Equilibrium radionuclide angiography 1. Principle

Equilibrium radionuclide angiography (ERNA) is a non-invasive means of quantitatively assessing cardiac function. It has been demonstrated to be a

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.

(c) Valvular heart disease

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 chemo-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, ^99mTc 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 ^99mTc 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

(‘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 ^99mTc 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.

(c) Computer systems

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^o 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

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.

(c) Stress protocols

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

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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