Nuclear Cardiology

INVESTIGATIONS
Nuclear cardiology
Andrew D Kelion
Nuclear medicine investigations involve the injection of a radiolabelled tracer (radiopharmaceutical), which is distributed
within the body according to its physiological properties. This
distribution can be imaged using an Anger gamma camera. The
most commonly performed nuclear cardiological investigation is
myocardial perfusion scintigraphy (MPS), which provides physiological information about the coronary circulation.
Myocardial perfusion scintigraphy

Indications
MPS is primarily indicated for the diagnostic and prognostic assessment of patients with suspected coronary disease in whom exercise
ECG is likely to be unreliable. This includes women, those unable
to exercise adequately, and those with a significantly abnormal
Whats new ?
Gated SPECT has become a routine part of myocardial
perfusion scintigraphy, and provides valuable
information about left ventricular function in addition to
perfusion
Attenuation correction is becoming an important aid to
reporting myocardial perfusion scintigraphy
The low risk (<1% per annum) associated with normal
myocardial perfusion scintigraphy applies even to
patients already known to have coronary artery disease,
though the warranty period is shortened
Patients in whom more than 10% of the left
ventricular myocardium is ischaemic on myocardial
perfusion scintigraphy derive prognostic benefit
from revascularization, whilst those with little or no
ischaemia do not
Andrew D Kelion is Consultant Cardiologist at Harefield Hospital,

Harefield, UK. He qualified from the University of Oxford, and trained
in cardiology in London, Reading and Oxford. His research interests
include use of myocardial perfusion scintigraphy in predicting the value
of coronary revascularization. He is currently President of the British
Nuclear Cardiology Society. Conflicts of interest: research grants from
GE Healthcare and Bristol-Myers Squibb, and consulting work for GE
Healthcare.
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INVESTIGATIONS
resting ECG. MPS may help in the management of patients already

known to have coronary disease (e.g. following myocardial infarction (MI), coronary angiography or coronary revascularization).
It may also be used to define the extent of myocardial viability in
patients with ischaemic left ventricular (LV) dysfunction.
Cardiac stress
At rest, myocardial perfusion distal to a flow-limiting coronary
stenosis usually remains normal because of progressive arteriolar
dilatation. During cardiac stress, there is less vasodilator reserve
available, and perfusion is lower than that downstream of an unobstructed vessel. Comparison of myocardial perfusion during cardiac
stress with that at rest is therefore an essential part of MPS.
Dynamic exercise stress (treadmill or bicycle) should be used
when possible. Many patients referred for MPS are unable to
exercise to their target heart rate, and pharmacological methods
are then required. There are two categories of drugs:
vasodilators (dipyridamole or adenosine) the first choice,
unless contraindicated by airways disease or unpaced heart
block
inotropes (dobutamine).
Adenosine causes direct coronary vasodilatation via A2a-receptors.
Dipyridamole acts indirectly, increasing endogenous adenosine by
inhibiting its breakdown and re-uptake. Dobutamine, a synthetic
-agonist, increases myocardial oxygen demand causing secondary
coronary vasodilatation.
Single-photon emission CT (SPECT) using a dedicated cardiac

gamma camera with two small heads fixed at 90. The head of a
gamma camera is essentially a sodium iodide crystal overlying an
array of photomultiplier tubes. When a gamma photon interacts
with the crystal, photons are produced in the visible spectrum
(scintillation); these are detected by the nearest photomultiplier
tube and signalled to a computer. A collimator placed in front of
the crystal allows entry only of photons travelling perpendicularly,
ensuring that the distribution of scintillations within the crystal
reflects the distribution of radionuclide within the patient lying
on the camera table beside it. Gamma cameras are sensitive
instruments, and require meticulous and regular quality control.
Simple planar imaging can be performed, but SPECT is usually
preferred. The heads of the camera rotate around the patient,
and a planar image is acquired at each of a series of steps. The
acquisition is reconstructed to produce a stack of transaxial
tomographic slices, which can be reorientated to display slices in
the standard orthogonal planes of the heart.
Radiopharmaceuticals and protocols

In MPS, a radiopharmaceutical is injected that is delivered to and
taken up by the myocardium in relation to its blood supply. The
agents in common clinical use are thallium-201 and the newer
technetium-99m-based tracers.
201
Tl, given as thallous chloride, is a cyclotron-generated isotope. It enters myocytes down the electrochemical gradient in a
manner similar to potassium. Following injection at peak stress, it
gradually equilibrates between the intracellular and intravascular
compartments, and so immediate imaging is required. Redistribution imaging is performed 4 hours later, to assess perfusion at rest.
For optimal assessment of myocardial viability, 201Tl is sometimes
re-injected at rest.
99m
Tc is produced from a generator and is complexed with an
organic molecule (sestamibi or tetrofosmin). 99mTcsestamibi and
99m
Tctetrofosmin diffuse passively into myocytes, where they bind
to mitochondria. The absence of significant redistribution means
that imaging can be performed conveniently 3060 minutes after
injection, but separate injections are required during stress and at
rest. A 2-day or a 1-day protocol may be used. A nitrate may be
given before the resting injection, to maximize uptake into viable
myocardium.
201
Tl is a superior perfusion tracer physiologically, but 99mTcbased agents have several practical advantages. The images produced are of higher quality, because the photons are of greater
energy, and can be gated to allow assessment of LV function. In
addition, the shorter half-life (6 hours vs 73 hours) reduces the
radiation exposure to the patient (typically 10 mSv vs 18 mSv).
and at rest (Figure 1). Perfusion defects appear as areas of relatively reduced radioactive counts, and may be fixed or reversible (Figure 2).
LV function can be assessed during MPS by gating image
acquisition to the patients ECG. Each RR interval is divided into
a fixed number of frames (typically eight or 16), and the radioactive counts for equivalent frames of consecutive cardiac cycles
are summed. Gated SPECT allows resting regional and global LV
function to be assessed at the same time as perfusion, providing
additional prognostic information and facilitating recognition of
artefacts.
Attenuation correction is available on some cameras, and seeks to
eradicate artefacts introduced into scans by soft tissue (Figure 2). A
transmission acquisition is obtained using a radioactive line source
or X-ray CT, which is used to correct the SPECT acquisition.
Clinical value
For the detection of angiographic coronary stenoses, the sensitivity and normalcy rate (percentage of very low-risk patients who
have a normal study) of MPS are both about 90%. More importantly, MPS provides prognostic information that is independent
Imaging
Single-photon emission CT (SPECT) acquisitions are obtained,
processed and compared following tracer injection during stress
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INVESTIGATIONS
Vertical long axis single-photon emission CT slices from three separate patients, illustrating three different appearances of the
anterior wall
The colour of each pixel corresponds to its count rate relative to that of the pixel with the highest count rate. Stress (left) and rest (right) images
are shown side by side for comparison.
a Fixed anterior perfusion defect. Fixed defects appear on both the stress and rest
images, and suggest previous infarction.
b Reversible anterior perfusion defect. Reversible defects appear on the stress image
only, and suggest a flow-limiting coronary stenosis in the coronary artery supplying a
viable area of myocardium. In practice, perfusion defects are often mixed.
c Anterior soft tissue attenuation. Several common artefacts may give the appearance
of perfusion defects, including anterior attenuation caused by breast tissue in
women, and inferior attenuation caused by the diaphragm in men. Left bundle
branch block can cause septal perfusion defects in the absence of coronary disease.
labelling with 99mTc-pertechnetate. The growth of echocardiography has led to a sharp decline in the number of ERNV studies
performed, but it remains useful when a reproducible technique is
required for serial assessment of LV ejection fraction (e.g. during
chemotherapy).
of clinical, exercise and even angiographic data. A normal study

is associated with an annual rate of cardiac death or non-fatal MI
of about 0.6%.1 This low risk persists for up to 5 years in patients
without known coronary disease, though the period of reassurance
is shorter in those with diabetes or known coronary disease.2 The
risk associated with an abnormal study increases in proportion to
the degree of abnormality. Different MPS indices predict different
aspects of risk: cardiac death is primarily a function of LV ejection
fraction, whereas non-fatal MI is mainly predicted by the extent of
reversible hypoperfusion.3 Only patients with significant reversible
hypoperfusion derive prognostic benefit from revascularization.4
MPS may be valuable in patients with ischaemic LV dysfunction,
to define the extent of hibernating myocardium with a potential to
recover function following revascularization. Hibernating myocardium is viable (near-normal tracer uptake on resting study), but
dysfunctional at rest (hypokinetic or akinetic on gated study) with
exhausted vasodilator reserve (reversibility between the stress and
rest study).
Iodine-123-metaiodobenzylguanidine (MIBG) imaging is sometimes used to assess the prognosis in patients with LV dysfunction.
Reduced uptake is associated with sympathetic denervation and
an adverse prognosis.
REFERENCES
1 Iskander S, Iskandrian A E. Risk assessment using single-photon
emission computed tomographic technetium-99m sestamibi imaging.
J Am Coll Cardiol 1998; 32: 5762.
2 Hachamovitch R, Hayes S, Friedman J D et al. Determinants of risk
and its temporal variation in patients with normal stress myocardial
perfusion scans. What is the warranty period of a normal scan? J Am
Coll Cardiol 2003; 41: 132940.
3 Sharir T, Germano G, Kang X et al. Prediction of myocardial infarction
versus cardiac death by gated myocardial perfusion SPECT: risk
Other nuclear cardiological investigations

Equilibrium radionuclide ventriculography (ERNV) provides
an accurate measure of global LV function following blood-pool
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INVESTIGATIONS
stratification by the amount of stress-induced ischemia and the

poststress ejection fraction. J Nucl Med 2001; 42: 8317.
4 Hachamovitch R, Hayes S W, Friedman J D et al. Comparison of
the short-term survival benefit associated with revascularization
compared with medical therapy in patients with no prior coronary
artery disease undergoing stress myocardial perfusion single photon
emission computed tomography. Circulation 2003; 107: 29006.
FURTHER READING
Anagnostopoulos C, Harbinson M, Kelion A D et al. Procedure guidelines
for radionuclide myocardial perfusion imaging. Heart 2004; 90
(Suppl 1): 110.
(UK procedure guidelines for MPS.)
Anagnostopoulos C, Underwood S R, eds. Myocardial perfusion
scintigraphy: the evidence. Heart 2004; 90 (Suppl. V): v140.
(A series of reviews covering many aspects of MPS in clinical
practice.)
Underwood S R, Anagnostopoulos C, Cerqueira M et al. Myocardial
perfusion scintigraphy: the evidence. Eur J Nucl Med 2004; 31:
26191.
(A review of the clinical evidence underpinning the use of MPS.)
Practice points
MPS provides physiological information, in contrast to the
anatomical information provided by coronary angiography
MPS is indicated for the assessment of patients with
suspected coronary disease in whom exercise ECG is likely to
be unreliable (women, those unable to exercise, those with
abnormal resting ECG); it may also help in the assessment of
some patients with known coronary disease
Normal MPS predicts a low risk of cardiac events (< 1%
per year); abnormal MPS predicts an adverse prognosis in
proportion to the degree of abnormality
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INVESTIGATIONS

Myocardial perfusion scintigraphy

Andrew D Kelion is Consultant Cardiologist at Harefield Hospital,

2006 Elsevier Ltd

resting ECG. MPS may help in the management of patients already

Single-photon emission CT (SPECT) using a dedicated cardiac

Radiopharmaceuticals and protocols

2006 Elsevier Ltd

of clinical, exercise and even angiographic data. A normal study

Other nuclear cardiological investigations

2006 Elsevier Ltd

stratification by the amount of stress-induced ischemia and the

2006 Elsevier Ltd

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