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Unit 7 Radionuclides in Cardiology
Unit 7 Radionuclides in Cardiology
Unit 7 Radionuclides in Cardiology
Structure
7.0 Objectives
7.1 Introduction
7.2 Radio Pharmaceuticals (Tracers)
7.2.1 Thallium (201TI)
7.2.2 99m Technetium (Tc) Labeled Tracers
7.2.3 Positron Emitters
7.3 Instrumentation
7.3.1 Gamma Camera
7.3.2 PET
7.0 OBJECTIVES
After reading this unit, you should be able to:
• enlist the names of radiopharmaceuticals and their usefulness in cardiovascular studies; and
• describe the technique, risk stratification, progonstication, viability assessment and follow-
up after revascularrization in patient with know or susptected coronary artery diseases in
myocardial perfusion imaging studies.
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7.1 INTRODUCTION
Nuclear cardiology has become a well established subspecialty in the field of cardiovascular
diseases. It employs radioisotopes and pharmaceutical agents labeled with isotopes for imaging of
the cardiovascular system. Unlike other imaging modalities which essentially display anatomical
details, nuclear studies or scintigraphy procedures demonstrate functional abnormalities. During
the last three decades, myocardial perfusion imaging (MPI) using Thallium (201Tl) for non-
invasive detection of coronary artery lesions, has this field has advanced to SPECT (single photon
emission computerized tomography), an excellent imaging technique, with newer Technetium
(99mTc) labeled tracers. The value of MPI in improved detection of coronary artery disease
(CAD), and assessment of ischaemic severity is well documented. Its role is valuable in risk
stratification, prognostication, viability assessment, and follow-up after revascularization in
patients with known or suspected CAD. Non-invasive assessment of global and regional left
ventricular function using gated first pass and equilibrium radionuclide angiography (RNA) is
now well established. It also allows for the quantitative assessment of the LV function
simultaneously with the evaluation of the LV perfusion. With the advent of positron emission
tomography (PET), the scope of functional imaging is now widened. Imaging of myocardial
glucose utilization in the setting of ischaemia helps in studying the pathophysiology of various
diseases. Metabolism in myocardium can be studied using 18 Fluorodeoxy glucose and 11C-fatty
acids.
1) Energy of gamma ray, 140keV, is optimal for gamma camera imaging and can produce
higher quality images than Thallium which has lower energy photons [60-83keV].
2) Shorter half-life, (6 hours as opposed to 73 hours of 201Tl) and hence 10-15 times higher
dose than thallium can be injected, which results in a higher count rate and shorter imaging
time.
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99mTc-Sestamibi
7.3 INSTRUMENTATION
7.3.1 Gamma Camera
Gamma Camera is the most commonly used equipment for nuclear imaging. It consists of the
following Fig. 7.1:
1) A large sodium iodide crystal, which is a scintillation type of detector of gamma rays, which
produces scintillations when gamma rays fall on it.
2) A large number of photomultiplier tubes, which amplify the light signal and convert it to
electrical signal for further processing.
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3) A collimator, a sheet of lead or tungsten between the crystal and the patient, achieves better
resolution of images (Fig. 7.2).
4) A computer and electronics to process the signals and reconstruct the images.
Fig. 7.1: Dual head gamma camera Fig. 7.2: Different collimators
Single and multi-crystal or double and triple detector cameras are available these days. Planar
imaging gives typically three standard views anterior, left anterior oblique and left lateral. This is
currently replaced by SPECT (single photon emission computerized tomography), which allows
cut sections or slices of left ventricle walls in three planes transverse, sagittal and coronal. Gated
SPECT is a further refined form of SPECT, where imaging is done with ECG gating.
7.3.2 PET
PET cameras can image positron emitting tracers. Each positron emits two gamma rays which are
detected by a pair of detector systems. High count rate images obtained by PET are of superior
quality and resolution. These are newer techniques used to image myocardial energy metabolism.
Check Your Progress 2
What kind of rays do radiopharmaceutical tracers emit and what kind of cameras are used to
record them?
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examination should be performed; baseline vital signs should be evaluated and a 12-lead ECG
performed.
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Reconstruction of Images
Before reconstruction, it is important to check the raw projection data for potential sources of
errors and artifacts. Any error during image acquisition (instruments, patient motion, or soft-tissue
attenuation artifacts) is likely to compromise the accuracy of the measurements.
Image Evaluation
The overall quality of the study must be initially assessed by looking for artifacts or other sources
of error (patient motion, breast or diaphragmatic attenuation) and to evaluate pulmonary and
noncardiac uptake. Reconstructed perfusion images are displayed in a standardized format (Fig.
7.5). On top are the short-axis stress and rest images. The second 2 lines display the vertical long-
axis stress/rest images. The final 2 lines contain the horizontal stress/rest images. Images are
usually reviewed in both a continuous color format, such as gray scale, and in a color scale.
In addition to viewing the wall motion from a 3-dimensional perspective, wall thickening can be
visualized by viewing the gated short, vertical long, and horizontal long axes. Polar maps can be
helpful in quantifying abnormalities in perfusion, regional ejection fraction, motion and wall
thickening. Also arterial territories are superimposed on the images (Fig. 7.5).
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ventricular sizes, uptake by the right ventricle, the presence or absence of transient ischaemic
dilation and lung uptake should be included. Comment on the size and severity of the defects.
Normal Findings
On perfusion studies result in almost identical stress/rest images with no defects. Tracer
distribution is uniform in all the walls of left ventricle.
Fixed Defects
In patients with infarcted myocardium, findings demonstrate fixed defects.
Reversible Defects
Findings in patients with myocardial ischaemia demonstrate reversible defects, i.e., defects on the
stress images without a similar defect on the rest images.
Wall Motion Analysis
GSPECT studies can be used to assess regional wall motion and left ventricular ejection fraction
when viewed in a cine display. If a perfusion defect is present on stress images and the associated
wall is seen to thicken (i.e.: brighten) during systole, one can predict that this represents an area
containing viable myocardial tissue. If no thickening is observed, the finding may represent an
area of infarction (scar).
Ejection Fraction
LV ejection fraction can be calculated from GSPECT data and provides incremental prognostic
information for risk stratification.
LV Dilatation
Left ventricular chamber dilatation may also be noted with pharmacologic stress and is associated
with an increased risk for subsequent cardiac event. This represents subendocardial ischaemia or
diffuse reduced subendocardial flow reserve.
Pulmonary Activity on Stress Imaging
An increase in tracer uptake in lung on stress imaging is a marker for severe underlying CAD. A
lung to heart ratio of greater than 0.33 is suggestive of underlying severe CAD.
Check Your Progress 3
What is meant by the term reversible defect on nuclide stress testing?
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Myocardial Perfusion: Clinical Applications
There is definite evidence in literature showing the incremental prognostic value of stress MPI
over clinical, historical, and exercise ECG data. This information can be applied in a clinically
relevant fashion. Risk stratification that identifies patients with normal scans as low risk is
possible and also increasing risk as a function of worsening scan abnormalities. These findings
have been reproduced in a number of patient subgroups defined on the basis of sex, symptoms,
age, and likelihood of CAD. Mildly abnormal scans, despite having a high likelihood of CAD, are
associated with a low risk of cardiac death, although with an intermediate risk of myocardial
infarction, perhaps identifying a patient subgroup suited for medical therapy.
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Diagnosis of CAD
The diagnostic role of MPI in CAD is well recognized. For example, a normal perfusion study in
a patient undergoing screening generally carries an excellent prognostic value. Normal function
and perfusion obviate the need for further invasive cardiac investigations. Patients with a normal
Sestamibi study have an overall annualized cardiac event (MI or cardiac death) rate of less than
0.5-2 per cent per year. Conversely, an abnormal Sestamibi exam which demonstrates a reversible
defect is associated with a significantly increased risk for cardiac events. An increased number of
reversible defects, the presence of defects in multiple vascular territories, and the severity and
extent of reversible defects are all associated with an increased risk for subsequent cardiac event.
Combined perfusion-function analysis can also differentiate ischaemic from non-ischaemic,
dilated cardiomyopathy. Although both the perfusion and the LV function are abnormal in
patients with ischaemic cardiomyopathy, LV dysfunction is present without any significant
perfusion abnormalities in patients with non-ischaemic cardiomyopathy.
Prognostic Value of Stress MPI in Patients with Known or Suspected CAD
Exercise stress MPI became established as an effective clinical tool for detecting coronary artery
disease, particularly in patients with abnormal resting electrocardiograms. Subsequently, the
technique was applied to the assessment of patient prognosis, and it was demonstrated that stress
myocardial perfusion imaging performed in conjunction with exercise provided important
prognostic information. MPI, whether with 201Thallium or 99mTechnetium, planar or SPECT
imaging, is a more powerful and independent predictor of outcome than any element of clinical or
historical information.
Myocardial Ischaemia
Nuclear myocardial scan is the best initial imaging study for the detection of myocardial
ischaemia. Currently, nuclear myocardial scans include both perfusion and gated wall motion
images. Coronary artery blood flow is assessed. The scans can also be used to accurately
determine the left ventricular ejection fraction, the end-systolic volume of the left ventricle,
regional wall motion, and wall thickening. The prognostic value is exceptional. Although
GSPECT is more expensive than stress echocardiography, its negative predictive value is better.
The cost is also significantly less than that of angiography.
Although myocardial perfusion SPECT imaging has several other indications, in almost all
patients, detecting myocardial ischaemia is the critical issue. For example, after a myocardial
infarction, a nuclear scan can demonstrate whether viable myocardium remains in the affected
area. This information helps in predicting whether bypass surgery, angioplasty, or stenting will be
of benefit. A nuclear scan obtained preoperatively (especially before major vascular surgery) also
aids in determining the risk primarily based on the presence or absence of myocardial ischaemia.
Newer metabolic imaging procedures involving positron emission tomography (PET) can help in
determining whether the region of the heart affected by a myocardial infarction remains viable.
One well-recognized application of GSPECT is to classify a fixed perfusion defect as a soft-tissue
(left breast or diaphragm) attenuation artifact or an infarct. Attenuation artifacts increase the false-
positive interpretation of the perfusion scans. Gating also increases the reader’s confidence in
interpretation of the perfusion scan, by decreasing the number of equivocal results.
Assessment of Severity
Exercise-induced angina produces defects in stress perfusion images and the magnitude of the
poststress regional or global dysfunction correlates with the severity of the ischaemia. Poststress
wall motion abnormality is more sensitive than a resting and stress wall motion abnormality and is
highly specific for a severe angiographic stenosis.
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Risk Stratification and Prognosis
LV functional status is well recognized as a predictor of future cardiac events after myocardial
infarction. MPI can be used to estimate the residual function after myocardial infarction. Patients
can be risk stratified on the basis of the LVEF and LV volumes. Patients with an LVEF > 45 per
cent or an ESV < 70 mL had a lower mortality rate, despite severe perfusion abnormalities,
whereas patients with an LVEF < 45 per cent or an ESV > 70 mL had a higher mortality rate,
even with mild-to-moderate perfusion abnormalities. GSPECT is also useful in preoperative risk
assessment of patients undergoing major noncardiac surgery and may predict perioperative
cardiac events.
Myocardial Viability
Restoration of the blood flow by surgical revascularization is an important modality of treatment
in patients with chronic CAD and LV dysfunction. Dysfunctional but viable myocardium is
potentially reversible, and thus, differentiation of the viable myocardium from the nonviable
myocardium before surgical intervention is crucial. Perfusion-metabolism mismatch—i.e.,
preserved metabolism (as shown by PET) in an area of decreased perfusion—Is considered as the
gold standard for myocardial viability assessment. GSPECT relies on demonstration of the
regional contractile function in a hypoperfused area as an indication of the viability.
Follow-up after Revascularization
The excellent reproducibility of GSPECT are particularly suited to assess the functional changes
after coronary revascularization. LV functional status can be compared before and after the
revascularization procedure. Functional improvement after coronary artery bypass grafting
(CABG) or percutaneous angioplasty is evident by an increase in the LVEF, a decrease in the
ESV, and an improvement in the regional contractile function.
Myocardial Hibernation and Assessment of Tissue Viability
Over the past two decades it has become clear that chronic left ventricular (LV) dysfunction is not
necessarily an irreversible process. In some patients, recovery of function may occur dependent
on the presence of dyssynergic yet viable myocardium. Detection of myocardial viability has now
become an important aspect in the diagnostic workup of patients with chronic LV dysfunction.
However, these patients may ultimately benefit the most from revascularization. Accurate
methods to detect viable myocardium are essential to select those patients in whom these risks are
justified.
Imaging the Acute MI
The purpose of reperfusion therapy in patients with acute MI is to achieve significant myocardial
salvage and to limit the extent of irreversible tissue damage. Salvaged myocardium is defined as
the difference between the initial area at risk and the final infarct size. Even a satisfactory
angiographic result after PTCA does not always imply effective tissue reperfusion with
consequent myocardial salvage. Technetium based perfusion agents such as Sestamibi or
Tetrofosmin can be injected in the emergency room to patients experiencing acute myocardial
infarction. After initiation of reperfusion therapy and stabilization, images can be obtained which
represent the extent of myocardium at risk at the time of infarction. Subsequent images performed
prior to discharge can be compared to the original exam and can assess the degree of myocardial
salvage and viability.
Sensitivity and Specificity
The sensitivity/specificity for SPECT Tc-Sestamibi and Tc-Tetrofosmin in the detection of
coronary artery disease are almost identical to thallium. Sensitivity is about 90 per cent and
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specificity is about 80 per cent. (Please refer also to the section and figures under Stress testing—
courtesy of Dr. S.C. Munsi and Dr. R.D. Lele).
Check Your Progress 4
What are the normal findings on a perfusion study of the heart?
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ERNA has been used as a standard technique for ventricular function measurements for many
years. Despite its accuracy and reproducibility, there has been a decline in this procedure in recent
years, mainly because of the widespread availability of echocardiography in clinical settings.
7.5.2 General Principles
Framing; Heartbeat Variation and Tolerance
In routine practice, acquisition of 24-32 frames per cardiac cycle is considered satisfactory. The
computer determines the length of the cardiac cycle based on the average of multiple R–R
intervals before the acquisition. A range of acceptable beats (“acceptance window”) is specified.
This is known as “tolerance” and is expressed as the per centage of the mean R–R interval.
Quantitation
LV volume is calculated by multiplying the number of pixels within the LV cavity with the size of
a pixel. LV volume can be generated for each of the frames in the cardiac cycle. The largest
volume and the smallest volume represent the end-diastolic volume (EDV) and the end-systolic
volume (ESV), respectively. LVEF is derived from the volumes using the formula (EDV –
ESV)/EDV x 100.
Once the endocardial edge is detected, regional endocardial wall motion (RWM) can be
quantitated by computing the distance of a given point on the endocardial surface between end-
diastole and end-systole.
2.6 PHARMACOLOGICAL STRESS AGENTS FOR
RADIONUCLIDE MYOCARDIAL PERFUSION IMAGING
For patients unable to exercise or in some circumstances where it is undesirable or unsafe,
pharmacological stress is an excellent alternative.
Patients with the following are suitable for pharmacological stress testing:
a) Poor physical conditioning; limiting non-cardiac symptoms (e.g. atigue) Left bundle branch
block (false-positive exercise perfusion scans)
b) Peripheral arterial disease; lung disease Spinal injuries; amputations; or orthopedic problems
(e.g. low back pain)
Pharmacological Stress Agents
There are two classes.
The vasodilators include adenosine and dipyridamole. These increase myocardial perfusion and
lead to a relative reduction in perfusion in territories supplied by obstructed vessels. These
regional variations are not normally associated with ischaemia because they are not accompanied
by an increase in myocardial oxygen demand.
The synthetic catecholamines include dobutamine and arbutamine. These also increase
myocardial perfusion but less than the vasodilators and they also increase myocardial oxygen
demand by increasing cardiac contractility and heart rate. They are therefore, more likely to
provoke ischaemia.
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diagnosis is of major concern because untreated PE is potentially fatal and unnecessary treatment
with anticoagulation has a high degree of morbidity and mortality. There are many imaging
approaches to PE, each with its own strengths and weaknesses. Usually, more than one test is
required to establish a diagnosis. For many years, ventilation-perfusion (V/Q) scintigraphy has
been the main imaging modality for the evaluation of patients with suspected PE. Below is a
description of each test and then a synopsis of possible imaging strategies.
7.7.1 Ventilation/Perfusion (V/Q) Scintigraphy
V/Q scan is the traditional imaging examination following a chest radiograph. The tracer is
99mTc-MAA (macroaggregated albumin), which is injected intravenously. Segmental perfusion
defects denote block in vessels. Following this, a ventilation study is performed using inhalation
of 99mTc-DTPA aerosols. If the segments with perfusion defects show filling up of aerosols, i.e.
‘mismatched defects’ is diagnostic of PE (Fig. 7.6). A negative perfusion scan virtually
eliminates PE. A high-probability ventilation/ perfusion scan, in conjunction with a high clinical
probability, is accurate in diagnosing over 95 per cent of PE.
Fig. 7.6: An example of a high probability ventilation/perfusion lung scan. There are multiple
perfusion defects (arrows) with normal ventilation in these regions
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2) a) Energy of gamma ray, 140keV, is optimal for gamma camera imaging and can
produce higher quality images than Thallium.
b) Technitium has shorter half-life, and hence 10-15 times higher dose than thallium can
be injected, which results in a higher count rate and shorter imaging time.
c) Technetium is easily available via a generator 24 hours a day. Thallium is cyclotron
generated and requires off-site delivery.
Check Your Progress 2
Gamma rays and Gamma Cameras
Check Your Progress 3
Reversible defects demonstrate myocardial ischaemia i.e., defects on the stress images without a
similar defect on the rest images.
Check Your Progress 4
Normal findings on perfusion studies result in almost identical stress/rest images with no defects.
Tracer distribution is uniform in all the walls of left ventricle.
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