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Oxford Specialist
Handbooks
Nuclear
Cardiology
Second Edition

Nikant Sabharwal
Consultant Cardiologist
John Radcliffe Hospital
Oxford, UK

Parthiban Arumugam
Consultant Nuclear Physician
Manchester Royal Infirmary
Manchester, UK

and

Andrew Kelion
Consultant Cardiologist
John Radcliffe Hospital
Oxford, UK

1
iv

1
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First Edition published in 2008
Second Edition published in 2017
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v

Foreword to the
second edition
For several years, nuclear cardiology has presented healthcare providers
and patients with important clinical information regarding the presence and
severity of coronary artery disease as well as other applications. Because
of its value, it is now an important part of non-​invasive evaluation, par-
ticularly in patients with suspected or known coronary artery disease. In
recent years, the indications for nuclear cardiology imaging procedures have
expanded beyond that important group of patient into other clinical arenas,
especially with the emergence of cardiovascular positron emission tomog-
raphy (PET) imaging. These include patients under consideration for device
implantation, cardiac amyloid or sarcoid involvement, infection sources
especially with devices, and vulnerable plaque imaging. Thus the knowledge
base of this vibrant field continues to expand, as do indications and changes
in instrumentation.
The performance and interpretation of nuclear cardiology studies is only
as good as the understanding by technologists and physicians of how the
images are obtained and the methodology behind them. While it is obvious
that this is important for technologists, it is equally valuable for the inter-
preting physicians to be able to distinguish real from not real abnormalities.
This Handbook by Drs Sabharwal, Arumugam, and Kelion is designed to
provide basic information on all important aspects of nuclear cardiology.
Each chapter provides background on important aspects of camera tech-
nology, tracers, processing for both single photon emission computed tom-
ography (SPECT) and PET, as well as a glimpse into the newer aspects of
cardiovascular PET for imaging inflammation and infection. As such, the
book is well suited for both physicians in training or who have completed
training, technologists, and finally those considering certification examina-
tions such as the Certification Board of Nuclear Cardiology (CBNC) exam
in the United States. The readers will not be disappointed.
Gary V. Heller
MD, PhD, MASNC, FACC, FAHA
vi

vi

Foreword to the
first edition
Drs Sabharwal, Loong, and Kelion have provided a superb and up-​to-​date
guide to the basic concepts and clinical applications of nuclear cardiology.
The handbook is very practically organized in condensed chapters that
cover all issues in an elegant manner. Nuclear cardiology has become an
important component in the daily, clinical management of patients with
cardiac disease, and this book provides a good introduction to physicians
who are not familiar with nuclear cardiology, but at the same time offers
an excellent update for clinicians who have been involved with nuclear car-
diology previously. The authors have created a perfect balance between
physics, equipment, and tracers on the one hand and clinical applications
on the other hand. The text is clear and the chapters are illustrated with
practical case examples.
The handbook can be divided into three major components: the first part
deals with the basics of nuclear cardiology, ranging from radiation physics to
imaging equipment, including collimators and gamma cameras.
The second and largest part of this handbook is dedicated to SPECT
myocardial perfusion imaging. Indeed, myocardial perfusion imaging with
SPECT has developed over the past decades into an extremely useful
technique in the daily management of patients with suspected or known
coronary artery disease. SPECT perfusion imaging has an excellent diagnos-
tic accuracy to detect coronary artery disease, in combination with either
physical exercise or pharmacological stress. Strong prognostic information
is also provided with SPECT perfusion imaging; it is well known that a nor-
mal stress-​rest myocardial perfusion study carries an excellent long-​term
prognosis. Alternatively, the risk for cardiovascular events increases in
parallel to the extent of perfusion abnormalities on stress-​rest perfusion
imaging. Accordingly, SPECT perfusion imaging has been implemented in
the daily clinical management and risk stratification of patients with known
or suspected coronary artery disease.
All aspects of SPECT myocardial perfusion imaging are discussed in this
superb handbook, including practical issues such as stress testing, available
tracers, and image interpretation. An elegant chapter is included on the clin-
ical use of SPECT perfusion imaging, covering the diagnostic and prognostic
value of the technique.
The third part of the book includes chapters on novel tracers and posi-
tron emission tomography (PET). One chapter concerns the use of new
iodine-​123 labelled tracers, including MIBG and BMIPP. Neuronal imaging
with MIBG is a promising technique, particularly useful for risk stratification
in patients with heart failure. BMIPP is a fatty acid analogue that permits
for ischemic memory imaging; in patients who encountered an episode of
ischemia, perfusion may have normalized, but oxidative metabolism can still
be reduced, and this can be imaged with BMIPP. These novel iodine-​123
labelled SPECT tracers reflect specific pathophysiological processes that
vi

FOREWORD TO THE FIRST EDITION vii

could not be imaged with SPECT before. PET is the most sophisticated
technique in nuclear cardiology. Extensive information on PET instrumen-
tation and radiopharmaceuticals is provided in a chapter dedicated to PET
imaging. The clinical applications of this technique are discussed in detail,
with special emphasis on viability imaging with F18-​fluorodeoxyglucose.
This handbook will be an extremely valuable guide to the use of nuclear
cardiology for physicians involved in the contemporary practice of clinical
cardiology.
Jeroen J Bax
Professor of Cardiology
Leiden University Medical Center
The Netherlands
vi

viii

Preface to the
second edition
Many cardiologists who do not work in the field of nuclear cardiology may
be surprised that there is a need for a second edition of this Handbook.
Some probably believe that myocardial perfusion scintigraphy (MPS), the
commonest investigation, is a tried and tested technique that has been
around for decades and has required little improvement. Others might say
that the subspecialty represents a static and outmoded approach to imaging
that has been superseded by newer modalities. Both views would be wrong.
In the 9 years since the publication of the first edition of this Handbook,
nuclear cardiology has seen a number of important technical refinements,
including the introduction of pharmacological stress using regadenoson,
solid-​state gamma cameras, and the more widespread and everyday use
of positron emission tomography imaging. In various ways, these have
improved patient safety, image quality, and diagnostic accuracy. At the same
time, the clinical evidence base for MPS in various situations has greatly
expanded, while an increasing number of non-​coronary indications for
radionuclide imaging have been established. We have tried to reflect all of
the important recent developments in this second edition, while sticking
to our original aim which was to produce ‘a readable, practical, and self-​
contained guide to nuclear cardiology, covering both technical and clinical
aspects’.
Cardiac imaging, certainly in the UK, has become an ever more competi-
tive business. Nevertheless, nuclear cardiology continues to play an active
and evolving role in the management of patients.
NS
PA
AK
August 2016
ix

ix

Preface to the
first edition
We hope that clinicians will find this a readable, practical, and self-​contained
guide to nuclear cardiology, covering both technical and clinical aspects.
No book can be a substitute for hands-​on experience in a high-​volume
centre, but we have tried to provide a foundation of essential knowledge
that should be common to physicians of any background training in the
subspecialty.
Nuclear cardiology requires a combination of technical and clinical exper-
tise which many medical practitioners find it hard to acquire in training.
Nuclear physicians and radiologists are well versed in radiation protection
and imaging technologies, but often have limited understanding of the sub-
tleties of current patient management in cardiology. They may fail to appre-
ciate the impact of the wording of their reports on the minds of referring
cardiologists. Conversely, cardiologists have a good understanding of stress
testing and the clinical implications of a given scan appearance, but often
lack a good grounding in the technical issues. They can often struggle to
satisfy national legal requirements for running a service, and may overlook
technical factors that make a particular scan appearance unreliable.
These deficiencies are mirrored in the available texts. Books specific-
ally about nuclear cardiology usually provide excellent detail on the clinical
aspects of the subspecialty, but readers are directed elsewhere for in-​depth
coverage of radiation physics and imaging technology. Books on general
nuclear medicine provide detailed technical information on radionuclide
imaging in general, but often gloss over the more clinical aspects of car-
diac imaging in the limited space available. Few books provide a practical
step-​by-​step guide to nuclear cardiology procedures, despite the standard-
ization of many aspects. We hope that we have gone some way towards
rectifying this.
NS
CL
AK
August 2007
x
xi

xi

Contents

Symbols and abbreviations xiii

1 Introduction to nuclear cardiology    1

2 Radiation physics, biology, and protection    9
3 The gamma camera   31
4 Single photon emission computed
tomography (SPECT)   43
5 Radionuclide ventriculography   63
6 Introduction to myocardial perfusion
scintigraphy   87
7 Stress testing for myocardial perfusion
scintigraphy   89
8 Radiopharmaceuticals used in myocardial
perfusion scintigraphy 127
9 Myocardial perfusion scintigraphy: image
interpretation 143
10 Myocardial perfusion scintigraphy: clinical value 191
11 Other nuclear cardiological investigations 241
12 Cardiac positron emission tomography (PET) 255

Index 283
xi
xi

xiii

Symbols and abbreviations

E cross-​reference
M website
AC attenuation correction
ACE angiotensin converting enzyme
ADMIRE-HF ADreview Myocardial Imaging for Risk Evaluation
in Heart Failure
ADP adenosine diphosphate
AL amyloid light chain
ALARA as low as reasonably achievable
ALS advanced life support
AMP adenosine monophosphate
ARSAC Administration of Radioactive Substances
Advisory Committee
ATP adenosine triphosphate
ATTR amyloid transthyretin-related
BARI 2D Bypass Angioplasty Revascularization Investigation
2 Diabetes
BGO bismuth germanate
BMI body mass index
BMIPP β-methyl-p-iodo-phenyl-pentadecanoic acid
BNP brain natriuretic peptide
Bq becquerel
CABG coronary artery bypass graft surgery
CASS Coronary Artery Surgery Study
CDRIE cardiac device-related infective endocarditis
CE-MARC Clinical Evaluation of MAgnetic Resonance imaging
in Coronary heart disease
CECaT Cost-Effectiveness of functional Cardiac Testing in the
diagnosis and management of coronary artery disease
Ci curie
CKD chronic kidney disease
CMR cardiac magnetic resonance
COURAGE Clinical Outcomes Utilizing Revascularization
and Aggressive druG Evaluation
CT computed tomography
CTA computed tomographic angiography
CTRCD cancer therapeutics-related cardiac dysfunction
vxi

xiv SYMBOLS AND ABBREVIATIONS

CvLPRIT Complete versus Lesion-only Primary percutaneous

coronary intervention trial
CZT cadmium–​zinc–​telluride
DECREASE Dutch Echocardiographic Cardiac Risk Evaluation
Applying Stress Echocardiography
DEFRA Department for Environment, Food and Rural Affairs
DH Department of Health
DIAD Detection of Ischemia in Asymptomatic Diabetics
DPD 3,3-diphosphono-1,2-propanodicarboxylic acid
ECG electrocardiogram
EDC end-​diastolic counts
EF ejection fraction
EMPIRE Economics of Myocardial Perfusion Imaging in Europe
END Economics of Noninvasive Diagnosis
ERASE Emergency Room Assessment of Sestamibi for
Evaluation of chest pain
ERNV equilibrium radionuclide ventriculography
ESC end-​systolic counts
ESC European Society of Cardiology
eV electron-volt
FAME Fractional flow reserve versus Angiography for
Multivessel Evaluation
FDG fluorodeoxyglucose
FFR fractional flow reserve
FPRNV first-​pass radionuclide ventriculography
FWHM full width at half maximum
GSO gadolinium oxyorthosilicate
GTN glyceryl trinitrate
Gy gray
H/​M ratio heart-​to-​mediastinum ratio
HCM hypertrophic cardiomyopathy
HeFPEF heart failure with preserved ejection fraction
HR heart rate
HSA human serum albumin
HSE Health and Safety Executive
ICD implantable cardioverter-​defibrillator
ICRP International Commission for Radiation Protection
INSPIRE AdenosINe Sestamibi SPECT Post-InfaRction
Evaluation
IRMER Ionising Radiation (Medical Exposures)
Regulations 2000
xv

SYMBOLS AND ABBREVIATIONS xv

IRR99 Ionising Radiations Regulations 1999

ISCHEMIA International Study of Comparative Health
Effectiveness with Medical and Invasive Approaches
keV kilo-electron-volt
LAD left anterior descending
LAO left anterior oblique
LBBB left bundle branch block
LCx left circumflex
LGE late gadolinium enhancement
LSO lutetium oxyorthosilicate
LV left ventricle/​ventricular
LYSO lutetium yttrium oxyorthosilicate
MARS Medicines (Administration of Radioactive Substances)
Regulations 1978/​1995/2006
MBF myocardial blood flow
MBq megabecquerels
mCi millicuries
MET metabolic equivalent of task
MeV mega-electron-volt
MI myocardial infarction
MIBG meta-​iodo-​benzyl-​guanidine
MIRD medical internal radiation dose
MPR myocardial perfusion reserve
MPS myocardial perfusion scintigraphy
MR-IMPACT Magnetic Resonance Imaging for Myocardial Perfusion
Assessment in Coronary artery disease Trial
mSv millisievert
MUGA multi-​gated acquisition
NICE National Institute for Health and Care Excellence
NOET bis(N-ethoxy, N-ethyl dithiocarbamato) nitride
NSTEMI/​UAP non-​ST elevation myocardial infarction and unstable
angina pectoris
NYHA New York Heart Association
OM obtuse marginal
PARR PET and Recovery following Revascularization
PCI percutaneous coronary intervention
PDA posterior descending artery
PET positron emission tomography
PHA pulse height analyser
PLA posterolateral artery
PMT photomultiplier tube
xvi

xvi SYMBOLS AND ABBREVIATIONS

POISE PeriOperative ISchemic Evaluation

PPCI primary percutaneous coronary intervention
PTP pretest probability
PYP pyrophosphate
QC quality control
R roentgen
RAO right anterior oblique
RCA right coronary artery
RNV radionuclide ventriculography
ROI region of interest
RPA Radiation Protection Advisor
RPS Radiation Protection Supervisor
RSA93 Radioactive Substances Act 1993
RV right ventricle/ventricular
SAM S-​adenosyl methionine
SC stroke counts
SDS summed difference score
SNM Society of Nuclear Medicine
SPARC Study of myocardial Perfusion and coronary Anatomy
imaging Roles in Coronary artery disease
SPECT single photon emission computed tomography
SPK simultaneous pancreas-kidney
SQR semi-quantitative ratio
SRS summed rest score
SSS summed stress score
STEMI ST-​elevation myocardial infarction
STICH Surgical Treatment for IschemiC Heart failure
STICHES Surgical Treatment for IschemiC Heart failure
Extended Study
SUV standardized uptake value
Sv sievert
TAC time–​activity curve
TID transient ischaemic dilatation
TIMI thrombolysis in myocardial infarction
WR radiation weighting factor
WT tissue weighting factor
WOMEN What is the Optimal Method for ischemia Evaluation
in womeN
1

Chapter 1 1

Introduction to nuclear
cardiology

Introduction 2
Important milestones 4
Relation to other imaging modalities 6
2

2 Chapter 1 Introduction to nuclear cardiology

Introduction
The cardiologist of the early twenty-​first century takes for granted the wide
range of imaging modalities at his/​her disposal, but it was not always so. At
the beginning of the 1970s, invasive cardiac catheterization was the only
reliable cardiac imaging technique. Subsequently, nuclear cardiology investi-
gations led the way in the non-​invasive assessment of cardiac disease. Some
of the principles underlying these investigations (e.g. electrocardiogram
(ECG)-​triggered gating) have also been of great importance in the develop-
ment of other imaging modalities.
Equilibrium radionuclide ventriculography was the first reliable non-​
invasive method of quantifying left ventricular function, and has been widely
performed since the mid 1970s. In combination with exercise it also pro-
vided the first stress–​rest imaging technique for assessing inducible ischae-
mia in patients with known or suspected coronary disease. Myocardial
perfusion scintigraphy (MPS) was slower to develop initially, but has now
become by far the dominant nuclear cardiology investigation.
3

Introduction 3
4

4 Chapter 1 Introduction to nuclear cardiology

Important milestones
General nuclear medicine
• 1927. Blumgart and Weiss used 214Bi to measure pulmonary circulation
time from a venous site in one arm to an arterial site in the other: the
first ‘first-​pass’ study.
• 1950. Cassen developed a sensitive directional γ-​ray detector for
imaging the distribution of 131I in the thyroid: the first rectilinear scanner.
• 1957. Hal Anger developed the gamma camera which bears his name
and which revolutionized radionuclide imaging; the first camera came
onto the market in 1961.
• 1960. Richards developed the 99Mo/​99mTc generator system; this
became commercially available in 1965, allowing 99mTc to become the
dominant radionuclide used in imaging.
Radionuclide ventriculography
• 1971. Strauss and colleagues pioneered equilibrium radionuclide
ventriculography: the blood pool was labelled with 99mTc-​albumin,
and gating was used to acquire separate diastolic and systolic images;
ejection fraction was calculated geometrically from left ventricular
regions of interest.
• 1972. The background-​corrected counts-​based approach was
introduced to measure left ventricular ejection fraction in the left
anterior oblique projection.
• 1974. Acquisition became possible throughout the cardiac cycle, with
generation of time–​activity curves, making equilibrium radionuclide
ventriculography more practical.
• 1976. Borer demonstrated the value of exercise equilibrium
radionuclide ventriculography as an investigation for coronary disease.
Myocardial perfusion scintigraphy
• 1964. Carr injected intracoronary 131Cs during cardiac catheterization to
image myocardial perfusion.
• 1970. Kawana proposed 199Tl as a myocardial perfusion tracer.
• 1973. Zaret used intravenous 43K to demonstrate exercise-​induced
regional reductions in myocardial perfusion in coronary disease.
• 1974. Lebowitz developed 201Tl, which had better imaging characteristics
than 43K; 201Tl became commercially available from 1976.
• 1978. Gould introduced pharmacological stress with dipyridamole.
• 1979. Jasczak developed the first single photon emission computed
tomography (SPECT) gamma camera; the first camera came onto the
market in 1984.
• 1984. Dobutamine was introduced as a stress agent for MPS.
• 1984. 99mTc-​sestamibi was described, and was approved for clinical use
in the USA in 1990.
• 1987. SPECT attenuation correction using a gadolinium-​153 source was
described.
• 1990. Adenosine was introduced as a stress agent for MPS.
5

Important milestones 5

• 1991. Gated SPECT was introduced, and became increasingly practical

with the introduction of multi-​headed gamma cameras during the 1990s.
• 1993. 99mTc-​tetrofosmin was described, and was approved for clinical
use in the USA in 1996.
• 1996. Hasegawa developed a combined SPECT-​CT scanner; the first
commercial system was available from 1999, using low-​resolution CT
predominantly for attenuation correction; subsequent refinements now
allow hybrid CT coronary angiography and MPS.
• 2005. Regadenoson was introduced as a stress agent for MPS.
• 2006. The first cadmium–​zinc–​telluride (CZT)-​based solid-​state gamma
camera was introduced to the market.
Positron emission tomography
• 1969. Brownell developed the first positron emission tomography
(PET) scanner for brain imaging; the first whole body scanner became
commercially available in 1977.
• 1976. 18F-​FDG was synthesized for use in PET imaging of cerebral
metabolism and tumours; it has subsequently proved useful in
the assessment of myocardial viability, as well as in infection and
inflammation imaging.
• 1982. 82Rb was described as a perfusion tracer in humans; the 82Sr/​82Rb
generator became commercially available in 1989, making routine MPS
with PET clinically feasible.
6

6 Chapter 1 Introduction to nuclear cardiology

Relation to other imaging modalities

Introduction
In the mid 1970s, scintigraphic techniques were the only methods avail-
able for imaging the heart non-​invasively. The last 40 years have seen major
developments in imaging technology, and nuclear cardiology now competes
with echocardiography, magnetic resonance imaging, and X-​ray computed
tomography (CT) in the investigation of cardiology patients. In some parts
of the developed world, most notably in North America, nuclear cardiology
(particularly MPS) is recognized as a mature subspecialty, underpinned by an
extensive literature. It has become firmly embedded in the management of
large numbers of patients. In other parts of the world, for example in the
UK, it has failed to become a mainstream investigation in most centres, often
for medico-​political rather than clinical reasons. In such countries there is
a danger that newer and more fashionable techniques, which demonstrate
similar aspects of cardiac physiology, will become widely established before
their clinical and cost-​effectiveness have been properly demonstrated.
Left ventricular function
Radionuclide ventriculography has been largely replaced by echocardiog-
raphy in the everyday assessment of left ventricular function, and appropri-
ately so. Gated SPECT provides an accurate assessment of left ventricular
function in the setting of MPS, but is not normally used as a stand-​alone
technique. Echocardiography is quick, widely available, and free of ionizing
radiation. It may be argued that the ejection fraction provided by the radio-
nuclide methods is more accurate and reproducible, but this is unimportant
in the majority of cases where it is only necessary to know whether the left
ventricle is normal or mildly/​moderately/​severely impaired.
Where accurate quantification is important, cardiac magnetic resonance
(CMR) imaging now represents an important challenge to the radionuclide
techniques as it appears to be more reproducible. However, CMR is expen-
sive and not widely available, and its superiority is more relevant to research
rather than clinical applications. Radionuclide ventriculography continues to
have a niche role, for example in the serial assessment of patients undergo-
ing chemotherapy.
Functional imaging in known or suspected coronary
artery disease
Echocardiography and CMR offer alternatives to MPS in the assessment of
patients with suspected or known coronary disease:
• Echocardiography:
• Stress echo (wall motion).
• Myocardial contrast echo (perfusion).
• CMR:
• Stress CMR (wall motion).
• Perfusion CMR.
7

Relation to other imaging modalities 7

It is likely that in expert hands these investigations provide more-​or-​less

equivalent clinical information to MPS. Moreover, they do not involve
exposure to ionizing radiation, which may be an advantage in young low-​
risk patients.
The attractions of MPS are primarily practical:
• Ability to deliver high-​volume service: a single dedicated cardiac
gamma camera can study well over 2000 patients per year, with little
requirement for hands-​on medical input except in reporting.
• Applicable to all patients:
• Imaging possible in all but most morbidly obese patients (due to
weight limitations on imaging table), for whom cardiac catheteriza-
tion is similarly impossible.
• No difficulties with imaging windows (cf. echo).
• Most cameras suitable for claustrophobic patients (cf. CMR).
• No problems for those with pacemakers or other metal implants
(cf. CMR).
• Operator independent: published evidence of good agreement between
observers in reporting.
• Published evidence of cost-​effectiveness:
• Diagnostic strategies that involve perfusion scintigraphy are cheaper
than those that do not, with no difference in clinical outcome.
• MPS delivered at high volume is no more expensive than stress echo-
cardiography, and certainly cheaper than CMR.
Challenge of multislice X-​ray computed tomography
Recently, multislice (64-​slice or above) X-​ray CT has established itself as a
realistic non-​invasive alternative to invasive coronary angiography. Its role
in relation to MPS is still evolving, but a number of points are already clear:
• The two techniques are not interchangeable: MPS is a functional
assessment, while CT provides anatomical information about plaque
burden (CT coronary calcium scoring) and stenoses (CT coronary
angiography).
• Assessed against invasive angiography, CT coronary angiography has
outstanding diagnostic sensitivity and negative predictive accuracy
(>99%). Moreover, the cardiac event rate after a normal CT scan (no
atheroma or luminal stenosis) is extremely low, with a longer ‘warranty
period’ than after MPS (10 years).
• The specificity and positive predictive accuracy of CT are less
impressive, with a tendency to overestimate stenosis severity in
comparison to invasive angiography.
• Whether identified by CT or invasive angiography, stenosis severity is an
unreliable predictor of functional relevance. Importantly, the outcome
after coronary revascularization is better predicted by physiology,
as assessed by fractional flow reserve (FFR) using a pressure wire at
invasive angiography.
8

8 Chapter 1 Introduction to nuclear cardiology

• The appropriateness of CT versus MPS as the initial diagnostic

investigation in suspected coronary disease will vary between patients.
CT, with its high negative predictive accuracy, may be particularly
appropriate in a lower-​probability population.
• Using FFR as the standard, the combination of CT and MPS has
substantially higher sensitivity and specificity than either investigation
alone.1 In a minority of individuals, dual assessment may be helpful
in providing a comprehensive assessment and avoiding unnecessary
invasive investigation.
• Whatever the theoretical issues, when compared head-​to-​head as the
initial diagnostic investigation in a randomized trial of 10 000 patients,
both CT and MPS yielded an identical cardiac event rate and quality of
life 2 years after investigation.2,3
References
1 Schaap J, Kauling RM, Boekholdt SM, et al. Incremental diagnostic accuracy of hybrid SPECT/​CT
coronary angiography in a population with an intermediate to high pre-​test likelihood of coronary
artery disease. Eur Heart J Cardiovasc Imaging 2013; 14: 642–​9.
2 Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for
coronary artery disease. N Engl J Med 2015; 372: 1291–​300.
3 Mark DB, Anstrom KJ, Sheng S, et al. Quality-​of-​life outcomes with anatomic versus func-
tional diagnostic testing strategies in symptomatic patients with suspected coronary artery dis-
ease: results from the PROMISE randomized trial. Circulation 2016; 133: 1995–​2007.
9

Chapter 2 9

Radiation physics, biology,

and protection

Atoms and nuclei 10

Radioactive decay 12
Statistics of radioactive decay 14
Interaction of X-​ray and gamma photons with matter 16
Dosimetry of radiation exposure 18
Biological effects of radiation exposure 20
Principles of radiation protection 22
Radiation protection of staff 24
Production of radionuclides 26
Dose calibration of radionuclides 28
Key UK legislation relevant to nuclear cardiology 30
10

10 Chapter 2 Radiation physics, biology, & protection

Atoms and nuclei

Atom
An atom is the smallest particle of matter exhibiting the characteris-
tic chemical properties of an element. It consists of a positively charged
nucleus, orbited by an equivalent number of negatively charged electrons
(if in the neutral or un-​ionized state).
Nucleus
An atomic nucleus consists of two types of particle called nucleons:
• Protons: positive charge, equal and opposite to that of an electron.
• Neutrons: neutral charge.
A nuclide is a defined type of nucleus, characterized by:
• Mass number, A: total number of nucleons (protons and neutrons).
• Atomic number, Z: number of protons, defining the chemical element of
the atom to which the nuclide belongs.
In conventional notation, a nuclide, X, is represented as AZX: for example, 146C
is a nuclide containing 14 nucleons in total, of which 6 are protons and
14 − 6 = 8 are neutrons. From the periodic table of elements (see Fig. 2.1), the
element with atomic number 6 is carbon, hence ‘C’. Given that an element is
uniquely defined by its atomic number, the notation for a nuclide can be further
shortened to AX (e.g. 14C = carbon-​14).
Nuclides can be grouped into families:
• Isotopes have the same number of protons and are the same element
(e.g. 201
81
Tl and 203
81
Tl).
• Isobars have the same mass number, A (e.g. 99 42
Mo and 99
43
Tc).
• Isotones have the same number of neutrons (e.g. 31H and 42He).
• In addition to a ground state, nuclides can exist at different energy levels
or excited states: isomers. A relatively stable isomer with a half-​life ≥1µs
is termed ‘metastable’ (e.g. 99mTc).
Electrons
Electrons are much less massive than nucleons, and carry a negative charge
which is equal and opposite to that of a proton.
Electrons are arranged in characteristic shells at increasing distance from
the nucleus (K, L, M, etc.), each of which can hold a maximum number
(2, 8, 18, etc.). Under normal circumstances, inner shells must be filled
before electrons can occupy outer shells. The chemical properties of a
given element are largely determined by the number of outer-​shell valence
electrons in its atoms which are available to form chemical bonds. The
removal or addition of electrons from/​to an atom leaves it positively or
negatively charged (ionized).
Whenever an electron is removed from an inner shell, its place must be
taken by an outer-​shell electron. The difference in binding energy between
the two shells is released as a photon of electromagnetic radiation, or by
the freeing of an outer-​shell (Auger) electron. If the energy of the photon
is >100eV it is termed an X-​ray, and its energy is characteristic for a par-
ticular element.
 1

Atoms and nuclei

Fig. 2.1 The periodic table of the elements.

11
12

12 Chapter 2 Radiation physics, biology, & protection

Radioactive decay
Of the approximately 1800 known nuclides, only about 300 are stable.
Stable nuclides are characterized by approximately equal numbers of pro-
tons and neutrons, or by an excess of neutrons for A >100. An unbal-
anced (‘parent’) nuclide is unstable, and attempts to achieve stability by
radioactive decay into a ‘daughter’ nuclide with the release of energy as
electromagnetic or particulate radiation. Such unstable nuclides are termed
radionuclides. A daughter nuclide may itself be unstable, and may decay fur-
ther via a series of steps until a stable nuclide is produced. Radioactive
decay processes are not affected by environmental conditions or chemical
binding.
There are three modes of radioactive decay:
• Alpha (α).
• Beta (β).
• Gamma (γ).
In all cases, the following are conserved:
• Energy (sum of mass energy by E = mc2, kinetic energy, and
electromagnetic energy).
• Mass number (total number of nucleons).
• Electric charge.
Alpha decay
The nucleus emits an α-​particle, which is a helium nucleus ( 42He) consisting
of two protons and two neutrons without orbital electrons, for example:
226
88 Ra →222
86 Rn + 2 he
4

Beta decay
A neutron changes into a proton or vice versa. The daughter nuclide is an
isobar of its parent (same mass number, but different atomic number, i.e.
element). There are three types of β-​decay:
β–​-​decay
A neutron changes into a proton with the release of a negatively charged
β-​particle (an electron) and an anti-​neutrino (required to conserve energy,
but of no biological relevance):
n → p+ + e − + µ
For example, decay of molybdenum-​99 to technetium-​99m in a technetium
generator:
−
99
42 Mo →99
43 tc + e + µ
m
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