Nuclear Medicine Imaging

A. Bockisch, K. Sattler, and S. J. Rosenbaum-Krumme

Basic Principles

Nuclear medicine has several applications in cardiac diagnosis, the most common being the assessment of left ventricular perfusion and myocardial viability. Imaging is generally performed with SPECT-capable gamma cameras (SPECT = single-photon emission computed tomography) or a positron emission tomography (PET) scanner. PET is the superior technique because of its better image quality and higher spatial resolution. While image quality and resolution are of less importance in the assessment of perfusion and viability, they have considerable importance in the evaluation of circumscribed anatomical structures, as in plaque imaging, for example. SPECT and PET use different types of radiotracer for imaging: gamma emitters and positron emitters, respectively. Different tracers have different kinetics and image more or less different physiological processes. Today there are more SPECT-capable gamma cameras than PET scanners available for patient care.

All nuclear medicine imaging is concerned primarily with the left ventricle. The right ventricle has a considerably smaller muscle mass with less perfusion and less energy consumption than the left ventricle, which makes it less accessible to scintigraphic investigation.

Myocardial Scintigraphy

Examination Technique

Myocardial scintigraphy is a noninvasive study which provides information on myocardial perfusion and myocardial viability.

Myocardial scanning is performed at rest and under stress conditions. The exact scan protocol depends on the type of radiotracer used (see p. 69, Table 4.2). It should be emphasized that nuclear medicine imaging evaluates function. Accordingly, the results of myocardial scintigraphy vary depending on diet, medication, physical conditioning, and so on. Optimum nuclear medicine testing for the presence and severity of coronary heart disease requires maximum age-appropriate stress conditions and the avoidance of negative chronotropic or antianginal medications (β-blockers, nitrates). On the other hand, scintigraphy can be used during medical therapy to determine the effect of the medication on myocardial perfusion. Ergometric stress is preferred in all patients who can tolerate exercise. Pharmacological stress can be used in patients who are uncooperative or cannot perform an ergometric protocol for noncardiac reasons (e. g., arthritis, amputation, neurological disease). Pharmacological stress can be induced with agents that cause coronary hyperemia (adenosine, dipyridamole) or agents that increase myocardial contractility (dobutamine).

Essential Point

To detect ischemia with high sensitivity, negative chronotropic and anti-anginal medications (β-blockers, nitrates) should be discontinued before testing. Exercise to maximum tolerance is encouraged.

SPECT technique is recommended for all nuclear medicine stress testing. Multihead gamma cameras should be used to improve the count statistics. Because of the eccentric location of the heart in the body, it is advantageous to position the gamma cameras at right angles (90° configuration) rather than opposite each other (180° configuration). Special “cardiac SPECT gamma cameras” are not widely available, and their costs are justified only at a sufficiently high level of usage.

In the simplest acceptable form of myocardial SPECT imaging, standard planes of section are calculated along the long, short, and transverse axes of the left ventricle. The results are displayed in a “bull’s-eye” format, in which the left ventricle is depicted as a series of apical to basal segments arranged in a circular pattern. The segments are numbered according to the 17-segment model of the left ventricle described by the American Heart Association.¹

These images routinely contain attenuation artifacts because the emitted photons are scattered or absorbed depending on the path length within the body. Photon attenuation in obese patients may cause apparent areas of decreased tracer uptake in the posterior heart wall, and in large-breasted women it can mimic decreased uptake in the anterolateral heart wall. These effects should not be misinterpreted as a perfusion defect (Table 4.1). Attenuation correction is a technique enabling the measurement of soft-tissue attenuation with the aid of an external source.² Attenuation correction thus requires an additional transmission scan with an external radiation source. The transmission and emission images—the actual SPECT images—are then used to compute attenuation-corrected scans. Attenuation correction improves the image quality and diagnostic accuracy of myocardial scintigraphy. The superiority of attenuation-corrected scans over uncorrected scans has been documented in several clinical studies and does not depend on the body mass index of the individual patient.³

ECG gating increases the logistic efforts of myocardial SPECT. In addition, it enables the evaluation of left ventricular function. In this technique, special software-based algorithms are used to define the wall contours of the myocardium. Ventricular volume is determined in each of the cardiac phases and is used to calculate the left ventricular ejection fraction. Wall motion and wall thickening can also be visualized. It has been shown that adding functional data to the perfusion data facilitates both the identification of patients with multivessel CHD, and assessment of the severity of ischemia due to persistent LV dysfunction in poststress images. It further allows an assessment for the prediction of cardiac events.4 ECG-gated data can also help narrow the differential diagnosis in cases where an attenuation artifact cannot be excluded. For example, when a wall-motion abnormality is detected in a wall segment with equivocal perfusion findings, it can be assumed that the segment is ischemic.

On the whole, gated SPECT images are more cost intensive in terms of quality control. It should also be noted that, with regard to technical aspects, myocardial SPECT image quality depends significantly on the count statistics in the image, i. e., on the administered activity and length of the examination. Neither of these values can be arbitrarily increased, setting limits on what can be accomplished with the technical improvements described above.

Essential Point

Whenever possible, gated SPECT with attenuation correction should be used in myocardial scintigraphy.

Tracers

Various radiotracers are available for myocardial scintigraphy, all of which have one property in common: within the range of physiological flow, all radiotracers are extracted from the blood in proportion to blood flow and become concentrated in myocardial cells. Because of their different kinetics, the tracers available for myocardial scintigraphy also require different imaging strategies.

Thallium Chloride

Thallium chloride Tl²⁰¹ (TlCl) is extracted by myocardial cells in proportion to blood flow. It is distinguished from other tracers by its high extraction in low-flow conditions, and has the longest range of linear uptake even under high-flow conditions. As a result, TlCl permits the most sensitive viability assessment of chronically ischemic myocardium and defines the extent of perfusion abnormalities most accurately.

Nevertheless, thallium 201 is an unfavorable nuclide for perfusion scanning, both in terms of the half-life and energy of the emitted photons. The relatively high radiation exposure (Table 4.2) limits the activity that can be applied and results in a “noisy” image. Thus, the interpretation of TlCl perfusion scans requires considerable experience and a well-defined image processing routine to avoid inaccurate findings due to image artifacts. Another problem with thallium chloride is that the low applicable activity of this tracer greatly limits its suitability for gated SPECT imaging.

TlCl is actively transported into cells by the Na⁺−K+ pump mechanism and leaves the cells very slowly by passive diffusion. This redistribution or “washout” of the agent is advantageous in that approximately similar stress-induced perfusion changes are detected globally in all myocardial segments. TlCl is injected intravenously approximately 1 minute before the end of exercise. Stress imaging begins immediately after the end of exercise, and the redistribution scan is obtained 3–4 hours later. Redistribution of the activity eliminates the need for an additional tracer injection (Fig. 4.1). Because the ischemic myocardium has not always recovered by 3 hours postinjection, it may be necessary to obtain a rest scan approximately 24 hours after application to differentiate ischemia from a fixed thallium defect present in both the stress and redistribution scans.

Sestamibi

Sestamibi is labeled with the metastable isotope technetium 99 m (Tc⁹⁹), which makes it ideal for radionuclide imaging. With a gamma emission of 140 keV and physical half-life of 6 hours, it causes only moderate radiation exposure. Despite the markedly lower radiation exposure compared with TlCl, the images are sharper and have good count statistics. Sestamibi (synonym for MIBI) can also be used in conjunction with gated SPECT imaging to obtain additional ventriculographic data.

Sestamibi has a flow-proportional uptake in myocardial cells and is concentrated in the mitochondria. In a typical examination, and even for several hours, redistribution does not occur. Two injections are therefore necessary, one for rest and one for stress imaging.

The two tests should ideally be done on different days. Since Tc^99m has a half-life of 6 hours, approximately 5% of the original activity is still present in the heart the following day, causing little if any interference with the second test if the rest images are obtained first. However, in view of the fact that a two-day examination would delay diagnosis and increase logistical costs, a one-day protocol has become standard. In this case rest scans are obtained first with ~200 MBq of technetium Tc^99m sestamibi, and stress scans are obtained at the earliest 2 hours later with ~600 MBq (Fig. 4.2). Because blood flow is usually at least twice as high during exercise as at rest, the activity from the rest study contributes only up to 5% to the stress study without distorting the results.

Fig. 4.1 Typical protocol for thallium myocardial scintigraphy. A single injection of thallium chloride Tl²⁰¹ is sufficient for stress and rest scans. The nuclide is redistributed after the end of exercise, allowing a rest scan to be obtained after a standard interval of ~3–4 hours.

Tetrofosmin

Tetrofosmin has properties similar to those of sestamibi, but because of its shorter biological half-life in the heart, the time window between injection and imaging is smaller than with sestamibi. Furthermore, tetrofosmin has a better heart/liver ratio owing to its more rapid hepatic clearance. Tetrofosmin, unlike TlCl, is not redistributed because it undergoes rapid chemical transformation to a compound that is no longer extracted by myocardial cells, and therefore two injections are required. All other statements pertaining to sestamibi also apply to tetrofosmin.