Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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highly accurate and reproducible technique, capable of assessing left and right

ventricular function even if infarction, hypertrophy or dilation has distorted the

shape of the ventricle. Assessment of right ventricular function, however, may

not be as accurate as with the first pass radionuclide angiography method.

This imaging modality makes use of an intravenously injected radionu-

clide that remains in the cardiac chambers in a concentration directly propor-

tional to the blood volume. Data are collected from several hundred cardiac

cycles to create an image of the beating heart, presented as a single cardiac

cycle. It can be used to assess global and regional wall motion, chamber size

and morphology, and ventricular function including ejection fraction. Acquisi

tions are made at rest or during exercise, or under pharmacological, isometric

mechanical, cold-pressor or mental stress. The procedure is also known as

gated cardiac blood pool imaging, multigated acquisition (MUGA) or radionu

clide ventriculography (RVG). ERNA studies are superior in counting statistics

to FPRNA studies, but are affected by arrhythmia.

5.2.3.2. Clinical indications

(a) Coronary artery disease

ERNA is an excellent test for the assessment of regional and global

ventricular dysfunction by detecting changes in regional wall motion, end-

systolic volume, ejection fraction and diastolic filling, making it useful in the

diagnosis of coronary artery disease and myocardial infarction. It is also used to

monitor therapeutic response and for long term follow-up.

(b) Congestive heart failure

Patients may undergo ERNA to distinguish ischaemic from non-

ischaemic, as well as systolic from diastolic, causes of congestive heart failure.

Changes in ventricular stroke volumes can be used to detect and quantify

valvular regurgitation. Periodic monitoring of cardiac function helps in the

determination of the optimal timing for valvular surgery.

(d) Doxorubicin cardiotoxicity

Serial studies evaluate the cardiac function of patients receiving chemo-

therapy to determine if therapy should be discontinued or possibly reinstituted.

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(e) Other indications

ERNA may be helpful in cardiomyopathy, asymmetrical septal

hypertrophy and chronic obstructive pulmonary disease (COPD).

(f) Contraindications

The following conditions are contraindications for ERNA:

—Severe arrhythmia;

—Uncontrolled unstable angina;

—Decompensated congestive heart failure;

—Uncontrolled hypertension (blood pressure more than 200/120 mm Hg);

—Acute myocardial infarction of less than two days evolution.

Stress testing should be avoided in cases of particular contraindications

for exercise, pharmacological procedures or other forms of cardiac challenge.

5.2.3.3. Radiopharmaceuticals

Technetium-99m is the only radionuclide that has been used for ERNA

studies. Historically,

99m

Tc human serum albumin was the agent of choice for

ERNA, but image quality was poor due to albumin trapping in the pulmonary

arterial tree. This was then replaced by

99m

Tc labelled red blood cells (RBCs),

which have a more favourable target-to-background ratio than albumin.

Activities are given in Table 5.5.

Labelling of RBCs requires reduction of technetium by stannous ions.

The reduced form binds to the globin chain of the haemoglobin molecule. The

optimal dose of stannous ions will maximize the amount of technetium bound

inside the cell and limit the proportion of circulating free pertechnetate that

would be taken up by the thyroid, kidneys and gastric mucosa. Three labelling

procedures can be used (Table 5.6):

in vivo, in vitro and modified in vivo

TABLE 5.5. RECOMMENDED ACTIVITIES FOR Tc-99m AGENTS

Adults Paediatrics

Tc-99m labelled RBCs 555–1100 MBq (15–30 mCi) 8–16 MBq (0.2–0.4 mCi)/kg

Tc-99m albumin 370–740 MBq (10–20 mCi) 4–12 MBq (0.1–0.3 mCi)/kg

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

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(‘in vivtro’). For in vivo labelling, the stannous ions, usually provided as a

pyrophosphate bone kit, are injected first, followed 20 min later by the

99m

pertechnetate dose.

Interference with the RBC labelling may be seen in patients receiving

heparin, which oxidizes stannous ions and reduces the labelling efficiency. With

such patients, human serum albumin may be used instead of RBCs. Dextrose,

mannitol and sorbitol, or the presence of antibodies to the RBCs, as seen in

certain autoimmune diseases or after receiving methyldopa or quinidine, may

also reduce tagging efficiency.

5.2.3.4. Equipment

(a) Cameras

Both large and small FOV cameras may be used for the procedure.

The more frequently used large FOV camera provides diagnostic quality

images. Small FOV cameras provide higher resolution images and are easily

manipulated into the required position. With either type of camera, the

detector must be positioned as close as possible to the patient’s chest during

acquisition. Multicrystal cameras are not recommended due to their lower

spatial resolution. An ECG gating device should be interfaced with the

camera.

TABLE 5.6. COMPARISON OF RBC LABELLING PROCEDURES

Procedure

Labelling efficiency

(%)

Advantages Disadvantages

In vivo 75–85 Easy to perform

Low exposure of

personnel

Low labelling efficiency

In vitro >95 Highest labelling

efficiency

More complex

Time consuming

In vivtro 90–93 Better labelling than

in vivo

Lower labelling efficiency

than in vitro

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(b) Collimator

A standard parallel hole, low energy, all-purpose collimator is sufficient

for most ERNA studies. High resolution collimators improve image quality but

require longer imaging times.

Current nuclear imaging computers are capable of acquiring ERNA data.

The software should be capable of handling 64

¥ 64 and 128 ¥ 128 acquisitions

at rates of 8–32 frames per cycle in frame and list mode, contain temporal,

spatial and Fourier filters, and allow for manual, automatic and semi-automatic

approaches.

5.2.3.5. Patient preparation

Resting ERNA studies require no special preparation. For exercise

studies, 3–4 h fasting prior to the procedure is recommended, and the patient

should be haemodynamically and clinically stable. Pharmacological stress is

recommended for patients unable to exercise. Cardiac medication, particularly

that affecting heart rate, should be withheld unless contraindicated by the

patient’s medical condition or if there is interest in testing the efficacy of the

drug.

5.2.3.6. Procedure

(a) Positioning

The patient should lie down comfortably to prevent movement during the

procedure. Three standard projections — left anterior oblique (LAO), anterior

and left lateral views — are acquired for 10–15 min each. The best septal view

is taken with the detector in a 40–50

LAO position. Some argue that this is the

only necessary view for ERNA studies since most referring physicians request

a study primarily to obtain an accurate LVEF value. The other views (details of

which are given in Table 5.7) should be obtained depending on the cardiac

structures being studied.

(b) Acquisition parameters

An adequate study contains 250 000–500 000 counts per frame, acquired

in approximately 5 min from 300–400 heartbeats. The data collected over the

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multiple cycles are synchronized or ‘gated’ with the patient’s R wave on an

ECG. This circumvents the problem of images becoming blurred by cardiac

motion. The standard method for gating is the forward gating technique, where

the ECG signal is used to identify the beginning of the acquisition. Another

method is reverse gating, where the last frame ends on the R wave instead of

the first frame being assigned to the R wave. Early systolic data are more

accurate with forward gating, while end-diastolic data are preserved with

reverse gating.

All commercially available systems exclude premature beats from the

data by setting an RR interval acceptance window around the average,

typically 10–15%, depending on the patient’s rhythm. A narrow window means

more homogeneous beats, making the study more accurate but with a

prolonged acquisition time if some arrhythmia is present. Increasing the

window will reduce the acquisition time at the expense of the diastolic portion

of the time–activity curve.

Frame mode is the typical acquisition method but list mode is the more

memory demanding one. List mode is particularly appropriate for studies of

diastolic function and is more flexible in adjusting the beat length window,

TABLE 5.7. IMAGING PROJECTIONS FOR ERNA (MUGA) STUDIES

View Structures seen

Left anterior oblique Right and left ventricles, clearly separated

Left circumflex artery territory

Left atrium

Anterior Right atrium

Right ventricle (inferior and apical aspects)

Left ventricle (anterolateral wall and apex)

Pulmonary artery

Ascending aorta

Left lateral Long axis of the left ventricle

Posterobasal segment of the left ventricle

Right ventricular outflow tract

Pulmonary artery

Left atrium

Descending aorta

Right anterior oblique Right ventricle

Superior vena cava

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which can be manipulated until the correct combination of width and

acceptable number of beats is reached.

The number of frames depends on the clinical problem, software capabil-

ities and acquisition time available. A higher number of frames improves the

temporal resolution, making the image more representative of the variations in

chamber volume. Sixteen frames per cycle are enough to assess the systolic

phase, while 32–48 frames per cycle are ideal in studying the diastolic phase but

longer acquisition times are required to achieve good frame statistics.

Treadmill exercise is inappropriate for ERNA because of chest motion.

Bicycle exercise is preferred and can be performed in both the upright and

supine positions: both place similar overall stress on the heart at any given

workload. Exercise in the supine position, however, places more strain on the

legs and may cause patients, particularly the older or those out of condition, to

stop exercising before an adequate cardiovascular stress is reached. Exercise in

the upright position is usually better tolerated.

A resting ERNA is usually performed first and in the same position that

will be used in the exercise study so that any changes reflect true cardiac

conditions rather than positional changes. Sufficient time should be allowed at

each workload for the heart rate to stabilize and for enough image statistics to

be acquired for reliable quantification. The period of peak exercise should be

of sufficient length for superior image quality. However, prolonging the

exercise by reducing the workload may lead to an immediate improvement of

the ventricular function and to an underestimation of an eventual ischaemic

reponse. An optional post-exercise image may be valuable in predicting

functional recovery after revascularization in segments with severe wall motion

abnormalities at rest.

Alternatives for patients unable to exercise include atrial pacing, cold

pressor testing, catecholamine infusion and coronary vasodilators such as

dipyridamole or adenosine.

(d) Data processing

Processing begins with a review on a cinematic display to evaluate the

adequacy of the counting statistics, ECG gating, RBC labelling and positioning

of the heart. Visual assessment of left ventricular systolic function is done

before calculation of LVEF. The whole activity from the left ventricle must be

encompassed by the ROI, drawn either manually or automatically. Discrep

ancies between the calculated LVEF and the visual assessment of left

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ventricular systolic function may reflect an error in data processing or edge

positioning.

It is recommended that the entire cycle be reviewed to obtain optimal

information. Fourier transform analysis of the data and the first and third

harmonics are used to filter the images and curve, to obtain functional

parametric images such as those of phase or amplitude, or fit ventricular

volume curves in order to determine systolic and diastolic function.

The peak left ventricular filling rate is often a useful parameter to detect

early dysfunction. The various processing parameters are listed in Table 5.8.

5.2.3.7. Interpretation

Step-by-step interpretation starts with the assessment of image quality,

particularly the target-to-background ratio, ECG gating and views obtained.

Next, the morphology, orientation and sizes of the cardiac chambers and great

vessels are evaluated and reported. Global left ventricular function is assessed

qualitatively, followed by a segmental analysis of regional function using a

cinematic display. Contraction abnormalities are reported as hypokinesia,

akinesia and dyskinesia. Resting and stress images are displayed side by side to

assess changes in chamber size, wall motion and ejection fraction. Quantitative

measurements of ventricular systolic and diastolic functions are made. Findings

of ERNA studies have been shown to be reliable and reproducible, with an

important influence on patient management.

For patients with coronary artery disease, wall motion abnormalities can

develop on exercise, with a fall in ejection fraction. With myocardial infarction,

there are regional wall motion abnormalities or ventricular dilatation and a

reduced LVEF. Distortion of the left ventricular contour and paradoxical wall

motion, usually in the anterior or anteroapical myocardium, are characteristic

findings of ventricular aneurysm. In patients under chemotherapy, a decrease

in LVEF by 10 units or more indicates cardiotoxicity. In cardiomyopathies,

there are diffuse wall motion abnormalities and a dilated left ventricle with

decreased LVEF. When left ventricular hypertrophy is present, a photopenic

area surrounding the left ventricle may be seen on the LAO view. If asymmet

rical septal hypertrophy exists, there is usually a small left ventricle with a

thickened septum and increased LVEF.

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BIBLIOGRAPHY TO SECTION 5.2.3

DEPUEY, E.G., et al., Nonperfusion applications in nuclear cardiology: Report of a

task force of the American Society of Nuclear Cardiology, J. Nucl. Cardiol. 5 (1998) 218–

231.

GARCIA, E.V. (Ed.), Imaging guidelines for nuclear cardiology procedures (Part 1),

J. Nucl. Cardiol. 3 (1996) 999.

GERSON, M.C. (Ed.), Cardiac Nuclear Medicine, 3rd edn, McGraw-Hill, New York

(1997).

PORT, S.C., WACKERS, F.J.T.H., Clinical application of radionuclide angiography, J.

Nucl. Cardiol. 2 (1995) 551.

ROZANSKI, A., BERMAN, D., GRAY, R., DIAMOND, G., Preoperative prediction

of reversible myocardial synergy by postexercise radionuclide ventriculography, New

England J. Med. 307 (1982) 212.

TABLE 5.8. PROCESSING PARAMETERS

Parameter Method

volume curve generation Obtained from a single ROI drawn at the ED

or using

multiple ROIs at each time point.

Background ROI 5–10 mm away from the ED border, with atrial,

splenic, descending aortic and LV counts excluded, time–

activity curve from background ROI should be flat.

LV EF Calculated from a Fourier filtered curve, or apply an ED

ROI to the ED image, an ES

ROI to the ES image, or

computed from LV counts from a single ED ROI.

Wall motion Visual assessment of cinematic display or analysis of

phase and amplitude images.

LV filling Measurement of the peak slope of the diastolic portion of

the LV curve.

LV emptying Measurement of the slope of a line connecting the ED

and ES time points.

LV vo lumes Calculated using count based or geometrical methods.

LV, left ventricle.

ED, end diastole.

ES, end systole.

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WITTRY, M.D., JUNI, J.E., ROYAL, R.D., HELLER, G.V., PORT, S.C., Procedure

guideline for gated equilibrium radionuclide ventriculography, Procedure Guidelines

Manual, Society of Nuclear Medicine, Reston, VA (1997).

5.2.4. Myocardial perfusion single photon emission tomography

5.2.4.1. Principle

Myocardial perfusion scintigraphy uses perfusion radiotracers that are

distributed in the myocardium (primarily the left ventricle) in proportion to

coronary blood flow. Areas of normal flow exhibit a relatively high level of

tracer uptake, while ischaemic regions present a relatively low uptake.

Regional coronary blood flow may be compared in conditions of rest, stress or

pharmacologically induced vasodilation. Thus, the coronary flow reserve can

be assessed, which is usually affected by significant coronary artery disease

(CAD).

Myocardial perfusion tracers are not taken up by an infarcted

myocardium. In addition to evaluating relative regional blood flow these

tracers are, therefore, also markers of myocardial viability. Myocardial

perfusion scintigraphy may be performed using either single photon or positron

emitting radionuclides. Among the commonly used single photon emitting

perfusion tracers are

201

Tl and the various

99m

Tc labelled perfusion tracers (e.g.

sestamibi and tetrofosmin). While having different physical and pharmaco

kinetic properties, these tracers have considerably overlapping clinical uses and

will therefore be considered in parallel in this section.

5.2.4.2. Clinical indications

The clinical indications for myocardial perfusion tomography are

summarized in Table 5.9.

(a) Detection of myocardial ischaemia and myocardium at risk

Myocardial perfusion imaging is a sensitive means to determine the

presence, location and extent of myocardial ischaemia. The presence of

extensive ischaemia or myocardium at risk indicates the need for more invasive

work-up, such as coronary angiography. Conversely, the absence of significant

ischaemia or myocardium at risk generally rules out the need for intervention.

Myocardial perfusion imaging can be performed in various settings: in

patients with suspected coronary artery disease, after myocardial infarction or

for the assessment of therapy.

5.2. NUCLEAR CARDIOLOGY

189

Myocardial perfusion imaging can also be used to evaluate the patho-

logical significance of coronary lesions already detected by angiography.

Angiographic coronary artery disease with a normal stress myocardial

perfusion scan has little prognostic significance according to accumulated data.

(b) Risk stratification and prognostication

Myocardial perfusion imaging has the ability to distinguish patients at

high risk of cardiac events from those at low risk. This helps clinicians to

determine which patients to manage aggressively with invasive procedures and

which ones to manage conservatively.

As with detecting myocardium at risk, stratification using mycardial

perfusion imaging can be done in various settings: in patients with suspected

coronary artery disease, after myocardial infarction as well as before non-

cardiac surgery (to determine the risk of perioperative cardiac events).

TABLE 5.9. CLINICAL INDICATIONS FOR MYOCARDIAL PERFUSION

IMAGING

Information Clinical settings

Detection of myocardial ischaemia and

myocardium at risk

Intermediate pre-test probability of

coronary artery disease,

post-myocardial infarction,

assessment of medical or operative therapy

Risk stratification and prognostication Suspected coronary artery disease,

post-myocardial infarction,

pre-operative cardiac risk assessment

Detection of stunned myocardium Post-myocardial infarction, post-

revascularization, post-stress testing

Significance of borderline angiographic

studies

Consideration for revascularization

procedures (PTCA

, CABG

)

Detection of hibernating myocardium Left ventricular dysfunction,

dilated cardiomyopathy of possible

ischaemic aetiology

Assessment of ventricular function

(ECG-gated SPECT study)

Ischaemic heart disease,

cardiomyopathy

PTCA, percutaneous transluminal coronary angioplasty.

CABG, coronary artery bypass graft.