure 17-8 for a single-photon emission
5-mm-wide strips separated edge to edge by computed tomography (SPECT) camera and
5-mm spaces. The four-quadrant bar phantom in Figure 18-5 for a PET system. Although the
shown in Figure 15-2 has four different strip complete profile is needed to fully character-
widths and spacings. To evaluate the intrinsic ize spatial resolution, a partial specification
resolution of a gamma camera, the bar is provided by its FWHM (Fig. 14-15). The
phantom is placed directly on the uncollimated FWHM is not a complete specification because
detector and irradiated with a uniform radia- PSFs or LSFs of different shapes can have the
tion field, typically a point source of radio� same FWHM. (Compare, for example, the dif-
activity at several meters distance from the ferent shapes in Figs. 18-5 and 18-7). However,
detector. To evaluate the resolution with a col- the FWHM is useful for general comparisons
limator, the phantom is placed directly on the of imaging devices and techniques. Roughly
collimated detector and irradiated with a point speaking, the FWHM of the PSF or LSF of an
source at several meters distance, or with a imaging instrument is approximately 1.4-2
sheet source of radioactivity placed directly times the width of the smallest resolvable
behind the bar phantom. Spatial resolution is bar pattern (Fig. 15-3). Thus an instrument
expressed in terms of the smallest bar pattern having an FWHM of 1╯cm should be able to
visible on the image. There is a certain amount resolve 5- to 7-mm bar patterns.
of subjectivity to the eva�luation, but not so In most cases, multiple factors contribute
much as with organ phantoms. to spatial resolution and image blurring. The
To properly evaluate spatial resolution method for combining FWHMs for intrinsic
with bar phantoms, one must ensure that the and collimator resolutions to obtain the
thickness of lead strips is sufficient so that overall system FWHM is discussed in Chapter
they are virtually opaque to the γ rays being 14 , Section C.4 and in Appendix G. In general,
imaged. Otherwise, poor visualization may if a system has n factors or components that
be due to poor contrast of the test image each contribute independently to blurring,
rather than poor spatial resolution of the individually characterized by FWHM1,
imaging device. For 99mTc (140╯keV╛) and FWHM2, . . ., FWHMn, the FWHM for the
similar low-energy γ-ray emitters, tenth-value system is given by
thicknesses in lead are approximately 1╯mm
or less, whereas for 131I (364╯keV╛), annihila- FWHMsys
tion photons (511╯keV), and so on, they are on ≈ FWHM12 + FWHM22 + … + FWHM2n
the order of 1╯cm (see Table 6-4). Most com-
(15-1)
mercially available bar phantoms are designed
for 99mTc and are not suitable for use with This equation provides an exact result when
higher-energy γ-ray emitters. all of the components have gaussian-shaped
FIGURE 15-2 Design (left) and gamma camera image (right) of a four-quadrant bar phantom used for evaluation of
spatial resolution.
236 Physics in Nuclear Medicine
Radiation intensity
at detector
Total counting
rate
Radiation intensity
or counting rate
Individual bar
pattern counting
rates
Distance
FIGURE 15-3 Counting-rate profiles obtained on a bar pattern phantom with an imaging system having FWHM reso-
lution approximately 1.6 times the width of individual bars and spaces.
blurring functions, but it is an approximation varies with distance (cycles per centimeter or
when nongaussian shapes are involved. Note cycles per millimeter). This is called the
that if the FWHM for any one factor is signifi- spatial frequency of the test pattern, custom-
cantly larger than the others, it becomes the arily symbolized by k.* The modulation of the
dominating factor for system FWHM. Thus, test pattern, which is a measure of its con-
for example, if FWHM1 >> FWHM2, it makes trast, is defined by
little sense to expend substantial effort toward
improving FWHM2. Min = ( Imax − Imin ) / ( Imax + Imin ) (15-2)
The most detailed specification of spatial
resolution is provided by the modulation where Imax and Imin are the maximum and
transfer function (MTF). The MTF is the minimum radiation intensities emitted by the
imaging analog of the frequency response test pattern. Min is the input modulation for
curve used for evaluating audio equipment. the test pattern and ranges from zero (Imax =
In audio equipment evaluations, pure tones of Imin, no contrast) to unity (Imin = 0, maximum
various frequencies are fed to the input of contrast). Similarly, output modulation Mout is
the amplifier or other component to be tested, defined in terms of the modulation of output
and the relative amplitude of the output image (e.g., image density or counting rate
signal is recorded. A graph of relative output recorded from the test pattern).
amplitude versus frequency is the frequency
response curve for that component (Fig. 15-4). Mout = (Omax − Omin ) / (Omax + Omin ) (15-3)
A system with a “flat” curve from lowest to
highest frequencies provides the most faithful
sound reproduction.
By analogy, one could evaluate the fidelity *Technically speaking, the notation k is used in physics
of an imaging system by replacing the audio to denote “cycles per radian,” and the notation − k or “k-
bar” is used to denote “cycles per distance.” Mathemati-
tone with a “sine-wave” distribution of activ- − = k/2π, because there are 2π radians per cycle.
cally, k
ity (Fig. 15-5). Instead of varying in time For notational simplicity, we use k for cycles per distance
(cycles per second), the activity distribution in this text.
Low
Relative output
Audio
Medium
Low
High
component
High
Frequency
FIGURE 15-4 Basic principles for generating frequency response curves for an audio system.
15 • Image Quality in Nuclear Medicine 237
Input Output
Radiation intensity, I
Imax
Counting rate or
image density
Imaging Omax
system
Omin
Imin
1/ k
Distance Distance
ImaxImin OmaxOmin
M in M out
ImaxImin OmaxOmin
FIGURE 15-5 Basic principles for determining the modulation transfer function of an imaging instrument. Input
contrast is measured in terms of object radioactivity or emission rate. Output contrast is measured in terms of count-
ing rate, image intensity, etc. Spatial frequency is k.
The ratio of output to input modulation is the but sometimes also for larger objects because
MTF for the spatial frequency k of the test of the importance of edges and sharp borders
pattern, for detection of low-contrast objects and for
accurate assessment of their size and shape.
MTF(k) = Mout (k) /Min (k) (15-4) Figure 15-6 illustrates some typical MTF
curves for a gamma camera collimator. The
The usefulness of the MTF (or frequency MTF curves have values near unity for low
response curve) derives from the fact that any frequencies but decrease rapidly to zero
image (or audio signal) can be described as a at higher frequencies. Thus the images of a
summation of sine waves of different frequen- radionuclide distribution obtained with this
cies. For audio signals, the sound “pitch” is collimator show the coarser details of the dis-
determined by its basic sine-wave frequency, tribution faithfully but not the fine details.
whereas superimposed higher frequencies Edge sharpness, which is a function of the
create the unique sound characteristics of the high-frequency MTF values, also is degraded.
instrument or human voice producing it. An This type of performance is characteristic of
audio system with a flat frequency response virtually all nuclear medicine imaging systems.
curve over a wide frequency range generates Note also that the MTF curve at higher fre-
an output that matches faithfully the sound quencies decreases more rapidly with increas-
of the instrument or voice producing it. Inex- ing source-to-collimator distance.
pensive audio systems generally reproduce The MTF curve characterizes completely
the midrange audio frequencies accurately and in a quantitative way the spatial resolu-
but have poor response at low and high fre- tion of an imaging system for both coarse and
quencies. Thus they have poor bass response fine details. Images of bar patterns and similar
(low frequencies) and poor sound “quality” test objects are quantitative only for specify-
(high frequencies). ing the limiting resolution of the imaging
An imaging system with a flat MTF curve system, for example, the minimum resolvable
having a value near unity produces an image bar pattern spacing. Bar-pattern images and
that is a faithful reproduction of the imaged MTF curves can be related semiquantitatively
object. Good low-frequency response is needed by noting that the spatial frequency of a bar
to outline the coarse details of the image and pattern having bar widths and spaces of x cm
is important for the presentation and detec- is one cycle per 2x cm. Thus a “5-mm bar
tion of relatively large but low-contrast pattern” has a basic spatial frequency of one
lesions. Good high-frequency response is nec- cycle per centimeter (one bar and one space
essary to portray fine details and sharp edges. per centimeter). Roughly speaking, bar pat-
This is of obvious importance for small objects terns are no longer visible when the MTF for
238 Physics in Nuclear Medicine
1.0
Source-to-collimator
distance
0.8
2.5 cm
0.6
MTF
5 cm
0.4
0.2
10 cm
0
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
Spatial frequency (cm1)
FIGURE 15-6 Modulation transfer function curves for a typical parallel-hole collimator for different source-to-colli-
mator distances. (Data from Ehrhardt JC, Oberly LW, Cuevas JM: Imaging Ability of Collimators in Nuclear Medicine.
Publication No. [FDA] 79-8077. Rockville, MD, U.S. Department of Health, Education, and Welfare, 1978.)
their basic spatial frequency drops below a tomographic instruments in all three spatial
value of approximately 0.1. MTF curves thus directions. Note that in all cases the diameter
can be used to estimate the minimum resolv- or width of the source should be much smaller
able bar pattern for an imaging system. than resolution capability of the imaging
In practice, MTFs are not determined using device (d FWHM/4). Additional discussions
sinusoidal activity distributions, as illus- about the measurement of MTFs and their
trated in Figure 15-5, which would be difficult properties can be found in references 2 and 3.
to construct. Instead, they are obtained by Another useful feature of MTFs is that
mathematical analysis of the LSF or PSF. they can be determined for different compo-
Specifically, the MTF of an imaging system nents of an imaging system and then com-
can be derived from the Fourier transform bined to determine the system MTF. This
(FT) of the LSF or PSF.* The one-dimensional feature allows one to predict the effects of the
(1-D) FT of the LSF is the MTF of the system individual components of the system on the
measured in the direction of the profile, that MTF of the total system. For example, one
is, perpendicular to the line source. Similarly, can obtain the MTF for the intrinsic resolu-
the 1-D FT of a profile recorded through the tion of the Anger camera detector, MTFint(k),
center of the PSF gives the MTF of the system and another for the collimator, MTFcoll(k). The
in the direction of the profile. Alternatively, a system MTF then is obtained by point-by-
2-D FT of the 2-D PSF provides a 2-D MTF point multiplication of the intrinsic and col-
that can be used to determine the frequency limator MTFs at each value of k:
response of the system at any angle relative
to the imaging detector. This sometimes is MTFsys (k) = MTFint (k) × MTFcoll (k) (15-5)
useful for imaging systems that have asym-
metrical spatial resolution characteristics, In general, the MTF of a system is the product
such as detector arrays with rectangular ele- of the MTFs of its components.
ments. Some PET detector arrays have this If two systems have MTF curves of the
property (see Chapter 18, Section B). same general shape, one can predict confi-
It also is possible to obtain a 3-D represen- dently that the system with the higher MTF
tation of the MTF from a complete 3-D data values will have superior spatial resolution;
set for the PSF. This is potentially useful for however, the situation is more complicated
characterizing the spatial resolution of when comparing two systems having MTF
curves of different shapes. For example,
Figure 15-7 shows MTF curves for two colli-
*More specifically, the MTF is the modulus, or amplitude,
mators, one of which would be better for visu-
of the FT, the latter generally being a complex number. alizing large low-contrast structures (low
See Appendix F for a more detailed discussion of FTs. frequencies), the other for fine details (high
15 • Image Quality in Nuclear Medicine 239
1.0
0.8
MTF 0.6
0.4
0.2
0
0.2 0.4 0.6 0.8 1.0
Spatial frequency (cm1)
FIGURE 15-7 Modulation transfer function (MTF) curves for two different collimators. One has better low-frequency
resolution for coarse details (blue line), whereas the other is better for fine details (orange line). (Data from Ehrhardt
JC, Oberly LW, Cuevas JM: Imaging ability of collimators in nuclear medicine. Rockville, MD, U.S. Department of
Health, Education, and Welfare, Publ. No. [FDA] 79-8077, 1978, p 20.)
frequencies). To gain an impression of com- interest, such as a lesion, relative to the signal
parative image quality in this situation, one level in surrounding parts of the image. Thus
would probably have to evaluate organ phan- if Ro is the counting rate over normal tissue
toms or actual patient images obtained with and R is the counting rate over a lesion, the
these collimators. contrast of the lesion is defined as
R − Ro
C =
C. CONTRAST Ro
(15-6)
∆R
Image contrast refers to differences in inten- =
Ro
sity in parts of the image corresponding to
different levels of radioactive uptake in the where Δâ•›Râ•› is the change in counting rate over
patient. In nuclear medicine, a major compo- the lesion relative to the surrounding back-
nent of image contrast is determined by the ground.* Contrast sometimes is expressed as
properties of the radiopharmaceutical. In a percentage, for example, C = 0.1 = “10%
general, it is desirable to use an agent having contrast.”
the highest lesion-to-background uptake or Perhaps the major factor affecting contrast
concentration ratio. Some aspects of radio- is added background counting rates that are
pharmaceutical design that affect this issue superimposed more or less uniformly over the
were discussed in Chapter 5, Section F. Phys- activity distribution of interest. For example,
ical factors involved in image formation also suppose that in the absence of background
can affect contrast. In general, factors that counts a certain object (e.g., a lesion) has
affect contrast in nuclear medicine also affect
the statistical noise levels in the image. More
specifically, they affect the contrast-to-noise *This equation is related to, but not the same as, the
ratio (CNR), which is discussed in detail in equations for modulation given in Equations 15-2 and
the next section. Here we focus only on some 15-3. The definition used here has the disadvantage that
it does not apply when Ro = 0. However, this situation
factors that affect contrast. rarely, if ever, applies in nuclear medicine, and the defini-
A general definition of contrast is that it is tion in Equation 15-6 is more straightforward for the
the ratio of signal change of an object of analysis of contrast and CNR.
240 Physics in Nuclear Medicine
1
C′ = 0.2 ×
R Rb 1 + ( R b / R )
o
Counting rate
1
R = 0 .2 ×
1 + 1
Ro Rb
1
Rb = 0.2 × = 0.1 (10%)
Ro 2
250
200
150
100
50
0
10 20 30 40
Voxel Number
True activity distribution 20% energy window
Unscattered photons only 50% energy window
FIGURE 15-9 Effect of scatter and pulse-height analysis on image contrast. The images were generated by Monte
Carlo simulations mimicking a clinical study of myocardial function using the radiotracer 201TlCl. Count profiles
through the images also are shown. These profiles are taken along the line shown in the image of the true activity
distribution. The images also demonstrate blurring of the activity distribution caused by the finite camera resolution.
(Courtesy Dr. Hendrik Pretorius and Dr. Michael King, University of Massachusetts Medical School, Worcester, MA).
septal penetration, which has similar effects) that may already be near the borderline of
on the LSF and MTF of an imaging system. detectability. These effects are apparent in
The addition of long “tails” to the LSF results Figure 15-9, which demonstrates a percepti-
first in the suppression of the MTF curve at ble loss of image sharpness as well as overall
low frequencies. This is reflected in poorer image contrast when the added background
contrast of large objects that would make is present.
large low-contrast objects more difficult to An important contributor to background
detect or characterize. The high-frequency radiation in conventional planar imaging is
portion of the MTF curve also is suppressed, radioactivity above and below the object of
which has the effect of shifting the limiting interest. Image contrast is improved in emis-
frequency for detection of high-contrast sion computed tomography (SPECT and PET)
objects (e.g., bar patterns) to lower frequen- (see Chapters 17 and 18) because it permits
cies. Thus the contrast-degrading effects of imaging of an isolated slice without the super-
added background decrease the visibility of imposed activities in overlying and underly-
all structures in the image, particularly those ing structures. Tomographic techniques offer
242 Physics in Nuclear Medicine
With
Relative counts scatter
Without
scatter
Scatter only
A
6 4 2 0 2 4 6
Distance (cm)
1.0
0.9
0.8
0.7
Without
scatter
0.6
With
MTF
0.5 scatter
0.4
0.3
0.2
0.1
B
0 0.2 0.4 0.6 0.8
Spatial frequency
FIGURE 15-10 Illustration of effects of scatter and septal penetration on line-spread function (LSF) (A) and modula-
tion transfer function (MTF) (B) of an imaging system. The long “tails” on the LSF have the effect of suppressing the
MTF curve at both low and high spatial frequencies.
significant improvements for the detection of The preceding discussion relates to the
low-contrast lesions. Figure 15-11 illustrates effects of various types of background radia-
this effect. Details of emission computed tomo- tion on input contrast to the imaging system.
graphic imaging are presented in Chapters 16 It is possible with computers to apply “back-
to 18; however, even at this point, the benefits ground subtraction” or “contrast enhance-
of removing the interfering effects of overlying ment” algorithms and thereby restore the
and underlying activity should be evident. original contrast, at least in terms of the
15 • Image Quality in Nuclear Medicine 243
Planar image
SPECT images
FIGURE 15-11 Planar (upper left) and single-photon emission computed tomographic (SPECT) (center) images of a
thoracic phantom. Note the improved contrast and visibility of the voids in the cardiac portion of the phantom when
overlying and underlying activity are removed in the SPECT images. (Courtesy Dr. Freek Beekman, Delft University
of Technology, Netherlands.)
relative brightness levels between a lesion Structured noise also can arise from
and its surrounding area. However, these imaging system artifacts. Nonuniformities in
techniques also enhance the statistical noise gamma camera images (see Fig. 14-10) are
levels in the image as well as the contrast of one example. Various “ring” or “streak” arti-
any underlying artifacts, such as gamma facts generated during reconstruction tomog-
camera image nonuniformities. Thus the crit- raphy are another (e.g., see Figs. 16-11 and
ical parameter to consider regarding com- 16-13).
puter enhancement techniques is their effect
on CNR. This concept is discussed in the fol- 2. Random Noise and
lowing section. Contrast-to-Noise Ratio
Random noise, also called statistical noise or
quantum mottle, is present everywhere in a
D. NOISE
nuclear medicine image. Even when the size
of an object is substantially larger than the
1. Types of Image Noise limiting spatial resolution of the image, sta-
Image noise generally can be characterized as tistical noise can impair detectability, espe-
either random or structured. Random noise cially if the object has low contrast. The
refers to the mottled appearance of nuclear critical parameter for detectability is the
medicine images caused by random statistical CNR of the object in the image. In the follow-
variations in counting rate (Chapter 9). This ing discussion, we present an analysis and
is a very important factor in nuclear medicine some illustrations of the effects of CNR on
imaging and is discussed in detail in this detectability of objects in 2-D planar nuclear
section. images.
Structured noise refers to nonrandom vari- Suppose that a 2-D image contains a circu-
ations in counting rate that are superimposed lar lesion of area A having contrast C (Equa-
on and interfere with perception of the object tion 15-6) against a uniform background
structures of interest. Some types of struc- counting rate, Ro (cpsâ•›/cm2). The number of
tured noise arise from the radionuclide distri- counts recorded in a background area of the
bution itself. For example, in planar imaging, same size as the lesion during an imaging
uptake in the ribs may be superimposed over time, t, is
the image of the heart in studies to detect
myocardial infarction with 99mTc-labeled pyro- No = Ro × A × t
phosphates. Bowel uptake presents a type of
structured noise in studies to detect inflam- π (15-8)
= Ro × d2 × t
mation or abscess with 67Ga. 4
244 Physics in Nuclear Medicine
where d is the diameter of the lesion. The Equation 15-12 applies to somewhat idealized
statistical variation of counts in background conditions of more or less circular objects
areas of size A is against a relatively uniform background of
nonstructured noise. Such conditions rarely
σ No = No apply in nuclear medicine. Nevertheless, this
equation can be used to gain some insights
π d2 (15-9)
= Ro × ×t into lesion detectability and the factors that
4 affect it.
EXAMPLE 15-2
Thus the fractional standard deviation of
counts due to random statistical variations is Estimate the minimum contrast for detec-
tion of circular objects of 1-cm and 2-cm
σ No diameter in an area of an image where the
Cnoise =
No background information density is IDo = 400
1 counts/cm2.
= (15-10)
π d2 Answer
Ro × ×t
4 Rearranging Equation 15-12 and inserting
the specified information density,
As indicated by the notation in Equation
15-10, this factor can be considered as the 4 4 0 .2
C ≥ = =
“noise contrast” for a circular area of diameter d IDo 400 d d
d in background areas of the image. The ratio
of lesion-contrast to noise-contrast is defined Thus for a 1-cm diameter object, the minimum
as its CNR. contrast required for detectability is approxi-
C mately 0.2 (20%), whereas for a 2-cm diame-
CNR = ter object it is approximately 0.1 (10%).
Cnoise
≈ C × d × Ro × t (15-11) Example 15-2 shows that, all other factors
being the same, the contrast required for
≈ C × d × IDo detectability is inversely proportional to
object size.
where we have used the approximation
π/4 ≈ 1. The quantity IDo = (Ro × t) is the EXAMPLE 15-3
background information density of the image Estimate the minimum diameter for detec-
and has units (counts/cm2). The absolute tion of an object that has 10% contrast, |C|
value of contrast, |C|, is used in Equation = 0.1, in an area of the image where the back-
15-11 to indicate that it applies to either posi- ground information density is 100 counts/cm2.
tive or negative contrast.
To detect a lesion or other object in an Answer
image, the observer must be able to distin- Rearranging Equation 15-12 and inserting
guish between the lesion or object and noise- the specified parameters,
generated contrast patterns in background
areas of the same size in the image. A sub- 4 4
d ≥ = = 4 cm
stantial amount of research has gone into this C IDo 0.1 400
subject. The conclusion is that, to be detect-
able, an object’s CNR must exceed 3-5. This Examples 15-2 and 15-3 illustrate that the
factor is known as the Rose criterion, after the minimum size requirement for object detect-
individual who did basic studies on this ability decreases inversely with the square
subject.4 The actual value depends on object root of information density, from 2╯cm with
size and shape, edge sharpness, viewing dis- IDo = 400 counts/cm2 in Example 15-2 to 4╯cm
tance, observer experience, and so forth. with IDo = 100 counts/cm2 in Example 15-3.
Choosing a factor of 4, the requirement for At first glance, it would seem that adding
detectability becomes CNR ≥ 4, and Equation background radiation to an image would
15-11 can be written as improve lesion detectability, by increasing
C × d × Ro × t ≥ 4 information density, IDo. However, as illus-
(15-12) trated by Example 15-1, background radiation
C × d × IDo ≥ 4 also degrades lesion contrast. The following
15 • Image Quality in Nuclear Medicine 245
example illustrates the overall effect of back- an imaging time of 1╯min. Ignore the effects
ground radiation on object detectability. of attenuation and source-to-detector distance
for this comparison.
EXAMPLE 15-4
Example 15-3 indicates that a 4-cm diameter Answer
object with 10% contrast should be detectable In both cases, the uptake in normal tissues
against a background information density of would generate a background counting rate of
IDo = 100 counts/cm2. Suppose that back- Ro = 10╯cm × 10╯cpm/cm2 per centimeter thick-
ground radiation with the same information ness = 100╯cpm/cm2. For the 1-cm diameter
density, (IDb = 100 counts/cm2) is added to the lesion, the count rate over the center of the
image. Estimate the minimum detectable lesion is
lesion size after this is done.
(9 cm × 10 cpm/cm 2 per cm)
Answer + (1 cm × 20 cpm/cm 2 per cm)
According to Example 15-1, the addition of
background radiation with IDb = IDo decreases = 110 cpm/cm 2
contrast by a factor of 2, from C = 0.1 to Câ•›′ = Thus the contrast of the 1-cm diameter lesion
0.05. At the same time, the background infor- is (110 − 100)/100 = 0.1 (10%). For a 1-min
mation density increases from 100 counts/cm2 imaging time, its CNR (Equation 15-11) is
to 200 counts/cm2. Rearranging Equation
15-12 and inserting these values, one obtains CNR1 cm = 0.1 × 1 × 100 × 1 = 1
4 4 For the 2-cm diameter lesion, the counting
d ≥ = ≈ 5.7 cm
C′ IDo 0.05 200 rate over the center of the lesion is
medicine imaging. Specifically, the intrinsic Thus the contrast of the “cold” lesion is (91
contrast of a lesion can depend on whether its − 100)/100 = –â•›0.09 (–9%), in which the minus
contrast is generated by preferential uptake sign indicates “negative” contrast. For a 1-min
or by preferential suppression of uptake rela- imaging time, the CNR for radiopharmaceuti-
tive to surrounding normal tissues. The fol- cal B is
lowing example provides an illustration.
CNR B = 0.09 × 1 × 100 × 1 = 0.9
EXAMPLE 15-6
Suppose that two radiopharmaceuticals are which is well below the threshold of detect-
available for a study. Radiopharmaceutical A ability specified by the Rose criterion.
generates contrast by selective uptake in a
lesion that is 10 times higher than the uptake Example 15-6 illustrates the basis for the
in surrounding normal tissue, whereas radio- generally held (and generally accurate) belief
pharmaceutical B generates contrast by sup- that “cold” lesions are more difficult to detect
pression of uptake in the same lesion, to a than “hot” ones. One way to overcome this
level that is 1/10 (10%) of the uptake in sur- deficit is to inject more radioactivity for
rounding tissue. Thus the uptake ratio is “cold” lesions; however, the specified levels of
10â•›:â•›1 in both cases. Assume that a 1-cm thick uptake in normal tissue in this example leads
lesion is present in a total thickness of 10╯cm to comparable radiation doses in both cases
of tissue. Ignoring the effects of attenuation and thus the higher level of radioactivity
and source-to-detector distance, calculate the required for radiopharmaceutical B would
CNR generated by the two radiopharmaceu- presumably lead to greater radiation dose.
ticals. For both radiopharmaceuticals, assume Specific comparisons of radiopharmaceuticals
that the uptake in normal tissue generates a vary, depending on details of the uptake dis-
counting rate of 10╯cpm/cm2 per centimeter tribution and properties of the radionuclides
thickness of tissue and that imaging time is involved.
1╯min in both cases. These examples illustrate that contrast
and information density can be limiting factors
Answer for lesion detection, even when the size of the
For both radiopharmaceuticals, the uptake lesion easily exceeds the spatial resolution
in normal tissues generates a background limits of the imaging system. Figure 15-12
counting rate of Ro = 10╯cm × 10╯cpm/cm2 per further illustrates this point for images of a
centimeter thickness = 100╯cpm/cm2. For heart phantom. Although spatial resolution
radiopharmaceuÂ�tical A (“hot” lesion), the and contrast are the same for all the images
uptake of the lesion is 10 times greater and the shown in this figure, there are marked differ-
counting rate over the lesion is ences in lesion visibility because of differences
in information density and noise.
(9 cm × 10 cpm/cm 2 per cm) Although not specifically included in the
+ (1 cm × 100 cpm/cm 2 per cm) analysis of CNR presented earlier, spatial
resolution of the imaging system also affects
= 190 cpm/cm 2 the detectability of small, low-contrast objects.
As shown in Figure 15-13, high-resolution col-
Thus the contrast of the hot lesion is (190 − limators (or imaging detectors) provide better
100)/100 = 0.9 (90%). For a 1-min imaging image contrast and improved visibility for
time, its CNR (Equation 15-11) is fine details, even for smaller numbers of
counts in the image. In essence, “sharpening”
CNR A = 0.9 × 1 × 100 × 1 = 9 the edges of lesions lowers the CNR required
for detectability (Rose criterion) specified in
This value easily exceeds the requirement for Equation 15-12.
detectability given by the Rose criterion. Nevertheless, the tradeoff between improved
collimator resolution and decreased collima-
For the “cold” lesion, the uptake by the lesion tor sensitivity (see Equations 14-7 and 14-8),
is 1/10 of the uptake in normal tissue. Thus as well as the requirement for greater infor-
the counting rate over the lesion is mation density, eventually establishes a
(9 cm × 10 cpm/cm 2 per cm) point of diminishing returns in the effort to
detect smaller and smaller lesions by improve-
+ (1 cm × 1 cpm/cm 2 per cm) ments in imaging resolution. In the end,
= 91 cpm/cm 2 detectability in nuclear medicine is limited by
15 • Image Quality in Nuclear Medicine 247
axis of the display and in contrast along the to bias and other sources of differences in the
other. An example is the Rollo phantom, observer’s detection thresholds in different
shown in Figure 15-14A↜. This phantom con- experiments. This is especially true for phan-
sists of solid spheres of four different diame- toms having a design similar to the one illus-
ters immersed in four different thicknesses of trated in Figure 15-14, because the observer
a radioactive solution of uniform concentra- has a priori knowledge of the locations of the
tion. Images of this phantom thus contain simulated lesions. Thus such a phantom does
cold lesions of different sizes and contrasts not test for the possibility of false-positive
(Fig. 15-14B). results, that is, the mistaken detection of
To perform a C-D study with this or a objects that actually are not present in the
similar phantom, images are obtained using image. This is particularly important for
the different imaging systems or techniques noisy images in which noise not only can
to be evaluated. An observer then is given the mask the presence of real objects but also can
images, usually without identification and in create apparent structures that masquerade
random order to avoid possible bias, and as real objects. Finally, C-D phantoms gener-
asked to indicate the smallest diameter of ally are lacking in clinical realism.
sphere that is visible at each level of contrast.
Borderline visibility may be indicated by 2. Receiver Operating Characteristic
selecting a diameter between two of the diam- Studies
eters actually present in the image. The Some of the deficiencies of the C-D method
results then are presented on a C-D diagram outlined earlier are overcome by the ROC
as illustrated by Figure 15-15. A C-D study method. For an ROC study, a set of images is
can be helpful for comparing detectability of obtained with the different imaging systems
both large low-contrast lesions as well as or techniques to be tested. Phantoms contain-
small high-contrast lesions. For example, in ing simulated lesions can be used, but it also
Figure 15-15, system A would be preferred for is possible to use actual clinical images. In the
the former and system B for the latter. simplest approach, each image contains either
Because of the subjective nature of C-D one or no lesions. The former are called posi-
studies, the use of multiple observers is rec- tive images and the latter are called negative
ommended. Also, because observers may images. The images are given to the observer,
change their detection threshold from one who is asked to indicate whether a lesion is
study to the next or as they gain familiarity present or absent in each image, as well as
with the images, it usually is helpful to repeat where it is and his or her confidence that
the readings for verification of results. it actually is present. Usually the confidence
C-D studies have a number of limitations. levels are numbered and four different levels
Because they are subjective, they are susceptible are permitted; for example, 1 = definitely present,
Lesion diameter
(inches)
1.0 0.75 0.50 0.375
0.66
0.44
0.33
0.22
A B
FIGURE 15-14 Example of a phantom, the Rollo phantom, which can be used to obtain images for a contrast-detail
study. A, Phantom. B, Example image. (From Rollo FD, Harris CC: Factors affecting image formation. In Rollo FD
[ed]: Nuclear Medicine Physics, Instrumentation, and Agents. St. Louis, 1977, CV Mosby, p 397.)
15 • Image Quality in Nuclear Medicine 249
2 = probably present, 3 = probably not present, ROC curves are shown in Figure 15-16. The
and 4 = definitely not present. Then the fol- ROC curve should lie above the ascending
lowing results are calculated for each confi- 45-degree diagonal, which would represent
dence level: “guessing.” The farther the curve lies above
the 45-degree line, the better the performance
True-positive fraction (TPF) = fraction of of the imaging system and observer.
positive images correctly identified as posi- An ROC curve shows not only the true-
tive by the observer positive detection rate for an observer or an
imaging system or technique but also its rela-
False-positive fraction (FPF) = fraction of tionship to the false-positive detection rate.
negative images incorrectly identified as Thus it is relatively immune to the sources of
positive by the observer observer bias that can occur in C-D studies,
for example, a tendency to “over-read” to
Two other parameters that are calculated avoid missing a possible lesion or test object.
are the true-negative fraction (TNF) = (1 − It also is applicable to other types of detection
FPF), and the false-negative fraction (FNF) = questions, such as the presence or absence of
(1 − TPF). The TPF is sometimes called the disease, which might be indicated by a general
sensitivity and TNF the specificity of the test pattern of uptake within an organ, as opposed
or the observer. to the simple detection of individual lesions.
The ROC curve then is generated by plot- As with C-D studies, the interpretation of
ting TPF versus FPF for progressively relaxed ROC results sometimes can be challenging.
degrees of confidence, that is, highest confi- For example, the ROC curves for two different
dence = level 1 only, then confidence levels 1 imaging systems can “cross,” leading to some
+ 2, then confidence levels 1 + 2 + 3, and so ambiguity in the results. One approach to sim-
forth. An example of data and the resulting plifying the interpretation is to report the
250 Physics in Nuclear Medicine
1.0
0.8
Data “Guessing”
0.4
0.0
0.0 0.2 0.4 0.6 0.8 1.0
False-positive fraction (FPF)
FIGURE 15-16 Example of results from an ROC study. , data points; orange line, fitted curve; blue line, 45-degree
line, which is equivalent to “guessing.” Area under the curve (shaded in darker blue) is Az, which is one measure of
detection accuracy.
results of an ROC study as a single number. verification of “truth” when clinical images
Most commonly the parameter calculated is are used.
the area under the ROC curve, usually denoted Another potential problem is the possible
by Aâ•›z. This number can range from zero (all presence of multiple lesions on a single image.
readings wrong) to 1 (all readings correct). A Conventional ROC methodology allows only
value of 0.5 indicates an overall accuracy of for a single “yes-no” interpretation of each
50%, which is equivalent to “guessing.” image. This allows straightforward calcula-
An extensive amount of theoretical and tions of false-positive rates. However, if mul-
experimental work has been done on the prop- tiple lesions are possible, as in many clinical
erties of Aâ•›z, including such issues as statisti- images, the potential number of false positives
cal com�parisons of values obtained from is virtually infinite, making the calculation of
different ROC studies. References 5 to 7 false-positive rates difficult, if not impossible.
present detailed analyses of these and other Alternative methods, called the free-response
practical issues in ROC studies. Aâ•›z also has operating characteristic, that allow for the
an interesting practical interpretation: It is presence of multiple lesions have been devel-
the probability that, given a side-by-side pair oped and are discussed in reference 9.
of images, one of which has a lesion or test Finally, even a “perfect” image evaluation
object and the other does not, the observer will technique with a clearly defined outcome
correctly identify the image with the lesion.8 might not provide the final answer regarding
Despite their power and potential useful- the merit or value of an imaging device or
ness, ROC studies also have a number of limi- technique. Even after the physician or scien-
tations. Perhaps the most challenging is the tist has demonstrated that he or she has
verification of absolute “truth” for images developed a truly “better” device or technique
obtained from clinical studies. Ideally, the in terms of lesion or disease detectability,
outcome of the ROC study itself (i.e., the there is still the bottom-line question: “So
tested images) should not be used for this what?” Does the improved detectability alter
determination. This means that other equally the care of the patient or the outcome of that
or even more reliable information about the care? Does it improve the patient’s quality of
presence or absence of disease in the patient life? In an age of cost-consciousness, what are
must be available. Often nonimaging tests the cost-benefit tradeoffs? For example, from
(e.g., surgical results) must be obtained for a public health perspective, is it really worth
15 • Image Quality in Nuclear Medicine 251
spending a small fortune to detect the next 3. Vayrynen T, Pitkanen U, Kiviniitty K: Methods for
smaller size of lesion, as compared with measuring the modulation transfer function of
gamma camera systems. Eur J Nucl Med 5:19-22,
directing those funds toward simpler health 1980.
measures, such as education and behavior 4. Rose A: Vision: Human and Electronic. New York,
modification? These are difficult questions to 1973, Plenum Press, pp 21-23.
answer, but efforts are being made to develop 5. Swets JA, Pickett RM: Evaluation of Diagnostic
Systems: Methods from Signal Detection Theory, New
methodology for answering them in a quanti- York, 1982, Academic Press.
tative and objective manner. The general 6. Metz CE: ROC methodology in radiologic imaging.
term for these investigations is efficacy Invest Radiol 21:720-733, 1986.
studies. Additional discussion of this topic can 7. Metz CE: Fundamental ROC analysis. In Beutel J,
be found in reference 10. Kundel HL, Nan Metter RL, editors: Handbook of
Medical Imaging, Bellingham, WA, 2000, SPIE,
Chapter 15.
8. Hanley JA, McNeil BJ: The meaning and use of the
REFERENCES area under the receiver operating characteristic
1. Barrett HH, Yao J, Rolland JP, Myers KJ: Model (ROC) curve. Radiology 143:29-36, 1982.
observers for assessment of image quality. Proc Natl 9. Chakraborty DP: The FROC, AFROC, and DROC
Acad Sci 90:9758-9765, 1993. variants of the ROC analysis. In Beutel J, Kundel
2. Cunningham IA: Introduction to linear systems HL, Nan Metter RL, editors: Handbook of Medical
theory. In Beutel J, Kundel HL, Nan Metter RL, Imaging, Bellingham, WA, 2000, SPIE, Chapter 16.
editors: Handbook of Medical Imaging, Bellingham, 10. Fryback DG, Thornbury JR: The efficacy of diagnos-
WA, 2000, SPIE, Chapter 2. tic studies. Med Decis Making 11:88-94, 1991.
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chapter
16
Tomographic
Reconstruction in
Nuclear Medicine
A basic problem in conventional radionuclide CT, See Chapter 19, Section B). The mathe-
imaging is that the images obtained are matical basis is the same for ECT and TCT,
two-dimensional (2-D) projections of three- although there are obviously differences in
dimensional (3-D) source distributions. Images details of implementation.
of structures at one depth in the patient ECT produces images in which the activity
thus are obscured by superimposed images of from overlying (or adjacent) cross-sectional
overlying and underlying structures. One planes is eliminated from the image. This
solution is to obtain projection images from results in a significant improvement in
different angles around the body (e.g., poste- contrast-to-noise ratio (CNR), as already has
rior, anterior, lateral, and oblique views). The been illustrated in Figure 15-11. Another
person interpreting the images then must advantage of SPECT and PET over planar
sort out the structures from the different nuclear medicine imaging is that they are
views mentally to decide the true 3-D nature capable of providing more accurate quantita-
of the distribution. This approach is only tion of activity at specific locations within the
partially successful; it is difficult to apply to body. This is put to advantage in tracer kinetic
complex distributions with many overlapping studies (Chapter 21).
structures. Also, deep-lying organs may The mathematics underlying reconstruc-
have overlying structures from all projection tion tomography was first published by
angles. Johann Radon in 1917, but it was not until
An alternative approach is tomographic the 1950s and 1960s that work in radio�
imaging. Tomographic images are 2-D repre- astronomy and chemistry resulted in practical
sentations of structures lying within a selected applications. The development of x-ray CT in
plane in a 3-D object. Modern computed the early 1970s initiated application of these
tomography (CT) techniques, including posi- principles for image reconstruction in medical
tron emission tomo�g�raphy (PET), single imaging. An interesting historical perspective
photon emission tomography (SPECT), and on the origins and development of tomo-
x-ray CT, use detector systems placed or graphic image reconstruction techniques is
rotated around the object so that many differ- presented in reference 1.
ent angular views (also known as projections) Instrumentation for SPECT imaging is dis-
of the object are obtained. Mathematical algo- cussed in Chapter 17 and instrumentation for
rithms then are used to reconstruct images of PET is discussed in Chapter 18. Although the
selected planes within the object from these instruments differ, the same mathematics
projection data. Reconstruction of images can be used to reconstruct SPECT or PET
from multiple projections of the detected images. In this chapter, we focus on the basic
emissions from radionuclides within the body principles of reconstructing tomographic
is known as emission computed tomography images from multiple projections. A detailed
(ECT). Reconstruction of images from trans- mathematical treatment of image reconstruc-
mitted emissions from an external source tion is beyond the scope of this text. The
(e.g., an x-ray tube) is known as transmission reader is referred to references 2 to 4 for more
computed tomography (TCT or, usually, just detailed accounts.
253
254 Physic in Nuclear Medicine
Sum of
activity
along line
of response
Projection
profile
Gamma
camera
Line of
response
Object
FIGURE 16-1 Cross-section of the response characteristics of an idealized gamma camera. Each collimator hole views
the radioactivity within a cylinder perpendicular to the face of the gamma camera, called its line of response. Under
idealized conditions (such as no attenuation or scatter) the signal recorded by the detector at that point reflects the
sum of activity within the line of response. For a row of holes across the detector, the gamma camera generates a
projection profile as shown. The projection profiles provide the data from which the image is reconstructed.
16 • Tomographic Reconstruction in Nuclear Medicine 255
1-D projection
profiles at
different angles
Rotating
gamma
camera
ECT
ALGORITHM
Object
f(x,y)
Reconstructed
image of section
through object
FIGURE 16-2 Rotating the gamma camera around the object provides a set of one-dimensional projection profiles for
a two-dimensional object, which are used to calculate the two-dimensional distribution of radioactivity in the object.
ECT, emission computed tomography.
Figure 16-2. Note that the data collected cor- coordinate system and is illustrated in Figure
respond to a slice through the object perpen- 16-3. If the camera is rotated by an angle ϕ
dicular to the bed and that this is called the with respect to the (x,y) coordinate system of
transverse or transaxial direction. The direc- the scanned object, the equations for transfor-
tion along the axis of the bed, which defines mation from (x,y) to (r,s) coordinates can be
the location of the slice, is known as the axial derived from the principle of similar triangles
direction. and are given by
We assume that N projections are recorded
at equally spaced angles between 0 and 180 r = x cos φ + y sin φ (16-1)
degrees. Under the idealized conditions
assumed here, the projection profile recorded and
at a rotation angle of (180 + ϕ) degrees would
be the same (apart from a left-right reversal) s = y cos φ − x sin φ (16-2)
as the profile recorded at ϕ degrees. Thus the
data recorded between 180 and 360 degrees These equations can be used to determine
would be redundant; however, for practical how radioactivity at a location (x,y) in the
reasons (e.g., attenuation), SPECT data often object contributes to the signal recorded at
are acquired for a full 360-degree rotation. location r in the projection acquired at rota-
This is discussed further in Chapter 17. tion angle ϕ.
For purposes of analysis, it is convenient One commonly used way to display a full
to introduce a new coordinate system that set of projection data is in the form of a 2-D
is stationary with respect to the gamma matrix p(r,ϕ). A representation of this matrix,
camera detector. This is denoted as the (r,s) generically known as a sinogram, is shown for
256 Physic in Nuclear Medicine
0°
Projection
profiles
Point source
180°
pixels in the (x,y) coordinate system. For together, an approximation of the distribution
mathematical convenience, the image matrix of radio�activity within the scanned slice is
size usually is a power of 2 (e.g., 64 × 64 or obtained. Mathematically, the backprojection
128 × 128 pixels). Pixel dimensions Δâ•›x and Δy of N profiles is described by
can be defined somewhat arbitrarily, but
usually they are related to the number of pro- 1 N
files recorded and the width of the sampling
f ′( x, y) = ∑ p( x cos φi + y sin φi, φi ) (16-3)
N i=1
interval along r.
The most basic approach for reconstructing where ϕi denotes the ith projection angle and
an image from the profiles is by simple back- fâ•›′â•›(x,y) denotes an approximation to the true
projection. The concepts will be illustrated for radioactivity distribution, fâ•›(x,y).
a point source object. Figure 16-5A shows pro- As illustrated in Figure 16-5B, the image
jection profiles acquired from different angles built up by simple backprojection resembles
around the source. An approximation for the the true source distribution. However, there
source distribution within the plane is is an obvious artifact in that counts inevitably
obtained by projecting (or distributing) the are projected outside the true location of the
data from each element in a profile back object, resulting in a blurring of its image.
across the entire image grid (Fig. 16-5B). The The quality of the image can be improved by
counts recorded in a particular projection increasing the number of projection angles
profile element are divided uniformly amongst and the number of samples along the profile.
the pixels that fall within its projection path.* This suppresses the “spokelike” appearance
This operation is called backprojection. When of the image but, even with an infinite number
the backprojections for all profiles are added of views, the final image still is blurred. No
matter how finely the data are sampled,
simple backprojection always results in some
apparent activity outside the true location for
*In practice, counts are assigned to a pixel in proportion the point source. Figure 16-6 shows an image
to the fraction of the pixel area contained within the line
of response for the projection element. However, owing to reconstructed by simple backprojection for a
the complexity of the notation, this part of the algorithm somewhat more complex object and more
is not included here. clearly illustrates the blurring effect.
Backprojection
of profile at 0°
across image
matrix
Backprojection after
Object 2 angles 8 angles 256 angles
A B
FIGURE 16-5 Illustration of the steps in simple backprojection. A, Projection profiles for a point source of radioactivity
for different projection angles. B, Backprojection of one intensity profile across the image at the angle corresponding
to the profile. This is repeated for all projection profiles to build up the backprojected image.
258 Physic in Nuclear Medicine
A B C
FIGURE 16-6 A, Computer-simulation phantom used for testing reconstruction algorithms. B, Sinogram of simulated
data for a scan of the phantom. C, Image of simulation phantom for simple backprojection of data from 256 projection
angles. 1/r blurring is apparent in the object, and edge details are lost. (Computer simulations performed by Dr. Andrew
Goertzen, University of Manitoba, Canada)
Mathematically, the relationship between 1-D image profile as a spatially varying func-
the true image and the image reconstructed tion, fâ•›(x), the profile is represented as a sum-
by simple backprojection is described by mation of sine and cosine functions of different
spatial frequencies, k. The amplitudes for dif-
f ′ ( x, y) = f ( x, y) ∗ (1/r) (16-4) ferent spatial frequencies are represented in
the FT of fâ•›(x), which is denoted by F(k). The
where the symbol * represents the process operation of computing the FT is symbolized
of convolution described in Appendix G. A by
profile taken through the reconstructed
image for a point source that is reconstructed F (k) = F [ f ( x)] (16-5)
from finely sampled data decreases in pro-
portion to (1/r), in which r is the distance The function fâ•›(x) is a representation of the
from the center of the point-source location. image profile in image space (or “object
Because of this behavior, the effect is known space”), whereas F(k) represents the profile
as 1/r blurring. Simple backprojection is in “spatial frequency space,” also called
potentially useful only for very simple situa- k-space. FTs can be extended to 2-D func-
tions involving isolated objects of very high tions, fâ•›(x,y), such as a 2-D image. In this
contrast relative to surrounding tissues, case, the FT also is 2-D and represents
such as a tumor with avid uptake of a radio- spatial frequencies along the x- and y-axes,
pharmaceutical that in turn has very low F(kx, ky), in which kx and ky represent orthog-
uptake in normal tissues. For more compli- onal axes in 2-D k-space. Symbolically, the
cated objects, more sophisticated reconstruc- 2-D FT is represented as
tion techniques are required.
F (kx, ky ) = F [ f ( x, y)] (16-6)
2. Direct Fourier Transform Mathematically, a function and its FT are
Reconstruction equivalent in the sense that either one can be
One approach that avoids 1/r blurring is derived from the other. The operation of con-
Fourier transform (FT) reconstruction, some- verting the FT of a function back into the
times called direct Fourier transform recon- original function is called an inverse FT and
struction or direct FT. Although direct FT is is denoted by
not really a backprojection technique, it is
presented here as background for introducing F −1
[ F (kx, ky )] = f ( x, y) (16-7)
the filtered backprojection (FBP) technique in
the next section. FTs can be calculated quickly and conve-
Basic concepts of FTs are discussed in niently on personal computers, and many
Appendix F. Briefly, in the context of nuclear image and signal-processing software pack-
medicine imaging, the FT is an alternative ages contain FT routines. The reader is
method for representing spatially varying referred to Appendix F for additional informa-
data. For example, instead of representing a tion about FTs.
16 • Tomographic Reconstruction in Nuclear Medicine 259
The concept of k-space will be familiar to The projection slice theorem provides a
readers who have studied magnetic resonance means for obtaining 2-D k-space data for
imaging (MRI), because this is the coordinate an object from a series of 1-D measurements
system in which MRI data are acquired. To in object space. Figure 16-7 and Equation
reconstruct an image from its 2-D FT, the full 16-8 provide the basis for reconstructing an
2-D set of k-space data must be available object from its projection profiles as follows:
(Equation 16-7). In MRI, data are acquired 1. Acquire projection profiles in object space
point-by-point for different (kx, ky) locations in at N projection angles, ϕi, i = 1, 2, …, N as
a process known as “scanning in k-space.” previously described.
There is no immediately obvious way to 2. Compute the 1-D FT of each profile.
directly acquire k-space data in nuclear medi- 3. Insert the values of these FTs at the appro-
cine imaging. Instead, nuclear medicine CT priate coordinate locations in k-space. Note
relies on the projection slice theorem, or that values are inserted in polar coordi-
Fourier slice theorem. In words, this theorem nates along radial lines through the origin
says that the FT of the projection of a 2-D in k-space. For a specific value of kr in the
object along a projection angle ϕ [in other FT of the projection acquired at a rota-
words, the FT of a profile, p(r,ϕ)], is equal to tional angle ϕ, the data are inserted at rect-
the value of the FT of the object measured angular coordinates given by
through the origin and along the same angle,
k′x = kr cos φ
ϕ, in k-space (note, the value of the FT, not
(16-9)
the projection of the FT). Figure 16-7 illus- k′y = kr sin φ
trates this concept. Mathematically, the
general expression for the projection slice where primed notation is used to indicate
theorem is that the coordinate locations do not corre-
spond exactly to points on a rectangular
F [ p(r, φ)] = F (kr , φ) (16-8) grid. The inserted values are closely spaced
near the origin and more widely spaced
where F(krâ•›,â•›ϕ) denotes the value of the FT farther away from the origin. This “over-
measured at a radial distance kr along a line representation” of data near the origin in
at angle ϕ in k-space. k-space is one explanation for the 1/r
1-D Fourier
transform in r
p(r,φ) P(kr ,φ)
r kr
s y ks ky
Inverse
r 2-D Fourier
kr
transform
in k x,k y
φ φ
x kx
f (x, y)
F(k x,k y)
Left Right
FIGURE 16-7 Concepts of the projection slice theorem. (Left) p(r,ϕ) is a one-dimensional (1-D) profile of the 2-D object
fâ•›(x,y) at projection angle ϕ. The theorem states that the 1-D Fourier transform of this projection profile (right) is equal
to the values of the 2-D Fourier transform of the object, Fâ•›(kx, ky), along a line through the origin of k-space at the same
angle ϕ.
260 Physic in Nuclear Medicine
blurring that occurs in simple backprojec- multiplying each projection FT by |kr|, the
tion, as was discussed in Section B.1. absolute value of the radial k-space coordi-
4. Using the values inserted in polar coordi- nate at each point in the FT. Thus the
nates, interpolate values for kx and ky on a value of the FT is increased (amplified) lin-
rectangular grid in k-space. early in proportion to its distance from the
5. Use the interpolated values in k-space and origin of k-space. Figure 16-8 illustrates
a standard 2-D (inverse) FT (Equation the profile of a ramp filter, with filter
16-7) to compute the image of the object. amplitude denoted by H(kr). Applying the
With noise-free data, perfect projection ramp filter produces a modified FT for each
profiles (i.e., line integrals that represent pre- projection, given by
cisely the sum of activity along a line mea-
sured through the object) and perfect P ′ (kr , φ) = kr P (kr , φ) (16-10)
interpolation, the direct FT reconstruction
technique is capable of producing an exact where P(krâ•›,â•›ϕ) is the unfiltered FT.
representation of the object. Additional crite- 4. Compute the inverse FT of each filtered FT
ria regarding the required numbers of projec- profile to obtain a modified (filtered) projec-
tion profiles and sampled points across each tion profile. This is given by
profile are discussed in Section C.
p′(r, φ) = F −1
[ P′(kr, φ)]
A major drawback of direct Fourier recon-
(16-11)
struction is that the interpolation from polar =F −1
[ kr P (kr, φ)]
to rectangular coordinates in k-space is com-
putationally intensive. As well, it can lead to 5. Perform conventional backprojection using
artifacts in the image, if not done carefully. A the filtered profiles. Mathematically, the
more elegant (and practical) approach, called result is
filtered backprojection (FBP), is described in
the next section. 1 N
f ( x, y) = ∑ p′( x cos φi + y sin φi, φi ) (16-12)
N i =1
3. Filtered Backprojection
Like the direct FT algorithm, FBP employs Step 5 is essentially the same as simple back-
the projection slice theorem but uses the projection, but with filtered profiles. However,
theorem in combination with backprojection unlike Equation 16-3, in which fâ•›′ (x,y) is only
in a manner that eliminates 1/r blurring. The an approximation of the true distribution,
steps are as follows: FBP, when applied with perfectly measured
1. Acquire projection profiles at N projection noise-free data, yields the exact value of the
angles (same as direct FT). true distribution, fâ•›(x,y). Figure 16-9 schemat-
2. Compute the 1-D FT of each profile (same ically illustrates the process of FBP for a
as direct FT). In accordance with the pro- pointlike object.
jection slice theorem (see Fig. 16-7 and The only difference between simple and fil-
Equation 16-8), this provides values of the tered backprojection is that in the latter
FT for a line across k-space. method, the profiles are modified by a recon-
3. Apply a “ramp filter” to each k-space struction filter applied in k-space before they
profile. Mathematically, this involves are backprojected across the image. The effect
H (kr)
k
kmax
16 • Tomographic Reconstruction in Nuclear Medicine 261
Backprojection
of filtered
profile at 0°
across image
matrix
FIGURE 16-9 Illustration of the steps in filtered backprojection. The one-dimensional Fourier transforms of projection
profiles recorded at different projection angles are multiplied by the ramp filter. After taking the inverse Fourier
transform of the filtered transforms, the filtered profiles are backprojected across the image, as in simple
backprojection.
of the ramp filter is to enhance high spatial frequency, this also leads to degradation of
frequencies (large kr) and to suppress low signal-to-noise ratio (SNR). For this reason,
spatial frequencies (small kr). The result of images reconstructed by FBP appear noisier
the filtering is to eliminate 1/r blurring.* One than images reconstructed by simple backpro-
way to visualize the effect is to note that, jection. (This is a general result of any image
unlike unfiltered profiles (see Fig. 16-5), the filtering process that enhances high frequen-
filtered profiles have both positive and nega- cies to “sharpen” images.) In addition, filters
tive values (see Fig. 16-9). The negative por- that enhance high frequencies sometimes
tions of the filtered profiles near the central have edge-sharpening effects that lead to
peak “subtract out” some of the projected “ringing” at sharp edges. This is an unwanted
intensity next to the peak that otherwise byproduct of the positive-negative oscillations
would create 1/r blurring. introduced by the filter, illustrated in the fil-
Amplification of high spatial frequencies in tered profile at the top of Figure 16-9.
FBP also leads to amplification of high- To minimize these effects on SNR and
frequency noise. Because there usually is little artifacts at sharp edges, the ramp filter
signal in the very highest frequencies of a usually is modified so as to have a rounded
nuclear medicine image, whereas statistical shape to somewhat suppress the enhance-
noise is “white noise” with no preferred ment of high spatial frequencies. Figure
16-10 illustrates a ramp filter and two other
commonly used reconstruction filters. Also
shown are the equations describing these
*More precisely, 1/r blurring is the convolution of the true filters. A variety of reconstruction filters have
image with a blurring function, b(r) = 1/r (Equation 16-4). been developed, each with its own theoretical
As discussed in Appendix G, convolution in image space rationale. Filters also play a role in the sup-
is equivalent to multiplying by the FT of the blurring pression of artifacts caused by aliasing in
function in k-space, which for b(r) is B(kr) = 1/|kr|. Thus
multiplying by |kr| in k-space is equivalent to deconvolv-
FT-based reconstruction techniques, as dis-
ing the blurring function in image space, thereby elimi- cussed in Section C. Additional discussions of
nating the blurring effect. these filters can be found in reference 4.
262 Physic in Nuclear Medicine
Ramp: H(k) | k |
2kcut-off |k|
SheppLogan : H(k) sin
2kcut-off
k
Hann : H(k) 0.5 | k | 1cos
kcut-off
1 FIGURE 16-10 Ramp filter and two other recon-
struction filters that are designed to prevent arti-
facts and noise amplification caused by the sharp
0.8 Ramp cut-off of the ramp filter at the maximum frequency
kmax. Note that all of the filters shown have the same
Amplitude H (k /kmax)
0.2
Hann
0
0 0.2 0.4 0.6 0.8 1
Frequency (k/kmax)
resolutions, much the same as the sampling at least twice per cycle. Coarser sampling
interval, Δâ•›r, across the image profile can be does not allow higher spatial frequencies to
adjusted to vary the in-plane resolution. In be recovered and leads to image artifacts
PET systems, the distance between image known as aliasing. Mathematical aspects of
slices and the slice thickness often is fixed by aliasing are discussed in detail in Appendix
the axial dimensions of the segmented scintil- F, Section C.
lator crystals typically used in the detectors Thus the linear sampling distance sets a
(See Chapter 18, Sections B and C). limit on spatial resolution for the imaging
system. This limit (kmax in Equation 16-13)
also is known as the Nyquist frequency, kNyquist
(see also Equation F-9). The highest spatial
C. IMAGE QUALITY IN FOURIER frequency that is present in an image profile
TRANSFORM AND FILTERED depends on the spatial resolution of the
BACKPROJECTION TECHNIQUES collimator-detector system. Higher resolution
implies higher frequency content. As a rule of
In this section, we discuss some general issues thumb, the sampling requirement for an
involving image quality in reconstruction imaging detector is
tomography based on the direct FT and FBP
techniques. These issues affect all reconstruc- ∆ r ≤ FWHM / 3 (16-14)
tion tomography based on these techniques,
including both x-ray CT and ECT. Additional where FWHM is the full width at half
aspects that are specifically relevant to maximum of its point-spread function (see
SPECT and PET image quality are discussed Chapter 15, Section B.2).
in Chapters 17 and 18, respectively. The Figure 16-11 shows images of a computer-
issues discussed here do not pertain directly simulation phantom that were reconstructed
to iterative reconstruction techniques, which with progressively coarser sampling of the
are discussed separately in Section D. image profiles. Undersampling not only
results in image blurring but also creates
1. Effects of Sampling on image artifacts resulting from the effects of
Image Quality aliasing.
Projection data are not continuous functions The Nyquist frequency is the highest
but discrete point-by-point samples of projec- spatial frequency represented in k-space and
tion profiles. The distance between the sample thus defines an upper frequency limit for
points is the linear sampling distance. In addi- the reconstruction filter. However, a lower-
tion, projection profiles are acquired only at a frequency filter cut-off, kcut-off < kNyquist can be
finite number of angular sampling intervals used in the reconstruction. This improves
around the object. The choice of linear and SNR by suppressing the high-frequency end
angular sampling intervals and the cut-off fre- of the spatial frequency spectrum, where a
quency of the reconstruction filter (see Fig. large fraction of the signal is statistical
16-10), in conjunction with the spatial resolu- noise. Lowering the cut-off frequency also
tion of the detector system, determine the degrades spatial resolution, because the
spatial resolution of the reconstructed image. higher frequencies also contain the fine
The effects of the imaging system depend on details of the image. Thus the choice of the
the type of detector, collimator, and so forth reconstruction filter and its cut-off frequency
and are discussed in Chapters 17 and 18. Here involve a tradeoff between spatial resolution
we discuss briefly those aspects that are and SNR in the image. This is illustrated in
related to the reconstruction process, which Figure 16-12, which shows images of a
are applicable to all types of imaging devices. computer-simulation phantom reconstructed
The sampling theorem5 states that to with a Shepp-Logan filter with different
recover spatial frequencies in a signal up to a cut-off frequencies.
maximum frequency kmax requires a linear The angular sampling interval (angle
sampling distance given by between projections) should provide sampling
around the periphery at approximately the
same intervals as the linear sampling dis-
∆ r ≤ 1/(2kmax ) (16-13)
tance. Thus if projections are acquired around
a FOV of diameter D, the minimum number
This means that the highest spatial frequency of angular views, Nviews, should be approxi-
to be recovered from the data must be sampled mately the length of the 180-degree arc over
264 Physic in Nuclear Medicine
∆r = 0.2 cm ∆r = 0.4 cm
C D
16 • Tomographic Reconstruction in Nuclear Medicine 265
which projections are acquired (πâ•›D/2) divided For FOV = 30╯cm, this amounts to
by the linear sampling distance, Δâ•›r:
Nsamp ≥ 30 / (1/ 3) ≈ 90 samples per profile
N views ≥ π D/ 2∆ r (16-15)
According to Equation 16-15, the number of
Figure 16-13 illustrates the effect of angular views should be such that
sampling interval on images of a computer-
simulation phantom. Spokelike artifacts N views ≥ (π × 30) / [2 × (1/ 3)] ≈ 140 views
are evident around high-intensity objects
when the number of angular samples is Thus 140 views over a 180-degree degree
inadequate. arc, with linear sampling at approximately
0.33-cm intervals, would fully support the
EXAMPLE 16-1 available system resolution.
Suppose you are working with an ECT system
that has spatial resolution FWHM ≈ 1╯cm and The closest power-of-two image reconstruc-
FOV = 30╯cm. Estimate the sampling inter- tion and display matrix that would meet the
val, Δâ•›r, and the number of angular views, sampling requirements in Example 16-1 is 128
Nviews, that would support the available spatial × 128. One possibility would be to interpolate
resolution of the system. the sampled profiles from 90 samples to 128
samples. A more practical option, however, is
Answer to acquire 128 samples over 30╯cm, which
From Equation 16-14, the sampling interval would somewhat exceed the linear sampling
should be requirement. If this were done, Equation 16-15
would suggest that additional views would be
∆r ≤ 1 cm / 3 ≈ 0.33 cm needed to support the smaller value of Δâ•›r;
FIGURE 16-13 Effect of the number of angular samples recorded on the reconstructed image of a computer-simulation
phantom. Spokelike streak artifacts are evident when an inadequate number of projections are used. (Computer simu-
lations performed by Dr. Andrew Goertzen, University of Manitoba, Canada.)
266 Physic in Nuclear Medicine
however, 140 views still would provide the and some positron emission mammography
number of angular views needed to support systems).
the system resolution and this number would A second requirement for coverage is that
not have to be increased. On the other hand, the entire object (or at least the parts contain-
going in the opposite direction, that is, acquir- ing radioactivity) must be included in all pro-
ing only 64 samples and fewer angular samples jections. If some parts of the object are not
for reconstruction on a 64 × 64 matrix would included in all projections, the data will be
lead to a loss of image detail and introduce the inconsistent between different projections.
possibility of image artifacts, as illustrated in There are a number of ways in which this can
Figures 16-11 and 16-13. happen. For example, the FOV of the detector
may be insufficient to provide full coverage
2. Sampling Coverage and from all directions. Figure 16-15 illustrates
Consistency Requirements the effect of incomplete coverage of the object
In addition to meeting the requirements during some parts of the scan.
described in the preceding section regarding Two other possible sources of inconsistency
linear and angular sampling intervals, the between projections are patient movement
data acquired must provide full coverage of and missing or distorted values in individual
the object. Thus it is necessary that data be profiles caused by instrumentation failures,
acquired over a full 180-degree arc. If an arc such as an unstable element in a detector
less than 180 degrees is used, geometric dis- array. Figure 16-16 illustrates some effects of
tortions are produced. Figure 16-14 demon- these types of inconsistencies.
strates that an inadequate angular-sampling
range causes data to flare out past the true 3. Noise Propagation, Signal-to-Noise
objects and produces geometric distortions Ratio, and Contrast-to-Noise Ratio
perpendicular to the direction of the absent Noise propagation, SNR, and CNR differ in
projections. This is a problem for a number ECT from their behavior in conventional
of systems developed in nuclear medicine planar imaging. In conventional planar
that are classified as “limited-angle tomogra- imaging, the SNR for an individual pixel is
phy” (e.g., rotating slant-hole tomography essentially equal to Npixel , in which Npixel is
FIGURE 16-15 Effects of having some profiles that do not cover the entire object. Left, Sinogram of computer-
simulation phantom. Right, Reconstructed image. (Computer simulations performed by Dr. Andrew Goertzen, University
of Manitoba, Canada.)
FIGURE 16-16 Effects of missing projection elements on reconstructed image. Left, Sinogram of computer-simulation
phantom. Right, Reconstructed image. This simulation would apply to a SPECT image reconstructed from profiles
acquired over a 180-degree sampling range with a single-headed camera, with one region of the detector “dead.” (Com-
puter simulations performed by Dr. Andrew Goertzen, University of Manitoba, Canada.)
the number of counts recorded for that pixel. square matrix of size D × D = D2 with pixel
In ECT, the computation of noise and SNR is size Δâ•›r × Δâ•›r = Δâ•›r 2. It can be shown that the
much more complicated because the intensity SNR for an individual pixel in the resulting
level for each pixel is derived by computations image of the object is given by6
involving different views and many other
pixels in the image. In addition, a variety of 12 N image
mathematical manipulations, such as filtering SNR pixel ≈ (16-16)
operations, are performed along the way. As a π2 ( D / ∆ r ) 3
result, although SNR still depends on the
square root of the total number of counts Equation 16-16 indicates that SNR decreases
recorded during the imaging procedure, the when pixel size, Δâ•›r, is made smaller, that is,
relationship between those counts and the as spatial resolution is improved.* The
SNR of individual pixels is more complicated.
Suppose that an ECT image is acquired of
a cylindrical object of diameter D containing
*Note that Equation 16-16 specifically assumes that pixel
a uniform concentration of radioactivity. width is the same as the sampling interval, Δâ•›r. Often in
Suppose further that projection data are nuclear medicine, interpolation techniques are used to
acquired with a linear sampling interval Δ r generate images with pixels that are smaller than the
across all projection profiles, that a total sampling interval. Equation 16-16 is valid in these situ-
ations provided that the sampling interval rather than
of Nimage counts are recorded during the pixel size is used in the equation. Some texts describe Δâ•›r
imaging procedure, and that the image is as the “resolution element” to avoid confusing it with
reconstructed by FBP with a ramp filter on a pixel size.
268 Physic in Nuclear Medicine
< Npixel > from which the percent noise level is 100%/56
SNR pixel ≈ 12 / π 2 × (16-17) ≈ 1.8%.
4 npixels For the image reconstructed by FBP, the
result is as given in Example 16-2:
where <â•›Nâ•›pixelâ•›> is the average number of
counts recorded per reconstructed pixel in the SNR pixel ≈ 12.33
object. This can be simplified even further by
noting that 12 /π 2 = 1.103 ≈ 1, for more from which the percent noise level is
approximate work. 100%/12.33 ≈ 8.1%.
Equation 16-17 indicates that SNR per
pixel improves in proportion to the square The “noise enhancement” factor for recon-
root of the average number of counts recorded struction tomography illustrated in Example
per pixel. This part of the equation is 16-3 is the result of noise propagation from
16 • Tomographic Reconstruction in Nuclear Medicine 269
pixels at many locations in the imaged object image is < Npixel> ≈ 10 counts per minute (cpm)
into the pixel of interest in the backprojection × 1╯min = 10. Thus from Equation 16-17, the
process, as well as the ramp filtering SNR per pixel for the ECT image would be
operation.
Example 16-3 applies to the SNR of a single 10 10
SNR pixel ≈ ≈ ≈1
pixel in images of a uniform object. The result 4
100 10
would seem to imply a statistical disadvan-
tage for the detection of low-contrast objects Using the definition given in Equation 15-6,
by ECT. However, for purposes of applying the contrast of the lesion in the ECT image is
the Rose criterion for detectability of lesions
and other objects (see Chapter 15, Section C = (1 − 10) /10 = −0.9
D.2) this must be converted to CNR for the
object of interest. Using the definitions given Substituting these values into Equation
in Chapter 15, it can be shown that the CNR 16-18, one obtains
for a lesion that occupies n pixels in an ECT
image is CNR ≈ −0.9 × 1 × 1 ≈ 0.9
CNR ≈ C × n × SNR pixel (16-18) which is the same result as obtained for
planar imaging. In neither case would the
where the absolute value indicates that CNR lesion be detectable using the Rose criterion.
always is a positive quantity. Although the
noise characteristics in ECT differ somewhat Example 16-4 shows that, for the same
from those of planar imaging (particularly level of object contrast and total number of
regarding possible artifacts), the same general counts in the image, and in the absence of
rules for detectability apply for ECT and attenuation and distance effects, there is no
planar images, that is, CNR ≥ 4. intrinsic difference in CNR between ECT and
planar imaging. This result is obtained, in
spite of the apparent statistical disadvantage
EXAMPLE 16-4 of ECT illustrated in Example 16-3, because
Consider the situation described for radio- of the increased contrast of the low-contrast
pharmaceutical B in Example 15-6. In that lesion in an ECT image as compared with a
example, the radiopharmaceutical produced projection image. On the other hand, the
“cold” lesions with uptake that was 10% of the sophisticated data manipulations of ECT do
surrounding normal tissue and a CNR of only not improve the detectability of the lesion.
0.9 for a 1-cm diameter lesion. Using the This is not too surprising, because it should
same parameters, estimate the CNR that not be possible to improve CNR when noise is
would be achieved using the same radiophar- generated by counting statistics by applying
maceutical, spatial resolution, and total mathematical manipulations (e.g., recon-
imaging time with ECT. Assume that the struction tomography and contrast enhance-
normal tissue fills a volume of (10 × 10 × ment) of otherwise comparable data.
10╯cm) and, as in Example 15-6, ignore the Thus it is inaccurate to conclude that ECT
effects of attenuation and source-to-detector improves detectability of lesions or other
distance. objects by improving CNR. Rather, the
primary advantage of ECT for detecting low-
Answer contrast lesions derives from its ability to
The planar image described for Example 15-6 remove confusing overlying structures that
could be obtained by facing the detector may interfere with detectability of those
toward any face of the cubic volume of tissue lesions, such as ribs overlying a lesion in the
and acquiring counts for a 1-min imaging lungs. Not only does an object become more
time. For purposes of computing the SNR of detectable when overlying clutter is removed
an ECT image, many projection views would by ECT, but its shape and borders become
be required (e.g., 60 1-sec views), but the total more clear.
number of counts recorded in 1╯min of imaging An additional advantage of ECT is the
time, in the absence of attenuation and dis- ability to determine more accurately the con-
tance effects, would be the same as for planar centration of radioactivity in a particular
imaging. The total number of pixels in the volume of tissue. For example, in Example
ECT image is npixels = 10 × 10 = 100, and 16-4, the same planar image would be
the average number of counts per pixel in the obtained if the lesion were twice as thick
270 Physic in Nuclear Medicine
along the viewing direction, but with half the and precomputing factors), reconstruction
uptake suppression and thus twice the con- times have become practical and iterative
centration as originally specified in Example methods are finding their way into more
15-6. However, such a difference would be general use.
readily evident on the ECT image (assuming
the CNR requirements for detectability were
met). Some appreciation for all of these advan- 1. General Concepts of Iterative
tages can be gained by inspection of Figure Reconstruction
15-11. The general concepts of iterative reconstruc-
tion are outlined in Figure 16-17. In essence,
the algorithm approaches the true image,
D. ITERATIVE RECONSTRUCTION f (x,y), by means of successive approximations,
ALGORITHMS or estimates, denoted by f╛╛*(x,y). Often the
initial estimate is very simple, such as a blank
A viable and increasingly used alternative or uniform image. The next step is to compute
to FBP is a class of methods known as the projections that would have been mea-
iterative reconstruction. These methods are sured for the estimated image, using a process
computationally more intensive than FBP called forward projection. This process is
and for this reason have been more slowly exactly the inverse of backprojection. It is per-
adopted in the clinical setting. However, as formed by summing up the intensities along
computer speeds continue to improve, and the potential ray paths for all projections
with a combination of computer acceleration through the estimated image. The set of
techniques (e.g., parallel processors), and projections (or sinogram) generated from
intelligent coding (e.g., exploiting symmetries the estimated image then is compared with
Measured
projection data
sinogram p (r,φ)
Object
f(x,y)
ECT system
Forward
Image projection Calculated
estimate Compare
projection converged?
f *(x,y) data p(r,φ) Yes
No
Reconstructed
image
Update
image
estimate
FIGURE 16-17 Schematic illustration of the steps in iterative reconstruction. An initial image estimate is made and
projections that would have been recorded from the initial estimate then are calculated by forward projection. The
calculated forward projection profiles for the estimated image are compared to the profiles actually recorded from the
object and the difference is used to modify the estimated image to provide a closer match. The process is repeated until
the difference between the calculated profiles for successively estimated images and the actually observed profiles
reaches some acceptably small level.
16 • Tomographic Reconstruction in Nuclear Medicine 271
the actually recorded projections (or sino- image and the profiles actually recorded from
gram). Most likely, they will not agree, because the scanned object. The second component is
it is unlikely that the initial estimate of f╛╛*(x,y) performed by the search or update function,
closely resembles the true image. However, which uses the output of the cost function to
the difference between the estimated and update the estimated image. A general goal of
actual projections can be used to adjust the algorithm development is to devise versions
estimated image to achieve closer agreement. of these functions that produce convergence
The update-and-compare process is of the estimated image toward the true image
repeated until the difference between the as rapidly and accurately as possible. One
forward-projected profiles for the estimated area of algorithmic differences is the method
image and the actually recorded profiles falls for dealing with statistical noise. For example,
below some specified level. With proper design some algorithms give more weight to portions
of the image updating procedure, the esti- of projections (or sinograms) that contain the
mated image progressively converges toward highest number of counts, and thus the lowest
the true image. Figure 16-18 shows the prog- percentage levels of statistical noise (see
ress of the estimated image during iterative Chapter 9, Section B.1). Another approach is
reconstruction with an increasing number of to incorporate some sort of “prior informa-
iterations. tion,” such as the expected shape or smooth-
The two basic components of iterative ness of the image. Some algorithms also
reconstruction algorithms are (1) the method “force” the reconstructed image to be non-
for comparing the estimated and actual pro- negative. A concise history and review of iter-
files and (2) the method by which the image ative reconstruction methods are presented in
is updated on the basis of this comparison. In reference 7.
generic terms, the first component is per- Two factors make iterative reconstruction
formed by the cost function, which measures computationally more intensive than FBP.
the difference between the profiles generated First, most iterative algorithms require
by forward projections through the estimated several iterations to converge to an acceptable
FIGURE 16-18 Brain images generated for different numbers of iterations by an iterative reconstruction algorithm.
Image resolution progressively improves as the number of iterations increases. In practice, the iterations are performed
until an acceptable level of detail is achieved or until further iterations produce negligible improvement. (Courtesy Dr.
Richard Leahy, University of Southern California, Los Angeles, CA.)
272 Physic in Nuclear Medicine
image, and each of these iterations is essen- profile.) Because of the statistical weighting
tially equivalent to a separate backprojection factor, the algorithm often is referred to as the
procedure. Backprojection is the most time- ML-EM method. A detailed discussion of this
consuming part of the FBP algorithm but only algorithm and its theoretical underpinnings
needs to be done once for FBP. Forward pro- are beyond the scope of this text but can be
jection is similarly time-consuming in itera- found in references 8 and 9. Here we present
tive reconstruction algorithms. only a description of how it is implemented.
Second, iterative algorithms often incorpo- In the EM algorithm, the reconstruction
rate factors that account for the specific char- process is formulated as follows
acteristics of the imaging device, such as
collimator and object scatter, system geome-
try, and finite detector resolution. Simple p j = ∑ Mi, j fi (16-19)
forward projection along a single ray path no i
estimated intensity value f of pixel i in the of angular views results in a more or less
(k + 1)st iteration of the EM algorithm is as uniform loss of spatial resolution across the
follows: reconstructed image. If only partial angular
coverage of the object is obtained (e.g., from
fik pj
fik+1 = × ∑ Mi, j 0 to 120 degrees instead of over the full
∑ Mi, j j k
∑ Ml, j fl
(16-20) 180 degrees), the resolution is likely to be
j
l
degraded along the direction of the missing
data. Because iterative algorithms are non-
where k refers to the immediately preceding linear in nature, the exact effects of under-
kth iteration. The term in parentheses in sampling are object and algorithm
the denominator on the right hand side of dependent.
Eq. 16-20 represents a summation over all
image pixels. This term must be evaluated
first before the summation over the j projec- E. RECONSTRUCTION OF FAN-BEAM,
tion elements can be computed. Therefore CONE-BEAM AND PINHOLE SPECT
it is given a different pixel index, l, instead DATA, AND 3-D PET DATA
of i, to avoid confusion.
The number of iterations can be fixed, or The discussion thus far has focused on recon-
the iteration process can be terminated when structing projection data in which the acquired
some measure of the difference between rays for a given projection angle are parallel
images from one iteration to the next (e.g., and the projection data arises from parallel
the sum of the squares of differences for all sections through the body. This is the situa-
pixels in the reconstructed image) falls below tion when a parallel-hole collimator is used.
some predetermined value. In theory, with Tomographic reconstruction also can be per-
perfectly measured noise-free data and an formed using data acquired with fan-beam,
exact matrix M, the algorithm eventually cone-beam, or pinhole collimators. The ratio-
would converge to the point where the esti- nale for using these collimators is that they
mated projection data, ∑ l Ml, j flk exactly can provide higher spatial resolution
equals the measured projection data, pj, for (converging-hole or pinhole collimators) or
each profile. At that point greater coverage (diverging-hole collimators—
see Chapter 14, Section D). However, these
fik+1 = fik (16-21) collimators introduce an added degree of com-
plexity for reconstruction tomography of
that is, there is no further change in the esti- SPECT data, because they do not provide
mated image and the estimated activity image simple parallel-ray line integral projections
is identical to the true activity distribution. such as were illustrated in Figure 16-2.
In practice, this never happens, owing to inac- Similar issues arise in PET scanning. In addi-
curacies or simplifications in M and statisti- tion to acquiring projection data for trans-
cal noise. Therefore some practical limit must verse sections through the body, PET scanners,
be set for an acceptable difference that will be as discussed in Chapter 18, Section C, also are
used to terminate the reconstruction process. capable of acquiring additional projection
The computational issues relating to itera- data at oblique angles with respect to these
tive reconstruction techniques already have transverse slices. Accurately incorporating
been mentioned. Equation 16-20 (which rep- this additional projection data requires 3-D
resents only a single-slice version of the algo- reconstruction algorithms.
rithm) illustrates this point. Nevertheless,
the ML-EL algorithm can produce high- 1. Reconstruction of Fan-Beam Data
quality images with good quantitative accu- We should first distinguish between fan-beam
racy and is now a selectable option on many versus cone-beam collimators. Figure 16-19
PET and SPECT cameras. schematically illustrates the difference. Con-
The sampling and noise-propagation rules sider first the fan-beam collimator shown at
summarized in Section C do not apply to the top of the figure. In this collimator, each
iterative reconstruction. Although insuffi- row of holes across the collimator has its own
cient sampling also has consequences for focal point. Sequential rows of collimator
iterative algorithms, the aliasing and streak- holes are stacked and evenly spaced, parallel
ing artifacts associated with FBP are not to each other, along the z-axis of the object.
seen. More typically, undersampling in the Apart from overlapping coverage resulting
linear sampling distance or in the number from the finite diameters of the collimator
274 Physic in Nuclear Medicine
z r
Fan-beam
z r
Cone-beam
FIGURE 16-19 Schematic illustrations of fan-beam and cone-beam collimators. Cross-sections are shown for perpen-
dicular viewing angles.
holes, each row of holes provides its own rotation around the object. However, whereas
independent and nonoverlapping projection complete coverage can be obtained with a
profile. 180-degree rotation using a parallel-hole col-
Data from a fan-beam collimator cannot be limator, the required rotation for a converging-
inserted directly into algorithms used for beam collimator is (180 + θ) degrees, in which
reconstructing data acquired with a parallel- θ is half the fan angle for the collimator (see
beam collimator. However, the data can be Fig. 14-20). Conversely, for a diverging colli-
rearranged so that these algorithms can be mator, the required angle of rotation is (180
used. One approach is to re-sort the fan-beam − θ) degrees.
data into parallel-beam data. Figure 16-20
illustrates how this is done for a few elements
of adjacent projection profiles. Once the 2. Reconstruction of Cone-Beam
data have been re-sorted, any of the algo- and Pinhole Data
rithms discussed in the preceding sections for In a cone-beam collimator (Fig. 16-19, bottom),
parallel-beam collimators can be used. Alter- all of the holes are directed toward (or away
native, and more elegant, approaches refor- from) a common focal point. Each row of holes
mulate the FBP algorithm itself to handle across the center of the collimator provides a
fan-beam data. These are discussed in refer- projection profile, but the profiles all intersect
ences 2 and 7. at the center. (This also applies to the pinhole
A fan-beam collimator provides complete collimator.) It is not possible to re-sort the
3-D coverage of a volume of tissue in a single data acquired from a single rotation of a
16 • Tomographic Reconstruction in Nuclear Medicine 275
Fan-beam
data sets
Re-sorted into
parallel-ray
data sets
FIGURE 16-20 Procedure for creating parallel-beam projections from a set of fan-beam projections.
cone-beam collimator around the object into a 3-D cone-beam data; however, computing
full set of parallel-ray projections. Only one time increases dramatically as compared with
set (corresponding to the projections acquired already time-consuming single-slice iterative
from a single slice across the center of colli- algorithms. The matrix M (Equation 16-19)
mator, oriented perpendicular to the axis of becomes very large for a full 3-D algorithm
rotation) can be re-sorted in this way. There- and, even with accelerated approaches and
fore to obtain complete projection coverage of specialized computer hardware, full 3-D
a volume of tissue to allow accurate recon- image reconstructions are typically at least
struction of multiple slices, a more complex an order of magnitude slower than multislice
rotation is required. 2-D image reconstructions.
One approach is to perform a helical scan
around the object, translating the collimator 3. 3-D PET Reconstruction
along the z-axis as it rotates about that axis. PET scanners typically consist of multiple
This provides a dataset that can be re-sorted detector rings (see Chapter 18, Section B).
into a complete set of parallel projections for Projection data acquired within a given detec-
multiple slices through the object. An alterna- tor ring can be reconstructed into a trans-
tive approach is to use approximations and verse image with the methods described
interpolations to convert the cone-beam data previously in Sections B and D. However,
into fan-beam data. The most popular of these PET scanners also can acquire projection
methods is called the Feldkamp algorithm, data at oblique angles between detector rings
described in reference 10. These methods (see Chapter 18, Section C and Fig. 18-24). To
work best when the cone angle is small. incorporate these additional projection angles
Finally, iterative algorithms, conceptually requires some form of 3-D reconstruction
similar to those described in Section C, have algorithm. 3-D algorithms have been devel-
been developed for direct reconstruction of oped based on both FBP and iterative
276 Physic in Nuclear Medicine
detector projection-ray
rings measured oblique rebinned into the
projection-ray transverse plane at
axial location (ab)/2
direction
axial
transverse
direction
FIGURE 16-21 Illustration of single-slice re-binning in which an oblique projection-ray between the detector pair a
and b is “re-assigned” to the projection data for the non-oblique slice corresponding to a transverse detector pair at
axial location (a + b)/2.
5. Oppenheim AV, Wilsky AS: Signals and Systems, 9. Lange K, Carson R: EM reconstruction algorithms for
Englewood Cliffs, NJ, 1983, Prentice-Hall, pp emission and transmission tomography. J Comput
513-555. Assist Tomogr 8:306-316, 1984.
6. Hoffman EJ, Phelps ME: Positron emission tomogra- 10. Feldkamp LA, Davis, LC, Dress JW: Practical cone-
phy: Principles and quantitation. In Phelps ME, beam algorithm. J Opt Soc Am 1:612-619, 1984.
Mazziotta JC, Schelbert HR, editors: Positron Emis- 11. Daube-Witherspoon ME, Muehllehner G: Treatment
sion Tomography and Autoradiography: Principles of axial data in three-dimensional PET. J Nucl Med
and Applications for the Brain and Heart, New York, 28:1717-1724, 1987.
1986, Raven Press, pp 237-286. 12. Lewitt RM, Muehllehner G, Karp JS: Three-
7. Leahy RM, Clackdoyle R: Computed tomography. In dimensional image reconstruction for PET by multi-
Bovik A, editor: Handbook of Image and Video Pro- slice rebinning and axial image filtering. Phys Med
cessing, Burlington, MA, 2005, Elsevier Academic Biol 39:321-339, 1994.
Press, pp 1155-1174. 13. Defrise M, Kinahan PE, Townsend DW, Michel C,
8. Shepp LA, Vardi Y: Maximum likelihood reconstruc- Sibomana M, Newport DF: Exact and approximate
tion for emission tomography. IEEE Trans Med Imag rebinning algorithms for 3D PET data. IEEE Trans
1:113-122, 1982. Med Imag 16:145-148, 1997.
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chapter
17
Single Photon
Emission Computed
Tomography
collimation is achieved using a lead aperture SPECT in smaller clinics, dedicated and
ring, with 12 equally spaced 2.4-mm-wide compact cardiac SPECT systems with high
slits, that rotates in front of the stationary sensitivity have been developed. In contrast
detector array (Fig. 17-2A). Axial collimation to the SPECT systems discussed so far, the
is achieved using a set of stacked stationary majority of these cardiac systems involve
lead foils. As the collimator ring rotates the patient sitting upright in a chair during
through one slit interval (30 degrees), the the examination.
system acquires a complete set of fan-beam Figure 17-3A shows a triple-headed SPECT
projection data. system designed for cardiac applications.3
A system based on similar principles is the Note the much smaller size of the detector
CERASPECT system.2 In this case, the detec- heads compared with general-purpose SPECT
tor is a single annular NaI(Tl) crystal (31╯cm systems. The detector heads use pixelated
inner diameter × 8╯mm thick × 13╯cm wide) cesium iodide [CsI(Tl)] scintillator crystals,
coupled to 63 5-cm diameter PM tubes via read out by avalanche photodiodes (Chapter
glass light guides (Fig. 17-2B). A parallel-hole 7, Section C.3). The size of each CsI(Tl) pixel
collimator with six segments rotates in front is 6╯mm, and there are 768 pixels in each
of the detector, simultaneously providing six detector head, providing a detector FOV of
angular views. Each collimator segment has approximately 16╯cm × 20╯cm. In this system
a different FOV. This gives a higher weight- the detectors are fixed and the patient chair
ing to activity at the center of the object rotates to provide the necessary angular sam-
(which is viewed by all six collimator seg- pling for tomographic reconstruction. The
ments) in comparison to activity toward the distance between the detectors and the chair
periphery of the object (which is seen by a can be adjusted to accommodate patients
smaller number of collimator segments). This of different size. With a low-energy, high-
nonuniform weighting helps compensate for resolution (LEHR) collimator (see Table 14-1),
the effects of photon attenuation (see Sections the reported spatial resolution of the SPECT
B.1 and B.2) and provides more uniform images is 11╯mm (for a 20-cm detector-object
signal-to-noise ratio across the image. separation) and the sensitivity for each detec-
Both of these systems were designed pri- tor head is ~72 cps/MBq (160 cpm/µCi).
marily for brain imaging applications, and Because of the vertical orientation of the
both provide better image resolution than a patient, the entire system can fit in a room as
conventional SPECT system by placing the small as 2.4╯m × 2.4╯m.
collimated detector relatively close to the Another type of cardiac SPECT system
head. The reconstructed spatial resolution is replaces standard scintillation Anger camera
approximately 8╯mm at the center of the designs with detector heads made up of pixels
brain, improving to approximately 5╯mm at of the dense semiconductor cadmium zinc tel-
the edge of the brain. By comparison, a typical luride (CZT) (Chapter 7, Section B).4 This
single-head SPECT system operated with a system contains 10 small detector heads, dis-
radius of rotation of 12.5╯cm (appropriate for tributed in an arc over the chest of the patient
brain imaging) would have a resolution of (Fig. 17-3B). Each detector head [2-mm CZT
approximately 12.5╯mm full width at half pixels tiled on a 40-mm (transaxial) by 160-mm
maximum (FWHM) at the center of the brain (axial) area] is equipped with a parallel-hole
(see Fig. 14-16). These systems also have collimator and can rotate independently to
roughly twofold to threefold higher sensitivity sample different projection angles, enabling a
than a single-headed gamma camera with complete projection dataset to be acquired for
a general-purpose parallel-hole collimator, tomographic reconstruction. The patient chair
because multiple sets of projection data can is stationary. The reconstructed spatial reso-
be acquired simultaneously. This enables lution is quite dependent on the location in the
higher resolution to be achieved without FOV, and is nonisotropic, ranging between
injecting more radioactivity or lengthening approximately 8 and 14╯mm. The sensitivity
the imaging time. of the system is on the order of ~400 cps/MBq
(900 cpmâ•›/â•›µCi) for each detector head. The
3. SPECT Systems for Cardiac Imaging high sensitivity derives from the use of a
One of the most common uses for SPECT is shorter collimator with larger holes compared
to image myocardial function in patients with with the LEHR collimator.
a range of cardiovascular diseases. Because of A third design employs principles similar to
the relatively small FOV required for this the brain system shown in Figure 17-2A and
application, and the increasing use of cardiac described in Section 2. A multislit collimator
282 Physics in Nuclear Medicine
Field-of-view
Aperture ring
Scintillator bars
Detector module
Slice collimation
Detector
Collimator
Fields-of-view
B
FIGURE 17-2 Cross-sectional views showing the design of two SPECT systems designed for brain imaging. A, The
SPRINT system developed at the University of Michigan. This system employs a rotating collimator with 12 axial slits.
Transverse and axial views are shown. B, The CERASPECT system developed by Digital Scintigraphics, Inc., Cam-
bridge, MA. In this system, each collimator segment has a different field-of-view diameter. (A, From Rogers WL,
Clinthorne NH, Shao L, et╯al: SPRINT II: A second-generation single-photon ring tomograph. IEEE Trans Med Imag 7:291-297,
1988; B, From Genna S, Smith AP: The development of ASPECT, an annular single-crystal brain camera for high-efficiency
SPECT. IEEE Trans Nucl Sci 35: 654-658, 1988.)
17 • Single Photon Emission Computed Tomography 283
Detector
heads
Patient
chair
Rotating
CZT
detector
FIGURE 17-3 Photographs of dedicated cardiac SPECT scanners: A, A system with three detector heads. The patient
sits upright in the chair and the chair rotates in front of the detectors to acquire the projection angles necessary for
tomographic reconstruction. B, A system comprising nine cadmium zinc telluride detector heads arranged in an arc
around the patient. Each detector head rotates independently to provide different angular views. The patient remains
stationary in the chair. (A, Courtesy Digirad Corp., Poway, CA; B, Courtesy Spectrum Dynamics Ltd. Caesarea, Israel.)
permit high magnification of the object onto detector heads, each with a single pinhole col-
the detector with pinhole or converging hole limator, that rotate around the animal and
collimators (see Fig. 13-7). The second related translate along the animal to produce the
factor is that the organ of interest can always angular projections required for reconstruc-
be positioned within a few millimeters (rather tion tomography.
than many centimeters in humans) of the col- More advanced systems employ collimators
limator. Because of the strong dependence of with multiple pinholes to improve sensitivity.
spatial resolution on source-to-collimator dis- Such collimators also can increase the FOV
tance (see Fig. 14-16), much higher resolution along the axial direction without the need
can therefore be obtained. Furthermore, if to translate the animal. In the most straight-
pinhole collimation is used, the sensitivity forward implementation, the pinholes are
also increases rapidly as objects of interest arranged with sufficient distance between
are moved close to the pinhole aperture (see them such that the image of the animal
Fig. 14-21B and Equation 14-16). projected through adjacent pinholes does not
Thus the most common approach to small- overlap on the detector (Fig. 17-4, left). In
animal imaging with SPECT has been to use some systems, the projections are allowed
pinhole collimation, with some magnification. to overlap to a certain degree, which enables
Indeed, standard clinical SPECT systems more pinholes to be used for a given detec-
have been used to great effect in small-animal tor area and magnification (Fig. 17-4, right).
imaging using a pinhole or multipinhole col- However, this leads to ambiguity in the pro-
limator. However, to achieve optimal resolu- jection data in the region of overlap, and
tion and sensitivity performance, in a compact tomographic reconstruction into SPECT
device suited to a laboratory environment, images must use algorithms that properly
dedicated small-animal SPECT systems have model this ambiguity.
been developed. Although there are many Some multipinhole animal SPECT systems
different designs, these systems commonly are completely stationary and designed such
consist of a series of compact detector heads, that they simultaneously acquire sufficient
with interchangeable pinhole collimators that angular data for tomographic reconstruction
have apertures ranging from approximately with no moving parts. This type of system is
0.3╯mm to 2╯mm in diameter, allowing the particularly suited for rapid dynamic studies,
operator to trade off between improved spatial often of interest when evaluating the biodis-
resolution (smaller pinholes) or improved sen- tribution of a novel radiotracer in the first
sitivity (larger pinholes) (see Equations 14-15 seconds and minutes after injection. These
and 14-16). The detector heads often use pix- systems consist of an annular collimator
elated NaI(Tl) or CsI(Tl) scintillator arrays sleeve containing many pinholes each project-
(similar to those shown in Fig. 13-15B) or ing a different angular view of the radionu-
arrays of CZT semiconductor elements to clide distribution onto a detector that sits
achieve high intrinsic spatial resolution. The behind the collimator. Figure 17-5 shows one
simplest systems consist of two opposing such collimator and a drawing showing how
Object
Pinhole
apertures
Detector
Regions of
overlap
FIGURE 17-4 Illustration of multiple pinhole systems used for small-animal SPECT. Left, Two pinholes spaced far
enough apart to avoid overlap of projections. Right, Increased number of pinholes provides increased sensitivity, but
comes at the expense of a partial overlap in the projection data viewed through adjacent pinholes.
17 • Single Photon Emission Computed Tomography 285
A B
FOV
CFOV
Pinhole
Cylindrical
C collimator
FIGURE 17-5 A, Photograph of multiple-pinhole collimator for a stationary small-animal SPECT system. There are
75 pinholes viewing the object from different angles. B, Cut-away view of the pinhole collimator showing angulation
of pinholes and dense sampling in the central region. C, Transverse and axial sections through the center of the
collimator showing sensitive region for each pinhole and extent of field of view. (Courtesy MILabs, Utrecht, The
Netherlands).
the pinholes are angled to cover a large FOV applications. A useful review of small-animal
without the need for any movement. SPECT systems is given in reference 6.
Using these approaches, small-animal
SPECT systems routinely reach a resolution
in the range of 1╯mm, and in some instances B. PRACTICAL IMPLEMENTATION
are able to produce images with a recon- OF SPECT
structed resolution much smaller than 1╯mm.
Sensitivity can be high as well, because of the Ideally, the signal level for a voxel in a SPECT
large number of pinholes used. Numbers are image is linearly proportional to the amount
commonly in the 0.5 to 2 × 103 cps/MBq of activity contained within the volume of
(~1000-4000 cpm/â•›µCi) range, but depend tissue in the patient that corresponded to the
strongly on the number and diameter of the location of that voxel. This would be useful
pinhole apertures used, and the source-to- not only for quantitative applications, such as
pinhole distance. For systems in which the perfusion studies, but also for visual interpre-
projections overlap, the measured sensitivity tations of the image. In practice, this ideal
must be interpreted with caution, as the result is not achieved because the realities of
information content of an event detected in a data acquisition do not match the idealized
region of overlap is not as high as for an event assumptions made for the development of
in a system in which the projections do not reconstruction algorithms. As shown in Figure
overlap. Almost all small-animal systems use 16-1, it was assumed that the line of response
some form of iterative reconstruction algo- (or a projection element) for a single hole in a
rithm with detailed modeling of the collima- parallel-hole collimator is an extended cylin-
tor apertures for reconstructing images at der, but the actual response resembles a
the highest possible resolution. Figures 17-6A diverging cone. It was further assumed that
and B show photographs of two SPECT the signal recorded was proportional to the
systems designed for small-animal imaging total activity within the line of response, but
286 Physics in Nuclear Medicine
A B
C
FIGURE 17-6 Photographs of two small-animal SPECT systems: A, This stationary system uses the cylindrical multi�
pinhole collimator shown in Figure 17-5, and views are projected onto three large-area Anger cameras with no overlap
between projections. With no need to move the detectors, fast dynamic studies can be performed. B, This system
employs four 12.7╯cm × 12.7╯cm pixelated cadmium zinc telluride (CZT) detector heads and multipinhole collimators.
Some rotation of the detectors is necessary to obtain all projection angles. The use of CZT provides excellent energy
resolution. C, Photograph of one detector module from the system shown in B. The detector measures 2.54╯cm × 2.54╯cm
and has a 16 × 16 array of CZT elements on a 1.59-mm pitch. The CZT thickness is 5╯mm. Twenty-five of these modules
are tiled together to form a 12.7╯cm × 12.7╯cm detector head. (A, Courtesy MILabs, Utrecht, The Netherlands; B, Copyright
Gamma Medica, Northridge, CA and GE Healthcare, Waukesha, WI; used with permission of GE Healthcare; C, Copyright
Gamma Medica, Northridge, CA.)
in fact the signal from activity closest to the activity present. They also can lead to arti-
detector is more heavily weighted than from facts and seriously degraded image quality. To
deeper-lying activity, because of attenuation avoid this, one must use somewhat modified
by overlying tissues. Finally, it was assumed approaches to data acquisition or apply post-
that activity outside the line of response did processing of the acquired data. This is always
not contribute to the signal for the projection the case when backprojection algorithms are
element, whereas there may be crosstalk used, because they are rigorously grounded
between elements resulting from scattered in the idealized assumptions noted earlier.
radiation or septal penetration through the Some of the discrepancies can be accounted
collimator. To further complicate matters, for with iterative algorithms, such as the
most of the discrepancies vary with the energy maximum likelihood-expectation maximiza-
of the γ rays involved. tion algorithm (see Chapter 16, Section D.2),
Some of the discrepancies between the ide- which can incorporate these factors in its
alized assumptions and the actual situation probability matrix. In this section, we describe
in SPECT are illustrated in Figure 17-7. The some general approaches that are valid and
discrepancies distort the desired linear rela- potentially useful for all reconstruction
tionship between signal level and amount of algorithms.
17 • Single Photon Emission Computed Tomography 287
5 cm
10 cm
T0.46 15 cm
20 cm
T0.21
water T0.10
Transmission T ex
B for 140-keV rays in water, 0.155 cm1
A
FIGURE 17-7 A, Volumes of tissue viewed by a collimator hole at two different angles separated by 180 degrees. Differ-
ences in the volumes viewed results in different projections from the two viewing angles. B, Attenuation leads to further
differences in these two projections, emphasizing activity that is close to the gamma camera compared with activity
further away that has to penetrate more tissue to reach the gamma camera. Values are shown for the attenuation of the
140-keV γ rays from 99mTc in water.
99m
Tc-Line source response Water
Air
26
26 22
22 18
100
100 18 14
14
10
10
6
6
2
2
−30 −20 −10 0 10 20 30 mm
−20 −10 0 10 20 30 mm
Water
Arithmetic-mean
Air 26
26
22
22
18
100
18 14
100
14 10
10
6
6
2
Geometric-mean
Air Water
26
26
22
22
18
18
100
100 14
14
10
10
6
6
2
2
−30 −20 −10 0 10 20 30 mm
−20 −10 0 10 20 30 mm
FIGURE 17-8 Line-spread functions versus distance in air (left) and in water (right) for high-resolution parallel-hole
collimator on a gamma camera. The line source measured 2.5╯mm in diameter and was mounted inside a tank measur-
ing 410╯mm in length, 310╯mm in width, and 300╯mm in thickness. Measurements were made either with the tank
empty (in air) or filled with water. Top, single detector only; middle, arithmetic mean of opposing detector profiles;
bottom, geometric mean of opposed detector profiles. (From Larsson SA: Gamma camera emission tomography: Development
and properties of a multisectional emission computed tomography system. Acta Radiol Suppl 363:1-75, 1980.)
created from the arithmetic and geometric resolution with distance from the collimator
means of opposing views. The profiles across that is characteristic for a parallel-hole
the top are for a single view with the source collimator (see also Figs. 14-18 and 14-19).
in air and for the same view with the The profile for the source in water shows
source in water. The profile for the source in similar degradation of spatial resolution with
air illustrates the degradation of spatial increasing distance but, in addition, shows
17 • Single Photon Emission Computed Tomography 289
decreasing amplitude of response owing to attenuation are only partially corrected for by
attenuation of photons by the overlying thick- the arithmetic mean.
ness of water. The response profile for the arithmetic
The middle row of Figure 17-8 shows response mean has its minimum amplitude when the
profiles for the arithmetic mean. The profiles source is near the center of the water phantom.
for the source in air show significantly improved Figure 17-9 shows simulated SPECT images
uniformity of spatial resolution with depth, as of a water-filled cylinder containing a solution
compared with the single-view profile directly of uniform concentration of activity for differ-
above it. The profiles for the source in water ent γ-ray energies, using the arithmetic mean
show similar improvement in uniformity of of opposing views. Also shown are profiles of
spatial resolution with depth; however, there the images across the center of the phantom.
still is marked variation in the amplitude of As one might expect from the profiles illus-
the profile versus distance (and depth in trated in Figure 17-8, there is a marked
water), indicating that the effects of photon decrease in intensity at the center of the
Tc-99m
I-131
0.8 TI-201
No attenuation
0.6
Pixel value
0.4
0.2
0 4 8 12 16 20
Radial position (cm)
FIGURE 17-9 Top, Simulated SPECT images of 20-cm diameter water-filled cylinders containing uniform concentra-
tions of 99mTc (140╯keV), 131I (364╯keV), and 201Tl (70╯keV). Bottom, Arithmetic mean of count profiles through the center
of the simulated images. Note the reduction in image intensity at all points in the image caused by attenuation, with
the largest reduction occurring at the center of the cylinder. The amount of attenuation is energy dependent, with
greatest attenuation occurring at the lower γ-ray energies.
290 Physics in Nuclear Medicine
phantom. The strongest effect occurs for the The bottom row of Figure 17-8 shows pro-
lowest energy γ rays. It is apparent from files in air and in water for the geometric
Figure 17-9 that relatively strong attenuation mean of opposing views. In this case, both the
effects are present with the arithmetic mean amplitude and the width of the profile remains
for all of the photon energies commonly used nearly constant at all distances and depths in
in SPECT imaging. the water phantom.
Figure 17-10 shows simulated images and Tables 17-1 and 17-2 summarize numerical
profiles for phantoms of different sizes with data derived from the profiles in Figure 17-8.
µ = 0.155╯cm-1, corresponding to the attenua- From this summary, it can be seen that
tion of 140-keV photons of 99mTc in water. As attenuation has much stronger effects than
the diameter of the phantom increases, the distance. The combined effects of distance
images and count profiles demonstrate pro- and attenuation result in a 100-fold range
gressively greater suppression at the center in counts recorded with a single detector
of the image. (see Fig. 17-8, top right). With the arithmetic
10 cm 20 cm 30 cm
1 10 cm
20 cm
0.8 30 cm
0.6
Pixel value
0.4
0.2
−15 −10 −5 0 5 10 15
Radial position (cm)
FIGURE 17-10 Top, Simulated SPECT images of water-filled cylinders of different diameters containing uniform
concentrations of 99mTc (140╯keV). Bottom, Count profiles through the centers of the images. The strong dependence of
attenuation on cylinder size is evident.
TABLE 17-1â•…
NUMERICAL DATA FOR FIGURE 17-8 (LEFT COLUMN) 99mTc LINE SOURCE IN AIR
TABLE 17-2â•…
NUMERICAL DATA FOR FIGURE 17-8 (RIGHT COLUMN) 99mTc LINE SOURCE IN WATER
a b
Detector 1 Detector 2
Point source
of activity
FIGURE 17-11 Point source of activity within an attenuating medium of thickness D. The attenuation can be com-
pensated for by using the geometric or arithmetic mean and a correction for total tissue thickness, D.
17 • Single Photon Emission Computed Tomography 293
These analyses and equations are accurate must be modified for more complicated source
for a single radioactive source. When multiple distributions.7
sources are present, the situation is more
complicated, as shown in Example 17-1.
2. Attenuation Correction
EXAMPLE 17-1 Conjugate-counting techniques, especially
Derive the equation for the geometric mean using the geometric mean, can substantially
of counts from two point sources located along reduce the variation of width and amplitude
a line between two detectors, and show why of counting rate profiles that are present in
it cannot be described only in terms of the single-view profiles. However, even with the
unattenuated counts, I01, and I02, and µ and D geometric mean, there are residual scaling
(distance between the detectors) as can be factors caused by attenuation [exp(−µâ•›D/2) in
done for a single point source (Equation 17-5). Equation 17-6]. Thus, for quantitative accu-
Assume that a parallel-hole collimator is racy, attenuation corrections are required.
being used and therefore that the unattenu- A relatively simple method for attenuation
ated counts do not depend on distance. correction is to correct projection profiles gen-
erated with the geometric or arithmetic mean
Answer before reconstruction using an estimate for
tissue thickness, D. The attenuation correc-
D tion is particularly simple for the geometric
mean (Equation 17-6) and is given by multi-
a b plying the projection profiles by an attenua-
Detector 1 A1 A2 Detector 2 tion correction factor (ACF) of
c d 1
ACF = = eµ D / 2
− µD / 2
(17-7)
e
A constant value for µ, the linear attenua-
Referring to this figure: tion coefficient of tissue, is assumed. An esti-
mate for tissue thickness D can be derived
a+b= D from a preliminary uncorrected image or by
assuming a standard body size and shape.
c+d = D
As demonstrated in Example 17-1, simply
We represent the unattenuated counts from generating profiles using the geometric mean
source A1 as I01 and from source A2 as I02. The does not correctly deal with attenuation in
measured counts at detector 1 will be the general case in which γ rays are emitted
at different locations in the FOV. An alterna-
I1 = I01 e− µa + I02 e− µc tive approach is to calculate an ACF for each
The measured counts at detector 2 will be pixel after image reconstruction. In this
method, an initial image, fâ•›′(x,y), is recon-
I2 = I01 e− µb + I02 e− µd structed by filtered back-projection without
any attenuation correction. The contours of
The geometric mean is this image are used to obtain an estimate of
the attenuation path length through the
I1 × I2 = [ I01
2 − µ ( a +b)
e 2 − µ ( c +d )
+ I02 e + I01 I02 e− µ ( a + d) tissue for all projection views. Once again, it
is assumed that the linear attenuation coef-
+ I01 I02 e− µ (c + b) ]
1/2
ficient at a given energy is constant for
= [( I01 all body tissues. The ACF for each pixel
2
+ I02
2
) e− µD + I01 I02 e− µ(a+ d) (x,y) in the reconstructed image then is cal-
+ I01 I02 e− µ (c + b) ]
1/ 2
culated by
1
Only the first term in the last expression ACF ( x, y) = N
1 (17-8)
depends solely on I01, I02, µ, and D. The other
two terms contain exponential terms e−µ(c+b)
∑ e− µdi
N i =1
and e−µ(a+d) that depend on the relative loca-
tions of the two sources between the detec- where di is the attenuation path length for the
tors. Therefore attenuation effects depend on pixel at projection view i and µ is the assumed
the source distribution, and the simple correc- constant value for the attenuation coefficient.
tion scheme for point sources and line sources The reconstructed image fâ•›′(x,y) is corrected on
294 Physics in Nuclear Medicine
A B
C D
FIGURE 17-13 Examples of transmission source geometries that are being employed for attenuation correction in
SPECT. The black arrows show the direction of γ rays emitted from collimated transmission source; the gray arrows
show the direction of motion of moving line sources. A, Flood source. B, Collimated moving line source. C, Two orthogo-
nal moving collimated line sources on dual-headed gamma camera. D, Stationary line source (collimated in axial
direction irradiating opposite detector head (fan-beam collimator) in a triple-headed gamma camera.
not require frequent replacement. 153Gd (T1/2 scan is acquired with the object of interest in
= 242 days, Eγ = 97 and 103╯keV) and 123mTe the FOV. This is the transmission scan. The
(T1/2 = 120 days, Eγ = 159╯keV) are among the relationship between the reference (Iref) and
radionuclides suitable for this purpose. transmission (Itrans) counts in any particular
To obtain an attenuation map, two sepa- projection element is given by the usual expo-
rate scans are acquired with the transmission nential relationship for γ-ray attenuation
source. Typically one of the geometries shown
in Figure 17-13 is used and the gamma Itrans = Iref e−µx (17-12)
camera system is rotated through 360 degrees
to acquire a full set of projection views. The Taking the natural logarithm of the ratio of
first scan is acquired with no object in the the two scans results in
FOV of the SPECT camera. This is referred
to as the blank or reference scan. The second ln( Iref /Itrans ) = µx (17-13)
296 Physics in Nuclear Medicine
Projection profiles of µâ•›x represent the sum of therefore attenuation) between the transmis-
the attenuation coefficients along each line of sion and emission photons must be taken into
response account in applying the information from the
transmission map.
µx = ∑ µ i ∆ xi (17-14) Emission and transmission scans can be
i
acquired simultaneously if the separation
between the photon energies of the transmis-
where µâ•›i is the linear attenuation coefficient sion source and the emission radionuclide is
for the iâ•›th pixel and Δâ•›xâ•›i is the pathlength of sufficient to allow them to be acquired in two
the line of response through the ith pixel. This separate energy windows. This is shown sche-
is analogous to the standard emission projec- matically in Figure 17-15. Even if two differ-
tion profiles that represent the sum of the ent windows are used, however, some events
radioactivity along each line of response. from the higher-energy radionuclide will be
Using the methods described in Chapter 16, recorded in the lower-energy window. This
Section B, the projection profiles of µâ•›x (calcu- effect, known as downscatter, arises from two
lated from the transmission scan profiles causes. The first is spillover from higher-
using Equation 17-13) are reconstructed, energy events into lower-energy regions of the
resulting in images of µâ•›i. Figure 17-14 shows spectrum (e.g., see Fig. 10-3). These events
a SPECT attenuation map reconstructed from may arise from partial absorption of higher-
transmission and reference scans. energy photons in the detector or from natural
The attenuation map can be used to more broadening of the photopeak.
accurately compute the ACFs in the Chang A second cause is γ rays that have experi-
algorithm (Section B.2) by taking into account enced a partial loss of energy in Compton-
the nonuniform attenuation at each source scattering interactions in the body. For
location in Equation 17-8. It can also be incor- emission scans using 99mTc (140╯keV), down-
porated in the forward-projection step of the scatter from a 123mTe transmission source
modified Chang algorithm to more accurately (159╯keV) can appear in the emission source
compute the error term. More commonly, window. Conversely, when 153Gd is used as the
tissue attenuation information is directly transmission source, downscatter from 99mTc
incorporated into iterative reconstruction can appear in the transmission source window.
algorithms (Chapter 16, Section D) in which Even if the emission and transmission scans
it becomes another factor in the calculation of are acquired sequentially, rather than simul-
the probability matrix M in Equation 16-19. taneously, the patient normally is injected
The probability for γ rays emitted from a with a 99mTc-labeled radiopharmaceuÂ�tical
given pixel i reaching projection element j is prior to transmission imaging, and hence
reduced by the probability of attenuation in downscatter is still an issue with 153Gd trans-
the tissue lying between the point of emission mission sources.
and the detection point in the gamma camera. Downscatter can be estimated and correc-
For both filtered backprojection and iterative tions can be applied for it in ways that are
algorithms, the difference in energy (and similar to the methods used for correcting for
scattered radiation in the emission scan. For
example, one can use an energy window
between the transmission and emission
windows to estimate the level of downscatter.
These methods are similar to those employed
for scatter corrections, which are discussed in
the following section.
4. Scatter Correction
The idealized model used for developing the
filtered backprojection reconstruction algo-
rithms described in Chapter 16 assumed that
only radioactivity within the line of response
for a projection element contributed to the
FIGURE 17-14 Attenuation map of the thorax recon- signal for that element. In practice, the signal
structed from the reference and transmission scans
obtained with a moving line transmission source. (Data
can include events that have been scattered
courtesy Dr. Freek Beekman, Delft University of Technology, into the line of response from radioactivity
The Netherlands.) elsewhere in the body. With the typical 20%
17 • Single Photon Emission Computed Tomography 297
Counts
100 keV
153Gd
events
140 keV
99mTc
events
Downscatter
Energy
Transmission Emission
window window
FIGURE 17-15 Dual-energy windows used to simultaneously acquire SPECT emission (99mTc) and transmission (153Gd)
data. Note the presence of downscatter from the 99mTc activity in the 153Gd window. The magnitude of the downscatter
contamination depends on the relative amounts of 99mTc activity in the body and 153Gd activity in the transmission
source, the amount of scattering material in the field of view, the details of how the transmission source is collimated,
and the precise energy windows that are used.
pulse-height analyzer (PHA) window that is only rarely for energies 100╯keV, the total
used for 99mTc, events that have scattered absorption) of γ rays. Because of the broad-
through angles as large as 50 degrees still beam geometry (Chapter 6, Sections D.2 and
have a 50% probability of being accepted. D.3) of SPECT imaging systems, some of the
Compared with the effects of attenuation, scattered γ rays are detected, leading, on
the effects of scattering are of lesser magni- average, to a reduction in the “apparent”
tude. Nevertheless, Compton scattering, and attenuation coefficient that is measured rela-
at low γ-ray energies (100╯keV) coherent scat- tive to narrow-beam attenuation coefficients.
tering (see Chapter 6, Section C.5), still can One can provide an averaged correction for
have a significant effect on image quality and scatter by using the apparent or broad-beam
on the quantitative relationship between the value for µ in Equations 17-7 and 17-8. For
reconstructed image intensity and source example, for the 140-keV γ rays from 99mTc in
activity. In a typical patient study with a 99mTc- a typical patient, the broad-beam attenuation
labeled radiopharmaceutical, even using a coefficient is ~0.12╯cm−1 as compared with a
narrow 15% PHA window, the ratio of the narrow-beam value of 0.155╯cm−1. Although
number of detected scattered photons to the this works well in objects with uniform radio-
number of nonscattered photons may be as activity distributions in a uniform attenua-
large as 40%. The presence of scattered events tion medium (Fig. 17-16), it does not properly
results in reduced image contrast (the tails of
the point-spread function [PSF] are elevated
Chang correction ( 0.12 cm1)
with respect to the peak) and leads to an over-
estimation of the concentration of radioactivity
in the pixel (see Fig. 17-12, bottom). The loss
of image contrast may obscure clinically
important details, particularly “cold” areas in
the images, for example, areas of low radio�
pharmaceutical accumulation in the heart FIGURE 17-16 Effect of Chang attenuation correction on
caused by coronary artery disease or infarction. 20-cm uniform cylinder data in Figure 17-12 using a
A first-order correction for scatter can be broad-beam attenuation coefficient of µ = 0.12╯cm−1. Note
the improvement in the uniformity of the profile, which
made by recognizing that scatter and attenu- is due to compensation for scattered events. (Data courtesy
ation are part of the same phenomenon. Dr. Freek Beekman, Delft University of Technology, The
Attenuation is caused by the scattering (and Netherlands.)
298 Physics in Nuclear Medicine
take into account the spatial distribution general on the size of the source, the exact
of the scattered events and is therefore of settings of the energy windows, and the
limited accuracy in more realistic imaging energy resolution of the gamma camera detec-
situations. tor. The accuracy of this method is limited by
A second simple method that has been used the fact that γ rays in the scatter window are
to correct for scattered events involves mea- more likely to have undergone multiple
suring the scatter component in the projec- Compton interactions than scattered events
tion profiles using a line source (or point in the photopeak window; therefore the
source) immersed in a scattering medium spatial distributions of the scatter recorded in
that is representative of the dimensions of the the two energy windows may differ.
body. By measuring projection profiles of the Many variants on the use of multiple-energy
source with and without the scattering windows for scatter correction have been
medium, the distribution of scattered events developed. Some SPECT systems use as many
in the projection profile can be determined. as 32 separate energy windows to more accu-
This can be considered to be the line-spread rately model the scatter distribution. Accurate
function (LSF) of the scattered events and can scatter corrections require very good spatial
be deconvolved (see Appendix G) from the linearity and uniformity of the gamma camera
measured projection profiles measured in detector (Chapter 14, Section B) to avoid creat-
patient studies to correct for scatter. The ing artifacts in the scatter correction process.
accuracy of this correction is limited by differ- Scatter corrections also increase the statisti-
ences in radioactivity distribution and atten- cal noise in the reconstructed image because
uation distribution between the phantom in of the inevitable propagation of noise in the
which the scatter response is measured, and subtraction process (Chapter 9, Section C.1).
the patient, and by the spatially invariant Note that for all the corrections described
nature of the correction. here, if scattered events are not “removed”
One of the most commonly used methods prior to applying attenuation corrections, the
to correct for scattered γ rays is to simultane- scattered events also are amplified during the
ously acquire counts with a photopeak window attenuation correction procedure. Therefore it
and a lower-energy scatter window. For is important that scatter corrections precede
example, the photopeak window for 99mTc attenuation corrections.
might be set to 127-153╯keV and the scatter Attenuation maps, described in the preced-
window to 92-125╯keV (Fig. 17-17). The result- ing section, also can be used in conjunction
ing scatter projection profiles then are multi- with iterative reconstruction algorithms to
plied by a weighting factor and subtracted correct for scattered radiation. In essence, the
from the photopeak profiles to obtain scatter- matrix M in Equation 16-19 can be modified
corrected projection data. The weighting to account for the probability of scatter from
factor applied to the counts in the scatter a source at a location (x,y) into a specified
window for the subtraction process must be detector element. This probability can be
determined experimentally and depends in calculated by combining knowledge of the
Counts
Unscattered
events
Scattered
events
48 mm 36 mm 30 mm 24 mm 18 mm 12 mm 9 mm 6 mm
300
250
Counts (arb. units)
200
150
100
50
0
FIGURE 17-18 Illustration of partial-volume effect. The cylinders shown in the top row have diameters ranging from
48╯mm down to 6╯mm, and each contains the same concentration of radionuclide. The middle row shows a simulation
of the images that would result from scanning these cylinders on a SPECT system with an in-plane spatial resolution
of 12-mm full width at half maximum. The cylinders are assumed to have a height much greater than the axial resolu-
tion. The bottom row shows count profiles through the center of the images. Although each cylinder contains the same
concentration of radionuclide, the intensity, and therefore the apparent concentration, appears to decrease when the
cylinder size approaches and then becomes smaller than the resolution of the SPECT system. The integrated area
under the count profiles does, however, accurately reflect the total amount of activity in the cylinders.
0.8
FIGURE 17-19 Recovery coefficient
versus object size [in units of
size/full width at half maximum
(FWHM)] using the data from Figure
Recovery coefficient
0
0 0.5 1 1.5 2 2.5 3 3.5 4
Cylinder diameter / FWHM
17 • Single Photon Emission Computed Tomography 301
that it leads to a gamma camera counting even smaller nonuniformities can lead to
rate of ~10,000 cps. At this counting rate, major artifacts in reconstructed images. The
dead time and pile-up effects are negligible. artifacts often appear as rings in images
The well-mixed phantom is placed at the acquired with single-headed SPECT systems
center of the axis of rotation of the SPECT or as arcs in images acquired with multi-
system. A 360-degree circular orbit SPECT headed systems. The intensity of the artifact
scan, with a radius of rotation of 150╯mm, is is inversely proportional to the distance of the
performed. Typically 128 projection views are nonuniformity from the axis of rotation. This
acquired, with each projection view contain- is because nonuniformities in peripheral
ing on the order of 100,000 counts. Uniformity areas are spread across a larger area of the
corrections, or any other corrections that may image during reconstruction, whereas a non-
alter the number of counts in the projection uniformity near the axis of rotation affects
images, are turned off. a concentrated area near the center of the
The total time T required to complete the image, which can lead to strong artifacts.
acquisition and the total number of counts N Flood-field uniformities of 1% or better are
recorded across all the projection views are desirable for gamma camera detectors used
determined. The system volume sensitivity for SPECT. To detect nonuniformities at this
(SVS) is then given by level, it is necessary that sufficient counts be
acquired to ensure that the measurement is
N (counts) / T (sec) not limited by counting statistics. Poisson
SVS(cps/Bq/mL) =
A(Bq/mL) counting statistics dictate that 10,000 counts
(17-15) are required per image element to reach an
uncertainty of 1% in a planar image (Equa-
Sometimes, the measurement is reported as tion 9-6). If an image matrix of 64 × 64 is used,
the volume sensitivity per axial centimeter, in a total of ~41 million counts will be required
which case Equation 17-15 is divided by the in the uniformity image.
axial length of the phantom, in this case In many cases, it also is instructive to
20╯cm. measure the reconstructed image uniformity
of a SPECT system. At the present time, there
is no specific National Electrical Manufactur-
3. Other Measurements ers Association procedure for this measure-
of Performance ment, but a reasonable approach would be to
Other important performance parameters of use the data acquired using the methods
a SPECT system are energy resolution, count- described in Section C.2 for measuring volume
rate performance, and dead time. These sensitivity. An image of the uniform cylinder
parameters are the same, irrespective of would be reconstructed with appropriate
whether a gamma camera is used for planar attenuation and scatter corrections and with
imaging or for SPECT; therefore the measure- the use of clinically relevant reconstruction
ments described in Chapter 14, Sections E.5 algorithms and filters. The reconstructed
and E.6, are equally applicable to SPECT. images are visually inspected for any notice-
able artifacts or structured noise. Care must
4. Quality Assurance in SPECT be taken to ensure that the scatter and atten-
As described in Chapter 14, Section E, quality uation corrections themselves are not the
assurance programs are important to ensure cause of any artifacts.
that an imaging system is functioning cor- A test that is specific to SPECT systems is
rectly. Many of the quality assurance proce- the measurement of system alignment. It is
dures used for gamma cameras also serve to critical that the mechanical center of rotation
ensure high-quality images when the gamma (COR) coincide with the COR defined for the
camera is used for SPECT. However, there are projection data used for reconstruction. If the
certain differences in the requirements and camera detector sags or wobbles as it rotates
additional measurements that should be around the patient, additional blurring or ring
made when a gamma camera is used for artifacts may be introduced into the image.
SPECT imaging. Because it is extremely difficult to make a
One difference relates to the specifications mechanically or rotationally perfect gantry,
of flood-field uniformity discussed in Chapter most manufacturers measure the alignment
14, Section E.4. In planar imaging, nonunifor- of their systems prior to shipment and incor-
mities of a few percent are acceptable for pro- porate software that corrects on a projection-
ducing images of diagnostic quality. In SPECT, by-projection basis for any small deviations
17 • Single Photon Emission Computed Tomography 303
from the COR. An additional requirement for multiheaded SPECT systems, differences in
multiheaded systems is that all the heads ErrCOR and ErrAX between detector heads
be accurately aligned in the axial direction. must also be assessed to determine any rela-
Otherwise, each head records data from a dif- tive misalignment of the heads. The recom-
ferent slice, which leads to additional blurring mended methods for doing this can be found
or artifacts in the axial direction. in reference 12.
System alignment errors can be measured
by recording profiles from different projection
angles for a point source placed off-center in D. APPLICATIONS OF SPECT
the FOV of the SPECT system. A typical pro-
tocol involves recording an even number It is estimated that there are more than
of projection profiles N at equal angular inter- 5,000 SPECT-capable systems worldwide.
vals over 360 degrees. For example, projec- Not surprisingly, the major uses of SPECT as
tions could be acquired at 0, 90, 180, and opposed to planar imaging are for situations
270 degrees. For each projection profile, the involving organs with complex geometry or
centroid (rcen, zcen) of the image of the point structure, for which accurate 3-D localization
source on the gamma camera face is deter- of signals is critical for patient diagnosis and
mined, in which r is the radial coordinate (as management.
defined in Fig. 16-3) and z is the axial coordi- The most frequent use of SPECT is for
nate. The average COR error (ErrCOR) is then studies of myocardial perfusion for assessing
given by coronary artery disease and heart muscle
damage following infarction. Figure 17-20
1 N shows a series of SPECT images that reflect
ErrCOR = ∑ rcen
N n =1
(17-16)
perfusion of the heart. It is common to perform
cardiac perfusion studies both under resting
The individual x and y components of the conditions and also following a “stress” to the
COR error are given by averaging rcen for the heart created by exercise or by the injection
projection data at ϕ = 0 degrees and 180 of a drug that causes vasodilation (e.g., ade-
degrees for x and ϕ = 90 degrees and 270 nosine). These are called rest/stress studies.
degrees for y, in which the projection angle is In some cases, SPECT studies are gated to
defined as shown in Figure 16-3. The average the electrocardiogram signal from the heart,
axial deviation ErrAX of the detector heads and data from specific portions of the cardiac
(caused by detector tilt) can be calculated cycle (e.g., end-systolic or end-diastolic) can
from be isolated. This reduces blurring caused by
1 N motion of the heart and leads to improved
ErrAX = ∑ z − zcen
N n =1
(17-17) image sharpness and contrast. However, the
number of events contributing to the image
are reduced (data are acquired only for a
in which zcen is the PSF centroid in the z direc- fraction of the cardiac cycle), leading to
tion and z is the mean value of zcen. In poorer signal-to-noise ratio for a fixed data
FIGURE 17-20 SPECT images showing perfusion in the heart muscle of a normal adult using 99mTc-sestamibi as the
radiopharmaceutical. The image volume has been resliced into three different orientations as indicated by the schemat-
ics on the left of each image row. SPECT data were acquired over 64 views with a data acquisition time of 20╯sec/view.
Images were reconstructed with filtered backprojection onto a 128 × 128 image array. (Images courtesy Siemens Medical
Systems USA, Inc., Hoffman Estates, IL.)
304 Physics in Nuclear Medicine
acquisition time. Figure 17-21 shows a com- disorders, brain tumors, and psychiatric
parison between gated and ungated SPECT disease (Fig. 17-22). Commonly used radio-
images of the heart. Myocardial perfusion tracers are 99mTc-hexamethylpro pyleneamine
studies usually are carried out using 201Tl, oxime (99mTc-HMPAO) and 99mTc-ethyl cystein-
99m
Tc-sestamibi, or 99mTc-tetrofosmin. ate dimer (99mTc-ECD). A number of research
Cerebral perfusion studies with SPECT also groups also are developing novel SPECT radio-
are widespread, with applications including tracers that bind to specific receptor popula-
cerebrovascular disease, dementia, seizure tions in the brain, enabling the imaging of
Gated
Ungated
FIGURE 17-21 Comparison of gated (top row) and ungated (bottom row) SPECT images showing perfusion in the heart
muscle of a normal adult following the injection of 1100 MBq of 99mTc-sestamibi. Images were acquired on a triple-
headed gamma camera with low-energy, high-resolution parallel-hole collimators. Ninety projection views were acquired
in 4-degree steps (30 projections per head), and the total imaging time was approximately 20 minutes. Data acquisition
started 30 minutes after radiotracer injection. Short-axis views of the heart are shown. In the gated study, the cardiac
cycle is divided into eight equal time intervals. Based on the electrocardiographic trigger, events are histogrammed
into the appropriate interval. The gated images in this figure correspond to the time interval that represents end-
diastole. Cardiac gating leads to a small improvement in apparent image contrast by reducing blurring caused by
cardiac motion. (Images courtesy Dr. Steve Meikle, University of Sydney, Australia.)
FIGURE 17-22 Transaxial SPECT images showing perfusion in the brain of a normal adult following injection of 890
MBq of 99mTc-HMPAO. Data were acquired on a triple-headed gamma camera with low-energy, high-resolution
fan-beam collimators. One hundred twenty projection views were collected in 3-degree increments (40 views per camera
head) with an imaging time of 40╯sec/view. Total imaging time was approximately 30 minutes, with acquisition
commencing 50 minutes after radiotracer injection. (Courtesy Dr. Steve Meikle, University of Sydney, Australia.)
17 • Single Photon Emission Computed Tomography 305
1 2 3 C 4 5
D
A
6 7 8 9 10
1 cm
16 17 18 19 20
FIGURE 17-24 Dynamic SPECT images showing a single reconstructed coronal image slice over time following the
intravenous injection of 34 MBq of 99mTc-HIDA into a mouse. Each image represents a 15-second acquisition over a period
of 300 seconds starting at the time of injection. The dynamic sequence of images shows the temporal sequence of uptake
and clearance of the radiopharmaceutical in the liver. (Courtesy Félicie Sherer, Université Libre de Bruxelles, Belgium; Steven
Staehlens, Ghent University, Belgium; and Freek Beekman, Delft University of Technology, The Netherlands).
306 Physics in Nuclear Medicine
antibodies and peptides for tumor localiza- 2. Genna SG, Smith AP: The development of ASPECT,
tion, and ultimately also for tumor therapy by an annular single-crystal brain camera for high-
efficiency SPECT. IEEE Trans Nucl Sci 35:654-658,
substituting the imaging radionuclide with a 1988.
β emitter that can cause localized cell death. 3. Babla H, Bai C, Conwell R: A triple-head solid state
Other areas in which SPECT is used camera for cardiac single photon emission tomogra-
include imaging of infection and inflamma- phy (SPECT). Proc SPIE 6319:63190M, 2006. DOI:
10.1117/12.683765.
tion and measurement of liver and kidney 4. Erlandsson K, Kacperski K, van Gramberg D, Hutton
function. An extensive discussion of the BF: Performance evaluation of D-SPECT: a novel
clinical applications of both planar gamma SPECT system for nuclear cardiology. Phys Med Biol
camera imaging and SPECT can be found in 54:2635-2649, 2009.
reference 13. 5. CardiArc. Accessed October 11, 2011 from http://
www.cardiarc.com.
SPECT also has seen growing use for pre- 6. Meikle SR, Kench P, Kassiou M, Banati RB: Small-
clinical studies and basic biomedical research, animal SPECT and its place in the matrix of molecu-
often with dedicated small-animal SPECT lar imaging technologies. Phys Med Biol 50:R45-61,
systems such as those described in Section 2005.
7. Sorenson JA: Quantitative measurement of radio�
A.4. Studies may be performed in small activity in vivo by whole-body counting. In Hine GJ,
animals to study the biodistribution over time Sorenson JA, editors: Instrumentation of Nuclear
of a potential new therapeutic entity, for Medicine, Vol 2, New York, 1974, Academic Press, pp
example peptides, antibodies, nanoparticles, 311-348.
or cells that have been radiolabeled to allow 8. Chang LT: A method for attenuation correction in
radionuclide computed tomography. IEEE Trans
them to be imaged. A second common use is to Nucl Sci 25:638-643, 1978.
measure the effect of a new therapy. For 9. Jaszczak RJ, Chang LT, Stein NA, Moore FE: Whole-
example, the ability of implanted stem cells to body single-photon emission computed tomography
improve myocardial perfusion could be moni- using dual, large-field-of-view scintillation cameras.
Phys Med Biol 24:1123-1142, 1979.
tored by SPECT in an animal model using the 10. Bailey DL: Transmission scanning in emission
same radiotracers for perfusion that are used tomography. Eur J Nucl Med 25:774-787, 1998.
in the clinic. Figure 17-23 shows perfusion 11. King MA, et al: Attenuation, scatter and spatial reso-
images of the myocardium in a mouse obtained lution compensation in SPECT. In Wernick MN,
with a small-animal SPECT system. Figure Aarsvold JN, editors: Emission Tomography: The
Fundamentals of PET and SPECT, Amsterdam,
17-24 shows a single image slice from a fast 2004, Elsevier Academic Press, pp 473-498.
dynamic SPECT study showing the uptake 12. Performance Measurements of Scintillation Cameras:
of the radiopharmaceutical 99mTc-HIDA (see National Electrical Manufacturers Association
Table 5-5) in the liver following injection into (NEMA) Standards Publication NU 1-2007. Rosslyn,
VA, 2007, NEMA.
a mouse. Some of the major applications for 13. Sandler MP, et al, editors: Diagnostic Nuclear Medi-
small-animal SPECT systems are discussed cine, ed 4, Baltimore, 2002, Lippincott Williams &
in reference 14. Wilkins.
14. Franc BL, Acton PD, Mari C, Hasegawa BH: Small-
animal SPECT and SPECT/CT: Important tools for
REFERENCES preclinical investigation. J Nucl Med 49:1651-1663,
2008.
1. Rogers WL, et al: SPRINT II: A second-generation
single-photon ring tomograph. IEEE Trans Med Imag
7:291-297, 1988.
chapter
18
Positron Emission
Tomography
The second major method for tomographic simultaneously, in 180-degree opposing direc-
imaging in nuclear medicine is positron emis- tions, usually within a few tenths of a mm to
sion tomography (PET). This mode can be a few mm of the location where the positron
used only with positron-emitting radionu- was emitted, depending on the energy and
clides (see Chapter 3, Section G). PET detec- range of the positrons. Near-simultaneous
tors detect the “back-to-back” annihilation detection of the two annihilation photons
photons that are produced when a positron allows PET to localize their origin along a line
interacts with an ordinary electron. Although between the two detectors, without the use
the annihilation photons could be detected of absorptive collimators. This mechanism
using single photon emission computed is called annihilation coincidence detection
tomography (SPECT) systems operating in (ACD). Detection of a pair of annihilation
conventional single-photon counting mode, photons in opposing detectors actually defines
these systems are not optimally designed for the volume from which they were emitted.
the relatively high energy of annihilation Most ACD detectors have square or rectangu-
photons (511╯keV). They have relatively low lar cross sections. Thus the volume is essen-
detection efficiencies at these energies and tially a box of square or rectangular cross
require relatively inefficient high-energy col- section, with dimensions equal to those of the
limators. As well, SPECT systems do not take detectors (Fig. 18-1).
advantage of the back-to-back directional Coincidence logic (Chapter 8, Section F and
characteristics of annihilation photons. This Fig. 8-15) is employed to analyze the signals
unique feature is exploited advantageously from the opposing detectors. For many PET
with special annihilation-coincidence detector scanners, this is accomplished by having the
systems for PET. electronics attach a digital “time stamp” to
PET has gained widespread clinical accep- the record for each detected event. Typically,
tance and now is firmly established alongside this is done with a precision of approximately
planar imaging and SPECT in clinical nuclear 1 or 2 nanoseconds (1 nsec = 10−9 sec). The
medicine. In this chapter, we describe the coincidence processor examines the time
basic features of annihilation coincidence stamp for each event in comparison with
detection, the design and performance char- events recorded in the opposing detectors. A
acteristics of PET detectors and scanners, coincidence event is assumed to have occurred
and some of the important clinical applica- when a pair of events are recorded within a
tions of PET. specified coincidence timing window, which
typically is 6 to 12 nanoseconds.
Although annihilation photons are emitted
A. BASIC PRINCIPLES OF
simultaneously, a small but finite coincidence
PET IMAGING window width is needed to allow for differ-
ences in signal transit times through the
1. Annihilation Coincidence Detection cables and electronics, as well as different
When a positron undergoes mutual annihila- distances of travel by the two photons from
tion with a negative electron, their rest the annihilation event to the detectors (see
masses are converted into a pair of annihila- Section A.2). In addition, the detectors in a
tion photons (see Fig. 3-7). The photons have PET scanner do not have perfect timing preci-
identical energies (511╯keV) and are emitted sion and therefore have a finite timing
307
308 Physics in Nuclear Medicine
Annihilation event
Detector Detector
Object containing
positron-emitting
radionuclide
Accepted by coincidence detection
Rejected by coincidence detection
FIGURE 18-1 Volume (╛╛green shaded area) from which a pair of simultaneously emitted annihilation photons can be
detected in coincidence by a pair of detectors. Not all decays in this volume will lead to recorded events, because it is
necessary that both photons strike the detectors. Outside the shaded volume, it is impossible to detect annihilation
photons in coincidence unless one or both undergo a Compton scatter in the tissue and change direction.
resolution. Uncertainties that govern the The ability of ACD to localize events on the
timing resolution can arise from the statisti- basis of coincidence timing, without the need
cal nature of the signal (which is produced by for absorptive collimation, is referred to as
the conversion of 511-keV photons into light, electronic collimation. As was discussed in
electrons, or electron-hole pairs in the detec- Chapter 14, Section C, the lead septa in stan-
tor) and from electronic noise in the detector dard parallel-hole collimators, which are nec-
and associated circuits. Uncertainties also essary to obtain adequate spatial localization,
can arise from the electronic method used to also are responsible for the relatively low sen-
determine the time at which the interaction sitivity of these collimators. Because ACD
occurred (see Chapter 8, Section F). For a pair does not require a collimator to define spatial
of similar detectors, the timing uncertainties location, its sensitivity (number of events
typically are well described by a gaussian dis- detected per unit of activity in the object) is
tribution, and the timing resolution is defined much higher than is obtainable with the
as the full width at half maximum (FWHM) absorptive collimators used for conventional
of this distribution. For scintillation detec- planar imaging and for SPECT. For compa-
tors, the timing uncertainty is reduced, and rable midplane resolution, the sensitivity of
the timing resolution improved, by using PET is many times higher than for SPECT.
brighter and faster scintillators that produce In addition, by incorporating multiple
a large number of light photons over a short opposing detectors in a complete ring or other
time interval immediately after an interac- geometric array around the patient, and oper-
tion occurs. Timing resolution is typically in ating each detector in the array in coincidence
the range of 0.5 to 5 nsec, depending on which with multiple detectors on the other side of
scintillator and photodetector is used. the array, data for multiple projection angles
The need for a finite window width permits can be acquired simultaneously (Fig. 18-2).
other types of events to occur in coincidence, Indeed, with a stationary ring or geometric
as discussed in Section A.9. Also, as discussed array that completely surrounds the patient,
in Section A.4, the annihilation photons are it is possible to acquire data for all projection
not always emitted in precise back-to-back angles simultaneously. This allows the perfor-
directions. The effects of these deviations mance of relatively fast dynamic studies and
from the ideal are discussed in the sections the reduction of artifacts caused by patient
indicated. motion.
18 • Positron Emission Tomography 309
FIGURE 18-2 Array of detectors operating in electronic coincidence with detectors on the opposite side of the ring.
This allows simultaneous acquisition of projection views from many different angles. Solid and dotted lines illustrate
two simultaneously acquired projection views.
such as LSO and LaBr3, can be used (see a rectangular box of area d × h at the face of
Tables 7-2 and 18-2). Several commercially either detector. Between these extremes, it is
built systems incorporate some level of time- the frustum of a pyramid with lower base size
of-flight information using these materials. equal to the size of the detectors and upper
Although there are scintillators with even base size increasing linearly from zero at mid-
faster decay components, such as BaF2, these plane to the size of the detectors at their face.
are not favored because the signal-to-noise Alternatively, consider an uncollimated
improvements that can be realized from time- pair of gamma camera detectors, also operat-
of-flight information is typically more than ing in coincidence mode (Fig. 18-4B). If their
offset by their lower density and therefore intrinsic spatial resolution (see Chapter 14,
lower efficiency for detecting 511-keV annihi- Section A.1) is a gaussian function with
lation photons. FWHM = Rint, then the spatial resolution of
the detector pair for ACD also is a gaussian
3. Spatial Resolution: Detectors function with FWHM = Rint / 2 at midplane.
The spatial resolution of ACD with discrete The ACD response profile becomes wider as
detector elements is determined primarily by the source moves toward either detector, with
the size of the individual detector elements. its FWHM eventually becoming equal to Rint
As shown in Figure 18-4A, for elements of at the face of either detector. Assuming that
width d, a one-dimensional (1-D) slice through the resolution of the imaging detector is the
the ACD point-source response profile at same in all directions, the 2-D ACD response
midplane between the detector pair is a profile is obtained by rotating the 1-D gauss-
triangle. The detector resolution, Rdet has a ian function around its center.
FWHM = d/2. As the source moves toward For both discrete or gamma camera–type
either detector, the response profile becomes detectors, the spatial resolution of ACD varies
trapezoidal, eventually becoming a box of by only approximately 30% in the central 60%
width d at the face of either detector. Consid- of the space between the detectors (Fig. 18-5).
ering a 2-D detector with width d and height By comparison, the resolution of a parallel-
h, the ACD response profile becomes a 3-D hole collim�ator can vary by several hundred
function, which is a pyramid at midplane and percent over a comparable range (see Fig.
18 • Positron Emission Tomography 311
Intrinsic resolution
FWHM R int
FWHM d/2
FWHM R int / 2
Source
Intrinsic resolution
FWHM R int
Discrete Continuous
A detectors B detectors
FIGURE 18-4 Spatial resolution of detector pair (Rdet) for coincidence detection. A, For discrete detectors, spatial reso-
lution is determined by the width of the detector element, d. At midplane, the coincidence response function is a triangle
with full width at half maximum (FWHM) = d/2. As the source is moved closer to one of the detectors, the response
function becomes trapezoidal in shape, eventually becoming a rectangle of width, d. B, For continuous detectors, spatial
resolution is determined by the intrinsic resolution of the detector, Rint. At the midplane, the coincidence response
function is approximately gaussian, with FWHM = Rint / 2 . Near the face of a detector, it becomes FWHM = Rint.
312 Physics in Nuclear Medicine
12.9
12
11.7
8
)
m
10.5
(c
nt
8
oi
-p
id
m
m
Relative count rate
6
fro
e
nc
4
ta
is
4
D
9.8
0 0
20 0 20
Distance (mm)
FIGURE 18-5 Measured line-spread functions for a pair of 17-mm-wide coincidence detectors as a function of source
position between the two detectors. The detector separation was 42╯cm. The FWHM varies by only 30% within the
central 24╯cm (57%) of the space between the two detectors. (From Hoffman EJ, Huang S-C, Plummer D, Phelps ME:
Quantitation in positron emission computed tomography: VI. Effect of nonuniform resolution. J Comput Assist Tomogr
6:987-999, 1982.)
18 • Positron Emission Tomography 313
TABLE 18-1â•…
SOME POSITRON-EMITTING NUCLIDES USED FOR IN VIVO IMAGING
Maximum
Radionuclide Half-Life β+ fraction β+ Energy How Produced
11
C 20.4╯min 0.99 960╯keV Cyclotron
13
N 9.96╯min 1.00 1.19╯MeV Cyclotron
15
O 123╯sec 1.00 1.72╯MeV Cyclotron
18
F 110╯min 0.97 635╯keV Cyclotron
62 62
Cu 9.74╯min 0.98 2.94╯MeV Generator (from Zn)
64
Cu 12.7╯hr 0.19 580╯keV Cyclotron
68 68
Ga 68.3╯min 0.88 1.9╯MeV Generator (from Ge)
76
Br 16.1╯hr 0.54 3.7╯MeV Cyclotron
82 82
Rb 78╯sec 0.95 3.35╯MeV Generator (from Sr)
124
I 4.18 days 0.22 1.5╯MeV Cyclotron
The extrapolated range applies to the result is that the average distance measured
highest-energy positrons emitted by a radio- from the origin of the positrons to the end of
nuclide. However, positrons, like β particles, their path is significantly smaller than their
are emitted with a spectrum of energies. Only extrapolated range.
a small fraction have the full amount of For purposes of defining the spatial resolu-
energy available from the decay (see Fig. 3-2). tion of ACD, the distance of interest is the
In addition, the extrapolated range is the effective positron range. This is the average
maximum distance that the electron would distance from the emitting nucleus to the end
travel if it were not significantly deflected of the positron range, measured perpendicu-
in any of its interactions and traveled in lar to a line defined by the direction of the
essentially a straight line to the end of its annihilation photons (Fig. 18-6). This dis-
range. In reality, most electrons (and posi- tance always is smaller than the extrapolated
trons) travel a tortuous path, often with mul- range for the positrons emitted by the
tiple large-angle deflections (see Fig. 6-4). The radionuclide.
Positron-emitting
radionuclide
Positron
Actual
positron Positron
range path
Effective
positron
range
511 keV
photon
511 keV
photon
Annihilation event
FIGURE 18-6 Blurring caused by positron range effects. The perpendicular distance from the decaying atom to the
line defined by the two 511-keV annihilation photons is referred to as the effective positron range.
314 Physics in Nuclear Medicine
Figure 18-7 shows the positron range dis- A second factor involving the physics of
tribution for point sources of 18F ( Eβmax = positrons is that the annihilation photons
0.635╯MeV) and 15O ( Eβmax = 1.72╯MeV). Accord- almost never are emitted at exactly 180-
ing to Figure 6-10, the extrapolated ranges degree directions from each other (Fig. 18-9).
for these positrons in water would be appro� This effect, which is due to small residual
ximately 2╯mm and 8╯mm, respectively; momentum of the positron when it reaches
however, the FWHMs of their distribution the end of its range, is known as noncolinear-
profiles are only 0.1╯mm and 0.5╯mm. ity. The angular distribution is approximately
Note as well that the positron range distri- gaussian with FWHM approximately 0.5
butions shown in Figure 18-7 have long tails degree. The effect on spatial resolution,
and thus are not well described by gaussian expressed in terms of FWHM, is linearly
functions. Therefore the FWHM is not the best dependent on the separation of the ACD
indicator of the effect of positron range on ACD detectors, D, and is given by
spatial resolution. Instead, the root mean
square (rms) effective range often is used. R180° = 0.0022 × D (18-2)
Figure 18-8 shows the general relationship
between rms effective range and maximum A typical value of D for a whole-body PET
positron energy. Typical rms effective ranges scanner is 80╯cm. Thus the FWHM for blur-
(and thus the blurring caused by positron ring caused by noncolinearity is approxi-
ranges) are on the order of 0.5 to 3╯mm. Note mately 2╯mm.
that positron range is inversely proportional The system resolution of an ACD or PET
to the density of the absorber. Thus rms ranges detector system is obtained by combining the
would be proportionately higher in lung tissue individual resolution components, in the same
and airways (ρ ~ 0.1-0.5╯g/cm3) and lower in manner as the component resolutions are
dense tissues such as bone (ρ ~ 1.3-2╯g/cm3). combined to determine the system resolution
10 2500
18F (Emax 635 keV) 100,000 Events 18F
2000
5
1500
Events
0
1000 0.102 mm FWHM
10,000 Events 0
10
10 5 0 5 10 2 1 0 1 2
End point coordinate (mm) End point coordinate (mm)
10 800
15O (Emax 1720 keV) 100,000 Events 15O
700
5 600
500
Events
400
0
300 0.501 mm FWHM
200 4.14 mm FWTM
5
100
10,000 Events 0
10
10 5 0 5 10 8 6 4 2 0 2 4 6 8
End point coordinate (mm) End point coordinate (mm)
FIGURE 18-7 Results of Monte Carlo simulations showing the distribution of annihilation sites for positron-emitting
point sources in water for 18F ( Eβmax = 0.635╯MeV) and 15O ( Eβmax = 1.72╯MeV). The profile of the distribution is broader
for 15O because of its higher average positron energy, which leads to a longer positron range prior to annihilation.
(From Levin CS, Hoffman EJ: Calculation of positron range and its effect on the fundamental limit of positron emission
tomography system spatial resolution. Phys Med Biol 44:781-799, 1999.)
18 • Positron Emission Tomography 315
82
Rb
2.5
0
0 0.5 1 1.5 2 2.5 3 3.5
Maximum energy (MeV)
Positron
Non-colinearity
511 keV
photon 511 keV
photon
Annihilation event
Error due
to non-colinearity
FIGURE 18-9 Noncolinearity of annihilation photons resulting from residual momentum of the electron and positron
at annihilation. Noncolinearity leads to positioning errors. Angles are exaggerated in this example for purposes of
illustration. Actual range of angles is about ±0.25 degree, centered at 180 degrees.
for a gamma camera system (see Chapter 14, the discrete detector elements or the intrinsic
Section C.4). Thus resolution of continuous detectors (see Section
A.3 and Fig. 18-4). For typical whole-body
Rsys ≈ 2
Rdet + Rrange
2
+ R180
2
° (18-3) PET scanners, with either discrete detector
elements or gamma camera detectors, the
where Rdet is the spatial resolution of the effects of positron range and noncolinearity
detector system, as determined by the size of combine to add anywhere from a few tenths
316 Physics in Nuclear Medicine
that line. Thus a more appropriate measure hexagonal, or octagonal arrays. Each detector
for distributed sources is the average geomet- element is operated in coincidence with many
ric efficiency within the sensitive volume for detectors on the opposing side of the ring, as
ACD. Midway between the two detectors, this shown in Figure 18-12. This multicoincidence
is given by operation has useful and important conse-
quences for both the magnitude and unifor-
1 mity of geometric efficiency.
g ACD ≈ 2 × × [ Adet / π D2 ] The simplest way to visualize its effects on
3
(18-7) geometric efficiency is to consider a complete
2 Adet ring of detectors on a diameter D, with detec-
≈
3π D 2 tor height h in the axial dimension and detec-
tor width d << D in the plane of the ring.
where D is the distance between the detectors Assume that any interdetector gaps are “very
and Adet is the area of the detector facing the small,” so that the individual elements form a
source. virtually continuous ring of detector material.
The term in brackets in Equation 18-7 is For a point source located precisely at the
the geometric efficiency for a single detector center of the ring, the geometric efficiency
for a point source located at the midpoint of would be equal to the solid angle subtended
the centerline between the detectors. (As dis- by the ring, because if either annihilation
cussed in Chapter 11, Section A.2, this expres- photon is intercepted by the ring, it is virtually
sion is valid when the detector dimensions assured that the second photon is traveling
are “small” in comparison with the source-to- the proper direction to be intercepted as well.
detector distance.) The factor of 2 accounts for From simple geometric considerations, if h <<
the fact that two detectors are used and that D, it can be shown that the solid angle, and
if one photon is emitted in a proper direction thus the geometric efficiency, for a point source
toward one detector, the other photon is virtu- precisely at the center of the ring is given by
ally assured of being emitted in the proper
direction toward the other. The factor of 1/3 gACD,RING ≈ h/D (18-8)
is the average geometric efficiency across the
sensitive volume at midplane, that is, the Under the conditions described, geometric
average height of a pyramid. efficiency is relatively constant as the source
Actual PET systems typically employ many is moved away from the center of the ring but
small detector elements arranged in circular, still in its center plane; however, as the source
Useful field-
of-view
is moved axially toward the ends of the ring, photons onto the detectors and by gaps
the geometric efficiency still has a triangular between detector elements. Corrections for
shape. Thus the average geometric efficiency this and other image nonuniformities are
for a source distributed within the sensitive described in Section D.1.
volume for ACD across the width of the It is noteworthy that, by segmenting large
ring is half the value given by Equation 18-8, detectors into smaller elements and operating
that is, them in coincidence with multiple elements
h in the opposing array, it is possible to improve
g ACD, RING ≈ (18-9) the spatial resolution in PET with only a
2D modest loss of geometric efficiency. This effect
Equations 18-8 and 18-9 also are valid for is seen in Equation 18-9, in which geometric
polygonal arrays, with D representing the efficiency depends on the diameter of the ring,
diameter of a circle drawn tangential to the D, but not on the width d of the individual
surface of the array. As long as h << D, they detector elements. Most of the loss of sensitiv-
also apply to continuous detectors that use ity that does occur is due to the requirement
gamma camera electronics, rather than dis- for interelement spacing and shielding, which
crete detector elements, to determine event is only approximately 0.2 to 0.3╯mm in practi-
locations. cal systems. For comparison, from fundamen-
In addition to increasing geometric effi- tal principles, the geometric efficiency of
ciency and improving its uniformity, multico- absorptive collimators is degraded approxi-
incidence detection with a ring or polygonal mately as the square of spatial resolution
array of detectors also allows simultaneous (Equation 14-8). This presents a formidable
acquisition of multiple projection views challenge for improving spatial resolution in
without moving the detectors. Suppose the imaging applications based on single-photon
ring consists of N individual detector ele- counting, including SPECT.
ments. When each detector in the ring or The benefits of multicoincidence operation
array is operated in coincidence with a bank extend as well to the third (axial) dimension
of detectors on the opposite side, as illustrated in multi-ring PET systems. This is discussed
in Figure 18-12, a total of N/2 fan-beam further in Section C.
projections are acquired. These fan-beam pro- As is the case for any imaging system, the
jections typically are arranged to form parallel- sensitivity of a PET system also depends
beam profiles, as illustrated in Figures 16-20 critically on the detection efficiency of the
and 18-2. However, as illustrated in Figure detector, which enters as a squared term
18-11, data from adjacent pairs of detector in Equation 18-6. As was discussed in Chapter
usually are assigned to the same projection 11, Section A.3, detection efficiency is given
profile, thereby decreasing the number of by
views to N/4.
The number of detectors that are enabled ε = 1 − e− µ x
l (18-10)
for multicoincidence detection determines the
width of the fan-beam projections and thus where µl is the linear attenuation coefficient
the diameter of the useful FOV. Sources of the detector material and x is the detec�
located within the circle illustrated in Figure tor thickness. Values of µl for several detector
18-12 are seen in all projections. Once a materials of interest for PET are given in
source is included within the useful FOV, a Table 18-2. Also indicated are values of ε for
further increase in fan-beam width does not 2-cm-thick detectors of each material, without
increase the counts recorded from that source. a low-energy threshold and with an energy
Sources outside the circle are not seen in threshold that eliminates 50% of the detected
some views, which could be a cause of image pulses. Values for ε2 in this table are useful
artifacts (see Chapter 16, Section C.2). Typical for calculating scanner sensitivity and ACD
PET systems operate with each detector in counting rates (Equation 18-6). These values
coincidence with approximately two-thirds illustrate why materials such as BGO, LSO,
the total number of detectors in the ring. and LYSO (Chapter 7, Section C.4) are pre-
Geometric efficiency varies somewhat ferred over NaI(Tl) for PET imaging.
across the useful FOV of the detector ring. In Overall sensitivities for PET systems for a
part, this is because the solid-angle for coin- small-volume source of activity located near
cidence detection changes with source posi- the center of the scanner range from 0.2%
tion. There also are geometric effects caused to 0.5% (0.002-0.005╯cps/Bq) for single-ring sys�
by differences in angle of incidence of the tems or for multi-ring systems operated in
322 Physics in Nuclear Medicine
TABLE 18-2â•…
LINEAR ATTENUATION COEFFICIENTS AND DETECTION EFFICIENCIES FOR SOME
SCINTILLATORS AT 511╯keV*
2-D acquisition mode (one slice per ring; events are called prompt coincidences. The
Section C.1). For multi-ring systems in which discussion and analysis presented thus far
coincidences between rings are allowed for 3-D assumes that all prompt coincidences arise
data acquisition (see Section C.2), the sensitiv- from a pair of photons produced from the
ity typically is 2% to 10% (0.02-0.10╯cps/Bq). same annihilation event and that the anni-
For comparison, the sensitivities for SPECT hilation event occurs somewhere within the
systems with a general-purpose parallel-hole coincidence volume between the detectors
collimator are in the range of 0.01% to 0.03% (see Fig. 18-1). These events are called true
(0.0001-0.0003╯cps/Bq), depending on the number coincidences. Equation 18-6 describes the
of detector heads (see Chapter 14, Section E.7). sensitivity of the system for these events.
The substantially greater sensitivity of PET However, other prompt coincidence events
versus SPECT systems is due primarily to also can occur within the resolving time of
their ability to achieve a high degree of spatial the detector system.
resolution without the use of absorptive Two examples are shown in Figure 18-13.
collimators. Random coincidences (also called accidental
coincidences) occur when annihilation photons
from two unrelated positron annihilation
9. Event Types in Annihilation events are detected in two different detectors,
Coincidence Detection within the coincidence timing window, and
ACD produces an output whenever two recorded as a single coincidence event. This
events are recorded within a specified coinci- can happen if one photon from each annihila-
dence timing window. Generically, any such tion event is detected in each detector element.
FIGURE 18-13 True coincidence event (left), scatter coincidence event (center), and random or accidental coincidence
(right). Scatter and accidental coincidences yield incorrect positional information and contribute a relatively uniform
background to the image that results in a loss of contrast. (Courtesy Dr. Magnus Dahlbom, University of California—
Los Angeles.)
18 • Positron Emission Tomography 323
Random coincidences are not rare events, In actual PET scanners, the ratio of
because the volume of tissue from which the random-to-true coincidence counting rates
photons for a random coincidence event could typically ranges from approximately 0.1 to 0.2
arise generally is much larger than the poten- for brain imaging to greater than 1 for appli-
tial volume for true coincidence events. cations where large amounts of activity may
The random coincidence counting rate in a be nearby, but outside the true coincidence
detector pair is given by volume of the scanner. The latter could apply,
for example, to some types of abdominal
Rrandom = ∆T × Rsingle,1 × Rsingle,2 (18-11) imaging when large amounts of activity are
excreted into the bladder. Random coinci-
where ΔT is the coincidence timing window dences occur more or less uniformly across
used by the system* and Rsingle,1 and Rsingle,2 the FOV of the scanner, causing a loss of
are the single-channel counting rates in the image contrast as well as inaccuracies in
two detectors of the pair. Unlike true coinci- quantification of activity within the patient.
dence events, which can occur only when the Methods for correcting for random coinci-
source is located within the volume that is dences are discussed in Section D.2.
geometrically defined by the sides of the A second category of nonvalid prompt
detector pair (see Fig. 18-1), random coinci- coincidences are scatter coincidences. These
dences can arise from activity anywhere in occur when one (or both) of the photons from
the region between the detectors, including an annihilation event outside the sensitive
activity outside the useful FOV for a ring or volume for true coincidence events under-
array of detectors. Thus the single and goes scattering and is detected in a detector
random coincidence counting rates depend in other than the one that would be appropri-
a complicated way on both the source and ate for a true coincidence event. The scatter-
detector geometry. A detailed analysis of these ing event shown in Figure 18-13 occurs
factors is beyond the scope of this text. Refer- within the patient, but it also can occur
ence 1 provides a more comprehensive analy- within components of the scanner. Because
sis. Nonetheless, some general observations the two annihilation photons were emitted
can be made. simultaneously, they reach the detectors vir-
In general, the greater the total amount of tually simultaneously, apart from small
activity used in a study, the higher the ratio time-of-flight differences (see Section A.2).
of random-to-true coincidence rates. This is Because these differences are very small, the
because the random coincidence rate increases detector system and its associated coinci-
as the square of the amount of activity present dence logic cannot typically distinguish them
(product of single-channel counting rates in from valid events.
Equation 18-11), whereas the true coincidence As is the case for the random-to-true coin-
rate increases only linearly with the amount cidence ratio, the ratio of scatter-to-true
of activity administered (Equation 18-6). A coincidence counting rates depends in a com-
second general observation is that the ratio of plicated way on the source distribution and
random-to-true coincidence rates decreases in detector geometry. Placement of lead shield-
proportion to the width of the coincidence ing on either side of the detector ring, or of
timing window. However, as noted in Sections thin tungsten septa between detector rings in
A.1 and A.2, there are lower limits for this a multi-ring PET system, reduces the likeli-
value, because of electronic and time-of-flight hood of accepting scattered photons. However,
considerations. Finally, a general way to unlike the random-to-true ratio, the scatter-
reduce the single-channel counting rate from to-true ratio does not depend on the amount
activity outside the true coincidence volume is of activity administered, because both the
to use tungsten septa to restrict the FOV of scatter and true coincidence rates increase
individual detectors (see Section B.3). In turn, linearly with this parameter. It also does not
this reduces the random coincidence rate. depend on the width of the coincidence timing
window because scatter coincidences arise
from the same positron annihilation event,
*The value of ΔT used here refers to the time separation and the two photons actually do arrive almost
between any two events that is determined by the elec- simultaneously at the two detectors. In clini-
tronics to indicate a prompt coincidence event (see cal studies, the scatter-to-true coincidence
Chapter 8, Section F). This differs from the definitions
used in some articles and texts and leads to an additional
ratio ranges from 0.2 to 0.5 for brain imaging
factor of 2 in the version of Equation 18-11 in those and from 0.4 to 2 for abdominal imaging. The
publications. higher end of these ranges applies for 3-D
324 Physics in Nuclear Medicine
acquisitions, which do not use interplane The block detector, designed in the mid-
septa (see Section C.2). 1980s by Casey and Nutt,3 allows small detec-
Scatter coincidences provide incorrect tor elements to be used (improving spatial
localization of the positron annihilation event. resolution) while reducing the number of
The degree of position error depends on the PMTs required to read them out (controlling
scattering angle and location of the scatter cost). Figure 18-14 shows a typical block
event. Scatter coincidences lead to a broad detector. A large piece of scintillator (most
distribution of mispositioned events, gener- commonly BGO, LSO, or LYSO), is segmented
ally peaked toward the center of the object. into an array of many elements by making
Methods for minimizing the acceptance of partial cuts through the crystal with a fine
scattered photons and for correcting for resid- saw. The cuts between the elements are filled
ual scatter coincidences are discussed in with a reflective material that serves to reduce
Section D.3. and control optical cross-talk between scintil-
lator elements. The array of crystals is read
out by four individual PMTs. The depth of the
B. PET DETECTOR AND SCANNER saw cuts is determined empirically to control
DESIGNS the light distribution to the four PMTs in a
fairly linear fashion.
As discussed in Section A.6, detection effi- To determine the segment of the crystal in
ciency (Equation 18-10) is an important which an annihilation photon is detected, the
parameter in PET scanner sensitivity and per- signals from a four-PMT array are combined
formance. Sodium iodide detectors, which are as follows:
the “workhorse” for many nuclear medicine
applications, also have been used for PET ( PMTA + PMTB ) − ( PMTC + PMTD )
X=
scanners. Indeed, as discussed in Section B.3, PMTA + PMTB + PMTC + PMTD
it is possible to use appropriately modified
dual-headed SPECT systems for PET imaging. ( PMTA + PMTC ) − ( PMTB + PMTD )
Y=
However, because of the relatively high energy PMTA + PMTB + PMTC + PMTD
of the 511-keV annihilation photons, sodium
iodide generally is not the detector material of (18-12)
choice for PET imaging. For these reasons,
most PET scanners use denser higher-Z scin- where PMTA, PMTB, and so forth are the
tillation detectors arranged in rings or banks signals from different PMTs. It will be recog-
of discrete elements around the scanned object. nized that these are essentially identical to
These systems not only provide a high detec- Equations 13-1 and 13-2 for position localiza-
tion efficiency but they allow the simultaneous tion for an Anger camera, except that only
collection of data for all projection angles with four PMTs are used here. The X and Y signals
a completely stationary set of detectors. In this then are used to determine the subelement of
section, we discuss the design of modern PET the array in which the annihilation photon
detector systems and scanners. Reference 2 is was detected.
a useful review describing emerging detector Figure 18-15 shows the image obtained
technologies for PET. from uniform irradiation of a block detector.
The image is not uniform. Rather, the calcu-
lated locations for recorded events are clus-
1. Block Detectors tered in small localized areas corresponding
Early PET systems used individual detector to the individual detector elements. There is
units consisting of a piece of scintillator a small amount of overlap, but the individual
coupled to a photomultiplier tube (PMT). The elements are clearly resolved. Although the
individual detectors were arranged in a ring array pattern is nonlinear, the separation is
or in multiple rings around the subject. As sufficiently clear to allow each (x,y) location
illustrated in Figure 18-4, the response profile in the image to be assigned to a specific detec-
at midplane of a pair of coincidence detectors tor element in the array, for example, by using
is a triangle with FWHM equal to one half the a look-up table.
width of the detector. Thus to improve The major advantage of the block detector
the intrinsic resolution of a PET scanner, the is that it enables many detector elements
detectors must be made smaller. However, (e.g., 8 × 8 = 64) to be decoded using only four
the cost increases rapidly if each detector PMTs. This dramatically lowers the cost per
element requires its own PMT. detector element while providing high spatial
18 • Positron Emission Tomography 325
Reflector material
packed in saw cuts
Four single-channel
photomultiplier tubes
PMTC
Y PMTA
PMTD PMTB
X
FIGURE 18-14 Block detector commonly used in clinical PET scanners. A piece of BGO or LSO scintillator is cut into
an array of smaller elements that are read out using four single-channel photomultiplier tubes (PMTs). The cuts in
the material are filled with an opaque reflective material that, along with the depths of the cuts, helps control the
distribution of scintillation light reaching the PMTs.
(Chapter 13, Section B), with the continuous the overall detector performance is slightly
scintillator plate replaced by an array of dis- degraded as compared with a detector of the
crete scintillator elements. Although this same dimensions made purely from LSO. The
approach reduces the cost per detector phoswich design also can be combined with
element of a PET system (by reducing the the quadrant-sharing approach.
number of PMTs and electronic channels
required compared with a block detector), it 3. Whole-Body PET Systems
has the disadvantage of higher dead time Figure 18-18 illustrates several different
losses, because each PMT views signals from whole-body PET scanner designs that have
a larger volume of scintillator. been developed, some using block detectors
The second modification of the basic block comprising discrete scintillator elements as
detector design is to use layers of two differ- introduced previously (A, B, C) and others
ent scintillator materials, creating what is that use continuous large-area gamma camera
known as a phoswich (Fig. 18-17). This approach detectors (D, E, Fâ•›). Systems that use a sta-
makes use of the difference in decay times of tionary ring or polygonal array of detectors (A,
the two scintillators. By monitoring the decay C, E, and Fâ•›), with the detectors operating in
time of the pulse, the event can be localized multicoincidence mode, can acquire data for
into either the upper or lower layer. For all projection angles simultaneously and these
example, combinations of LSO (decay time designs have been the basis for most commer-
~╛40╯nsec) and GSO (decay time ~╛60╯nsec) cial systems. Others (B, D) use only a few
scintillators can be used. Because the location opposing banks of detectors, which must be
of photon interaction can be determined to rotated to get full tomographic information.
within half the total scintillator thickness, Most PET systems use a ring diameter of 80
this reduces the DOI effects (described in to 90╯cm. After inserting scatter shielding and
Section A.5) by approximately a factor of 2. a shroud to cover the detectors and other com-
The disadvantage of this approach is that ponents, the clear bore of the scanner typically
manufacturing of the detectors is more is 55 to 60╯cm, which is sufficient to comfort-
involved and that the light output and stop- ably accommodate most patients. The FOV in
ping power of GSO are worse than LSO. Thus the axial direction is determined by the axial
Scintillator 1
Scintillator 2
Signals
Four single-channel
photomultiplier tubes
FIGURE 18-17 Phoswich detector constructed from two scintillator materials with different decay times. By analyzing
pulse decay time, an event can be assigned to either the upper or lower layer, reducing the effective thickness of the
detector by one half and providing some depth of interaction information.
A B C
D E F
FIGURE 18-18 PET scanner geometries based on discrete scintillator elements (top row) or continuous scintillator
plates (bottom row). A, Full ring of modular block detectors. B, Partial ring of modular block detectors. C, Hexagonal
array of quadrant-sharing panel detectors. D, Dual-headed gamma camera with coincidence circuitry. E, Hexagonal
array of gamma camera detectors. F, Continuous detectors using curved plates of NaI(Tl). A complete set of profiles
can be acquired without motion with systems shown in A. C, E, and F, whereas detector motion is required with systems
shown in B and D.
328 Physics in Nuclear Medicine
extent of the detectors and typically is in the (thickness). The inside diameter of the detec-
range of 15 to 40╯cm. tor ring is 92.7╯cm and the clear bore of the
Figure 18-19 shows schematically the design of scanner is 59╯cm. The 18 crystals (three rings
a representative whole-body PET scanner based of three blocks) in the axial direction cover an
on block detectors. This scanner employs 336 axial FOV of 15.2╯cm. The gantry can be tilted
BGO block detectors, arranged in three rings ± 20 degrees from the vertical, which can
of 112 blocks per ring.4 Each block is cut into be useful for aligning the scan planes with the
a 6 × 6 array of elements, with element sizes optimal viewing angle for an organ of interest.
of 4╯mm (transaxial) × 8.1╯mm (axial) × 30╯mm The system contains a set of tungsten interplane
Septa
68Ge rod
source
Lead end
shielding
Septa
15.2 cm
68Ge rod
source
BGO block
detector
59 cm
92.7 cm
~120 cm
FIGURE 18-19 Drawings showing transaxial (top) and axial (bottom) cross-sections through a representative whole-
body PET scanner.
18 • Positron Emission Tomography 329
septa of 1-mm thickness and 12-cm length direction and uses the scintillator LYSO. Its
between the crystal rings. The septa can design and performance capabilities are
be extended or retracted to provide varying broadly similar to those of the scanner des�
levels of scatter rejection, as described in more cribed previously. The trend in recent years
detail in Section C.2. They also provide shield- has been to improve spatial resolution by
ing from potential high concentrations of further reducing the dimensions of the detec-
activity outside the scanning volume of inter- tor elements (4╯mm × 4╯mm is current state-
est, which helps control the random and of-the-art), and to increase the number of
scatter coincidence rates, as described in detectors along the axial direction to improve
Section A.9. axial coverage of the body, increase sensitivity
The scanner also incorporates a rod source and thus reduce imaging times for studies
made from 68Ge (T1/2 = 273 days) to perform that cover the whole body. A second trend has
transmission scans for attenuation correc- been to improve the detectors and electronics
tions. The source is permanently mounted in to provide sufficient timing resolution that
the system and is retracted into a lead shield time-of-flight information (see Section A.2)
when not in use. This is discussed further in can be extracted. Commercial systems with a
Section D.4. Typically, the system uses a coin- coincidence timing resolution of better than
cidence timing window of 12.5 nanoseconds 600 psecs (corresponding to a spatial localiza-
and an energy window of 300 to 650╯keV. The tion of ~9╯cm) are now available.
intrinsic spatial resolution of the detectors is Gamma camera technology similar to that
approximately 3╯mm, whereas the system used for conventional planar imaging and
resolution is approximately 4.5╯mm near the SPECT (see Chapters 13, 14, and 17) also has
center of the FOV and approximately 6.2╯mm been employed for PET imaging. In one
near the periphery of the scanner bore, the approach, coincidence timing circuitry has
difference being due primarily to DOI effects been installed between the heads of dual-
(see Section A.5). The axial (slice thickness) headed scanners and the collimators removed
resolution is approximately 4.2╯mm at the for PET imaging. The spatial localization pro-
center of the scanner, whereas near the periph- vided by the detector heads allows many coin-
ery of the FOV, approximately 20-cm distance cidence lines to be acquired simultaneously.
axially from the center, it is approximately The basic concept is illustrated in Figure
6.9╯mm. The scanner simultaneously acquires 18-18D. These systems can still be used for
data for 35 slices, separated center-to-center planar or SPECT imaging, by replacing the
by 4.25╯mm, in 2-D acquisition mode. In 3-D collimators.
acquisition mode (see Section C.2), the number The performance of standard gamma
of slices and slice thickness in the axial direc- cameras for PET suffers from a number of
tion can be chosen arbitrarily. limitations. Chief among these is the rela-
Figure 18-20 shows photographs for tively low detection efficiency of the camera
another whole-body PET scanner, which is detectors for 511-keV annihilation photons
described in reference 5. This system has (see Figs. 11-4 and 11-5). As well, although
smaller detector dimensions in the axial removing the collimator allows simultaneous
A B
FIGURE 18-20 A, Modular cassette from a PET scanner containing eight block detectors. These cassettes are mounted
on the PET scanner gantry to form complete rings of detector blocks that surround the patient. B, Clinical PET scanner
based on rings of these block detectors. (Courtesy GE Healthcare, Waukesha, WI.)
330 Physics in Nuclear Medicine
C B
FIGURE 18-21 A, Photograph of a high-resolution brain imaging system. B, Interior of the scanner, showing the eight
panels of detectors arranged in an octagonal geometry that are made up of phoswich detectors read out by photo�
multiplier tubes in a quadrant-sharing configuration. C, Phantom images from this system (right) compared with those
obtained from a typical whole-body PET scanner (left). The improvement in spatial resolution arising from the smaller
detector dimensions is apparent. (Courtesy Dr. Adriaan Lammertsma VU Medical Center, Amsterdam, Netherlands,
and Siemens Medical Solutions, Knoxville, TN.)
18 • Positron Emission Tomography 331
A
2-D direct and cross planes /1
D
FIGURE 18-24 Two-dimensional (2-D) and 3-D data acquisition schemes for PET. Axial cross-sections through a multi-
ring scanner are shown on the left and corresponding axial sensitivity profiles on the right. A, 2-D direct plane data
acquisition. B, 2-D direct and cross-plane data acquisition. C, 2-D high-sensitivity data acquisition. D, Full 3-D data
acquisition. For clarity, lines of response are shown only for selected axial positions in C and D.
334 Physics in Nuclear Medicine
structures of interest as close to the center of compared with Equation 18-9, this adds
the axial FOV as possible. Multi-ring PET another factor of 2 to the sensitivity at the
systems have relatively high overall sensitiv- center of the FOV. The final result is
ity, as shown by the following example.
EXAMPLE 18-2 Sensitivity 3D ≈ 32 × 2 × 0.18 × 0.00409
Consider a 32-ring PET scanner with BGO ≈ 0.047 = 4.7%
detector elements that are 6-mm-wide × 6-mm
axial height × 2-cm-thick. The crystals are For an extended source, for example, a line
tightly packed on a 73.3-cm-diameter ring, source that has length comparable to the total
such that each ring contains 384 crystals. In thickness of the 32-ring array, the average
single-slice mode, each ring is operated in sensitivity of the scanner across the axial
coincidence only with other detector elements FOV is given by Equation 18-9, and the 3-D
within the same ring. In 3-D acquisition result given previously would be reduced by
mode, each ring is operated in coincidence a factor of 2.
with all other rings. Estimate the sensitivity
for a source located at the center of scanner The estimated sensitivity in Example 18-2
bore for single-slice and 3-D modes. Assume for 3-D operation is 2-3 orders of magnitude
that the source is comparable in size to the greater than the sensitivity achieved with a
axial length of the detector crystals, and that gamma camera for single-photon imaging
a low-energy threshold that passes 50% of with absorptive collimation (see Chapter 14,
detected events is used. Section E.7). Note as well that the additional
rings extend the volume of coverage, so that
Answer a volume of tissue can be imaged in less time
For a small-volume source, comparable in size with a multi-ring scanner, as compared with
to the axial thickness of a single detector ring, a single-ring device.
Equation 18-9 applies. For such a source, the Reconstruction of 3-D PET data also is
average geometric efficiency at the center of more complex, because the projection data
a single-ring is arises not only from transverse slices used
for 2-D reconstruction, but also from many
1 6 mm oblique angles through the subject. Thus the
g RING ≈ × ≈ 0.00409 = 0.409% full 3-D image volume must be considered
2 733 mm during the reconstruction process. Fully 3-D
Fourier-based and iterative reconstruction
From Table 18-2, the intrinsic efficiency algorithms are both available; however, com-
(squared) for coincidence detection with putation times are roughly an order of mag-
2-cm-thick BGO crystals and an energy nitude longer than for 2-D reconstructions,
threshold that passes 50% of detected pulses because they involve backprojections and
is 0.18. When combined with geometric effi- computations in three dimensions rather
ciency (Equation 18-6), this gives a total than two. Approximate 3-D reconstruction
detection efficiency (sensitivity) for single- algorithms have been developed in which the
slice acquisition of 3-D dataset is reduced to a 2-D dataset using
rebinning methods (see Chapter 16, Section
E.3). In many situations, any loss in accuracy
Sensitivity RING ≈ 0.18 × 0.00409
resulting from the approximations made in
≈ 0.00074 = 0.074% these algorithms is small when compared
with the benefit of enabling 3-D PET data
In 3-D mode, all 32 rings are operated in to be reconstructed in clinically acceptable
coincidence with each other (Fig. 18-24D). timeframes.
Because of the increased solid-angle of cover- Despite the increased computational and
age, this immediately increases the geometric data storage requirements for 3-D PET, the
efficiency for a source located at the center of large increases in sensitivity that it produces
the axial FOV by approximately a factor of 32 has resulted in it being offered as an option on
(ignoring small geometric effects). As well, a all commercial whole-body PET systems. In
small-volume source at the center of the axial some systems, interplane septa have been
FOV more closely approximates a true point completely eliminated and only 3-D acquisi-
source, for which Equation 18-8 applies. As tion is possible. All small-animal and breast
18 • Positron Emission Tomography 335
normalization factor for a specific pair of the end of each clock cycle (typically 256
detectors is computed from nanoseconds), the computer checks to see if
any events have occurred, and if so, whether
N i, j they occurred with arrival times within ΔT
Normi, j = (18-13)
<N> nanoseconds of each other, where ΔT is width
of the coincidence timing window (typically 4
where <â•›Nâ•›> is the average value of Nâ•›(â•›iâ•›,â•›j) for to 12 nanoseconds). If two photons arrive
all of the coincidence detector pairs in the within this time interval, they are recorded
scanner. Hence, the average normalization as a valid event and the appropriate memory
factor is equal to 1. location corresponding to that particular
The normalization factor then is used to detector pair is incremented by +1.
correct the counts recorded for each detector An estimate of the random coincidence rate
pair in a scan of a patient, C(i,â•›j), as follows: can be obtained by delaying the coincidence
timing window by a time that is much greater
Ci, j than its width. For example, the coincidence
CNorm i, j = (18-14) timing window might be delayed by 64 nano-
Normi, j
seconds, for example, from 64 to 76 nano�
where CNormâ•›iâ•›,â•›j are the corrected counts. This seconds for a 12-nanosecond window. With this
correction is applied to the projection (sino- amount of time delay, only events that have
gram) data prior to image reconstruction. arrival times separated by between 64 and 76
Statistical errors caused by the finite nanoseconds are accepted. No true (or scat-
number of counts in the normalization scan tered) prompt coincidences will be detected in
will increase the noise levels in the corrected the delayed window, because photons from the
data, which is undesirable. In 3-D mode, PET same decay will always arrive at the detectors
scanners can have on the order of 108 lines of within a few nanoseconds of each other.
response. To achieve a statistical uncertainty However, the rate of random coincidences will
of ~3% in the normalization factor would be the same in the delayed and undelayed
therefore require a normalization scan with a windows because the rate at which uncorre-
total of approximately 1000 × 108 = 1011 counts. lated photons strike the detector is the same
Even at relatively high total counting rates of for both windows. Thus the delayed window
approximately 500,000╯cps, this would require count provides an estimate of the number of
approximately 55 hours of scanning time. random coincidence events. This number is
Thus the straightforward approach outlined subtracted from the total number of coinci-
previously must be modified to reduce the dence events for the detector pair. The correc-
number of counts required without increasing tion occurs on-line in most PET systems and
statistical noise. Most of the modified methods usually is transparent to the user.
are based on computing the efficiencies of the The events recorded in the delayed window
individual detector elements (rather than all are not the same ones as are recorded in
possible detector pairs) and then combining the undelayed window. Rather, the delayed
them to estimate the efficiency of the detector window provides a separate and independent
pairs. Details of these methods are beyond measure of the random event rate. Subtract-
the scope of this text but are discussed in ing the number of random events recorded in
reference 12. the delayed window results in an increase in
the statistical noise level for the measure-
2. Correction for Random Coincidences ment (see Chapter 9, Section C.1). Specifi-
As discussed in Section A.9, random coinci- cally, if Ntrue is the number of true coincidence
dences add a relatively uniform background events recorded, Nscatter the number of scatter
across the reconstructed image, suppressing coincidences, and Nrandom is the number of
contrast and distorting the relationship random coincidences subtracted from the
between image intensity and the actual total, the uncertainty in the remaining (true
amount of activity in the image. There are two plus scatter) coincidences is
approaches to estimating the random coinci-
dences so that they can be subtracted from the σ( Ntrue + Nscatter ) = ( Ntrue + Nscatter ) + (2 × Nrandom)
measured projection data: the delayed window
method and the singles method. (18-15)
In most PET scanners, the arrival time of
each photon is recorded and “tagged” with an Thus even if accurate corrections can be
accuracy of approximately 2 nanoseconds. At made, the random coincidence rate should be
18 • Positron Emission Tomography 337
minimized to avoid unduly increasing the sta- It is not possible to distinguish between
tistical noise level of the image. scatter events in the body versus scatter
The second method for estimation of events in the detector crystal on the basis of
random coincidences is based on Equation pulse amplitude. Therefore simple correction
18-11. If the rate at which single (not coinci- schemes based on dual-energy windows are
dence) events occur in each detector is mea- far less successful in PET imaging than in
sured, and the coincidence timing window ΔT SPECT imaging. Two main approaches cur-
is known, then the rate of random coinci- rently are used for scatter correction in PET.
dences for any pair of detectors can be com- The first approach uses information from the
puted. Because the rate of single events is original scatter-contaminated image and
typically at least an order of magnitude higher transmission image (see Section D.4) to derive
than the rate of coincidence events, the sta- the correction. The emission image shows the
tistical noise level in the estimate of the distribution of the activity in the subject. The
number of random events is small in compari- transmission image reflects the attenuation
son with that in the measurement of the coefficient of the tissue. At 511╯keV, virtually
number of prompt coincidences, and the all attenuation is due to Compton scatter.
uncertainty in the remaining coincidences Using these two images and computer model-
after random coincidences have been sub- ing of photon interaction physics (see Chapter
tracted is given by 6, Section C.3) with some simplifying assump-
tions, it is possible to derive an estimate of
σ( N true + Nscatter ) ≈ N true + Nscatter + N random the underlying distribution of scattered
events and their contribution to individual
(18-16) profiles. The estimated contribution of scat-
tered radiation then is subtracted from the
This method requires that each detector projection profiles and the reconstruction is
module continuously monitors the rate at repeated with the scatter-corrected data.
which it is detecting single events. As described in Chapter 19, Section E, with
the advent of hybrid PET/CT scanners, the
3. Correction for Scattered Radiation scatter distribution also can be computed
Scattered radiation in PET imaging leads to from the registered CT images, in which the
a hazy background in the reconstructed CT image is used in place of a PET transmis-
images, generally more concentrated toward sion image. This method works very well
the center of the image. As with random coin- when all the sources of radioactivity that
cidences, this leads to a decrease in image could lead to detected scatter events are con-
contrast and to errors in the quantitative tained within the FOV of the scanner. When
relationship between image intensity and the large amounts of activity are just outside the
amount of activity in the object. The fraction FOV of the scanner, problems can arise.
of scattered events in PET can be very high, Another drawback of this approach is that it
especially in 3-D imaging of the abdomen, is computationally intensive.
where it may be as high as 60% to 70%. This A second method for scatter correction is
large value has three major causes. First, based on an examination of projection profiles
only one of the two annihilation photons immediately outside the object. After correct-
needs to be scattered for a scatter coincidence ing for random coincidences, the only events
to occur. Second, the energy resolution of PET that should fall into these projection elements
detectors using dense scintillators such as are those that are mispositioned because of
BGO and LSO is inferior to NaI(Tl) detectors scatter. Based on the premise that scatter is
because of their lower light output. This a low-frequency phenomenon with little struc-
requires the use of a wider pulse-height ana- ture, data from the tails of the projection
lyzer window to capture the photopeak events. profiles can be extrapolated using simple
Finally, the predominant mode of interaction smoothly varying functions across the entire
in scintillators at 511╯keV is Compton scatter- projection. Both gaussian and cosine func-
ing, and many unscattered annihilation tions have been used for this purpose. The
photons deposit less than 511╯keV of energy extrapolated scatter distribution then is sub-
in the detector. Thus to increase the detection tracted from the projections prior to image
efficiency for photons that undergo Compton reconstruction. This method is rapid and,
scattering in the crystal, the analyzer window because it involves a direct measurement of
is widened even further to capture these scatter levels, it accounts for scatter from
events. radioactivity outside the FOV. However, it can
338 Physics in Nuclear Medicine
only approximate the true scatter distribu- measurement, called the blank scan, is made
tion and, in situations in which the scatter without the subject in the scanner. The subject
distribution is complex, or when the object then is placed in the scanner and the mea-
fills the whole FOV with no portion of the surement is repeated. This is known as
profile to examine outside the object, the the transmission scan. The attenuation
technique may result in significant errors. correction factor A for a detector pair (i,â•›j) is
These can range from a few percent for brain given by
imaging to tens of percent at the heart-lung
interface. Blanki, j
Ai, j = (18-18)
Transi, j
4. Attenuation Correction
Attenuation correction is by far the largest where Blankiâ•›,â•›j and Transiâ•›,â•›j are the counts in
single correction in PET. Fortunately, the cor- the blank and transmission scans for the
rection is relatively easy to derive. Consider detector pair.
a source located at a depth x inside an object To obtain transmission data for all coinci-
of thickness T as shown in Figure 18-25. Both dence detector pairs, it is necessary to scan
of the photons from an annihilation event in the transmission source around the scanning
the source must be detected to record a valid volume for both the blank and transmission
event. Assuming that they are emitted in scans. Typically, a rod source, with its length
the appropriate directions, the probability extending along the axis of the scanner, is
that both photons will reach the detector is placed in a holder near the surface of the
given by the product of their individual scanner bore, and the holder rotates around
probabilities the central axis so that data are acquired for
all pairs. The most commonly used source
Pdet = e− µx × e− µ (T − x) material is 68Ge (parent of 68Ga, T1/2 = 273
(18-17) days). The blank scan needs to be performed
= e − µT
only once a day because it remains constant
where µ is the linear attenuation coefficient over a period that is short compared with
of tissue at 511╯keV and is approximately the half-life of the radionuclide in the
0.095╯cm−1 for soft tissue, 0.12 to 0.14╯cm−1 for rod source. The transmission scan is per-
bone, and 0.03 to 0.04╯cm−1 for lung. Note that formed prior to injecting the patient with
the probability that both photons will reach the radiotracer. It is important that the
the detector is independent of the source loca- patient not move between the transmission
tion along the line joining the two detectors. and emission scan. Otherwise serious arti-
Equation 18-17 is similar to Equation 17-5 facts can occur, including the appearance of
for the geometric mean in SPECT, except that areas of abnormally high or low radiotracer
it applies for all source distributions, whereas uptake.
the geometric mean equation applies only for Conceptually, the simplest approach is to
point or plane sources at a fixed depth, x. As obtain the transmission scan before injecting
was the case for SPECT, transmission mea- the radiotracer to be imaged. This eliminates
surements can be used to correct for attenu- any possible interference between the activity
ation in PET. In PET, two measurements are that is present for the two scans.
taken with a source located on a line joining A second approach, called postinjection
each pair of coincidence detectors. The first transmission scanning, is to perform the
x
Detector 1 Detector 2
Point source
of activity
FIGURE 18-25 Parameters involved in the derivation of attenuation correction for PET (equation 18-17 in the text).
18 • Positron Emission Tomography 339
transmission scan immediately after the Although these techniques work well, the
emission scan but while there is still radio- widespread use of hybrid PET/CT scanners
tracer activity in the patient. This can save has significantly reduced the use of transmis-
a significant amount of time, because the sion scans using external radionuclide sources
patient does not have to be on the table for attenuation correction. Instead, informa-
waiting for uptake after the transmission tion from the CT scan is used to perform
scan before the emission scan is performed. attenuation correction. The methods for
Another advantage of this approach is that CT-based attenuation correction are discussed
it reduces the chances of patient motion and in Chapter 19, Section E.
misalignment between the emission and
transmission scans. However, it requires the 5. Dead Time Correction
ability to distinguish transmission events Like all radiation detectors, PET detectors
from emission events caused by residual exhibit dead time and pile-up effects at high
radiotracer in the body. This is possible counting rates. The mispositioning of events
because the emission radiations generally caused by pile-up and possible approaches for
are emitted from locations spread through- minimizing pile-up described in the context of
out the body, whereas the transmission radi- the gamma camera (see Chapter 14, Section
ations are emitted from a very small volume. A.4) apply as well to block detectors used for
Thus the transmission source irradiates only PET. Dead time corrections must be applied.
a small subset of detector pairs at any one Otherwise, the amount or concentration of
time, and its counting rate in those irradi- radioactivity will be underestimated at high
ated pairs generally is much higher than the counting rates. Most PET scanners use empir-
counting rate in the same detectors caused ical dead time models in which the observed
by emission radiations. To implement this counting rate as a function of radioactivity
method, the scanner must have the means concentration is measured for a range of object
to track the location of the transmission sizes and at different energy thresholds. The
source and identify which detectors are resulting data are then fit with paralyzable or
being irradiated by it. A disadvantage of the nonparalyzable dead time models (see Chapter
postinjection approach is that the count-rate 11, Section C.2). Some systems apply a global
performance of the detectors must be suffi- dead time correction factor for the system,
cient to handle the emission and transmis- whereas others apply corrections to individual
sion activities simultaneously. pairs of detector modules.
Finally, it is possible to acquire transmis- Dead time losses are dominated by the
sion and emission data at the same time. single-channel counting rate, which are much
This approach, known as simultaneous higher than the coincidence counting rate.
emission/transmission scanning, is the most Corrections can be as large as a factor of 2,
efficient way to use scanner time in many although generally it is desirable to keep
situations. As with postinjection transmis- them below this level. Situations in which the
sion scanning, it is necessary to track the corrections can be large include first-pass
location of the rod source. Because the rod cardiac studies, imaging studies near the
source irradiates only a small and known bladder when there are high levels of excreted
subset of detector pairs at any one time, radioactivity, and studies with very short-
emission data can be acquired simultane- lived radiotracers, such as 15O, which require
ously from the remaining nonirradiated high starting levels of activity to maintain
pairs. For irradiated detector pairs, the adequate counting statistics over the course
counting rate from the transmission source of a study.
is much higher than the emission counting
rate, so the emission counts do not seriously
affect the accuracy of the transmission data. 6. Absolute Quantification of PET
A disadvantage of simultaneous emissionâ•›/ Images
transmission scanning is that the relatively All of the corrections described earlier are
“hot” transmission source can contribute applied to the projection or sinogram data
random and scatter coincidence events to the prior to reconstruction of the image. If accu-
emission data. Even with corrections, these rately applied, after reconstruction, the voxel
events contribute to statistical noise and intensity in the image will be directly propor-
some degradation of image quality. For this tional to the amount of radioactivity in that
reason, postinjection transmission scanning voxel. Calibration to absolute concentrations
generally is the preferred approach. of radioactivity usually is accomplished by
340 Physics in Nuclear Medicine
103
600
400 Rtrue
Count/sec
Rrandom
Rscatter
NECR
200
0
0 2 4 6 8 10
Activity (Ci/cc)
FIGURE 18-26 Example of various coincidence counting rates and noise equivalent counting rate (NECR) for a clinical
whole-body scanner. These data predict that for the phantom used in this study, the best signal-to-noise (corresponding
to the peak of the NECR curve) in the reconstructed image would be achieved with an activity concentration of ~4 µCi/
cc (~150╯kBq/cc).
13
N-ammonia or 82RbCl to evaluate myocar- Control Alzheimer’s disease
dial viability and stratify patients with coro-
nary artery disease with regard to bypass
surgery. In the brain, PET is used diagnosti-
cally in a range of neurodegenerative diseases
(Alzheimer’s disease, Parkinson’s disease)
and dementia, for epilepsy, neurodevelopmen-
tal disorders and in psychiatric disorders.
Metabolic FDG images of a patient with
Alzheimer’s disease compared with those of a
normal control are shown in Figure 18-28.
Many other PET radiotracers are used for
research studies and are being developed for
future clinical use. These include radioligands
that bind to specific receptors systems in the
brain, and radiotracers that target cell-surface
molecules specific to certain types of tumors.
Positron-emitting radionuclides also have
been used to radiolabel cells (e.g., stem cells)
and drug delivery vehicles such as nanopar-
ticles. Many of these radiotracers are first
FIGURE 18-28 Transaxial image slices showing 18F-
evaluated in animal models using a dedicated fluorodeoxyglucose uptake at two different levels of the
animal PET scanner. Figure 18-29 shows an brain in a normal volunteer (control) and in a patient at
image of the binding of the radioligand an early stage of Alzheimer’s disease. Data acquisition
11
C-raclopride to dopamine receptors in the times were ~╛30 minutes and injected doses were 370╯MBq
rat brain. (10╯mCi). Arrows indicate metabolic deficits in the
patient’s images. This distinct pattern of reduced metab-
olism is seen in all patients with Alzheimer’s disease and
increases in severity and extent are seen as the disease
progresses.
FIGURE 18-29 Coronal image of rat brain acquired on a small-animal PET scanner following injection of 11C-raclopride.
The location of the brain is indicated by the ellipse. This radiotracer binds to the dopamine receptors in the brain,
which are located primarily in the striatum (arrows). Images were acquired before (left) and after (right) a pharmaco-
logic intervention that damages the dopaminergic neurons on one side of the brain. A clear reduction in the binding
of the radiotracer is observed on that side.
3-dimensional lutetium oxyorthosilicate-based whole- 12. Badawi RD, Marsden PK: Developments in component-
body PET/CT scanner with the national electrical based normalization for 3D PET. Phys Med Biol 44:
manufacturers association NU 2-2001 standard. 571-594, 1999.
J Nucl Med 46:2083-2091, 2005. 13. Performance Measurements of Positron Emission
6. De Jong HWAM, van Velden FHP, Kloet RW, et al: Tomographs: National Electrical Manufacturers
Performance evaluation of the ECAT HRRT: an LSO- Association (NEMA) Standards Publication NU2-
LYSO double layer high resolution, high sensitivity 2007, Rosslyn, VA, 2007, NEMA.
scanner. Phys Med Biol 52:1505-1524, 2007. 14. Performance Measurements of Small Animal Posi-
7. MacDonald L, Edwards J, Lewellen T, et al: Clinical tron Emission Tomographs: National Electrical Man-
imaging characteristics of the positron emission ufacturers Association (NEMA) Standards Publication
mammography camera: PEM Flex Solo II. J Nucl NU4-2008, Rosslyn, VA, 2007, NEMA.
Med 50:1666-1675, 2009.
8. Constantinescu CC, Mukherjee J: Performance eval-
uation of an Inveon PET preclinical scanner. Phys BIBLIOGRAPHY
Med Biol 54: 2885-2899, 2009.
Additional general references are the texts indi-
9. Rowland DJ, Cherry SR: Small-animal preclinical
cated in references 1 and 11. Also pertinent are the
nuclear medicine instrumentation and methodology.
following:
Sem Nucl Med 38:209-222, 2008.
10. Larobina M, Brunetti A, Salvatore M: Small animal Phelps ME, editor: Molecular Imaging and its Biological
PET: A review of commercially available systems. Applications, New York, 2004, Springer-Verlag.
Curr Med Imag Rev 2:187-192, 2006. Zanzonico P: Positron emission tomography: A review of
11. Bendriem B, Townsend DW: The Theory and Practice basic principles, scanner design and performance, and
of 3D PET, Netherlands, Kluwer, 1998, Dordrecht. current systems. Sem Nucl Med 34:87-111, 2004.
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chapter
19
Hybrid Imaging:
SPECT/CT and PET/CT
Virtually all modern positron emission tomog- decrease in the accumulation of a radiotracer
raphy (PET) scanners and an increasing for example), but also on knowing precisely
number of single photon emission computed where that signal originated, it has been
tomography (SPECT) systems are integrated common practice for several decades to com-
with an x-ray computed tomography (CT) plement tomographic nuclear medicine scans
scanner. These hybrid imaging systems are with CT or MRI scans. Typically, these scans
capable of acquiring PET or SPECT images, were acquired on separate instruments, pos-
along with spatially registered CT images, in sibly days apart. Thus correlating informa-
quick succession. This chapter discusses the tion in the two studies was hampered by the
features of these hybrid systems and describes difficulty of spatially registering the images
how the CT scans not only provide anatomic and the effect of any changes in the patient’s
context to improve diagnostic interpretation condition (especially during active treatment)
of nuclear medicine studies, but also can be during the time that elapsed between the two
used as the basis for performing corrections studies.
for photon attenuation and scatter in PET The power of hybrid imaging systems, in
and SPECT. which a PET or SPECT scanner is integrated
with a CT scanner, is that the two scans are
acquired in quick succession, and thus the
A. MOTIVATION FOR HYBRID data can be considered to be in fairly good
SYSTEMS spatial and temporal registration (see Sec-
tions C and D). With good spatial registration,
Both SPECT and PET provide functional it also becomes possible to consider using the
information, using radiotracers that are CT scan, which provides a map of tissue
designed to measure physiologic or metabolic attenuation values (Section B), to compute
parameters, or that bind or interact with the corrections for photon attenuation and
specific molecular targets on the cell surface, scatter for the PET and SPECT studies (see
or within cells. Although for some radio� Section E). It also is more convenient for the
tracers, the regional anatomy is obvious (e.g., patient and more efficient from a scheduling
cardiac perfusion studies), there are many perspective, as both datasets are acquired in
cases in which the nuclear medicine study a single imaging session. Hybrid systems also
does not provide much in the way of ana- are common in small-animal and preclinical
tomic information. Even in cases in which imaging studies. Just as in the clinical envi-
there is some anatomic information, the ronment, the anatomic information provided
spatial resolution is poor compared with by CT can be helpful both for interpreting and
techniques such as CT and magnetic reso- quantitatively analyzing PET and SPECT
nance imaging (MRI), both of which can studies.
provide images of the human body at a reso- To date, the focus has been largely on the
lution of 1╯ mm or better. integration of PET and SPECT with x-ray CT.
Because clinical decisions may depend not As described in Sections C and D, from a
only on detecting a signal (an increase or technical perspective it has been relatively
345
346 Physics in Nuclear Medicine
straightforward to integrate these modalities Because the flux of x rays is so high, images
with only minor modifications to the hard- with excellent counting statistics can be
ware for either system. Much of the integra- acquired very rapidly, on the order of seconds.
tion in hybrid PET/CT or SPECT/CT systems This section provides a very brief overview of
occurs at the software and system control x-ray CT to aid in the discussion of hybrid
level. Hybrid systems that combine PET PET/CT and SPECT/CT systems that follows.
and MRI also are under development. MRI More details on x-ray CT can be found in
has advantages over CT for some structural Reference 1.
imaging applications because of the high
contrast it can produce in soft tissues; 1. X-ray Tube
however, integration is much more challeng- The x-ray tube is a vacuum tube containing a
ing, and the cost of a combined device could cathode, which consists of a filament (helical
be high. Nonetheless, human scanners have coil of tungsten wire) through which a current
been installed and a brief overview of the is passed. As the filament is heated, electrons
status of hybrid PET/MRI systems is given in are liberated, and are accelerated and focused
Section F. by an applied bias voltage towards a high-
density metal (typically tungsten) anode (Fig.
19-1). When the electrons interact in the
B. X-RAY COMPUTED TOMOGRAPHY anode material, they produce both continuous
bremsstrahlung radiation (see Chapter 6,
X-ray CT is a form of transmission computed Section A.1) as well as discrete characteristic
tomography that is based on the reconstruc- x rays at energies that correspond to the elec-
tion techniques described in Chapter 16. It tron binding energies of the anode material
shares many of the features of transmission (see Chapter 2, Section C.2).
scanning that already have been described The current passing though the filament
for attenuation correction for SPECT (see controls the number of electrons emitted from
Chapter 17, Section B.3) and PET (see the filament, and thus the current flowing
Chapter 18, Section D.4) imaging. However, through the x-ray tube (the tube current) as
instead of an external radionuclide source, a well as the flux of x rays produced when these
CT scanner uses an x-ray tube that generates electrons strike the anode. The tube current
a high flux of x rays in a relatively narrow typically is approximately 10% to 20% of the
beam that are transmitted through the body. current passed through the heating filament.
Hot cathode
filament (0 V)
Electron beam
Rotating tungsten anode
(~80-140 kV)
X rays
Focal spot
Vacuum enclosure
Rotor
FIGURE 19-1 Schematic of an x-ray tube with a rotating anode. An alternating current is passed through the cathode
filament, heating it up and releasing electrons. The electrons are accelerated by the potential difference between the
cathode and anode, and strike the tungsten anode producing x rays. The anode rotates such that the location of the
focal spot on the tungsten anode changes over time to avoid melting the anode at high x-ray tube currents. For further
details, see text.
19 • Hybrid Imaging: SPECT/CT and PET/CT 347
physical height of the detector in the axial gantry (Fig. 19-3). Low-voltage power is sup-
direction. Slice thicknesses of 1 to 5╯mm were plied to the gantry via slip-ring technology
typical. To acquire multiple image slices, the rather than by cables. The slip rings consist
patient bed was stepped incrementally of conductive brushes that slide over the
through the system. surface connections providing continuous
Two-dimensional (2-D) detector arrays are electrical contact and allowing the gantry to
used in most modern scanners, allowing mul- rotate continuously. Data can be taken off the
tiple slices through the body to be acquired gantry in the same way or, more commonly, by
simultaneously. To ensure complete sampling wireless transmission. This enables very fast
for tomographic reconstruction, the patient data acquisition as the patient moves through
bed usually is translated while the detectors the gantry while it rotates at speeds of 1 to 3
rotate about the patient, creating a helical revolutions per second. A large axial stack of
trajectory. Individual detector sizes are small, images can be acquired in just a few seconds.
typically in the range of 0.25 to 1.25╯mm,
in order to achieve high spatial resolution. 4. CT Reconstruction
Systems typically come with 16, 32, or 64 The projection data for CT typically are col-
rows of detectors, allowing this many slices to lected as the scanner performs a helical tra-
be obtained in a single rotation of the system. jectory, where the patient bed is translated
Each row may consist of approximately 1000 through the scanner while the x-ray tube and
detector elements; thus modern multi-slice detector rotate. They are readily sorted into
CT scanners can have a total of approximately stacks of sinograms with each sinogram con-
10,000 to 100,000 individual detector ele- taining the data for a single transaxial section
ments. Signals from smaller detectors some- through the patient. Images commonly are
times may be binned together to improve reconstructed using the same types of filtered
signal-to-noise ratio or reduce dose at the backprojection methods discussed in Chapter
expense of spatial resolution. For example, 16, Section B.
signals from 2 × 2 detectors of size 0.5 × For CT, the measured projection data cor-
0.5╯mm2 may be combined to create a “virtual” respond to the transmission of x rays through
detector measuring 1 × 1╯mm2. the subject. For a given line of response (a ray
CT detectors have very high efficiency for connecting the x-ray focal spot and a detector
the x-ray energies of interest (40-140╯keV). element), the measured intensity, I, is
Virtually all x-rays incident on a detector − ∑ µi ∆ xi
I = I0 e i (19-1)
element interact and produce a signal.
However, small gaps between the individual where I0 is the initial x-ray intensity directed
detector elements cause the overall efficiency along the line of response, µi is the linear
to be less than 100%. attenuation coefficient (Chapter 6, Section D)
for the ith pixel and Δxi is the pathlength of the
3. X-ray CT Scanner line of response through the i th pixel. X-ray CT
The CT scanner consists of the x-ray tube and seeks to reconstruct the linear attenuation
a step-up high-voltage power supply, along coefficient µ; therefore the measured data
with the detector, mounted on a rotating must be transformed prior to reconstruction
X-ray tube
X-ray beam
Patient Patient
Patient bed
Detector array
FIGURE 19-3 Schematic showing the components and geometry of a CT scanner. The x-ray tube and detector rotate
in the transaxial plane while the patient bed translates along the axial direction, resulting in a helical trajectory of
the x-ray beam around the patient. Multiple image slices can be rapidly acquired.
19 • Hybrid Imaging: SPECT/CT and PET/CT 349
by taking the logarithm of the ratio of the this normalization results in roughly equiva-
incident x-ray intensity with respect to the lent pixel intensities in the reconstructed CT
measured intensity. The transformed projec- image, independent of x-ray tube and filtra-
tion, p, used in the reconstruction algorithm tion settings.
is therefore given by: CT numbers calculated from Equation 19-3
I are called Hounsfield units (HU), named after
p = log 0 = ∑ µ i ∆ xi (19-2) the inventor of medical CT scanning. By defi-
I i nition, water has a value of 0╯HU, air spaces
The reconstruction of these projections in the lungs have values that can approach
yields images in which the pixel values cor- –1000╯HU, and bone can have values as high
respond to µ, the linear attenuation coeffi- as 3000╯HU.
cient of the tissue in that pixel. Thus a CT CT projection data are subject to the same
scan provides an image of the linear attenu- sampling requirements as nuclear medicine
ation coefficients inside the body. data (see Chapter 16, Section C.1). Angular
Given the x-ray energies used and the rela- projection data are captured as the system
tively low atomic number of most tissue con- rotates and acquired at ~1000 to 2500 projec-
stituents, the majority of x-ray interactions in tion angles. The linear sampling distance is
the body are by Compton scatter (see Chapter governed by the detector element spacing and
6, Section C.3). Because Compton scatter typically is in the range of 0.25 to 1╯mm. Thus
depends primarily on tissue density (see the sampling of projection data in CT data�sets
Chapter 6, Section D.1), the pixel value in CT is sufficient to support much higher spatial
images is roughly proportional to tissue resolution than is obtained in nuclear medi-
density. Higher-density materials such as cine studies; however, the size of the projec-
bone show up with high pixel values, whereas tion datasets also is much larger. In practice,
lower-density tissues such as lung show up the spatial resolution obtained in CT is limited
with low pixel values. by the focal-spot size of the x-ray tube and also
Note that the reconstructed values repre- by radiation dose considerations. A recon-
sent some average of µ across the range of structed spatial resolution of approximately
energies present in the x-ray beam (see Fig. 1╯mm is typical in many clinical scenarios.
19-2) and therefore depend strongly on the Figure 19-4 shows examples of recon-
x-ray tube voltage and filtration. For this structed CT images of the human body. In
reason, pixel values in CT images usually are this study, a large number of transverse
expressed on a normalized scale, with respect slices were obtained to produce a volumetric
to the values for water, as follows: dataset covering the entire abdominal region.
A transverse and coronal view are shown. In
µ ( x, y) − µ water many clinical studies, native tissue contrast
CT number ( x, y) = 1000 ×
µ water is augmented by the injection or ingestion
of a contrast agent. These agents, typically
(19-3) containing high-Z elements such as iodine
For soft tissues (which are fairly similar to (injected agents) or barium (ingested agents),
water in density and attenuation coefficient), serve to increase x-ray attenuation in tissues
Liver
in which they are present. They are used to based on high-purity germanium, that could
increase contrast in the vasculature, in be used both to efficiently detect the gamma-
highly perfused organs and tissues with ray emissions from radionuclides as well as x
leaky blood vessels (e.g., tumors), to detect rays. Although a prototype system was devel-
internal bleeding, or to highlight the diges- oped, the challenge of devising a single detec-
tive and excretory tracts of the body. tor technology that could span the quite
differing requirements of SPECT (e.g., good
C. SPECT/CT SYSTEMS energy resolution) and CT (e.g., high x-ray
flux) was considerable. Therefore approaches
that integrated existing SPECT and CT
1. Clinical SPECT/CT Scanners systems were pursued. Figure 19-5 shows the
Early attempts to develop hybrid SPECT/ first such system, developed at the University
CT systems were pioneered by Dr. Bruce of California–San Francisco, by combining a
Hasegawa and co-workers in the early 1990s.2 single-headed SPECT system with a single-
One concept was to develop a single detector, slice CT scanner.3
B
CT SPECT
19 • Hybrid Imaging: SPECT/CT and PET/CT 351
Gamma camera
heads
X-ray tube
X-ray detector
Rotating gantry
B
FIGURE 19-6 Examples of two clinical SPECT/CT scanners. A, The two gamma camera heads are mounted on a
rotating gantry that is separate from the high-speed slip-ring CT system. B, Two gamma camera heads and the x-ray
tube and detector are mounted on a common rotating gantry. See text for further details on these two systems.
(A, Courtesy Siemens Medical Solutions, Malvern, PA. B, Courtesy Philips Healthcare, Andover, MA.)
such as the pituitary), and initial data on components of these systems typically use
the use of SPECT/CT in the heart and brain lower-voltage (up to 80╯kVp) and lower-flux
has appeared. An example of a SPECT/ x-ray tubes compared with clinical systems,
CT imaging application is shown in Figure because of the smaller size of the objects being
19-7. SPECT/CT also has potential as a useful imaged. Generally, they also use x-ray tubes
tool for computing indi�vidualized radiation with a smaller focal-spot size (typically 50-100
dosimetry for radionuclide therapies and is microns), and higher-resolution detectors to
increasingly used in the research setting improve spatial resolution. Resolution also
for evaluating the biodistribution of new can be improved by increasing the object-to-
radiotracers. detector distance and magnifying the projec-
tions on the detector when the subject is
2. Small-Animal SPECT/CT Scanners significantly smaller in dimensions than the
SPECT/CT systems also have been developed detector area.
for small-animal imaging. An example of such Most systems employ a 2-D x-ray detector
a system is shown in Figure 19-8A. The CT that co-rotates with the x-ray tube around the
19 • Hybrid Imaging: SPECT/CT and PET/CT 353
FIGURE 19-7 SPECT/CT image of a patient with osteomyelitis (infection of the bone) behind the right eye. The SPECT
scan was performed following the injection of 22.2╯MBq (600╯µCi) of 111In-labeled white blood cells. The helical CT scan
used 140╯kVp x rays with an exposure of 30╯mAs per slice. A single transaxial slice is shown. The SPECT scan shows
accumulation of the radiolabeled white blood cells at the site of infection, and the fused SPECT/CT scan (SPECT in
pseudocolor, CT in grayscale) allows the precise anatomic location of the infection to be determined. Total acquisition
time for the two scans was approximately 20 minutes. (Courtesy GE Healthcare, Waukesha, WI.)
Kidneys
Tumor
A B
FIGURE 19-8 A, SPECT/CT system for small-animal imaging. The SPECT system consists of four gamma camera
detector heads with multi-pinhole collimators. B, SPECT/CT images of an 111In-labeled radiotracer targeted to a tumor
in a mouse model of cancer. The SPECT image (â•›pseudocolor) shows accumulation of the radiotracer in the tumor, as
well as excretion via the kidneys. The CT image (grayscale) shows the underlying mouse anatomy (A, Courtesy
Professor Stephen Mather, Barts Cancer Institute, London.)
354 Physics in Nuclear Medicine
of the patient bed through the two systems number of CT slices available in their PET/
and a large degree of software integration CT scanners.
that controls the position of the patient bed Figure 19-10 shows an example of a modern
and sequential acquisition of PET and CT clinical PET/CT scanner.7 The PET compo-
data, as well as image reconstruction, attenu- nent of this system employs 28,336 LYSO
ation correction, and visualization and analy- scintillator elements, each with dimensions of
sis of the reconstructed PET/CT datasets. 4 × 4╯mm in cross-section, by 22╯mm in thick-
One important practical consideration, result- ness. These elements are arranged in 28 flat-
ing from the long travel length of the patient panel modules, each consisting of a 23 × 44
bed, is to ensure that the bed deflection does array of elements, and read out by 15 PM
not change as the bed is cantilevered through tubes. Anger logic (see Chapter 18, Section
the two imaging systems, which would result B.1 and B.2) is used to determine the element
in misalignment of PET and CT images. in which an interaction took place. The
Mechanical designs typically incorporate a scanner has an axial field-of-view of 18╯cm, a
rail system or additional supports for the bed transverse field-of-view of 57.6╯cm, and a
to prevent this. patient port diameter of 71.7╯cm.
The description of PET scanner designs The scanner also incorporates time-of-
and configurations presented in Chapter 18, flight information (see Chapter 18, Section
Section B, applies also to the PET component A.2), with a timing resolution on the order of
of current hybrid PET/CT systems. These 600 psecs. The CT component most commonly
PET systems all consist of multiple circumfer- has a 16- or 64-slice detector. The 64-slice
ential rings of scintillation detectors arranged detector consists of 64 rows of 690 detectors
around the patient to provide a complete set in each row, with each detector measuring
of projection angles without any rotation of 0.625╯mm in the axial direction, giving an
the detectors. axial coverage of 64 × 0.625╯mm = 400╯mm.
The CT component may range from a rela- The x-ray tube used with this system has a
tively simple single-slice system to state-of- maximum voltage of 140╯kV. At this voltage,
the-art 64-slice CT scanners. These systems the maximum x-ray tube current is 430╯mA.
use slip-ring technology (see Section B.3) to At a voltage of 120╯kV, the x-ray tube can be
permit rapid rotation of the x-ray tube and operated at a current of up to 500╯mA. Rota-
detectors, and are capable of acquiring tion times can be as fast as 0.4 seconds.
complete angular projections for a large The primary application of PET/CT is for
number of contiguous slices in times ranging whole-body imaging of cancer patients with
from a few seconds to a few minutes, depend- the radiotracer FDG. The CT component
ing on how many slices can be acquired simul- helps to identify the precise anatomic location
taneously (which depends on the number of of foci of increased FDG uptake that may be
rows of x-ray detector elements). Most manu- due to primary tumors or their metastases.
facturers offer a range of options for the An example of such a study is shown in Figure
CT PET
FIGURE 19-10 Hybrid PET/CT scanner. The axial separation between the PET and CT components is adjustable.
(Courtesy Philips Healthcare, Andover, MA.)
356 Physics in Nuclear Medicine
19-11. Images of tissue attenuation from the scanner. This design allows each modality to
CT scan usually are used to derive the PET be used separately if desired. Like small-
attenuation correction factors (see Section E). animal SPECT/CT, applications of PET/CT
However, some PET/CT systems also still relate to imaging the biodistribution of new
have an option to use radionuclide transmis- radiopharmaceuticals, studying the biodistri-
sion sources for attenuation correction as bution of new therapeutics, and monitoring
described in Chapter 18, Section D.4. the effect of new therapeutics in animal
models of human disease.
2. Small-Animal PET/CT Scanners
CT scanners, identical or very similar to those
offered in small-animal hybrid SPECT/CT E. ATTENUATION AND SCATTER
systems (see Section C.2), also are available CORRECTION USING CT
with the small-animal PET scanners described
in Chapter 18, Section B.5. Figure 19-12 One of the key advantages of hybrid SPECT/
shows a PET/CT scanner that consists of CT or PET/CT scanners is the ability of CT
independent PET and CT components that to rapidly acquire transmission images of
can be docked together to form a hybrid high statistical quality that can be used for
Transverse slice
Coronal slice
CT
PET
B
A
FIGURE 19-12 A, Dockable PET/CT scanner for small-animal imaging. B, Example image from such a system in which
the PET (â•›pseudocolor) and CT (grayscale) data have been fused and rendered in 3D. The PET scan shows accumulation
of the radiopharmaceutical 64Cu-Oxo-DO3A-trastuzumab in a tumor growing on the flank of a mouse (arrow). (A,
Courtesy Siemens Preclinical Solutions, Knoxville, TN. B, Courtesy D. Yapp, C. Ferreira, and F. Benard, The British
Columbia Cancer Agency and Nordion.)
attenuation correction and for scatter correc- A simple approach is to use image segmen-
tion of PET and SPECT studies. The CT tation (see Chapter 20, Section B.5) to sepa-
scan replaces the need for a lengthy transmis- rate tissues based on their pixel values in the
sion scan using external radionuclide sources CT scan into three broad classes: air, soft
(see Chapter 17, Section B.3, and Chapter tissue, and bone. Then the known linear
18, Section D.4) and thus decreases total attenuation coefficients for each of these
imagi n g time for attenuation-corrected PET materials at the emission energy of the radio-
and SPECT studies. As was shown in Chap- nuclide can be substituted for the CT number
ters 17 and 18, attenuation correction is criti- to yield an attenuation map appropriate for
cal for reconstructing quantitatively accurate attenuation correction at that energy. This
SPECT or PET images. Even for more quali- attenuation map then is used in iterative
tative clinical evaluation, attenuation correc- reconstruction algorithms or forward-projected
tion often is necessary to avoid distracting into sinogram space, to compute the attenua-
artifacts and nonuniformities, and to enable tion correction factors to apply to the emission
accurate diagnostic interpretation. Reference study in the same way that transmission
8 discusses the methods by which CT scans scans acquired using external radionuclide
are used for attenuation correction and com- sources were applied in Chapter 17, Section
pares them with attenuation correction based B.3. This approach suffers from significant
on the use of external radionuclide transmis- limitations, because pixels at tissue boundar-
sion sources. ies can contain a mixture of materials (e.g.,
bone and soft tissue) and do not fall into
any of these three categories. Also, many
1. Computing Attenuation Correction tissues, most notably the lung, have a range
Factors from CT Scans of densities, which causes the linear atten�
Use of the CT scan to correct for photon atten- uation coefficient to vary from location to
uation in PET or SPECT requires that the location.
pixel intensity in the CT image (expressed as Therefore more sophisticated techniques,
CT numbers in HU; see Section B.4) be con- which provide a continuous mapping from CT
verted into the linear attenuation coefficient, number to µ at the radionuclide emission
µ(E), at the photon emission energy E of the energy, typically are used to create the atten-
radionuclide used in the nuclear medicine uation map. Two factors, however, complicate
study. For PET, this energy always is 511 keV. this mapping. First, the x-ray beam consists
For SPECT, the energy depends on the radio- of photons with a range of energies with
nuclide used. varying attenuation coefficients. Fortunately,
358 Physics in Nuclear Medicine
a relatively straightforward solution is to use effective x-ray energy of 80 keV to the 511-keV
the effective energy of a known x-ray spec- energy appropriate for PET is shown, although
trum. The effective energy is defined as the conceptually the same approach can be taken
energy of a monochromatic (single-energy) for radionuclides such as 99mTc (140-keV emis-
x-ray beam having the same attenuation coef- sion) used in SPECT. Pixels in the CT scan
ficient as the polychromatic x-ray spectrum with CT numbers â•›60╯HU are scaled to µ(E)
used in the measurement. For example, for using a linear fit to the data points for air,
a filtered 130-kVp x-ray spectrum suitable water and soft tissue. Pixels with CT numbers
for CT, the effective energy is approximately ╛60╯HU are scaled with a second linear fit
80 keV. that passes through data points for bone. This
The second problem is that the energy plot provides a continuous mapping from
scaling for pixels containing significant reconstructed CT number to the energy-
amounts of bone is quite different than that specific attenuation coefficient µ(E). Note that
for pixels containing primarily soft tissue, the slopes of the fitted lines are energy-
blood, or air (Fig. 19-13). This is because bone, dependent and must be computed for each
with its relatively high atomic number (caused radionuclide energy. Furthermore, the slope
by its calcium content) has a significant prob- of the line for bone varies somewhat with
ability of causing photoelectric interactions at x-ray tube voltage and filtration and, strictly
x-ray energies. However, at typical nuclear speaking, should be computed for each differ-
medicine energies (140 keV and above), the ent kVp setting used.
strong drop in photoelectric absorption prob-
ability with increasing energy (see Chapter 6,
Section D) means that almost all interactions 2. Possible Sources of Artifacts for
are by Compton scatter. Interactions in the CT-Based Attenuation Correction
lower-Z soft tissues, on the other hand, are There are a number of possible sources for
almost exclusively by Compton scatter, at introducing artifacts or biases when using
both x-ray and nuclear medicine energies. For CT-based attenuation correction in nuclear
this reason, no single energy-scaling relation- medicine:
ship holds across all tissue types. • The CT image typically is acquired at
Therefore a bilinear fitting approach often much higher spatial resolution than the
is taken, as illustrated in Figure 19-13. In PET or SPECT study. If the resolutions
this specific example, the mapping from an are not matched, then artifacts can occur
0.20
0.18
0.16 Bone
0.14
(cm1) at 511 keV
0.12
Soft tissues
0.10
Water
0.08
0.06
0.04
0.02
Air
0.00
1000 500 0 500 1000 1500
HU (80 keV effective x-ray energy)
FIGURE 19-13 Plot of the linear attenuation coefficient at 511 keV versus CT number in Hounsfield units for an
effective x-ray energy of 80 keV for soft tissues, air, water, and bone. A bilinear fit to these points commonly is used
to scale the CT numbers for attenuation correction of the PET data. See text for further details. Data obtained from
reference 9.
19 • Hybrid Imaging: SPECT/CT and PET/CT 359
Truncation
and artifacts
B
A
FIGURE 19-14 Two sources of artifacts in CT-based attenuation correction of PET data. A, Respiratory motion artifacts
in the CT scan (arrow) leads to artifacts in the activity distribution in the reconstructed PET images. B, Truncation
of the body in a CT scan leads to underestimation of attenuation from the missing tissues and artifacts at the edge of
the field-of-view. Both of these factors can introduce substantial quantitative errors and artifacts in PET images recon-
structed with attenuation correction based on the CT images. (Images courtesy Dr. Paul Kinahan, University of Wash-
ington, Seattle, WA.)
360 Physics in Nuclear Medicine
thus they change the relationship transmission maps can be used for scatter
between CT number and µ(E) shown in correction in SPECT and PET respectively.
Figure 19-13. Although this is theoreti-
cally a problem, empirically, it is rare
that CT-based attenuation correction F. HYBRID PET/MRI AND SPECT/MRI
leads to artifacts from exogenous con-
trast administration. Furthermore, if the There are many clinical situations in which
CT scan is acquired solely for attenua- MRI,10 rather than CT, is the anatomic
tion correction and anatomic localiza- imaging technique of choice. Furthermore,
tion, it will often be performed as a MRI can image functional and physiologic
low-dose study without administration of processes and, via magnetic resonance spec-
contrast agent. troscopic imaging, can also study metabolic
• For similar reasons, care must be exer- pathways. Thus an argument for the integra-
cised when imaging patients that have tion of nuclear medicine tomography with
surgical or dental implants made from MRI systems appears to be compelling.
high-Z materials. These have the poten- However, a number of considerations led to
tial to cause local artifacts because their CT-based hybrid systems emerging first, and
appearance on the CT image (high only in 2005 were the first practical hybrid
CT number) will not lead to the correct PET/MRI systems produced.11 SPECT/MRI
prediction of their effect on the attenua- systems are even less well developed.
tion of photons at nuclear medicine The integration of PET and SPECT with
energies. In addition to leading to the MR is challenging for a number of reasons.
wrong scaling, large metal implants First, clinical MRI systems typically have
can also cause significant artifacts in magnetic field strengths of 1 to 3╯T,* whereas
the CT images that can propagate into the field strengths of research and small-
the attenuation maps used for attenua- animal systems may be over 10T. Strong mag-
tion correction. Modern CT scanners, netic fields exist not only inside but often
however, use algorithms that can sig- around the edges of a MR system as well. The
nificantly reduce these artifacts and PM tube detector technology used in most
their effects on CT-based attenuation nuclear medicine systems is highly sensitive
correction. to even small magnetic fields. For example, in
• At the time of the CT scan, the patient SPECT, the PM tubes are shielded to guard
often already has been injected with the against magnetic field effects when rotating
radiopharmaceutical for the nuclear the gamma camera detector heads though the
medicine scan. However, the flux of earth’s magnetic field, which measures a
photons from the radiopharmaceutical is mere 30 to 60╯µT. Most PM tubes cannot
so low compared with the x-ray flux that operate at all in fields higher than approxi-
there is no detectable bias to the x-ray mately 0.01 T. Thus PM tube-based detectors
measurements and this potential must be kept far away from the magnet;
problem can be ignored. however, they can still be used in hybrid PET/
Although these factors need to be consid- MRI systems in which the two scanners are
ered, the advantages of the speed and high physically separate, and a bed on rails moves
statistical quality of CT-based attenuation the patient from one scanner into the other.
correction almost always outweigh such Second, unlike CT, magnetic resonance is
concerns. a relatively slow modality for acquiring high-
resolution, diagnostic-quality images over
3. Scatter Correction large tissue volumes. Typical clinical exami-
In addition to being used for attenuation cor� nations require several minutes, much like
rection, the scaled attenuation map also can PET and SPECT. This makes sequential
be used for calculation of a correction for imaging (which is the standard approach in
scattered radiation in the tomographic PET/CT and SPECT/CT) less attractive,
nuclear medicine study. At nuclear medicine because the total time of the examination can
energies, virtually all interactions in biologi- be rather long. Simultaneous imaging to
cal tissues are by Compton scatter, and thus improve throughput is possible, but only by
the attenuation map of µ(E) is equivalent to
a map of the coefficients for Compton scatter
interactions. Chapter 17, Section B.4, and
Chapter 18, Section D.3, describe how these *T, Tesla: the standard unit of magnetic field strength.
19 • Hybrid Imaging: SPECT/CT and PET/CT 361
creating a very compact PET or SPECT stand-alone systems to reduce magnetic field
system that can fit inside the bore of a magnet, and radiofrequency interference to acceptable
and operate in very strong magnetic fields. levels. As well, it combines two expensive
Early approaches used long light guides or diagnostic imaging modalities. It has yet to be
optical fibers to transport scintillation light demonstrated whether clinical applications
from PET detectors residing inside the bore will justify the cost of these systems. None-
of the magnet, to PM tubes placed several theless, PET/MRI is likely to emerge as a
meters outside the MRI scanner where the powerful tool for biomedical research. Figure
fringe magnetic field is low enough for their 19-15 shows an early hybrid PET/MRI system
operation. More recently, practical hybrid designed for imaging the human brain, and
PET/MRI systems have been developed for examples of the images it produces.
both small-animal and human applications
using detectors based on scintillator elements REFERENCES
read out by avalanche photodiodes (see 1. Bushberg JT, Seibert JA, Leidholdt EM, Boone JM:
Chapter 7, Section C.3), which are relatively The Essential Physics of Medical Imaging, ed 3,
immune to magnetic field effects. Chapter 10, Philadelphia, PA, 2012, Lippincott Wil-
Third, cost is an important consideration liams & Wilkins.
2. Lang TF, Hasegawa BH, Liew SC, et al: Description
in the clinical adoption of hybrid PET/MRI of a prototype emission-transmission computed
scanners. Integration of PET and MRI typi- tomography imaging system. J Nucl Med 33:1881-
cally requires at least some modification of 1887, 1992.
3. Tang HR, et al: Implementation of a combined x-ray
CT-scintillation camera imaging system for localizing
and measuring radionuclide uptake: experiments in
phantoms and patients. IEEE Trans Nucl Sci 46:551-
557, 1999.
PET 4. Buck AK, Nekolla S, Ziegler S, et al: SPECT/CT.
J Nucl Med 49:1305-1319, 2008.
5. Badea CT, Drangova M, Holdsworth DW, Johnson
GA: In vivo small animal imaging using microCT and
digital subtraction angiography. Phys Med Biol
53:R319-350, 2008.
6. Beyer T, Townsend DW, Brun T, et al: A combined
PET/CT scanner for clinical oncology. J Nucl Med
MRI 41:1369-1379, 2000.
7. Surti S, Kuhn A, Werner ME, et al: Performance of
Philips Gemini TF PET/CT scanner with special con-
sideration for its time-of-flight imaging capabilities.
J Nucl Med 48:471-480, 2007.
8. Kinahan PE, Hasegawa BH, Beyer T: X-ray based
attenuation correction for positron emission
A tomography/computed tomography scanners. Semin
Nucl Med 33:166-179, 2003.
9. Hubbell JH, Seltzer SM: Tables of x-ray mass attenu-
ation coefficients and mass-energy absorption coeffi-
cients from 1 keV to 20╯MeV for elements Z = 1 to 92
and for 48 additional substances of dosimetric inter-
est. Available at http://physics.nist.gov/PhysRefData/
XrayMassCoef/cover.html [accessed August 26th,
2011].
10. Bushberg JT, Seibert JA, Leidholdt EM, Boone JM:
B The Essential Physics of Medical Imaging, ed 3,
Chapters 12 and 13,, Philadelphia, PA, 2012, Lip-
FIGURE 19-15 A, Hybrid PET/MRI scanner. The PET
pincott Williams & Wilkins.
scanner is inserted inside the bore of the magnet to allow
11. Cherry SR, Louie AY, Jacobs RE: The integration of
simultaneous acquisition of PET and MRI images of the
positron emission tomography with magnetic reso-
brain. The field strength of the MRI scanner is 3╯T.
nance imaging. Proc IEEE 96:416-438, 2008.
B, Simultaneously acquired 18F-fluorodeoxyglucose PET
images (red color scale) superimposed on MRI images
(grayscale) in a normal subject. A single transverse, BIBLIOGRAPHY
coronal, and sagittal slice from the three-dimensional
The following is an informative general review on
PET/MRI dataset is shown. (Courtesy Dr. Ciprian Catana
hybrid imaging:
and Dr. A. Gregory Sorenson, MGH/HST, Athinoula A.
Martinos Center for Biomedical Imaging, Charlestown, Townsend DW: Multimodality imaging of structure and
MA.) function. Phys Med Biol 53:R1-R39, 2008.
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chapter
20
Digital Image
Processing in Nuclear
Medicine
Image processing refers to a variety of tech- purpose microprocessor. Such devices can be
niques that are used to maximize the infor- programmed to perform a wide variety of
mation yield from a picture. In nuclear tasks, but they are relatively large and not
medicine, computer-based image-processing very energy efficient. For very specific tasks,
techniques are especially flexible and power- an application-specific integrated circuit often
ful. In addition to performing basic image is used. ASICs are compact and energy effi-
manipulations for edge sharpening, contrast cient, but their functionality is hardwired
enhancement, and so forth, computer-based into their design and cannot be changed.
techniques have a variety of other uses that Examples of their uses include digitizing
are essential for modern nuclear medicine. signals (analog-to-digital converters) and
Examples are the processing of raw data for comparing signal amplitudes (pulse-height
tomographic image reconstruction in single analyzers and multichannel analyzers). Other
photon emission computed tomography categories of microprocessors include digital
(SPECT) and positron emission tomography signal processors (DSPs) and graphics pro-
(PET) (see Chapters 16 to 18), and correcting cessing units. These devices have limited pro-
for imaging system artifacts (e.g., Chapter 14, grammability, but they are capable of very
Section B, and Chapter 18, Section D). fast real-time signal and image processing,
Another important example is time analysis such as 3-D image rotation and similar types
of sequentially acquired images, such as is of image manipulations.
done for extracting kinetic data for tracer The technology of microprocessors and
kinetic models (see Chapter 21). Computer- computers is undergoing continuous and
based image displays also allow three- rapid evolution and improvement, such
dimensional (3-D) images acquired in SPECT that a “state-of-the-art” description rarely
and PET to be viewed from different angles is valid for more than a year or, in some
and permit one to fuse nuclear medicine cases, even a few months. However, the end
images with images acquired with other result is that the usage of computers and
modalities, such as computed tomography microprocessors in nuclear medicine is ubiq-
(CT) and magnetic resonance imaging (MRI) uitous. They are used not only for acquisi-
(see Chapter 19). Computer-based acquisition tion, reconstruction, processing, and display
and processing also permit the raw data and of image data but also for administrative
processed image data to be stored digitally applications such as scheduling, report gen-
(e.g., on computer disks) for later analysis eration, and monitoring of quality control
and display. protocols.
All of these tasks are performed on silicon- In this chapter, we describe general con-
based processor chips, generically called cepts of digital image processing for nuclear
microprocessors. The central processing unit medicine imaging. Additional discussions of
(CPU) of a general purpose computer, such as specific applications are found in Chapters 13
a personal computer, is called a general to 19 and Chapter 21.
363
364 Physics in Nuclear Medicine
Active area of
gamma camera Detected Pixel corresponding
radiation event to event location
x Image matrix
FIGURE 20-2 Subdivision of the gamma camera detector area for generating a digital image. The photomultiplier
tube signals are analyzed using analog-to-digital converters to assign the digital matrix location for each detected
event.
for “binary digit”). In general, an n-bit binary in a pixel exceeds the allowed pixel depth, the
number can represent decimal numbers with count for that pixel is reset to 0 and starts over,
values between zero and (2n − 1). which can lead to erroneous results and image
Binary numbers are employed in computer artifacts.
systems because they can be represented con- Pixel depth also affects the number of gray
veniently by electronic components that can shades (or color levels) that can be repre-
exist only in an “on” or “off ” state. Thus an sented within the displayed image. In most
n-bit binary number can be represented by computer systems in use in nuclear medicine,
the “on” or “off ” state of a sequence of n such 8 bits equals a byte of memory and 16 bits
components. To communicate sensibly with equals a word of memory. The pixel depth,
the outside world, the binary numbers used therefore, frequently is described as “byte”
within the computer must be converted into mode or “word” mode.*
decimal integers or into decimal numbers and
fractions. The latter are called floating point 2. Spatial Resolution and Matrix Size
numbers. The methods by which binary The spatial resolution of a digital image is
numbers are converted to decimal format are governed by two factors: (1) the resolution of
beyond the scope of this presentation and can the imaging device itself (such as detector or
be found in more advanced texts on computer collimator resolution) and (2) the size of the
systems. pixels used to represent the digitized image.
Digital images are characterized by matrix For a fixed field-of-view, the larger the number
size and pixel depth. Matrix size refers to the of pixels, that is, the larger the matrix size,
number of discrete picture elements in the the smaller the pixel size (Fig. 20-3). Clearly,
matrix. This in turn affects the degree of a smaller pixel size can display more image
spatial detail that can be presented, with detail, but beyond a certain point there is no
larger matrices generally providing more further improvement because of resolution
detail. Matrix sizes used for nuclear medicine limitations of the imaging device itself. A
images typically range from (64 × 64) to (512 question of practical importance is, At what
× 512) pixels. Matrix size virtually always point does this occur? That is, how many
involves a power of 2 (26 and 29 in the previous pixels are needed to ensure that significant
examples) because of the underlying binary detail is not lost in the digitization process?
number system used in the computer. The situation is entirely analogous to that
Pixel depth refers to the maximum number presented in Chapter 16 for sampling require-
of events that can be recorded per pixel. Most ments in reconstruction tomography. In par-
systems have pixel depths ranging from 8 bits ticular, Equation 16-13 applies—that is, the
(28 = 256; counts range from 0 to 255) to 16 bits
(216 = 65,536; counts range from 0 to 65,535).
Note again that these values are related to the *Most modern computer CPUs have 32-bit or 64-bit pro-
cessors. This means they can process data 32 or 64 bits
underlying binary number system used in the at a time; however, this is largely independent of image
computer. When the number of events recorded display and how pixel values are stored.
366 Physics in Nuclear Medicine
64 × 64 32 × 32
linear sampling distance, d, or pixel size, larger pixels) to diminish the visibility of
must be smaller than or equal to the inverse noise in the final digitized image.
of twice the maximum spatial frequency, kmax,
EXAMPLE 20-1
that is present in the image:
What is the approximate spatial resolution
d = 1/(2 × kmax ) (20-1) that can be supported for a 30-cm diameter
field-of-view using a 64 × 64 matrix? A 128 ×
This requirement derives directly from the 128 matrix? Assume that the original data
sampling theorem discussed in Appendix F, are noise free.
Section C.
Once this sampling requirement is met, Answer
increasing the matrix size does not improve
spatial resolution, although it may produce 64 × 64 matrix
a cosmetically more appealing image with
less evident grid structure. If the sampling A 64 × 64 image matrix results in a pixel size
requirements are not met (too coarse a of 300╯mm/64 = 4.69╯mm. From Equation
grid), spatial resolution is lost. The maximum 20-2, this would be suitable for image resolu-
spatial frequency that is present in an image tion given by
depends primarily on the spatial resolution FWHM 3 × pixel size = 14.06 mm
of the imaging device. If the resolution of
the device is specified in terms of the full 128 × 128 matrix
width at half maximum (FWHM) of its line-
spread function (Chapter 15, Section B.2), FWHM 3 × 300 mm/128 = 7.03 mm
then the sampling distance (pixel size) should
not exceed about one third of this value to The values calculated in Example 20-1 rep-
avoid significant loss of spatial resolution, resent the approximate levels of imaging
that is, system resolution that could be supported
FWHM without loss of imaging resolution for the
d (20-2) specified image and matrix sizes. The practi-
3 cal effects of undersampling depend as well
This applies for noise-free image data. With on the information contained in the image
added noise it may be preferable to relax the and whether it has a significant amount of
sampling requirement somewhat (i.e., use actual spatial frequency content near the
20 • Digital Image Processing in Nuclear Medicine 367
resolution limit of the imaging device. Practi- independently generated red, green, and blue
cal experimentation sometimes is required to color channels].
determine this for a particular type of imaging One commonly used color scale, the pseudo�
procedure. color scale (sometime known as the rainbow
or spectrum color scale), assigns different
3. Image Display colors from the visible spectrum, ranging
Digital images in nuclear medicine are dis- from blue at the low (“cool”) end, through
played on cathode ray tubes (CRTs) or flat- green, yellow, and red (“hot”), for progres-
panel displays such as liquid crystal displays sively increasing pixel values. This is an
(LCDs). In addition to their use at the site of intrinsically nonlinear scale, because the
the imaging device, displays are an essential viewer does not perceive equal significance for
component of picture archival communica- successive color steps. A somewhat more
tions systems (PACS) networks, for remote natural scale, the so-called heat or hot-body
viewing of images (see Section C). The spatial scale, assigns different shades of similar
resolution of the display device should exceed colors, such as red, yellow, and white, to pro-
that of the underlying images so as not to gressively increasing pixel values, corre-
sacrifice image detail. In general, the display sponding to the colors of an object heated to
devices used in nuclear medicine computer progressively higher temperature. In both
systems and in radiology-based PACS net- examples, the colors are blended to produce a
works comfortably exceed this requirement. gradual change over the full range of the
Typical high-resolution CRTs have 1000 or scale. Figure 20-4 shows the same image dis-
more lines and a typical LCD might have played with different color scales.
1536 × 2048 elements. The major problem with the use of color
Individual pixels in a digital image are dis- scales to represent pixel count levels is that
played with different brightness levels, they are somewhat unnatural and also can
depending on the pixel value (number of produce contours, such as apparently sharp
counts or reconstructed activity in the pixel) changes in pixel values, where none actually
or voxel value. On grayscale displays, the exist. A more practical use of color displays is
human eye is capable of distinguishing for color coding a second level of information
approximately 40 brightness levels when they on an image. For example, in combined-
are presented in isolation and an even larger modality imaging of PET or SPECT with CT
number when they are presented in a sequence (see Chapter 19), the anatomic (CT) image
of steps separated by sharp borders. Image often is displayed using a standard gray scale,
displays are characterized by the potential whereas the functional (PET) image is shown
number of brightness levels that they can using a color scale. Such a display clearly dif-
display. For example, an 8-bit grayscale ferentiates between the two types of images,
display can potentially display 28 = 256 differ- whereas a simple overlay of two grayscale
ent brightness levels. Such a range is more images would be confusing.
than adequate in comparison with the capa- Hard-copy images can be produced on
bilities of human vision. In practice, the effec- black-and-white transparency film from a
tive brightness scale often is considerably less CRT display. Single-emulsion films are used
than the physical limits of the display device to minimize blurring of the recorded image,
because of image noise. For example, if an especially when images are minified for
image has a root mean square noise level of compact display on a single sheet of film. The
1%, then there are not more than 100 signifi- CRT display intensity must be calibrated to
cant brightness levels in the image, regard- compensate for the sensitometric properties
less of the capabilities of the display device. of the recording film to match the monitor
Digital images also can be displayed in display. Computer printers are now commonly
color by assigning color hues to represent dif- used to record hard-copy images and a range
ferent pixel values. The human eye can dis- of different technologies and media are avail-
tinguish millions of different colors, and color able depending on requirements such as
displays are capable of producing a broader quality (resolution and gray-scale range), cost
dynamic range (i.e., number of distinguish- and printing speed.
ably different levels) than can be achieved in
black-and-white displays. For example, a 4. Acquisition Modes
true-color display with 24-bit graphics can Digital images are acquired either in frame
generate nearly 16.8 million different colors mode or in list mode. In frame-mode acquisi-
[224 = (28)3, in which the 3 represents the tion, individual events are sorted into their
368 Physics in Nuclear Medicine
A C
B D
FIGURE 20-4 The same reconstructed transaxial image slice rendered in different color scales. A, Grayscale, high-
intensity white; B, inverted grayscale, high-intensity black; C, hot-wire or hot-body scale; D, pseudocolor spectral scale.
The slice is from a PET scan of the brain using the radiotracer 18F-fluorodeoxyglucose. (Original image courtesy Siemens
Molecular Imaging, Knoxville, TN).
appropriate x-y locations within the digital improved, but the total counts per frame and
image matrix immediately after their position per pixel are reduced compared with slower
signals are digitized. After a preset amount of frame rates.
time has elapsed or after a preset number In list-mode acquisition, the incoming x
of counts have been recorded, the acquisition and y position signals from the camera are
of data for the image is stopped and the pixel digitized, but they are not sorted immediately
values [p(x,y) = number of counts per pixel] into an image grid. Instead, the x and y posi-
are stored in computer memory. tion coordinates for individual events are
When a series of such images is obtained stored, along with periodic clock markers
sequentially, individual images in the (e.g., at millisecond intervals). This permits
sequence are referred to as “frames.” Clearly, retrospective framing with frame duration
the image matrix size (e.g., 64 × 64, 128 × 128, chosen after the data are acquired.
and so forth) must be specified before the List-mode acquisition permits greater flex-
acquisition begins. Additionally, the time ibility for data analysis. However, it is not an
duration of the frame sets a limit on the tem- efficient method for using memory space
poral accuracy of the data. For example, if during acquisition for conventional imaging,
the frame is acquired during a 1-minute especially for high-count images, because
period, the number of counts recorded in each every recorded event occupies a memory loca-
pixel represents the integrated number of tion. Thus a 1-million count 128 × 128 image
counts during the 1-minute acquisition period recorded in list mode would require 1 million
and cannot be subdivided retrospectively into memory locations, whereas in frame mode
shorter time intervals. When faster framing the same image would require only approxi-
rates are used, such as for cardiac blood-pool mately 16,000 memory locations. However,
imaging, temporal sampling accuracy is list mode can actually be more efficient in
20 • Digital Image Processing in Nuclear Medicine 369
FIGURE 20-5 Effect of changing the distribution of gray levels on image contrast. Left, Original image with uniform
distribution of gray levels. Center, Gray scale compressed (fewer levels) in high-count (dark) regions to improve the
visualization of soft tissues. Right, Gray scale compressed in low-count (light) regions to suppress soft tissues and
visualize only bone. (Image courtesy Siemens Medical Solutions, USA, Inc.)
Sagittal plane
Coronal plane
Transverse plane
B
FIGURE 20-6 A, Orientation of transverse (also known as transaxial), coronal and sagittal sections. B, Orthogonal
views (transverse, coronal, sagittal) of an 18F-fluorodeoxyglucose PET brain study in which the imaging field-of-view
covers the entire head. (A, Reproduced from http://en.wikipedia.org/wiki/File:Human_anatomy_planes.svg#file. B,
Images courtesy CTI PET Systems, Inc., Knoxville, TN.)
20 • Digital Image Processing in Nuclear Medicine 371
Projection image
2-D views of the object from many projection combine images acquired with different radio-
directions. Another approach is to display only nuclides or acquired with different modali-
the surface pixel values (surface rendering). ties. Most image-processing software allows
An approach that highlights internal features one to add, subtract, multiply, and divide
is to display only the pixel with the maximum single images or 3-D image volumes. These
value along the projection direction (maximum operations typically are applied on a pixel-by-
intensity projection). pixel basis. Figure 20-8 is an example of a
By computing projection views at a set of simple frame arithmetic operation: subtrac-
angles around the object and presenting them tion. The study illustrated is a visual stimula-
in a continuous loop, one can create movies in tion using 15O-labeled water as a flow tracer.
which it appears that the object is rotating in Visual stimulation, created by having the
space. This sometimes is called cine mode. subject view a strobe light, caused an increase
These and other rendering and display algo- in blood flow to the occipital (visual) cortex,
rithms are discussed in some of the suggested while the remainder of the brain remained
readings at the end of the chapter. largely unaffected. Subtraction of an image
Another important application of image taken from a resting control study from the
processing is image arithmetic. There are a image obtained in the stimulation study pro-
number of applications in which one wishes vides a display of the blood flow changes
to see differences between images or to occurring as a result of stimulation.
372 Physics in Nuclear Medicine
FIGURE 20-8 Cerebral blood-flow images (H215O PET) acquired in the resting state (left) and during visual stimula-
tion using a flashing light (center). The stimulus causes a small increase in blood flow in the visual cortex that is virtu-
ally invisible on the image acquired during visual stimulation; however, the increase is clearly visible when the
resting-state image is subtracted from it (right).
Most digital images in nuclear medicine radiotracer distribution in the body. Conven-
are, in essence, pictures of the count density tional 2-D images also can provide informa-
in the organ or tissue of interest. Instead of tion about the relative concentration of
presenting the data in this format, one may radiotracer in different areas. Regions of
desire to first process the image data on a interest (ROIs) are used to extract numerical
pixel-by-pixel basis using a model that repre- data from these images. The size, shape, and
sents the functional process and display the position of ROIs can be defined and positioned
calculated result. Such an image, in which the by the user, using a selection of predefined
pixel values represent a calculated parame- geometric shapes (e.g., rectangles, circles).
ter, sometimes is called a parametric image. Alternatively, irregular ROIs can be created
For example, a digital ventilation image can using a cursor on the image display. The com-
be divided by a perfusion image to produce a puter then reports ROI statistics such as the
parametric image that shows the ventilation/ mean pixel value, the standard deviation of
perfusion ratio. Other examples of calculated the pixel values, and the number of pixels in
functional parameters are discussed in the ROI (Fig. 20-9). Software tools that use
Chapter 21. edge-detection algorithms also are available
for automated definition of ROIs (see Section
2. Regions and Volumes of Interest B.5).
Care must be taken in the use of ROIs to
Both PET and SPECT can provide semiquan- accurately place them on the tissues of inter-
titative, or when all appropriate corrections est, especially for applications in which
are applied, quantitative images of the radiotracer uptake or concentration are
0.0 min 0.75 min 1.25 min 1.75 min 2.25 min 2.75 min
4.5 min 7.5 min 10.5 min 13.5 min 20 min 30 min
0.3
0.25
Striatum
Radioactivity (µCi/mL)
0.2
0.15
Cerebellum
0.1
0.05
0
0 20 40 60 80 100 120
Time (min)
FIGURE 20-10 Top, PET images of the same two-dimensional (2-D) slice through the brain at different times after
administration of a bolus injection of 18F-fluoroDOPA. A region of interest (ROI) is drawn over the right striatum on
the last image and then copied to all other time points. Bottom, Time-activity curve (TAC) showing the mean value in
the ROI, converted with a calibration factor from counts per second per pixel to absolute concentration of radioactivity,
versus time for the striatum. Also shown is a TAC for the cerebellum, taken from a different 2-D image slice, demon-
strating how different brain regions can have different kinetics. Analysis of such TACs is discussed in Chapter 21.
(Adapted from Cherry SR, Phelps ME: Positron emission tomography. In Sandler MP, Coleman RE, Patton JA, et╯al
[eds]: Diagnostic Nuclear Medicine, 4th ed. Baltimore, Williams & Wilkins, 2002, p. 79.)
20 • Digital Image Processing in Nuclear Medicine 375
FIGURE 20-11 Effect of image smoothing using a gaussian filter with a full width at half maximum of 4╯mm (center)
and 8╯mm (right). Smoothing improves the signal-to-noise ratio in the images but at the expense of spatial
resolution.
location of edge
normal controls. A summary of modern image
d 2p/dx 2
FIGURE 20-14 Series of images illustrating the segmentation of the lungs on a transmission scan acquired on a
single-photon emission computed tomography system. (Original image courtesy Dr. Freek Beekman, University Medical
Delft University of Technology, The Netherlands.)
FIGURE 20-15 Top three rows, Co-registered slices from three 18fluorodeoxyglucose PET scans acquired at 1-year
intervals on the same subject. Images in each column represent the same anatomic slice, after co-registration. Bottom
row, Corresponding co-registered slices from a magnetic resonance imaging scan acquired at the time of the third PET
scan (intermodality co-registration). Images were co-registered using the Automated Image Registration software
developed by Roger Woods of the University of California-Los Angeles. Note the excellent agreement in structures
included and their locations in each slice. Some images were truncated (particularly in the left column) because parts
of the brain were outside the field-of-view in some scans. (From Woods RP, Mazziotta JC, Cherry SR: Optimizing
activation methods: Tomographic mapping of functional cerebral activity. In Thatcher RW, Hallett M, Zeffiro T, et╯al
[eds]: Functional Neuroimaging: Technical Foundations. San Diego, Academic Press, 1994, p. 54.)
378 Physics in Nuclear Medicine
addition to freeing up the image acquisition imaging equipment support this standard.
computer for additional studies, it allows a The objective of DICOM is to enable vendor-
variety of other activities to proceed simulta- independent communication not only of
neously. For example, it allows a medical phys- images but also of associated diagnostic and
icist to reprocess a study from his or her office therapeutic data and reports.
while physicians are viewing the same images A true archival system not only should
in the reading room or even at a different hos- store the image or processed image data but
pital and researchers are downloading the also should be organized around a logical
studies onto a computer in the research retrieval system that permits correlation of
laboratory. images with other types of data (e.g., reports)
Many nuclear medicine departments there- for a given patient study. That is, it should
fore employ high-speed networks to connect have the capacity of a computer database
their imaging systems together with other system and interface seamlessly with radiol-
computer systems in the institution and, via ogy, nuclear medicine, and hospital informa-
the Internet, to the outside world. These tion systems. In addition, the system must be
departments use PACS to store and move capable of protecting patient information by
images from acquisition sites to more conve- providing access only to authorized users.
nient viewing stations and to provide a
common basis for handling nuclear medicine
and all other diagnostic imaging modalities.2 REFERENCES
PACS systems in hospitals with large radiol- 1. Hill DLG, Batchelor PG, Holden M, Hawkes DJ:
ogy and nuclear medicine departments must Medical image registration. Phys Med Biol 46:R1-R45,
be capable of handling huge amounts of data, 2001.
typically several gigabytes per day (1 Gb = 2. Bick U, Lenzen H: PACS: The silent revolution. Eur
Radiol 9:1152-1160, 1999.
1012 bytes). 3. Mildenberger P, Eichelberg M, Martin E: Introduction
To facilitate the exchange and handling of to the DICOM standard. Eur Radiol 12:920-927, 2002.
images from multiple different imaging
modalities and from different vendors each
with their own custom software, image file BIBLIOGRAPHY
format standards have been developed. The General references on image processing
central standard in radiology is the Digital Gonzalez RC, Woods RE: Digital Image Processing, ed 3,
Upper Saddle River, NJ, 2008, Pearson Prentice Hall.
Imaging and Communications in Medicine (Chapters 2, 3, 6, and 10 are especially relevant.)
(DICOM) standard described in reference 3, Robb RA: Biomedical Imaging, Visualization, and Analy-
and all manufacturers producing diagnostic sis, ed 2, New York, 1999, Wiley-Liss.
chapter
21
Tracer Kinetic
Modeling
The spatial distribution of a radiotracer in the Tracer kinetic models may be very simple.
body is time varying and depends on a number For example, one method for evaluating renal
of components such as tracer delivery and function is to measure the uptake of 99mTc-
extraction from the vasculature, binding to labeled dimercaptosuccinic acid (DMSA) using
cell surface receptors, diffusion or transport a single region of interest (ROI) positioned
into cells, metabolism, washout from the over each kidney at one instant in time. “Func-
tissue, and excretion from the body. Thus the tion” in this case is determined in relative
temporal component often is very important rather than absolute physiologic units. A more
in nuclear medicine studies, and the timing rigorous approach for evaluating kidney func-
of the imaging relative to the administration tion is to measure glomerular filtration rates
of the radiopharmaceutical must be carefully (GFRs), in mLâ•›/min, using a tracer that is fil-
chosen such that the images reflect the bio- tered by the kidneys, such as 99mTc-labeled
logic process of interest. Furthermore, the diethylene triamine pentaacetic acid (DTPA).
rate of change of radiotracer concentration In this case, it is necessary to obtain serial
often provides direct information on the rate images of the kidneys and also to collect blood
of a specific biologic process. This chapter dis- samples to measure tracer concentration in
cusses how the temporal information that can the blood as a function of time. Using these
be obtained from nuclear medicine studies is data and applying an appropriate mathemati-
incorporated to provide quantitative mea- cal model, one can then calculate the GFR.
sures of physiologic parameters, biochemical Each of these approaches permits an
rates, or specific biologic events. Further assessment of “renal function” that is based
examples are provided in reference 1. on a different model for the behavior of the
kidneys. The approach of choice depends on
the medical or biologic information desired, as
A. BASIC CONCEPTS well as on the equipment available and accept-
able level of technical complexity. Developing
Dynamic nuclear medicine studies enable a model requires the investigator to synthe-
the radiotracer concentration to be measured size a large amount of biologic information
as a function of time, as shown in Figure into a comprehensive description of the
20-10. With an understanding of the biologic process of interest. This chapter summarizes
fate of the radiotracer in the body, it is pos- some of the principles and techniques in
sible to construct mathematical models with developing these models and presents some
a set of one or more parameters that can be examples of tracer kinetic models currently
fit to explain the observed time-activity used in nuclear medicine.
curves. In some cases the model parameters The following example illustrates the prin-
can be related directly to physiologic or bio- ciple of tracer kinetic techniques. Figure 21-1
logic quantities. Examples include tissue shows a hollow tube with a substance flowing
perfusion (measured in mLâ•›/minâ•›/g) and the through it. If a small amount of tracer is
rate of glucose use (measured in mol/min/g). injected instantaneously at time t and at
The mathematical models that describe the point A and the measured activity at point B
time-varying distribution of radiopharma- is plotted as a function of time, the resultant
ceuticals in the body are known as tracer time-activity curve represents a histogram of
kinetic models. the transit times for the tracer molecules
379
380 Physics in Nuclear Medicine
A B
Flow
Activity
Activity
t Time t Time
FIGURE 21-1 Illustration of use of tracer kinetics for measurement of flow. The system consists of a hollow tube
characterized by flow in the direction indicated. A bolus of tracer introduced at time t and point A produces a time-
activity curve at location B that depends on flow. Relatively higher flow (solid line) results in less dispersion and a
shorter average transit time, whereas a lower flow rate (dashed line) produces a longer average transit time. (Adapted
from Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission Tomography and Autoradiography: Principles and
Applications for the Brain and Heart. New York, 1986, Raven Press.)
TABLE 21-1â•…
SELECTED EXAMPLES OF TRACERS USED IN NUCLEAR MEDICINE
Process Tracer
Blood flow/perfusion:
Diffusible (not trapped) H215O, 133
Xe, 99m
Tc-teboroxime (heart)
201 99m
Diffusible (trapped) TlCl (heart), Tc-sestamibi (heart),
13 82 99m
NH3 (heart), RbCl, Tc-ECD (brain),
99m
Tc-tetrofosmin (heart), 62Cu-PTSM, 99m
Tc-HMPAO (brain)
99m
Nondiffusible (trapped) Tc-macroaggragated albumin (lung)
11
Blood volume CO, 51Cr-RBC, 99m
Tc-RBC
99m 99m
Ventricular function Tc-pertechnetate, Tc-DTPA
99m
Esophageal transit time/reflux Tc-sulphur colloid
99m 111
Gastric emptying Tc-sulphur colloid, In-DTPA
99m 99m
Gallbladder dynamics Tc-disofenin, Tc-mebrofenin
111
Infection In-WBC, 67Ga-citrate, 99m
Tc-WBC
133 81 99m
Lung ventilation Xe, Kr, Tc-technegas™
Metabolism:
15
Oxygen O2
11
Oxidative C-acetate
18
Glucose F-fluorodeoxyglucose
11 123
Free fatty acids C-palmitic acid, I-hexadecanoic acid
99m 18 –
Osteoblastic activity Tc-MDP, F
18
Hypoxia F-fluoromisonidazole, 62Cu-ATSM
18
Proliferation F-fluorothymidine
11
Protein synthesis C-leucine, 11C-methionine
Receptor systems:
18
Dopaminergic F-fluoro-L-dopa, 11C-raclopride, 18
F-fluoroethylspiperone, 11C-CFT
18
Benzodiazepine F-flumazenil
11
Opiate C-carfentanil
11
Serotonergic C-altanserin
123
Adrenergic I-mIBG
111
Somatostatin In-octreotide
18
Estrogen F-fluoroestradiol
ATSM, diacetyl-bis (N4-methylthiosemicarbazone); CFT, [N-methyl-11C]-2-β-carbomethoxy-3-β-(4-fluorophenyl)-tropane;
DOPA, 3,4-dihydroxyphenylalanine; DTPA, diethylenetriamine penta-acetic acid; ECD, ethyl cysteinate dimer; HMPAO,
hexamethyl propylene amine oxime; MDP, methylene diphosphonate; mIBG, metaiodobenzylguanidine; PTSM,
pyruvaldehyde bis(N4-methylthiosemithiocarbazone); RBC, red blood cell; WBC, white blood cell.
If a tracer is labeled with an element not investigation. One common use of tracers in
originally present in the compound (this is clinical nuclear medicine is to examine gross
often the case with radionuclides such as 99mTc, function and distribution, including blood flow,
123
I, and 18F), it should behave similarly to the filtration, and ventilation. Although the ele-
natural substance or in a way that differs ments represented by radionuclides such as
99m
in a known manner. The strictness of this Tc, 67Ga, 111In, and 123I are not normally
requirement depends on the process under present in biologic molecules, it is possible to
382 Physics in Nuclear Medicine
Answer
From Equation 21-2:
Vd = (1000 kBq) / (0.2 kBq/mL)
= 5000 mL Tissue
Vt
This result gives the total distribution volume, Cb V1
that is, total blood volume. The RBC volume
is given by Cb
Blood
VRBC = H × Vd
B λ V1/Vt
= 0.4 × 5000 mL
= 2000 mL FIGURE 21-2 A, Partition coefficient, λ, for tracers that
can diffuse or be transported into tissue from blood. The
value of λ is given by the ratio of tissue-to-blood concen-
More commonly, a compartment will be trations of the tracer when it has reached an equilibrium
open; that is, the tracer will be able to escape or steady-state condition. B, Partition coefficient also
from it. This applies, for example, to tracers equals the ratio of the apparent distribution volume in
that are distributed and exchanged between tissue, V1, assuming the same tracer concentration as
blood-to-tissue volume (or mass), to Vt. (From Phelps ME,
blood and tissue. In this case, after the tracer Mazziotta JC, Schelbert HR: Positron Emission Tomog-
reaches its equilibrium distribution,* the con- raphy and Autoradiography: Principles and Applications
centration in blood will typically be different for the Brain and Heart. New York, 1986, Raven Press.)
from that in the tissue (Fig. 21-2A). The ratio
of tissue concentration Ct (Bq/g) to blood con-
centration Cb (Bq/mL) at equilibrium, is called mass) of tissue; therefore combining these
the partition coefficient, λ, defined by relationships and Equation 21-3 yields
The equilibrium blood concentration, Cb, can Thus another interpretation of the partition
be directly measured by taking blood samples. coefficient is that it is the distribution volume
If one assumes that the concentration of per unit mass of tissue for a diffusible sub-
tracer in tissue is the same as the concentra- stance or tracer. This interpretation is
tion in blood (Fig. 21-2B), and applies Equa- employed in some models for estimating blood
tion 21-2, this leads to an apparent distribution flow and perfusion, as discussed in Section E.
volume in tissue given by V1 = Atâ•›/Cb, in which
At is the activity in the tissue. One also knows 4. Flux
that At = Ct × Vt, in which Vt is the volume (or Flux refers to the amount of substance that
crosses a boundary or surface per unit time
(e.g., mgâ•›/min or molâ•›/â•›min) (Fig. 21-3). It also
can refer to the transport of a substance
*Note that “equilibrium” in this case means that the between different compartments in terms of
concentration of the tracer in the compartments has flux per unit volume or mass of tissue (e.g.,
reached a constant value with time. It does not imply molâ•›/minâ•›/mL or mgâ•›/minâ•›/g).
equilibrium in the thermodynamic sense, that is, that
there is no further transport of tracer between tissue and Flux is a general term that can refer to a
blood. Thus tracer equilibrium is synonymous with the variety of processes. For example, the total
term steady state (see Section B.6). mass of RBCs moving through a blood vessel
384 Physics in Nuclear Medicine
Capillary
membrane
Blood “Free” tracer “Product” in FIGURE 21-3 Three-compartment system consist-
in tissue tissue ing of reactants in blood (Rb) and tissue (Rt) and
product in tissue (P). Fluxes between the compart-
ments, indicated by arrows, are products of the first-
k1 [Rb] k3 [Rt] order rate constants and the respective compartmental
Rb Rt concentrations. (Adapted from Phelps ME, Mazziotta
P
JC, Schelbert HR: Positron Emission Tomography
k2 [Rt] k4 [P] and Autoradiography: Principles and Applications for
the Brain and Heart. New York, 1986, Raven Press.)
per unit time is a flux. The “boundary” or the half-time of turnover, t1/2, that is, the time
“surface” in this case could be any transverse required for the original amount of tracer in
plane through the vessel. The amount of the compartment to decrease by 50% (assum-
glucose moving across a cell membrane per ing no back transfer into the compartment),
unit time also is a flux. Fluxes therefore may is given by
either be closely related or unrelated to blood
flow.
t1 / 2 = 0.693 /k (21-6)
5. Rate Constants
Rate constants describe the relationships Thus the fractional rate constant k is anal-
between the concentrations and fluxes of a ogous to the decay constant λ for radioactive
substance between two compartments. For decay, whereas the mean transit time is anal-
simple first-order processes, the rate constant, ogous to the average lifetime of a radionuclide
k, multiplied by the amount (or concentra- (see Chapter 4, Section B.3). In first-order
tion) of a substance in a compartment deter- models, transport out of a compartment
mines the flux: through a single pathway (without back-
transport) is described by a single exponential
flux = k × amount of substance in compartment function, e–kt, analogous to the radioactive
(21-5) decay factor e–λ t.
If there is more than one potential pathway
For first-order processes, the units of k are for a tracer to leave a compartment, each
(time)–1. If “amount” refers to the mass of characterized by a separate rate constant, ki,
tracer in the compartment, the units of flux then the turnover time of the tracer in the
are mass/time (e.g., mg/min). If “amount” compartment is the inverse of the sum of all
refers to con�centration of tracer in the com- these rate constants and the half-time of
partment, the units of flux are mass/time per turnover is
unit of compartment volume (e.g., mg/min/
mL), or mass/time per unit of compartment t1 / 2 = 0.693 / (k1 + k2 + … + km ) (21-7)
mass (e.g., mg/min/g). Note that, as illus-
trated by Figure 21-3, different directions of where m is the number of pathways by which
transport between two compartments can be the tracer can leave the compartment.
characterized by different rate constants. Most compartment models used in nuclear
A first-order rate constant also may repre- medicine are based on the assumption that
sent the fractional rate of transport of a sub- first-order kinetics describe the dynamics of
stance from a compartment per unit time. For the system of interest. The tracer kinetics of
example, a rate constant of 0.1╯min–1 corre- such systems are linear. That is, doubling the
sponds to a transport of 10% of the substance input (amount or concentration) doubles the
from the compartment per minute. The output (flux) of the system. As shown in
inverse of the rate constant, 1/k, is sometimes Section E, linear first-order tracer kinetic
referred to as the turnover time, or mean models adequately describe many systems
transit time, τ, of the tracer in the compart- even when the dynamics of the natural sub-
ment (in this example, 10 minutes). Similarly, stances are nonlinear.
21 • Tracer Kinetic Modeling 385
A more general expression for the relation- back into blood without undergoing any bio-
ship among rate constants, fluxes, and con- chemical reactions. This is a common occur-
centrations (or masses) is rence in actual biochemical systems and
introduces a reserve capacity into the system
flux = k × (mass or concentration of substance) n that can accommodate changes in metabolic
(21-8) supply and demand (e.g., by changing k3).
Figure 21-4 illustrates the relationship
where n refers to the order of the reaction. between first-order rate constants and the
The units of rate constants for nth order reac- relative concentrations of the substrates in a
tions (in terms of concentration) are biochemical sequence. If a substrate (S) and
[concentrations(1—n) • time–1]. Thus only first- enzyme (E) combine to form a substrate-
order rate constants represent a constant enzyme complex (SE), which then dissociates
fractional turnover and Equations 21-6 and into a product (P) with release of the enzyme,
21-7 apply only to first-order processes. the fluxes of the first-order reaction steps are
Figure 21-3 illustrates a three-compartment concentrations multiplied by the correspond-
system consisting of a blood compartment ing rate constants. If a small amount of
separated by a membrane barrier (e.g., capil- labeled substrate is introduced into the
lary wall) from two sequential tissue com- system at time zero, the tracer will go through
partments. R and P refer to chemical reactant the reaction steps, producing concentrations
and product, whereas the subscripts b and t of labeled S, SE, and P as shown in the graphs
refer to reactant in blood and tissue compart- in Figure 21-4. If k3 (the forward rate con-
ments, respectively. [Rb],* [Rt], and [P] are the stant for the reaction converting SE to E and
blood and tissue concentrations of reactant P) is reduced by 50% with all the other rate
and product, whereas the fluxes between the constants remaining unchanged, the concen-
compartments are the first-order rate con- trations of labeled S, SE, and P are then rep-
stants, k1, k2, k3, and k4, multiplied by corre- resented by the dotted orange lines in Figure
sponding concentrations. The thicknesses of 21-4. Decreasing k3 causes a slower produc-
the arrows in Figure 21-3 are proportional to tion of P and causes a compensatory increase
the magnitude of the corresponding rate con- in labeled S and SE.
stant. In this example, the rate constants into
and out of tissue are larger than the corre- 6. Steady State
sponding rate constants between the reactant The term steady state refers to a condition
and product compartments in tissue. Thus in which a process, parameter, or variable is
the majority of the reactant initially trans- not changing with time. For example, a flux
ported into the tissue space is transported through a biochemical pathway is said to be in
a steady state when the concentration of reac-
tants and products are not changing with time.
*The notation [X] is used to denote the concentration In all tracer kinetic models, it is assumed that
(usually in units of g/mL or mol/mL) of substance X. the underlying process that is being measured
k0 k1 k3 k5
k2 k4
Time (t) t t
FIGURE 21-4 Illustration of tracer kinetics of a chemical reaction sequence. First-order rate constants (k0, k1, k2, k3,
k4, k5) characterize the various reaction steps, whereas S refers to substrate, E refers to enzyme, P is product, and SE
is the substrate-enzyme complex. The time-activity relationships for concentrations of labeled S, SE, and P are shown
for a particular value of k3 (solid purple line) and with k3 reduced by 50% (dotted orange line). (From Phelps ME,
Mazziotta JC, Schelbert HR: Positron Emission Tomography and Autoradiography: Principles and Applications for the
Brain and Heart. New York, 1986, Raven Press.)
386 Physics in Nuclear Medicine
term blood flow, symbolized by F, is used to extraction are useful for studying the trans-
denote either blood flow or blood flow per port properties of substrates and drugs.
mass of tissue. The units indicate which An important concept relating the pro-
quantity is being discussed. cesses of blood flow, flux, and extraction is
In addition to its dependence on blood the Fick principle. This principle is based on
flow, the uptake of a tracer by tissue depends the conservation of mass and states that,
on tissue extraction and clearance. Extrac- under steady-state conditions, the net uptake
tion is defined in two different contexts: net of a tracer (or other substance) is simply the
and unidirectional. Net extraction refers to difference between the input to and output
the difference in steady-state tracer concen- from the organ or tissue. If the input (arte-
trations between the input and output blood rial) concentration of the tracer is CA (mg/
flow of an organ. If the input (arterial) con- mL) and the output (venous) concentration is
centration is CA, and the output (venous) CV (mgâ•›/mL), and the blood flow to the organ
concentration is CV, the net extraction frac- is F (mLâ•›/min), then the net uptake rate, U
tion, En, is defined as (mg/min), is given by
If there is no metabolism of the tracer, that As an example, if the arterial and venous
is, if all the tracer delivered to the tissue concentrations of oxygen and the blood flow
eventually is returned to the blood, the net to an organ are measured, Equation 21-14
extraction is zero. This situation applies, for can be used to determine the oxygen utiliza-
example, to inert diffusible blood flow tracers tion rate for that organ. If blood flow F in
when steady-state conditions for the tracer Equation 21-14 is replaced by blood flow per
are reached. mass of tissue (perfusion), then the uptake or
Unidirectional extraction refers to the utilization is given in units of utilization per
amount of tracer extracted only from blood to mass of tissue (mg/min/g).
tissue. It does not include the amount trans- The Fick principle can be employed only
ferred back from tissue to blood. Thus the under steady-state conditions. An alternative
unidirectional extraction fraction, Eu, gener- approach that is applicable to non–steady-
ally is larger than the net extraction fraction. state conditions is the Kety-Schmidt method,
An exception to this general rule occurs with which is discussed in Section E.4.
O2. Virtually all oxygen extracted by tissue is The extraction of tracers generally occurs
metabolized; thus the net and unidirectional across membranes or through the fenestra-
extraction fractions are the same. For essen- tions* found in capillaries. The extraction
tially all other substances, a major portion of fraction of a tracer depends on the capillary
what is extracted by the tissue is transported surface area, S, the capillary permeability for
back to blood. This is the situation repre- the tracer, P, and blood flow through the capil-
sented by the bidirectional transport in the laries, F. A simple model relating these quan-
model shown in Figure 21-3. tities was developed by Renkin2 and Crone.3
Extraction fractions are expressed as frac- Figure 21-6 illustrates an idealized capillary
tions or as percentages and can be measured
using tracer kinetic techniques. To determine
net extraction, it is necessary to measure the
input and output concentrations of the tracer
in the blood under steady-state conditions, F F
that is, after the concentrations have reached
constant values. The route of administration
of the tracer is unimporÂ�tant in this case. For P×S
example, the tracer can be administered by
FIGURE 21-6 Renkin-Crone capillary model. The capil-
constant infusion or as a bolus into a periph- lary is assumed to be a rigid tube, and extraction from
eral vein. blood to tissue is characterized by the product of the
Unidirectional extraction can be measured permeability, P, and surface area, S. Blood flow through
by observing the rate of uptake by the tissue the capillary is F.
or organ immediately after injection of
the tracer, that is, when the blood concentra-
tion is maximum and the tissue concentration *Fenestrations are small gaps found between the junc-
is zero. Measurements of unidirectional tions of cells in the capillary wall.
388 Physics in Nuclear Medicine
(i.e., rigid tube) through which is passing a wall, P × S, or decreasing the blood flow
tracer with flow F. It is assumed that the through the capillary. For a given value of P
concentration of tracer across the cross- × S, the greater the flow, F, the shorter the
section of the capillary at any point along its residence time of the tracer in the capillary,
length is constant and that the extraction of and, thus, the less the chance that the tracer
tracer from the capillary to the tissue at any will escape through the capillary wall. This is
point is proportional to the concentration of illustrated graphically in Figure 21-7.
the tracer in the blood. It is further assumed On the other hand, the amount of material
that extraction is unidirectional; that is, there entering the tissue depends on the product of
is no back-transfer of the tracer from tissue blood flow times extraction fraction, F × E.
to blood. This product is sometimes referred to as
For this simple model, it can be shown that clearance and has the same units as flow (i.e.,
the unidirectional extraction fraction Eu for mLâ•›/min or mLâ•›/minâ•›/g). In essence, it repre-
the capillary is given by sents “virtual flow” from the capillary into the
tissue. Typically the increased amount of
Eu = 1 − e− ( P × S/F ) (21-15) tracer that is delivered to the capillary with
increasing blood flow more than offsets the
Thus the extraction fraction depends only decrease in the extraction fraction, with the
on the permeability-surface area product, P × net result that clearance increases with flow.
S (mLâ•›/min), and on flow, F. This equation also This is illustrated graphically in Figure 21-8.
can be stated in terms of perfusion, by replac- Note that for small values of P × S, that is,
ing blood flow with perfusion (mLâ•›/minâ•›/g) and low flow across the capillary membrane, clear-
the permeability-surface area product with P ance is low and reaches a plateau value for
× S for a capillary network per mass of tissue relatively low values of capillary blood flow,
(mLâ•›/minâ•›/g). F, whereas for large values of P × S, clearance
continues to increase with increasing flow
EXAMPLE 21-2 through the capillaries. This indicates that
What is the unidirectional extraction fraction the clearance or deposition of a tracer into
for the diffusible tracer 13NH3 in the brain if tissue will have a high or low dependence on
P × S = 0.25╯mLâ•›/minâ•›/g and blood flow to the blood flow, depending on whether it has a
brain (perfusion) is 0.50╯mLâ•›/minâ•›/g? high or low value of P × S.
Clearance of tracers from tissue to blood
Answer also is used in tracer kinetic modeling. The
From Equation 21-15: most common use of tissue-to-blood clearance
is in the measurement of bidirectional trans-
Eu = 1 − e− (0.25 / 0.50) = 0.39 port and blood flow.
2.0
P × S 5.0
1.6
Clearance (E × F )
1.2 P × S 2.0
0.8 P × S 1.0
0.4 P × S 0.5
P × S 0.2
0.0
0.4 0.8 1.2 1.6 2.0 2.4 2.8
Flow (mL/min/g)
FIGURE 21-8 Clearance (flow × unidirectional extraction fraction) versus flow for various values of the permeability-
surface area product, P × S, for the Renkin-Crone model (solid red lines, Equation 21-15) and for a compartmental
model description (dashed red lines, Equation 21-20). P × S is in units of mLâ•›/minâ•›/g. The solid blue line corresponds
to the situation where E=1. (From Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission Tomography and Auto-
radiography: Principles and Applications for the Brain and Heart. New York, 1986, Raven Press.)
Tissue
k1 extraction P × S
0.8
0.4
k1
k3
0.0 1 2 3
1.2 k2
Count rate
0.8
0.4
0.0
1.2
k1
k3
2 3
Count rate
0.8
k2
1 k4
0.4 4
k5
0.0
0 20 40 60 80 100 0 20 40 60 80 100
Time (min) Time (min)
FIGURE 21-11 Input function and tissue response (sum of the tracer concentration in tissue) for two different models
and for two different shapes of input functions. Different input functions produce different tissue responses for a given
model configuration (top two rows), whereas the same input function produces different tissue responses for two dif-
ferent model configurations (bottom two rows). (From Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission
Tomography and Autoradiography: Principles and Applications for the Brain and Heart. New York, 1986, Raven Press.)
392 Physics in Nuclear Medicine
The impulse response of a linear system is the the radiotracer distribution are generated
system’s response when presented with an and an appropriate model is applied.
impulse as an input function. An impulse is in Once the RBCs have distributed uniformly
essence a function of infinitely short duration throughout the vascular system (i.e., equilib-
with an undefined magnitude at the origin and rium is reached), the gamma camera images
that has an integrated value of one if summed will reflect regional blood volume. If the dis-
over all time. It can be thought of as an “ideal- tribution of activity over the left ventricle is
ized bolus” input given instantaneously (i.e., plotted as a function of time by gating the
beyond zero time it has a zero value). In reality, acquisition to the electrocardiogram signal,
a practical “impulse” delivery of tracer to a changes in ventricular volume caused by
system has a duration shorter than the short- cardiac contractions can be seen (Fig. 21-12).
est vascular transit time through the organ. This permits calculation of the ventricular
In this case there is no significant clearance ejection fraction (EF) because the relative
of the tracer from the organ until after all the number of counts within the ventricle is pro-
tracer has been delivered. portional to the blood volume of the ventricle
(see Section B.3).
E. EXAMPLES OF DYNAMIC IMAGING EXAMPLE 21-3
AND TRACER KINETIC MODELS 99m
Tc-labeled RBCs are injected intravenously
and the number of counts within the left ven-
In this section we show examples of the use tricle are plotted as a function of time (Fig.
of dynamic imaging and tracer kinetic models 21-12) after the labeled RBCs have equili-
that are relatively simple and instructive. In brated within the blood pool. Calculate the
research applications of nuclear medicine, a left ventricular EF using the data shown.
wide variety of more complex models are
employed that are beyond the scope of this Answer
text. In many cases, there is considerable The EF is defined as the difference between
debate over the exact formulation of these the end-diastolic volume (EDV) and the end-
complex models and the interpretation of the systolic volume (ESV) divided by EDV.
model parameters. Research in this area is of Therefore,
continued importance, particularly with the EF = (EDV − ESV ) /EDV
ongoing development of new radiotracers.
= (13 − 7) /13
1. Cardiac Function and Ejection = 46%
Fraction
99m
Tc-labeled RBCs are used for dynamic
(first-pass) and equilibrium-gated studies of 2. Blood Flow Models
the heart. If a bolus of 99mTc-labeled RBCs is Many tracer kinetic methods and models to
injected intravenously and their distribution measure blood flow exist. Virtually all such
through the thorax as a function of time is methods are included in one of three
imaged dynamically with a gamma camera,
the images will show the flow of blood
through the venous system into the right
atrium and right ventricle, to the lungs, and
then to the left atrium, left ventricle, and out
through the aorta to the systemic circulation.
counts/frame
13
Abnormalities in this flow pattern (such as
Relative
categories: trapping, clearance, and equilib- If labeled microspheres are injected into
rium techniques. These techniques can be the left atrium or ventricle, they are distrib-
implemented by administering compounds uted to individual organs in proportion to the
labeled with either gamma-emitting or blood flow to the organ. If the total activity of
positron-emitting isotopes and imaging their microspheres injected is At, blood flow to an
distribution with gamma cameras, single- organ can be calculated from
photon emission computed tomography
(SPECT), or positron emission tomography F (mL / min) = C.O.(mL / min) × ( A o /At )
(PET) scanners (see Table 21-1). All three (21-21)
techniques require measuring the concentra-
tion of tracer in arterial blood if quantitative where Ao is the activity of microspheres accu-
estimates of blood flow in units of mLâ•›/min or mulated in the organ (assuming 100% are
mLâ•›/minâ•›/g (perfusion) are desired. trapped) and C.O. is the cardiac output (mL
In trapping methods, tracers are used that of blood per minute). Ao is determined by
are distributed to organs in proportion to tissue sampling or from quantitative imaging
blood flow but that are then trapped, either measurements. Cardiac output must be mea-
physically in the circulation (e.g., trapping of sured independently as described later. Organ
macro�aggregated albumin labeled with 99mTc perfusion, that is, blood flow per gram of
in the pulmonary capillaries in lung perfusion tissue, is then given by
studies), or metabolically in tissue (e.g., 13NH3
and 99mTc-sestamibi). F (mL / min / g) = C.O. × [( A o /mo ) At ]
Clearance methods require injecting meta-
bolically inert labeled tracers that also are (21-22)
distributed in proportion to flow but that do
not remain trapped in the vascular or tissue where Ao╛╛/mo is the concentration of activity
spaces. The rate of washout, or clearance, of in the organ or the measured tissue sample.
these tracers depends on blood flow. Either If the labeled microspheres are not 100%
nondiffusible tracers that remain within the trapped, Ao will be reduced and Equations
vascular compartment or diffusible tracers 21-21 and 21-22 will lead to underestimations
that distribute in both the tissue and vascu- of flow or organ perfusion. This effect is illus-
lar compartments can be used. As discussed trated graphically in Figure 21-8 for tracers
later, with both classes of tracers, the math- with a P × S product below the value required
ematical approach to measuring blood flow is for 100% clearance over the blood flow range
similar. studied.
Equilibrium techniques require adminis- Frequently, cardiac output is difficult to
tering a continuous supply of a diffusible measure. In such cases, flow to a single organ
blood flow tracer, waiting until a tracer steady can be determined by a modification of the
state has been reached, and then imaging the method just described, known as the reference
distribution. This approach uses very short sample technique. In this technique, arterial
half-life radionuclides such as 15O (T1/2 = 122 blood is withdrawn at a rate S (mLâ•›/min) during
seconds) in which equilibrium is established the time when the microspheres are flowing to
by removal of the tracer from tissue by the the organ, and the total activity of the blood
rate of blood flow and the rate of radioactive sample withdrawn, As, is determined. Blood
decay. This method is not commonly used and flow to the organ then is calculated from
is not discussed further here.
F = S(mL / min) × ( A o /As ) (21-23)
3. Blood Flow: Trapped Radiotracers
A simple trapping method for measuring where Ao is the activity of microspheres
blood flow employing nondiffusible tracers is trapped in the organ. Perfusion of blood into
the labeled microsphere technique. Micro- the organ is calculated from
spheres are spherical or irregularly shaped
small particles that are larger than capillar- F = S × [( A o /mo ) /As ] (21-24)
ies and embolize (become lodged in) the first
capillary bed they encounter. They remain Although the microsphere technique is con-
within the capillary system for a time that is ceptually simple, it requires injection of the
sufficiently long so that particle breakdown tracer into the left atrium (rather than intra-
and excretion are insignificant during the venously) to avoid extraction of particles
measurement period. by the lungs. This technique also causes
394 Physics in Nuclear Medicine
F = λâ•›/τ. λ
=
∫ 0
(CA (t) − CV (t)) dt
= τ (21-29)
The problem of V varying with flow, dis- F CE
cussed earlier for nondiffusible tracers, does
not exist to any significant degree with diffus- where CA(t) and Câ•›Vâ•›(t) are the arterial and
ible tracers. The term V with diffusible tracers venous concentrations as a function of time
is the tissue volume that does not change and CE is the equilibrium concentration in the
appreciably with changes in blood flow. Thus blood, usually approximated by a venous
changes in 1/τ are directly proportional to value at a selected time (e.g., 10 minutes)
flow. In addition, τ is longer for diffusible after the initiation of the inhalation. Typical
tracers (i.e., 30 to 100 seconds for brain) than values for this approach are τ = 2 minutes,
for nondiffusible tracers (3 to 6 seconds for which, from Equation 21-27 yields a flow of
brain). Because of the longer values of τ and approximately 0.5╯mLâ•›/minâ•›/g of brain tissue.
the linear relationship between τ and blood A completely analogous approach with nuclear
flow with diffusible tracers, they usually medicine imaging devices (e.g., PET and
provide more accurate and convenient mea- SPECT) permits one to perform these calcula-
surements of blood flow than those obtained tions regionally in the brain or other tissues
with nondiffusible tracers. However, λ usually and also produces estimates of blood flow
is measured in normal tissue, and it may vary using compartmental modeling approaches
from this value in pathologic tissues. For with a measured arterial input function and
example, 15O-labeled water has little variabil- serial images of the tissue (i.e., venous efflux
ity,1 whereas 133Xe has considerable variabil- concentration measurements are not neces-
ity4 between normal and diseased tissue. sary).6 Freely diffusible tracers used for
An example of the application of the central studies of cerebral blood flow include 15O-
volume principle is the Kety-Schmidt method water and 15O-butanol, and these are typi-
for measuring cerebral blood flow with cally introduced into the body by intravenous
inhaled, diffusible, inert gasses (e.g., nitrous bolus injection. Equilibrium approaches to
oxide or krypton).5 This approach is based on measuring blood flow using continuous infu-
the assumption of a constant partition coef- sion of short half-life (usually 15O-labeled) dif-
ficient of 1╯mL╛/g in the case of nitrous oxide fusible tracers also have been developed.7
and krypton in the brain. Blood flow is given One very simple method for determining
by (Equation 21-26) the mean transit time in nuclear medicine
396 Physics in Nuclear Medicine
A (0)
known, blood flow) is the “area/height”
method. A very short bolus of a freely diffus-
ible tracer such as 133Xe is injected. A gamma
camera then is used to image the washout of
A (t )
the tracer from the organ of interest over
time. It can be shown that the mean transit
time is8
∞
λ
=τ=
∫0
A(t) dt
(21-30)
Time (min)
F A(0)
FIGURE 21-13 Tissue time-activity curve following
in which A(t) is the amount of the tracer in bolus injection of a blood flow tracer. The total amount of
activity detected in a given tissue region is plotted as a
tissue as a function of time after the injection function of time. The maximum activity at time zero
and A(0) is the amount of tracer in the tissue represents A(0). From Equation 21-30, the mean transit
just after the bolus has been delivered. Figure time, τ, is given by the area under the curve divided by
21-13 illustrates this approach graphically. the height of the curve, A(0). This method often is referred
to as the “area/height” method.
Vm
0.0
Km 0.4 0.8 1.2 1.6 2.0 2.4 2.8
Substrate concentration (mg/mL)
FIGURE 21-14 Graphical illustration of Michaelis-Menten enzyme kinetics. The rate of a reaction (i.e., the reaction
flux R) is plotted against substrate concentration [S] using Equation 21-32. Note that when the substrate concentration
equals Km, the reaction rate is Vm/2. As the substrate concentration increases, the reaction rate gradually approaches
Vm. (From Phelps ME, Mazziotta JC, Schelbert HR: Positron Emission Tomography and Autoradiography: Principles
and Applications for the Brain and Heart. New York, 1986, Raven Press.)
substrate S, then [S′] is of a much lower value As an example of an analog tracer approach
than [S]. Therefore to modeling an enzymatic process, consider
the Sokoloff deoxyglucose method9 or the
Vm × [S] analogous approach with PET using 18F-labeled
R≅ (21-35)
[S] + K m FDG for measuring glucose metabolism in the
brain.10 Glucose supplies 95% to 99% of the
Vm′ × K m /K m′ brain’s energy in normal physiologic states,
R′ ≅ [S ′ ] (21-36)
[S] + K m and the rate of glucose use is an excellent
indicator of energy-requiring functions of the
R is simply the original rate of the process brain.
(Equation 21-32) unaffected by the presence FDG is an analog of glucose that is similar
of the tracer S′, whereas R′ is a linear function to glucose in several respects. Like glucose, it
of [S′] as long as [S′] remains much less than is transported from the blood to the brain by
[S] (i.e., as long as the tracer condition holds). a carrier-mediated diffusion mechanism.
Therefore the tracer concentration [S′] is lin- HexoÂ�kinase catalyzes the phosphorylation of
early related to the reaction rate R′ and linear glucose to glucose-6-PO4 and FDG to FDG-
modeling techniques are appropriate for 6-PO4. In both the transport and phosphoryla-
describing this process. Dividing Equation tion steps, FDG is a competitive substrate
21-36 by Equation 21-35 yields with glucose. FDG-6-PO4, however, is not a
significant substrate for further metabolism.
R′ Vm′ × K m [S ′ ] As shown in Figure 21-15, it is not converted
= (21-37)
R Vm × K m′ [S] into glycogen to any significant extent and is
not further metabolized in the glycolytic
The reaction rate of the measured or pathway. The FDG-6-PO4 also does not diffuse
“traced” process, R′, is therefore directly across cell membranes and is therefore meta-
related to the “natural” or unknown rate R by bolically trapped in tissues, which is conve-
a ratio of the Michaelis-Menten constants and nient both from an imaging and modeling
the relative concentrations of S and S′. In viewpoint.
some cases (e.g., direct isotopic substitution If glucose metabolism in the tissue of inter-
labeling of biologic compounds such as 11C for est is assumed to be in a steady state (i.e., it
12
C), the Michaelis-Menten constants for the has a constant rate), then the rate of the hexo-
tracer and natural substance are essentially kinase reaction will be the rate of the entire
the same and Equation 21-37 would reduce to process of glycolysis (see Section B.6). A com-
a simple ratio of [S′] to [S]. With analog tracers partmental configuration for the FDG model
the Michaelis-Menten constants are different is shown in Figure 21-16. The three-
than the natural substance but Equation compartment model consists of FDG in
21-37 still applies. plasma, FDG in tissue, and FDG-6-PO4 in
398 Physics in Nuclear Medicine
Glycogen
Glucose-1-PO4
Hexokinase
Glucose
Glucose Glucose-6-PO4
Glucose
Fructose-6-PO4
CO2H2O
Hexokinase
FDG
FIGURE 21-15 Transport and metabolic pathways for glucose and 2-deoxy-2[18F]fluoro-D-glucose (FDG). Physically,
the “free” compartment represents a combination of the interstitial space and the cytosol (the fluid component inside
the cell, excluding the nucleus) in both of which unphosphorylated glucose and FDG are uniformly distributed. The
red crosses indicate that FDG-6-PO4, unlike glucose-6-PO4, is not further metabolized.
tissue corresponding to comparable distribu- indices, whereas the corresponding terms for
tions of glucose, although glucose continues glucose do not have an asterisk.
on through metabolism. The first-order rate Let MRGlc* (µmol/min/g) refer to the meta-
constants k1* and k2* describe the transport of bolic rate of FDG and MRGlc (µmol/min/g) be
FDG from the blood to brain and brain to the metabolic rate for glucose. If Ct is the
blood, respectively, whereas the first-order concentration of free (unphosphorylated)
rate constants k3* and k4* describe the phos- glucose in the tissue space and Ct* is the cor-
phorylation of FDG and dephosphorylation of responding concentration for FDG (second
FDG-6-PO4. The asterisk refers to FDG compartment, top row, Fig. 21-16), then, from
k *2 k *4
C *p C *t C *m
FIGURE 21-16 Three-compartment FDG model with the four first-order rate constants describing transport between
the compartments. Cp, Ct, and Cm are the concentrations of glucose in plasma, tissue, and metabolized glucose (glucose-
6-PO4) in tissue, respectively. Cp*, Ct* , and Cm* are the corresponding concentrations for FDG.
21 • Tracer Kinetic Modeling 399
Equation 21-37 and the fact that the rate of a tissue uses FDG and glucose. The full
phosphorylation (i.e., flux as described in Sec- expression of LC also includes an additional
tions B.4 and B.5) equals k3 × Ct for glucose term including the influence of dephosphory-
and k3* × Ct* for FDG, it follows that lation of glucose on the net metabolic rates
of FDG and glucose. This latter term is nor-
MRGlc* Vm* × K m × Ct* k3* × Ct* mally quite close to 1 but is intrinsically
MRGlc = =
k3 × Ct (21-38) included in the measured values of LC by
* × Ct
Vm × K m Equation 21-42.
Although the lumped constant describes
Equation 21-38 assumes that k4* and k4 are the differences between FDG and glucose
very small and the forward rate of phosphory- metabolism, it is actually glucose metabolism
lation of glucose and FDG approximate the net itself that is of interest physiologically. It can
metabolic rates. Vm and Km are the Michaelis- be shown that MRGlc is given by1
Menten constants for the hexokinase-mediated
phosphorylation of FDG (*) and glucose (no *). Cp k1* k3*
If the ratio of terms defined by Equation MRGlc = (21-43)
21-38 is a constant, then LC k2* + k3*
MRGlc = MRGlc*/constant (21-39) The term k1* / (k2* + k3* ) is the partition coeffi-
cient (λ*) for FDG. To understand this, con-
If plasma glucose (Cp) and plasma FDG ( Cp*) sider the tracer steady state when the flux of
concentrations are constant and both sides of FDG into tissue is balanced by the flux out.
Equation 21-38 are multiplied by Cp /Cp*, then Thus,
MRGlc* / Cp* Vm* × K m × Ct* / Cp* flux in = flux out (21-44)
MRGlc / C = (21-40)
p Vm × K m* × Ct / Cp
k1* Cp* = k2* Ct* + k3* Ct* (21-45)
But, from Equation 21-3, the ratios Ct* /Cp*
and Ctâ•›/Cp are the partition coefficients (i.e., k1* Ct*
tissue-to-blood concentration ratios) of FDG = (21-46)
(λ*) and glucose (λ). If the numerator and k2* + k3* Cp*
denominator of the left side of Equation 21-40
are divided by blood flow (F ), the numerical It is apparent from Equation 21-46 that the
value of the equation does not change; thus, partition coefficient, k1* / (k2* + k3* ) , is simply
with these substitutions, the tissue-to-plasma concentration ratio.
Because LC is the correction factor that con-
MRGlc* /(Cp* × F ) Vm* × K m × λ* verts the transport and phosphorylation steps
= (21-41) measured with FDG to those for glucose, one
MRGlc /(Cp × F ) * ×λ
Vm × K m can perform the following transformation
from values for FDG to those for glucose:
This ratio of terms is defined as the lumped
constant (LC) of the FDG model. The left side [ k1* / (k2* + k3* )] × k3*
= [ k1 /(k2 + k3 )] × k3 (21-47)
of Equation 21-41 is simply the net extraction LC
* ) divided by the net (i.e., steady-
of FDG ( Enet
state) extraction of glucose (Enet). Therefore, Since k1/(k2 + k3) = Ct/Cp, the tissue concentra-
tion of glucose, Ct, can be obtained from the
* ) / ( Enet )
LC = ( Enet (21-42) plasma concentration, Cp, by
That is, the lumped constant of the FDG Cp × k1 / (k2 + k3 ) = (Ct /Cp ) × Cp = Ct (21-48)
model is just the steady-state ratio of the net
extraction of FDG to that of glucose at con- Thus, from the general equation for calculat-
stant plasma levels of FDG and glucose. The ing fluxes (Equation 21-5),
lumped constant is a direct consequence of
Equation 21-37 and illustrates the principle MRGlc (µmol/g/min) = k3 × Ct (21-49)
of competitive enzyme kinetics applied to
tracer kinetic modeling. Intuitively, the Equations 21-43 and 21-49 are valid only if
lumped constant is simply a correction term the dephosphorylation rate is negligible com-
that measures the net difference in the way pared with the rate of phosphorylation.
400 Physics in Nuclear Medicine
Models that include dephosphorylation are In words, Equation 21-50 can be expressed
described in reference 1. as
Equation 21-43 produces a local estimate
of MRGlc if Cp (the steady-state plasma Regional Glucose
glucose value) is measured, if LC is known Metabolic Rate
and if the rate constants for FDG (k1*, k2*, and
k3*) are determined for each region of organ of Plasma Glucose Conc.
=
interest. The equations and procedures for Lumped Constant
measuring these rate constants are given in Total 18 F Free 18 FDG (21-51)
references 1 and 10. Although this technique in Region − in Region
generates local estimates of MRGlc, it does ×
require imaging the organ over time and iter- Total Net 18 FDG
atively solving for the rate constants in Equa-
Transported to the Region
tion 21-43. In actual practice, an operational
equation for the FDG model usually is The total 18F minus free 18FDG equals the
employed that uses predetermined popula- tissue concentration of the reaction product,
tion values for the FDG rate constants and FDG-6-PO4.
requires only a single tissue measurement of Equation 21-50 requires knowledge of the
the total tissue concentration of 18F (18FDG + typical kinetics of the transport and phos-
18
FDG-6-PO4) obtained from ROI analysis of phorylation processes to make intelligent
the image data. This operational equation decisions about scan duration and imaging
originally was developed by Sokoloff and time. Typically, approximately 40 minutes
coworkers9 for autoradiographically deter- are required for the tracer to reach a near
mining MRGlc with 14C-deoxyglucose. This steady state in tissue after a bolus intrave-
technique still requires knowledge of the time nous injection of FDG. A PET image usually
course of FDG input function [Cp* (t) ], the is obtained at this time. The ROI value over
plasma glucose concentration Cp, the lumped the tissue or organ of interest, together with
constant value (LC ), and average values of the other model parameters described
the rate constants. The Sokoloff operational earlier, is then used to calculate local values
equation of the deoxyglucose model, which of MRGlc. Figure 21-17 illustrates a para-
does not include the dephosphorylation of metric image of MRGlc in the brain obtained
DG-6-PO4, is given by using Equation 21-50 with data from an
FDG PET image. A parametric image is one
in which the parameter of interest (in this
MRGlc =
case MRGlc) is calculated on a pixel-by-pixel
T
C i* (T ) − [ k1* × e− ( k2 + k3 ) T × ∫ C p* (t ) × e( k2 + k3 ) t dt]
* * * * basis.
0
The FDG model contains several simplifi-
T C p* (t ) * (t )
T Cp cations based on the approaches outlined in
LC ∫ dt − e− ( k2 + k3 ) T × ∫
* * * *
× e( k2 + k3 ) t dt the preceding sections. The strategy of using
0 C p 0 Cp
an analog tracer effectively eliminates many
alternative biochemical pathways for glucose
(21-50) metabolism and makes possible the simple
three-compartment model. Additionally, the
where Ci*(T ) is the total 18F tissue concentra- transport (between the first two compart-
tion at time T. ments) and phosphorylation steps (between
The quantities highlighted in blue in Equa- the second two compartments) represent com-
tion 21-50 are measured in each study. bined steps of more complicated multistep
Average estimates of the rate constants and processes. The exchange between substruc-
LC obtained from separate experiments are tures within each compartment is assumed to
used as a part of the routine calculation of be rapid compared with exchange between
MRGlc with Equation 21-50. The use of compartments.
average estimates of the rate constants over Even though blood flow has a major effect
the normal range of MRGlc values causes on tracer delivery, it is not included in the
little error at late times (i.e., imaging FDG model explicitly. The extraction of FDG
40 minutes after injection) because they normally is low enough (i.e., low value of P ×
appear with terms in Equation 21-50 with S) that the delivery of FDG has a low depen-
negative exponentials that become small dence on blood flow. In addition, the initial
when T becomes large. flow dependence on the delivery of FDG
21 • Tracer Kinetic Modeling 401
0.6 µmol/min/g
progressively diminishes with time after an imaging study, the radioligand and recep-
injection. tor are likely to disassociate. The discussion
In the tracer kinetic model, the FDG con- that follows assumes this case.
centration in the vascular compartment A simple model for the interaction of a
shown in Figure 21-16 is measured by taking radioligand, L, with a receptor, R, is
blood samples from the systemic circulation. kon
Typically, it is assumed that the measured
L+R ← → RL
(21-52)
koff
tissue data contain no significant counts from
activity in the vascular space. In Equation where kon and koff are the rate of association
21-50 this is a good approximation at the and dissociation of L and R, respectively. At
typical imaging time of 40 minutes after injec- equilibrium, if the system is closed, there is
tion. Models have been developed that add no net change in the concentrations, and
the vascular compartment to equations therefore
describing the tissue time-activity curve
because in kinetic studies for measuring the kon [L][R ] = koff [RL] (21-53)
rate constants, the amount of FDG in the
tissue vascular pool is significant at early where [L], [R], and [RL] are the equilibrium
times after injection. concentrations of the unbound ligand, the recep-
The deoxyglucose and FDG methods have tor, and the bound receptor-ligand complex,
been used to measure exogenous glucose use respectively. The ratio koffâ•›/kon is known as the
in many organs and tissues using autoradiog- equilibrium dissociation constant and is given
raphy and PET, respectively. Examples the notation Kd. The total concentration of
include brain, heart, tumors, liver, kidney, receptors is given by [R] + [RL] and is com-
and peripheral tissues. monly denoted as Bmax. Rearranging Equation
21-53 in terms of Kd and Bmax yields
6. Receptor Ligand Assays
Cell-surface receptors are important molecu- Bmax [L ]
[RL ] = (21-54)
lar targets that may be overexpressed or under�- [L ] + K d
expressed in a range of important diseases
states, for example in Parkinson’s disease and It is possible to measure [RL] as a function
many cancers. PET and SPECT can provide of [L] in vitro and then fit the data to estimate
images of the distribution of these receptors both Kd and Bmax. Thus quantitative informa-
by using tracers known as radioligands that tion on the receptor concentration, and the
are designed to bind specifically to the recep- strength of binding of the ligand to the recep-
tor of interest.11,12 In most cases the binding tor (commonly known as the affinity, and
is reversible, that is, over the time course of given by 1/Kd), can be obtained. In humans,
402 Physics in Nuclear Medicine
such a study is impractical because it would estimate a parameter related to the in vitro
require several injections of radioligand at BP as defined by Equation 21-55. Under the
different concentrations. As well, at higher assumption that Kd does not change signifi-
concentrations of the ligand there would be cantly with disease progression or treatment,
concerns about possible pharmacologic effects images of BP will roughly reflect the relative
resulting from the high levels of receptor concentration of receptors, Bmax, in tissue.
occupancy. However, if a PET or SPECT study Such techniques have been widely applied to
is carried out at tracer levels such that [RL] studies of receptor systems in the brain.
is small compared with [R] (i.e., the fraction To see how the parameter BP is related to
of receptors occupied by the ligand is, for quantities that can be measured in a PET or
example, 10% or less), then Bmax ≈ [R], and SPECT scan, we start with a compartmental
now from Equation 21-53, we see that model as shown in Figure 21-18A. The injected
radioligand is delivered via the flowing blood
Bmax [RL ] (plasma compartment) and is extracted with
= (21-55)
Kd [L ] rate constant K1 into the free compartment in
the tissue. The rate constant K1 represents
The ratio Bmax/Kd is known as the binding the product of the blood flow and the uni�
potential (BP) and equals the ratio of bound directional extraction fraction (see Section
radioligand to free radioligand concentration C.1) and has units of mLâ•›/minâ•›/g.*
at equilibrium in this simple model. Although
the situation in vivo following injection of a
radioligand is quite complex, it turns out with *By convention, K1 is denoted by a capital K because it
appropriate modeling of dynamically acquired has different units than the other rates constants, which
PET or SPECT data that it is possible to are in units of inverse time.
Plasma
compartment Free Bound
compartment compartment
K1 k3
k2 k4
FIGURE 21-18 A, A general four-compartment
model describing a radioligand that reversibly binds
k5 k6
to a specific receptor. The rate constants for the
exchange of the radioligand between compartments
are denoted by K1 through k6, and the concentration
of the radioligand in each compartment is denoted
Cnon-specific by C. B, A simplified version of the model in A in
which the exchange between the “free” and “nonspe-
cifically bound” compartments is assumed to be
rapid (k5 and k6 >> k3 and k4) allowing these two
Non-specifically bound compartments to be combined into a single compart-
A compartment ment representing nondisplaceable radioligand.
This reduces the number of model unknowns to four,
Plasma increasing the robustness with which kinetic param-
compartment eters can be estimated. This model is used in the
Non-displaceable Bound analysis of many radioligand studies with PET and
compartment compartment SPECT.
K1 k3
k2 k4
B
21 • Tracer Kinetic Modeling 403
Once in the tissue, there are four possible K1 Cplasma (t) + k4 Cbound (t) =
fates for the radioligand. It can continue to
exist in free form, it can bind to the receptor k2 k4 Cbound (t)
+ k4 Cbound (t)
of interest, it can bind nonspecifically in the k3
tissue to other proteins, or it can be trans- C K k (21-59)
ported back to the blood. Because any binding ⇒ bound = 1 3
is reversible, there are rate constants both for Cplasma k2 k4
binding of the ligand and for its dissociation.
In sum, this model has four different com- This is the ratio of the specifically bound
partments and six different rate constants. radioligand to the radioligand concentration
Because of the limited temporal resolution in plasma at equilibrium. This is another
and signal-to-noise characteristics of nuclear form of BP and is given the symbol BPP. Both
medicine images, it is not possible to robustly definitions for BP can be found in the litera-
estimate six different kinetic rate constants ture and only recently has consensus emerged
from a dynamic PET or SPECT study. The on nomenclature.13
model therefore is simplified by making Equations 21-58 and 21-59 relate a param-
the assumption that there is rapid exchange eter closely related to the in vitro equilibrium
between the free and nonspecifically bound BP to kinetic rate constants that may be mea-
compartments, and that these two com� sured individually, or in combination, from a
partments can be combined together. This is dynamic sequence of reconstructed PET or
a reasonable assumption if the radioligand SPECT scans. There are several computa-
has only low affinity binding to nonspecific tional approaches for taking radioactivity
targets such that it associates and dissoci- values from such a dynamic sequence and
ates rapidly (that is, k5 and k6 are large converting them into estimates of the BP
compared with k3 and k4). This combined through the integration of Equations 21-56
compartment often is referred to as the non- and 21-57. The method used depends on the
displaceable compartment. This results in available data, for example, whether arterial
the simplified kinetic model in Figure blood samples were taken during the scan
21-18B, which consists of three compart- such that the Cplasma(t) is known, and must
ments with four rate constants. also account for the fact that neither PET or
Based on conservation of mass, we can SPECT can differentiate between radioactiv-
write simple differential equations for the ity in CND and Cbound. Rather, the measure-
concentration in the “nondisplaceable” and ments are the sum of the radioligand in these
“specifically bound” compartments as two compartments as a function of time.
Methods for computing BP from PET and
dCND (t) SPECT data are reviewed in some detail in
= K1 Cplasma (t) − k2 CND (t)
dt (21-56) references 11 and 12. These types of approaches
− k3 CND (t) + k4 Cbound (t) that integrate carefully designed radioli-
gands, experimental protocols, and kinetic
dCbound (t) models are being used to study a number of
= k3 CND (t) − k4 Cbound (t) (21-57)
dt important receptor systems, particularly in
the brain (see Table 21-1). A representative
At equilibrium, there would be no net trans- example of such a study is shown in Figure
fer of radioligand between compartments; 21-19.
therefore, from Equation 21-57,
1.0
0.9
0.8
0.7
[11C]MRB (baseline)
0.6
0.5
0.4
0.3
[11C]MRB (10 mg methylphenidate)
0.2
0.1
0.0
Binding
potential
MRI
FIGURE 21-19 Images showing pixel-by-pixel calculations of binding potential (BPND) averaged over 11 healthy sub-
jects for (S,S)-[11C] methylreboxetine (MRB), a radioligand that selectively binds to the norepinephrine transporter (top
row). This transporter is responsible for removing the neurotransmitters norepinephrine and dopamine from the syn-
apses between neurons and is known to play an important role in several neurologic disorders, including attention
deficit–hyperactivity disorder (ADHD). In this study, a decrease in binding potential was observed after administration
of 10╯mg of methylphenidate 75 minutes prior to radioligand injection (middle row). Methylphenidate is a drug that
is used to treat ADHD. This study shows that methylphenidate binds to the norepinephrine transporter, thereby reduc-
ing the availability of receptor sites to which the radioligand may become bound. Sagittal, coronal, and transverse
views are shown with corresponding anatomic slices from magnetic resonance imaging (bottom row). (Adapted from
Hannestad J, Gallezot J-D, Planeta-Wilson B, et al: Clinically relevant doses of methylphenidate significantly occupy
norepinephrine transporters in humans in vivo. Biol Psych 68:854-860, 2010.)
regarding the fate of the tracer in a biologic 2. Renkin EM: Transport of potassium-42 from blood to
system and the quality of the image data that tissue in isolated mammalian skeletal muscles. Am
J Physiol 197:1205-1210, 1959.
are used as input to the model. In nuclear 3. Crone C: Permeability of capillaries in various
medicine, it rarely is possible to extract more organs as determined by use of the indicator
than three or four independent parameters in diffusion method. Acta Physiol Scand 58:292-305,
a model because of the finite temporal resolu- 1963.
4. Lassen NA: Tracer Kinetic Methods in Medical Physi-
tion and signal-to-noise ratio of the ROI data. ology, New York, 1979, Raven Press.
In situations in which the fate of the tracer is 5. Kety SS, Schmidt CF: The nitrous oxide method for
complex (multiple metabolites, multiple modes the quantitative determination of cerebral blood flow
of transport, and so forth), there can be consid- in man: Theory, procedure, and normal values. J Clin
erable debate on the appropriate formulation Invest 27:476-483, 1948.
6. Holden JE, Gatley SJ, Hichwa RD, et al: Regional
of the model and the exact physiologic or func- cerebral blood flow using positron emission tomo-
tional meaning of the derived parameters. graphic measurements of fluoromethane kinetics.
Once rigorous investigative studies are carried J Nucl Med 22:1084-1088, 1981.
out to validate a tracer kinetic model, it often 7. Huang S-C, Phelps ME, Hoffman EJ, Kuhl DE:
A theoretical study of quantitative flow measure-
is possible to use simplified versions of the ments with constant infusion of short-lived isotopes.
model that provide semiquantitative indices Phys Med Biol 24:1151-1161, 1979.
for use in the clinical setting, where it may not 8. Zieler K: Equations for measuring blood flow by
be possible to acquire dynamic sequences of external monitoring of radioisotopes. Circ Res 16:309-
images or obtain blood samples. 321, 1965.
9. Sokoloff L, Reivich M, Kennedy C, et al: The [C-14]
deoxyglucose method for the measurement of local
cerebral glucose utilization: Theory, procedure, and
REFERENCES normal values in the conscious and anesthetized
albino rat. J Neurochem 28:897-916, 1977.
1. Gambhir SS: Quantitative assay development for 10. Huang SC, Phelps ME, Hoffman EJ, et al: Nonin�
PET. In Phelps ME, editor: PET: Molecular Imaging vasive determination of local cerebral metabolic
and Its Biological Applications, New York, 2004, rate of glucose in man. Am J Physiol 238:E69-E82,
Springer-Verlag, pp 125-216. 1980.
21 • Tracer Kinetic Modeling 405
depends on the type and energy of the radia- For radiations of interest in nuclear medicine
tion, and how exactly the radiation deposits (γ rays, x rays, electrons, and positrons) the
its energy in the tissue. For example, an α radiation weighting factor is equal to 1.
particle has a short range in tissue and depos- Therefore the equivalent dose or dose equiva-
its all of its energy in a very localized region. lent in Sv (or rem) is numerically equal to the
In contrast, γ rays and electrons deposit their absorbed dose in Gy (or rads).
energy over a wider area. Table 22-1 shows
the radiation weighting factors, wR, used to
calculate equivalent dose for different types B. CALCULATION OF RADIATION
and energies of radiation. The SI unit of DOSE (MIRD METHOD)
equivalent dose is the sievert* (Sv). It is
related to the average absorbed dose D in an
organ or tissue, T, by 1. Basic Procedure and Some Practical
Problems
HT = D T × wR (22-3) The absorbed fraction dosimetry method
allows one to calculate the radiation dose
Equivalent dose replaces an older quantity delivered to a target organ from radioactivity
known as the dose equivalent. The dose equiv- contained in one or more source organs in the
alent is based on the absorbed dose at a point body (Fig. 22-1). The source and target may
in an organ (rather than an average across be the same organ, and, in fact, frequently the
the whole organ) and is weighted by quality most important contributor to radiation dose
factors, Q, that are similar to wR. The unit for is radioactivity contained within the target
dose equivalent also is the Sv. organ itself. Generally, organs other than the
The traditional unit for dose equivalent is target organ are considered to be source
the roentgen-equivalent man (rem). The con- organs if they contain concentrations of radio-
version factor between traditional and SI activity that exceed the average concentra-
units is tion in the body.
The general procedure for calculating the
1 rem = 10−2 Sv = 1 cSv = 10 mSv radiation dose to a target organ from radioÂ�
(22-4) activity in a source organ is a three-step
process, as follows:
*This unit is named after Rolf M. Sievert, best known for 1. The amount of activity and time spent
his development of elaborate mathematical models, by the radioactivity in the source organ
including the Sievert integral, which for many years pro- are determined. Obviously, the greater
vided the basis for calculating radiation doses from the activity and the longer the time that
implanted radium needles. He also constructed and per-
formed many basic measurements with ionization it is present, the greater is the radiation
chambers. dose delivered by it.
2. The total amount of radiation energy
emitted by the radioactivity in the
TABLE 22-1â•… source organ is calculated. This depends
WEIGHTING FACTORS FOR DIFFERENT primarily on the energy of the radio�
TYPES OF RADIATION IN THE nuclide emissions and their frequency of
CALCULATION OF EQUIVALENT DOSE† emission (number per disintegration).
Radiation
3. The fraction of energy emitted by the
Weighting source organ that is absorbed by the
Type of Radiation Factor, wR target organ is determined. This depends
on the type and energy of the emissions
x rays 1
(absorption characteristics in body
γ rays 1 tissues) and on the anatomic relation-
Electrons, positrons 1 ships between source and target organs
Neutrons Continuous function
(size, shape, and distance between them).
of neutron energy Each of these steps involves certain difficul-
ties. Step 2 involves physical characteristics of
Protons >2╯MeV 2 the radionuclide, which generally are known
α particles, fission 20 accurately. Step 3 involves patient anatomy,
fragments, heavy which can be quite different from one patient
ions to the next. Step 1 is perhaps the most trouble-
†Data from reference 1. some. Such data on radiopharmaceutical
22 • Internal Radiation Dosimetry 409
Source
organs
Target
organ
distribution as are available usually are which the activity is present. The product of
obtained from studies on a relatively small these two factors is the cumulated activity A
number of human subjects or animals. There in the source organ. The SI unit for cumulated
are variations in metabolism and distribution activity is the becquerel • sec (Bq • sec). The
of radionuclides among human subjects, espe- corresponding traditional unit is the µCi • hr
cially in different disease states. Also, the dis- (1╯µCi = 3.7 × 104 Bq; 1╯hr = 3600╯sec; there-
tribution of radioactivity within an organ may fore, 1╯µCi • hr = 3.7 × 104 × 3600 = 1.332 ×
be inhomogeneous, leading to further uncer- 108 Bq • sec = 1.332 × 102╯MBq • sec). Cumu-
tainties in the dose specification for that organ. lated activity is essentially a measure of the
Because of these complications and vari- total number of radioactive disintegrations
ables, radiation dose calculations are made for occurring during the time that radioactivity
anatomic models that incorporate “average” is present in the source organ. The radiation
anatomic sizes and shapes. The radiation dose delivered by activity in a source organ is
doses that are calculated are average values proportional to its cumulated activity.
of D for the organs in this anatomic model. Each radiotracer has its own unique spatial
An exception is made when one is specifically and temporal distribution in the body, as
interested in a surface dose to an organ from determined by radiotracer delivery, uptake,
activity contained within that organ, for metabolism, clearance and excretion, and
example, the dose to the bladder wall result- the physical decay of the radionuclide. The
ing from bladder contents. This is considered amount of activity contained in a source organ
to have a value one-half the average dose therefore generally changes with time. If the
to the organ or, in this case, the bladder time-activity curve is known, the cumulated
contents. activity for a source organ is obtained by mea-
In spite of the refined mathematical models suring the area under this curve (Fig. 22-2).
used in the absorbed fraction model, the Mathematically, if the time-activity curve is
results obtained are only estimates of average described by a function A(t), then
values. Thus they should be used for guide-
∞
line purposes only in evaluating the potential
radiation effects on a patient. A ≈ ∫ A(t) dt (22-5)
0
2. Cumulated Activity,
A where it is assumed that activity is adminis-
The radiation dose delivered to a target organ tered to the patient at time t = 0 and is mea-
depends on the amount of activity present in sured to complete disappearance from the
the source organ and on the length of time for organ (t = ∞).
410 Physics in Nuclear Medicine
AreaA
Activity (Bq)
Time (sec)
EXAMPLE 22-1
To estimate the radiation dose received
from a particular radiotracer, time-activity What is the cumulated activity in the liver for
curves for all the major organs are required. an injection of 100╯MBq of a 99mTc-labeled
These can be obtained from animal studies sulfur colloid, assuming that 60% of the
(which are then extrapolated with some injected colloid is trapped by the liver and
uncertainty to the human), imaging studies retained there indefinitely?
in normal human subjects, prior knowledge of
the tracer kinetics, or some combination of Answer
these approaches. Time-activity curves can be
quite complex, and thus Equation 22-5 may
A = 1.44 × 100 MBq × 0.60 × 6.0 hr
be difficult to analyze. Frequently, however,
= 518.4 MBq i hr
certain assumptions can be made to simplify
this calculation. = 1.87 × 106 MBq i sec
Situation 1: Uptake by the organ is “instan-
taneous” (i.e., very rapid with respect to the Situation 2: Uptake is instantaneous, and
half-life of the radionuclide), and there is no clearance is by biologic excretion only (no
biologic excretion. The time-activity curve physical decay, or physical half-life very long
then is described by ordinary radioactive in comparison with biologic excretion). In
decay (Equations 4-7 and 4-10): this situation, biologic excretion must be
carefully analyzed. Frequently, it can be
A(t) = A 0 e−0.693t / Tp (22-6) described by a set of exponential excretion
components, with a fraction f1 of the initial
where Tp is the physical half-life of the radio- activity A 0 being excreted with a (biologic)
nuclide and A0 is the activity initially present half-life Tb1, a fraction f2 with half-life Tb2,
in the organ. Thus and so on (Fig. 22-4). The cumulated activity
∞ then is given by
A ≈ A 0 ∫ e−0.693t / Tp dt ∞
A ≈ A 0 ∫ f1 e−0.693t / Tb1 dt
0
(22-7) 0
Tp A 0 ∞
= = 1.44Tp A 0 + A 0 ∫ f2 e−0.693t / Tb 2 dt + …
0.693
0
A0
Area within
rectangle
0.8A0
equals
Activity
FIGURE 22-3 Illustration of relation- 0.6A0
ship between A and average lifetime Area under
(1.44 Tp) of a radionuclide for simple red curve
exponential decay. 0.4A0
1.44T1/2
0.2A0
0
0 1 2 3 4 5 6
Time (number of half-lives)
A0
f1 A0
f2 A0
Total
Activity
0.01A0
Time
by the lungs. What is the cumulated activity Situation 3: Uptake is instantaneous but
in the lungs if 60% of the activity is excreted clearance by both physical decay and biologic
from the lungs with a biologic half-life of 15 excretion are significant. In this case, if
minutes and 40% with a biologic half-life of biologic excretion is described by a single-
30 minutes? component exponential curve with biologic
half-life Tb, and the physical half-life is Tp,
Answer then the total clearance is described by a
Because 99mTc physical decay is much slower single-component exponential curve with an
than the biologic excretion process, we may effective half-life Te given by*
assume that no physical decay occurs during
the time that activity is present in the lungs. 1 1 1
= + (22-9)
Thus (Equation 22-8) Te Tp Tb
A = (1.44 × 1/ 4 hr × 0.60 × 100 MBq)
+ (1.44 × 1/ 2 hr × 0.40 × 100 MBq)
= (21.6 + 28.8) MBq i hr
*Equation 22-9 can be derived from Equations 4-2 and
= 50.4 MBq i hr 4-9 by treating biologic excretion as the equivalent of a
= 1.81 × 105 MBq i sec second pathway in a “branching” radioactive decay
scheme.
412 Physics in Nuclear Medicine
A ≈ 1.44Te A 0 (22-11)
where Tu is the biologic uptake half-time. In
this case, cumulated activity is given by
If there is more than one component to
the biologic excretion curve, then each compo-
A ≈ 1.44 A 0 Te (Tue / Tu ) (22-13)
nent has an effective half-life given by Equa-
tion 22-9 for that component, and the
cumulated activity is computed with effective where Te is the effective excretion half-life
half-lives replacing biologic half-lives in (Equation 22-10) and Tue is the effective
Equation 22-8. uptake half-time
Tu Tp
Tue = (22-14)
EXAMPLE 22-3 Tu + Tp
Suppose in Example 22-2 that because of a
EXAMPLE 22-4
metabolic defect 60% of the activity is excreted
from the lungs with a half-life of 2 hours and A radioactive gas having a half-life of 20
40% with a half-life of 3 hours. What is the seconds is injected in an intravenous solu-
cumulated activity in the lungs for a 100╯MBq tion. It appears in the lungs with an uptake
injection for this patient? half-time of 30 seconds and is excreted (by
exhalation) with a biologic half-life of 10
Answer seconds. What is the cumulated activity in
The effective half-lives for the two compo- the lungs for a 250-MBq injection?
nents of biologic excretion are (Equation
22-10) Answer
The effective uptake half-time is (Equation
Te1 = 6 × 2 / (6 + 2) = 1.5 hr 22-14)
*Essentially the energy emitted per nuclear disintegra- The summation Σi includes values of ϕi and Δi
tion: 1╯MeV/dis = 1.6 × 10−13╯Gy • kg/Bq • sec. for all the emissions of the radionuclide and
414 Physics in Nuclear Medicine
values of ϕi(rk ← rh) for the source-target pair. Eckerman are given in Table 22-2. Most of the
A is the cumulated activity in the source values for their adult male model are similar
organ h. The energy absorbed by the target to the model originally developed by the
organ divided by the target organ mass mt MIRD committee; however, there are some
gives the average absorbed dose in grays to significant differences as well, such as in the
the target organ from activity in the source mass and values of ϕ for bone marrow. Con-
organ: sequently, the Cristy and Eckerman models
now have replaced the older MIRD model.
A Calculations of ϕ are complex, and the
D(rk ← rh ) =
mt
∑ φ (r
i k ← rh )∆ i tables are quite lengthy for “penetrating”
i
(22-18) radiations (photons with energy 10 keV )
because of the energy dependence of photon
The total dose to the target organ then is attenuation and absorption; however, the sit-
obtained by summing the doses from all of the uation is simpler for nonpenetrating radia-
source organs, h, in the body. tions (photons with energy 10 keV and
Values of ϕ have been calculated for math- electrons), for which it can be assumed that
ematical humanoid models incorporating all of the emitted energy is “locally absorbed,”
organs and anatomic structures of “average” that is, within the source organ itself. For
size and shape (Fig. 22-5). The model used for these emissions, ϕ = 1 when the target and
many years was that published by the MIRD the source are the same organ, ϕ = 0 other-
committee of the Society of Nuclear Medi- wise. In dosimetry calculations, it is useful to
cine.3 Cristy and Eckerman4 subsequently sum the equilibrium absorbed dose constants
developed a series of models representing for the nonpenetrating radiations and treat
newborn, 1-year-old, 5-year-old, 10-year-old, them as a single parameter, Δnp, because the
15-year-old, and adult individuals. Stabin absorbed fractions for all of these emissions
and associates extended the model to women are equal (unity when the source and target
and pregnant women.5 Organ masses for the are the same organ, zero otherwise).
adult male phantom developed by Cristy and
EXAMPLE 22-7
Compute the absorbed dose delivered to the
ANTERIOR VIEW OF THE PRINCIPAL ORGANS IN THE
HEAD AND TRUNK OF THE PHANTOM
lung by nonpenetrating radiations in the
problem described by Examples 22-4 and
0 5 10 ORGANS NOT 22-5.
centimeters SHOWN
Adrenals Answer
Brain
Stomach The nonpenetrating radiations are the β par-
Marrow
Pancreas
ticles (Δβ= 4.80 × 10–14╯Gy • kg/Bq • sec), conver-
Skull
Skin sion electrons (Δe = 6.24 × 10–15╯Gy • kg/Bq •
Spine Spleen sec), and 5 keV characteristic x-rays (Δx = 1.60
Ovaries × 10–16╯Gy • kg/Bq • sec). Thus Δnp = 5.44 ×
Arm bone Testes 10–14╯Gy • kg/Bq • sec. Cumulated activity is A
Thymus
Ribs Thyroid = 9.65 × 108 Bq • sec. Lung mass is 1╯kg (see
Lungs Uterus Table 22-2). Thus the average radiation dose
Leg bones delivered by these emissions to the lungs is
Heart
Kidneys D = (9.65 × 108 Bq i sec)
Liver
Small intestine × (5.44 × 10 −14 Gy i kg/Bq i sec)
Upper large
intestine Lower large × (φ = 1) /1 kg
intestine
Pelvis
= 5.25 × 10−5 Gy (5.25 mrad)
Bladder
TABLE 22-2â•…
ORGAN MASSES FOR THE CRISTY AND ECKERMAN ADULT MALE PHANTOM
It is the fraction of radiation emitted by the The dose reciprocity theorem is useful
source organ that is absorbed per gram of when tables for ϕ are not available for all
target organ mass. The absorbed dose equa- source-target organ pairs. If ϕ (rk ← rh) is
tion can be written using specific absorbed known, then ϕ (rh ← rk) can be obtained from
fractions as the dose reciprocity theorem. Rewriting Equa-
tion 22-21 in terms of ϕ:
A∑ Φ i (rk ← rh )∆ i (22-20)
D(rk ← rh ) =
i
φ(rh ← rk ) φ(rk ← rh )
The dose reciprocity theorem says that for = (22-22)
a given organ pair the specific absorbed frac- mh mk
tion is the same, regardless of which organ is
the source and which is the target: mh
φ(rh ← rk ) = × φ(rk ← rh ) (22-23)
Φ i (rk ← rh ) = Φ i (rh ← rk ) (22-21) mk
Answer
ASP = 1.44 × 6.0 hr × 0.30 × 100 MBq The effective half-life of 131I in the thyroid for
= 259.2 MBq i hr this patient is (Equation 22-10)
= 9.33 × 105 MBq i sec
Te = 8 × 2 / (8 + 2) = 16 /10 days
ARM = 1.44 × 6.0 hr × 0.10 × 100 MBq = 1.38 × 105 sec
= 86.4 MBq i hr
Therefore the cumulated activity per MBq
= 3.11 × 105 MBq i sec administered is (Equation 22-11)
99m
A = 1.44 × (1.38 × 105 sec)
The values of S for Tc are (see Table 22-3)
× 0.60 × 1 MBq
= 1.19 × 105 MBq i sec/MBq adminisstered
S(LI ← LI) = 3.16 × 10 −6 mGy/MBq i sec
S(LI ← SP) = 7.22 × 10−8 mGy/MBq i sec The dose per MBq • sec is (see Table 22-4):
S(LI ← RM) = 8.96 × 10−8 mGy/MBq i sec S(THY ← THY ) = 1.57 × 10−3 mGy/MBq i sec
22 • Internal Radiation Dosimetry 417
Thus the average absorbed dose for the medicine procedure with that from other
thyroid is medical procedures that use radiation sources.
For these reasons, it would be convenient to
D (THY ← THY ) condense radiation dose estimates such as
those in Table 22-6 into a single number.
= (1.19 × 105 MBq i sec/MBq administered) There are two different approaches to doing
× (1.57 × 10−3 mGy/MBq i sec) this: whole-body (or total-body) dose and effec-
tive dose.
= 187 mGy/MBq administered
The whole-body or total-body dose is the
(or 692 rads/mCi) total energy deposited in the body divided by
the total mass of the body, or in terms of the
One could include the radiation dose to the S factor for the total body (TB):
thyroid from activity in other organs in the
calculation performed in Example 22-9; D(TB ← TB) =
A × S(TB ← TB)
however, inspection of Table 22-4 reveals that
in comparison to the thyroid as the source (22-26)
organ, other organs have much smaller values This parameter was used for many years as
of S (by approximately a factor of 500). This, the standard for evaluating the risks of dif-
plus the fact that other organs concentrate ferent nuclear medicine procedures. However,
much less of the activity than the thyroid, the whole-body dose does not take into account
eliminates the need to consider them as the nonuniformity of dose distribution among
source organs in this calculation. the organs in the body, and its validity for
Examples 22-8 and 22-9 represent simpli- comparing the risks of different nuclear medi-
fied situations in which only a few organs are cine procedures is therefore questionable.
involved and where the cumulated activities The effective dose, E, was introduced by
of the organs are relatively easy to estimate. the International Commission on Radiologi-
In many cases, the calculations are more cal Protection (ICRP)1,10 as an attempt to
involved, with complex time-activity curves characterize a nonuniform internal dose by a
and more widespread distribution of the single number. This quantity was intended
radiopharmaceutical among different organs. primarily for estimating radiation risks and
To facilitate dosimetry calculations, a soft- doses received by radiation workers, although
ware program8 has been developed to calcu- its extension to clinical nuclear medicine
late the absorbed dose to major organs from studies has been supported by the ICRP. The
commonly employed radionuclides using the effective dose represents the whole-body dose
Cristy and Eckerman4 and Stabin5 phantom that would result in the same overall risk as
models of human anatomy. This greatly sim- the nonuniform dose distribution actually
plifies dose calculations, although it still is delivered. This is achieved by assigning dif-
necessary to provide the cumulated activity ferent weighting factors to the doses delivered
data for each organ for the radiopharmaceuti- to individual organs. The most recent recom-
cal of interest. Estimated radiation doses for mended values for the tissue weighting
a large number of commonly used radio� factors, wT, are shown in Table 22-7. The
pharmaceuticals are available from the Oak effective dose, which has units of sieverts, is
Ridge Institute for Science and Education.9 calculated from
By way of example, radiation dose estimates
E = ∑ wT × DT × wR = ∑ wT × HT
for 18F-fluorodeoxyglucose (FDG) PET studies
based on the Cristy and Eckerman adult male T T
(22-27)
phantom are reproduced in Table 22-6. where DT is the average absorbed dose in
organ T, wT is the tissue weighting factor for
organ T, and the summation is over all the
7. Whole-Body Dose and Effective organs listed in Table 22-7. HT is the equiva-
Dose lent dose defined in Section A. As noted in
The complete output of a dose calculation is Section A, wR = 1 for all radiations used in
an estimate of the radiation dose for all the diagnostic nuclear medicine procedures. An
major organs in the body. This provides a older quantity, effective dose equivalent (HE),
large amount of information that is difficult which uses slightly different tissue weighting
to assimilate into a perception of the risk factors, may be encountered in publications
of a specific radiopharmaceutical study, or for and in regulations established prior to 1991.
comparison of the dose from a nuclear Text continued on page 424
418
Physics in Nuclear Medicine
TABLE 22-3â•…
S VALUES (mGy/MBq • sec) FOR Tc-99m IN THE ADULT MALE PHANTOM*
Source Organs
Lower Upper
Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Adrenals 1.80E-04 4.18E-10 5.05E-08 3.13E-07 2.25E-08 7.46E-08 2.73E-07 9.58E-08 2.53E-07 2.85E-07 7.24E-07 4.35E-07 2.33E-07 1.12E-07
Brain 4.18E-10 4.23E-06 3.17E-09 1.49E-10 1.57E-11 3.91E-11 4.27E-10 4.68E-11 3.14E-09 2.54E-09 1.58E-10 8.16E-10 7.63E-09 2.21E-08
Breasts 5.05E-08 3.17E-09 1.14E-05 3.33E-08 2.28E-09 7.35E-09 5.73E-08 8.00E-09 2.41E-07 2.61E-07 1.99E-08 6.82E-08 2.33E-07 4.25E-08
Gallbladder wall 3.57E-07 1.54E-10 3.41E-08 3.37E-05 6.49E-08 4.38E-07 3.05E-07 7.53E-07 1.03E-07 1.22E-07 4.09E-07 8.70E-07 7.46E-08 1.19E-07
Lower large intestine wall 1.98E-08 1.32E-11 2.42E-09 5.93E-08 1.23E-05 5.92E-07 9.10E-08 2.14E-07 4.06E-09 4.90E-09 5.50E-08 1.44E-08 3.29E-09 1.34E-07
Small intestine 7.46E-08 3.91E-11 7.35E-09 4.58E-07 7.16E-07 4.22E-06 2.08E-07 1.25E-06 1.57E-08 2.06E-08 2.13E-07 1.16E-07 1.35E-08 1.12E-07
Stomach wall 2.85E-07 2.52E-10 5.93E-08 2.93E-07 1.24E-07 2.13E-07 8.53E-06 2.86E-07 1.66E-07 2.65E-07 2.53E-07 1.48E-07 1.19E-07 1.09E-07
Upper large intestine wall 9.41E-08 4.76E-11 7.51E-09 7.78E-07 3.10E-07 1.36E-06 2.65E-07 8.37E-06 2.12E-08 2.65E-08 2.12E-07 1.88E-07 1.81E-08 1.10E-07
Heart wall 2.85E-07 2.54E-09 2.61E-07 1.04E-07 5.42E-09 2.06E-08 2.33E-07 2.97E-08 5.48E-06 1.19E-05 8.22E-08 2.33E-07 4.40E-07 9.20E-08
Kidneys 7.24E-07 1.58E-10 1.99E-08 3.89E-07 7.10E-08 2.13E-07 2.73E-07 2.12E-07 6.45E-08 8.22E-08 1.32E-05 2.93E-07 6.66E-08 9.79E-08
Liver 4.35E-07 8.16E-10 6.82E-08 8.20E-07 1.80E-08 1.16E-07 1.47E-07 1.87E-07 2.13E-07 2.33E-07 2.93E-07 3.16E-06 1.97E-07 7.52E-08
Lungs 2.33E-07 7.63E-09 2.33E-07 7.09E-08 4.50E-09 1.35E-08 1.10E-07 1.77E-08 4.59E-07 4.40E-07 6.66E-08 2.09E-07 3.57E-06 9.36E-08
Muscle 1.12E-07 2.21E-08 4.25E-08 1.14E-07 1.23E-07 1.12E-07 9.96E-08 1.07E-07 8.83E-08 9.20E-08 9.79E-08 7.52E-08 9.34E-08 1.93E-07
Ovaries 3.14E-08 1.52E-11 2.61E-09 1.11E-07 1.26E-06 9.23E-07 5.85E-08 7.71E-07 4.55E-09 6.15E-09 7.02E-08 3.81E-08 5.39E-09 1.44E-07
Pancreas 1.09E-06 4.15E-10 6.22E-08 6.75E-07 5.21E-08 1.42E-07 1.23E-06 1.62E-07 2.65E-07 3.57E-07 4.97E-07 3.86E-07 1.74E-07 1.24E-07
Red marrow 2.53E-07 1.01E-07 5.52E-08 1.02E-07 2.01E-07 1.79E-07 7.50E-08 1.43E-07 1.11E-07 1.11E-07 1.71E-07 8.32E-08 1.11E-07 9.07E-08
Bone surfaces 2.67E-07 2.99E-07 7.76E-08 1.14E-07 1.82E-07 1.49E-07 1.03E-07 1.27E-07 1.60E-07 1.60E-07 1.62E-07 1.24E-07 1.66E-07 1.84E-07
Skin 3.41E-08 3.97E-08 7.63E-08 3.09E-08 3.62E-08 3.01E-08 3.41E-08 3.09E-08 3.41E-08 3.70E-08 3.79E-08 3.62E-08 4.02E-08 5.72E-08
Spleen 4.58E-07 5.19E-10 4.37E-08 1.33E-07 6.53E-08 1.01E-07 7.83E-07 1.05E-07 1.24E-07 1.67E-07 6.63E-07 7.22E-08 1.64E-07 1.03E-07
Testes 1.54E-09 1.46E-12 0.00E+00 6.91E-09 1.40E-07 2.61E-08 2.90E-09 1.92E-08 5.16E-10 6.16E-10 3.10E-09 1.57E-09 3.67E-10 9.89E-08
Thymus 5.66E-08 6.88E-09 2.29E-07 1.43E-08 2.04E-09 4.66E-09 3.65E-08 5.43E-09 8.87E-07 7.35E-07 1.73E-08 5.93E-08 2.85E-07 1.06E-07
Thyroid 8.11E-09 1.35E-07 3.01E-08 2.45E-09 2.48E-10 4.87E-10 2.62E-09 7.69E-10 5.17E-08 4.33E-08 2.95E-09 8.64E-09 8.82E-08 1.16E-07
Urinary bladder wall 7.55E-09 6.02E-12 1.33E-09 4.22E-08 4.98E-07 2.12E-07 1.73E-08 1.61E-07 2.22E-09 2.17E-09 1.87E-08 1.16E-08 1.33E-09 1.40E-07
Uterus 1.89E-08 1.31E-11 2.62E-09 1.16E-07 5.17E-07 8.37E-07 5.05E-08 3.97E-07 4.87E-09 5.47E-09 6.42E-08 3.29E-08 4.10E-09 1.43E-07
Total body 1.72E-07 1.25E-07 1.03E-07 1.36E-07 1.49E-07 1.59E-07 1.17E-07 1.41E-07 1.17E-07 1.65E-07 1.58E-07 1.59E-07 1.44E-07 1.33E-07
Source Organs
Lower Upper
TABLE 22-3 CONTINUED Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Source Organs
419
420
TABLE 22-4â•…
Source Organs
Lower Upper
Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Adrenals 1.97E-03 3.40E-09 1.65E-07 8.41E-07 7.95E-08 2.20E-07 7.93E-07 2.54E-07 6.95E-07 7.91E-07 2.05E-06 1.21E-06 6.71E-07 3.31E-07
Brain 3.40E-09 2.91E-05 1.43E-08 1.88E-09 2.62E-10 5.20E-10 3.50E-09 6.17E-10 1.68E-08 1.56E-08 1.47E-09 5.53E-09 3.34E-08 7.10E-08
Breasts 1.65E-07 1.43E-08 1.01E-04 1.09E-07 1.40E-08 3.33E-08 1.83E-07 3.85E-08 7.32E-07 7.97E-07 7.53E-08 2.18E-07 6.73E-07 1.36E-07
Gallbladder wall 9.04E-07 1.51E-09 1.15E-07 3.12E-04 1.79E-07 1.18E-06 8.17E-07 1.99E-06 2.79E-07 3.49E-07 1.09E-06 2.35E-06 2.16E-07 3.40E-07
Lower large intestine wall 7.68E-08 2.21E-10 1.42E-08 1.56E-07 1.19E-04 1.62E-06 2.52E-07 6.49E-07 1.91E-08 2.40E-08 1.67E-07 5.21E-08 1.65E-08 3.79E-07
Small intestine 2.20E-07 5.20E-10 3.33E-08 1.21E-06 1.94E-06 4.01E-05 5.41E-07 3.45E-06 5.72E-08 7.44E-08 5.93E-07 3.28E-07 5.05E-08 3.18E-07
Stomach wall 7.22E-07 2.68E-09 1.93E-07 7.80E-07 3.66E-07 5.96E-07 7.04E-05 7.97E-07 4.61E-07 7.00E-07 6.98E-07 4.24E-07 3.26E-07 3.13E-07
Upper large intestine wall 2.58E-07 6.23E-10 3.31E-08 2.07E-06 8.60E-07 3.80E-06 7.01E-07 7.57E-05 7.68E-08 9.14E-08 5.82E-07 5.16E-07 6.40E-08 3.11E-07
Heart wall 7.91E-07 1.56E-08 7.97E-07 2.88E-07 2.60E-08 7.44E-08 6.71E-07 9.44E-08 4.20E-05 1.09E-04 2.29E-07 6.37E-07 1.19E-06 2.64E-07
Kidneys 2.05E-06 1.47E-09 7.53E-08 1.03E-06 2.22E-07 5.93E-07 7.22E-07 5.85E-07 2.01E-07 2.29E-07 1.18E-04 8.19E-07 1.97E-07 2.89E-07
Liver 1.21E-06 5.53E-09 2.18E-07 2.20E-06 6.41E-08 3.28E-07 4.11E-07 5.29E-07 5.81E-07 6.37E-07 8.19E-07 2.15E-05 5.48E-07 2.21E-07
Lungs 6.71E-07 3.35E-08 6.74E-07 1.94E-07 2.19E-08 5.05E-08 3.07E-07 6.16E-08 1.25E-06 1.19E-06 1.97E-07 5.49E-07 3.40E-05 2.67E-07
Muscle 3.31E-07 7.10E-08 1.36E-07 3.27E-07 3.48E-07 3.18E-07 2.85E-07 3.03E-07 2.50E-07 2.64E-07 2.89E-07 2.21E-07 2.67E-07 1.42E-06
Ovaries 1.13E-07 2.65E-10 1.45E-08 2.99E-07 3.52E-06 2.47E-06 1.81E-07 2.08E-06 2.59E-08 3.16E-08 2.17E-07 1.20E-07 2.67E-08 4.07E-07
Pancreas 2.88E-06 4.18E-09 1.97E-07 1.83E-06 1.41E-07 3.98E-07 3.32E-06 4.46E-07 6.94E-07 9.41E-07 1.41E-06 1.03E-06 4.76E-07 3.53E-07
Red marrow 7.32E-07 2.77E-07 1.83E-07 3.07E-07 6.10E-07 5.14E-07 2.38E-07 4.27E-07 3.36E-07 3.36E-07 5.18E-07 2.63E-07 3.37E-07 2.75E-07
Bone surfaces 4.79E-07 5.34E-07 1.50E-07 1.90E-07 3.09E-07 2.46E-07 1.77E-07 2.14E-07 2.70E-07 2.70E-07 2.83E-07 2.17E-07 2.96E-07 3.28E-07
Skin 1.15E-07 1.40E-07 2.49E-07 1.02E-07 1.14E-07 9.94E-08 1.15E-07 1.02E-07 1.15E-07 1.20E-07 1.34E-07 1.18E-07 1.30E-07 1.89E-07
Spleen 1.25E-06 5.74E-09 1.51E-07 3.38E-07 1.77E-07 2.93E-07 2.09E-06 2.78E-07 3.26E-07 4.39E-07 1.87E-06 2.16E-07 4.54E-07 3.01E-07
Testes 1.02E-08 4.79E-11 0.00E+00 3.33E-08 4.43E-07 9.10E-08 1.86E-08 7.48E-08 4.30E-09 4.95E-09 1.91E-08 1.03E-08 3.16E-09 3.02E-07
Thymus 1.86E-07 3.52E-08 8.03E-07 5.65E-08 1.20E-08 2.20E-08 1.34E-07 2.73E-08 2.41E-06 1.98E-06 6.83E-08 1.77E-07 7.95E-07 3.11E-07
Thyroid 3.16E-08 4.21E-07 1.03E-07 1.50E-08 2.38E-09 3.04E-09 1.57E-08 5.97E-09 1.43E-07 1.36E-07 1.93E-08 3.51E-08 2.54E-07 3.38E-07
Urinary bladder wall 3.53E-08 1.34E-10 9.12E-09 1.60E-07 1.30E-06 5.76E-07 7.23E-08 4.55E-07 1.30E-08 9.31E-09 7.47E-08 5.03E-08 8.80E-09 3.97E-07
Uterus 8.02E-08 2.41E-10 1.70E-08 3.31E-07 1.39E-06 2.18E-06 1.51E-07 1.03E-06 2.53E-08 2.96E-08 2.00E-07 1.04E-07 2.03E-08 4.04E-07
Total body 8.01E-07 6.71E-07 6.33E-07 4.02E-07 6.01E-07 6.98E-07 4.26E-07 5.47E-07 4.33E-07 7.86E-07 7.71E-07 7.71E-07 7.22E-07 7.11E-07
Source Organs
Lower Upper
TABLE 22-4 CONTINUED Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Source Organs
421
422
TABLE 22-5â•…
Source Organs
Lower Upper
Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Adrenals 2.59E-03 1.13E-08 4.60E-07 2.06E-06 2.06E-07 5.70E-07 2.06E-06 6.48E-07 1.74E-06 2.05E-06 5.22E-06 3.01E-06 1.74E-06 8.54E-07
Brain 1.13E-08 4.62E-05 3.99E-08 6.70E-09 9.01E-10 1.78E-09 1.06E-08 2.11E-09 4.95E-08 4.78E-08 4.84E-09 1.76E-08 9.70E-08 1.90E-07
Breasts 4.60E-07 3.99E-08 1.46E-04 3.01E-07 4.30E-08 9.55E-08 4.92E-07 1.13E-07 1.90E-06 2.06E-06 2.07E-07 5.85E-07 1.74E-06 3.64E-07
Gallbladder wall 2.21E-06 5.00E-09 3.17E-07 4.38E-04 4.59E-07 3.00E-06 2.06E-06 4.89E-06 6.98E-07 9.32E-07 2.84E-06 5.85E-06 5.54E-07 8.70E-07
Lower large intestine wall 2.06E-07 7.54E-10 4.30E-08 3.97E-07 1.64E-04 4.11E-06 6.64E-07 1.74E-06 5.57E-08 7.00E-08 4.28E-07 1.40E-07 4.93E-08 9.65E-07
Small intestine 5.70E-07 1.78E-09 9.55E-08 3.00E-06 4.74E-06 5.49E-05 1.34E-06 8.69E-06 1.59E-07 2.06E-07 1.50E-06 8.38E-07 1.40E-07 8.07E-07
Stomach wall 1.74E-06 9.18E-09 5.23E-07 1.90E-06 9.34E-07 1.52E-06 1.03E-04 2.06E-06 1.16E-06 1.74E-06 1.74E-06 1.11E-06 8.23E-07 8.07E-07
Upper large intestine wall 6.81E-07 2.11E-09 9.54E-08 5.21E-06 2.21E-06 9.64E-06 1.74E-06 1.07E-04 2.06E-07 2.38E-07 1.47E-06 1.31E-06 1.75E-07 7.91E-07
Heart wall 2.05E-06 4.78E-08 2.06E-06 7.29E-07 7.64E-08 2.06E-07 1.74E-06 2.38E-07 6.32E-05 1.53E-04 5.86E-07 1.58E-06 3.00E-06 6.80E-07
Kidneys 5.22E-06 4.84E-09 2.07E-07 2.68E-06 5.85E-07 1.50E-06 1.74E-06 1.47E-06 5.39E-07 5.86E-07 1.68E-04 2.06E-06 5.08E-07 7.44E-07
Liver 3.01E-06 1.76E-08 5.85E-07 5.53E-06 1.75E-07 8.38E-07 1.04E-06 1.36E-06 1.45E-06 1.58E-06 2.06E-06 3.40E-05 1.38E-06 5.70E-07
Lungs 1.74E-06 9.70E-08 1.74E-06 4.91E-07 6.36E-08 1.40E-07 7.92E-07 1.74E-07 3.16E-06 3.00E-06 5.08E-07 1.38E-06 4.69E-05 6.80E-07
Muscle 8.54E-07 1.90E-07 3.64E-07 8.38E-07 8.86E-07 8.07E-07 7.28E-07 7.75E-07 6.33E-07 6.80E-07 7.44E-07 5.70E-07 6.80E-07 2.21E-06
Ovaries 2.69E-07 9.16E-10 4.47E-08 7.75E-07 9.02E-06 6.17E-06 4.90E-07 5.22E-06 7.81E-08 9.21E-08 5.70E-07 3.17E-07 7.62E-08 1.04E-06
Pancreas 7.11E-06 1.39E-08 5.23E-07 4.73E-06 3.65E-07 1.03E-06 8.22E-06 1.12E-06 1.74E-06 2.37E-06 3.64E-06 2.53E-06 1.23E-06 9.02E-07
Red marrow 1.90E-06 6.96E-07 4.91E-07 7.91E-07 1.58E-06 1.31E-06 6.32E-07 1.12E-06 8.85E-07 8.85E-07 1.34E-06 6.96E-07 8.85E-07 7.12E-07
Bone surfaces 1.06E-06 1.20E-06 3.49E-07 3.95E-07 6.65E-07 5.22E-07 3.79E-07 4.58E-07 5.85E-07 5.85E-07 6.17E-07 4.74E-07 6.64E-07 7.28E-07
Skin 3.17E-07 3.81E-07 6.65E-07 2.70E-07 3.01E-07 2.70E-07 3.17E-07 2.70E-07 3.17E-07 3.17E-07 3.65E-07 3.18E-07 3.48E-07 5.07E-07
Spleen 3.16E-06 1.91E-08 4.12E-07 8.25E-07 4.59E-07 7.59E-07 5.21E-06 6.96E-07 8.07E-07 1.11E-06 4.75E-06 5.54E-07 1.14E-06 7.75E-07
Testes 3.19E-08 1.66E-10 0.00E+00 9.69E-08 1.18E-06 2.54E-07 5.73E-08 2.06E-07 1.39E-08 1.59E-08 5.88E-08 3.20E-08 1.03E-08 7.91E-07
Thymus 4.90E-07 1.03E-07 2.21E-06 1.59E-07 3.66E-08 6.20E-08 3.65E-07 7.94E-08 6.02E-06 4.91E-06 1.90E-07 4.60E-07 2.06E-06 8.07E-07
Thyroid 8.92E-08 1.11E-06 2.86E-07 4.62E-08 7.87E-09 9.46E-09 4.78E-08 1.92E-08 3.64E-07 3.64E-07 5.87E-08 9.67E-08 6.65E-07 8.70E-07
Urinary bladder wall 1.03E-07 4.63E-10 2.87E-08 4.43E-07 3.16E-06 1.44E-06 2.06E-07 1.17E-06 3.98E-08 2.71E-08 2.06E-07 1.43E-07 2.71E-08 1.01E-06
Uterus 2.21E-07 8.35E-10 5.26E-08 8.54E-07 3.47E-06 5.38E-06 3.97E-07 2.53E-06 7.48E-08 8.74E-08 5.23E-07 2.70E-07 5.88E-08 1.03E-06
Total body 1.49E-06 1.17E-06 1.10E-06 9.67E-07 1.21E-06 1.34E-06 9.19E-07 1.14E-06 9.10E-07 1.46E-06 1.43E-06 1.43E-06 1.30E-06 1.28E-06
Source Organs
Lower Upper
TABLE 22-5 CONTINUED Gallbladder Large Small Large Heart Heart
Target Organs Adrenals Brain Breasts Contents Intestine Intestine Stomach Intestine Contents Wall Kidneys Liver Lungs Muscle
Source Organs
423
424 Physics in Nuclear Medicine
EXAMPLE 22-10
Although effective dose is regarded as a
Estimate the effective dose E for an adult better indicator of overall radiation risk than
male following the injection of 250╯MBq of whole-body dose for radiation protection pur-
18
F-FDG. Assume any organs or tissues not poses, there still is debate about its relevance,
shown in Table 22-6 have a radiation dose and care should be taken in its use and inter-
of 1.5 × 10–2 mGy/MBq (approximately the pretation. In particular, effective dose is not
average of those that are listed). recommended for use in radionuclide therapy
applications, nor should it be used to evaluate
Answer the risk from a radionuclide study to a specific
Using the available dose values in Table 22-6 individual. This is because calculations of E
and the tissue weighting factors in Table 22-7, are based on an “average” human, whereas
and assuming that wR = 1, then the effective the actual dose can vary considerably with
dose is given by: body shape and size, as well as the specific
E = 0.12 × (1.3 × 10 −2 mGy/MBq) distribution of the radionuclide in the indi-
× 250 MBq (red marrow) vidual. This, along with some other general
limitations of internal radiation dose esti-
+ 0.12 × (3 × 10 −2 mGy
y/MBq) mates, is discussed in the next section.
× 250 MBq (colon, as sum of upper
and lower large intestine walls) 8. Limitations of the MIRD Method
+ 0.12 × (1.7 × 10 mGy/MBq)
−2
There are a number of important limitations
× 250 MBq (lung) in the MIRD approach for calculating radia-
tion dose. Although Equation 22-18 is funda-
+ 0.12 × (1.3 × 10−2 mGy/MBq) mentally correct, the values of ϕ are currently
× 250 MBq (stomach) based on simplistic models of human anatomy
that assume specific relationships in the
+ 0.12 × (9.2 × 10−3 mGy/MBq) shape, size, and location of various organs
× 250 MBq (breast) (see Fig. 22-5). More realistic models of the
+ 0.08 × (1.3 × 10−2 mGy/MBq) human body, based on medical imaging data
and advanced computer modeling, are cur-
× 250 MBq (gonads) rently under development for dosimetry pur-
+ 0.04 × (1.9 × 10−1 mGy/MBq) poses. The MIRD formulation also implicitly
assumes that activity is distributed uniformly
× 250 MBq (bladder) within each organ and, furthermore, that
+ 0.04 × (1.5 × 10−2 mGy/MBq) energy is uniformly deposited throughout the
× 250 MBq (esophagus) organ. The assumption can cause a signifi-
cant error in the calculated dose from nonpen-
+ 0.04 × (1.6 × 10−2 mGy/MBq) etrating radiation (e.g., Auger electrons) when
× 250 MBq (liver) the activity is taken up in specific regions or
cell types within an organ. Local radionuclide
+ 0.04 × (1.0 × 10−2 mGy/MBq) concentrations and, hence, the absorbed dose
× 250 MBq (thyroid) can be much higher than organ average cal-
culations might suggest.
+ 0.01 × (1.2 × 10−2 mGy/MBq) , also
Calculation of cumulated activity, A
× 250 MBq (bone surfaces) is problematic. Initially, with a new radio-
+ 0.01 × (1.9 × 10−2 mGy/MBq) pharmaceutical, this must be determined
from animal studies. There can be significant
× 250 MBq (brain) differences between the kinetics of a tracer in
+ 0.01 × (1.5 × 10−2 mGy/MBq) an animal model and in the human. Once a
radiopharmaceutical is approved for human
× 250 MBq (salivary glands) use, it is possible to obtain human data to
+ 0.01 × (8.4 × 10 −3 mGy/MBq) estimate A. However, values for healthy sub-
× 250 MBq (skin) jects may differ widely from those for patients
and from one patient to the next because of
+ 0.00923 × (2.67 × 10 −1 mGy/MBq) pathophysiologic effects on uptake, clearance,
× 250 MBq (sum of 13 listed and excretion of the radiopharmaceutical.
remainder tissues) Despite these limitations, the MIRD
method is a useful tool for comparing the
= 5.8 mSv (or 0.58 rem) average dose to various organs in patients for
22 • Internal Radiation Dosimetry 425
TABLE 22-6â•…
RADIATION DOSE ESTIMATES FOR 18F-FLUORODEOXYGLUCOSE IN AN ADULT SUBJECT*
Organ wT
Red marrow, colon, lungs, stomach, 0.12 each REFERENCES
breast Society of Nuclear Medicine (MIRD) and ICRP pub-
Gonads 0.08 lications, along with data available from refer-
ences 6 and 9, provide the basic data for calculating
Bladder, liver, esophagus, thyroid 0.04 each absorbed doses:
Brain, skin, salivary glands, bone 0.01 each 1. International Commission on Radiological Protec-
surfaces tion: Recommendations of the International Commis-
sion on Radiological Protection. ICRP Publication
Remainder tissues (adrenals, 0.12 total 103; Ann ICRP 37(2-4), 2007.
extrathoracic region, gallbladder, (0.00923 2. Eckerman KF, Endo A: MIRD: Radionuclide Data
heart, kidneys, lymphatic nodes, each) and Decay Schemes, New York, 2008, Society of
muscle, oral mucosa, pancreas, Nuclear Medicine.
prostate [males], small intestine, 3. Snyder W, Ford M, Warner G: Estimates of Specific
spleen, thymus, uterus/cervix Absorbed Fractions for Photon Sources Uniformly
[females]) Distributed in Various Organs of a Heterogeneous
Phantom [MIRD Pamphlet No. 5 (revised)], New
*From reference 1. York, 1978, Society of Nuclear Medicine.
4. Cristy M, Eckerman K: Specific Absorbed Fractions
of Energy at Various Ages from Internal Photon
Sources (ORNL Report ORNL/TM-8381 V1-V7),
Oak Ridge, TN, 1987, Oak Ridge National
a wide variety of nuclear medicine procedures. Laboratory.
It also is an essential tool in the approval 5. Stabin, M, Watson E, Cristy M, et al: Mathematical
process for new radiopharmaceuticals. In cir- Models of the Adult Female at Various Stages of Preg-
nancy (ORNL Report ORNL/TM-12907), Oak Ridge,
cumstances in which the assumptions on TN, 1995, Oak Ridge National Laboratory.
which the MIRD approach is based are unac- 6. Radiation Dose Assessment Resource (RADAR):
ceptable, more complex and involved methods http://www.doseinfo-radar.com [accessed December
can be used. For example, microdosimetric 17, 2011].
(cellular level) calculations should be done for 7. Stabin MG, Siegel JA: Physical models and dose
factors for use in internal dose assessment. Health
radiopharmaceuticals that have very nonuni- Phys 85: 294-310, 2003.
form uptake in radiosensitive organs. As well, 8. Stabin MG, Sparks RB, Crowe E: OLINDA/EXM: The
radiation dose estimates for therapeutic second generation personal computer software for
426 Physics in Nuclear Medicine
internal dose assessment in nuclear medicine. J Nucl A general guide for performing internal dosimetry
Med 46: 1023-1027, 2005. calculations with the MIRD approach is the
9. Stabin MG, Stubbs JB, Toohey RE: Radiation Dose following:
Estimates for Radiopharmaceuticals (ORNL Report
Loevinger R, Budinger T, Watson E: MIRD Primer for
NUREG/CR-6345), Oak Ridge, TN, 1996, Oak Ridge
Absorbed Dose Calculations, New York, 1991, Society
Institute for Science and Education. Also available
of Nuclear Medicine.
electronically at http://orise.orau.gov/files/reacts/
dosetables.pdf [accessed December 17, 2011]. The following book is useful for MIRD calculations
10. International Commission on Radiological Protec- at the cellular level:
tion: 1990 Recommendations of the International
Goddu SM, Howell RW, Bouchet LG, et al: MIRD Cellular
Commission on Radiological Protection (ICRP Publi-
S Values, New York, 1997, Society of Nuclear
cation No. 60), New York, 1991, Pergamon Press.
Medicine.
Chapter 22 dealt with the radiation dose have a beneficial effect on health, resulting
received by patients undergoing nuclear med- from stimulation of the immune system.4 This
icine procedures. This chapter deals primarily effect is known as radiation hormesis. A vigor-
with the exposure of personnel who work in ous debate about the biologic consequences of
nuclear medicine clinics and research labora- low levels of ionizing radiation, the relevance
tories and who are exposed to radiation in of absorbed dose estimates in assessing health
their normal working environment. Stored risks, and the effect of these findings on regu-
radioactive materials, handling of calibration lations pertaining to radiation exposure is
sources, preparation of radioactive materials likely to continue for some years to come.
for patients and phantoms, and proximity to Whatever the outcome of this debate, and
patients or phantoms to whom these prepara- even though the risks to personnel occupa-
tions have been administered all are potential tionally exposed to ionizing radiation in the
sources of radiation exposure. An additional nuclear medicine environment clearly are
problem is the potential for radiation expo- small (based on decades of historic data),
sure to nonlaboratory personnel, such as common sense dictates that radiation expo-
patient relatives, attending nursing staff, and sures in and around the nuclear medicine
even passers-by in the hallways adjacent to laboratory be kept as low as is reasonably
the laboratory. achievable.
The quantities of radioactive material used When considering possible health effects to
and radiation levels encountered in a nuclear nuclear medicine patients or occupationally
medicine laboratory generally are well below exposed personnel, it also is important to
what is necessary to cause any type of “radia- place the dose received in perspective by con-
tion sickness.” Of more concern are the long- sidering the radiation dose received by all of
term effects that may possibly result from us from natural background sources. These
chronic exposures to even low levels of radia- sources include naturally occurring radionu-
tion. The most important of these effects clides in the body (e.g., 40K), cosmic radiation,
are genetic damage to cells (mutagenesis), and radionuclides that occur naturally in the
damage to chromosomes (clastogenesis), and environment. Effective doses to individuals
carcinogenesis. per year from these natural sources average
Presently, our understanding of the effects approximately 2.4╯mSv (typical range
of chronic exposure to low levels of radiation 1-13╯mSv).5 As shown in Example 22-10, a
is far from complete. Radiation protection 250-MBq injection of 18F-fluorodeoxyglucose
regulations and guidelines currently are leads to an effective dose of roughly 5.8╯mSv
based on a linear nonthreshold (LNT) model, (equal to the dose that would be received in
which assumes that there is no “threshold approximately 1.7 years from nature). The
dose” for these long-term effects and that the average effective dose to the extremities of
risk increases linearly with radiation dose.1 nuclear medicine technical personnel is on
There also are experiments, data, and pro- the order of 4╯mSv per year.6
posed radiation injury models that are incon- The analysis of problems in the handling
sistent with the LNT model.2,3 Some scientists of radiation sources and the development of
argue that studies involving low levels of safe handling practices are the general con-
radiation suggest that low doses actually cerns of the broad field of health physics. The
427
428 Physics in Nuclear Medicine
practices that are prescribed by this analysis radiation effects than are adults. The
are sometimes expressed formally as regula- developing embryo and fetus are espe-
tions and sometimes as “common sense” rec- cially sensitive.
ommendations. In this chapter we primarily 4. The type of radiation involved. In
discuss aspects of health physics and radia- general, densely ionizing radiation [i.e.,
tion safety practices as they apply to the high-linear energy transfer radiation
nuclear medicine laboratory. However, a (see Chapter 6, Section A.4)] such as α
further responsibility arises because nuclear particles, fission fragments, and other
medicine scientists and practitioners often nuclear particles, are more damaging
are among the first people contacted (e.g., by per gray of absorbed dose than is less
the media) for information on public-health densely ionizing radiation, such as β
radiation issues. Therefore it is wise to know particles and γ rays.
where reliable sources of information can be The dose-modifying factors in this list are
found. A number of international organiza- taken into account in preparing regulations
tions such as the International Commission and making recommendations for handling
on Radiological Protection (ICRP), the United of radioactive materials. For example, regu-
Nations Scientific Committee on the Effects lations specify different dose limits for differ-
of Atomic Radiation and the International ent parts of the body, for different time
Atomic Energy Agency provide useful reports periods, and for different age groups. To
and literature. Selected references and web- account for the differing hazards of different
sites are provided at the end of this chapter. types of radiation, the equivalent dose,
defined previously (see Chapter 22, Section
A. QUANTITIES AND UNITS A), is used. For most of the radiation encoun-
tered in nuclear medicine, the equivalent
dose in sieverts (or rems) is numerically
1. Dose-Modifying Factors equal to the absorbed dose in grays (or rads),
For health physics purposes, specification of although it must be emphasized that equiva-
the radiation absorbed dose in grays (see lent dose and absorbed dose are not the
Chapter 22, Section A) is inadequate for a same quantity and have different units. To
complete and accurate assessment of poten- account for differing hazards for different
tial radiation hazards. Although the relative organs and tissue types, the equivalent dose
risk of potential injury increases with increas- is modified by organ-specific weighting
ing absorbed dose values, several other dose- factors to compute the effective dose (see
modifying factors also must be taken into Chapter 22, Section B.7) to an individual.
account. In some older texts, and in current United
1. The part of the body exposed. Total-body States federal regulations (see Section B),
exposure carries a greater risk than the related quantities dose equivalent (in
partial-body exposure. Exposure of place of equivalent dose) and effective dose
major organs in the trunk of the body is equivalent (in place of effective dose) may be
more serious than exposure to the encountered. The conceptual difference is
extremities. The active blood-forming that equivalent dose is based on the average
organs, the gonads, and the lens of the absorbed dose in a specific tissue or an organ,
eye are especially sensitive to radiation whereas dose equivalent is based on the
damage. A superficial dose to the skin absorbed dose at a point in tissue. There also
(e.g., from an external source of β par- are differences in the scaling factors used to
ticles) is less hazardous than the same convert the absorbed dose into these quanti-
dose delivered to greater depths (e.g., ties. These quantities are summarized in
from an external source of γ rays or from Table 23-1. Broadly speaking, for nuclear
internally deposited radioactivity). medicine applications, equivalent dose and
2. The time span over which the radiation dose equivalent, as well as effective dose and
dose is delivered. A given number of effective dose equivalent, have similar numer-
grays delivered over a short period (e.g., ical values.
minutes or hours) has a greater poten-
tial for damage than the same dose 2. Exposure and Air Kerma
delivered over a long period (e.g., months For the purpose of describing radiation levels
or years). in a radiation environment, an additional
3. The age of the exposed individual. Chil- quantity—exposure—has traditionally been
dren are more susceptible to injurious used. Exposure refers to the amount of
23 • Radiation Safety and Health Physics 429
TABLE 23-1â•…
QUANTITIES USED IN HEALTH PHYSICS
References:
ICRP Publication 26: Ann ICRP 1: 3, 1977.
ICRP Publication 51: Ann ICRP 17: 2-3, 1987.
ICRP Publication 60: Ann ICRP 21: 1-3, 1991.
ICRP Publication 103: Ann ICRP 37: 2-4, 2007.
ICRP, International Commission on Radiological Protection.
ionization of air caused by a γ-ray or x-ray quantity known as air kerma. Kerma stands
source. The traditional unit of exposure is the for kinetic energy released in media. Exposure
roentgen (R), with subunits of milliroentgens refers to the ionization charge produced in air,
(1╯mR = 10−3╯R), microroentgens (1╯µR = whereas air kerma refers to the amount of
10−6╯R), and so on. An exposure of 1╯R implies kinetic energy released in air (Table 23-1).
ionization liberating an amount of charge More precisely, the air kerma is the sum of
equal to 2.58 × 10−4 coulombs/kg of air, or the kinetic energy of all charged particles pro-
approximately 2 × 109 ionizations per cc of dry duced by interactions from a source of x rays
air at standard temperature and pressure. An or γ rays (through Compton scatter, photoelec-
exposure rate of 1╯R╛/min implies that this tric absorption, or pair production) per kg of
amount of ionization is produced during 1 air. The units of air kerma are grays ( J/kg),
minute. The SI unit for exposure is the the same as for absorbed dose. If all of the
coulomb/kg, with no special name. Thus 1 photon energy transferred to charged parti-
coulomb/kg ≈ 3876╯R and 1╯R = 2.58 × 10−4 cles is deposited locally (in air, bremsstrah-
coulombs/kg. lung production is negligible, so this is a
The use of the SI units for exposure is cum- reasonable assumption), then the absorbed
bersome, and therefore in the transition to SI dose in air has the same value as the air
units, exposure is being replaced by a related kerma. Using the fact that 33.7╯eV of energy
430 Physics in Nuclear Medicine
is required to produce an ion pair in air (see The factor f depends on the mass attenua-
Table 7-1), and assuming bremsstrahlung tion coefficients (Chapter 6, Section D.1) of the
losses can be ignored, the relationship medium of interest and of air and is energy
between exposure, X, and air kerma, K, can dependent. Figure 23-1 shows the value of f as
be calculated as: a function of energy for bone and for soft
tissues. For soft tissues, f ≈ 1.1. The value is
K (Gy) ≈ X (C/kg) × 33.7 (23-1) close to unity because the mass attenuation
properties of soft tissues and air are similar.
The conversion between traditional units of For low-energy photons (E 100╯keV), the
exposure and air kerma is given by: value of f for bone is greater than unity.
Because of photoelectric absorption by the
K (Gy) ≈ X (R) × 0.00869 (23-2) heavier elements in bone (Ca and P), energy
absorption in bone is greater than energy
Exposure and air kerma are useful quanti- absorption by air at these energies; however,
ties because they can be measured using for most of the γ-ray energies commonly
ionization chambers, which are basically employed in nuclear medicine, the value of f
ionization-measurement devices (Chapter 7, for bone also is close to 1.
Section A.2). Specific instruments used for Thus for practical purposes air kerma (in
health physics measurements are described grays) is approximately equal numerically to
in Section E. the absorbed dose in grays that would be
If the air kerma in Gy is known at a certain received by an individual at that location, and
location, the absorbed dose in Gy that would in turn, as described in Section A.1, the
be delivered to a person at that location can absorbed dose in grays is numerically equal
be estimated by means of a scaling factor, f. to the equivalent dose in sieverts. Because of
This factor is defined as the ratio of the their approximate numerical equivalence,
absorbed dose in the medium of interest, Dmed, grays and sieverts, or in traditional units,
to the absorbed dose in air, Dair: roentgens, rads and rems, are sometimes
(mis)used as approximately interchangeable
f = Dmed /Dair ≈ Dmed /K (23-3) quantities; however, one should be aware that
5.0
4.0
Water
3.0 Muscle
Bone
Scaling factor, f
2.0
1.0
0.5
0.01 0.10 1.00 10.00
they represent distinctly different physical limited-scope licenses. The NRC permits the
quantities. institutional radiation safety committee to
authorize individuals to use radionuclides
under the license rather than requiring them
B. REGULATIONS PERTAINING TO to be listed specifically on the license.
THE USE OF RADIONUCLIDES The NRC also issues regulations that must
be observed by licensees in the use of radio�
Regulations for the transport, handling, and active materials. These regulations are pub-
exposure to ionizing radiation vary from lished in Title 10 of the Code of Federal
country to country. The discussion in this Regulations (CFR). Two of the more relevant
section limits itself to the regulations in place sections of these regulations for nuclear medi-
in the United States in 2012 and uses selected cine are Part 20 (10CFR20), covering radia-
regulations to highlight important regulatory tion protection, and Part 35 (10CFR35),
concepts. A complete discussion of the many covering medical uses. The NRC regulations
regulations involved is beyond the scope of are based primarily on the recommendations
this chapter. Also, the regulations are under of two advisory bodies, the ICRP and the
constant review and subject to periodic National Council on Radiation Protection
changes. Therefore the regulations presented and Measurement (NCRP), as discussed in
in this section should not be used to deter- Section B.7. The NRC also periodically issues
mine compliance without checking that they regulatory guides to assist licensees in the
are still current. Further information may interpretation and implementation of its
be obtained in the references at the end regulations.
of the chapter or from institutional health In addition to the NRC, several other gov-
physicists. ernment agencies are involved in the regula-
tion of radioactive materials, such as the U.S.
Department of Transportation (shipping reg-
1. Nuclear Regulatory Commission ulations) and the U.S. Food and Drug Admin-
Licensing and Regulations istration (pharmaceutical aspects).
The use and distribution of radioactive mate-
rials in the United States are under the 2. Restricted and Unrestricted Areas
primary control of the Nuclear Regulatory The NRC regulations prescribe different
Commission (NRC). The NRC issues licenses maximum radiation limits for restricted and
to individuals and to institutions to possess unrestricted areas. A restricted area is one
and use radioactive materials. In addition to “… access to which is controlled by the licensee
medical uses, industrial, research, educa- for the purposes of protection of individuals
tional, and other uses of radioactive materials from exposure to radiation and radioactive
also require NRC licensing. In some states, materials.” Normally, restricted areas are not
the NRC has entered into an agreement to accessible to the general public, and generally
transfer its regulatory and licensing functions they are occupied only by individuals whose
to a radiation control agency within the state. employment responsibilities require them to
Such states are called agreement states. work with radioactive materials and other
Medical licenses generally fall into one of radiation sources. Such individuals (e.g.,
two categories: specific licenses of limited nuclear medicine physicians, technicians, and
scope or specific licenses of broad scope. radiochemists) are said to be occupationally
Limited-scope licenses are for limited kinds exposed. Administrative staff, janitorial per-
and quantities of radionuclides, which are sonnel, and facilities maintenance personnel
listed specifically in the license. They may be generally are not included in this category.
issued to individual physicians (e.g., in private Restricted areas must be clearly marked with
offices) or to institutions (e.g., hospitals). radiation warning signs.
Licenses issued to institutions also list the of
individuals authorized to practice under the 3. Dose Limits
license. The dose limits specified in 10CFR20 are
Broad-scope licenses are issued to larger based on the general recommendations by the
institutions that require greater licensing ICRP and NCRP (Section B.7) that an indi-
flexibility (e.g., basic research as well as vidual’s total effective dose (see Chapter 22,
medical uses in a university setting). Broad- Section B.7) should not exceed 50╯mSv (5╯rem)
scope licenses generally cover more radio� per year. Furthermore, 10CFR20 requires
nuclides and greater quantities than do that the deep-dose equivalent (dose
432 Physics in Nuclear Medicine
equivalent at a depth of 1╯cm in tissue) to any limits are shown in Table 23-2 for radionu-
individual organ or tissue (excluding the lens clides that are used in nuclear medicine.
of the eye) should not exceed 500╯mSv (50╯rem)
per year. The limit for shallow-dose equiva- 5. Environmental Concentrations and
lent (dose equivalent at a depth of 0.007╯cm Concentrations for Sewage Disposal
in tissue) to the skin and extremities also is The NRC regulations also specify the environ-
500╯mSv (50╯rem) per year. The most restric- mental concentrations of radioactivity in air
tive limit is to the lens of the eye, which has and water and the concentration of radio�
an annual limit of 150╯mSv (15╯rem). The nuclides disposed of into sewage water, which
annual occupational dose limits for minors would lead to the annual dose limits described
(<18 years of age) are 10% of the annual dose in Section B.3 for the general public. Radio�
limits specified for adult workers. The dose active concentrations in sewage are of concern
equivalent to an embryo or fetus should not because they may eventually reach public
exceed 5╯mSv (0.5╯rem). water supplies. These limits assume continu-
These dose limits, which apply to occupa- ous inhalation or ingestion by the general
tionally exposed personnel, are called occupa- public over a period of 1 year, and they further
tional dose limits. Occupational dose limits do assume that the average person breathes 2 ×
not include radiation doses received by the 104╯mL of air per minute and has an annual
occupationally exposed individual while that water intake of 7.3 × 105╯mL. Sewer water is
individual is undergoing a medical examina- assumed to be diluted by a factor of 10 before
tion, nor do they include any radiation dose it is ingested. The methods for calculating
from natural radiation sources, such as cosmic these concentrations are described in
rays and naturally occurring radioactivity in 10CFR20. Table 23-3 shows these concentra-
the environment. tions for several radionuclides of interest.
Note that the regulations require the
licensee to control radiation doses not only 6. Record-Keeping Requirements
from licensed materials but from “other The NRC regulations require that rather
sources in the licensee’s possession” as well extensive records be kept by the licensee.
(e.g., nonlicensed radioactive materials or an These include, among others, personnel
x-ray generator). Thus a licensee would be in dosimetry and radiation survey records
violation of the regulations if the occupation (Section E), wipe testing records for sealed
limits were exceeded even if most of the sources, summaries of quality control checks
radiation dose were caused by nonlicensed on radiation monitoring equipment, inventory
sources.
For individual members of the public, the
annual effective dose equivalent limits are
1╯mSv (0.1╯rem). Radiation levels in un�
restricted areas should deliver a radiation TABLE 23-2â•…
dose of less than 0.5╯µSv/hr (0.05╯mrem/hr), CONCENTRATION OF AIRBORNE
assuming continuous occupation of the area. RADIOACTIVITY THAT WOULD RESULT IN
Transient radiation levels of up to 20╯µSv/hr THE ANNUAL DOSE LIMITS DESCRIBED IN
(2╯mrem/hr) are permitted. SECTION B.3 FOR OCCUPATIONALLY
EXPOSED PERSONNEL
4. Concentrations for Airborne
Radioactivity in Restricted Areas Air Concentration
A particular problem in nuclear medicine Radionuclide µCi/mL kBq/mL
laboratories is the potential for leakage or 3
H 2 × 10 −5
0.74
escape of radioactive gases (e.g., 133Xe used in
pulmonary function studies) or volatile radio- 11
C 2 × 10−4 7.4
active material (e.g., concentrated 131I solu- 14
C 1 × 10 −6
3.7 × 10−2
tions). The NRC regulations specify the 18
F 3 × 10−5 1.1
concentrations for airborne radioactive mate-
rials that would result in the annual dose
99m
Tc 6 × 10 −5
2.2
limits described in Section 3. These calcula- 125
I 3 × 10 −8
1.1 × 10−3
tions assume that the workers are chronically 131
I 2 × 10 −8
7.4 × 10−4
exposed to these concentrations during a
2000-hour working year and that 2 × 104╯mL
133
Xe 1 × 10−4 3.7
of air is breathed per minute. Concentration Data from 10CFR20, Appendix B, Table 1.
23 • Radiation Safety and Health Physics 433
TABLE 23-3â•…
ENVIRONMENTAL CONCENTRATIONS (AIRBORNE AND WATER) AND SEWAGE
CONCENTRATIONS THAT WOULD RESULT IN THE ANNUAL DOSE LIMITS DESCRIBED IN
SECTION B.3 FOR THE GENERAL PUBLIC IF CONTINUOUSLY INHALED OR INGESTED
Environmental Concentrations
Air Water Sewage Concentration
Radionuclide µCi/mL kBq/mL µCi/mL kBq/mL µCi/mL kBq/mL
3
H 1 × 10 −7
3.7 × 10 −3
1 × 10−3
3.70 × 10 1
1 × 10 −2
3.70 × 102
11
C 6 × 10 −7
2.2 × 10 −2
6 × 10−3
2.22 × 10 2
6 × 10 −2
2.22 × 103
14
C 3 × 10−9 1.1 × 10−4 3 × 10−5 1.11 × 100 3 × 10−4 1.11 × 101
18
F 1 × 10−7 3.7 × 10−3 7 × 10−4 2.59 × 101 7 × 10−3 2.59 × 102
99m
Tc 2 × 10 −7
7.4 × 10 −3
1 × 10−3
3.70 × 10 1
1 × 10 −2
3.70 × 102
125
I 3 × 10−10 1.1 × 10−5 2 × 10−6 7.40 × 10−2 2 × 10−5 7.40 × 10−1
131
I 2 × 10 −10
7.4 × 10 −6
1 × 10−6
3.70 × 10 −2
1 × 10 −5
3.70 × 10−1
133
Xe 5 × 10−7 1.9 × 10−2 — — — —
Data from 10CFR20, Appendix B, Tables 2 and 3.
TABLE 23-5â•…
γ RAY AIR KERMA RATE CONSTANTS FOR SEVERAL RADIONUCLIDES OF INTEREST IN
NUCLEAR MEDICINE
The appearance of d2 in the denominator of air kerma rates. The relationship between the
Equation 23-4 is an expression of the inverse- two is given by
square law (see Chapter 11, Section A.2).
Because γ rays and x rays are emitted isotro-
XR (R/hr) ≈ KR (mGy/hr) × 0.115 (23-5)
pically (e.g., with no preferred direction) radi-
ation intensity and dose levels decrease as the
square of the distance from the source. The equivalent dose rate to a particular
tissue or organ and the effective dose rate to
EXAMPLE 23-1 an individual can be estimated from the air
Calculate the air kerma rates at 10-cm and kerma rates using the appropriate radiation
300-cm distances from a syringe containing weighting factors and tissue weighting factors
1╯GBq of 99mTc. (see Chapter 22, Sections A and B.7), but
strongly depend on patient geometry and the
Answer direction from which the radiation is incident
The air kerma rate constant Γ is 0.0141╯mGy on the individual. Some publications estimate
2
• m /GBq • hr (see Table 23-5). Therefore from dose equivalent rates in mSv/hr using simpli-
Equation 23-4, at 10╯cm fied tissue models. These values are numeri-
cally higher than the air kerma rates as they
KR = 1 GBq × 0.0141 mGy i include the conversion from air kerma to
tissue absorbed dose (a factor of ~1.11 in soft
m2 /GBq i hr ÷ (0.12 ) m2 tissue), and also are increased by the contri-
= 1.41 mGy/hr butions of Compton-scattered photons within
the body.
and at 300╯cm, Equation 23-4 is accurate for distances
that are large in comparison to the physical
KR = 1 GBq × 0.0141 mGy i size of the source; however, it is not valid at
very small distances. For example, it predicts
m2 /GBq i hr ÷ (32 ) m2 that the air kerma rate, and therefore the
= 1.57 × 10 −3 mGy/hr equivalent dose, becomes infinite as d
= 1.57 µGy/hr approaches zero. A practical situation in
which this problem arises is in the estimation
of equivalent dose rates on contact with the
The strong effect of distance on radiation dose source, for example, equivalent dose rates to
equivalent rate is illustrated by Example 23-1. the hand while handling syringes and vials.
In some texts, exposure rates, XR These equivalent dose rates have been deter-
(roentgens/hr), may be encountered instead of mined experimentally for 99mTc. They range
436 Physics in Nuclear Medicine
from about 0.14╯mSv/MBq • hr on the surface As shown by Example 23-1, distance can
of larger syringes (10 to 20╯mL) up to approxi- have a marked effect on radiation levels.
mately 0.7╯mSv/MBq • hr for smaller syringes Increasing distance always has a dose-
(1 to 2╯mL).7 Equivalent dose rates to the reduction effect. Direct contact with radiation
hands on contact with syringes containing sources should be avoided by any available
~1000╯MBq of 99mTc can be in the range of means, such as by using tongs to handle vials.
several mSv/min, an obvious matter of concern Patient study areas (e.g., imaging rooms)
in operations requiring handling of these should be arranged to permit the technician
sources. The use of syringe shielding there- to operate instrumentation at reasonable dis-
fore is indicated and can significantly reduce tances (e.g., 2╯m) from the patient. Separate
the radiation dose. waiting areas should be provided for patients
Time, Distance, Shielding (TDS) Rules. who have been injected with radioactivity and
The basic principles for reducing radiation for relatives, orderlies, and patients not
doses from external sources are described by requiring radioactive injections. Reception
the “TDS” rules, for time, distance, and areas should not be used as waiting areas for
shielding: radioactive patients. Storage areas for gen-
1. Decrease the time of exposure. erators, radioactive trash, and other high-
2. Increase the distance from the source. level sources should be remote from regularly
3. Use shielding when practical and occupied areas of the laboratory. Special
effective. attention should be given to their location in
Time of exposure is decreased by working relation to unrestricted areas. (They also
with or in the vicinity of radiation sources as should be remote from imaging rooms and
rapidly as possible, consistent with good tech- counting rooms to minimize instrument back-
nique. Personnel should spend as little time ground levels.)
as possible in “hot labs” and other high-level Examples of effective use of shielding are
radiation areas. In particular, these areas lead pigs for storage of vials and generators,
should not be used for visiting, discussing lead-lined syringe holders, lead aprons, lead
problems unrelated to activities in the area, bricks for lining storage areas, and lead-
and so on. Laboratory monitors should be lined drawing stations (Fig. 23-2). Leaded
used in these areas to warn personnel when glass provides comfortable viewing and radia-
high-level radiation sources are present. tion protection simultaneously, especially
FIGURE 23-2 Examples of protective shielding devices used in nuclear medicine. Left, Shielded syringe holder
designed for positron-emitting radionuclides. Right, Lead-lined drawing station for preparing and handling low-energy
gamma-emitting radioactive materials (150╯keV) such as 99mTc. Lead-lined glass provides a good view of the work
area. (Photographs courtesy Biodex Medical Systems, Inc., Shirley, NJ.)
23 • Radiation Safety and Health Physics 437
for low-energy γ-ray and x-ray emitters workers. Patient sweat or excreta, linens
(200╯keV). Dose calibrators should be used on imaging tables, spillage occurring
enclosed in a shielded area, using lead sheets during transfer of activity between containers
or bricks, to avoid unnecessary exposure and syringes, radioactive trash, and radio�
during measurement of radiopharmaceutical active gases released during pulmonary func-
activity. tion tests are examples of potential sources.
Table 6-4 lists tenth-value thicknesses A radioactive material that has been acci-
of lead for several γ-ray and x-ray emitters. dentally or carelessly ingested is an “uncon-
Small thicknesses of lead (1╯mm) provide trolled source”; once it is inside the body,
effective shielding for low-energy emitters there is very little that can be done to reduce
(e.g., 133Xe and 99mTc). Lead-lined aprons, the radiation dose that it will deliver. (Tech-
which usually contain 0.25-mm- or 0.5-mm niques developed by the weapons and reactor
-equivalent lead thicknesses, provide a modest industries for speeding the elimination of
amount of radiation protection, but probably radioactive materials from the body generally
not enough to warrant their routine use in the are slow to act and thus are useful only for
nuclear medicine laboratory; however, they very long-lived radionuclides, and impractical
may be useful for specific applications, such for nuclear medicine.) The cardinal rule for
as during handling of large quantities of keeping radiation doses from internal sources
133
Xe (Eγ = 81╯keV) or during elution of a 99mTc ALARA is to prevent the entry of the radioÂ�
generator (Eγ = 140╯keV). Greater thickness active material into the body in the first place.
(>1╯cm) is required for higher-energy γ-ray To a certain extent, this is a matter of careful
emitters, such as 131I (Eγ = 364╯keV); however, design of laboratory facilities, but equally as
lead is still an effective shielding material at important, it is a matter of developing good
these energies. Concrete and similar materi- laboratory work habits.
als find limited use for general purpose shield- Some basic rules for avoiding internal radi-
ing in nuclear medicine. ation doses are the following:
Shielding is very effective for β emitters. A 1. No eating, drinking, smoking, or apply-
few millimeters of almost any solid material ing of cosmetics should occur in areas
will stop even the most energetic β particles where open sources may be present
(see Fig. 6-10 and Table 6-1). In this (e.g., hot labs and patient study areas).
case, however, low-Z materials (e.g., plastic, 2. Lab coats and gloves should be worn
ordinary glass) are preferred over high-Z when handling radioactive sources.
materials (e.g., leaded glass) to minimize Gloves should be handled so as to avoid
bremsstrahlung production (see Equation contamination of their inside surfaces.
6-1). A good shielding arrangement for a high- Lab coats, aprons, and other protective
energy β emitter, such as 32P, is to use a plastic clothing should stay in the laboratory
or glass container for the radioactive material (i.e., they should not worn outside the
to stop the β particles and then to place this in lab or taken home).
a lead container to absorb the bremsstrahlung 3. No foodstuffs or drinks should be stored
radiation (see Fig. 6-3). A similar approach can where radioactive sources are kept,
be employed with positron emitters; however, such as in laboratory refrigerators.
the thickness of the lead must be substantial 4. Pipetting should never be done by
(tenth-value thickness for 511-keV photons is mouth.
13.4╯mm) to provide effective shielding against 5. Personnel should wash their hands
the annihilation radiation. after working with radioactive sources
(a sink should be available in the labo-
ratory), and they should be checked
3. Reduction of Radiation Doses from for contamination on a laboratory radi-
Internal Sources ation monitor (Section E.1). Hands
Types of Sources. Nearly all nuclear medicine should also be monitored before going
personnel are required at one time or another to lunch or on breaks and before leaving
to work with radioactive sources in open or at the end of the day.
poorly sealed containers. There is always the 6. Work should be performed on absor-
possibility that in these operations some of bent pads to catch spills and prevent
the radioactive material will find its way into spattering of liquids.
the body, where it delivers a radiation dose as 7. Work with radioactive gases or other
an internal radiation source, or back to offices volatile materials (e.g., concentrated
or other areas accessible to nonradiation iodine solutions) should be performed
438 Physics in Nuclear Medicine
in a ventilated fume hood. These mate- offices, and so on, and away from imaging
rials also should be stored in a hood. and low-level counting rooms.
8. Work areas should be kept tidy. Radio- 2. Work surfaces and floors should be con-
active trash, contaminated pads, and structed using smooth, nonabsorbent
so forth should be disposed of promptly. materials free from cracks and crevices.
9. Radioactive storage areas (e.g., hot 3. Workbenches should be sufficiently
labs) should not be used to store other sturdy to support lead shielding.
materials, such as office supplies or 4. Washbasins and sinks should be conve-
linens. niently available where unsealed radio-
10. Needless contamination of light active materials are handled. It is
switches, doorknobs, and other items desirable that sinks in hot labs have
that could result in unsuspected con- foot- or elbow-operated controls.
tamination to personnel should be 5. The laboratory design should permit
avoided. separate storage of glassware and
11. Containers with sharp or broken edges work tools (e.g., tongs, stirring devices)
should not be used for radioactive not used with radioactive materials
materials. to prevent needless contamination or
12. Radioactive materials should be stored mixture with similar items used with
when they are not in use. radioactive preparations.
Studies with radioactive gases, such as
133
Xe, require special attention because of the 5. Procedures for Handling Spills
potential for escape of radioactivity into the Accidental spills of radioactive materials are
laboratory and beyond. Optimally, the labora- infrequent occurrences in well-run nuclear
tory ventilation system should be designed to medicine laboratories. Also, the quantities of
maintain the laboratory under negative pres- radioactivity used in nuclear medicine do not
sure relative to its surroundings and should create “life-threatening” hazards. Neverthe-
be separate from other ventilation systems to less, radioactive spills should not be treated
prevent spread of airborne activity into other as events completely without hazard, and
areas of the hospital. A gas-trapping system laboratory personnel should be aware of the
should be used to collect gases exhaled by the appropriate procedures to follow when spills
patient. do occur.
Most of the rules listed earlier in this The steps to follow in dealing with a radio-
section are of the common-sense variety and active spill are (1) to inform, (2) to contain,
perhaps seem obvious; however, it is surpris- and (3) to decontaminate.
ing how often they are violated through for- 1. Individuals in the immediate work area
getfulness or indifference. This may explain should be informed that a spill has
the surprisingly high incidence of internal occurred so they can avoid contamina-
radionuclides found in some studies of nuclear tion if possible. Individuals outside the
medicine laboratory personnel (e.g., >70% immediate area should be warned so
incidence of radioactive iodine in thyroid they do not enter it. The radiation officer
glands).6 Clearly, adherence to proper labora- should be informed so that he or she
tory work rules is fundamental to the ALARA may begin supervising further action as
concept. soon as possible.
2. By whatever means are reasonably pos-
4. Laboratory Design sible, but without risking further hazards
The principles of ALARA are enhanced by to themselves, laboratory personnel
careful attention to laboratory design. Several should attempt to contain the spill to
design aspects have been mentioned already prevent further spread of contamination.
in relation to other problems, such as negative A flask that has been tipped over should
relative air pressure in laboratories employing be uprighted. Absorbent pads should be
volatile or gaseous radioactive materials and thrown over a liquid spill. Doors should
availability of a fume hood with its own be closed to prevent the escape of air-
exhaust system for storage of these materials. borne radioactivity (e.g., gases, powders).
Some additional principles to be considered in The spill area should be closed off to
laboratory design are the following: prevent entry, especially by persons who
1. Hot labs and radioactive storage areas might not be aware of the spill. Personnel
should be located away from other busy monitoring for contamination should be
work areas, public corridors, secretarial started as soon as possible, so that
23 • Radiation Safety and Health Physics 439
meters give reasonably accurate estimates of clicking noise when radiation is detected in
exposure rates (±10%) over most of the nuclear addition to having a meter display of count-
medicine energy range. Most ionization ing rate. A laboratory monitor should be used
chamber survey meters do not have sealed in any area where large quantities of radio-
chambers. Thus for greatest accuracy their activity are handled (e.g., in a radio�pharmacy
readings should be corrected for ambient tem- laboratory) to warn of the presence of high
perature and pressure variations (see Chapter radiation levels. They also are useful for
7, Section A.2, Equation 7-1). These correc- monitoring hands after operations requiring
tions are small at sea-level pressures and the handling of radioactivity.
room temperatures; however, the pressure
correction factor may be significant at higher 2. Personnel Dosimeters
elevations (~20% at 1600╯m). Personnel dosimeters are devices worn by
The accuracy of an ionization chamber laboratory personnel to monitor radiation
survey meter should be checked periodically doses from external sources. There are two
(e.g., annually, or following major repairs) general types: dosimeter badges, which are
using a radiation source producing a known used to measure cumulative doses over
radiation exposure level. Sealed sources used periods of weeks or months, and pocket dosim-
in radiation therapy departments are useful eters, which are generally used for monitoring
for this purpose. over a shorter term.
GM tube types of survey meters are more Dosimeter badges monitor radiation doses
sensitive than ionization chamber types using either a small piece of x-ray film, or
because they respond to individual ionizing much more commonly, thermoluminescent
radiation events. Most of these instruments dosimeter (TLD) chips (Fig. 23-3). TLDs gen-
have meters that display event counting rates erally use small “chips” of LiF, a material that
(cpm). Some types with thin mica or alumi- gives off light when heated after it has been
num entrance windows are suitable for detect- exposed to ionizing radiation. The amount of
ing α and β particles as well as γ rays and light given off is measured using a photoÂ�
x rays. Because of their relatively high sensi- multiplier tube while the chip is heated in an
tivity, GM-type survey meters are most useful oven inside a light-tight enclosure. The
for detecting small quantities of radioactivity amount of light given off is used to estimate
from minor spills, in waste receptacles, and the radiation dose received. There also are
so on. dosimeter badges based on optically stimu-
Laboratory monitors are very similar to lated (rather than heat-stimulated) lumines-
survey meters, but they are designed to be cence of materials such as Al2O3.
used at a fixed location rather than as por- Dosimeter badge services are provided by
table units. They are operated continuously; a number of commercial suppliers. New
thus they are genera�lly plugged into the badges are supplied at regular (e.g., monthly)
wall rather than battery operated. Most have intervals, and readings for the preceding
GM tube detectors and produce an audible period are reported back to the user, typically
FIGURE 23-3 Examples of personnel dosimeter badges. Left, Thermoluminescent dosimeter (TLD) badge, which
usually contains several TLD chips, with one chip being exposed through a thin Mylar window in the badge to permit
measurement of low-energy beta radiation. Right, Photograph of ring dosimeters that contain a single lithium fluoride
TLD chip and are useful for measuring the dose to the skin and hands from the handling of radionuclides. Bar codes
are used on most personnel monitors to permit easy identification and data logging when reading out the TLD chips.
(Courtesy Mirion Technologies, Irvine, CA.)
23 • Radiation Safety and Health Physics 441
within about a month. The reports provided Turner JE: Atoms, Radiation, and Radiation Protection,
by most companies are satisfactory for NRC 2nd ed. New York, 1995, Wiley.
record-keeping purposes.
Pocket dosimeters were described in Regulatory documents can be found on the website
Chapter 7, Section A.2 (Fig. 7-5). They are of the Nuclear Regulatory Commission at http://
essentially ionization chamber devices that www.nrc.gov [accessed October 14, 2011]. Relevant
provide an immediate readout of radiation documents on this website include the following:
doses and thus are especially useful for mea- NRC Regulations:
suring over short periods or when a rapid 10CFR20: http://www.nrc.gov/reading-rm/doc-collections/
cfr/part020/index.html
indication of results is needed, such as during 10CFR35: http://www.nrc.gov/reading-rm/doc-collections/
complicated radiopharmaceutical prepara- cfr/part035/index.html
tion procedures. NRC Regulatory Guides (available at http://www.nrc.gov/
reading-rm/doc-collections/reg-guides/occupational-
3. Wipe Testing health/rg/):
8.10: Operating Philosophy for Maintaining Exposures as
Wipe testing is used to detect small amounts Low as Reasonably Achievable
of radioactive contamination on bench-top sur- 8.18: Information Relevant to Ensuring that Occupa-
faces, on the outside of shipping packages, and tional Radiation Exposures at Medical Institutions
so on, or to detect small amounts of radioactive will be As Low As Reasonably Achievable
8.36: Radiation Dose to the Embryo/Fetus
leakage from sealed radioactive sources. The 8.39: Release of Patients Administered Radioactive
surface is wiped with an alcohol-soaked patch Materials
of gauze or cotton-tipped swab, which is then
counted in a well counter (for γ-emitting
nuclides) or a liquid scintillation counter (for The National Council on Radiation Protection and
Measurement website is at http://www.ncrp.com
β emitters). Contamination below the kBq [accessed October 14, 2011]. Important NCRP pub-
level can be detected by wipe testing. NRC lications in addition to those listed in the refer-
regulations require periodic wipe testing of ences are the following:
work areas and maintaining records of these Uncertainties in the Measurement and Dosimetry of
tests. External Radiation (NCRP Report No. 158), 2007.
Operational Radiation Safety Training (NCRP Report
No. 134), 2000.
REFERENCES Radionuclide Exposure of the Embryo/Fetus (NCRP
Report No. 128), 1998.
1. Evaluation of the Linear Nonthreshold Dose-Response
Operational Radiation Safety Program (NCRP Report
Model for Ionizing Radiation (NCRP Report No. 136).
No. 127), 1998.
Bethesda, MD, NCRP, 2001.
Limitation of Exposure to Ionizing Radiation (NCRP
2. Rossi HH: Sensible radiation protection. Health
Report No. 116), 1993.
Physics 70:394-395, 1996.
Implementation of the Principle of As Low as Reasonably
3. Simmons JA, Watt DE: Radiation Protection Dosime-
Achievable (ALARA) for Medical and Dental Personnel
try: A Radical Reappraisal. Madison, WI, 1999,
(NCRP Report No. 107), 1990.
Medical Physics Publishing Corp.
Radiation Protection for Medical and Allied Health Per-
4. Kondo S: Health Effects of Low-Level Radiation.
sonnel (NCRP Report No. 105), 1989.
Madison, WI, 1993, Medical Physics Publishing
Protection in Nuclear Medicine and Ultrasound Diagnos-
Corp.
tic Procedures in Children (NCRP Report No. 73),
5. Source and Effects of Ionizing Radiation (United
1983.
Nations Scientific Committee on the Effects of Atomic
Management of Persons Accidentally Contaminated with
Radiation, 2008 Report to the General Assembly), New
Radionuclides (NCRP Report No. 65), 1980.
York, 2010, United Nations. Available at http://
Safe Handling of Radionuclides (NCRP Report No. 30),
www.unscear.org/unscear/en/publications.html
1964.
[accessed October 14, 2011].
6. Sources and Magnitude of Occupational and Public
Exposures from Nuclear Medicine Procedures (NCRP
Report No. 124). Bethesda, MD, NCRP, 1996. The International Atomic Energy Agency website
7. Anger RT: Radiation protection in nuclear medicine. is at www.iaea.org [accessed October 14, 2011] and
In The Physics of Nuclear Medicine, Chicago, 1977, has several publications relevant to nuclear medi-
American Association of Physicists in Medicine. cine that can be downloaded from the website: For
example:
Nuclear Medicine Resources Manual, 2006.
BIBLIOGRAPHY Cyclotron Produced Radionuclides: Guidelines for
Setting Up a Facility, Technical Reports Series No.
A detailed discussion of health physics and radia-
471, 2009.
tion protection techniques can be found in the fol-
Quality Assurance for Radioactivity Measurement in
lowing textbooks:
Nuclear Medicine, Technical Reports Series No. 454,
Shapiro J: Radiation Protection: A Guide for Scientists, 2006.
Regulators, and Physicians, 4th ed. Cambridge, MA, Applying Radiation Safety Standards in Nuclear Medi-
2002, Harvard University Press. cine, Safety Reports Series No. 40, 2005.
442 Physics in Nuclear Medicine
International bodies providing information or rec- The United Nations Scientific Committee on the
ommendations regarding radiation dose: Effects of Atomic Radiation website is at
www.unscear.org/ [accessed October 14, 2011). Two
The International Commission on Radiological
comprehensive publications of interest are:
Protection website is at http://www.icrp.org
[accessed October 14, 2011). An important ICRP UNSCEAR 2008 Report: “Sources and effects of ionizing
publication with recommendations regarding dose radiation.”
limits is the following: UNSCEAR 2006 Report: “Effects of ionizing radiation.”
Recommendations of the International Commission on
Radiological Protection (ICRP Publication No. 103),
Annals of the ICRP, Vol. 37, 2-4, 2007.
appendix
A
Unit Conversions
443
This page intentionally left blank
appendix
B
Properties of the
Naturally Occurring
Elements
Atomic Weight* Density† KB‡
Name Symbol Atomic Number (12C scale) (g/cm3) (keV)
Actinium Ac 89 (227) 10.0 106.756
Aluminum Al 13 26.982 2.70 1.560
Antimony Sb 51 121.760 6.68 30.491
Argon Ar 18 39.948 1.63 §
3.203
Arsenic As 33 74.922 5.75 11.867
Astatine At 85 (210) — 95.730
Barium Ba 56 137.327 3.62 37.440
Beryllium Be 4 9.012 1.85 0.111
Bismuth Bi 83 208.980 9.79 90.526
Boron B 5 10.811 2.34 0.188
Bromine Br 35 79.904 3.10 13.474
Cadmium Cd 48 112.411 8.69 26.711
Calcium Ca 20 40.078 1.54 4.038
Carbon C 6 12.011 2.2 (graphite) 0.284
3.51 (diamond)
Cerium Ce 58 140.116 6.77 40.443
Cesium Cs 55 132.905 1.87 35.985
§
Chlorine Cl 17 35.453 2.90 2.822
Chromium Cr 24 51.996 7.15 5.989
Cobalt Co 27 58.933 8.86 7.709
Copper Cu 29 63.546 8.96 8.979
Dysprosium Dy 66 162.500 8.55 53.789
Erbium Er 68 167.260 9.07 57.486
Europium Eu 63 151.964 5.24 48.519
§
Fluorine F 9 18.998 1.55 0.685
Francium Fr 87 (223) — 101.147
Gadolinium Gd 64 157.250 7.90 50.239
Gallium Ga 31 69.723 5.91 10.367
Germanium Ge 32 72.610 5.32 11.103
Continued
445
446 Physics in Nuclear Medicine
HYDROGEN-3
3
1
H(12.35y)
0.0
0.0
β1 3
2He(stable)
449
450 Physics in Nuclear Medicine
CARBON-11 NITROGEN-13
13
11 7N(9.965m)
6 C(20.38m) 0.0
0.0
0.0
0.0 13 EC1,β 1
+ 6C(stable)
11
B(stable) EC1,β1
5
Half Life = 9.965 Minutes
Half Life = 20.38 Minutes Decay Mode(s): EC, β+
Decay Mode(s): EC, β +
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i) β 1 9.98E-01 4.918E-01* 4.91E-01
β+ 1 9.98E-01 3.855E-01* 3.85E-01 γâ•›± 2.00E 00 5.110E-01 1.02E 00
γâ•›± 2.00E 00 5.110E-01 1.02E 00 Kα1 X ray 2.38E-06 2.774E-04 6.59E-10
Kα1 X ray 1.62E-06 1.833E-04 2.97E-10 Kα2 X ray 1.19E-06 2.774E-04 3.30E-10
Kα2 X ray 8.10E-07 1.833E-04 1.48E-10 Auger-KLL 1.80E-03 2.564E-04* 4.61E-07
LISTED X, γ AND γâ•›± RADIATIONS 1.02E 00 LISTED X, γ AND γâ•›± RADIATIONS 1.02E 00
LISTED β, ce AND Auger RADIATIONS 3.85E-01 LISTED β, ce AND Auger RADIATIONS 4.91E-01
LISTED RADIATIONS 1.40E 00 LISTED RADIATIONS 1.51E 00
*AVERAGE ENERGY (MeV) *AVERAGE ENERGY (MeV)
BORON-11 DAUGHTER IS STABLE. CARBON-13 DAUGHTER IS STABLE.
OXYGEN-15
15
8O(122.24s)
0.0
CARBON-14
0.0
15 EC1,β
7N(stable)
14 1
6C(5730y)
0.0
Half Life = 122.24 Seconds
Decay Mode(s): EC, β+
FLUORINE-18
18
9F(109.77m)
0.0
0.0
18
8O(stable)
EC1,β1
SODIUM-22
22
11Na(2.602y)
0.0
1.2746
EC1,β
1
γ1
0.0
22
Ne(stable) EC2,β2
10
PHOSPHORUS-32 CHROMIUM-51
32
15 P(14.29d) 51
0.0 24
Cr(27.704d)
0.0
0.0
β 32 0.3201
1 16 S(stable)
EC1
γ1
Half Life = 14.29 Days
0.0
Decay Mode(s): β– 51 EC2
23V(stable)
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i)
β– 1 1.00E 00 6.947E-01* 6.95E-01 Half Life = 27.704 Days
LISTED β, ce AND Auger RADIATIONS 6.95E-01
Decay Mode(s): EC
LISTED RADIATIONS 6.95E-01
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
*AVERAGE ENERGY (MeV)
γ1 9.83E-02 3.201E-01 3.15E-02
SULFUR-32 DAUGHTER IS STABLE.
ce-K, γ 1 1.52E-04 3.146E-01 4.78E-05
ce-L1, γ 1 1.38E-05 3.194E-01 4.41E-06
COBALT-57
57
27
Co(270.9d)
0.0
0.7064
EC1
γ9
0.1365 EC2
γ2
0.0144
γ3 γ1
0.0
57
26Fe(stable)
COBALT-60 COPPER-62
60
27Co(5.271y) 62
29Cu(9.74m)
0.0
0.0
2.5057
γ3
β
1
1.3325 2.0488
β
3 EC8,β 2
γ4 γ3
0.0 1.1730
60
28Ni(stable)
EC9,β 3
γ6
Half Life = 5.271 Years
Decay Mode(s): β– 0.0
62 EC10,β 4
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i) 28Ni(stable)
COPPER-64
64
29
Cu(12.701h)
0.0
1.3459
γ1
EC1 0.0
0.0
β1 64
30Zn(stable)
64 EC2,β 1
28Ni(stable)
GALLIUM-67
67
31
Ga(78.26h)
0.0
0.8877
EC1
γ10 γ7
0.3935 EC2
γ9 γ6 γ5 γ4
0.1846 EC3
γ3 γ1
0.0933 EC4
γ2
0.0 EC5
67
30Zn(stable)
Half Life = 78.26 Hours Half Life = 78.26 Hours Half Life = 78.26 Hours
Decay Mode(S): EC Decay Mode(s): EC Decay Mode(S): EC
Radiation y(i) (Bq•s) –1
E(i) (MeV) y(i) × E(i) Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ1 3.07E-02 9.127E-02 2.80E-03 γ 10 1.45E-03 8.877E-01 1.29E-03
ce-K, γ 1 2.23E-03 8.161E-02 1.82E-04 Kα1 X ray 3.28E-01 8.639E-03 2.83E-03
γ2 3.83E-01 9.331E-02 3.57E-02 Kα2 X ray 1.67E-01 8.616E-03 1.44E-03
ce-K, γ 2 2.87E-01 8.365E-02 2.40E-02 Kβ1 X ray 4.49E-02 9.572E-03 4.30E-04
ce-L1, γ 2 2.54E-02 9.212E-02 2.34E-03 Kβ3 X ray 2.30E-02 9.572E-03 2.20E-04
ce-L2, γ 2 3.98E-03 9.227E-02 3.67E-04 Auger-KLL 4.67E-01 7.466E-03* 3.49E-03
ce-L3, γ 2 5.81E-03 9.229E-02 5.36E-04 Auger-KLX 1.33E-01 8.482E-03* 1.12E-03
ce-M, γ 2 5.17E-03 9.322E-02* 4.82E-04 Auger-KXY 1.31E-02 9.473E-03* 1.24E-04
γ3 2.09E-01 1.846E-01 3.87E-02 Auger-LMM 1.55E 00 9.444E-04* 1.46E-03
ce-K, γ 3 4.07E-03 1.749E-01 7.11E-04 Auger-LMX 1.43E-01 1.020E-03* 1.46E-04
ce-L1, γ 3 3.87E-04 1.834E-01 7.11E-05 Auger-MXY 3.49E 00 4.566E-05* 1.60E-04
γ4 2.37E-02 2.090E-01 4.94E-03 LISTED X, γ AND γâ•›± RADIATIONS 1.58E-01
ce-K, γ 4 1.90E-04 1.993E-01 3.79E-05 OMITTED X, γ AND γâ•›± RADIATIONS** 8.52E-05
γ5 1.68E-01 3.002E-01 5.04E-02 LISTED β, ce AND Auger RADIATIONS 3.54E-02
ce-K, γ 5 5.83E-04 2.906E-01 1.69E-04 OMITTED β, ce AND Auger 1.04E-04
RADIATIONS**
γ6 4.70E-02 3.935E-01 1.85E-02
LISTED RADIATIONS 1.93E-01
γ7 6.86E-04 4.942E-01 3.39E-04
OMITTED RADIATIONS** 1.89E-04
γ9 5.13E-04 7.944E-01 4.08E-04
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
ZINC-67 DAUGHTER IS STABLE.
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 457
GALLIUM-68 GERMANIUM-68
68 68
31Ga(68.0m) 32
Ge(271d)
0.0 0.0
2.3387
EC2
1.8832 0.0
EC3
γ4
68
31Ga(68.0m)
EC1
RUBIDIUM-82 YTTRIUM-90
82 90
37
Rb(1.3m) 39Y(64.0h)
0.0 0.0
1.7607
β
1 γ1
0.0
β 90
40Zr(stable)
2
2.1718
EC4,β 4 Half Life = 64 Hours
Decay Mode(s): β–
1.4748
EC6,β 6 Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ5 β 2
–
1.00E 00 9.348E-01* 9.35E-01
0.7765
EC7,β 7 Kα1 X ray 5.79E-05 1.578E-02 9.13E-07
ZIRCONIUM-89
89
40Zr(78.43h)
0.0
2.6221
EC1
2.5665 EC2
1.7445 EC4
4 3
0.9092 EC5,
1
5 1
0.0
89
39Y(stable)
MOLYBDENUM-99
99
42 Mo(66.0h)
0.0
1.1418
β
2
γ29
1.0040
β
4 γ28
0.9206
β
5
γ25
0.6715
γ19
0.5091
β
6
γ27 γ11
0.1811
γ2
0.1426
β
7
γ8 0.1405
γ4
0.0
99
43Tc(2.13E5y)
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 461
TECHNETIUM-99M
99m
43Tc(6.02h)
0.1426
γ1
0.1405
γ 3 γ2
0.0
99
43Tc(2.13E5y)
INDIUM-111
111
49 In(2.83d)
0.0
0.4167
γ1 EC1
0.2454
γ2
0.0
111
48 Cd(stable)
Half Life = 2.83 Days Half Life = 2.83 Days Half Life = 2.83 Days
Decay Mode(S): EC Decay Mode(s): EC Decay Mode(S): EC
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i) Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
γ1 9.05E-01 1.713E-01 1.55E-01 Kβ2 X ray 2.35E-02 2.664E-02 6.26E-04
ce-K, γ 1 8.27E-02 1.446E-01 1.19E-02 Kβ3 X ray 4.14E-02 2.606E-02 1.08E-03
ce-L1, γ 1 9.51E-03 1.673E-01 1.59E-03 Auger-KLL 1.06E-01 1.917E-02* 2.03E-03
ce-L2, γ 1 5.32E-04 1.676E-01 8.91E-05 Auger-KLX 4.55E-02 2.232E-02* 1.02E-03
ce-M, γ 1 1.95E-03 1.707E-01* 3.33E-04 Auger-KXY 5.85E-03 2.544E-02* 1.49E-04
ce-N+, γ 1 4.08E-04 1.713E-01* 6.99E-05 Auger-LMM 6.73E-01 2.590E-03* 1.74E-03
γ2 9.40E-01 2.454E-01 2.31E-01 Auger-LMX 3.06E-01 3.187E-03* 9.75E-04
ce-K, γ 2 5.03E-02 2.187E-01 1.10E-02 Auger-LXY 3.86E-02 3.583E-03* 1.38E-04
ce-L1, γ 2 5.15E-03 2.414E-01 1.24E-03 Auger-MXY 1.91E 00 5.104E-04* 9.75E-04
ce-L2, γ 2 1.38E-03 2.417E-01 3.32E-04 LISTED X, γ AND γâ•›± RADIATIONS 4.05E-01
ce-L3, γ 2 1.32E-03 2.419E-01 3.19E-04 OMITTED X, γ AND γâ•›± RADIATIONS** 2.00E-04
ce-M, γ 2 1.52E-03 2.448E-01* 3.71E-04 LISTED β, ce AND Auger RADIATIONS 3.44E-02
ce-N+, γ 2 3.01E-04 2.454E-01* 7.39E-05 OMITTED β, ce AND Auger 3.14E-05
RADIATIONS**
Kα1 X ray 4.43E-01 2.317E-02 1.03E-02
LISTED RADIATIONS 4.40E-01
Kα2 X ray 2.36E-01 2.298E-02 5.42E-03
OMITTED RADIATIONS** 2.31E-04
Kβ1 X ray 8.07E-02 2.609E-02 2.10E-03
*AVERAGE ENERGY (MeV)
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
CADMIUM-111 DAUGHTER IS STABLE.
464 Physics in Nuclear Medicine
IODINE-123
123
53I(13.2h)
0.0
0.8947
γ39 EC4
0.7836
EC5
γ36 0.6975
EC7
0.6879
γ29 γ12 EC8
0.5053
γ28 γ22 EC10
0.4400
EC12
γ30 γ16
0.1590
EC13
γ41 γ38 γ25 γ2
0.0
123
52Te(1E13y)
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 465
466
124
53I(4.18d)
0.0
0.0
124
52 Te(stable)
EC25,β
6
IODINE-124
Half Life = 4.18 Days Half Life = 4.18 Days Half Life = 4.18 Days
Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i) Radiation y(i) (Bq•s)–1 E(i) (MeV) y(i) × E(i)
+
β 2 2.92E-03 3.657E-01* 1.07E-03 γ 61 3.50E-03 2.079E 00 7.27E-03
+
β 5 1.12E-01 6.859E-01* 7.66E-02 γ 62 5.80E-03 2.091E 00 1.21E-02
+
β 6 1.12E-01 9.736E-01* 1.09E-01 γ 64 1.40E-03 2.099E 00 2.94E-03
γ± 4.53E-01 5.110E-01 2.31E-01 γ 65 1.10E-03 2.144E 00 2.36E-03
467
**EACH OMITTED TRANSITION CONTRIBUTES <â•›0.100% TO Σy(i) × E(i) IN ITS CATEGORY.
468 Physics in Nuclear Medicine
IODINE-125
125
53I(60.14d)
0.0
0.0355
γ1 EC1
0.0
125
52Te(stable)
IODINE-125—cont'd
IODINE-131
131
53 I(8.04d)
0.0
0.7229
β
1
γ18
0.6669
β
2
0.6370
β
3
γ16 γ12
0.3645
β
4
0.3411
β
5
γ4
0.1639
β
6 γ17 γ7
0.0802
γ19 γ14 γ1
0.0
131
54 Xe(stable)
Appendix C╇ •â•‡ Decay Characteristics of Some Medically Important Radionuclides 471
0.1606
β2
γ3 γ1
0.0810
β
3
γ2
0.0
133
55Cs(stable)
CESIUM-137
137
55Cs(30.0y)
0.0
0.6616
β
1
0.0
β 137
56Ba(stable)
2
THALLIUM-201
201
81Tl(3.044d)
0.0
0.1675 EC1
γ5
γ7 γ6
0.0322 EC2
γ3
0.0016 EC4
γ4 γ1
0.0
201
80 Hg(stable)
THALLIUM-201—cont'd
476
Appendix D╇ •â•‡ Mass Attenuation Coefficients for Water, NaI(Tl), Bi4Ge3O12, Cd0.8Zn0.2Te, and Lead 477
478
Appendix E╇ •â•‡ Selected Internally Administered Radiopharmaceuticals 479
Fourier transforms (FTs) play an important The concept of spatial frequency is illus-
role in tomographic reconstruction (see trated in Figure F-1. Slow oscillations
Chapter 16) and in computer implementation represent low spatial frequencies and rapid
of convolutions (see Appendix G). As well, they oscillations represent high frequencies. If fâ•›(x)
are the basis for the modulation transfer func- represents an image profile, the former would
tion (MTF), one of the methods for evaluating represent primarily the coarse structures,
spatial resolution of imaging systems (see whereas the latter would represent fine
Chapter 15) and many other methods for details.
image analysis and image processing. This Thus F(k) is a representation of the image
appendix is intended to provide an intuitive profile in k-space, or spatial-frequency space,
description of what the FT is, how it is calcu- whereas fâ•›(x) is a representation of the profile
lated, and some of its properties. For simplicity, in object space (sometimes also called distance
the analysis is presented for one-dimensional space). Either fâ•›(x) or F(k) is a valid represen-
examples. The extension to higher dimensions tation of the image intensity profile and, as
is relatively straightforward. A detailed treat- shown subsequently, either one can be derived
ment is beyond the scope of this text. The from the other. Another notation for the FT is
interested reader is referred to the excellent
texts by Bracewell for further information.1,2 F (k) = F [ f ( x)] (F-1)
High
frequency
Medium
frequency
FIGURE F-1â•… Sinusoidal functions representing
low, medium, and high spatial frequencies.
Low
frequency
and so on, we will restrict our analysis to the where i = −1 is a complex (“imaginary”)
discrete Fourier transform (DFT). number. Thus values for F are computed at N
In practice, a function representing a points at intervals Δâ•›k along the k-axis,
signal, such as an image intensity profile fâ•›(x), ranging from k = 0 to kmax = (N – 1)Δâ•›k. The
is sampled at a finite number of points, N, at “zero-frequency” term actually represents a
equally spaced intervals Δâ•›x. The range of x constant equal to the average value of fâ•›(x)
over which the function is sampled, NΔâ•›x, is within the digitized field of view, FOVx. We
the field-of-view along x, denoted by FOVx. For will designate the range of k-space over which
detectors with discrete detector elements, the the FT is computed, NΔâ•›k, as FOVk (i.e., the
sampling interval generally is the width of a “field of view” in k-space).
detector element and the number of samples The complex exponential term in Equation
is the number of elements across the detector F-3 represents Euler’s equation, which states
array. For gamma cameras, N and Δâ•›x (or that
FOVx) can be chosen somewhat arbitrarily
under computer control. In this case, FOVx
may or may not equal the physical field of view eiθ = cos θ + i sin θ (F-4)
of the detector. It simply refers to the distance
along the x-axis over which data are sampled, Thus in general, the values of Fm are complex
which may be smaller (or even larger) than numbers with “real” and “imaginary” parts.
the physical dimensions of the detector. This does not imply that the FT is some
Although N can be any integer, it usually is a sort of “imaginary” entity. Rather, the use
power of 2 (64, 128, 256, etc.). Using a power of complex numbers in Equation F-3 provides
of 2 allows one to use a very fast computa- a mathematically convenient way for com�
tional algorithm called the fast Fourier trans- puting the amplitudes of “cosine” functions
form (FFT). FFTs are provided in many versus “sine” functions in the representation
mathematical software packages. The basic of fâ•›(x).
algorithm is described in reference 3. Conversely, if one is provided with a set
Consider the case in which fâ•›(x) is sampled of N values for F, they can be used to compute
at N points over a range of x values from x = N values for f using the inverse discrete FT,
0 to (N – 1)Δâ•›x. The sampled data are repre- described by
sented as
N −1
f j = f ( j∆ x ) j = 0, 1, 2, .… N − 1 (F-2)
f ( j∆ x) = f j = ∑Fe κ
i 2 π jκ / N
(F-5)
Given N sampled points, the discrete FT of κ =0
distinguish between the two, Equation F-3 interval in object space. The relationships
sometimes is referred to as the forward FT. between data ranges and intervals are com-
Finally, if the original data are properly pletely symmetrical between object space
sampled (e.g., if they meet the requirements and k-space. Figure F-2 illustrates these
of the sampling theorem discussed later), the relationships.
inverse FT of the forward FT returns an exact Equations F-7 and F-8 have important
replica of the original data. In other words, practical ramifications. Specifically, a funda-
mental assumption underlying the discrete
F −1
[ F [ f ( x)]] = f ( x) (F-6) FT algorithm is that the sampled function fâ•›(x)
actually extends indefinitely along the x-axis,
repeating itself at intervals NΔâ•›x = FOVx. In
other words, it assumes that the sampled
C. SOME PROPERTIES OF FOURIER data simply repeat themselves to infinity in
TRANSFORMS both directions along the x-axis. Conversely,
it assumes as well that F(k) repeats itself at
Equations F-3 and F-5 are mathematically intervals NΔâ•›k, again to infinity, in both direc-
powerful, but not exactly transparent regard- tions along the k-axis. This means, for
ing how they operate. Therefore we will not example, that because of cyclic repetition,
attempt to analyze them in any detail. Rather, F(NΔâ•›k) = F(0). This result can be understood
we will focus only on some properties of the by observing that NΔâ•›k = FOVk and, according
discrete FT. to Equation F-8, FOVk = 1/Δâ•›x.
As noted previously, the FT of a function Thus if a sinusoidal oscillation with spatial
that is sampled at N points also has N values. frequency NΔâ•›k is present in the underlying
It can be shown that the following relation- sampled function, it would be sampled pre-
ships apply regarding data intervals and cisely once per cycle. Furthermore, with precise
range in k-space: timing, it would be sampled always at the
same point during the cycle. Thus the sampled
∆k = 1/FOVx (F-7) data for a spatial frequency k = NΔâ•›k would be
FOVk = 1/∆ x (F-8) indistinguishable from a “constant” signal
level (i.e., k = 0). Similarly, the next higher
Thus the data interval in k-space is inversely frequency, (N + 1)Δâ•›k, would be sampled less
proportional to the data range in object than once per cycle and would be indistin-
space, and conversely, the data range in guishable from a lower frequency, which turns
k-space is inversely proportional to the data out to be k1. This effect, in which a higher
FOVx1/k
x
x
k
FOVk1/x
FIGURE F-2â•… Illustration of the relationships between sampling ranges and sampling intervals in object space and
k-space.
484 Physics in Nuclear Medicine
frequency is falsely identified as a lower one, sampled function actually contained frequen-
is called aliasing.* cies out to ±10╯ cm−1. Because of underÂ�
From this illustration, it is apparent that sampling, frequencies between 8 and 10╯ cm−1
the highest spatial frequency that can be rep- are “wrapped around” and overlap the lower
resented accurately in a discrete FT is deter- end of the negative frequency portion of
mined by the sampling interval along the the spectrum. A similar wraparound of nega-
x-axis. However, there is yet another compli- tive frequencies occurs at the high end of
cation. Specifically, an image (or any object- the spectrum. When the FT is calculated,
space profile) can contain both positive and the overlapped portions are simply added
negative frequencies. For a cosine function, together in the aliased regions of the
there is no difference, because cos(–x) = cos(x). spectrum.
However, for a sine function, sin(–x) = –sin(x), This effect and its consequences for emis-
so the positive and negative oscillations are sion CT reconstruction are discussed in
reversed. In terms of the level of “detail” con- Chapter 16, Section C.1. Similar effects occur
tained in an image or profile, the difference in other applications of FTs [e.g., computa-
between positive and negative frequencies is tions of MTFs (see Chapter 15, Section B.2)].
unimportant. The practical importance is The sampling theorem also has practical ram-
that the use of “negative frequencies” allows ifications for data acquisition with arrays of
one to obtain consistent representations discrete detector elements. It can be shown
for the FT of a function fâ•›(x) that is shifted that a linear array of detector elements, each
along the x-axis, but otherwise unchanged. of width d, with negligibly small spacings
This is the basis of the “shift theorem,” which between elements, can detect spatial frequen-
is discussed in advanced texts.4 cies out to k = 1/d and even beyond. (See
The presence of negative frequencies means Figure F-5C, which is essentially the MTF for
that the highest spatial frequency that can an aperture of width d = 1.) However, with
be computed by a discrete FT is not NΔâ•›k, only one sample per distance d, the Nyquist
but only half this value. This frequency, called frequency is kNyquist = 1/(2d ) = (1/2) × (1/d ) (i.e.,
the Nyquist frequency, can be derived one half the frequency that would be desired
from Equations F-6 and F-7 and usually is for kmax = 1/d ). Thus spatial frequencies in the
expressed as range 1/(2d ) < k < 1/d are aliased back into
lower frequency portions of the spectrum,
kNyquist = 1/ (2 × ∆ x) (F-9) where they can cause distortions of the
recorded profile. One way to avoid this is to
This equation is the basis of the sampling acquire a second set of data with the detector
theorem,5 which states that, to accurately array “shifted” by one half the width of the
compute (or “recover”) a specified spatial fre- individual detector elements and to insert
quency requires a sampling rate of at least these data points between those for the
two samples per cycle at that frequency. Fre- “unshifted” data. This reduces the sampling
quencies higher than the Nyquist frequency interval from d to d/2, thereby suppressing
cannot be distinguished from lower frequen- the effects of aliasing.
cies. An example is illustrated in Figure F-3. This analysis applies when the spatial
Profiles (or signals) containing frequencies resolution of the individual detector elements
that are higher than the Nyquist frequency is essentially the width of the element. This
specified in Equation F-9 are said to be would apply, for example, to collimated linear
undersampled. arrays operating in single-photon counting
Undersampling and aliasing can lead to mode. The situation is yet more complicated
image distortions, errors in data analysis, in positron emission tomography (PET), for
and so forth. Figure F-4 illustrates their which the spatial resolution of a pair of detec-
effects in k-space. In this hypothetical tors of width d can be as small as d/2 (see
example, a sampling rate was used corre- Chapter 18, Section A.3). In this case, inter-
sponding to kNyquist = 8╯ cm−1; however, the leaving is essential to achieve the required
sampling frequency. Techniques for accom-
plishing this in PET imaging are described in
Chapter 18, Section A.6.
*Most readers will have seen examples of aliasing in It is important to realize that aliasing
motion pictures, in which undersampling in the frame
rate leads to the appearance of false and even backward
cannot be “undone” by postprocessing of
rotations of the spokes of wagon wheels, helicopter undersampled data. If one starts with an
blades, and so forth. undersampled data set, there is no way to
Appendix F╇ •â•‡ The Fourier Transform 485
Signal level
1
1
0 0.5 1 1.5 2
Distance (cm)
FIGURE F-3â•… Illustration of the effects of undersampling of a spatially varying source distribution. The red curve
represents the actual signal, which has a spatial frequency of 6 cycles per cm (6╯cm−1). Black dots represent sampled
points. The sampling distance is Δâ•›x = 0.1╯cm, for which the Nyquist frequency is 5╯cm−1. As a result of undersampling,
the sampled data for a spatial frequency of 6╯cm−1 cannot be distinguished from a signal corresponding to a spatial
frequency of 4╯cm−1 (╛╛green line). The false representation of higher frequencies as lower frequencies is called
aliasing.
Aliased regions
F (k)
Actual spectrum
Overlap
10 8 6 4 2 0 2 4 6 8 10
Spatial frequency, k (cm1)
FIGURE F-4â•… Illustration of the effects of aliasing in k-space. The graphs represent hypothetical Fourier transforms
(FTs). Data in object space were sampled at 16 points per cm (cm−1) for computing the FT. The Nyquist frequency for
this sampling rate is 8╯cm−1. However, the actual spatial-frequency spectrum (blue line) has significant frequency
content extending out to 10╯cm−1. As a result of undersampling, the replicated ends of the actual spectrum (orange line)
overlap and add to the calculated spectrum (heavy red line), creating an aliased region of the spectrum. The calculated
spectrum does not accurately represent the true FT for the object.
“unwrap” the spectral overlap illustrated in that is sufficiently small to meet the
Figure F-4. requirements of the sampling theorem
Aliasing can be avoided in a number of for all frequencies present in the data.
ways, including the following: One way to achieve this is to acquire
1. The most direct way is to use a sampling more data points along the sampled dis-
interval along the x-axis (or along what- tance. However, for applications involv-
ever object-space axis is being sampled) ing FFTs, this requires increasing the
486 Physics in Nuclear Medicine
number of samples (e.g., pixels) by a spatial frequency that has nonzero amplitude
power of 2, which could be impractical is k = 0, and that amplitude is equal to the
for reasons of dataset size, computation value of the constant.
time, and so on. Figure F-5B shows a cosine wave of spatial
2. If increasing the number of samples is frequency 1 cycle per cm and amplitude 1.0
not practical, one could use the same superimposed on a constant value of 1 unit.
number of samples but apply them over In this case, fâ•›(x) = 0.5 cos (2πâ•›x) + 1. The FT
a smaller field-of-view, thereby decreas- has an amplitude of 1 at k = 0, and amplitudes
ing the sampling interval Δâ•›x. This would of 0.5 each at ±1╯cm−1. This ambiguity arises
increase the Nyquist frequency (Equa- from the fact that the FT cannot distinguish
tion F-9); however, reducing FOVx also between positive versus negative cosine func-
has practical constraints. For example, tions at these frequencies. (They are in fact
the field-of-view must provide full cover- identical.) Thus it assigns half of the observed
age of the scanned portion of the body in amplitude to each value. (The FT of a sine
computed tomography. function is similar, except that the value for
3. A third alternative is to deliberately k = –1╯cm−1 is –0.5. This is because the FT
“blur” the input profile (or image) before cannot distinguish a positive sine wave of
it is recorded by the detectors so as negative frequency from a negative sine wave
to suppress the potentially undersam- of positive frequency.)
pled high-frequency components. In the Figure F-5C shows a “boxcar” function
context of image profiles, this means that (sometimes also called a “rect” function) for
the data projected onto the detector itself which fâ•›(x) = 1 when x is within the range –0.5
must be “blurred” (e.g., by using a coarser ≤ x ≤ +0.5 and fâ•›(x) = 0 outside this range. This
collimator). The obvious disadvantage of function crops up often in signal-processing
this approach is that the resulting image techniques that employ “windowing” filters to
also is blurred. eliminate portions of the spectrum outside a
If none of these options are practical, the windowed range in k-space. In this case, the
effects of undersampling can be minimized FT is a more complicated function (specifi-
(but not eliminated) by postprocessing steps. cally, a “sinc function”).
One approach for already undersampled data Figure F-5C illustrates that FTs can exist
is to simply “lop off ” or otherwise completely even for functions with unusual properties,
suppress portions of the frequency spectrum such as discontinuities. Also, although fâ•›(x)
that might be affected by aliasing. However, itself does not have apparent “high-frequency
as illustrated in Figure F-4, the potentially oscillations,” its FT has high-frequency com-
affected range is somewhat unpredictable and ponents. These components are necessary to
may be large. This also is a rather wasteful represent the sharp edges of the boxcar. Thus
approach, because one ends up throwing away the MTF of an imaging system must have a
not only frequencies above the Nyquist fre- good high-frequency response to faithfully
quency but any lower frequencies that they reproduce sharp edges and fine details. In
overlap after they are wrapped around in the addition, the figure indicates that windowing
spectrum. filters with sharp edges in k-space can create
“ringing artifacts” (sometimes called Gibbs
phenomenon) in object space. These features,
as well as illustrations of FTs of many other
D. SOME EXAMPLES OF FOURIER mathematical functions, are presented and
TRANSFORMS discussed in reference 1.
Finally, Figure F-6 shows a brain image, an
Figure F-5 shows some one-dimensional intensity profile for a strip across the image,
examples of functions and their FTs. Note and the FT of that profile. Note that most of
that the functions are represented as continu- the “information” is contained in the low-fre-
ous functions. If DFTs were involved, the quency portion of the spectrum. This does not
underlying functions would be the same, but mean that the high-frequency response (MTF)
the data would be represented by “points” on of the imaging system is unimportant. Indeed,
the curves, following the rules outlined in the because the high-frequency components are
preceding section. relatively weak to begin with, it is important
In Figure F-5A, fâ•›(x) is a constant, as would that the imaging system be able to faithfully
be all sampled values of it. Therefore the only preserve them.
Appendix F╇ •â•‡ The Fourier Transform 487
2 1.5
1.5 1
Fourier
F(k)
f (x)
1 transform 0.5
0.5 0
0 0.5
2 1 0 1 2 2 1 0 1 2
A Spatial domain (cm) Frequency domain (cm1)
2 1.5
1.5 1
Fourier
F (k)
f (x)
1 transform 0.5
0.5 0
0 0.5
2 1 0 1 2 2 1 0 1 2
B Spatial domain (cm) Frequency domain (cm1)
2 1.5
1.5 1
Fourier
F(k)
f(x)
1 transform 0.5
0.5 0
0 0.5
2 1 0 1 2 4 2 0 2 4
C Spatial domain (cm) Frequency domain (cm1)
FIGURE F-5â•… Three functions and their Fourier transforms (FTs). A, fâ•›(x) = 1.0. Its FT has only one value, at k = 0.
B, f (x) = cos(2πâ•›x) + 1. Its FT has values at k = 0 and at k = ±1╯cm−1, corresponding to the spatial frequency of the cosine
function. C, A boxcar function, fâ•›(x) = 1 when –0.5 < x < 0.5, fâ•›(x) = 0 otherwise. Its FT is a sinc function, sinc(x) =
[sin(πâ•›x)]â•›/(πâ•›x). Note that this also is the modulation transfer function of an aperture or a detector element of unit width.
488 Physics in Nuclear Medicine
250
200
150
Counts
100
50
0
0 32 64 96 128
Pixel (x )
FT
250
200
Amplitude
150
100
50
0
64 32 0 32 64
Frequency (pixels1)
FIGURE F-6â•… Frequency spectrum for a profile recorded through a brain image. The box on the image indicates the
sampling line for the profile (i.e., the direction x is vertical).
f (u) g(u)
5
4
2 2 2
1 1 1 1
0 0
f * g h
0.8
0.6 f(x)
Function value
0.0
3 2 1 0 1 2 3 4 5
x
Note: Page numbers followed by f indicate figures; those followed by t indicate tables.
Cardiac output, 393, 394 Chang multiplicative method, 294, Coincidence counting rates,
Cardiac studies 294f, 296, 297f 162-163, 322-324, 322f,
first-pass Channels of multichannel analyzer, 329-330
gamma camera for, 213, 214, 116-118, 116f in PET, 322-324, 322f, 329-330
392 Characteristic x rays, 10-13, 11f, random, 322-323, 322f, 329-330
labeled RBCs for, 392, 392f 12t correction for, 336-337
PET for, 339 after electron capture, 24-25 estimation of, 336, 340
SPECT system for, 81 after internal conversion, 23 scatter, 322-324, 322f, 329-330
frame rates in, 368 after ionization, 63 correction for, 337-338
gated, 234, 303, 304, 304f, 392, after photoelectron ejection, 74 true, 322-323, 322f
392f in radiation detector, 151 uncertainty in, 336, 337
motion blurring in, 234, 369 Charged particles. See also Alpha Coincidence detection. See also
with PET, 339 particles; Beta particles; Annihilation coincidence
short axis views in, 369 Electrons; Positrons. detection (ACD).
with SPECT, 281-283, 303, 305f, Cerenkov effect and, 68-70 of cascaded emissions, 162-163
306 definition of, 63 efficiency of, 162-163
Carrier-free samples, 37-38 energy losses and, 63-66, 67, 67f, for liquid scintillation counters,
production of, 46 68, 70. See also Energy 183f, 184
Carrier-free specific activity losses. spatial resolution for, 310,
(CFSA), 37-38, 56 interactions with matter, 63-68, 311f-312f
Carrier-mediated diffusion, 64f, 65f, 66f, 67f, 69f, 70 Coincidence rate, 319
389-390, 397 ranges of, 70-74, 70f, 72f-73f, Coincidence summing, 145,
Cassen, Benedict, 2, 3f, 195 73t 146f
Cathode ray tubes (CRTs), 123-124, ACD and, 312-314, 313f, Coincidence timing windows, 121,
123f, 367 314f 307
digital image and, 367 detector types and, 141 definition of, 121
hard copy derived from, 367 tracks of, 66-68, 67f in PET systems, 307, 322, 323,
Cathodes in ionization detectors, energy deposition along, 67-68, 329, 337
87, 88f, 99 67f Coincidence units (logic), 121-122,
Cd-109, 165t length of, 70-74, 70f, 72f-73f, 184
C-D studies. See Contrast-detail 73t in PET, 307
(C-D) studies. Charged-particle accelerators, Cold lesions, 246, 248, 269
CdTe detectors. See Cadmium 47-50, 48f-50f, 50t Coldfinger, 97, 97f
telluride (CdTe) detectors. Charge-sensitive preamplifiers, Collimation
Center of field-of-view (CFOV), 107-108, 109f absorptive, 201, 220, 312-321,
229-230 Chelation, 58 322
Center of rotation (COR) in SPECT, Chemical elements, 9. See also electronic, 308
302-303 Nuclides. Collimator efficiency
Central processing units (CPUs), properties of, 445 of converging collimators,
363 transmutation of, 20, 21, 24, 25, 225-228, 226f-227f
Central volume principle, 380, 27 definition of, 220, 223
394 Chemical properties, radioactive of diverging collimators, 225-228,
Kety-Schmidt method and, 395 decay and, 19-20 226f-227f
CERASPECT system, 280-281, Chemical purity, 59 of parallel-hole collimators, 222,
282f Chemical quenching, 106, 188 224f, 225t
Cerebral imaging Chi square test, 133-134, 134f of pinhole collimators, 225-228,
image co-registration and, in quality assurance, 172 226f-227f
375-376 Chromatography volume sensitivity and, 301
parametric, for glucose liquid scintillation counting with, Collimator resolution. See also
metabolism, 400, 401f 188 Spatial resolution.
PET in, 330-331, 330f NaI(Tl) detector with, 182, 183f of converging collimators,
SPECT in, 280-281, 282f, Chromium-51, 452 225-228, 226f-227f
304-305, 304f Ci. See Curie (Ci). definition of, 220, 222
Cerenkov counting, 188 Cine mode, 371 of diverging collimators, 225-228,
Cerenkov effect, 68-70 Classic method in internal 226f-227f
Cesium-137, 165t, 473 radiation dosimetry, 407 of parallel-hole collimators, 220,
Cesium antimony (CsSb), 98 Clearance, tracer, 388 222, 222f, 225t
Cesium fluoride (CsF), 102-103 Clearance methods for blood system resolution and, 225. See
Cesium iodide [CsI(Tl)], 100, 101t flow measurement, 394-396, also Parallel-hole
in compact gamma camera, 207 396f collimators: collimator
in intraoperative gamma probe, Cloud chambers, 66 resolution and.
193, 193f CNR. See Contrast-to-noise ratio of pinhole collimators, 225-228,
Cesium iodide [CsI(Tl)] detectors, (CNR). 226f
101t Cobalt-57, 165t source-to-collimator distance
for cardiac SPECT, 281, 296-299 Cobalt-60, 165t and, 223, 224f, 227-228,
in gamma-ray probes, 193 Cocktails, liquid scintillation, 105, 227f-228f
CFOV. See Center of field-of-view 187 system resolution and, 225, 227
(CFOV). Code of Federal Regulations, 431 Collimators, 196, 196f, 201-203. See
CFSA. See Carrier-free specific Coherent scattering, 77 also specific types.
activity (CFSA). in SPECT, 297 absorptive, 201
Chain reaction, nuclear, 43 Coincidence circuits, 184 cone-beam, 274-275, 274f
498 Index
Counting losses in gamma camera, Counting systems (Continued) Dead time/dead time losses,
213-214, 213f, 215f, 230 in vivo, 173, 192-194 168-171, 168f, 169f, 171f
Counting rates, 130 whole-body, 194 apparent, 213, 213f, 214
in annihilation coincidence Counting time, statistical determination of
detection, 321 reliability and, 132-133 fixed-rate pulser method for,
background, 131 Counting vials, 184-185 171, 171f
for calibration sources Count-rate performance in SPECT, two-source method for, 171,
absolute activity assays and, 302 171f
177 Coverage requirements in in gamma cameras, 213-214,
detection efficiency and, 164 reconstruction tomography, 213f, 230
mock sources and, 177 266, 266f-267f correction methods for,
coincidence. See Coincidence CPUs. See Central processing units 213-214
counting rates. (CPUs). in Geiger-Müller counters, 188
crosstalk and, 178-179 CR differentiation circuit, 111-112, in liquid scintillation counters,
dead time losses and, 168-171 111f-112f 168
detection efficiency and, 155 Cristy-Eckerman phantoms, 414, mathematical models of,
with absorbing medium, 163 414f, 415t 168-169
with cascaded emissions, Cross section in NaI(Tl) well counters, 179
162-163 activation, 53-54, 54f in paralyzable vs.
with full-spectrum counting, neutron-capture, 45-47, 46t nonparalyzable systems,
159, 163 Cross-plane data acquisition, 332, 168-169, 168f-169f
with scattering medium, 163 333f percentage, 169
differences between, 130-131 Crosstalk in PET, 326, 330, 332, 339,
with energy-selective counting, in liquid scintillation counting, 340
159 184, 185, 187, 187f in SPECT, 302
estimation of, 132 between projection elements, 286 window fractions and, 170, 213,
of gamma camera, 213-216, 230 in well-counter measurements, 213f
with multiple radionuclide 178, 178f, 179, 181-182 Decay. See Radioactive decay.
sources, 178-179 CRTs. See Cathode ray tubes Decay constant, 31, 32
noise equivalent, 340-341, 341f (CRTs). average lifetime and, 34
observed vs. true, 168-169, CsF. See Cesium fluoride (CsF). definition of, 31
168f-169f CsI(Tl). See Cesium iodide [CsI(Tl)] half-life and, 33-34
optimal division of, 133 detectors. Decay curve, universal, 35, 35f
for paralyzable vs. CsSb. See Cesium antimony (CsSb). Decay factors, 32-33, 33f
nonparalyzable counting CT. See Computed tomography approximation to, 32, 32f, 33
systems, 168-169, 168f-169f (CT). determination of, 34-35
in pulse-height spectrometry, Cumulated activity, 409-412, 410f, effective, 35-37, 36f
146, 147f 411f tables of, 34, 34t
of SPECT system, 302 average absorbed dose and, 408, Decay rate. See Activity.
statistical significance of, 414, 417, 424 Decay scheme diagrams, 20-21,
130-131 calculation of, 424 20f
total-spectrum, 170 mean dose per, 411f, 414f, of important radionuclides, 449,
uncertainty in, 130, 131, 132, 415-416, 418t-423t 449f-475f
133 for 18F, 415-416, 422t-423t Decay series, 27-28, 27f
Counting statistics. See Statistical for 131I, 415-416, 420t-421t Decay time of scintillators, 101t,
analysis. for 99mTc, 415-416, 418t-419t 104
Counting systems, 173-194 problems in determination of, Decontamination measures, 439
for Cerenkov counting, 188 424 Deep-dose equivalent, 431-432
comparison of, 132 in source organ, 409-410, 424 Degrees of freedom, 136, 136f,
components of, 107, 108f, 173 Curie (Ci), 32 140
dead times of, 168-171 Curie, Marie, 2 Delayed window method, 336-337
detectors for, 173 Curve stripping, 39 Delay-line methods, 111, 113
conventional NaI(Tl), 182 Cut-off frequency in PET, 319 Delta (δ) rays, 63, 66, 67f
gas-filled, 189-190 Cyclotrons, 47-49, 48f-49f, 50t Density of absorbers
gas-flow counters in, 190 negative-ion, 48-49, 49f attenuation coefficient and,
liquid scintillation, 182-189. See principles and design of, 47-49, 78-79
also Liquid scintillation 48f-49f energy losses and, 65
counters (LSCs). radionuclides produced in, 49-50, range of alpha particles and,
NaI(Tl) well counters in, 50t 71
173-182, 174f, 174t. See also in cyclotrons, 47-50, 50t range of electrons and, 72, 73,
NaI(Tl) well counters. CZT detectors. See Cadmium zinc 73f
paralyzable vs. nonparalyzable, telluride (CZT) detectors. range of positrons and, 314
168-169 Dental implants, artifacts from,
probe 360
miniature beta particle, 194 D Deoxyglucose method, 397, 400
miniature gamma-ray, 192-194, (d, n) reaction, 47, 50t Depreotide, 99mTc-labeled, 305
193f Dalton (Da), 8 Depth-of-interaction (DOI) effect,
NaI(Tl), 192, 192f Dalton, John, 9 316-318, 317f, 326, 329, 330,
quality assurance for, 171-172 Dark adaptation of samples, 185 331
semiconductor, 190-192, 191f Daughter nucleus, 19 Derandomizers, 213-214
in vitro, 173 De Hevesy, Georg, 2 Derived quantities, 7
500 Index
Detectability. See also Phantoms. Detection efficiency (Continued) Digital image processing
of cold vs. hot lesions, 246, 248, of liquid scintillation counter, (Continued)
248f, 297 157, 185 image display in, 367
contrast-to-noise ratio and, of NaI(Tl) conventional detector, color, 367, 368f
243-244 156, 182 grayscale, 367, 370f
in emission computed of NaI(Tl) well counter, 157, 174, image segmentation in, 373-375,
tomography, 269-270 175, 175f-176f, 179 377f
information density and, nonuniform, 160-162, 160f-161f in CT-based attenuation
244-245, 246 of PET systems, 324 correction, 357
observer performance studies Compton scattering and, image smoothing in, 373, 375f
of, 247, 248, 249f, 250-251, 337 image visualization in
250f normalization corrections to, orientation of sections in, 369,
Rose criterion for, 244, 269 335-336 370f
size and, 244, 245, 246, 247 in phantoms, 166 parametric images and, 372
spatial resolution and, 246-247, photofraction and, 159, 160f projection tool for, 369-371,
247f photopeak and, 163 371f
Detection efficiency, 155-166 radiation absorption and, 156 surface rendering in, 369-371
attenuation and, 156, 160-164 radiation scatter and, 156, windowing in, 369, 370f
calibration sources and, 164-166, 163-164 Laplacian technique in,
165f, 165t scatter outside of detector and, 373-375
cascaded gamma emissions and, 144, 163-164, 164f linear sampling distance and,
162, 163 of semiconductor detectors, 151, 365-366
in coincidence detection, 158, 164, 190 matrix size in, 365
162-163 total, 160-161, 160f microprocessors for, 363
complicating factors in, 160-164, Detector scatter events, 204-205 for multislice tomographic
160f, 161f, 164f Detectors. See Radiation images, 364
components of, 155-156 detectors. networks for, 378
definition of, 156 Detergents for LS sample overview of, 363
edge effects and, 160 preparation, 187 pixel depth in, 365
emission rates and, 155 Deuterons in cyclotron, 47, 48 pixels in, 364, 364f. See also
energy-selective counting and, DF. See Decay factors. Pixels.
156, 159 DFT. See Discrete Fourier regions of interest in, 372-373,
factors affecting, 155-156 transform (DFT). 372f
of gamma camera, 211, 212f DICOM. See Digital Imaging and spatial resolution and, 365-367,
detector thickness and, 211, Communications in Medicine 366f. See also Spatial
212f (DICOM). resolution.
nonuniformity and, 217 Diethylenetriamine penta-acetic steps in, 376-378
used for PET, 329-330 acid (DTPA), 5t, 60t, 381t, techniques of, 369-376
of gamma cameras 479 co-registration in, 375-376,
detector thickness and, 211, Differential spatial linearity, 377f
212f 229-230 edge detection in, 373, 375,
nonuniform, 217 Differential uniformity, 229-230 376f
of gas flow counter, 190 Differentiation circuits, 111-112, image smoothing in, 373, 375f
geometric, 156, 157f-158f 111f-112f regions of interest in, 372-373,
of absorptive collimators, 321 Diffusion, carrier-mediated, 389, 372f
edge effects on, 160 390, 395, 397 segmentation in, 373, 375,
of gas flow counter, 190 Diffusion constant, 389 377f
of liquid scintillation counters, Digital counters, 119-121, 120f time-activity curves in, 373,
157 Digital image processing, 363-378. 374f
of NaI(Tl) detectors, 156, 182 See also Digital images. visualization tools in, 369,
in whole-body counter, 194 acquisition modes in, 367-369 370f, 371-372, 371f, 372f
of NaI(Tl) well counters, 157, frame-mode, 367-368 terminology for, 364-365
174, 175 gated imaging, 245, 369 time-activity curves and, 365,
of PET systems, 319-322, 330, list-mode, 368-369 374f
331, 334 archival systems for, 378 visualization tools for, 369-372,
of semiconductor detector, binary numbers in, 364-365 370f-372f
190-191 computer processors for, 363 volume of interest in, 373
housing of detector and, 164 definition of, 363 voxels in, 364
intrinsic, 156, 158-159, 159f display in Digital images, 364-369. See also
calibration and, 164 cathode ray tube, 367 Image quality.
of coincidence detector, 310, hard copy, 367 acquisition modes of, 367-369
311f, 312, 315, 319 liquid crystal, 367 archiving of, 378
definition of, 156 edge detection in, 373-375 basic characteristics of, 364-365,
of gas-filled detectors, 158-159 equipment for, 376-378 364f, 365f
of NaI(Tl) detectors, 158-159 file format standards for, 378 computer networks for
nonuniform attenuation and, for gamma camera images, management of, 378
160-162, 161f, 162f 364 display of
of semiconductor detectors, detector area and, 364, 365f image structure and, 367,
158 image arithmetic in, 371 368f
of well-counter detector, 174, image co-registration in, 375-376, spatial resolution and,
175f 377f 365-367, 366f
Index 501
Digital images (Continued) Dose reciprocity theorem, 415 Effective positron range, 313, 313f
technologies for, 119-121, 119f, Dose-equivalent rate, 435 Efficacy studies, 250-251
120f, 121 Dose-modifying factors, 428 Efficiency. See Collimator efficiency;
visualization tools for, 367, Dose-rate constant, 434-435, 435t Detection efficiency.
368f Dosimeters e/γ conversion ratio, 24
file formats for, 378 badge, 440, 440f Ejection fraction, 392, 392f
gamma camera and, 197, 364, pocket, 89-90, 90f, 440 Electrical forces, 14
365f, 482 ring, 440, 440f Electromagnetic radiation, 8-9, 66.
hard copy of, 367 Dosimetry, internal radiation. See See also Gamma rays; Photons;
parametric, 372 Radiation dosimetry, internal. X rays.
retrieval of, 376, 378 Double differential shaping, 112, Electromagnetic spectrum, 8-9, 8f
spatial resolution of, 365-367, 112f Electrometers, 89
366f Double escape peaks, 144, 145f in dose calibrators, 89, 89f
terminology of, 364-365, 364f, Downscatter during transmission in survey meters, 89-91, 89f
365f scan, 296, 297f Electron capture (EC), 24-25
Digital Imaging and Dps. See Disintegrations per second competitive with positron
Communications in Medicine (dps). emission, 27, 27f, 26, 26f
(DICOM), 378 DTPA (diethylenetriamine penta- by cyclotron-produced
Digital signal processors, 363 acetic acid), 5t, 60t, 381t, 480 radionuclides, 49, 50t
Digitization, 117-118, 363 Dynamic imaging, 392-403. See in (EC, γ) decay, 24-25, 24f
Di-isopropylnaphthalene (DIN), also Cardiac studies; Tracer line of stability and, 28
105, 187 kinetic modeling. by reactor-produced
Dilution principle, 382-383 in blood flow measurement, radionuclides, 49, 46, 46t
Dilution quenching, 106 379-386, 394-396. See also Electron gun, 123
DIN. See Di-isopropylnaphthalene Blood flow: measurement of. Electron multiplication factor,
(DIN). in cardiac imaging, 392. See also 148-149
Direct Fourier transform Cardiac imaging. Electron shells, 9, 14
reconstruction, 258-260, in enzyme kinetic studies, Electron volt (eV), 8
259f-260f. See also 396-401 Electronic collimation, 308
Reconstruction tomography. with gamma camera, 197, Electronic instrumentation,
image quality in, 263-270 206-207, 207f 107-124
sampling in, 263-265 in glucose metabolism studies, amplifiers in, 110-113, 110f, 111f,
Direct substitution, 59-60 396-401 112f
Discrete Fourier transform (DFT), with PET, 335 dead time and, 168, 170
482 in receptor binding studies, in nuclear instrument module,
Discriminators, 114, 115f, 118, 121, 402 122-123
121f in receptor ligand assays, in rate meter, 120
of gamma camera, 201, 205 401-403, 402f, 404f coincidence units in, 121-122,
lower-level, 113, 114f with SPECT, 279-278, 284, 286f, 121f
upper-level, 113, 114f 305f, 306 for PET scanner, 307-308
Disintegrations per second (dps), in receptor binding studies, counters and rate meters in,
31 402 119-121, 119f, 120f, 121f
Disposal of radioactive waste, Dynodes, 98-99, 98f detectors in. See Radiation
439 detectors.
Distribution volume, 382-383, display technologies in, 123-124,
384f E 123f
blood flow measurement and, EC. See Electron capture (EC). high-voltage power supplies in,
393 (EC, γ) decay, 24-25 122
Diverging collimators, 202f, 203 competitive, 26 NIM (modular) systems in,
advantages and limitations of, ECD. See Ethyl-cysteine-dimer 122-123
228 (ECD). preamplifiers in, 107-110, 108t,
efficiency of, 225-228, 226f-227f ECT. See Emission computed 109f
performance characteristics of, tomography (ECT). of gamma camera, 219
225-228, 226f-227f Edge detection, 373, 375, 376f pulse-height analyzers in. See
resolution of, 225-228, 226f-227f Edge effects, 160 Pulse-height analyzers
source-to-collimator distance Edge packing, 217, 229 (PHAs).
and, 228, 228f Edge sharpness, 237, 260-261 time-to-amplitude converters in,
DMSA (2,3-dimercaptosuccinic Effective atomic number, 65, 101t, 118-119, 119f
acid), 60t 103-104 Electronic noise. See also Noise;
DOI. See Depth-of-interaction Effective decay factors, 35-37, 36f Signal-to-noise ratio (SNR).
(DOI) effect. Effective dose, 417, 425t, 429t counting uncertainty and, 131
DOPA, 18F-Fluoro, 372f, 373, 374f, from background radiation, 427 energy resolution and
381t recommended limits for, 434t with scintillation detectors,
Dose. See Radiation dose; Effective dose equivalent, 417, 428, 148, 149, 150, 150f
Radiation dosimetry, internal. 429t, 432, 434t, 435. See also with semiconductor detectors,
Dose calibrators, 89, 89f, 189-190, Equivalent dose. 152, 152f
189f regulatory limits for, 431-432 in liquid scintillation counters,
shielding of, 189-190, 189f, 437 for selected 184, 185, 186
Dose equivalent. See Effective dose radiopharmaceuticals, power supply and, 122
equivalent; Equivalent dose. 478-479 pulse shaping and, 110-111,
Dose limits, 431-432 Effective half-life, 411-412 111f
502 Index
Gamma cameras (Continued) Gamma rays (Continued) Gaussian spectral curve, 149
quality assurance for, 228-231 penetration by, 195 Geiger-Müller (GM) counters,
response characteristics of, 254, septal, 205, 220-221 92-96, 93f, 94f, 95f
254f prompt, 45-46 avalanche ionization in, 92-93,
scintillation event localization in pulse-height spectrum of, 94f
in analog camera, 198-200 142-147, 143f, 145f, 146f, backscatter and, 166-167, 167f
in digital camera, 200 147f, 151 for β-emitting radionuclides,
sensitivity of, measurement of, radiation safety and, 434, 435, 167
231 437 as gas flow counters, 190
single-headed, 206-207, 206f Gamma-ray converters, 158-159 counting curves for, 94, 95f
for small animal imaging, Gamma-ray probes dead time in, 168, 188
207-208 miniature, 192-194, 193f intrinsic efficiency of, 158-159
spatial linearity and, in oncology, 192-193 limitations of, 93, 95, 166-167
measurement of, 229-230 radiation detectors for, 193 pancake, 95-96, 95f
in SPECT, 279-280 Gas amplification power supply for, 122
in SPECT/CT, 350f, 351, 352f in Geiger-Müller counters, 92-93, principles and design of, 92, 93f,
static imaging with, 197 94f 95-96, 95f
system resolution of, 210-211, in ionization chambers, 91, 92f pulse signals of, 107, 107t
214, 225, 227-228 in proportional counters, 91, self-absorption and, 166-167,
measurement of, 229 92f 167f
technical advances in, 207 Gas chromatograph self-quenched, 93-94
in tomographic imaging, 254, with gas-filled detector, 190 as survey meter, 95-96, 95f,
254f, 255, 255f, 256f with liquid scintillation counter, 439
for PET, 4, 325-326, 327f, 188 Generators, 24, 50-53, 51f, 51t
329-330, 332, 334 with NaI(Tl) detector, 182, 183f contaminants in, 50-53, 58
for SPECT, 279-280, 280f, 281, Gas flow counters, 190 fission moly, 53
283, 301-303 Gas flow counting with LS systems, historical development of, 2
triple-headed, 206-207 188 radionuclide, 50-53, 51f-52f,
types of, 206-208, 206f, 207f, 208f Gas proportional counters. See 51t
uniformity measures for, 230 Proportional counters. safe handling of, 436
whole-body imaging with, 207f Gases, radioactive Geometric detection efficiency.
X- and Y-position signals in, dose limits for, 431-432 See Detection efficiency:
199-200 safe handling of, 437, 438 geometric.
Gamma probes, intraoperative, Gas-filled detectors, 87-96, Geometric mean, in conjugate
193f, 194 189-190. See also Geiger- counting, 287-293
Gamma rays. See also Photons. Müller (GM) counters; correction for, 293-294, 294f
annihilation, 25 Ionization chambers; Germanium-68, 165t
biologic effects of, 78, 428 Proportional counters. characteristics of, 457
in collimators, 201-203 advantages and limitations of, as rod source, in PET scanner,
Compton scattering of. See 102 328f, 329, 338
Compton scattering. applications of, 189-190 Germanium detectors, 89t, 96-97.
detection of. See Radiation in dose calibrators, 189-190 See also Radiation detectors;
detectors. energy deposition in, 141 Semiconductor detectors.
in electromagnetic spectrum, 8, in gas flow counters, 190 detection efficiency of, 158
8f Geiger-Müller counters, 92-96, intrinsic, 96, 158
energy of 93f-95f lithium-drifted, 89t, 96-97, 97f
attenuation and, 163-164, 164f intrinsic efficiency of, 158-159 spectrometry with, 151, 152f
in SPECT, 287-294 ionization chamber, 87-91, GFR. See Glomerular filtration
gamma camera resolution and, 89f-91f. See also Ionization rates (GFR).
211-213, 234 chambers. Gibbs phenomenon, 486
intrinsic efficiency and, 158, principles and design of, 87, 88f Glass, leaded, 436-437, 436f
159f, 174, 175f proportional counters, 91-92, Glass vials for liquid scintillation
nuclear transitions and, 15 92f counting, 184-185
photofraction and, 159, 160f, semiconductor, 96-97, 97f Glomerular filtration rate (GFR),
174, 174f Gated imaging, 369 379
pulse-height spectrum and, in cardiac studies, 234, 303, 304, Glucose. See also
142-147, 143f, 145f, 146f, 304f, 392, 392f Fluorodeoxyglucose (FDG).
147f, 151 with gamma camera, 197 metabolism of, 396-401
scatter and, 163-164, 164f motion blurring and, 245 FDG model of, 397-401, 398f
in vivo measurements and, 163 Gaussian blurring function, Michaelis-Menten hypothesis
interactions with matter, 74-78 235-236, 491 and, 396-397, 397f
in nuclear medicine, 1 Gaussian distribution, 127f, 128 parametric brain imaging and,
from nuclear transitions, 8-9, 8f, statistical tests and, 133, 135, 400, 401f
15 138 Sokoloff deoxyglucose method
in (α, γ) decay, 28 Gaussian function, convolution of, and, 397, 400
in (β+, γ) emission, 26 491 transport of, 389
in (β−, γ) emission, 21-22, 22f, Gaussian response profile of GM counters. See Geiger-Müller
23f annihilation coincidence (GM) counters.
in (EC, γ) decay, 24, 24f detector, 308, 310f Graphics processing units, 363
isomeric, 22-23, 23f, 24 Gaussian smoothing filters, 373, Gray (Gy), 89, 407, 433-434
in (n, γ) reaction, 46 375f Grayscale images, 367, 370f
506 Index
Left ventricular ejection fraction, Liquid chromatography, with Lutetium yttrium orthosilicate
392, 392f NaI(Tl) detectors, 182, 183f (LYSO), 101t, 102-103
Lesion detectability. See Liquid crystal display (LCD), 124, Lymph nodes, sentinel, gamma-ray
Detectability. 367 probes for, 192-193
Lesions. See Detectability. Liquid nitrogen in semiconductor
LET. See Linear energy transfer detectors, 97, 97f
(LET). Liquid scintillation (LS), 104-106, M
Licensing for use of radionuclides, 105f, 187-188 MAG3 (mercapto-acetyl-triglycine),
431, 432, 433 Liquid scintillation (LS) cocktails, 5t
Ligand, 60 105, 187 Magnetic resonance imaging
Light coupling. See Optical Liquid scintillation counters (MRI)
coupling. (LSCs), 184-185 combined with nuclear medicine
Light guide of gamma camera, 196, applications of, 105, 183-184, imaging, 376, 377f
196f, 198, 219 189 image reconstruction in, 4, 259
Light-emitting diodes (LEDs), automated multi-sample, in k-space, 259
219 188-189, 188f limitations of, 1
Limited-angle tomography, 266 calibration of, 185 with PET, 345-346, 360-361,
Limited-scope licenses, 431 Cerenkov counting with, 188 361f
Line broadening, 148. See also coincidence detection by, 184 with SPECT, 360
Energy resolution. components of, 105f, 182-184, stray fields from, gamma camera
Line integrals, 254, 254f 183f and, 197
Line of response, 254, 254f dark adaptation of samples and, Malignant melanoma, sentinel
actual vs. idealized, 285-286 185 nodes in, gamma-ray probes
conjugate counting and, 287 dead time in, 168 for, 193-193
scattering into, 296 efficiency of, 157, 185 Mass
in transmission scan, 295-296 flow counting with, 188 equivalence to energy, 8, 15-16,
Line of stability, 16, 16f gas/liquid chromatography with, 19
decay modes and, 28 188 units of, 7-8
Linear accelerators, 47 limitations of, 106 Mass attenuation coefficients, 79,
Linear attenuation coefficients, 78, mixtures of radionuclides in, 185, 158
81, 82, 83, 158 188-189 absorbed dose and, 430
of bone, 287, 294, 338 noise in, 184, 185, 186 table of, 476-477
coincidence rate and, 319 organic scintillators for, 104-106 Mass deficiency, 15
of collimator material, 221, 222 principles and design of, 182-184, Mass number (A), 13
detection efficiency and, 158, 183f Mass-energy conversion in
159 pulse signals of, 108t radioactive decay, 19
in PET, 321 pulse-height spectrometry with, Matrix of pixels, 365, 365f
of tissue, 192, 296 141, 153, 153f, 184, 185f Matrix size, 365-366, 366f
transmission scan and, 294, quenching in, 106, 188 Maximum intensity projection,
338 correction methods for, 369-371
Linear energy transfer (LET) 185-187, 186f-187f Maximum-likelihood (ML)
of charged particles, 68, 71 radionuclides counted with, 105, reconstruction, 272-273
of photons, 78 166, 182-184, 183t MCAs. See Multichannel analyzers
Linear nonthreshold (LNT) model, refrigeration of, 184 (MCAs).
427 sample preparation for, 106, MDA. See Minimum detectable
Linear regression, 139-140 187-188 activity (MDA).
Linear sampling distance, 263, 265 scintillator solutions in, 104-106, MDP. See Methylene diphosphonate
in annihilation coincidence 187 (MDP).
detection, 318, 318f vials for, 184-185 Mean dose per cumulated activity,
in imaging processing, 365-366 List-mode acquisition, 335, 411f, 414f, 415-416, 418t-419t
with iterative algorithms, 368-369 for 18F, 415-416,
273 Lithium fluoride, 422t-423t
performance measurement and, thermoluminescent, 440f for 131I, 415-416, 420t-421t
301 Logarithmic rate meters, 121, for 99mTc, 415-416, 418t-419t
pixel size and, 366 121f Mean free path, photon, 82, 82t
SNR and, 267 Logic pulses, 118-119 Mean transit time, 380, 380f,
Linear stopping power, 68 Lower-level discriminator, 113, 384
Line-spread function (LSF) 114f Mean value, 126, 127
distance from source vs., 288f LS. See Liquid scintillation (LS). arithmetic vs. geometric,
FWHM and, 235 LSCs. See Liquid scintillation 287-288, 288f
of gamma-camera collimators, counters (LSCs). confidence interval for, 127,
222-223, 222f, 224f, 225 LSF. See Line-spread function (LSF). 127t
modular transfer function and, LuAP, 101t, 103 t-test and, 135-137
238, 240-241, 242f Lumped constant (LC), 399, 400 uncertainty in, 128
pixel size and, 366 Lung perfusion, 393 Measurement errors, 125-126
in resolution evaluation, 235 Lung ventilation, 381t blunders, 125
scattered radiation and, 240-241, Lutetium oxyorthosilicate (LSO), propagation of, 128-130
242f 101t, 102-103 random, 125-126
septal penetration and, 240-241, in PET systems, 321, 322t, 324, systematic, 125
242f 325, 325f, 326 types of, 125-126
in SPECT imaging, 288f, 298 energy resolution and, 337 Measurement standards, 125
Index 509
Measurements. See also Statistical Modulation transfer function (MTF) NaI(Tl) detectors (Continued)
analysis. (Continued) counting applications of
constant multipliers and, 129 of SPECT system, 301 with gas/liquid
frequency distribution of, 126, system effects and, 238 chromatographs, 179
127f Moly shield, 53 with large sample volumes,
inaccurate, 125 Molybdenum-99, 45, 51f, 51t, 53 182
reproducible, 126 breakthrough of, 50-53, 84 with NaI(Tl) well counters,
sums and differences of, 129 characteristics of, 460 173, 174f, 174t
true value of, 126 detection of, with dose calibrator, cracked crystal in, 104, 150, 217
uncertainty in, 126-127, 129 189 dead times of systems with, 179
Medical Internal Radiation Dose production of, 44-45 detection efficiency of, 157, 174,
(MIRD) Committee, 28, 407, Molybdenum-99—technetium-99 175, 175f-176f, 179
414 generators, 50-53, 51f, 51t, intrinsic, 158-159
Medical Internal Radiation 60 with source in tissue, 163, 164f
Dosimetry (MIRD) method. See Monitoring of radiation. See total, 160-161, 161f
Absorbed fraction (MIRD) Radiation monitoring; digitization of signals from,
method. Radiation safety; Survey 117-118
Medical Internal Radiation meters. disadvantages of, 102
Dosimetry (MIRD) Motion, patient, 234, 234f energy linearity and, 147-148
publications, 28 attenuation correction artifacts energy resolution and, 148-151
Megaelectron volt (MeV), 8 and, 359 in gamma cameras, 196-198,
Melanoma, sentinel nodes in, breath-holding and, 359 196f
gamma-ray probes for, gated imaging and, 234, 368 crystal thickness in, 210, 210f,
192-193 in SPECT, 303, 304f 211, 211f
Metabolic tracers. See image quality and, 234, 266, limitations of, 216
Fluorodeoxyglucose (FDG); 359 limitations of, 182
Methylene diphosphonate in PET, 308, 339 linear attenuation coefficient of,
(MDP); Oxygen-15. Motion blurring, 234, 266 321, 322t
Metastable radionuclides, attenuation correction artifacts mass attenuation coefficients of,
generators of, 24, 50-53, 51t, and, 359 476-477
52f breath-holding and, 359 minimum detectable activity
Metastable state, 10f, 14-15 image quality and, 234, 266, with, 191
decay of, 22 359 in PET scanners, 321, 322t, 324,
Methylene diphosphonate (MDP), MRI. See Magnetic resonance 327f, 330, 337
5t, 60t, 207f, 479 imaging (MRI). photofraction with, 159, 160f
Metric units, 7 MTF. See Modulation transfer power supply for, 122
MeV. See Megaelectron volt (MeV). function (MTF). preamplifiers for, 108-109
Michaelis-Menten kinetics, Multichannel analyzers (MCAs), principles and design of, 91,
396-397, 397f 113, 116-118, 116f 100-102, 101f
Microcurie, 32 dead time of, 168 pulse-height spectrometry with,
Microdosimetry, 425 of liquid scintillation counters, 142-151. See also Pulse-
Microprocessors, 363 184 height spectrometry: with
Microsphere technique, 393 of NaI(Tl) well counters, 173, NaI(Tl) detectors.
Millibarn, 53-54 180f, 181 advantages of, 151
Miniature probes for surgery, for radiochemical identification, calibration for, 147-148
192-194 182 counting rate and, 146, 147f
Minimum detectable activity of semiconductor detectors, 190 crystal size and, 145-146, 146f,
(MDA), 131 Multi-pinhole collimators, 202f, 158, 159, 160f
with semiconductor detectors, 203 energy linearity in, 148-149,
191 Multiple scattering, intrinsic 148f
MIRD Committee. See Medical resolution and, 209, 210 energy resolution in, 148-151,
Internal Radiation Dose Multiprobe systems, 192 149f, 150f
(MIRD) Committee. Multi-slice imaging, 262-263 vs. semiconductor detectors,
MIRD method. See Absorbed Mu-metal shielding, 99, 101f 151, 152, 152f
fraction (MIRD) method; Muscle, f factor for, 430, 430f gamma-ray energy and, 147,
Radiation dosimetry, internal. Myocardial imaging 147f
MIRD publications. See Medical with 99mTc-labeled red cells, 392, scatter rejection in, 240
Internal Radiation Dosimetry 392f spectral structure in, 142-145,
(MIRD) publications. SPECT in, 281-283, 303, 305f, 143f, 144f, 145f, 146f
ML reconstruction. See Maximum- 306 timing methods in, 114-115
likelihood (ML) reconstruction. Myocardial perfusion. See Cardiac in SPECT
ML-EM method, 272-273 studies. in brain imaging, 280-281, 282f
Mn-54, 165t in cardiac imaging, 281-283
Mock calibration sources, 177 in CERASPECT system, 281,
Modulation transfer function N 282f
(MTF), 236-237, 487, 492 (n, γ) reaction, 45, 46 in small-animal imaging,
3-D representation of, 238 (n, p) reaction, 46, 47 281-283, 282f
derivation of, 238 NaI(Tl) detectors, 100-103, 182 in SPRINT II system, 280-281,
line-spread function and, 238, advantages of, 102, 190-191 282f
240-241, 242f amplifiers for, 113 through-hole, 180, 180f-181f
scatter and, 241, 242f for cardiac SPECT, 281-283 timing methods for, 114-116
510 Index
Regression analysis, 390 Sampling interval. See Angular Scattered radiation (Continued)
linear, 139-140 sampling intervals; Linear in vivo probe measurements
in tracer kinetic modeling, 390 sampling distance. and, 192
Regulations, U.S. government, 431, Sampling theorem, 263, 366, 483, window fraction and, 170
432, 433, 435-437, 436t-437t 484, 485 in SPECT/CT, correction of,
Rem, 408, 430 Saturation region, 87-88, 88f 356-360
Renal function, evaluation of, 379 Saturation specific activity, 56 in x-ray computed tomography
Renkin-Crone model, 387-388, Saturation voltage, 87-88, 88f (CT), 349
388f-389f, 390-391 Scalers, 119-120 Scintillation cameras, timing
Reproducibility of measurements, dead times of, 168 methods for, 114-115
126 Scaler-timers, 119-120, 119f Scintillation detectors, 97-106.
Resistor-capacitor pulse shaping, dead time losses in, 168 See also Radiation
111-112, 112f Scaling factor, for absorbed dose, detectors.
Resolution. See Energy resolution; 427, 430 amplifiers for, 111
Spatial resolution; Timing Scanner, rectilinear, 195-196 for intraoperative gamma probes,
resolution. SCAs. See Single-channel analyzers 194
Resolution volume of SPECT (SCAs). NaI(Tl), 100-103, 101f-103f,
system, 301-302 Scatter coincidences, 322-324, 101t. See also NaI(Tl)
Respiratory motion. See Motion 322f detectors.
blurring. with 3-D data acquisition, 332, for PET systems, 104, 316,
Restricted areas, 431 334 324-326, 325f, 326f, 327f,
radiation levels in, 431-432 with gamma camera, 329-330 328, 330-332, 337
Rest/stress studies, 303 septa and, 329 spatial resolution and,
Ring dosimeters, 440-441, 440f transmission scanning and, 339 314-315, 314f
Ringing artifacts, 486 uncertainty in, 336, 337 photodiodes in, 99-100
Ripple in HV power supply, 122 Scatter correction photomultiplier tubes for, 98-99,
Rise time in PET, 337-338 100f-101f, 101-102
of electronic signal, 111, 112 in SPECT, 296-299, 297f, 298f, with inorganic scintillators,
of scintillator light output, 309 302 100-103, 101f-103f
ROC studies. See Receiver- Scatter window, 298, 298f with organic scintillators,
operating characteristic (ROC) Scattered radiation, 166-167, 167f 105f
studies. background counting rates and, power supplies for, 122
Rod standards, 164, 165f 240-241, 241f preamplifiers for, 109, 110
Roentgen, Wilhelm, 2 backscattered, 75, 143f, 144, principles and design of, 97-98,
Roentgens, 89, 90, 429-430 166-167, 167f 98f
ROI. See Regions of interest beam geometry and, 80, 81, 81f, spectral blurring with, 148
(ROI). 84 time-to-amplitude converters for,
Rollo phantom, 247-248, 248f coherent, 77 118
Root mean square effective range, in SPECT, 297 Scintillators, 97
314 Compton-scattered. See Compton background noise associated
Rose criterion, 244, 269 scattering. with, 184
Rubidium-82, properties of, 58t detection efficiency and, 156, effective atomic number of,
Rutherford, Ernest, 9 163-164 103
Rutherford atomic model, 9 downscattered, 296 energy response of, nonlinear,
in gamma camera, 200, 204, 205, 148, 149-150
209 inorganic, 100-103, 101f, 101t,
S counting losses and, 213-214, 102f, 103f
Safety. See Radiation safety. 213f NaI(Tl), 100-103, 101f-103f,
Safety concerns. See Radiation energy resolution and, 212 101t. See also NaI(Tl)
safety. as multiple scattering, 209, detectors.
Sagittal sections, orientation of, 210 for PET, 316, 322t, 324, 326
369, 370f image contrast and, 240-241, properties of, 101t, 103, 103f
Sample volume 242f selection of, 103
with dose calibrator, 189-190 object scattered, 144-145, 205 organic, 104-106
with NaI(Tl) conventional in PET, 322-323, 322f, 329-330 in liquid solution, 97, 104-106,
detector, 182 correction for, 337-338 106f, 185, 187, 188
with NaI(Tl) well counter, 174, in PET/CT, correction of, 337, plastic, 105, 105f
175-177, 177f 356-360 solid, for flow counter, 187
Samples, dark adaptation of, in pulse-height spectrometry, SD. See Standard deviation (SD).
185 141, 212-213 Secondary electrons, 63, 64f, 66,
Sampling, 263, 264f, 265-266, 265f, Rayleigh scattering and, 77 67f, 78t
481, 482, 484, 487 scatter windows and, 298, 298f in photomultiplier tubes, 98-99,
in annihilation coincidence in SPECT, 286, 296, 299, 302 100f
detection, 318-319, 318f correction of, 296-299 Secondary emission in
performance measurement and, object scatter as photomultiplier tube, 98
301 with gamma camera, 205, Secondary ionization, 63, 64f,
pixel size and, 366 205f 141-142, 142f
preparation for liquid with Ge(Li) detector, 152f charged-particle interactions and,
scintillation counters, 106, with NaI(Tl) detector, 63, 68
187-188 144, 145, 147, 147f, photon interactions and, 77, 78t,
SNR and, 268 152f 141-142
Index 519
Secondary ionizing radiation, Sestamibi, 99mTc-labeled, 5t, 60t Silicon photodiodes, 99-100
74 blood flow measurement with, avalanche, 100, 332
Secondary photons, 77, 78t, 381t in compact gamma camera, 207
141-142 dose estimates for, 480 in gamma-ray probes, 193, 193f
Secondary solute, 105, 106 SPECT imaging with, 5t, 303f, Simple backprojection, 256-258,
Secular equilibrium, 40-41, 40f 304, 304f, 305 266f. See also Reconstruction
Segmentation, image, 357, 375, Sewage, dose limits and, 432, tomography.
377f 433t filtered backprojection vs.,
Self-absorption, 167, 167f Shallow-dose equivalent, 432 260-261
quench correction and, 187 Shell model of nucleus, 14 Simultaneous emission/
Semiconductor detectors, 96-97, Shells, electron, 9-13 transmission scans in PET
97f, 190-192, 191f. See also Shepp-Logan filter, 261, 262f, attenuation correction, 338-339
Radiation detectors. 263-265, 264f Single escape peaks, 144, 145f
advantages of, 96, 190-191, Shielding, 82t, 436-437, 436f Single photon emission computed
240 of α particles, 71 tomography (SPECT), 253,
amplifiers for, 111, 112, 113 background counting rates and, 279-306. See also Tomographic
applications of, 190-192 240 imaging.
cadmium telluride, 96-97 backscatter from, 144 advantages of, 253
cadmium zinc telluride, 96-97 beam geometry and, 82, 83 artifacts in, 286, 302
dead times of, 168 of β emitter, 65, 66f, 437 attenuation in, 285-293,
design of, 97, 97f Bremsstrahlung, 65, 67f 291t-292t
detection efficiency of, 151, 158, of dose calibrators, 189-190, 189f, conjugate counting and, 287
164, 190 437 correction of, 293-294
efficiency of, 158, 190-191 effectiveness of, 437 Chang multiplicative
energy resolution of, 151-152, lead. See Lead shielding. method, 294, 294f, 296,
152f, 190-192, 191f, 240 methods of, 436-437, 436f 297f
for gamma-ray probes, 193 Mu-metal, 99, 101f scatter correction and,
germanium, 96-97 for NaI(Tl) well counters, 296-299, 298f
intraoperative gamma probe as, 177-178 transmission scans and,
193f, 194 natural radioactivity in, 294-296, 295f-297f
limitations of, 96, 102, 190 177-178 attenuation maps for, 294-296,
lithium-drifted, 96-97, 97f pulse pile-up and, 214, 215f 296f
power supplies for, 122 for radiation safety, 436-437, binding potential and, 403
preamplifiers for, 107-110, 436f blank scans in, 295
108f TDS rules and, 436 blood flow measurements with,
pulse signals of, 108t tenth-value thickness and, 82, 393, 395
pulse-height spectrometry with, 82t, 437 in brain imaging, 280-281, 282f,
151-153, 151f-152f of whole-body counting chambers, 304-305, 304f
silicon, 96-97 194 in cancer, 305-306
applications of, 190 x-ray peaks caused by, 144, in cardiac imaging, 281-283, 303,
in scintillation detectors, 151 305f, 306
99-100 Shunt, intracardiac, detection of center of rotation in, 302-303
Semiconductor photodiodes. with labeled microspheres, CERASPECT system for,
See Silicon photodiodes. 394 280-281, 282f
Sensitivity with labeled RBCs, 392 clinical applications of, 303-306,
of collimator SI. See specific ionization (SI). 303f-305f
in gamma camera, 223, 224f, SI units. See Systeme International collimators in
225t, 227, 231 (SI) units. converging, 279-280
lesion detectability and, 246, Sievert (Sv), 408, 417, 428, 430 parallel-hole, 279-281
247f Signal amplification. See combined with x-ray CT. See
of PET, 308, 319-322 Amplifiers; Preamplifiers. SPECT/CT.
with 2-D data acquisition, Signal-to-noise ratio (SNR), 110. contrast in, 241-242, 243f, 297,
321-322, 332 See also Noise. 299
with 3-D data acquisition, amplifier time constant and, co-registered images in, 376
321-322, 332-334 110 current practice of, 4-5
of receiver operating in filtered backprojection, 3-D, 364
characteristic, 249 260-261, 263, 264f detector head orbits in, 280, 280f
Sentinel nodes, gamma-ray probes image smoothing and, 373, distortion sources and, 286
for, 192-193 375f downscatter in, 296
Septal penetration, 205, 220-221 preamplifier location and, 110 dynamic
background counting rates and, in time-of-flight PET, 309, 310 FASTSPECT system for,
240 in tomographic reconstruction, 279-278, 284, 286f
image contrast and, 240-241, 261, 263, 266-268 for receptor binding studies,
242f Silicon detectors, 96-97. See also 402
line-spread function and, Radiation detectors; flood-field uniformity in, 302
240-241, 242f Semiconductor detectors. gamma cameras for, 279-280
pinhole collimators and, 227 energy resolution of, 190 historical development of, 4
Septal thickness in collimators, instrinsic efficiency of, 158 image quality in, 302-303
203, 203f, 211, 220-221, lithium-drifted, 89t, 96-97, image reconstruction in, 301-303
220f-221f 97f imaging speed in, 280-281
Series decay, 27-28, 27f in scintillation detectors, 99 limitations of, 280
520 Index
Single photon emission computed Sinograms, 255-256, 256f, 270f, Spatial resolution (Continued)
tomography (SPECT) 271, 276 phantoms in, 234-235,
(Continued) Skin. See also Organs. 234f-235f
for low-contrast imaging, 241-242 contaminated, 439 point-spread function in, 235
multihead systems for, 280f, dose to, 428, 432, 434, 434t spatial frequency in, 245
281-299 Slant-hole collimators, 203 subjective, 234
multiple detector heads in, 279 Slice thickness, 301 factors affecting, 233-234, 235f
multislice images in, 262-263 in PET, 329 in-plane, 301
performance characteristics of, in SPECT, 301 intrinsic, 234
299-303 Slow neutrons, 43-44 Compton scattering and,
count-rate performance, 302 Small-animal imaging 209-211, 210f-211f
dead time, 302 3-D iterative reconstruction in, detector thickness and, 210,
energy resolution, 302 276 211f
spatial resolution, 301 gamma cameras for, 207-208 full width at half maximum
volume sensitivity, 301-302 PET in, 331-332, 331f, 342, and, 210-211, 221, 225t,
practical implementation of, 342f 229
285-299 PET/CT in, 356, 356f of gamma cameras, 209-211,
attenuation corrections in, SPECT in, 283-285, 286f, 305f, 210f-211f, 219, 234
293-294, 294f 306 bar phantom and, 235, 235f
conjugate counting in, 287, SPECT/CT in, 352-354, 353f in coincidence detection, 310,
288f Smoothing, image, 373, 375f 311f-312f
idealized assumptions and, Sn-113, as calibration standard, measurement of, 229
285-286 165t MTF for, 238
partial-volume effects in, 299, SNR. See Signal-to-noise ratio in PET systems, 329
300f, 373 (SNR). in SPECT systems, 299,
scatter corrections in, 296-299, Sodium-22, 165t 300f
297f, 298f, 302 Sodium iodide, 479t system resolution and, 229
transmission scans in, 294-296, Sodium iodide detectors. See γ-ray energy and, 210, 210f
295f-297f NaI(Tl) detectors. limits on, 209-210
vs. idealized assumptions, 286 Sokoloff deoxyglucose method, 397, measurement of, 210, 229
quality assurance for, 302-303 400 optimum, 210-211
quantitative images in, 372 Somatostatin receptors, 2, 305 system resolution and,
radiopharmaceuticals for, Source organs, 408, 413-414, 415, 210-211, 225, 227
304-306 416, 418t-424t lesion detectability and, 248,
recovery coefficients for, 299, Source-to-collimator distance 249f
300f collimator resolution and, 223, linear sampling distance and,
reference scans in, 295 224f, 227-228, 227f-228f 263, 365-366, 373
regions of interest in, 372-373 modulation transfer function matrix size and, 365-366, 366f
research applications of, 3, 403 and, 238, 238f patient motion and, 234
sensitivity of, 308, 321-322 in SPECT, 284 in PET. See Positron emission
in small-animal imaging, Spatial frequency, 236 tomography (PET): spatial
283-285, 286f, 305f, 306 Fourier transform and, 260f, 263, resolution in.
spatial resolution in, 280, 280f, 481, 483, 484, 485f, 486f, pixel size and, 365-366
281, 283, 284, 288, 289, 298, 487, 492 pixelation effects and, 234
299, 300f, 301 pixel size and, 366 reconstructed, measurement of,
SPECT/CT vs., 351-352 resolution and, 236, 237-238, 301. See also Reconstruction
spillover in, 299 237f, 238, 239f tomography.
SPRINT II system for, 280-281, Spatial frequency space. smoothing filter and, 375f
282f See k-space. in SPECT, 280, 280f, 281, 283,
system alignment in, 302-303 Spatial linearity of gamma 284, 288, 289, 298, 299, 300f,
systems for, 279-281, 280f, 282f, cameras, 229-230 301
283-285, 283f, 284f, 285f, Spatial resolution, 233-239. system resolution as. See System
286f See also Image quality. resolution.
used for PET, 307, 324 axial, 301 tomographic reconstruction and
tomographic reconstruction in, background subtraction and, collimator types and, 273, 279
253, 254, 255, 256 242-243 cutoff frequency and, 263, 264f,
volume sensitivity in, 301-302 collimator, 234. See also 301, 319
Single photon planar imaging, 1, Collimator resolution. with iterative algorithms,
5t, 241, 243, 243f. See also contrast enhancement and, 273-274
Gamma cameras. 242-243 sampling and, 265, 266, 267
Single-channel analyzers (SCAs), cut-off frequency and, 319 transaxial, 301
113-116, 114f, 118, 122 definition of, 209-211, 233-234 in x-ray CT, 349
counting rate and, 146-147 detectability and, 246-247 Specific absorbed fraction,
dead times of, 168 evaluation of, 234 414-415
of NaI(Tl) probe system, 207 full width at half maximum Specific activity, 37-38
NaI(Tl) well counters and, 173, and, 235-236 carrier-free, 37-38
178, 181 line-spread function in, 235 in nuclear medicine, 38, 56
for radiochemical identification, modulation transfer function of radionuclides, 57-58
181 in, 233, 236-237, of radiopharmaceuticals, 59
Singles method for random 237f-238f saturation level of, 56
coincidences, 337 objective, 234-239 Specific ionization (SI), 68, 69f, 71
Index 521