Interpreting myocardial perfusion scintigraphy using single-photon emission computed tomography. Part 1

Introduction

Single-photon emission computed tomography (SPECT) is an imaging method that enables, among other things, the evaluation of myocardial perfusion. The source emitting the radiation is the patient, who is administered a radioactive tracer. The name tomography stems from Greek tomos, meaning “section” or “cut”. Isotopic tomographic examination enables the determination of radiotracer accumulation in many sections. After the image is reconstructed, radiotracer activity is evaluated in sections along the short and long axis: the sagittal and frontal section.
The main element of the gamma camera is the scintillator crystal, which, under the influence of gamma radiation, emits photons visible as flashes of light (i.e., scintillations; hence the phrase “single-photon” in the name of the examination). The registered light impulses are multiplied by photomultipliers and converted into electric current of various intensity. In this manner, the radiotracer’s activity in the examined organ is visualized as a projection on a plane. The gamma camera, turning around the patient’s chest and imaging the isotope’s activity in many angular projections, enables the reconstruction of the 3D geometry of isotope activity within the heart.
A SPECT-CT device is additionally equipped with a tomograph integrated with the gamma camera. CT enables reconstruction with attenuation correction, facilitating the elimination of false perfusion deficits resulting from the attenuation of emission by extracardiac tissues. This type of examination involves both transmission and emission as it consists in both a tomographic examination (exposition to X-ray radiation) and a second, main tomographic examination, superimposed over the first one, for imaging left ventricular perfusion (emission scintigraphy).
The imaging of cardiac perfusion involves the use of radiopharmaceuticals; their uptake by muscle cells is directly proportional to blood flow. The most frequently used radioactive tracer is methoxy-isobutyl-isonitrile (MIBI) labeled with technetium 99m (99mTc-MIBI). Other radiotracers include tetrofosmin or thallium (201Tl). The latter, hardly used in Poland, differs from the compounds labeled with technetium in that it undergoes redistribution in the myocardium. A one-time administration of 201Tl at peak stress enables the performance of a one-day examination that will visualize radiotracer uptake during stress as well as rest because the radiotracer is redistributed after a while. However, the use of 201Tl is not widespread for two main reasons. Firstly, it is obtained with the use of a cyclotron; secondly, its long half-life requires the use of appropriately smaller activities, which in turn translates into worse image quality. Some laboratories use mixed protocols using both 201Tl and 99mTc [1]. Notwithstanding, most current perfusion investigations are performed with the use of non-redistributable compounds labeled with 99mTc. At the Silesian Center for Heart Diseases, the only radiopharmaceutical used for myocardial perfusion imaging is 99mTc-MIBI, and the most frequently employed acquisition protocol is the two-day protocol.
Figure 1 presents the 2-day and the one-day protocol using radiopharmaceuticals labeled with 99mTc. In low-risk patients, a stress SPECT-CT examination with attenuation correction is performed first to exclude coronary artery disease. If the stress examination shows normal perfusion and muscle contractility, no additional resting examination is required, which significantly reduces the patient’s exposition to radiation. In the remaining cases, the radiopharmaceutical must be administered twice.

Indications for the examination

The evaluation of cardiac perfusion using SPECT should be recommended to patients with an intermediate risk of coronary artery disease when other examinations evaluating the coronary reserve (such as electrocardiographic exercise testing or dobutamine stress echocardiography) yield ambiguous results. The examination can also be performed in patients with high indices of coronary artery calcification (CAC) revealed by CT in whom angio-CT with contrast was abandoned, patients in whom the evaluation of ostial lesions (especially in bifurcations) or coronary stents yields uncertain results, as well as in patients with borderline changes in order to assess their hemodynamic significance [2].
It should be noted that even in the case of patients with high CAC indices, the isotopic examination often does not reveal any significant perfusion disturbances; therefore, conducting invasive diagnostics in such cases is inexpedient. Performing perfusion scintigraphy in patients with high calcium scores can contribute to a significant reduction in the number of conventional coronary angiographies not ending with revascularization.
Another indication for performing a stress perfusion examination is myocardial bridging revealed by coronary angiography or angio-CT. In this case, the goal of the isotopic examination is to determine whether the systolic constriction of the vessel has any influence on left ventricular perfusion. In many cases, it turns out that the myocardial bridge does not cause ischemia [3].
Other uses for resting perfusion scintigraphy include the evaluation of myocardial vitality before revascularization procedures and differentiating ischemic cardiac injuries from injuries resulting from other causes. In these cases, a resting examination is sufficient.
Comparing the indications for perfusion scintigraphy and angio-CT examinations of the coronary arteries, it should be noted that, in contrast to tomography (which requires the administration of an iodic contrast agent), perfusion scintigraphy is not contraindicated in the presence of kidney failure.
In patients with steady heart rhythm, the count registration from the myocardial area is conducted synchronously in the individual phases of the cardiac cycle. In this mode of acquisition, the cardiac cycle is usually divided into 8 or 16 equal segments. Using ECG-gating in the examination enables the calculation of parameters that include the left ventricular ejection fraction, diastolic function parameters, as well as regional mobility and thickening of the left ventricular walls (interpreting the results of SPECT examinations using cardiac gating will be discussed in detail in the second part of this article). The option of phase analysis in gated examinations enables the quantitative evaluation of left ventricular systolic dyssynchrony in candidates for cardiac resynchronization therapy (Tab. I) [4].

Evaluation of myocardial perfusion

Depending on the type of myocardial perfusion disturbance, the examination may indicate post-MI scarring (when the resting examination shows reduced radiotracer uptake) or a reversible perfusion deficit (stress ischemia) when the radiotracer’s activity is reduced during the stress examination, but not during the rest examination. In other situations, the examination may reveal post-MI scarring along with surrounding ischemia (resulting, e.g., from insufficient collateral circulation) or the presence of concurrent post-MI scarring (permanent perfusion deficit) in an area supplied by one vessel and ischemia (reversible deficit) in another area.
In each case when a perfusion disturbance is found, its location should be determined in relation to the segments affected by ischemia. For this purpose, it is useful to transform the 3D tomographic image of left ventricular perfusion into a polar map (Fig. 2). It is created as a result of imaging the distribution of radiotracer activity in two dimensions (Fig. 3). The model established by the American Heart Association (AHA) divides the polar map into 17 segments. The outermost segments correspond to the basal segments, and segment 17 represents the cardiac apex (Fig. 4).
Computer software for the quantitative assessment of perfusion disturbances enables the comparison of the scintigraphic images obtained from the patient with a database containing averaged data from healthy individuals. The perfusion deficit on the polar map is evaluated with regard to its extent (Fig. 5). For this purpose, all areas on the polar map that contain values below the assumed threshold are blackened (blackout polar map). The extent of the deficit is calculated in relation to the surface of the middle layer, omitting the valve output in the left ventricular outflow tract, and is expressed in cm² or percentages. The second parameter describing perfusion deficit is the severity of radiotracer uptake reduction in relation to standard deviation (Fig. 6). In turn, the parameters that pertain to both the extent and severity of perfusion deficits are the segmental myocardial perfusion score (five-point scale; Tab. II) and the Total Perfusion Deficit (TPD) described below [5, 6].

Scoring left ventricular myocardial perfusion during rest and stress using 17 segments

Computer software for the semiquantitative evaluation of left ventricular perfusion is used to calculate the perfusion score considering both the extent and severity of ischemia in relation to the 17 segments of the polar map (Figs. 5 and 6). Normal perfusion (as compared with averaged gender-specific data from the population of healthy individuals) is indicated on the scale as a score of 0 (normal perfusion in relation to the control group). Mild and moderate perfusion impairment is indicated by 1 and 2 points, respectively. A score of 3 points indicates significant perfusion impairment, while a score of 4 points is used to indicate total impairment, meaning practically no perfusion (Tab. II).
An example of scoring perfusion using the 17-segment model of the left ventricle is presented on Figure 7. It is estimated that a left ventricular perfusion deficit with a score of 1 or 2 indicates that isotopic activity in this segment is approximately 60% in comparison to the area of radiotracer accumulation specified as 100%. Three points indicate radiotracer activity between 40% and 60%, while 4 points indicate radiotracer activity below 40% in relation to the area with 100% activity. Scoring perfusion disturbances in resting examinations is also useful for evaluating myocardial vitality.
The global scoring of myocardial perfusion uses measures such as: the Summed Stress Score (SSS), the Summed Rest Score (SRS), and the Summed Difference Score (SDS). The SSS is the sum of the individual scores from the 17 segments of the polar map obtained during stress. When the SSS amounts to less than 4, the perfusion is considered normal or minimally abnormal (no significant perfusion disturbances); a result of 4–8 points indicates mildly abnormal perfusion; 9–13 – moderately abnormal perfusion; and 13 or more – the presence of significant extensive ischemia (Tab. III).
With regard to the number of segments with abnormal perfusion, the ischemic area is described as small when it involves 1 or 2 segments, moderate when it involves 3 or 4 segments, or large when it involves 5 or more segments.

SDS – the difference between the SSS and the SRS

SDS can be calculated by subtracting the SRS from the SSS (SDS = SSS – SRS). This measure is used to describe the degree to which the deficit/ischemia is reversible. An SDS score of 0–1 indicates no ischemia; 2–4 points indicate mild ischemia; 5–6 points indicate moderate ischemia; while 7 or more points indicate severe ischemia, i.e., significant stress perfusion deficit (Tab. III).

Percentage measures of left ventricular perfusion (SS%, SR%, and SD%)

The fact that the polar map used to be divided into 20 segments, while the currently recommended division includes 17 segments, necessitated the introduction of normalized SSS, SRS, and SDS measures, i.e., respectively, SS%, SR%, and SD%. SS% is calculated by dividing the SSS by a number corresponding to the SSS value indicating a deficit of 4 in every segment (80 points for 20 segments or 68 points for 17 segments) and then multiplying the result by 100%. For example, when using the 17-segment division, the SS% for a SSS of 13 amounts to 19% (13 : 68  100%). SS% values up to 4% indicate normal perfusion; 5–9% – mild abnormality; 10–14% – moderate abnormality; 14% or more – significant abnormality (Tab. III). The SR% and SD% values are calculated in the same manner. Patients with SD% exceeding 10% are believed to benefit from revascularization regardless of their left ventricular ejection fraction [7]. In turn, optimal pharmacological therapy accompanied by changes in lifestyle is preferred in patients with SD% smaller than 10% [8, 9].

Total perfusion deficit

Total perfusion deficit (TPD) is calculated based on both the extent and severity of ischemia. As shown in Figure 8, the area below the lower margin of the normal values of the activity profile, but above the curve of the circular activity profile for a given slice shows the perfusion deficit for this slice [10]. The individual TPD values are calculated for all circular activity profiles of the myocardium and are added together as the total deficit of perfusion. The TPD is equivalent with the polar map’s segmental perfusion score, but it differs in that it is a constant value that does not pertain to the individual segments. The established normal values of TPD fall below 5%; TPD of 5–9% indicates slight abnormality; 10–14% – moderate abnormality; and 15% or more – significant abnormality (Tab. III).

Transient left ventricular dilatation and right ventricular radiotracer uptake

During the evaluation of perfusion results, one should consider transient ischemic dilatation of the left ventricle, a phenomenon that occurs in the course of multivessel coronary artery disease with balanced and generalized subendocardial ischemia affecting all walls of the left ventricle. Its occurrence should be treated as a positive result and an indication for conventional coronary angiography even in the absence of significant perfusion deficits.
Another abnormality that should be considered is the accumulation of the radiotracer in the right ventricle. Normally, the right ventricle is almost invisible in a scintigraphic examination; increased radiotracer uptake indicates right ventricular hypertrophy.

Assessing the risk of myocardial infarction or death due to cardiac causes based on the perfusion score

The presence and intensity of stress ischemia determines the management. If significant stress ischemia is revealed, the patient should be referred for conventional coronary angiography with revascularization in mind (SD% > 10). If the ischemic area after exercise is sufficiently small, conservative treatment is a reasonable alternative [8, 9].
In the context of the 17-segment model of the left ventricle, when the SSS falls between 0 and 3 (normal/minimally abnormal result), the risk of myocardial infarction or cardiac death is minimal; when the SSS falls between 4 and 7 (slightly abnormal result), the risk is low; when the SSS is between 8 and 12, the risk is considered intermediate; and when the SSS exceeds 12 points, the risk is high [11]. Other authors, using the 20-slice model of the left ventricular polar map, assess the risk as low for SSS values between 4 and 8, intermediate for SSS values between 9–13, and high for SSS values exceeding 13 [12]. A meta-analysis encompassing over 12,000 patients demonstrated that the risk of myocardial infarction or death amounted to 0.6% for patients with normal stress scintigraphy results and 7.4% for patients with abnormal results [13]. In another study, the annualized mortality rate in a group of 473 patients with normal results of stress cardiac SPECT examinations using Tc-99m-MIBI was only 0.2% over 3 years [14].

Conclusions

The proper interpretation of cardiac perfusion scintigraphy using the SPECT method not only enables the diagnosis of significant stress ischemia, but also provides valuable prognostic information determining the choice of treatment (optimal pharmacological therapy vs. invasive treatment) to be provided to patients, including those with borderline changes revealed by angio-CT or with high indices of coronary artery calcification.

Disclosure

Authors report no conflict of interest.

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