Eur

opea ne
n Association of Nuclear Medi ci

Myocardial Perfusion Imaging

A Technologist’s Guide
Contributors
Wim van den Broek Julie Martin
Chairman EANM TC; Chief Technologist Director of Nuclear Medicine
Dept of Nuclear Medicine, University Medical Dept of Nuclear Medicine, Guy’s and St Thomas’
Centre Hospitals
Nijmegen, The Netherlands London, United Kingdom

Alberto Cuocolo Giuseppe Medolago

MD MD
Dept of Biomorphological and Functional Dept of Nuclear Medicine, Ospedali Riuniti,
Sciences Bergamo, Italy
Federico II University, Naples, Italy

José Pires Jorge

Adriana Ghilardi Member of EANM TC Education Sub-Committee;
Chief Technologist Technologists Educator
Dept of Nuclear Medicine, Ospedali Riuniti, HECVSanté - filière TRM, Lausanne, Switzerland
Bergamo, Italy

Audrey Taylor
Sue Huggett
Chief Technologist
Member of EANM TC Education Sub-Committee
Dept of Nuclear Medicine, Guy’s and St Thomas’
Programme Coordinator for Nuclear Medicine
Hospitals
Technology
London, United Kingdom
Dept of Radiography, City University, London,
United Kingdom

Régis Lecoultre
Technologists Educator
HECVSanté - filière TRM, Lausanne, Switzerland

Under the auspices of the European Association of Nuclear Medicine

Technologist Committee Education Sub-Committee


 EANM
Contents
Foreword 4
Wim van den Broek

Introduction 5
Sue Huggett

Chapter 1 – Applications and Rationale of Myocardial Perfusion Imaging 7–13

Alberto Cuocolo

Chapter 2 – Patient Preparation 14–16

Julie Martin and Audrey Taylor

Chapter 3 – Stress Protocols 17–28

Adriana Ghilardi and Giuseppe Medolago

Chapter 4 – Preparation and Use of Imaging Equipment 29–35

Régis Lecoultre and José Pires Jorge

Chapter 5 – Imaging and Processing 36–43

Julie Martin and Audrey Taylor

References 44

This booklet was sponsored by an educational grant from Bristol-Myers Squibb Medical Imaging.
The views expressed are those of the authors and not necessarily of Bristol-Myers Squibb Medical
Imaging.


Foreword
Wim van den Broek
Technologists have become an important
group within the EANM. Since its inception,
the Technologist Committee of the EANM has
been working to improve the professional
expertise of nuclear medicine technologists
(NMTs) in Europe.
Expertise is the keyword; NMTs’ professional
and practical expertise is essential to ensur-
ing an expert nuclear medicine examination.
The NMT must safeguard patients’ wellbeing,
ensure each examination is performed cor-
rectly, and maintain an operating procedure
that guarantees the quality of the results.
In 1998, a start was made with the publica-
tion of ‘Competencies for the European NMT’,
which was followed by ‘Advanced Skills and
Responsibility Guidelines for the Senior NMT’
and other publications, all promoting good
practice for NMTs.

In early 2004, the idea of providing a series
of booklets on imaging for technologists was
born. By September 2004, thanks to the hard
work of the EANM Technologist Sub-Commit-
tee on Education, it was possible to achieve
the first goal in this series: this booklet on
myocardial perfusion scintigraphy (MPS) for
technologists.
I hope this booklet will find its way into the
pockets of technologists across Europe, and
prove a valuable aid in the daily work of NMTs
performing MPS scans.
Many thanks to all who have contributed to
this project, in particular the members of the
EANM Technologist Sub-Committee on Edu-
cation, and to Bristol-Myers Squibb Medical
Imaging for the sponsorship that made this
project possible.
Wim van den Broek
Chairman
EANM Technologist Committee
Introduction
Sue Huggett
In early 2004, the EANM Technologist Commit-
tee considered producing a booklet on myo-
cardial perfusion scintigraphy (MPS) for tech-
nologists. This was an exciting opportunity to
involve technologists from many European
countries in a collaborative effort to produce
a piece of work for and mainly by our own
profession. We wanted to provide informa-
tion for reference in a handy form that could
be kept nearby or even in the technologist’s
pocket when scanning.
Owing to the timescale, we decided that this
booklet should focus on traditional tomo-
graphic MPS and gated tomographic MPS
methods, with the possibility of further work
on PET methodologies to follow. Members
of the Education Sub-Committee drafted a
framework and set about finding contribu-
tors for the various sections. It was gratifying
that everyone we approached was happy to
help.
Of course, all nuclear medicine studies need to
be performed well to obtain optimal diagnos-
tic information. MPS in particular encompass-
es many areas of technologist practice, from
stressing and setting up ECG traces to analysis
and display. As a result, the opportunities to
maintain and improve quality are sizeable.
We hope this booklet will prove useful in all
areas.

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Knowledge of imaging theory can provide the
technologist with a deeper and more satis-
fying understanding of practical techniques,
improve decision-making, and allow the tech-
nologist to pass on accurate information to
patients, their carers, and other staff. Patient
care is always paramount, and being able to
explain why certain foods must be avoided
or why it is necessary to lie in awkward posi-
tions improves compliance and is satisfying
in its own right.
Protocols vary between departments, even
within the broader terms of the EANM Guide-
lines, and this booklet is not meant to supplant
these protocols but hopefully to supplement
and explain the rationales behind them. This
will hopefully lead to more thoughtful work-
ing practices. For example, both checking
for suitability and proper preparation before
a study can save time and reduce radiation
doses. Information from and about patients
can be incomplete or misleading, so under-
standing the importance of what they say
on arrival is vital if the technologist is to spot
potential problems early on.
In order to know when and how to apply
variations in the protocol for acquisition or
analysis, we must be aware of the rationales
behind certain strategies. For example, obese
patients attenuate more photons, so in such
cases it could be advisable to linger longer at
each angle or to use a different order filter if
total counts are low.
The same philosophy applies to equipment;
if you understand the consequences of any
suspicious QC results, you will know when to
pay closer attention to certain parameters. We
hope that this booklet can provide informa-
tion as and when it is needed so that the in-
tegration of theory and practice is facilitated
and encouraged.

The authors are indebted to a number of infor-

mation sources, not least local protocols, and
references have been given where original
authors were identifiable.

We apologise if we have inadvertently made

uncredited use of material for which credit
should have been given.


Applications and Rationale
of Myocardial Perfusion Imaging
Alberto Cuocolo
During the past two decades, the clinical role
of nuclear medicine procedures in cardiology
has evolved significantly. Initially, the diagnos-
tic role of nuclear medicine in detecting myo-
cardial ischaemia in patients with suspected
coronary artery disease was emphasised. Sub-
sequently, myocardial perfusion imaging has
made significant advances in the determina-
tion of prognosis in patients with ischaemic
heart disease, preoperative risk assessment
for patients undergoing non-cardiac surgery,
and assessment of the efficacy of revasculari-
sation in patients undergoing coronary artery
bypass surgery or interventional procedures.
More recently, particular attention has been
focused on the ability of nuclear cardiology
to characterise myocardial tissue and to assess
myocardial viability in patients with ischaemic
left ventricular (LV) dysfunction.
Common clinical indications for an MPS
study
1. Diagnosis of coronary artery disease: pres-
ence, location (coronary territory), and extent
(number of vascular territories involved)
2. Risk assessment (prognosis) in patients: both
after myocardial infarction and preoperatively
for major surgery that may be a risk for coro-
nary events
3. Assessment of myocardial viability: differen-
tiating ischaemia from scar, and predicting im-
provement of LV function after interventions

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4. Monitoring of treatment effect after coro-
nary revascularisation procedures
1. Diagnosis of coronary artery disease
Myocardial perfusion imaging with exercise or
pharmacological stress testing is an accepted
technique for the detection and localisation of
coronary artery disease (1,2).
During exercise or pharmacological stress, the
vasodilating capacity of microcirculation is lim-
ited and obstruction in the epicardial coronary
arteries becomes physiologically important,
providing a mechanism for the non-invasive di-
agnosis of obstructive coronary artery disease.
Myocardial perfusion abnormalities detected
during either exercise or pharmacological
stress are due to differential blood flow be-
tween normal and stenotic arteries.
The determination of these disparities is de-
pendent on the ability of different tracers to
reflect the changes in increased blood flow
produced by the stressors.
All myocardial perfusion imaging agents avail-
able for clinical use have shown a linear rela-
tionship up to approximately twofold higher
than baseline. Beyond this level, there appears
to be a decrease in the uptake of most agents
in relation to blood flow. The plateau effect dif-
fers demonstrably between tracers. Compared
to resting blood flow, it should be assumed
that exercise will typically cause a two- to
threefold increase in myocardial blood flow,
while stress in response to pharmacological
agents will typically be accompanied by a
three- to eightfold increase.
Myocardial perfusion tracers available for
clinical use include thallium (Tl-201) and
technetium-99m (Tc-99m) labelled agents
(e.g. sestamibi and tetrofosmin). The relation-
ship between blood flow and the activities
of these tracers has been widely studied.
Blood flow and thallium activity show a lin-
ear relationship up to at least 3 ml/min/gm.
However, at approximately 3 ml/min/gm
there appears to be a plateau effect such
that further increases in blood flow do not
change thallium activity. The extraction frac-
tion of sestamibi is less than thallium. Data
from animal studies demonstrate a linear re-
lationship between blood flow and sestamibi
uptake, up to approximately 2 ml/min/gm.
Above this level, uptake is not linked to in-
creasing flow in a linear fashion. Similar data
are emerging for tetrofosmin, though this
tracer demonstrates a plateau during stress at
a lower blood flow level than does sestamibi.
Thus, thallium, sestamibi, and tetrofosmin all
exhibit a plateau effect that occurs above
the typical blood flow range for exercise or
most pharmacological stress. The Tc-99m la-
belled tracer with the best extraction fraction
(higher than thallium) is teboroxime, which
shows a linear correlation within the range
of pharmacological stress. However, the rapid
clearance of this tracer from the myocardium
has made this agent difficult to use clinically.

All these tracers have different kinetic char-
acteristics, which must be considered when
attempting to maximise their clinical applica-
tion in stress imaging. Moreover, it must be
remembered that in clinical imaging ideal
conditions do not always exist.
Despite the differences in tracer kinetics,
comparative studies involving thallium and
Tc-99m labelled agents have failed to show
significant differences. Several clinical stud-
ies have documented the clinical impact of
thallium imaging in the detection of coronary
artery disease. In particular, the sensitivity of
single-photon emission computed tomog-
raphy (SPECT) thallium imaging has been
reported to be approximately 90%, with a
relatively low specificity of 60% to 70%. Since
their introduction, sestamibi and tetrofosmin
have been compared to thallium as the gold
standard in the identification of patients with
coronary artery disease. The reported respec-
tive average sensitivities and specificities of
sestamibi and tetrofosmin in the identifica-
tion of coronary artery disease have been
very similar to those obtained with thallium
imaging. However, some studies have re-
ported that sestamibi and tetrofosmin might
underestimate the total extent of myocardial
ischaemia, relative to thallium imaging, in pa-
tients with coronary artery disease (3). On the
other hand, significant differences regarding
the image quality have been reported in all
comparative studies performed. In particular,
images obtained using sestamibi or tetrofos-
 Chapter 1: Applications and Rationale of Myocardial Perfusion Imaging – Alberto Cuocolo
min are of superior quality to those obtained
with thallium and tend to show fewer soft tis-
sue attenuation artefacts. Better definition of
the myocardium, endocardial and epicardial
borders, and perfusion defects has been ob-
served. In general, there is much less statistical
noise when using sestamibi and tetrofosmin,
and the myocardial-to-background ratios are
reportedly similar to those obtained with
thallium imaging. Moreover, the permissible
administered dose for Tc-99m labelled agents
is much larger than for thallium. This results in
an increased pixel count density for Tc-99m
labelled tomographic projection images and
permits the use of higher resolution filters dur-
ing reconstruction.
Modern nuclear cardiology imaging tech-
niques coupled with the development of Tc-
99m labelled perfusion tracers now permit
simultaneous myocardial perfusion and LV
function studies in a single test. The potential
advantages of simultaneous assessment of
myocardial perfusion and LV function have
recently been outlined (4). Gated imaging of
the perfused myocardium is a well-established
technique for this purpose, using a single in-
jection of a Tc-99m labelled perfusion tracer.
Recent data has demonstrated the impact and
clinical role of these studies in the diagnosis
of patients with suspected or known coronary
artery disease; the addition of functional in-
formation to perfusion data has been shown
to improve the detection of multivessel dis-
ease.

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2. Risk assessment (prognosis) in patients
with coronary artery disease
Another key role of myocardial perfusion im-
aging is its ability to provide prognostic infor-
mation in patients following acute myocardial
infarction, in patients with chronic coronary
artery disease, and in patients scheduled for
major surgery (5). The utility of thallium scin-
tigraphy associated with exercise pharmaco-
logical stress testing for this purpose has been
widely documented. In particular, it has been
demonstrated that in patients without prior
myocardial infarction the number of reversible
thallium defects is the most important statis-
tically significant predictor of future cardiac
events. Moreover, the extent and severity of
thallium defects correlate with the occurrence
of cardiac events. Several studies have report-
ed similar results for the prognostic value of
thallium stress imaging, both after myocardial
infarction and in patients with suspected or
known coronary artery disease. The data from
these studies demonstrate that the extent of
perfusion abnormality found through SPECT
imaging is the single most important prog-
nostic predictor.
More recently, the prognostic value of Tc-99m
labelled myocardial perfusion agents has been
demonstrated with data comparable to that
of thallium imaging. In particular, the extent
of hypoperfusion in post-stress sestamibi im-
ages can be factored into the decision-mak-
ing process when deciding whether to select
medical therapy or revascularisation. Patients
with mild reversible perfusion defects who
are judged to be at low or intermediate risk
can usually be treated medically, whereas pa-
tients with high risk SPECT reversibility results
are candidates for further invasive strategies.
Moreover, a strategy incorporating stress MPS
is also cost-effective. A large study in stable
angina patients referred for stress myocardial
perfusion SPECT imaging or direct catheterisa-
tion revealed that costs were higher for the
initial invasive strategy in clinical subsets with
low, intermediate, or high pre-test likelihoods
of disease. Diagnostic follow-up costs of care
were 30-41% higher for patients undergoing
direct catheterisation, without any reduction in
mortality or infarction compared with patients
having stress perfusion imaging as the initial
test for coronary artery disease detection.
3. Assessment of myocardial viability
It has been demonstrated that a third of pa-
tients with chronic coronary artery disease
and LV dysfunction have the potential for
significant improvement in ventricular func-
tion after myocardial revascularisation. These
findings have several implications. Firstly,
there is the important relationship between
LV function and patients’ survival. In recent
years, numerous studies have demonstrated
that nuclear cardiology techniques involving
SPECT provide important viability information
in patients with coronary artery disease and
impaired ventricular function (6-12). Although
positron emission tomography (PET) remains
the most accurate technique for the detec-
10
tion of viable myocardium, different thallium
protocols have been used in previous studies
to assess myocardial viability in patients with
previous myocardial infarction and chronic LV
dysfunction. In particular, if the clinical issue
to be addressed is the viability of one or more
ventricular regions with systolic dysfunction
and not whether there is also inducible isch-
aemia, rest-redistribution thallium imaging
can yield useful viability data. In particular,
it has been demonstrated that quantitative
analysis of rest-redistribution images predicts
recovery of regional LV function and compares
favourably to the results of both thallium re-
injection imaging and metabolic PET imaging
(7). Optimal interpretation of thallium imaging
for the detection of myocardial viability can be
accomplished by measuring regional tracer
uptake and by selecting the most appropri-
ate cut-off to differentiate reversible from ir-
reversible LV dysfunction (8-10). Furthermore,
sestamibi and tetrofosmin showed similar re-
sults to those of thallium scintigraphy in the
identification of viable myocardium (8).
A quantitative analysis of tracer content as well
as the administration of nitroglycerin prior to
tracer injection increases the overall accuracy
of Tc-99m labelled agents for identifying vi-
able myocardium. Recent data indicate that
in patients with chronic myocardial infarction
and impaired LV function on nitrate treatment,
quantitative analysis of resting thallium and
sestamibi regional activities comparably pre-
dict recovery of regional and global ventricular
 Chapter 1: Applications and Rationale of Myocardial Perfusion Imaging – Alberto Cuocolo
function following revascularisation proce-
dures (11). Nitroglycerin most likely enhances
myocardial viability detection by increasing
coronary collateral flow, decreasing pre-load
and after-load, and direct vasodilatation of
stenotic segments in coronary arteries (12-
14). These physiological effects in combina-
tion may enhance the delivery of myocardial
perfusion agents to regions of myocardium
supplied by severely stenotic vessels.
In the assessment of myocardial viability, phar-
macological stress testing in combination with
wall motion analysis via gated images of the
perfused myocardium has been used (15). Al-
though the recovery of regional function after
revascularisation has generally been regarded
as the gold standard for detecting myocardial
viability, the clinical outcome after revasculari-
sation is a better and more valuable end-point.
The criteria for viability determination with re-
spect to its true clinical impact should be the
prediction of short- and long-term outcomes
such as cardiovascular mortality and recurrent
myocardial infarction (16). It should be kept
in mind that preserved myocardial perfusion
tracer uptake in zones of asynergy may have
a sub-optimal value for positive prediction of
improved segmental function after revascu-
larisation. However, it appears to predict a high
cardiac death and infarction rate with medi-
cal therapy and identifies a group of patients
with hibernating myocardium who would be
predicted to have an excellent outcome after
revascularisation. It has been demonstrated
11
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that the amount of dysfunctional myocardi-
um with preserved thallium uptake provides
independent prognostic information that is
incremental to that obtained from clinical,
functional, and angiographic data in patients
with chronic ischaemic LV dysfunction. In
particular, patients with a substantial amount
(>30% of the total left ventricle) of dysfunc-
tional myocardium with preserved tracer
activity exhibited the greatest LV functional
benefit after successful revascularisation (17).
Moreover, patients with more than 50% viable
myocardium represented a subgroup at high-
risk of cardiac death in whom successful revas-
cularisation improved survival (17). Altogether
these observations seem to lend further sup-
port to the choice of coronary revascularisa-
tion in patients with evidence of a substantial
amount of dysfunctional myocardium with
preserved myocardial perfusion tracer activ-
ity. Thus, it appears that the assessment of
myocardial viability should be a mandatory
step in clinical decision-making for patients
with reduced global and regional LV systolic
function, to better predict the potential value
of revascularisation in improving functional
status and survival.
4. Monitoring of treatment effect after
coronary revascularisation procedures
The use of exercise or pharmacological myo-
cardial perfusion imaging in the assessment of
interventions in chronic ischaemic heart dis-
ease is indicated for the evaluation of resteno-
sis after percutaneous transluminal coronary
angioplasty (PTCA) in symptomatic patients,
and in the assessment of ischaemia in symp-
tomatic patients after coronary artery bypass
grafting (CABG). Radionuclide techniques are
also indicated in the assessment of selected
asymptomatic patients after PTCA or CABG,
such as those with an abnormal electrocardio-
graphic response to exercise and those with
rest electrocardiographic changes precluding
identification of ischaemia during exercise.
SPECT exercise imaging is an excellent tool
for the detection of restenosis and disease
progression after PTCA after both one and
multivessel angioplasty, and in complete and
partial revascularisation. Hecht et al (18), study-
ing exercise tomographic thallium imaging in
the detection of restenosis after PTCA, showed
sensitivity of 93% for scintigraphic studies and
52% for exercise electrocardiographic studies,
specificity of 77% vs 64%, and accuracy of 86%
vs 57%, respectively. Moreover, it has been
demonstrated that, after PTCA, sensitivity and
accuracy of exercise electrocardiography in
the detection of restenosis were significantly
less than those of SPECT imaging for patients
with silent or symptomatic ischaemia (19).
Patients with less typical symptoms and in-
termediate probability of restenosis can be
accurately assessed for this PTCA complication
by myocardial perfusion imaging studies. In
the patients with recurrent atypical symptoms,
stress perfusion imaging should be performed
soon after the onset of symptoms in order to
determine whether persistent myocardial
12
ischaemia is the cause of chest pain. Myocar-
dial imaging studies offer several advantages
over stress electrocardiography, particularly
in patients with an abnormal resting electro-
cardiogram, multivessel coronary disease, or a
limitation to exercise stress testing. After PTCA,
nuclear cardiac imaging procedures are not
generally recommended in the absence of
recurrent symptoms, particularly since im-
aging abnormalities would not likely result
in either a changed therapeutic regimen or
repeat revascularisation. However, recent
data demonstrate that extent and severity
of myocardial ischaemia found via exercise
SPECT performed between 12 and 18 months
after percutaneous coronary intervention (PCI)
predict cardiac events during long-term fol-
low-up in both symptomatic and symptom-
free patients (20).
Exercise scintigraphy after CABG demonstrates
improved regional myocardial perfusion
in most patients. After CABG, the New York
Heart Association’s functional class improved
significantly. Early (less than 3 months) post-
CABG, myocardial imaging may be useful for
the detection of perioperative infarction, or if
early graft closure with recurrence of angina
symptoms is suspected. Beyond 3 months,
and following the recovery of hibernation
effects, non-invasive cardiac imaging is use-
ful for detecting asymptomatic graft attrition
and the recurrence of myocardial ischaemia.
However, this approach cannot be routinely
recommended in all patients who undergo
 Chapter 1: Applications and Rationale of Myocardial Perfusion Imaging – Alberto Cuocolo

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CABG because it would not be cost-effective
to screen this large population in the 1 to 2
years following CABG surgery.

Contraindications
Myocardial perfusion imaging is non-invasive
- the complication rate of dynamic exercise
and pharmacological stress tests is low and
well established (at most 0.01% deaths and
0.02% morbidity) (21-24). Therefore, except in
patients with unstable heart disease or other
contraindications to stress, the risk is not con-
sidered significant.

13
Patient Preparation
Julie Martin and Audrey Taylor

Patient identification • Any relevant clinical details

To minimise the risk of a misadministration, it
• That the patient has complied with the
is necessary to:
dietary and drug restrictions
• establish the patient’s full name and other
• If there are any known allergies or
relevant details prior to administration of
previous reactions to any drug/radio-
any drug or radiopharmaceutical
pharmaceutical/iodine-based contrast
• corroborate this data with information media or products such as Microspore/
provided on the diagnostic test referral Band-Aids
If the information on the referral form does not • That the results of correlative imaging (e.g.
match the information given from the identifi- echo, angiography, etc.) are available prior
cation process, then the radiopharmaceutical/ to the study taking place, and that any
drug should not be administered to the pa- recent interventions have been noted
tient. This should be explained to the patient
IF IN DOUBT, DO NOT ADMINISTER THE
and clarification sought as soon as possible by
RADIOPHARMACEUTICAL/DRUG, AND
contacting the referral source.
SEEK CLARIFICATION
The patient/parent/guardian/escort should
be asked the following questions and the in-
formation checked against their request form
and ward wristband if an inpatient.
“Please can you tell me you/your patient’s…
• full name.” - check any spellings as
appropriate, e.g. Steven vs Stephen
• date of birth.”
• address.”
A minimum of TWO corroborative details
should be asked and confirmed as correct.
The following information should be checked
with the patient/parent/guardian/escort where
appropriate.
• Referring Clinician/GP/Hospital

14
 Chapter 2: Patient Preparation – Julie Martin and Audrey Taylor
Patients with communication difficulties
Ideally, patients who for any reason are un-
able to identify themselves should wear an
identification wristband.
• Hearing difficulties - Use written questions
and ask the patient to supply the infor-
mation verbally or write their responses
down.
• Speech difficulties - Ask the patient to
write down their name, date of birth,
address, and other relevant details.
• Language difficulties - If an accompany-
ing person is unable to interpret the
questions, then the study should be
rescheduled to a time when a member of
staff/relative/interpreter with the appro-
priate language skills will be available.
• Unconscious patient - Check the patient’s
ID wristband for the correct name and
date of birth. If no wristband is attached,
ask the nurse looking after the patient to
positively confirm the patient’s ID.
• Confused patient - If an inpatient, check
the patient’s ID wristband for the correct
name and date of birth. If no wristband is
attached, ask the nurse looking after the
patient to positively confirm the patient’s
ID. If an outpatient, ask the person accom-
panying the patient to positively confirm
the patient’s ID.
• If a relative/friend/interpreter provides
information regarding the patient’s name,
15
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date of birth, etc., it is advisable for them
to sign as written evidence of confirmation
of the relevant details.
Patient information
Patients can be required to send in a list of
medications, approximate height, weight, and
asthma status so that stressing drugs can be
chosen in advance. They should be advised
to contact the department if they are diabetic
to ensure that they are given the appropriate
guidance regarding eating, medication, and
so on.
A full explanation of the procedure should be
given, including risks, contraindications and
side effects of stress agents used, time taken
for scan, the need to remain still, and so on.
Ideally, patients should be phoned before-
hand to remind them of their appointment
and to give them an opportunity to discuss
any concerns they may have.
Pregnancy
Women of child-bearing potential should
have their pregnancy status checked using a
form similar to that shown on the right.
• The operator administering the radiophar-
maceutical should advise the patient re-
garding minimising contact with pregnant
persons and children.
• The operator administering the radiophar-
maceutical should check that any accom-
panying person is not pregnant (e.g. escort
nurse).
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16
 Non-invasive cardiological techniques for coronary artery disease detection and risk stratification of patients with known
coronary artery disease employ both exercise and pharmacological stressors to induce flow heterogeneity or functional/
ECG abnormalities resulting from myocardial ischaemia.
Drug Interactions with Stress Testing (Table 1)

To Be Withheld Adenosine
Exercise Dobutamine
Before Stress Testing or Dipyridamole

Beta blockers
48 hours (4-7 days) 48 hours (4-7 days)
(Long-acting beta blockers)
Stress Protocols

Decrease oxygen myocardial

consumption, thus decreasing Mandatory for Desirable
exercise capacity and achievable diagnostic MPI
Recent publications suggest
MHR
that beta blockers may
Should be available
reduce MPI sensitivity
Reduce inotropic effects (to Optional for to counter any serious
be withheld if not medically prognostic MPI side effects

17
contraindicated)

Calcium channel blockers 48 hours 48 hours 48 hours

Adriana Ghilardi and Giuseppe Medolago

Decrease oxygen myocardial

consumption, thus decreasing Mandatory for
Recent publications
exercise capacity and achievable diagnostic MPI
suggest that
MHR
calcium channel blockers Desirable
interfere with
Reduce inotropic effects (to Optional for
Dipyridamole stress
be withheld if not medically prognostic MPI
contraindicated)

Nitrates 12-24 hours 12-24 hours 12-24 hours

Increase baseline blood flow,

dilating epicardial coronary
arteries, and decrease the Desirable
pressure inside the heart and
oxygen needs

Table continued on following page.

EANM
 (Table 1 cont.)

To Be Withheld
Exercise Adenosine or Dipyridamole Dobutamine
Before Stress Testing

Digitalis preparations
2 weeks 2 weeks
(digoxin, Lanoxin)

Mandatory for diagnostic test

Decrease oxygen needs in
Desirable
patients with LV dysfunction
Optional for prognostic test

Caffeine (coffee, tea, cola drinks, no

12-24 hours
chocolate, banana) but

As pharmacologic stress
Adenosine receptor antagonist
may be unplanned, all food
that inhibits pharmacologic
containing caffeine should
vasodilatation
be avoided

12 hours, but preferably 24

Dipyridamole
hours

18
Otherwise very low doses Dobutamine can be used as
Vasodilatation treatment should be used for the an alternative when Dipyrida-
stress test mole is not withheld

Aminophylline (all other drugs

1-5 days
containing Theophylline)

Adenosine receptor antagonist

that inhibits pharmacologic
vasodilatation

It should be emphasised that, in the room where the test procedure is carried out, a resuscitation trolley,
a defibrillator, and appropriate cardioactive medication should be available to treat any emergency, e.g.
cardiac arrhythmias, atrioventricular block, hypotension, and persistent chest pain. An intravenous line is
also mandatory to inject the tracer at the peak of the test. The equipment and supplies in the cart must be
checked on a daily basis.
 Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago
Exercise stressing
There are two main types of exercise:
1. Dynamic or isotonic exercise
(bicycle ergometry)
2. Static or isometric exercise
(treadmill protocol)
Exercise is preferred to pharmacological stress
for testing a physiological imbalance between
oxygen supply and demand due to impaired
flow reserve, as it can be graduated in order
to identify an ischaemic threshold related to
heart workload. This can be easily estimated
by the double product or rate-pressure prod-
uct, which is the product of heart rate and
systolic blood pressure at the peak of exercise.
Exercise testing should be undertaken under
the supervision of a physician properly trained
to perform such a test.
In both cases, the patient is prepared with a
standard 10-12 lead ECG set-up. HR, BP, and
ECG are registered at rest, at the end of each
stage, and also during recovery. ECG monitor-
ing is mandatory during the whole test.
1. Bicycle ergometry
a) Protocol
Bicycle protocols involve incremental work-
loads calibrated in watts or kilopond (KPD)
metres/minute. 1 watt is equivalent to 6 KPD.
Mechanically or electronically braked bicycles
can be used. Electronically braked bicycles are
more commonly used and preferred because
they provide a constant workload regardless
19
EANM
of changes in pedalling rate (usually ranging
from 60 to 80 rpm) and are less dependent on
patient cooperation.
The principle of the test is to gradually increase
the resistance to pedalling via a standardised
protocol while keeping the rate of pedalling
constant, thereby controlling the workload
the patient is performing.
Most protocols begin at a workload of 25 watts
and increase in 25 watt increments every 2-3
min. Younger or fitter subjects may start at
50 watts or more, with adequate increments
every 2-3 min. It takes about 1-2 min for the
cardiovascular system to adjust and stabilise
heart rate (HR) and blood pressure (BP) at each
new workload.
Exercise is usually completed when the patient
reaches 85% of predicted maximum heart rate
(max. = (220 – age) x 0.85). The patient is then
required to keep on pedalling at a minor work-
load (25-50 watts) for a few more minutes in
order to recover and return to near resting
values of HR and BP.
250W
Injection
200W
150W
100W
50W
25-50W
0 3 6 9 12 1 5 min
Figure 1
b) Advantages
• Patient motion is limited.
c) Disadvantages
• Patient might not be used to riding a bicycle.
2. Treadmill
a) Protocol
Like any exercise test, the treadmill protocol
should be consistent with the patient’s physi-
cal capacity and the purpose of the test. Sev-
eral standardised treadmill exercise protocols
exist; each of them is motor driven, and speed
and gradient (steepness) can be varied. Bruce
designed the most widely used. The standard
Bruce multistage maximal treadmill protocol
has 3 min periods (steps) to achieve a steady
state before workload is increased. The patient
starts at a relatively slow treadmill speed (1.7
mph/2.7 km/h), which is gradually increased
until the patient has a good stride. The ramp
angle is usually initially 10% grade, and this
angle is then progressively increased at fixed
3 min intervals (stages). It takes about 1-2 min
for the cardiovascular system to adjust and
Standard Bruce Protocol (Table 2)
Stage Duration (min) Total Time (min)
1 3
2 3
3 3
4 3
5 3
6 3
stabilise heart rate (HR) and blood pressure
(BP) at each new workload.
The Bruce protocol can be modified to in-
clude two 3 min warm-up stages at the same
speed (1.7 mph/2.7 km/h) but with no slope
(0% grade), followed by a second stage of 1.7
mph and 5% grade. This modified protocol is
suitable for elderly patients or patients whose
exercise capacity is limited by cardiac disease
or any difficulties with physical performance.
To avoid overestimation, it is important to en-
courage the patient not to grasp the handrails
of the treadmill during exercise. There is an
increase of as much as 20% in functional ca-
pacity when handrail support is permitted.
Exercise is usually completed when the pa-
tient reaches 85% of predicted maximum
heart rate (max. = (220 – age) x 0.85) (Table
2). The patient is then required to continue
walking at a minor ramp angle for a few more
minutes to recover and return to near resting
values of HR and BP.
Speed (mph) Grade (%)
3 1.7 10
6 2.5 12
9 3.4 14
12 4.2 16
15 5.0 18
18 6.0 20
20
 Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago

EANM
b) Advantages evaluated for complex ventricular disease and
• Most patients find exercise by walking nat- multivessel disease.
ural and easy to perform compared with
cycling.

c) Disadvantages
• BP measurements are often difficult to ob-
tain due to patient motion and gripping of
the support railing. ECG tracings may have
more motion artifacts at high workloads
due to patient motion.

Endpoints for exercise stressing

1. Reaching 85% of predicted maximum
heart rate
2. Typical chest pain (angina) or equivalent
(dyspnoea)
3. Ischaemic ECG abnormalities: diagnostic
ST depression of >2-3 mm, horizontal or
down sloping
4. Significant ventricular or supraventricular
arrhythmia on ECG
5. Progressive reproducible decrease in sys-
tolic BP
6. Abnormal elevation of systolic BP7. Maxi-
mum stress (fatigue)

Safety and risks

The risk associated with exercise stressing is
determined by the clinical characteristics of
the patient referred for the procedure. In a
non-selected patient population, mortality is
less than 1% and morbidity less than 0.05%;
thus, the risk of complications is greatest in
post-infarction patients and in those being

21
Absolute and Relative Contraindications to Exercise Testing

Absolute Relative

Acute myocardial infarction or recent change on Less serious noncardiac disorder

resting ECG
Significant arterial or pulmonary hypertension
Active unstable angina
Tachyarrhythmias or bradyarrhythmias
Serious cardiac arrhythmias
Moderate valvular or myocardial heart disease
Acute pericarditis
Drug effect or electrolyte abnormalities
Endocarditis
Left main coronary obstruction or its equivalent
Severe aortic stenosis
Hypertrophic cardiomyopathy
Severe left ventricular dysfunction
Psychiatric disease
Acute pulmonary embolus or pulmonary
infarction
Acute or serious noncardiac disorder
Severe physical handicap or disability

Limitations to Exercise Testing

Peripheral arteriosclerosis vascular disease

Disabling arthritis
History of stroke
Orthopaedic problems
Chronic pulmonary disease
Extremity amputations (diabetic patients)
Poor motivation to exercise
Poor exercise capacity due to noncardiac endpoints, e.g. fatigue
Beta-blocking drugs limiting heart rate response
Left bundle branch block (false positive exercise perfusion scans)
Early post-MI (<5 days)

22
 Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago
Pharmacological stressing
Pharmacological stress is increasingly being
employed as an alternative to exercise testing
for detection of physiologically significant cor-
onary artery disease and for prognostication. A
substantial number of patients referred to the
nuclear cardiology laboratory are incapable of
exercising either on a treadmill or a bicycle.
Patients with orthopaedic, neurological, or
peripheral vascular disease can be evaluated
for the presence of coronary artery disease
using a pharmacological vasodilation (in com-
bination with nuclear imaging). In addition,
patients on beta-blocking medication who are
unable to increase their heart rate adequately
by physical exercise can be studied success-
fully with pharmacological vasodilation.
The patient is prepared with a standard 10-12
lead ECG set-up in the supine position. HR, BP,
and ECG are registered at rest and every min-
ute during the whole test and the recovery
period. ECG monitoring is mandatory during
the whole test.
There are three main types of pharmacologi-
cal stressors:
• Dipyridamole
• Adenosine
• Dobutamine
23
EANM
1. Dipyridamole infusion protocol
Dipyridamole is the pharmacological test of
which there is the most extensive clinical
experience. It was the first pharmacological
stress test agent to be introduced (in the early
1980s); it was initially administered as capsules
(with many gastro-intestinal side effects) and
later as an i.v. infusion.
Dipyridamole is a synthetic indirect vasodilator.
Intravenous infusion of Dipyridamole blocks
the normal facilitated cellular uptake (in vas-
cular endothelium and red blood cell mem-
branes) of the natural vasodilator Adenosine,
which regulates coronary blood flow to meet
myocardial metabolic demands. Adenosine
is synthesised and released by endothelial
cells as part of local vaso-regulatory systems.
Thus, Dipyridamole increases the extracel-
lular interstitial concentration of Adenosine
available to react with the specific Adenosine
receptors that stimulate the relaxation of vas-
cular smooth muscle cells with consequent
coronary vasodilatation and increased blood
flow.
In a patient without coronary artery disease,
Dipyridamole infusion causes vasodilatation
and increases coronary blood flow to 3 to 5
times baseline levels. In contrast, in patients
with significant coronary artery disease, the
vessels distal to the stenosis are already di-
lated, sometimes maximally, to maintain nor-
mal resting flow. In these patients, infusion
of Dipyridamole does not cause any further
vasodilatation in the stenotic vascular bed.
Conversely, in the adjacent myocardium,
which is supplied by normal vessels, a sub-
stantial increase in blood flow occurs. Thus,
heterogeneity of myocardial blood flow is
produced; vascular territories supplied by
diseased coronary arteries are relatively hy-
poperfused compared with normal regions
(‘coronary steal’).
a) Protocol
Dipyridamole is infused over a 4 min period at
a dose of 0.56 mg/kg diluted in normal solu-
tion saline (20 ml). Maximal dilatory effect is
achieved approximately 4 min after comple-
tion of the infusion. This is usually associated
with a slight increase in heart rate and de-
crease in systolic blood pressure. Radiotracer
is injected at the 7th minute of the infusion.
In some laboratories, Dipyridamole infusion is
combined with handgrip exercise to reduce
background activity of the tracer in the ab-
dominal viscera. In some laboratories, at the
end of Dipyridamole infusion and after the
i.v. administration of the radiotracer, the in-
travenous antidote Aminophylline is also ad-
ministered to rapidly reverse any undesirable
Dipyridamole-associated side effects.
b) Drug interactions (see Table 1)
Ongoing treatment with beta blockers does
not affect the efficiency of Dipyridamole; in fact,
pharmacological dilatation represents the pro-
tocol of choice for patients on beta blockers.
24
Dipyridamole protocol is particularly well
suited to patients with left bundle branch
block. The false positive rate with this proto-
col is only 2-5%, compared with 30-40% for
exercise testing.
c) Safety and risks
The side effects of Dipyridamole are often
more severe and more difficult to control.
The risks associated with this procedure are
determined by the clinical characteristics of
the patient. It should be undertaken under the
supervision of a physician properly trained to
perform such a test; any side effects, though
often slightly more severe and harder to
control than with other stress agents, can be
quickly reversed with the intravenous antidote
Aminophylline.
d) Absolute and relative contraindications to
Dipyridamole testing
• bronchospasm
• drug intolerance
e) Limitations
Like any other drug, Dipyridamole pharmaco-
logical efficacy is slight or moderate in some
patients (‘non-responders’), thus reducing the
accuracy of the stress testing.
2. Adenosine infusion protocol
Unlike Dipyridamole, Adenosine is a natural
vasodilator. It is synthesised from ATP in the
vascular endothelium, and rapidly metabo-
lised through active cellular uptake and en-
 Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago
zymatic degradation in myocardial cells and
vascular smooth cells (the T1/2 of exogenously
infused Adenosine is about 10 sec).
By directly stimulating A2 purine receptors in
the heart, endogene and exogene Adenosine
has an important role in the natural regulation
of coronary flow (vasodilatation) and cardiac
demand (lowering BP). By stimulating A1 pu-
rine receptors in SA and AV node, it inhibits
norepinephrine release from sympathetic
nerve endings, reduces AV node conduction
velocity, and has negative inotropic and chro-
notropic effects.
Although both Dipyridamole and Adenosine
exhibit similar physiological effects on coro-
nary and systemic circulation, the vasodila-
tor effect of Dipyridamole is more prolonged
(up to 20-40 min) than that of Adenosine. In
contrast, the regional and systemic vascular ef-
fects of Adenosine appear earlier (within 20-30
sec) and quickly disappear after discontinua-
tion of the infusion (T1/2 in plasma is about
15 sec). Maximal effect has been observed
invasively after 60 sec and continues as long
as the drug is infused. These metabolic char-
acteristics explain the lesser rate of side effects
for Adenosine compared to Dipyridamole (see
Table 3).
a) Protocol
Adenosine is infused over a 4-6 min period at a
dose of 140 μg/kg/min. Radiotracer is injected
during the 5th or 6th minute of the infusion.
25
EANM
Many laboratories use the 2 plus 2 Adenosine
protocol, which is very convenient, effective,
and well tolerated. In this protocol, the radio-
tracer is injected after 2 min of infusion, and
the infusion then continues for an additional 2
min to clear the tracer from the blood.
In some laboratories, Adenosine infusion is
combined with handgrip exercise to reduce
background activity of the tracer in the ab-
dominal viscera. In some laboratories, at the
end of Adenosine infusion and after the i.v. ad-
ministration of the radiotracer, the intravenous
antidote Aminophylline is also administered
in order to rapidly reverse any undesirable
Adenosine-associated side effects.
b) Drug interactions (see Table 1)
Adenosine testing is the protocol of choice
in patients with significant arrhythmias or a
psychiatric history. Furthermore, Adenosine
testing is safe for stress testing soon after
acute MI.
c) Safety and risks
The risks associated with this procedure are de-
termined by the clinical characteristics of the
patient referred for the procedure. It should be
undertaken under the supervision of a physi-
cian properly trained to perform such a test;
any side effects, though often slightly more
severe and harder to control than with other
stress agents, can be rapidly reversed with the
intravenous antidote Aminophylline.
d) Absolute and relative contraindications to e) Limitations
Adenosine testing Like any other drug, Adenosine pharmaco-
• bronchospasm logical efficacy is slight or moderate in some
• drug intolerance patients (‘nonresponders’), thus reducing the
accuracy of the stress testing.
Reported Side Effects of Intravenous Dipyridamole and Adenosine
(% of Patients) (Table 3)
Dipyridamole Adenosine
Ranhosky et al (1) Cerqueira et al (2)
Cardiac % of Patients % of Patients
Fatal MI 0.05 0
Nonfatal MI 0.05 0
Chest pain 19.7 57
ST-T changes on ECG 7.5 12
Ventricular ectopy 5.2 N.R
Tachycardia 3.2 N.R
Hypotension 4.6 N.R
Blood pressure liability 1.6 N.R
Hypertension 1.5 N.R
AV block 0 10
Noncardiac
Headache 12.2 35
Dizziness 11.8 N.R
Nausea 4.6 N.R
Flushing 3.4 29
Pain (nonspecific) 2.6 N.R
Dyspnoea 2.6 15
Paraesthesia 1.3 N.R
Fatigue 1.2 N.R
Dyspepsia 1.0 N.R
Acute bronchospasm 0.15 0
N.R = Not Recorded

26
 Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago

3. Dobutamine infusion protocol
The Dobutamine stress protocol is a demand-
/supply-type protocol simulating a physical
stress test.
The rationale for using this pharmacologi-
cal approach is that Dobutamine infusion
increases heart rate, blood pressure, and
myocardial contractility; this increases myo-
cardial oxygen demand and, in the presence
of a functionally significant coronary stenosis,
causes a mismatch between oxygen supply
and demand that produces abnormal systolic
wall motion.
Dobutamine is a synthetic sympathomimetic
α1/β2 and β2 agonist:
1. Cardiac β1 adrenergic stimulation results in
increased myocardial contractility and heart
rate (HR) - the inotropic effect is greater.
2. The stimulation of cardiac α1 and β1 tends
to offset the β2 effect on the vascular arteriolar
smooth muscle cells leading to vasoconstric-
tion, i.e. an increase in blood pressure (BP).
EANM
target HR. Radiotracer is injected when target
HR is reached.
Dobutamine quickly clears from the blood
(T1/2 of about 2 min). It is useful to empha-
sise that it is relatively common (in 15-20% of
patients) to observe a blood pressure fall at
higher doses of Dobutamine, both in patients
with or without CAD, due to a mechano-re-
ceptor reflex initiated in the left ventricle. This
reaction does not carry the same significance
as a blood pressure fall during exercise testing.
If symptoms occur, simple leg elevation will
help; occasionally, in the presence of severe
symptoms, small doses of beta blocker anti-
dote are needed.
b) Absolute or relative contraindications to
Dobutamine testing
• severe arrhythmias
• psychiatric disorders

a) Protocol
Dobutamine is first diluted to a concentra-
tion of 1 mg/ml and infused at incremental
doses of 5, 10, 20, 30 and 40 μg/kg/min at 3
min intervals, until symptoms or attainment of
target HR. If the target HR cannot be reached
by Dobutamine infusion alone (most often
due to ongoing beta blocker medication),
adjunctive small i.v. doses of Atropine (0.25-
0.50 mg/push) should be used to reach the

27
c) Reported Side Effects of Intravenous Dobutamine Infusion
(% of Patients) (Table 4)
Cardiac % of Patients
Chest pain 19.3
Arrhythmias (all types) 15.0
Ventricular premature beats 15.0
Atrial premature beats 3.0
Noncardiac
Headache 3.0
Nausea 3.0
Dyspnoea 3.0

All side effects and severe symptoms are usually easily reversible with small doses of antidote beta blockers
i.v. (Metropolol). Sometimes, ongoing treatment with beta blockers is a problem when using the Dobutamine
protocol as it can be very difficult (or impossible) to reach the target HR, even after addition of Atropine. In this
situation, a pharmacological vasodilatation protocol (using Dipyridamole or Adenosine) should be used.

28
Preparation and Use of Imaging Equipment
Régis Lecoultre and José Pires Jorge
Quality control procedures that must be
performed satisfactorily
The end goal of any SPECT gamma camera
quality control programme is the production
of high-quality images for the best possible
diagnostic service to the patient.
Prior to initiating a routine quality control
programme for a newly purchased gamma
camera, it must undergo acceptance test-
ing in order to ascertain that its performance
corresponds to the manufacturer’s specifica-
tions and that it is fit for clinical use.
After acceptance testing, a quality control
protocol must be set up in each department
and followed in accordance with national
guidelines. The following quality control test
schedule is typical:
a) Daily energy peaking
b) Daily flood uniformity tests
c) Daily gamma camera sensitivity
measurement
d) Weekly linearity and resolution
assessment
e) Weekly centre-of-rotation calibration
f ) Quarterly multipurpose SPECT phantom
evaluation
A routine quality control programme for
SPECT gamma cameras should include qual-
ity control procedures appropriate for planar
scintillation cameras [see (a) to (d) below], and
specific SPECT quality controls [see (e) to (f )
below].
29
EANM
a) Daily energy peaking
This quality control procedure consists of
‘peaking’ the gamma camera for relevant ener-
gies prior to obtaining flood images. In cardiac
imaging, technologists are mainly concerned
with Tc-99m and Tl-201. For each radionuclide
used, energy peaking must be undertaken on
a daily basis.
Checking the peaking is necessary to ascer-
tain that:
• the camera’s automatic peaking circuitry
is working properly
• the shape of the spectrum is correct
• the energy peak appears at the correct
energy
• there is no accidental contamination of
the gamma camera
It is recommended that the spectra obtained
during peaking tests are recorded.
b) Daily flood uniformity tests
After a successful peaking test, it is recom-
mended that a uniformity test is performed
on a daily basis. Flood fields are acquired and
evaluation of camera uniformity can be made
via a visual assessment. Quantitative param-
eters should also be computed regularly and
recorded in order both to demonstrate sud-
den variations from the norm and to alert the
technologist to a progressive deterioration of
the equipment.
On cameras that have interchangeable unifor-
mity correction maps, it is vital that the one
being used is accurate, up-to-date and for the
correct nuclide.
c) Daily gamma camera sensitivity
measurement
A practical means of measuring sensitivity is to
record the time needed to acquire the flood
field using the known activity. This should not
vary by more than a few percent from one
day to another.
d) Weekly linearity and resolution
assessment
Linearity and resolution should be assessed
weekly. This may be done by using transmis-
sion phantoms.
e) Weekly centre of rotation calibration
The centre of rotation (COR) measurement
determines the offset between the axis of
rotation of the camera and the centre of the
matrix used for reconstruction, as these do not
automatically correspond.
The calibration of the centre of rotation is
made using a reconstruction of a tomographic
acquisition of a point source placed slightly
offset from the mechanical centre of the rota-
tion of the camera. A sinogram is formed from
the projections and used to fit the maximum
30
count locations to a sine wave. Deviations be-
tween the actual and fitted curves should not
exceed 0.5 pixels.
f ) Quarterly multipurpose SPECT phantom
evaluation
Multipurpose plastic phantoms filled with a
radioactive solution approximate realistic con-
ditions of clinical scattering and attenuation.
The multipurpose phantom includes remov-
able cold rod sections and spheres simulating
cold lesions. The main purpose of imaging this
phantom is to determine the SPECT system’s
limits of resolution. It is recommended that the
phantom be filled with 750-1000 MBq of Tc-99m
and the data acquired with an energy setting of
140 keV, a 20% energy window and a 128 x 128
pixel matrix for 128 projections over 360˚.
Collimator
In myocardial imaging the current tracers are
Tl-201 and Tc-99m labelled agents. The choice
of a collimator for a given study is determined
mainly by tracer activity. This influences the
statistical noise content of the projection im-
ages and the spatial resolution. The number
of counts must be maximised, possibly at the
expense of some resolution.
Collimators vary in terms of the relative length
and width of the holes. The longer the hole,
the better the spatial resolution obtained but
the lower the count sensitivity. Conversely, a
larger hole gives better count sensitivity but
with a loss of spatial resolution.
 Chapter 4: Preparation and Use of Imaging Equipment – Régis Lecoultre and José Pires Jorge
When using thallium, owing to the limited
dose and the long half-life of this isotope, the
count sensitivity will be greatly reduced. Tra-
ditionally, a low-energy general purpose col-
limator is recommended for use with Tl-201.
For Tc-99m imaging, count sensitivity is no
longer a major limitation so a high-resolution
collimator is recommended.
In myocardial SPECT imaging, however, the
major problem is the reduced spatial reso-
lution that occurs if the source-to-detector
distance is lengthened by the anatomical
situation of heart. Nevertheless, the resolu-
tion of an HR collimator decreases less with
distance from the source than does that of
a GP collimator. Although the choice of col-
limator is crucial, we should bear in mind that
other technical aspects play an important role
in determining the optimal spatial resolution;
these include the matrix size, the number of
angles and the time per view.
Matrix used and zoom factor
The goal of SPECT is to ascertain the distribu-
tion of injected activity in the patient’s body,
and in particular in the heart. The images (or
projections from the angles around the pa-
tient) create multiple raw data sets. Each of
these is electronically stored so that later on
they can be processed and their information
extracted. Each matrix contains the repre-
sentation of the data in one projection. It is
characterised by the number of pixels, each
pixel representing part of the object. Pixels
31
EANM
are square and typically organised in arrays of
64 x 64 or 128 x 128.
a) Matrix
The choice of matrix is dependent on four
factors:
i. Resolution:
The chosen matrix should not degrade the in-
trinsic resolution of the object. The commonly
accepted rule for SPECT (1) is that the pixel size
should be one third of the FWHM resolution of
the organ, which will depend on its distance
from the camera face. Spatial resolution of a
SPECT system is of the order of 18-25 mm at
the centre of rotation (2). Thus a pixel size of
6-8 mm is sufficient.
ii. Noise:
This is caused by the statistical fluctuations of
radioactive decay. Noise decreases with the
total number of counts, and if the matrix size is
doubled (to 128 instead of 64), the number of
counts per pixel is reduced by a factor of four.
128 x 128 matrices produce approximately
three times more noise in the image after re-
construction than do 64 x 64 matrices (3).
iii. Data size:
Of course, if there are four times more pixels
in each projection (128 versus 64), four times
more computer memory is needed for raw
data and approximately eight times more for
all processing. The processing time will also
increase. All new generation computers have
more memory and resources for data calcula-
tion, but may take some time to come onto
the nuclear medicine market.
iv. Software:
Sometimes, set protocols restrict the software
options available to the technologist. This re-
striction may be needed to ensure that re-
sults can be compared with reference studies
or databases. It is very important to ensure
reproducibility in this way before setting up
individual acquisitions. The reconstruction
processing cannot replace information lost
in the acquisition.
b) Zoom
The pixel size is dependent on the camera FOV
(field of view). When a zoom factor of 1.0 is
used, the pixel size (mm) is the UFOV (mm)
divided by the number of pixels in one line.
When a zoom factor is used, the number of
pixels per line should first be multiplied by this
factor; the FOV should then be divided by the
result of this multiplication.
Example:
Acquisition with matrix 64, zoom 1.0 and
UFOV 400mm:
Pixel size (mm) = 400/64 = 6.25 mm
Same acquisition with a zoom factor of 1.4:
Pixel size (mm) = 400/(1.4 x 64) = 4.46 mm
c) Preferred orbits
Either circular or elliptical orbits can be used in
32
Figure 2a Figure 2b
cardiac SPECT imaging (Fig 2). A circular orbit
(a) is defined by a fixed distance from the axis
of rotation to the centre of the camera sur-
face for all angles. Elliptical orbits (b) follow
the body outline more closely.
With a circular orbit, the camera is distant from
the heart at some angles, causing a reduction
of spatial resolution in these projections. This
will reduce the resolution of the reconstructed
images.
With an elliptical orbit, spatial resolution is
improved as the camera passes closer to the
heart at all angles. Nevertheless, the distance
from the heart to the detector varies more sig-
nificantly with an elliptical orbit than a circular
orbit. This may generate artifacts that simulate
perfusion defects when reconstructing using
filtered back projection.
Programmes that allow the camera to learn
and closely follow the contours of the body
are available and improve resolution, although
this is at the expense of computing power to
modify the data before reconstruction.
 Chapter 4: Preparation and Use of Imaging Equipment – Régis Lecoultre and José Pires Jorge

The loss of spatial resolution with a circular
orbit must be offset against the potential ar-
tifacts that may be generated by an elliptical
or contoured orbit.
When selecting an orbit in cardiac SPECT im-
aging, it is most important to choose one that
does not truncate or clip the heart. This should
be checked after the acquisition while the pa-
tient is still available so that the acquisition can
be repeated if necessary.
ECG Gating
a) The ECG
The principal of the electrocardiogram is that
the electrical activity of the heart is detectable
on the body’s surface via electrical potential
differences between sites. These differences
can be recorded with electrodes coupled to
EANM
an electrocardiograph machine.
The ECG sequence:
Excitation of the atrium begins in the region
of the sino-atrial node (SN). One positively
charged electric wave goes through both atria
(‘depolarisation’). This is represented by the P
wave on the ECG, and causes contractions. The
electric stimulation then reaches the atrioven-
tricular knot (AV) and, after a short stop whilst
the ventricles fill, progresses along the bundle
of His and Purkinje fibres. This step in ventricle
stimulation is seen in the QRS complex. After
a 1 sec pause, the ventricles repolarise (this is
visible as the T wave). The repolarisation of the
atria occurs at the same time as the QRS waves
and is therefore not visible on the ECG.

Example of an ECG (Figure 3)

R Wave
RR Interval

T Wave

P Wave

S Wave
Q Wave

33
b) Acquisition
For gating, only the contraction signal is need-
ed and the R wave (the biggest signal from the
QRS complex) is used (Fig 4).
The three lead ECG is not for medical diagnosis
but for acquisition synchronisation. It provides
the most distinct R signal when the patient is
in the right position for acquisition.
Positive or negative signals can be used
equally but, if required, the inversion can be
done easily by changing over the two cables.
If necessary, the signal can be amplified elec-
tronically on the ECG machine.
For a reliable trace, it is best to fix an electrode
onto each shoulder (first moving the arm into
the acquisition position) and a third one onto
the abdomen, right lateral. It’s best to fix this
lead on the righthand side as most acquisi-
tions are done with a 180˚ rotation over the
lefthand side of the patient.
It is possible to define between 8 and 32 im-
ages per cardiac cycle, depending on how
much information is wanted on ventricular
wall motion. Two issues affect this choice:
i. The total counts and hence ‘noise’:
When the number of images is increased in
order to reach a given number of counts per
frame, the total acquisition time is extended.
34
ii. The data volume:
If one acquisition is considered, every division
of the cardiac cycle multiplies the data volume
(or the number of frames) by the same factor.
This is why 8 or 16 images per cycle are usually
used for SPECT. Each image of the cycle can
be called a bin.
c) Artifacts
The greatest source of artifacts during gated
acquisition is a changing HR. If any cycles differ
significantly in length then the information in
the total image will not be representative of
the same stage of contraction in each cycle,
but will instead be a mixture. Each image in
one gated cycle is written initially to the buffer.
If the length of its cardiac cycle is subsequently
found to be more than ± 10% of a preset value
based on prior observation of the patient’s
heartbeat, this cycle should be rejected from
the final sum.
It may be impossible to do gated acquisitions
on a patient who has a very unstable HR.
HR changes could be due to physical stress; if
the patient has come directly from the exer-
cise bicycle or has run along the corridor, their
HR will decrease after a few minutes, and the
window will have been wrongly set. Another
explanation of this problem is psychological
stress or anxiety. Conversely, if the patient’s HR
increases over time, it may be that the patient
is either becoming impatient or in an uncom-
fortable or painful position.
 Chapter 4: Preparation and Use of Imaging Equipment – Régis Lecoultre and José Pires Jorge

EANM
Gating via an ECG signal (Figure 4)

In some systems it is possible to exceed the defined time per projection in order to com-
plete cardiac cycles that were not in the acceptance window. We speak of an effective
acquisition time per projection. This is a good solution but the window definition should
be good.

35
 Three radiopharmaceuticals for myocardial perfusion imaging are currently available in the European market.
Thallium was the first to be introduced, followed by Tc-99m sestamibi and Tc-99m tetrofosmin.
Radiopharmaceutical Features

Thallium Tc-99m sestamibi Tc-99m tetrofosmin

Photo peak energy (keV) 6-80 (98%) 140 140

135 (2%)
167 (8%)

More scatter Optimal for gamma Optimal for gamma camera

(worse resolution) camera (better resolution) (better resolution)
More attenuation Less attenuation Less attenuation

Half-life (hours) 73.1 6 6

Julie Martin and Audrey Taylor

Cyclotron product to be Always available Always available

Imaging and Processing

ordered (24 months shelf life at room (6 months shelf life

temperature) at 2-8°C)

36
Ready for use Preparation 20 min (including Preparation 15 min
10 min boiling)

Effective dose adult (μSv/MBq) 231 Stress: 7.4 Stress: 6

Rest: 8.5 Rest: 6.8

Higher dosimetry Favourable dosimetry Favourable dosimetry

(for testes 30x higher than (allows higher dose) (allows higher dose)
with Tc tracers)

Extraction fraction (%) 85 65 54

Myocardial uptake (%) Max Stress Stress

3.7 at 5 min: 1.5 at 5 min: 1.3
at 60 min: 1.4 at 60 min: 1.1
Rest: 1.2 Rest: 1.2

Best uptake More myocardial counts under Less linear myocardial uptake
stress with increasing blood flow
 Redistribution Yes Not significant No

1 injection 2 injections 2 injections

(± 1 injection)
At stress, imaging within 5-10
min (possible upward creep
artifacts)
Greater flexibility in imaging Greater flexibility in imaging
time and in protocol choice time and in protocol choice
Acquisition could be repeated Acquisition could be repeated
at stress if: at stress if:
• Patient moved • Patient moved
• Supine + prone • Supine + prone
• Technical issue • Technical issue

Standard dose* (MBq) 111 1-day protocol 1-day protocol

Above 70 kg (± 37) 1st dose: 250 1st dose: 250
2nd dose: 750 2nd dose: 750
2-day protocol 2-day protocol
1,000 1,000

37
+ 1.1/kg + 10/kg (daily dose) + 10/kg (daily dose)

Dose limited by dosimetry Higher dose (improved image Higher dose (improved image
quality) quality)

ECG-gated SPECT No Yes Yes

Not recommended as lower Improved specificity for Improved specificity for

counts statistics (results less perfusion analysis perfusion analysis
reproducible) Ventricular function Ventricular function

* Allowable upper limits of radiotracers may differ from country to country. Please refer to the Summary of Product
Characteristics in each European country.
Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor

EANM
Dosage for Children
The following table* from the Paediatric Committee of the EANM may be used (1):

Fraction of Adult Administered Activity

3 kg = 0.1 22 kg = 0.50 42 kg = 0.78
4 kg = 0.14 24 kg = 0.53 44 kg = 0.80
6 kg = 0.19 26 kg = 0.56 46 kg = 0.82
8 kg = 0.23 28 kg = 0.58 48 kg = 0.85
10 kg = 0.27 30 kg = 0.62 50 kg = 0.88
12 kg = 0.32 32 kg = 0.65 52–54 kg = 0.90
14 kg = 0.36 34 kg = 0.68 56–58 kg = 0.92
16 kg = 0.40 36 kg = 0.71 60–62 kg = 0.96
18 kg = 0.44 38 kg = 0.73 64–66 kg = 0.98
20 kg = 0.46 40 kg = 0.76 68 kg = 0.99

* This table summarizes the views of the Paediatric Committee of the European Association of Nuclear
Medicine. It should be taken in the context of ”good practise“ of nuclear medicine and local regulation.

Thallium Dosimetry by Age of Patient

Thallium should be avoided for children because of its dosimetry (2).

Thallium-201 Adult 15 y-old 10 y-old 5 y-old 1 y-old

Effective dose (μSv/MBq) 231 319 1,265 1,724 2,940

Drug interactions with radiopharmaceuticals

None yet known.

Delay between Injection and Imaging - Tc-99m Sestamibi and Tc-99m Tetrofosmin

First study Second study Imaging period Waiting period bet-

between injection rest/ ween injections (min)
stress and scan (min)

Rest Stress 30-60 100

Stress Rest 30-60 100-180

38
 Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor
Imaging should begin 30-60 min after injec-
tion to allow for hepato-biliary clearance; lon-
ger delays are required for resting images and
for stress with vasodilators alone due to higher
liver uptake.
After the injection, patients are asked to walk
around and then eat a fatty meal to aid tracer
clearance from the liver and gall bladder.
Patients are also asked to drink two or three
glasses of water 15 min prior to imaging.
Thallium studies
Imaging should begin within 5 min of the
stress study injection and be completed
within 30 min of injection. This ensures that
redistribution has not yet taken place. Redis-
tribution imaging should be performed 3-4
hours after stress injection.
If the redistribution images are unsatisfactory,
some centres then give a resting injection
(ideally after sublingual nitrates) and image
again after a further hour.
Dual-isotope protocol
Some centres perform a dual-isotope protocol
with thallium injected at rest, followed by a Tc-
99m labelled agent injected at stress.
Patient positions
The patient should be supine with both arms
above the head and supported in a comfort-
able position. Knee support is also helpful and
patient comfort is essential to minimise mo-
39
EANM
tion. Prone imaging has been used in some
centres to reduce the incidence of inferior
attenuation artifacts, but it can produce an-
terior artifacts and is not recommended in
isolation.
In some centres female patients are imaged
without underclothes. A chest band can be
used to minimise breast attenuation and to
ensure reproducible positioning during later
image acquisition. This can however increase
attenuation depending on how the band is
applied so careful attention must be paid to
technique when the breasts are strapped.
Chest bands can also be used in males to re-
duce motion.
The patient is positioned so that the heart is
in the field of view. Immobilisation aids should
be used to minimise patient movement and
to ensure patient comfort, with arms raised
above head. It may be more comfortable for
the patient to have their left arm above their
head and their right arm either under their
bottom or in a pocket, but take care if the in-
jection site is in the right arm. However, it is
important that the patient is not rotated.
The camera is positioned to minimise patient-
camera distance for the complete 180˚ SPECT
rotation.
It is extremely important that the same op-
erator performs both stress and rest studies
whenever possible. It is essential that the
camera/patient positioning is reproduced as
closely as possible for rest and stress in order
to ensure accurate comparison between the
images. Where available, parameters such as
bed height and lateral movements can be re-
corded for reproducibility.
The study can be performed using an LFOV
camera or dedicated cardiac camera (e.g.
Optima), with an LEHR collimator when us-
ing the Technetium agents, and LEGP when
using Thallium and software zoom.
Gated SPECT with or without attenuation cor-
rection should be used as appropriate.
Provision of both attenuated corrected and
non-attenuated data should be available
where possible.
ECG gating can be performed (unless HR is
irregular), particularly with Tc-99m labelled ra-
diopharmaceuticals. 8/16 frames per cardiac
cycle should be acquired for accurate calcula-
tion of left ventricular ejection fraction, depen-
dent on the camera used.
The technologist should adjust the time per
view if the count rate is lowered, e.g. due to
patient size, tissued injection or imaging de-
lays.

Image magnification
A software zoom can be used, depending on
the chosen camera.

Suggested Acquisition Parameters

Matrix 64 x 64
Frame time Thallium 40 sec/view
Tc-99m agents 30-40 sec/view
No. of projections 32 or 64 depending on camera
used (dual or single head)
180˚

40
 Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor
Processing instructions - reconstruction
Filtered back projection using Butterworth
and Hanning filters is the most common
method of reconstruction. Cut-off frequen-
cies as per the manufacturer’s recommenda-
tions, e.g. 0.5 cycles per cm (order 5 or 10) and
0.75 cycles per cm respectively can be chosen;
these should be the same for each patient
and should not be altered to compensate for
low-count images in order to maintain consis-
tency of appearance. Iterative reconstruction
is preferred if attenuation correction has been
performed, and can also be used without at-
tenuation correction.
The long axis of the left ventricle runs from the
apex to the centre of the mitral valve, and defi-
Display of a Tc-99m Sestamibi SPECT (Figure 5)
41
EANM
nition of this axis can be manual or automatic.
Automatic definitions should be checked and
adjusted if necessary. The definition should
be consistent in both stress and rest stud-
ies, bearing in mind that the orientation of
the ventricle may change slightly between
acquisitions.
The transverse tomograms are reoriented into
three sets of oblique tomograms: (1) short axis
(perpendicular to the long axis of the left ven-
tricle), (2) vertical long axis (parallel to the long
axis of the left ventricle and to the septum),
and (3) horizontal long axis (parallel to the long
axis of the left ventricle and perpendicular to
the septum) (Fig 5).
Short axis - stress
Short axis - rest
Vertical long axis - stress
Vertical long axis - rest
Horizontal long axis - stress
Horizontal long axis - rest
Image evaluation
The planar projection images and the recon-
structed tomograms should be inspected
immediately after acquisition by an operator
or practitioner in order to identify technical
problems that might require repeat acquisi-
tion. These might include:
• injection site or external objects passing
across the heart
• patient motion
• inaccurate ECG gating
• problems related to the detector(s), such
as drift in energy window and artifact(s)
generated by transition between the two
detectors
• inappropriate collimation or energy
windows
• gut activity encroaching into the heart
wall
Image display
Stress and rest images should be appropri-
ately aligned and presented in a format that
allows ready comparison of corresponding
tomograms, such as interactive displays that
triangulate the three planes or display the full
set of tomograms. Each tomographic acquisi-
tion should be displayed with the top of the
colour scale at the maximum within the myo-
cardium for each set.
42
Displays with the top of the colour scale at
the maximum of each individual tomogram
and those that use the same maximum for
stress and rest images should not be used.
Care should be taken if the maximum lies
outside the myocardium and manual adjust-
ment or masking of extracardiac activity may
be required. The bottom end of the colour
scale should be set to zero and background
subtraction should be avoided. Neighbour-
ing pairs of tomograms can be summed for
display according to local preference.
Check that all images have the correct patient
details displayed.
Attenuation correction
A number of techniques have been devel-
oped for correcting emission tomograms for
attenuation, in an effort to reduce or eliminate
attenuation artifacts. Many of these incorpo-
rate additional corrections for scatter and for
depth-dependent resolution recovery. Al-
though initial results are encouraging, each
method behaves differently and none over-
comes artifacts entirely, some even introduc-
ing new forms of artifact through overcorrec-
tion. The effectiveness of these techniques in
routine clinical practice is currently uncertain.
They should be used only in experienced cen-
tres and preferably as part of a formal evalu-
ation of their value. Corrected images should
not be used without reviewing them along-
side the uncorrected images.
 Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor

EANM
Aftercare
The operator administering the radiopharma-
ceutical should advise the patient with regard
to minimising contact with pregnant women
and children for 24 hours. After each study,
and prior to the patient leaving the depart-
ment, it is advisable to check that the data
has been correctly acquired on the computer
and to view the cine/sinogram to ensure that
there is/are no patient movement/artifacts.
The patient should be told that the procedure
is completed, when the results will be sent and
that they can return to taking routine tablets,
eating, and drinking.

43
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170,000 tests. JAMA 1971;217:1061-1066.
22. Cerqueira MD, Verani MS, Schwaiger M, et al. Safety
profile of adenosine stress perfusion imaging: results from
the Adenoscan multicenter trial registry.J Am Coll Cardiol
1994;23:384-389.
23. Lette J, Tatum JL, Fraser S, et al. Safety of dipyridamole
testing in 73,806 patients: the multicentre dipyridamole
safety study.J Nucl Cardiol 1995;2:3-17.
24. Mertes H, Sawada SG, Ryan T, et al. Symptoms, adverse
effects, and complications associated with dobutamine
stress echocardiography: experience in 1118 patients. Cir-
culation 1993;88:15-19.
Chapter 2
Further Reading
Pennell and Prvulovich. Clinicians Guide to Nuclear Medici-
ne - Nuclear Cardiology Series Ed.Ell 1995 BNMS
Procedure Guidelines for Radionuclide Myocardial Perfu-
sion Imaging. Adopted by the British Cardiac Society, the
British Nuclear Cardiology Society, and the British Nuclear
Medicine Society obtainable from
http://www.bncs.org.uk
Chapter 3
References
1. RanhoskyA, Kempthorne-Rawson J. The safety of intrave-
nous Dipyridamole Thallium myocardial perfusion imaging.
Circulation 1990;81:1425-1427.
2. Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian
AS. Safety profile of adenosine stress perfusion imaging:
results of the Adenosine multicenter trial registry. J Am Coll
Cardiol 1994;23:384-389.
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Chapter 4
References
1. Groch MW, Erwin WD. SPECT in the Year 2000: Basic Prin-
ciples. J Nucl Med Technol 2000;28:233-244.
2. De Puey EG, Garcia EV, Berman D. Cardiac Spect Imaging.
Lippincott Williams & Wilkins 2001.
3. Garcia EV, Cooke CD, Van Train KF, Folks R, Peifer J, De Puey
EG, Maddahi J, Alazraki N, Galt J, Ezquerra N, et al. Technical
Aspect of Myocardial SPECT Imaging with Technetium-99m
Sestamibi. Am J Cardiol 1990;66:23E-31E.
Further Reading
Nuclear Medicine and PET, Technology and Techniques /
Christian / Mosby
Principles and Practice of Nuclear Medicine / Paul J.Early,
D.Bruce Soddee
Chapter 5
References
1. Paediatric Task Group European Association Nuclear
Medicine Members. A radiopharmaceutical schedule for
imaging in paediatrics. Eur J Nucl Med 1990;17:127-129.
2. Adsorbed doses from ICRP publication 80. ICRP publica-
tion 80. Radiation dose to patients from radiopharmaceu-
ticals. Addendum 2 to ICRP Publication, Pergamon Press,
Oxford 1998.
Further Reading
Pennell and Prvulovich. Clinicians Guide to Nuclear Medici-
ne - Nuclear Cardiology Series Ed.Ell 1995 BNMS
Procedure Guidelines for Radionuclide Myocardial Perfusion
Imaging. Adopted by the British Cardiac Society, the British
Nuclear Cardiology Society, and the British Nuclear Medici-
ne Society obtainable from http://www.bncs.org.uk
Imprint

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