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NUCLEAR MEDICINE
AND MOLECULAR IMAGING
5th EDITION
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iii
F OR EWOR D
Nuclear Medicine and Molecular Imaging: The Requisites is a new Readers of Nuclear Medicine and Molecular Imaging: The Requi-
title for this well-received text now appearing its fifth edition. sites will feel this vitality almost palpably as they work their way
The change in title reflects the remarkable advances in trac- through the book. In particular, PET and PET/CT have become
er-based medical imaging that have taken place over the last two cornerstones in cancer diagnosis and management with PET/
decades. These advances have clearly extended the diagnostic MRI becoming more important in both cancer diagnosis and
utility and value of nuclear medicine and molecular imaging in neurological studies.
clinical patient care. The Requisites in Radiology titles have now become old
Predictably much of the fifth edition of Nuclear Medicine and friends to generations of radiologists. The original intent of the
Molecular Imaging: The Requisites is focused on new molecular series was to provide the resident or fellow with a text that might
imaging methods and the latest advances in their clinical appli- be reasonably read within several days at the beginning of each
cation including positron emission tomography (PET), SPECT/ subspecialty rotation and perhaps reread several times during
CT, PET/CT and PET/MRI hybrid imaging. The intense interest subsequent rotations or during board preparation. The series is
in hybrid imaging provides clear recognition of the increased not intended to be exhaustive but rather to provide the basic
value now placed on functional and molecular information in conceptual, factual, and interpretive material required for clin-
disease diagnosis. ical practice. After more than 30 years of experience with the
Although retitled, Nuclear Medicine and Molecular Imaging: series, it is now clear that the books are also sought out by prac-
The Requisites continues to follow the format of the first four ticing imaging specialists for the efficiency of their presenta-
editions. The basic science chapters are designed to present tion format and the quality of their material. With more people
important principles of physics, instrumentation, and nuclear reaching the point of requiring re-certification, the Requisites
pharmacy in the context of how they help shape clinical prac- books are again proving helpful.
tice. The physics content of the fifth edition has been expanded The first four editions of Nuclear Medicine and Molecular
and integrated to reflect current technology. Topics on regula- Imaging: The Requisites were well received in the radiology
tory issues, radiation safety and quality control have been added and nuclear medicine community. For the retitled fifth edi-
as well as material on the “non-interpretive” aspects of nuclear tion, Dr. Janis M. O’Malley and Dr. Harvey A. Ziessman have
medicine and molecular imaging practice. again done a terrific job in putting together this substantially
The clinical chapters continue to follow a logical progression updated edition. Congratulations to them. I expect that this
from basic principles of tracer distribution and localization to fifth edition will be deemed to be even more outstanding than
practical clinical applications. Knowledge of how radiopharma- its predecessors.
ceuticals localize temporally and spatially in normal and dis- We hope that Nuclear Medicine and Molecular Imaging: The
eased tissues is the best deductive tool available for analyzing Requisites will serve residents in radiology as a concise and
images. The best use of new tracers such as Ga-68 DOTA, the useful introduction to the subject and will also serve as a very
F-18 amyloid agents and F-18 PMSA agents requires this kind manageable text for review by fellows and practicing nuclear
of knowledge of the underlying mechanisms of disease and medicine specialists and radiologists.
therewith tracer localization. James H. Thrall, MD
Adding new tracers and new SPECT, PET, PET/CT, and Radiologist-in-Chief Emeritus, Massachusetts General Hospital
PET/MRI applications to the nuclear medicine armamentar- Distinguished Juan M. Taveras Professor of Radiology, Harvard
ium has injected new, unprecedented, vitality into the specialty. Medical School, Boston, Massachusetts
iv
P R E FA C E T O T H E 5 T H E D I T I O N
OF THE REQUISITES, NUCLEAR
MEDICINE
This is the 5th edition of Nuclear Medicine: The Requisites. How- agents highlighted. The popular chapter, “Pearls, Pitfalls, and
ever, we are now titled Nuclear Medicine and Molecular Imaging: Frequently Asked Questions,” again provides an excellent con-
The Requisites. We are deeply indebted to Dr. James H. Thrall for cluding summary. Protocols and key facts are again organized
developing the concept of the Requisite series and his involve- in many boxes and tables for easy identification.
ment as a coauthor of Nuclear Medicine: The Requisites for the Over the years, it has been an honor to help guide and train
first four editions, in 1995, 2001, 2006, and 2014. Since the last the most incredibly gifted physicians and introduce them to
edition, there have been many exciting changes in the field, par- the incredible field of nuclear medicine. Our students have
ticularly concerning new PET agents and therapy techniques. also taught us a lot along the way, and their feedback has been
The 5th edition builds on the success of the prior editions, pro- essential as we continue to strive to improve as educators. In
viding a concise, easy to read review that is suitable not only for addition, hearing from colleagues around the globe how the text
radiology and nuclear medicine residents and fellows preparing has helped them or their trainees has been another wonderful
for their service rotations or board exams but also serves a use- way to continue developing new material. Hopefully, our expe-
ful tool for those in practice at all levels of expertise, particularly riences are reflected here and provide a foundation for another
when targeting knowledge gaps during maintenance of board successful text.
certification reviews.
All chapters have been significantly updated and contain
numerous stunning new images. The first section of the book
ACKNOWLEDGEMENTS
is again devoted to technical matters: basic principles and con- We would like to thank those who have contributed to the
cepts of radiation production, instrumentation and detection, preparation of this book. Selected images were provided by:
radiopharmaceuticals and quality control, radiation safety, and Suzanne Lapi, PhD; Kirk Fry, MD, PhD; Jonathon McConathy,
regulatory matters. New topics have been introduced including MD, PhD; Steven P Rowe, MD, Bital Savir Baruch MD, Corina
PET/MR, and important facts the Authorized Users of radio- M Millo, MD; Khun Visith Keu, MD; Lauren L Radford, PhD;
pharmaceuticals are highlighted. The second section of the Mark Muzi, PhD; Les Foto; Farrokh Dehdashti, MD; and Hong-
book is focused on clinical imaging and therapy, emphasizing gang Liu. Hong-gang Liu also produced some of graphics in
physiological mechanisms and pharmacokinetics. Because animated images. Suzy Lapi and Jon McConathy helped with
of the rapid progress in oncology, particularly in the areas of editing the chapters on brain imaging and Molecular Imaging.
prostate cancer and neuroendocrine tumor imaging and treat- We would also like to thank our spouses and family for all
ment, these section have been extensively updated with import- their support during our work on each of these editions.
ant details on the use of newly approved imaging and therapy Janis O’Malley thanks her mom, Lanis Petrik.
v
PART 1 Basic Principles 10 Gastrointestinal System, 220
11 Urinary Tract. 256
1 Radioactivity and Radionuclides, 1
12 Oncology: F-18 Fluorodeoxyglucose Positron
2 Radiation Detection & Ancillary Instrumentation, 14
Emission Tomography, 288
3 Single-Photon Emission Computed Tomography, Positron
13 Oncology-Beyond Fluorodeoxyglucose, 339
Emission Tomography, and Hybrid Imaging, 28
14 Central Nervous System, 364
4 Radiopharmaceuticals, 42
15 Inflammation and Infection, 409
5 Molecular Imaging, 64
16 Cardiovascular System, 441
17 Pearls, Pitfalls, and Frequently Asked Questions, 480
PART 2 Clinical Studies
6 The Skeletal System, 75
Appendix 1: Dosimet ry, 493
7 The Pulmonary System, 125
Appendix 2: The Periodic Table of the Elements, 495
Index, 496
8 Endocrine System, 152
9 Hepatic, Biliary, and Splenic Scintigraphy, 180
vi
PART 1 Basic Principles
1
Radioactivity and Radionuclides
In nuclear medicine, radiopharmaceuticals given to the patient Elements are organized in the periodic table of the elements
emit the radiation used to create images or perform therapy. In (see Appendix 2). All atoms of the same element have the same
order to understand how these agents perform and what safety number of protons. The proton number is also referred to as the
considerations are involved in their use, it is necessary to be famil- atomic number or Z. Thus, all carbon atoms have 6 protons, all oxy-
iar with some basic aspects of the physics behind radioactive decay. gen atoms have 8 protons, and all iodine atoms have 53 protons—
This chapter discusses radioactive molecules, different types of that is, they have Z numbers of 6, 8, and 53, respectively. Atoms of
radioactive decay, and how these emissions interact with matter. a particular element can, however, have a varying number of neu-
trons (referred to as the neutron number, N). For example, in addi-
ATOMIC STRUCTURE OF MATTER tion to their 8 protons, some oxygen atoms have 8 neutrons, and
others have 7 or 10 neutrons. The total number of nucleons (Z plus
Electronic Structure of the Nucleus N) is known as the atomic mass or atomic number, A. Therefore, in
All matter is made up of atoms, which in turn are made up of the oxygen example, A would be 15, 16, and 18 for atoms that have
protons, electrons, and neutrons. Positively charged protons 8 protons plus 7, 8, or 10 neutrons, respectively.
and uncharged neutrons have a similar mass and are known as Unlike an element, which is characterized only by its number
nucleons because they are located in the nucleus. Although of protons (Z), a nuclide is a nuclear entity characterized by a
much less massive, electrons orbiting the nucleus possess an certain nuclear composition of protons and neutrons as well as
opposite negative charge equal in magnitude to that of the pro- a certain energy level. Shorthand notation has been agreed on to
tons (Table 1.1). Some properties of atomic particles are listed, describe the makeup of specific nuclides:
along with important constant values, in Table 1.2.
Atomic mass Element
The attraction of the opposite charges keeping the electron in
orbit around the nucleus is known as an electrostatic force (or A
ZX N
coulombic force; the coulomb is the unit for electric charge). On
the other hand, there is also a repulsive, electrostatic force in the
nucleus from the like-charged protons pushing apart. The Proton number Neutron number
nucleus is held together by the attractive strong nuclear force
each nucleon exerts on the other nucleons. Although more To illustrate this, consider the element iodine, which has 53
powerful than electrical forces, these strong forces act only over protons (Z = 53). If one particular nuclide of the element iodine
extremely short distances. The actual atomic mass is less than has 78 neutrons (N = 78), the atomic mass (A) of 53 + 78 equals
the sum of the masses of all its nucleons. This difference in mass, 131. It can be written as:
or mass deficit, is manifest in the nuclear binding energy hold-
A
ing the nucleus together (as related by the equation E = mc2).
131
I
53 78
TABLE 1.1 Properties of Atomic Particles Z
Mass N
Particle Charge (amu or u)a Mass (MeV)b Mass (kg)
Because the atomic number can be inferred by the element’s
Proton +1 1.0073 938.21 1.673 × 10–27
symbol, and N = A – Z, this can be shortened:
Neutron 0 1.0087 939.51 1.675 × 10–27
Electron –1 0.000549 0.511 9.11 × 10–31 131 131 131
I I I
53 78 78
aOne amu = 1.661 × 10–27 kg or 1/12 atomic mass carbon (1 nucleon
from carbon-12 atom). This can also be written as I-131 or iodine-131. The term iso-
bEnergy as related by E = mc2.
tope describes nuclides of the same element, that is, nuclides
1
2 PART 1 Basic Principles
TABLE 1.2 Summary of Physical Constants BOX 1.1 Important Terms Related
Unit of charge 1 amp·sec to Atomic Matter
Coulomb (C) 6.24 × 1018 electrons Nucleon—components of the atomic nucleus: protons and neutrons
Electron volt (eV) 1.602 × 10–19 J Atomic number Number of protons, or Z
Charge of 1 electron –1.6 × 10–19 C Neutron number Number of neutrons, or N
Charge of 1 proton + 1.6 × 10–19 C Atomic mass Sum of the nucleons—protons and neutrons (Z + N)—or
Planck’s constant (h) 6.63 × 10–34 m2·kg/s atomic number or A
Elements Atoms with the same number of protons (Z)
Avogadro’s number 6.02 × 1023 molecules/g·mole
Nuclides Nuclear entity comprised of a particular number of protons
Calorie (cal) 4.2 Joules (Z) and neutrons (N) as well as energy state of the
Speed of light in a vacuum 3.0 × 108 m/sec nucleus
Angstrom (Å) 10–10 m Radionuclides Unstable nuclides: isotopes emitting radiation attempting
to reach stability
Isotopes Atoms with the same number of protons: P for proton,
with the same number of protons (Z) but potentially differing P for isotope.
atomic numbers. Radioisotopes are isotopes that undergo radio- Isotones Atoms with the same number of neutrons: N for isotone
active decay. For example, some common isotopes of iodine are Isobars Atoms with the same atomic number A: A for isobar
as follows: Isomer Nuclide with same Z and N (so same A) but a different
energy level
131
I I
125
I
124 123
I
53 78 , 53 72, 53 71, 53 70
M for metastable; M for isomer.
In medicine, different isotopes have varying properties, such
as the types of radiation they emit and how long they remain
radioactive, which can determine their usefulness. For example,
the beta and high-energy gamma emitter 131I (I-131) is used for
treating thyroid cancer and performing thyroid uptake mea-
surements; 125I (I-125), a low-energy gamma and x-ray emitter,
is used in biological assays and prostate cancer brachytherapy;
124I (I-124), a positron emitter, can image thyroid cancer with a
TABLE 1.3 Terms Used to Describe where ν is frequency, λ is the wavelength, and c = 3 × 108 m/s.
Electrons The photon energy (E) is related to the frequency of the EM
wave by
Term Comment
Electron Basic elementary particle E = hv
Orbital electron Electron in one of the shells or orbits in an atom where h is Planck’s constant (6.626 × 10–34 J/s)
Electron in the outermost shell of an atom; responsible
Valence electron for chemical characteristics and reactivity Relating these equations, v = c so E = hc , thus:
Electron ejected from an atomic orbit by energy
Auger electron released during an electron transition 12.4
E (keV) = with the λ measured in angstroms Å .
Electron ejected from an atomic orbit because of Å
internal conversion phenomenon as energy is given
Conversion electron off by an unstable nucleus Visible light has energy slightly less than 1 eV, whereas x-rays
Electron ejected from an atomic orbit as a conse- and gamma rays have energies in the range of several thousand
quence of an interaction with a photon (photoelectric eV (or keV) to tens of millions eV (MeV).
interaction) and complete absorption of the photon’s
X-rays and gamma-ray photons do not differ in their energy
Photoelectron energy
levels but in their origin. X-rays are generated from interactions
Electron ejected from orbit after absorbing a portion of
outside the nucleus, whereas gamma rays are generated by tran-
Compton electron a photon’s energy during Compton scatter
sitions within the nucleus. Once created, nothing distinguishes
an x-ray from a gamma ray (e.g., A 100-keV x-ray is absolutely
identical and indistinguishable from a 100-keV gamma ray).
Potential Binding
Energy Energy Production of X-Rays
orbital shell
X-rays are produced in two ways: (1) as a result of the transition
Highest Lowest of atomic electrons from one orbit to another and (2) from the
N
deacceleration of passing charged particles as they interact with
other charged particles, usually as a result of columbic electrical
M
interactions.
L
Characteristic X-Rays
In the first instance, excited electrons may be removed from their
K
atomic orbit or elevated to a higher-energy orbit. An electron from
an outer orbit can drop down to fill the vacancy, and the excess
energy, the difference in the binding energy of the shells, can be
nucleus emitted as an x-ray photon, a fluorescent x-ray (Fig. 1.4A). This is
also known as a characteristic x-ray because it is specific to not only
each element but also to the orbital shell from which it originated.
Lowest Highest Consider the case of fluorescent or characteristic x-rays from elec-
Fig. 1.2 Orbital binding energy. tronic transitions within an iodine atom with the following binding
Increasing Wavelength
Ultra-
Gamma rays X-rays Infrared Radio waves
violet
Radar TV FM AM
Visible light
Fig. 1.3 Electromagnetic energy spectrum. Photon energies (eV) and wavelengths of x-rays and gamma
ultraviolet, visible light, infrared, and radio waves.
4 PART 1 Basic Principles
Characteristic
Orbital Orbital energy transfer
X-ray
electron electron
vacancy e- vacancy e-
e- e-
M L K n e- M L K n Auger
electron
A B
Fig. 1.4 Interactions may result in (A, left) emission of characteristic (fluorescent) x-rays or (B, right) Auger
electrons.
energies: K = 35, L = 5, and M = 1 keV. Thus, the energy of the flu- 160
orescent x-rays resulting from the transition of electrons from the L Neutron rich
to the K shell (referred to as Kα fluorescent x-rays) is 30 keV 140 (Beta minus decay) Proton rich
(35 − 5 keV) and that from the transition from the M to the K shell
(referred to as Kβ x-rays) is 34 keV (35 − 1 keV). (Electron
capture
120 and
Auger Electrons positron
decay)
There is an alternative outcome to characteristic x-ray emission, 100
where the transition can cause an outer-shell electron to be ejected.
”
ility
This electron is called an Auger (pronounced oh-zhey) electron
Neutron number N
tab
80
(see Fig. 1.4B). The kinetic energy (KE) of the resultant Auger elec-
f “s
tron is determined by the binding energy of the orbits involved:
eo
N
Lin
60
KEAuger = BEInner − BEOuter − BEAuger
Z
Using the example of the iodine atom binding energies again for
40
the transitions shown in Fig. 1.4B, the calculation would then be:
KEAuger = BEK shell − BEL shell − BEM shell
20
= 35keV − 5keV − 1keV = 29keV
The probability of an Auger electron being emitted is greater
in lower Z elements and from outer shells where the binding 0
energy is lower. X-ray fluorescence, on the other hand, is the 20 40 60 80 100
more likely outcome when binding energy is higher, such as in Atomic number Z
higher Z elements and from inner-shell electrons. Fig. 1.5 Graph of neutrons (N) versus protons (P) for various nuclides. For
elements with a low atomic number, the two are roughly equal (Z = N).
Particle Deceleration and Bremsstrahlung X-Rays With increasing atomic number, the relative number of neutrons increases.
Stable nuclear species tend to occur along the “curve of stability.”
X-rays can also be produced as a charged particle deaccelerates
as it passes an atom. In nuclear medicine, this commonly
involves electrons or beta particles passing through soft tissue.
RADIOACTIVITY AND RADIOACTIVE DECAY
In this case, the negatively charged particle is slowed as it inter- The protons and neutrons can only exist in the nucleus in a
acts with the positively charged nucleus it is passing, causing it limited number of combinations. The remaining unstable
to slow. The energy it loses is emitted as radiation referred to as atoms may transform to a lower-energy stable state through
bremsstrahlung (from the German for “braking”) radiation. The radioactive decay (or disintegration), with the excess energy
magnitude of the bremsstrahlung production increases linearly resulting in either particulate emissions or electromagnetic
with the kinetic energy of the incident electron and the Z num- radiation. The initial nuclide, or radionuclide, is known as the
ber of the target material. Thus, bremsstrahlung x-ray produc- parent, and the resultant one after radioactive decay is known
tion is more likely to occur at higher energies and with high-Z as the daughter. Although the daughter nucleus created from a
targets. As a result, radiographic systems can generate x-rays by radioactive decay has a lower energy than the parent nucleus,
directing an energetic electron beam into a tungsten (Z = 74) it may not be stable, and thus subsequent radioactive decays
target. On the other hand, the intensity of the bremsstrahlung may result.
radiation is relatively low when beta particles pass through soft Fig. 1.5 shows a plot of the stable nuclides as a function of
tissue. the Z number on the x-axis and the N number on the y-axis. At
Chapter 1 Radioactivity and Radionuclides 5
B C
Fig. 1.6 “Proton-rich” radionuclides that decay by positron emission can be made in a cyclotron or particle
accelerator. (A) Varying in size and appearance, cyclotrons may be self-shielded or housed in a thick cement
vault (as shown) to reduce radiation exposure. Beam lines (arrow) extending from the central unit direct high-
speed charged particles to bombard desired targets. (B) The bottom of the cyclotron contains the accelerating
electrodes (short arrows). (C) Electromagnetic fields created by a large magnet (arrowhead) in the upper por-
tion of the cyclotron constrain the particles to circular orbits. (Photos courtesy of Anthony F. Zagar, University
of Alabama at Birmingham.)
low Z numbers, stable elements tend to have equal numbers of Proton-rich radionuclides can be created by bombarding a cer-
protons and neutrons (e.g., carbon-12, nitrogen-14, and oxy- tain target material with high-energy protons that can overcome
gen-16) and lie along or near the Z = N line. However, as the nuclear forces. Typically, a particle accelerator such as a cyclotron is
nucleus becomes larger, the repulsive force of the nuclear pro- used, increasing kinetic energy by accelerating charged particles to
tons grows, and more neutrons are necessary in the stable high speeds in a spiral path using alternating high-frequency volt-
nucleus to provide additional attractive nuclear force. Other age and electromagnetic fields (Fig. 1.6). Conversely, in artificial
factors also contribute to the stability and instability of the production of neutron-rich radionuclides, one typically must use a
nucleus. For example, nuclides with even numbers of protons nuclear reactor to bombard a target with a neutron flux (Fig. 1.7).
and neutrons tend to be more stable than those with odd Z and
N configurations. Modes of Radioactive Decay
Unstable nuclides fall to either the right or the left of the A decay scheme is a way to illustrate the transition from parent
curve of stability, with those to the right considered proton rich to daughter nuclides. In a decay scheme, higher energy levels
and those to the left neutron rich. As unstable radionuclides are toward the top of the figure, and higher Z numbers are to the
decay to entities that are closer to the curve of stability, pro- right of the figure. Transitions that lead to a reduction in energy
ton-rich radionuclides tend to decay in a manner that will are represented by an arrow pointing down. If it also results in a
reduce the Z number and increase the N number, and neu- daughter nuclide with a change in the Z number, the arrow will
tron-rich radionuclides tend to decay in a way that decreases the point to the left with a decrease in the Z number and to the right
N number and increases the Z number. if Z is increased.
6 PART 1 Basic Principles
Alpha Decay
An unstable heavy atom may decay to a nuclide closer to the
curve of stability by emitting an alpha particle (α) consisting of
2 protons and 2 neutrons (essentially an ionized helium atom):
A A −4 A −4 4
Z
X→ Z−2Y + α = Z−2Yjo 9 + 2 He
The daughter nucleus may not be stable, and thus the emis-
sion of an alpha particle often will lead to the emission of a
series of radiations until the nucleus is stable. The decay scheme
for the decay of radium-226 (Ra-226) to radon-222 (Rn-222) is
shown in Fig. 1.8.
Beta-Minus Decay
Neutron-rich radionuclides tend to stabilize by decreasing
the number of neutrons through a radioactive-decay process
referred to as beta-minus (β–), also known as negatron or
beta decay. Factors such as weak forces between nucleons
transfer energy, transforming a neutron into a proton (N – 1
and Z + 1). This is an isobaric transition with no change to
Fig. 1.7 Fission and neutron capture radionuclide production in a nuclear
the atomic mass (A). An example of the beta-minus decay
reactor. Samples can be lowered into the reactor as shown, with water scheme for I-131 is shown in Fig. 1.9. Excess energy is emit-
acting as shielding against neutrons. The blue glow is caused by the ted from the nucleus as an antineutrino and a negative beta
emission of electrons from the radioactive products; when charged par- particle (or negatron). This process can be written as
ticles move faster than the speed of light in a medium such as water, follows:
the emitted radiation is called Cherenkov radiation. (Courtesy of the Uni-
A A
versity of Missouri Research Reactor Center.) X
Z N
= Z+1YN−1 + β − + −υ antineutrino
226
Ra (1600 yr)
88
448 keV
2
186 keV
1
222
Rn (3.8 days)
86
Fig. 1.8 Alpha decay. The emission of an alpha particle (2 protons and 2 neutrons) results in the atomic
number (Z) decreasing by 2 and the atomic mass (Z + N) decreasing by 4. Decay of radium-226 to the daugh-
ter Rn-222 shows the arrow pointed down, indicating a decrease in energy, and to the left because of the
decrease in Z.
Chapter 1 Radioactivity and Radionuclides 7
131 18
I (8 days)
53 9 F (110 min)
364 keV
(81%)
18
8O (stable)
131 Fig. 1.10 Positron (β+) decay results in a loss of 1 proton (Z – 1) in pro-
Xe (stable)
54 ton-rich radionuclides. Because 1 neutron is gained, the atomic mass of
Fig. 1.9 Beta minus (β –) decay scheme for iodine-131 to the daughter the daughter is unchanged, another example of isobaric transition. F-18
Xe-133. β– decay (negatron emission) results in the daughter with one decay by positron emission results in the daughter product, O-18. The
more proton in the nucleus (Z + 1), so the arrow points to the right. arrow points down and to the left, indicating the decrease in Z.
Because a neutron is lost (N – 1), this is an isobaric transition with the
atomic mass unchanged.
201
81Tl (73 hr)
The antineutrino is very difficult to measure because it has
virtually no mass or charge associated with it, only energy. The
negative beta particle is indistinguishable from an electron
with the same mass and electric charge, differing only in that EC
the beta particle is emitted from the nucleus and the electron
orbits the nucleus. In addition to the Mo-99 used to make
Tc-99m, several β–-emitting radionuclides play an important
167 keV
role in nuclear medicine for therapy applications: I-131, phos-
(3%)
phorus-32 (P-32), yttrium-90 (Y-90), and lutetium-177 32 keV
(10%)
(Lu-177).
201
Beta-Plus (Positron) Decay 80 Hg (stable)
Unstable proton-rich radionuclides can reduce Z and increase Fig. 1.11 Electron capture is an alternate transition that can occur to
N numbers through either beta-plus decay or electron capture. In reduce the proton number and does not require that an energy thresh-
beta-plus decay, the parent nucleus emits a positively charged old be met. Tl-201 decays by electron capture, with the daughter (Hg-
beta particle, a positron (β+). The resulting daughter nucleus has 201) containing one fewer proton (Z – 1) than the parent.
one fewer proton and one more neutron than the parent, an iso-
baric transition: Electron Capture. An alternative to beta-plus decay for
A A proton-rich radionuclides is electron capture (EC). In this
X = Y
Z N Z−1 N+1
+ β + + υ neutrino process, an inner-shell, orbital electron is absorbed into the
average β + kinetic energy: Eβ + ≈ Emax /3 nucleus, leading to the reduction of Z and increase of N by 1.
The positron has the same mass as a beta-minus particle or However, no energy threshold exists for EC to occur. In cases in
electron, with a charge of the same magnitude but the opposite. which the transition energy is less than the 1022-keV threshold,
In fact, the positron is the antiparticle of the electron; if they are EC is the only possible decay process, but either process is
brought into close contact, they will be annihilated and trans- possible when the energy is greater than 1022 keV. For F-18,
formed into two 511-keV photons, traveling at 180 degrees in positron decay occurs 97% of the time, and EC occurs 3% of the
opposite directions. This annihilation process is the basis of time. The capture of an orbital electron leads to an inner-shell
PET imaging. The 511-keV value derives from the energy equiv- vacancy, which in turn leads to the emission of fluorescent
alence of the mass of the beta particle, similar to the rest mass of x-rays or Auger electrons. Radionuclides that decay through EC
an electron (using E = mc2 as previously discussed). exclusively include thallium-201 (Tl-201; Fig. 1.11), gallium-67
For positron decay to occur, the transition energy must be in (Ga-67), and indium-111 (In-111). These are all produced in a
excess of a 1022-keV threshold (twice 511 keV) to overcome the cyclotron.
production of the positron and addition of an orbital electron to Isomeric Transition. In some cases, an excited radionuclide
maintain electric neutrality. These radionuclides are typically decays from one energy level to another while retaining the
produced using a cyclotron. Some positron-emitting radionu- same Z and N numbers. This is referred to as an isomeric
clides of interest include fluorine-18 (F-18; Fig. 1.10), nitro- transition because the nuclide decays from one isomer (energy
gen-13 (N-13), carbon-11 (C-11), gallium-68 (Ga-68), and level) to another. This transition may result in the emission of a
rubidium-82 (Rb-82). gamma ray, the energy of which is determined by the energy
8 PART 1 Basic Principles
99m reciprocal of Tm, the fraction of the radioactive atoms that decay
43 Tc (6.01 hr) per unit time, is referred to as the decay constant, λ:
1
λ=
Tm
Thus, the number of atoms (dN) that decay in a short time
140.5 keV (89%) interval (dt) is given by:
dN = λdt
Integrating this equation over time leads to:
N = N0e−λt
where N0 is the initial number of radioactive atoms, and N is the
99 number remaining after some time, t.
43 Tc This equation describes exponential decay in which a certain
Fig. 1.12 Isomeric transitions involve a change in the energy state of a fraction of the material is lost in a set period. This fraction is
radionuclide, such as Tc-99m to Tc-99.
referred to as the decay fraction, DF:
99 DF = e−λt
42Mo (2.8 days or 66 hr)
Thus, the number of radioactive atoms remaining, N, is also
given by:
N = N0 × DF
142.7 keV
Also, Nd is the number of atoms that have decayed in time, t,
140.5 keV
and can be calculated with:
Nd = N0 × (1 − DF)
0.0
The time necessary for half of the material to decay is defined
99 5 as the half-life (T1/2). The half-life is related to the mean life and
43Tc (2.1 10 yr)
the decay constant by the following equations:
Fig. 1.13 Decay scheme of Mo-99. Beta-minus emission to Tc-99m,
followed by isomeric transition to Tc-99. 0.693
T1/2 = ln (2) Tm =
difference of the initial and eventual energy levels. In some λ
cases, an alternate process called internal conversion can occur, Alternatively, one can determine the decay constant from the
resulting in the emission of an orbital electron, a conversion half-life by:
electron. The kinetic energy is calculated as the difference in the 0.693
two energy levels minus the electron’s binding energy. λ=
T1/2
Perhaps the most important isomeric transition for
nuclear medicine involves technetium. The term metastable One can also express the radioactive decay equation using
(i.e., almost stable) is used if the daughter nucleus remains the half-life:
in the excited state for a considerable amount of time (>1 − 0.693t
microsecond, which is long by nuclear standards). Mo-99 N = N0e T1/2
INTERACTIONS BETWEEN RADIATION AND The β– kinetic energy is variable because it shares energy with
the antineutrino produced during the decay event. The maxi-
MATTER mum kinetic energy of the beta particle (Emax) is defined by the
Charged-Particle Interactions With Matter difference in the energy levels of the parent and daughter
A charged particle may transfer energy in different ways. First, nuclide. However, it is the average kinetic energy that is used
it can be attracted and slowed by the opposite charge of the when calculating the impact of the β– on cells and tissues, esti-
nucleus or orbiting electrons in target material atoms. The mated as 1/3 of Emax (Eβ ≈ Emax /3), similar to the calculation
resulting kinetic energy loss is released as radiation (radiative previously described for positrons.
losses). Bremsstrahlung radiation occurring with a β– emitter is
one example of this type of interaction. The energy of radiative Photon Interactions in Matter
losses is directly proportional to the Z number of the target as High-energy photons (gamma rays, x-rays, bremsstrahlung
well as to the incident particle’s energy. radiation, and annihilation radiation) can also transfer energy
Charged particles can also directly transfer energy to the to the electrons, nuclei, or atoms as a whole that they encoun-
atom’s orbital electrons, resulting in electron excitations and ter. Unlike charged particles, which directly create ionized
ionizations. While excited, electrons can temporarily move to a atoms, the high-energy photons act indirectly, transferring
shell farther from the nucleus. As de-excitation occurs, trans- their energy to charged particles, specifically electrons, which
ferred energy leads to the emission of Auger electrons or elec- in turn create most of the excitations and ionizations that occur
tromagnetic radiation. This radiation can have a wide range of in the matter. Thus they are considered secondary ionizing
energies, including visible or ultraviolet radiation for outer-shell radiations.
transitions and fluorescent x-rays for the inner-shell At low energy levels (a few keV), photons are scattered in a
transitions. manner that does not deposit energy, referred to as Rayleigh
When the energy from charged-particle interactions pro- scattering. Photons with energy in excess of several MeV can
duces ionized electrons and atoms in tissues, the majority of the result in pair production of a negatron and a positron (effectively
ionized electrons are low energy. However, some interactions a negative and positive electron). However, in energy ranges
result in high-energy electrons, referred to as delta rays, which most common in nuclear medicine (from several tens of keV to
in turn can also cause excitation and ionization. In the energies approximately 1 MeV), the two most prominent modes of pho-
of practical interest in nuclear medicine, nearly all of the energy ton interaction are the photoelectric effect and Compton scatter-
from a charged-particle interaction (greater than 99%) is ing. Factors involved in the various types of interaction are
expended in excitation and ionization (or collisional losses) outlined in Table 1.4.
compared with radiative losses.
The rate at which a material causes a charged particle to lose Photoelectric Effect
energy (per unit length of the matter) is referred to as its stop- The photoelectric effect (Fig. 1.15) occurs when a photon trans-
ping power. A related quantity is linear energy transfer (LET), fers all of its energy to an orbital electron, causing it to be ejected
which is the amount of energy deposited locally (i.e., not lost to from the atom and creating an electron-shell vacancy. The
energetic electrons, delta rays, or radiative loss) per unit length. kinetic energy of the liberated photoelectron equals the incident
The stopping power and LET values depend on the type of radi- photon’s energy minus the binding energy of the electron’s ini-
ation, its energy, and the density of the material through which tial orbital shell. As the shell vacancy is filled by electrons from
it travels. Radiation with a higher LET value has been shown to outer shells, fluorescent x-rays and Auger electrons are also
cause more damage to cells. Alpha particles have a higher LET emitted. Paradoxically, the probability of photoelectric interac-
than beta particles or electrons. tions is highest for tightly bound orbiting electrons (i.e., those in
Although densely ionizing, alpha particles deposit their the inner shells of high Z elements). These electrons are most
energy over a very short distance, a small fraction of a millime- likely the ones in the innermost orbital shell where the binding
ter in soft tissues. Also, although they are easily stopped by the energy is just under the photon’s energy. In addition, the chance
skin, these high-energy particles cause substantial cell death of this interaction dramatically decreases as incident photon
when internalized, making them both extremely dangerous if energy increases. The probability of the photoelectric interac-
accidentally ingested as well as highly effective in therapeutic tion (or PPE) is given by:
applications (e.g., Ra-223 in prostate cancer).
3 3
Comparatively, β– particles travel for much longer distances, PPE α Z /E
ranging from several millimeters to several centimeters depend-
ing on their initial energy. They can be stopped by material such where Z = atomic number, and E = incident photon kinetic
as a thin sheet of aluminum or a few millimeters of soft tissue. energy.
Chapter 1 Radioactivity and Radionuclides 11
In soft tissues (low Z), the photoelectric effect is much less occurring. Higher-energy incident photons lose less energy to
common than Compton scatter. It is, however, more prevalent the electron, and deflection is less significant (i.e., the scatter
in the high-Z materials used for shielding (e.g., lead) or for pho- angle is narrower), such that both the scattered photon and elec-
ton detection (sodium iodide crystals). Photoelectric effect tron tend to travel in a more forward direction.
interactions can also occur in the gamma camera’s photomulti- Whereas the photoelectric effect is important at lower
plier tubes, which contain high-Z materials, such as cesium. energies and more likely involves inner-shell electrons in
high-Z materials, Compton scatter predominates in soft tis-
Compton Scatter sues in the moderate-energy ranges of gamma-ray and x-ray
The incident photon does not disappear in Compton scatter. photons in nuclear medicine imaging and tends to involve
Rather, it transfers a portion of its energy to an orbital electron outer-shell electrons. Because the energy of the incident pho-
(a Compton electron), which is then ejected from the atom. The ton is much greater than the shell’s binding energy, the colli-
photon is deflected or scattered, at an angle θ from its original sion occurs as if involving a free electron. Compton
path (Fig. 1.16). The electron and scattered photon may go on to interactions tend to depend on electron density but are rela-
ionize or excite other atoms. tively independent of the Z number or incident photon
The sum of the kinetic energies of the scattered photon and energy. Because electron density is fairly consistent among
the Compton electron will equal the initial photon’s energy. the atoms in soft tissues, the probability increases with
With lower-energy incident photons, more energy is transferred increasing material density rather than its Z number. Electron
to the electron, and there is greater backscatter of the resulting density is higher when hydrogen atoms are present, so tissues
photon (i.e., the angle between the incident and scattered pho- with high water content are more affected than anhydrous
tons tends to be wider), with even 180 degrees of backscatter tissues.
12 PART 1 Basic Principles
Photoelectron
Nucleus
Nucleus
Vacancy
Incident photon
A B
Characteristic
x-ray
Vacancy
Nucleus
Electron
transition
between
shells
C
Fig. 1.15 Photoelectric absorption. (A) An incident photon interacts with an orbital electron. (B) The electron
is ejected from its shell, creating a vacancy. The electron is either ejected from the atom or moved to a shell
further from the nucleus. (C) The orbital vacancy is filled by the transition of an electron from a more distant
shell. Consequently, a characteristic x-ray is given off.
Chapter 1 Radioactivity and Radionuclides 13
SUGGESTED READING
Chandra R, Rahmin A. Nuclear Medicine Physics: The Basics. 8th ed.
Philadelphia: Williams & Wilkins; 2012.
Cherry SR, Sorenson JA, Phelps ME. Physics in Nuclear Medicine. 4th
ed. Philadelphia: WB Saunders; 2012.
Compton
Eckerman KF, Endo A. MIRD: Radionuclide Data and Decay Schemes.
Nucleus
electron 2nd ed. Reston, VA: Society of Nuclear Medicine; 2008.
Loevinger R, Budinger TF, Watson EE. MIRD Primer for Absorbed
Dose Calculations. Reston, VA: Society of Nuclear Medicine; 1988.
Powsner RA, Powsner ER. Essentials of Nuclear Medicine Physics. 3rd
ed. West Sussex, UK: Wiley-Blackwell; 2013.
Angle Saha GP. Physics and Radiobiology of Nuclear Medicine. 4th ed. New
of scatter Compton- York: Springer; 2013.
scattered
photon
Incident
photon
Fig. 1.16 Compton scatter. An incident photon interacts with an outer
or loosely bound electron, giving up a portion of its energy to the elec-
tron and undergoing a change in direction at a lower kinetic energy level.
2
Radiation Detection & Ancillary
Instrumentation
Janis M. O’Malley, Harvey Ziessman, Frederic Fahey
The passage of radiation, such as x-rays and gamma rays, through of the detector. For photons, the intrinsic efficiency, DI, is given
a given material leads to ionizations and excitations that can be to first order by:
used to quantify the amount of energy deposited. This property
DI = (1 − e ‐ μx )
allows measurement of the level of intensity of a radiation beam
or small amounts of radionuclides, including from within the where μ is the linear attenuation coefficient for the material of
patient. The appropriate choice of detection approach depends interest at the incident photon energy, and x is the thickness of
on the purpose. In some cases, the efficient detection of min- the detector. Thus the intrinsic efficiency can be improved by
ute amounts of the radionuclide is essential, whereas in other using a thicker detector or choosing a photon energy and detec-
cases the accurate determination of the energy or location of the tor material that optimizes the value of μ.
radiation deposited is most important. A variety of approaches The extrinsic efficiency is the fraction of photons or particles
to radiation detection are used, including those that allow for emitted from the source that strike the detector. It depends on
in vivo imaging of radiopharmaceuticals. the size and shape of the detector and the distance of the source
from the detector. If the detector is a considerable distance from
the source (i.e., a distance that is >5 times the size of the detec-
RADIATION DETECTION tor), the extrinsic efficiency, DE, is given by:
Consider the model of a basic radiation detector, as shown DE = A/ 4πd 2
in Fig. 2.1. The detector acts as a transducer that converts
radiation energy to electronic charge. Applying a voltage where A is the area of the detector, and d is the distance from the
across the detector yields a measurable electronic current. source to the detector. This equation defines the inverse square
Radiation detectors typically operate in either of two modes, law. For example, if the source-to-detector distance is doubled,
current mode or pulse mode. Detectors that operate in cur- the intensity of the radiation beam is reduced by a factor of 4.
rent mode measure the average current generated within the The total detection efficiency is the product of the intrinsic and
detector over some characteristic integration time. This aver- extrinsic efficiencies:
age current is typically proportional to the exposure rate to DT = DI × DE
which the detector is subjected or the amount of radioactivity
within the range of the detector. In pulse mode, each individ- In pulse mode, the pulse height is proportional to the energy
ual detection is processed with respect to the peak current (or deposited within the detector. However, the uncertainty in the
pulse height) for that event. This pulse height is proportional energy estimation, referred to as the energy resolution, depends
to the energy deposited in the detection event. The histogram on the type of detector used and the energy of the incident radi-
of pulse heights is referred to as the pulse-height spectrum. It ation. For a photon radiation source of a particular energy, the
is also referred to as the energy spectrum because it plots a feature associated with that energy is referred to as the photo-
histogram of the energy deposited within the detector. peak, as shown in Fig. 2.2. The width of the photopeak, as char-
Certain properties of radiation detectors characterize their oper- acterized by the full width at half of its maximum (FWHM)
ation. Some are applicable to all detectors, whereas others are used value normalized by the photon energy represented as a per-
for detectors that operate in pulse mode. These characterizations centage, is used as a measure of the energy resolution of the
are not only useful for describing the operation but can also give detector.
insight into the benefits and limitations of the particular detector. When the detector is subjected to a radiation beam of low
The detection efficiency depends on several factors, includ- intensity, the count rate is proportional to the beam intensity.
ing the intrinsic and extrinsic efficiency of the detector. The However, the amount of time it takes for the detector to process
intrinsic efficiency is defined as the fraction of the incident radi- an event limits the maximum possible count rate. Two models
ation particles that interact with the detector. It depends on the describe the count rate limitations: nonparalyzable and paralyz-
type and energy of the radiation and the material and thickness able. In the nonparalyzable model, each event takes a certain
14
Chapter 2 Radiation Detection & Ancillary Instrumentation 15
Voltage source
+ –
+ Anode Geiger-Müller
Incident region
for the collection of all of the liberated ions (no recombination). efficiency because they affect the linear attenuation coefficient
This level is referred to as the saturation voltage, and the result- of the scintillation material. The amount of emitted light affects
ing plateau in Fig. 2.3 is the ionization chamber region. When both energy and, in the gamma camera, spatial resolution. Res-
operating in this region, the amount of charge collected is pro- olution is determined by the statistical variation of the collected
portional to the amount of ionization caused in the detector and light photons, which depends on the number of emitted pho-
thereby to the energy deposited within the detector. Ionization tons. Finally, the response time affects the temporal resolution
detectors or chambers typically operate in current mode and of the scintillator. The most common scintillation crystalline
are the detectors of choice for determining the radiation beam material used in nuclear medicine is thallium-doped sodium
intensity level at a particular location. They can directly mea- iodide (NaI) with lutetium oxyorthsilicate (LSO) or lutetium
sure this intensity level in either exposure in roentgens (R) or air yttrium oxyorthosilicate (LYSO) most commonly used in posi-
kerma in rad. Dose calibrators and the ionization meters used to tron emission tomography (PET).
monitor the output of an x-ray device or the exposure level from Once the light is emitted in a scintillation detector, it must be
a patient who has received a radiopharmaceutical are examples collected and converted to an electrical signal. The most com-
of ionization (or ion) chambers used in nuclear medicine. monly used device for this purpose is the photomultiplier tube
If the voltage is increased further, the drifting electrons (PMT). Light photons from the scintillator enter through the
within the device can attain sufficient energy to cause further photomultiplier entrance window and strike the photocathode,
ionizations, leading to a cascade event. This can cause substan- a certain fraction of which (approximately 20%) will lead to the
tially more ionization than with an ionization chamber. The total emission of photoelectrons moving toward the first dynode. For
ionization is proportional to the amount of ionization initially each electron reaching the first dynode, approximately a million
liberated; therefore these devices are referred to as proportional electrons will eventually reach the anode of the photomultiplier
counters or chambers. Proportional counters, which usually tube. Thus the photomultiplier tube provides high gain and
operate in pulse mode, are not typically used in nuclear med- low noise amplification at a reasonable cost. Other solid-state
icine. If the voltage is increased further, the drifting electrons light-detection approaches are now being introduced into
attain the ability to cause a level of excitations and ionizations nuclear medicine devices. In avalanche photodiodes (APDs),
within the gas. The excitations can lead to the emission of ultra- the impinging light photons lead to the liberation of electrons
violet radiation, which also can generate ionizations and fur- that are then drifted in the photodiode, yielding an electron ava-
ther excitations. This leads to a terminal event in which the level lanche. The gain of the APD is not as high as with the PMT (sev-
of ionization starts to shield the initial event, and the level of eral hundred compared with about a million), but the detection
ionization finally stops. This is referred to as the Geiger-Müller efficiency is substantially higher (approximately 80%). A second
process. In the Geiger-Müller device, every event leads to the solid-state approach is the silicon photomultiplier tube (SiPMT).
same magnitude of response, irrespective of the energy or the This device consists of hundreds of very small APD channels
type of incident radiation. Thus the Geiger-Müller meter does that operate like small Geiger-Müller detectors—that is, each
not directly measure exposure, although it can be calibrated in detection is a terminal event. The signal from the SiPMT is the
a selected energy range to milliroentgens per hour (mR/hr). number of channels that respond to a particular detection event
However, the estimate of exposure rate in other energy ranges in the scintillator. SiPMTs have moderate detection efficiency
may not be accurate. The Geiger-Müller survey meter is excel- (approximately 50%) and operate at low voltages. One further
lent at detecting small levels of radioactive contamination and advantage of APDs and SiPMTs compared with PMTs is that
thus is often used to survey radiopharmaceutical packages that they can operate within a magnetic field. Thus the development
are delivered and work areas within the nuclear medicine clinic of positron emission tomography/magnetic resonance (PET/
at the end of the day. MR) scanners has involved the use of either APDs or SiPMTs.
Solid-state technology is used to detect the light from a scin-
tillation detector and also can be used to directly detect gamma
SCINTILLATION DETECTORS rays. The detection of radiation within a semiconductor detector
Some crystalline materials emit a large number of light pho- leads to a large number of electrons liberated, resulting in high
tons upon the absorption of ionizing radiation. This process is energy resolution. The energy resolution of the lithium-drifted
referred to as scintillation, and these materials are referred to germanium (GeLi) semiconductor detector has approximately
as scintillators. As radiation interacts within the scintillator, a 1% energy resolution compared with the 10% energy resolution
large number of excitations and ionizations occur. On de-exci- associated with a sodium iodide scintillation detector. However,
tation, the number of light photons emitted is directly propor- thermal energy can lead to a measurable current in some semi-
tional to the amount of energy deposited within the scintillator. conductor detectors such as GeLi, even in the absence of radia-
In some cases, a small impurity may be added to the crystal to tion, and thus these semiconductor detectors must be operated
enhance the emission of light and minimize the absorption of at cryogenic temperatures. On the other hand, semiconductor
light within the crystal. Several essential properties of scintil- detectors such as cadmium telluride (CdTe) or cadmium zinc
lating materials can be characterized, including density, effec- telluride (CZT) can operate at room temperature. CdTe and
tive Z number (number of atomic protons per atom), amount CZT do not have the excellent energy resolution of GeLi, but
of light emitted per unit energy, and response time. The density at approximately 5%, it is still significantly better than that of
and effective Z number are determining factors in the detection sodium iodide.
Chapter 2 Radiation Detection & Ancillary Instrumentation 17
detections lead to a terminal event of the same magnitude—a than 10% from the calibrated activity decay corrected to the
“click.” The device is excellent for detecting small amounts of day of the test. The accuracy test should be performed during
18 PART 1 Basic Principles
acceptance testing, annually thereafter, and after a major repair of standards of known activity concentration (kilobecquerel per
or move. milliliter), the patient’s GFR can be estimated.
The linearity protocol tests that the dose calibrator operates The thyroid probe consists of an NaI crystal on a stand with
appropriately over the wide activity range to which it is applied. the associated counting electronics. The patient is administered
The device is tested from 10 μCi (370 kBq) to a level higher a small amount of radioactive iodine. The probe is placed at a
than that routinely used in the clinic and perhaps as high as 1 certain distance from the thyroid, and a count is obtained. In
Ci (37 GBq). The activity readings are varied by starting with addition, a count is acquired of a known standard at the same
a sample of the radioactivity of Tc-99m at the highest value to distance. The thyroid uptake of iodine can be estimated from
be tested (e.g., tens of gigabequerels). The activity readings are these measurements.
then varied by either allowing the source to radioactively decay The quality control program for both the well counter and
over several days or using a set of lead shields of varying thick- the thyroid probe includes the energy calibration, the energy
nesses until a reading close to 370 kBq is obtained. Each reading resolution, the sensitivity, and the chi-square test. For the energy
should not vary by more than 10% from the line drawn through calibration, the energy window is set for the calibration source
the calculated activity values. The linearity test should be per- of a particular radionuclide—for example, the 662-keV peak of
formed during acceptance testing, quarterly thereafter, and after Cs-137. The amplifier gain is varied until the maximum count is
a major repair or move. found that corresponds with the alignment of the window with
The constancy protocol tests the reproducibility of the read- the 662-keV energy peak. In addition, the counts in a series of
ings compared with a decay-corrected estimate for a reference narrow energy windows across the peak can be measured to
reading obtained from the dose calibrator on a particular day. estimate the energy resolution. A standard window can be set,
Today’s constancy reading cannot vary from the decay-cor- and the counts of a known calibration source can be counted
rected reference reading by more than 10%. The constancy test and normalized by the number of nuclear transformations to
varies from accuracy in that it evaluates the precision of the estimate the sensitivity in counts per transformation (or counts
readings from day to day rather than accuracy. The constancy per second per becquerel). Finally, the chi-square test evaluates
test should be performed on every day that the device is used to the operation of the counter by comparing the uncertainty of
assay a dose to be administered to a patient. the count to that expected from the Poisson distribution.
There are two nonimaging scintillator devices, the well
counter, and the thyroid probe that are routinely used in the
nuclear medicine clinic. The well counter is used for both radi-
THE PATIENT AS A RADIOACTIVE SOURCE
ation protection and clinical protocols. The thyroid probe can In nuclear medicine, the patient is administered a radiophar-
provide clinical studies with a fraction of the equipment costs maceutical that distributes according to a specific physiological
and space requirements of the use of nuclear imaging equip- or functional pathway. The patient is then imaged using exter-
ment. However, these devices also require comprehensive qual- nal radiation detectors to determine the in vivo distribution
ity control programs. and dynamics of the radiopharmaceutical through which the
The well counter consists of an NaI crystal with a hole in it, patient’s physiology can be inferred, providing this essential
allowing for test tubes, and other samples can be placed within information to the patient’s doctor to aid in diagnosis, prog-
the device for counting. The samples to be placed in the counter nosis, staging, and treatment. The equipment used to acquire
is practically surrounded by the detector, with a geometrical these data will be described in the sections ahead. Single-pho-
efficiency in excess of 90%. Thus the well counter can measure ton emission computed tomography (SPECT) and PET are
very small amounts of radioactivity, on the order of a kilobec- described in the next chapter. However, before examining how
querel. The well counter should not be confused with the dose the instrumentation operates, it is instructive to understand the
calibrator, which is a gas-filled ionization chamber that can nature of the signal itself—that is, the radiation being emitted
measure activities up to 37 GBq. It is used to test packages of from within the patient.
radiopharmaceuticals to ensure that no radioactivity has been The radiopharmaceutical is administered to the patient most
spilled on the outside of the package or leaked from the inside. commonly by intravenous injection but also in some cases
The device also can be used to measure removable activity from through other injection routes, such as intraarterial, intraper-
working surfaces where radioactivity has been handled or from itoneal, or subdermal. In other cases, the radiopharmaceutical
sealed sources such as calibration sources to ensure that the may be introduced through the gastrointestinal tract or through
radioactivity is not leaking out. the breathing of a radioactive gas or aerosol. After administra-
The well counter can also be used for the assay of biologi- tion, the path and rate of uptake depend on the particular radio-
cal samples for radioactivity for a variety of clinical evaluations. pharmaceutical, the route of administration, and the patient’s
For example, after the administration of Tc-99m diethylenetri- individual physiology. However, the characteristics and param-
amepentaacetic acid (DTPA), blood samples can be counted at eters associated with the radiopharmaceutical in vivo distribu-
several time points (e.g., at 1, 2, and 3 hours) to estimate the tion and dynamics are of considerable clinical importance. In
patient’s glomerular filtration rate (GFR). The amount of radio- some cases, the enhanced uptake of the radiopharmaceutical in
activity in a 0.2-mL blood sample will be very small, and thus the certain tissues (e.g., the uptake of fluorodeoxyglucose [FDG] in
well counter is the appropriate instrument for these measure- tumors) may be of most clinical importance, whereas in other
ments. By making these measurements and the measurements cases it may be the lack of uptake (e.g., the absence of Tc-99m
Chapter 2 Radiation Detection & Ancillary Instrumentation 19
Collimator
Crystal
Positioning
pulses
Position computer
X-ray or Gamma
gamma ray (X)
camera
photon oscilloscope
(Y) and
computer
memory
Addition Pulse
circuit height
analyzer
(z)
“Z” pulse
Fig. 2.6 Schematic of gamma scintillation camera. The diagram shows a photon reaching the NaI crystal
through the collimator and undergoing photoelectric absorption. The photomultiplier tubes (PMTs) are opti-
cally coupled to the NaI crystal. The electrical outputs from the respective PMTs are further processed through
positioning circuitry to calculate (x, y)-coordinates and through additional circuitry to calculate the deposited
energy of the pulse. The energy signal passes through the pulse height analyzer. If the event is accepted, it is
recorded spatially in the location determined by the (x,y)-positioning pulses.
In the mid-1950s, Hal Anger developed his first prototype The detection material of the gamma camera is typically a sin-
of the gamma camera, which allowed a section of the body to gle, thin large-area NaI scintillation crystal. Some smaller cameras
be imaged without a raster scan, opening the door for the pos- rely on a 2D matrix of smaller crystals, but most rely on a single
sibility of both dynamic and physiologically gated studies. Fur- large crystal. In the most common gamma camera designs, the NaI
ther developments of the technology took place over the next 10 crystal is about 30 cm × 50 cm in area and 9.5 mm thick. Some
years, and the first commercial gamma camera was introduced cameras designed for imaging only photons with energies below
in the mid-1960s. With further advances that have improved and 150 keV may have thinner crystals. Others used more commonly
stabilized the operation of the instrument, along with the addi- for higher-energy photons may be thicker, but the 9.5-mm thick-
tion of tomographic capability, the gamma camera remains the ness provides a reasonable compromise because it detects more
most commonly used imaging device in the nuclear medicine than 85% of the photons with energies of 140 keV or lower and
clinic. stops about 28% of the 364-keV gamma rays emitted by I-131. NaI
A block diagram of the gamma camera is shown in Fig. 2.6. is hygroscopic and thus damaged by water. It is hermetically sealed
Gamma rays emitted from within the patient pass through the and has a transparent light guide on the side adjacent to the PMT
holes of an absorptive collimator to reach the NaI crystal. On array and aluminum on the side closer to the collimator. The NaI
interaction of the gamma ray with the NaI scintillating crystal, crystal is the most fragile component of the gamma camera, being
thousands of light photons are emitted, a portion of which are susceptible to both physical and thermal shock. When the collima-
collected by an array of PMTs. By taking weighted sums of the tor is not in place, the bare NaI crystal must be treated with extreme
PMT signals within the associated computer, the two-dimen- care. In addition, the environment in the room must be controlled
sional (2D) x- and y-location and the total energy of the detec- so that the air temperature is maintained at a reasonable level (18-
tion event deposited are estimated. If the energy deposited is 24°C) and is not subject to wide variations over a short period.
within a prespecified energy window (e.g., within 10% of the The PMT array consists of about 60 to 100 photomultiplier
photopeak energy), the event is accepted, and the location of tubes that are each about 5 cm in diameter. The PMTs are usually
the event recorded. In this manner, the gamma camera image hexagonal and arranged in a hexagonal close-packed array to col-
is constructed on an event-by-event basis, and a single nuclear lect as many light photons as possible. Although PMTs are used
medicine image may consist of hundreds of thousands of such in practically all gamma cameras, some small camera designs are
events. Each component of the gamma camera will be described. using avalanche photodiodes to collect the scintillation light. The
Chapter 2 Radiation Detection & Ancillary Instrumentation 21
signal from each PMT is input into the gamma camera host com-
puter. First, the sum of all of the PMT signals is used to estimate
the energy deposited in the detection event. In addition, each
PMT has a weight associated with its position in both the x- and
y-direction. For example, the PMTs on the left side of the camera
may have a low weight, and those on the right side of the cam-
era would have a higher weight. For a particular detection event,
if the weighted sum of the signal is low, the event would be on
the left side, and if it were high, it would be on the right side of
the camera. However, the weighted sum as described is depen-
dent not only on the position of the event but also on the total
amount of light collected, which is directly proportional to the
energy deposited. Therefore the sum must be normalized by
the energy estimate. This approach to determining the position
of the detection event is often referred as Anger logic, in honor
of the developer of the gamma camera, Hal Anger. This leads
to an estimate of the detection event location to within 3 to 4
mm, which is referred to as the intrinsic spatial resolution of the
camera.
However, distortions can occur in images with respect to both
the energy and position estimates. Detection events directly
over PMTs lead to the collection of slightly more light than the
events between PMTs and therefore to a slightly higher pulse
height. Energy calibration notes the shift in the pulse height
spectrum as a function of position. Subsequently, an opposite
shift is applied on an event-by-event basis, leading to improved
energy resolution and greater energy stability. In addition, there
is an inherent nonlinearity, with events being bunched over
PMTs and spread out between PMTs. Analogous to energy cal-
ibration, linearity calibration determines the spatial shift from
linearity as a function of position across the entire field of view.
Again, these shifts in both energy and position are applied on
an event-by-event basis, providing an image that is free of lin-
ear distortion. A very-high-count uniformity calibration map
Fig. 2.7 Pinhole collimator. The image is inverted. The image is mag-
is acquired that characterizes the remaining nonuniformities nified if the distance from the aperture to the object is smaller than
inherent in the gamma camera acquisition process. These uni- the distance from the aperture to the gamma camera crystal. Spatial
formity calibration maps are used to generate uniformity cor- resolution improves and sensitivity decreases as the aperture diameter
rections that are applied during each acquisition. decreases. The sensitivity also decreases with the source-to-aperture
distance, according to the inverse square law. In general, the pinhole
collimator provides the best spatial resolution and the lowest sensitivity
COLLIMATORS of any collimator used in nuclear medicine.
Although the NaI crystal, PMTs, and electronics can estimate the
location of a detection event to within 3 to 4 mm, the direction- The simplest is the pinhole collimator (Fig. 2.7). It consists of
ality of the event is not known. Gamma rays from a point source a single, small hole or aperture located a set distance (typically
could be detected anywhere across the field of view, and the counts on the order of 20 cm) from the surface of the NaI crystal. Pho-
detected at a particular location in the NaI crystal could have also tons from one end of the source that pass through the aperture
originated from practically anywhere within the patient. Thus col- will be detected on the opposite side of the detector. In addi-
limation is required to determine the directionality of the detected tion, objects that are closer to the aperture will be magnified
event. Because gamma rays cannot be easily focused, absorptive compared with those farther away. If b is the distance from the
collimation must be used—that is, all photons not heading in the aperture to the object and f is the distance from the aperture to
desired direction will be absorbed by the collimator, and those the detector, the amount of magnification, M, is given by:
heading in the correct direction will be allowed to pass. There- M = f/b
fore absorptive collimation is inherently very insensitive because
practically all of the emitted photons will be absorbed and only a Magnification can be of significant value when imaging
very few will be accepted. In general, only 0.01% (i.e., 1 in 10,000) small objects using a camera with a large field of view. Magnifi-
of the photons emitted from the patient will be accepted by the cation will minimize the effect of the intrinsic spatial resolution
collimator and incorporated into the image. of the camera and thus enhance overall system resolution. The
22 PART 1 Basic Principles
Based on this equation, the larger of the two values, the intrinsic
or the collimator resolution, will dominate the system resolu-
tion. Except at distances very close to the collimator face, the
collimator spatial resolution is substantially greater than the
intrinsic resolution, and thus the collimator spatial resolution
is, in general, the more important factor. In cases involving
magnification, the intrinsic spatial resolution, RI, is modified
by magnification, thus minimizing the effect of intrinsic spatial
resolution on system spatial resolution:
√
( )2
RI
RE = = R2C
M
12 25
2 5
1 6 11 1 6 11
Distance from collimator (cm) Distance from collimator (cm)
Fig. 2.10 System sensitivity (left) and spatial resolution (right) as a function of the source-to-collimator dis-
tance. The system spatial resolution of all collimators degrades (increases in value) with distance. The pinhole
collimator (blue) provides the best spatial resolution (lowest value) but the lowest sensitivity, which varies
according to the inverse square law. The converging collimator (green) provides very good spatial resolution
with a sensitivity that increases with distance as the source approaches the focal distance of the collimator.
The high-resolution parallel-hole collimator (pink) has good resolution and reasonable sensitivity. The gener-
al-purpose, parallel-hole collimator (red) has poorer spatial resolution than the high-resolution collimator but
with a 50% increase in sensitivity. It is noted that the sensitivity of the two parallel-hole collimators does not
vary with distance.
is the central 50% of the area of the UFOV. The U.S. National
Electronic Manufacturers Association, a trade association of
electronic manufacturers, has defined parameters for gamma
camera manufacturers to use to characterize the performance
of their equipment. Although some of these parameters may be
difficult to assess in the clinic, they still provide the basis for
many of the quantitative measures used in the gamma camera
quality control program.
The uniformity (or flood) test evaluates the consistency of the
response of the gamma camera to a uniform flux of radiation (Fig.
2.11). It should not be confused with the high-count uniformity
calibration. The uniformity test can be applied either intrinsically
or extrinsically. For the intrinsic test, the collimator is removed and
exposed to the radiation from a point source of small activity
(about .05 mCi (2 MBq) at a distance far enough to ensure uniform
Fig. 2.11 Uniformity (flood) phantom image. irradiation of the camera’s field of view (at least 2 m). Extrinsic
flood images are acquired with a large-area uniform source con-
radiopharmaceutical and that any quantitation performed with taining approximately 3 mCi to 10 mCi (111 to 370 MBq). This
the camera yields values that are as accurate and precise as possible. may consist of a thin water-filled source into which the radionu-
Gamma camera quality control involves tests that are either clide of choice (e.g., Tc-99m) is injected and thoroughly mixed.
quantitative or qualitative. For the quantitative tests, vari- More commonly, a solid, sealed, large-area source of Co-57 (122-
ous parameters are used to measure the characteristics of the keV gamma ray, 270-day half-life) is used. For routine testing, 5 to
gamma camera system. Some of these parameters are evaluated 20 million counts are acquired and the images evaluated qualita-
intrinsically (i.e., without a collimator, to characterize the optics tively for any notable nonuniformities. The daily flood should be
and electronics of the system) and other parameters extrinsi- acquired before administering the radiopharmaceutical to the first
cally to include the collimator. If extrinsic tests are performed patient to ensure that the camera is working properly. Extrinsic
frequently (e.g., daily), they should be performed using the col- floods for all collimators used with the camera may be acquired on
limators most commonly used in the clinic. However, it may an annual basis.
be best to perform the tests with all of the collimators used in Gamma camera spatial resolution can be evaluated either
the clinic at least annually. Certain parameters may be evalu- intrinsically or extrinsically, qualitatively or quantitatively. In
ated in different parts of the gamma camera’s field of view. The general, it may be evaluated quantitatively only during accep-
useful field of view (UFOV) is the portion of the field of view the tance testing and perhaps during annual testing using very small
manufacturer has designated to be the proper extent for clinical point or line sources. The spatial resolution is characterized by the
imaging. Although the UFOV typically covers more than 95% width of the image of the small source. Typical values for intrinsic
of the total field of view, it may not extend to the very edge of the spatial resolution range from 3 to 4 mm. Extrinsic values depend
NaI crystal or collimator face. The central field of view (CFOV) on the particular collimator being evaluated and the distance
Chapter 2 Radiation Detection & Ancillary Instrumentation 25
at which the test was performed, but for collimators commonly bar phantom image can also be used to qualitatively test spatial
used in the clinic, the extrinsic spatial resolution at 10 cm ranges linearity by evaluating the straightness of the bars in the image.
from about 8 to 12 mm. In the clinic, a qualitative assessment of Other performance parameters or characteristics that can be
extrinsic spatial resolution, typically a four-quadrant bar phan- tested include the sensitivity, energy resolution, count rate per-
tom (Fig. 2.12), is more commonly performed. Each quadrant formance, and multiwindow registration. The sensitivity is most
of this phantom comprises alternating lead and spacing equal to commonly evaluated extrinsically using a small-area source (e.g.,
the width of the bars of varying sizes (e.g., 2.0, 2.5, 3 0, and 3.5 10 × 10 cm) of known activity (typically approximately
mm). For extrinsic spatial resolution at the collimator surface, the 1.1 -3.2 mCi (40 - 120 MBq)` of Tc-99m) placed on the collima-
phantom is placed on the collimator with the large-area unifor- tor being evaluated, counted for 1 minute and reported as the
mity source on top of it. The user reviews the resultant image and counts per minute per unit activity. For parallel-hole collimators,
determines how many of the quadrants of the phantom can be the distance of the source to the collimator is inconsequential
discerned as separate bars. In general, the bars that can be dis- because the sensitivity does not vary with distance. For the pin-
cerned should be approximately 60% of the quantitative spatial hole or focusing collimators, a standard distance such as 10 cm
resolution value. Thus, if the intrinsic spatial resolution is 3.5 mm, should be used. The sensitivity value will obviously depend on
it should be possible to discern 2-mm bars of the four-quadrant the collimator being evaluated, ranging from 5.0 to 8.5 cpm/kBq
bar phantom. The extrinsic spatial resolution at the surface of the for typical high-resolution and general-purpose collimators. For
most commonly used collimator in the clinic is qualitatively eval- the energy resolution, a pulse height (or energy) spectrum is
uated routinely on either a weekly or monthly basis. The num- acquired of a known radionuclide, typically Tc-99m, and the
ber of quadrants that can be discerned should be compared with width of the photopeak is determined in a manner similar to that
those determined during acceptance testing. The four-quadrant used for spatial resolution normalized by the gamma-ray energy.
A typical gamma camera will have an energy resolution of 9% to
11% at 140 keV. As discussed previously, radiation detectors take
a certain amount of time to process each event and, if events are
registered too quickly, some may be lost as a result of dead time
or count rate losses. The count rate performance can be evalu-
ated by using two sources of reasonably high activity to calculate
the dead time value in microseconds or by varying the exposure
rate to which the camera is exposed and recording the observed
count rate. For modern cameras, the maximum observable count
rate is typically between 200,000 and 400,000 counts per second
(cps). Finally, the multiwindow registration can be characterized.
As previously discussed, the gamma camera position estimate
obtained using Anger logic must be normalized by the energy
deposited so that the position estimate does not vary as a func-
tion of photon energy. For this test, point sources of gallium-67,
which emits photons of three different energies (90, 190, and 300
keV), are placed in several locations within the gamma camera
Fig. 2.12 Four-quadrant bar phantom image for spatial resolution. field of view and the image location of each of the points sources
Weekly or Monthly
Spatial resolution Requires a “resolution” phantom such as the four-quadrant bar
Linearity check Qualitative assessment of bar pattern linearity
Annually
System uniformity High count flood with each collimator
Multiwindow registration For cameras with the capability of imaging multiple energy windows simultaneously
Count rate performance Vary counts using decay or absorber method
Energy resolution Easiest in cameras with built-in multichannel analyzers
System sensitivity Count rate performance per unit of activity for each collimator
26 PART 1 Basic Principles
are evaluated to make sure that they do not vary depending on appropriate quality control program for a specific gamma camera
which photopeak was imaged. depends on manufacturer recommendations and the clinical use
These parameters should be evaluated and compared with and stability of performance for that particular camera.
manufacturer specifications during acceptance testing. It is highly The x- and y-location of each accepted detection event is digi-
recommended that these tests be performed by a qualified nuclear tally stored within the acquisition host computer associated with
medicine physicist. After acceptance testing, quality control tests the gamma camera. These data can be captured in two ways—
will be run at various frequencies (daily, weekly, monthly, quar- matrix and list mode. In matrix mode, a specific matrix size (64 ×
terly, or annually), and the evaluation may be qualitative rather 64, 128 × 128, 256 × 256, and so on) is predetermined depending
than quantitative in these cases. Table 2.1 summarizes the rec- on the assumed spatial resolution of the imaging task. For tasks
ommended frequency for each of the described tests. These rec- that involve higher spatial resolution, a larger matrix would be
ommendations are for the typical gamma camera, and the most required. The chosen matrix size is mapped to the field of view,
and each estimated (x,y)-location is assigned to a particular pic-
ture element or pixel within the image matrix. The value of that
pixel is then incremented by 1. In this manner, a 2D histogram
of the event locations is generated, and at the end of the acquisi-
tion, the value in a particular pixel is the total number of events
assigned to that pixel during the data acquisition process. An
example with a 6 × 6 matrix is shown in Fig. 2.13. To display
the image, the number of counts in a particular pixel is assigned
a color or gray value according to a certain color scale lookup
table on the computer monitor. An example might be that the
pixel with the most counts is assigned the color white, pixels with
no counts are assigned black, and all other pixels are assigned a
A shade of gray. Alternatively, the colors of the rainbow could be
used, with violet indicating zero counts and red indicating the
highest count. In addition, many other color tables could be used.
In many cases, more than one image is acquired during the
imaging procedure. In some cases, a time-sequence of image
frames, also known as a dynamic study, may be acquired. For
example, a frame may be acquired every minute for 20 minutes. A
multiphase study may be acquired, in which ten 30-second frames
are followed by five 60-second frames, followed by five 120-second
frames. In other instances, the data acquisition may be associated
with a physiological gating signal such as the electrocardiogram
(ECG) or a respiratory gate. In the cardiac example, counts from
different parts of the heart cycle could be placed in different
B frames, resulting in frames from the end of diastole to the end of
systole and back again. In matrix mode, these multiframe acquisi-
tions would be obtained by establishing the desired number of the
frames in the computer a priori. During the acquisition process,
the appropriate pixel for each event would need to be determined,
in addition to the appropriate frame within the heart cycle.
In list mode, the (x,y)-location of each event is stored using
the highest level of digitization possible as a stream. In addition,
timing and physiological gating marks may be stored periodi-
cally. For example, a timing mark may be stored every millisec-
ond, as can the time of the R peak in the ECG (Fig. 2.14). After
the acquisition is complete, the user can then select the desired
matrix size and the temporal or physiological framing rate a
posteriori. Based on these criteria, a postacquisition program
C is run to format the data as defined. The user could then decide
Fig. 2.13 Digital image. Consider a nuclear medicine image acquired to reformat the data to a different set of parameters. In this way,
in matrix mode using a 6 × 6 matrix. (A) The calculated positions based list mode acquisition is very flexible because it does not require
on Anger logic a number of events. (B) A 6 × 6 matrix superimposed
the user to define the acquisition matrix and framing a priori.
onto these events demonstrates into which of the pixels of the matrix
each event would fit. (C) The number of events (dots) in each pixel is On the other hand, it typically requires more computer storage
recorded and assigned a particular shade of gray or another color to and running the formatting program to view the data. For these
create the digital matrix. reasons, matrix mode is most commonly used.
Chapter 2 Radiation Detection & Ancillary Instrumentation 27
Fig. 2.14 List-mode data acquisition. In list mode, the (x,y)-position of each detection event is determined at
the highest available resolution and stored in sequence. In addition, time markers and physiological signals
(such as the timing of the R wave from the electrocardiogram trigger) are periodically stored. Once the acqui-
sition is completed, the desired matrix size, time sequence, and physiological gate framing can be selected,
and a formatting program is run to provide the acquired data for viewing and analysis.
Each pixel in the planar nuclear medicine image can be con- which the patient’s physiology or function can be inferred to
sidered its own detector, and thus the total counts in a pixel are further define the patient’s medical picture. A rigorous quality
governed by Poisson statistics similar to a well counter or a thy- control program must be maintained for all equipment used in
roid probe. Therefore the standard deviation of the pixel counts the nuclear medicine clinic to ensure the integrity of the data
is simply estimated by the square root of the pixel counts. In obtained from the patient. The quality control program for
addition, the sum of Poisson distributed values is also a Poisson the gamma camera includes acceptance testing and tests that
distributed value. Therefore, if a region of interest is defined on need to be performed on a routine basis. The nuclear medicine
a planar nuclear medicine image and the pixel values within that image acquired with the gamma camera provides a snapshot
region are added, the result is also Poisson distributed. Nuclear of the patient’s in vivo radiopharmaceutical distribution from
medicine studies are often quantified by defining regions of a certain view and at a particular point in time. These images
interest (ROIs) over features of interest and subsequently com- can also be acquired as a dynamic (time-sequence) study or
paring the counts. In some cases, the counts from different in conjunction with a physiological gate such as the ECG.
views of the patient can be combined to provide more accurate ROIs can be drawn about specific features to provide regional
quantitation. For example, taking the geometrical mean (square quantitation or TACs of dynamic processes. Nuclear medicine
root of the product of the counts) of similar regions from oppo- instrumentation continues to evolve, including the develop-
site, conjugate views such as the anterior and posterior views, ment of devices designed for a specific clinical task, such as
can provide an estimate that, to first order, does not depend breast imaging. It is expected that this development will con-
on the depth of the activity within the body. Theoretically, this tinue in the years ahead.
approach works for point sources, but it also has been shown
to work reasonably well for extended sources. The counts are
determined from the ROIs drawn about each lung, right and
SUGGESTED READING
left, on images acquired from both the anterior and posterior Chandra R, Rahmim A. Nuclear Medicine Physics: The Basics. 8th ed
views of the patient. The geometrical mean of the counts in each Philadelphia: Williams & Wilkins. 2018.
lung is calculated, and the differential function of each lung is Cherry SR, Sorenson JA, Phelps ME. Physics in Nuclear Medicine. 4th
estimated by dividing the counts for that lung by the sum of ed. Philadelphia: WB Saunders. 2012.
counts for both lungs. International Atomic Energy Association. Nuclear Medicine Physics: A
Handbook for Teachers and Students. Vienna, Austria: Internation-
In a dynamic study, the region of interest counts in each
al Atomic Energy Agency. 2014.
frame can be plotted as a function of time. The resulting plot International Atomic Energy Association. Planning a Clinical PET
is referred to as the time–activity curve (TAC). In the case of Centre. Vienna, Austria: International Atomic Energy Agency.
relatively short-lived radionuclides, each value along the plot 2010.
should be decay corrected to the beginning of the acquisition or International Atomic Energy Association. Quality Assurance for PET
the time of radiopharmaceutical administration. In the example and PET-CT Systems. Vienna, Austria: International Atomic Ener-
of a Tc-99m MAG3 renal study, a TAC can be used to evaluate gy Agency. 2019.
both renal perfusion and clearance of the agent. International Atomic Energy Association. Quality Assurance of SPECT
Radiation detection and counting form the cornerstone Systems. Vienna, Austria: International Atomic Energy Agency. 2009.
of nuclear medicine. Detectors of all types—gas detectors, International Atomic Energy Association. Quality Control Atlas for
scintillators, and semiconductors—are used every day in the Scintillation Camera Systems. Vienna, Austria: International Atom-
ic Energy Agency. 2019.
nuclear medicine clinic. Some are used for ancillary purposes
National Electrical Manufacturers Association. Performance Mea-
that support the clinic, such as those used in the context of surements of Positron Emission Tomographs. Rosslyn, VA: National
radiation protection. Others are used specifically to acquire Electrical Manufacturers Association. 2018.
biological data for a particular clinical purpose. Most nota- Powsner RA, Powsner ER. Essentials of Nuclear Medicine Physics. 3rd
bly, the gamma camera is used to obtain images of the in vivo ed. Malden, MA: Blackwell Science. 2012.
distribution of the administered radiopharmaceutical from
3
Single-Photon Emission Computed
Tomography, Positron Emission Tomography,
and Hybrid Imaging
DATA ACQUISITION OF EMISSION reviews the current approaches to the acquisition and recon-
struction of SPECT and PET, including the use of hybrid imag-
TOMOGRAPHYN ing such as PET/CT, PET/MR and SPECT/CT, and the quality
Conventional or planar radionuclide imaging suffers a major lim- control necessary to ensure high-quality clinical results.
itation in the loss of object contrast as a result of background All tomographic modalities used in diagnostic imaging,
radioactivity. In the planar image, radioactivity underlying and including SPECT, PET, CT, and magnetic resonance imaging
overlying the object of interest is superimposed on that coming (MRI), acquire raw data in the form of projection data at a vari-
from the object. The fundamental goal of tomographic imaging ety of angles about the patient. Although SPECT and PET use
systems is a more accurate portrayal of the three-dimensional different approaches to acquiring these data, the nature of the
(3D) distribution of radioactivity in the patient, with improved data is essentially the same. Image reconstruction involves the
image contrast and definition of image detail. This is analogous to processing of these data to generate a series of cross-sectional
the way computed tomography (CT) provides better soft tissue images through the object of interest.
contrast than planar radiography. The Greek tomo means “to cut”; The geometries associated with the acquisition of SPECT
tomography may be thought of as a means of “cutting” the body and PET are illustrated in Fig. 3.1. In the simple SPECT example
into discrete image planes. Tomographic techniques have been using a parallel-hole collimator, the data acquired at a particular
developed for both single-photon and positron imaging, referred location in the gamma camera crystal originated from a line
to as single-photon emission computed tomography (SPECT) passing through that point perpendicular to the surface of the
and positron emission tomography (PET), respectively. sodium iodide (NaI) crystal face and is referred to in the figure
Restricted or limited-angle tomography keeps the plane of as the line of origin (see Fig. 3.1, left). Thus the data at this point
interest in focus while blurring the out-of-plane data in much can be seen to represent the sum of counts that originated along
the same way as conventional x-ray tomography. Various this line, or ray, referred to as a ray sum. These ray-sum values
restricted-angle systems have been investigated, including across the patient are referred to as the projection data for this
multi-pinhole collimator systems, pseudo-random, coded- cross-sectional slice at this particular viewing angle. For PET,
aperture collimator systems, and various rotating slant-hole the ray sum represents the data collected along a particular line
collimator systems. Although clinical use has been limited, of response (LOR) connecting a pair of detectors involved in a
resurgent interest has been shown for specific imaging applica- coincidence detection event (see Fig. 3.1, right).
tions, including those designed for cardiac and breast imaging. For a SPECT acquisition, the projection image acquired at
Tomographic approaches that acquire data over 180 or 360 each angle consists of the stack of projections for all slices within
degrees provide a more complete reconstruction of the object the camera field of view at that angle. Fig. 3.2, on the right, shows
and therefore are more widely used. Rotating gamma camera projections from a SPECT brain scan at five different viewing
SPECT systems offer the ability to perform true transaxial angles. For a particular slice (see Fig. 3.2, dashed white line), a
tomography. PET uses a method called annihilation coincidence row of the projection data for each angle can be stacked such that
detection to acquire data over 360 degrees without the use of the displacement along the projection is on the x-axis and the
absorptive collimation. The most important characteristic of viewing angle is on the y-axis (see Fig. 3.2, right). This plot is
these approaches is that only data arising in the image plane of referred to as the sinogram, because the resulting plot of a point
interest are used in the reconstruction of the tomographic source resembles a sine-wave plot turned on its side. A more
image. This is an important characteristic leading to improved complicated object such as a brain scan can be perceived as many
image contrast compared with methods using restricted-angle such sine waves overlaid on top of each other for each point
tomography. As will be discussed, the reconstruction of these within the object. The sinogram, represents the full set of projec-
data has historically been done with filtered back-projection. tion data necessary to reconstruct a particular single slice. A sep-
However, iterative techniques such as ordered subsets expecta- arate slice is made in the sinogram for each cross-sectional slice
tion maximization (OSEM) are increasingly used. This chapter through the object. The set of projection views and the set of
28
Chapter 3 Single-Photon Emission Computed Tomography 29
Tomographic Reconstruction
Images, like time signals, can be considered as either a spatial
variation of the signal or a sum of signals of varying frequencies.
It is intuitive to consider images as a spatial variation in the sig-
nal because some part of the image will be bright and other parts
will be dark. In nuclear medicine, the bright and dark areas may
correspond to regions of high and low radiopharmaceutical
uptake, respectively. Conversely, it is not intuitive to consider an
Fig. 3.2 Single-photon emission computed tomography (SPECT) projec-
tion images and sinograms. Right, projection images of a SPECT brain
image to comprise signals of varying frequency, although this is
scan at five different viewing angles. For a particular slice (indicated by the in fact the case. On the other hand, we do naturally perceive
dashed white line), the projection data can be stacked to form the sino- audio signals in terms of frequencies. A choral performance
gram (left). (From Henkin RE. Nuclear Medicine. St. Louis: Mosby; 2006.) comprises sopranos, altos, tenors, and basses, and the combina-
tion of these voices hopefully leads to a very pleasurable experi-
sinograms are alternative means of displaying the projection ence. On the other hand, we cannot perceive a presentation of
data associated with a tomographic acquisition. Each projection the audio signal as a temporal variation of the signal and intui-
view displays the projection data across all slices with a separate tively identify it as music. The music is fully described by either
image for each angle, whereas the sinogram displays the projec- representation, and there may be cases in which either the tem-
tion data across all angles with a separate sinogram for each slice. poral (i.e., real) or the frequency representation is the best
The geometry of PET acquisition (see Fig. 3.1, right) involves approach for considering the audio data. The same is true for
the data acquired along a particular LOR connecting two image data, except the variations are in space rather than time.
30 PART 1 Basic Principles
Backprojections
Image
profiles
Intersection of of point
backprojected source
rays at location
of point source
A B
Fig. 3.3 Simple back-projection. (A) The counts in each position along the projection are back-projected across
the reconstruction matrix because the algorithm has no knowledge as to the origin of the event. This process
is referred to as simple back-projection. (B) Simple back-projection leads to streak artifacts that render all but
the simplest objects discernable.
Image data may be best represented in either spatial (real) or caused by uneven sampling of frequency space during the
frequency space. The mathematician Joseph Fourier noted in back-projection process, where low frequencies are sampled at a
1807 that any arbitrary signal can be generated by adding a large much higher rate than higher frequencies. To compensate for
number of sine and cosine signals of varying frequencies and this, a filter, called the ramp filter, is applied during the recon-
amplitudes. The plot of amplitude as a function of frequency is struction that increases linearly with frequency (Fig. 3.4).
referred to as the Fourier transform, and it defines the compo- Applying back-projection in conjunction with such filtration is
nents of the image at each frequency. The low frequencies pro- referred to as filtered back-projection. With a very large number
vide the overall shape of the object, whereas the high frequencies of accurate, noiseless projections, filtered back-projection will
help define the sharp edges and fine detail within the image. yield an excellent, almost perfect reconstruction.
Audio signals can be manipulated by emphasizing certain fre- However, with true clinical data, the projections are noisy,
quencies (low or high); the same is true for images. Image noise and thus the ramp filter will tend to accentuate the high-frequency
is typically present in all frequencies; if the low frequencies are noise in the data. Therefore a windowing filter is applied, in
emphasized, the image may be less noisy but blurry, whereas addition to the ramp filter, to smoothly bring the filter back to
emphasizing the high frequencies will accentuate both the edges zero at frequencies above the pertinent content in the study.
of the objects and the noise. Such image manipulation is referred Commonly used windowing functions include the Hamming
to as filtering because it allows certain spatial frequencies to be and Butterworth filters (see Fig. 3.4). With these filters, a cutoff
realized while removing others. frequency is defined, which is the point at which they return to
Since the initial development of CT 40 years ago, filtered zero, with no higher frequencies being incorporated into the
back-projection has been the most common approach to recon- reconstructed image. Noting that low frequencies yield the
structing medical tomographic data, including SPECT, PET, overall shape and high frequencies yield the sharp edges and
and CT, although iterative techniques were introduced into the fine detail, the appearance of the resultant reconstructed image
clinic for use with PET more than a decade ago. However, fil- can be altered by varying the cutoff frequency. Selecting a cutoff
tered back-projection is still used in SPECT and remains the frequency that is too low will yield a blurry reconstruction (Fig.
most common method for CT. In back-projection, it is assumed 3.5, A, far left), and one that is too high will yield a noisy recon-
that all of the data detected at a particular point along the pro- struction (see Fig. 3.5, C, second from the right). However, an
jection originated from somewhere along the line emanating appropriate choice for cutoff frequency will provide an image
from this point. For SPECT using parallel-hole collimation, this that is a fair compromise between noise and detail (see Fig. 3.5,
would be the line of origin passing through the detection point B, second from left). With an appropriate choice of cutoff fre-
and perpendicular to the NaI crystal surface. For PET, events quency, filtered back-projection is a simple, fast, and robust
would be assumed to have come from the LOR connecting the approach to image reconstruction.
two detectors involved in the annihilation coincidence detec- Iterative reconstruction provides an alternative to filtered
tion event. In general, back-projection makes no assumptions of back-projection that tends to be less noisy, tends to have fewer
where along the line the event occurred, and thus the counts are streak artifacts, and often allows for the incorporation of certain
spread evenly along the line. In other words, the counts are physical factors associated with the data acquisition into the
back-projected along the line of origin or LOR. All of the counts reconstruction process, leading to a more accurate result. In
from every location along every projection are back-projected iterative reconstruction, an initial guess as to the 3D object that
across the reconstructed image (Fig. 3.3, A). The result is could have led to the set of acquired projections is estimated. In
referred to as simple back-projection; it has substantial streak addition, a model of the imaging process is assumed that may
artifacts that, in all but the simplest objects, render the recon- incorporate assumptions regarding photon attenuation and
structed image indiscernible (see Fig. 3.3, B). These streaks are Compton scatter. It may also include other assumptions
Chapter 3 Single-Photon Emission Computed Tomography 31
0.5
collimator can be incorporated into the reconstruction process.
Based on this model and the current estimate of the object, a
Cut-off new set of projections is simulated that is then compared with
frequency the real, acquired set. Variations between the two sets, parame-
terized by either the ratio or difference between pixel values, are
then back-projected and added to the current estimate of the
0.25 0.5 object to generate a new estimate (Fig. 3.6). These steps are
Frequency
(cycles/pixel)
repeated, or iterated, until an acceptable version of the object is
reached. The goodness of the current estimate is typically based
1.0 on statistical criteria such as the maximum likelihood. In other
words, the process generates an estimate of the object that has
Hamming
the highest statistical likelihood to have led to the set of acquired
projection data. A commonly used approach for the reconstruc-
Amplitude
than after the complete set of projections. If the data are orga-
0.5 nized into 15 subsets, in general, the data can be reconstructed
about 15 times faster while generating a result of similar image
quality. A similar result can be produced with 15 ordered sub-
sets and 3 iterations as would be obtained with 45 iterations
Cut-off frequency using the complete set. The most common approach that uses
ordered subsets in the clinic is referred to as OSEM. Fig. 3.5, D
0.25 0.5
Frequency (far right) shows an OSEM reconstruction compared with a fil-
(cycles/pixel) tered back-projection of the same object. The use of faster algo-
Fig. 3.4 Ramp, Hamming, and Butterworth filters. The ramp filter is rithms such as OSEM and the development of faster computers
a “high-pass” filter designed to reduce background activity and the have allowed iterative reconstruction of SPECT and PET data in
star artifact. Hamming and Butterworth filters are “low-pass” filters
5 minutes or less, which is considered acceptable for clinical
designed to reduce high-frequency noise.
A B C D
Fig. 3.5 Effect of different filtration on reconstruction. (A) Single-photon emission computed tomography
(SPECT) study reconstructed with a cutoff frequency that is too smooth. The image is very blurry. (B) SPECT
study reconstructed with an appropriate cutoff frequency, with a moderate noise level and sharpness. (C)
SPECT study reconstructed with a cutoff frequency that is too sharp. The level of detail is good, but an
excessive amount of image noise is present. (D) SPECT study acquired with iterative reconstruction ordered
subsets expectation maximization (OSEM).
32 PART 1 Basic Principles
Fig. 3.7 Cardiac single-photon emission computed tomography (SPECT) images reformat data into multiple
planes. The top two rows are short-axis views obtained perpendicular to the long axis of the left ventricle. The
middle two rows are horizontal long-axis images, and the bottom two rows are vertical long-axis images. The
patient has a large fixed perfusion defect involving the inferior wall of the left ventricle. The ability to reformat
the data allows for more precise and accurate localization of abnormalities.
packages for quality control. However, these data tend to be The most common device used for SPECT is the rotating
noisy, making it difficult to view small variations in intensity. gamma camera, which consists of one or more gamma camera
Currently, a common approach is to reproject the transaxial heads mounted onto a special rotating gantry. Nearly all
images to generate a series of planar images that have the benefit gamma cameras marketed today incorporate SPECT capabil-
of greatly reduced noise. The reprojection method often used is ity. Early systems used a single gamma camera head, whereas
the maximum-intensity projection scan (MIPS), created by modern systems more commonly have two detector heads.
reprojecting the hottest point along each particular ray for any Dual-head systems that allow flexibility in configuration
given projection. These MIPS images emphasize areas of between the heads are very popular. For body imaging, the
increased accumulation of radioactivity while providing an heads are typically arrayed parallel to each other; for cardiac
overall impression of the area of increased radioactivity in rela- imaging, they are often placed at right angles (Fig. 3.8). Some
tion to the normal structures in individual tomographic slices. cameras are permanently configured in the 90-degree position
In some cases the MIPS images are distance weighted to make for dedicated cardiac imaging. Multiple heads are desirable
activity that is farther from the viewer appear less intense, because they allow more data to be collected in a given period.
thereby enhancing the 3D effect. Rotational SPECT is photon poor compared with x-ray CT,
and thus SPECT imaging protocols commonly take 10 to 30
Single Photon Emission Computed Tomography minutes for the acquisition of a data set. Therefore it is desir-
SPECT allows true 3D image acquisition, reconstruction, and able to obtain as many counts as possible while completing the
display of the radiopharmaceuticals routinely used in conven- imaging within a reasonable time to limit the effects of patient
tional nuclear medicine. Over the past 30 years, SPECT has motion and to minimize pharmacokinetic changes during the
developed, particularly in the field of nuclear cardiology, to the imaging time. Rotational SPECT has highlighted the need to
point at which SPECT has become the standard imaging method. improve every aspect of gamma camera system performance.
In SPECT, a series of projection images is acquired about the Flood field nonuniformities are translated as major artifacts in
patient. In most cases, these projection images are acquired by tomographic images because they distort the data obtained
rotating the imaging device about the object, but in other cases from each view or projection. Desirable planar characteristics
they may be acquired by viewing the object with multiple devices of a camera to be used for SPECT are an intrinsic spatial reso-
or through multiple pinhole apertures. These projection data are lution of 3.5 mm (as estimated by the full width at half maxi-
then reconstructed as described in the previous section, leading mum [FWHM]), linearity distortion of 1 mm or less, and
to the generation of a series of slices through the object. corrected integral uniformity within 3%. All contemporary
34 PART 1 Basic Principles
Gantry
Fig. 3.8 Two configurations for a dual-detector single-photon emission computed tomography (SPECT)
system.
F I N I S .
E R R ATA .
P. line
32 19 for to r. too.
67 22 for he r. they.
72 27 After r. Aft.
75 24 and will be paid not only &c.
115 4 Ch. x.
115 5 Ezion
125 16 r. some other Parts.
FOOTNOTES:
[1] Put metaphorically for a Ship’s Cockpit; and answers to the
dark Cellaring of a House.
[2] At the Changes of the Moon appears a Pillar of Fire in the
North, which darting its Rays every way, moves from Place to
Place, enlightning not only Greenland, but Iceland and Norway;
and sometimes further, till the returning Sun obscures it. (Harris,
p. 635. Vol. II.)
[3] Finis Terræ, the Westermost Extremity of Europe, and formerly
thought a Ne plus ultra.
[4]
Sold 2 half-worn Suits for a Pipe of Wine.
3 Second-hand Wigs — — Ditto.
Loaf-Sugar sells 20d. per lib.
Cheshire-Cheese, 8.
Bisket, 2.
Beef per piece 10.
Bought Citron at 15d.
Lemons per C. 20.
[5] Vide Harris’s Voyages.
[6] Ten-pounders are like Mullets, but full of small Bones, like
Herring-bones.
[7] Old-wives; a scaly, flat Fish, half as thick as long, called so
from some Resemblance the Face is fancied to have, with that of
a Nun’s.
[8] Cavalloes; a bright, silver-colour’d Fish, with a prickly Ridge on
each side, half its length.
[9] Barricudoes; a well-tasted Fish, one Foot and an half long, not
wholesome if the Roof of the Mouth be black.
[10] Sucking-Fish; something like the Dog-Fish; underneath he
has an oval Flat, of three Inches and an half over, granulated like
a Nutmeg-grater; with this he sticks so fast, as difficultly to be torn
from the Deck. He often infests the Shirk, sticks fast, and sucks
his Nourishment from him.
[11] Cat-Fish, so called from four slender Fibres like Whiskers,
sprouting from the under part of his Mouth.
[12] Lollas, are Places cleared of Wood, but barren; the
Habitations only of Bug a bugs, the Species of an Ant; build not
above a Foot and half high; are whitish, smaller than the common
sort, sting, and devour Cloaths.
[13] Lugars; open, clear Places, sowed with Rice, &c.
[14] Plantanes and Bananoes are a very common Fruit, shaped
like Cucumbers, but slender and longer; peeled of their Coat, they
are roasted and eat as Bread, fried, or eaten raw. The latter is the
juicier, and of a preferable Taste. The Plant bearing them grows
as high as a Cherry-tree, with a Leaf three Yards long, and one
over; an admirable Detergent in foul, sanious Ulcers, stripped of
the inner Skin, and applied as you do Housleek in Corns.
[15] The Pine-Apple is their Prince of Fruits; does not grow so
high, but about the Bigness of a Pæony; a beautiful green and
yellow; firm and juicy as a Melon; eaten with Wine and Sugar.
Some of strong Fancy, imagine all sorts of Fruit to be tasted in it;
to me, it always left a stinging abstergent Flavour.
[16] Lime-trees, about as big as our Apple, arise by several Roots,
and have an oval Leaf; the Fruit smaller, but of sharper Scent and
Flavour than Lemons. In the Woods also are many Sevil-Orange
Trees, the Fruit largest and best tasted of any I ever met.
[17] Papais, the Size of a moderate Melon, green as that, and full
of Seeds, which thrown out, and the outside pared, is used with
Meat, buttered and salted. They grow 20 or 30 Foot high. Bosman
says, Male and Female (the Alcoran, that all Fruits grow so, p.
213.) the Male blossoming, but bearing no Fruit.
[18] Rice is sown in swampy Grounds; grows the height of our
Wheat, and from the top of the Stems shoot very slender Stalks,
bearing the Rice grained one above another to a vast Increase; a
Peck yielding above 40 Bushels: Yet such is their Idleness, there
is often a Deficiency supplied from Sherbro, &c.
[19] The Civet is about as large as a Ram Cat, comes from about
Sherbro; it’s Head like a Foxes. The Male only affords this, at the
rate of 3 or 4 Grains a day, gathered with a Quill out of a little Cod
or Hole, near the Intestin. rectum.
[20] General Phips at Cape Corso, was so nettled at this (he
receiving but 19 for 21) that it took his Stomach off Victuals two or
three Days.
For as in Fight the Gun or Drum
Will make the Warriour’s Stomach come;
So eke in Play; if two miss Fire,
The Stomach palls with wax’ning Ire.
[21] The Word Fetish is used in a double Signification among the
Negroes: It is applied to Dress and Ornament, and to something
reverenced as a Deity (a Lake, a Stone, a Tree, &c.) both so far
agree, as to be regarded as a Charm. That by a Peculiarity, and
this by some inherent Essence, can attract Good, or divert Evil.
Here they sometimes hide the Fetish in secret parts of the Woods;
on urgent Occasions make a sort of Appeal to them, separating
some the Friday, some the Saturday, and keep within doors the
whole day, in a Moaning, or what you may call a Devotion to it.
[22] Salaries 80l. per Ann.
[23] Boiled by the Negroes to the bigness of half-penny Rolls, and
an Accy purchases nine a day of them for a Month. The English
bake it.
A lean Goat you may get by chance for five Accys; a Muscovy
Duck, a Parrot, or couple of Chickens, for one.
[24] Miscell. Curiosa. Vol. iii. has a Journal of the Weather at
Cape Corso for 12 Months, from Mr. Hillier, who says, that was a
Year of the most Rain that could be remembred.
[25] Tittwees, like a large Wolf or Mastive, very fierce, and rob
their Towns in the Night, of what Kid or Poultry they find.
Tigers, not so adventurous, but are seen by them sometimes:
There are two now in the Castle.
Serpents. I have heard the Gentlemen of the Factory say, they
have been seen here 30 foot long, able to swallow a Child whole;
(Bosman says, a Man, or a full-grown Deer.)
Deer. Those whose Feet are tipped, and used as Tobacco-
Stoppers, are the bigness of a large Cat. The General had one in
his Kitchen, the Feet as thick as the middle Finger; whence I
judge, those very slender ones we see, are the Abortives of this
Animal.
[26] These sort of Tryals have much the same View with the
Water of Jealousy among the Jews, or Ordeal with our Saxon
Ancestors, that is, a Tryal by Fire or Water: The former was
proving their Innocency by walking on hot Plough-Shears un-hurt:
The latter was used hot or cold. They run their Arm into it scalding
hot; or the Priest gave an Imprecation to a Draught of Holy-Water.
The Person swore to his Innocence, and being tied Hands and
Feet, was thrown into a River or Pond; if he sunk, he was
adjudged innocent, if he floated, guilty: And these ways continued
till K. Hen. III.
Another way with the Saxons, was single Combat; if a Woman,
she appointed her Champion.
Another, since we are upon Tryal, was by two Ounces of Bread
and Cheese taken after the Communion, the Priest thus
imprecating; May it stick in your Throat, turn pale, your Limbs
convulsed, &c. if guilty; but if innocent, may you swallow it easily,
&c.
Rapin.
[27] Hæmac is a Brasil word, and signifies a Net slung to rest in;
made there from the Rind of a Tree.
[28] Milton. B. 10, & 11.
[29] A Negrish Name.
[30] See the Appendix to the Navy-Surgeon, in which are Physical
Observations on the Moisture and Density of the Air.
[31] There is a square Fort on the Larboard Point of the Bay, and
Anchorings about a League from it.
[32] Some pretend to have found what they call a material
Thunder-bolt; such a one is said to have fell on the Turkish
Mosque at Adrianople A. D. 1693; and such are shewn in the
Museums of Princes. At Copenhagen they have a large piece of
metallick Substance, said to be Thunder-bolt.
[33] A Word used by our Sailors, for the Grout is made of it.
[34] Moquissin is a name given to any thing they think has an
incomprehensible Virtue. V. Geographic. Atlas.
[35] The Portuguese, who trade hither from Erasil, chuse their
Cargoes all Boys and Girls, if they can, as more ductile for
Conversion; there being Fathers appointed to instruct them in
their Creed, and to baptize them, on their arrival; but then they are
Papists.
[36] Made of a peculiar Earth from Germany, and bear (those that
are good) the most intense heat.
[37]
There’s but the twinkling of a Star,
Between a Man of Peace and War.
Hud.
[38] At this Place I would observe, in relation to heaving the Lead,
that there is a Nisus in Bodies of Water from below upwards,
which makes ’em to sink neither so fast, nor so direct, at any
considerable Depth, as near the Surface; all at 200 Fathom or
less, being bottomless; i. e. unfathomable.
This Nisus, or resisting Motion to the Descent of Bodies, is not
only perceptible in the Lead, but more sensibly declares itself,
first, in that black or green Skim, seen sometimes on the Surface
(even smelling) after long Calms, the Product of some intestine
Motion.
2. That Divers, or any floating Bodies, emerge with greater Force
than they sunk.
3. Mr. Boyle’s 20th Experiment observes, that a glass Bubble let
open into the Receiver, on the Exsuction of the Air, the Water in it
manifestly rises a greater Height; consequently the Expansion
and Rarefaction of the Air by the Heat of the Sun, makes room for
this Spring in the Water, to exert itself; and therefore the Tides
themselves would more difficultly yield to the distant Attractions of
the Sun and Moon (I should think) without adding to that Theory
this conjoined Force, or natural Propensity of the Sea, to swell
before.
In respect to sinking the Lead, also may be added, a greater
Coldness, and a greater Saltness of the Sea, in proportion to the
Depths; (both which are very probable,) and will create a greater
Buoyancy, or Resistance to sinking, as will likewise the drawing
out a greater Quantity of Line, (less apt to demerge.) So that
although falling Bodies in Air, have their Velocities encreased, the
nearer they approach the Earth, yet contrarily in Water, it
diminishes with the Descent.
[39] Depend much on the preceding Season, (hot and dry
Weather) apt to raise greater Plenty of elastick Vapours on the
Terra firma, and will explode themselves now here, now there, as
the greater Rarefaction of Air (more towards one Island than
another) may invite.
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TRANSCRIBER’S NOTE
The numerical dates in the Sidenotes (on pages 255 to 265) have all been
italicized for consistency eg Mar. 10..
Except for those changes noted below, all misspellings in the text, and
inconsistent or archaic usage, have been retained.
Pg 35: ‘some hunred Leagues’ replaced by ‘some hundred Leagues’.
Pg 48: the footnote anchor [16] was missing, and has been added to ‘[16]Limes,
Oranges’.
Pg 68: ‘weighed Auchor’ replaced by ‘weighed Anchor’.
Pg 97: ‘our Rigth of’ replaced by ‘our Right of’.
Pg 97: ‘The Heigth of’ replaced by ‘The Height of’.
Pg 104: ‘ars sold’ replaced by ‘are sold’.
Pg 132: ‘a Change full as bad’ replaced by ‘a Charge full as bad’.
Pg 193: ‘joined also in in a’ replaced by ‘joined also in a’.
Pg 199: ‘ridiculous, scaramouch’ replaced by ‘ridiculous, and scaramouch’
(catchword ‘and’ was missing).
Pg 202: ‘we re- our’ replaced by ‘we repeated our’.
Pg 207: ‘off the 1sland’ replaced by ‘off the Island’.
Pg 209: ‘Food or Necessarieis’ replaced by ‘Food or Necessaries’.
Pg 243: ‘Bitts of 7d½’ replaced by ‘Bitts of 7½d’.
Pg 261: ‘1721/2’ inserted before ‘Jan 6.’ as a new Sidenote.
Pg 263: ‘1722’ inserted before ‘May 1.’ as a new Sidenote.
Pg 265: ‘1722/3’ inserted before ‘Jan 1.’ as a new Sidenote.
Catalog: ‘by furnish- them’ replaced by ‘by furnishing them’.