Myocardial imaging with thallium-201: the controversy over its clinical usefulness in ischemic heart disease.

Several uses of thallium myocardial imaging (assessment of questionable stenosis and detection of infarction) provide unique information and are useful adjuncts in the diagnostic workup and treatment of patients with coronary artery disease. Screening studies with thallium to detect the presence or absence of coronary artery disease have generated considerable controversy. Much of this conflict can be resolved by a careful analysis of the purpose of the screening study, the sensitivity and specificity of the imaging test, and the prevalence of disease in the subgroup under study. With the principles outlined, thallium imaging can be used to make patient-care decisions with a reasonable degree of confidence.

Implementation of a digital image superposition algorithm for radionuclide images: an assessment of its accuracy and reproducibility.

An operator-interactive algorithm to achieve superposition of organ images has been used with a dedicated nuclear medicine computer system. Its purpose is to achieve organ registration in 128 X 128 digitized images before a direct numerical comparison of the regional distribution of a deposited radiotracer is performed. The accuracy and reproducibility of the algorithm for myocardial images has been tested by four operators, using a set of 28 image pairs in which the relative position of the heart differed by more than 10 mm for each pair. Comparing their results with the known displacements on two occasions provided an assessment of these two important parameters. The accuracy and reproducibility for superposing myocardial images by this digital technique are found to be well within the spatial resolution (FWHM) of the imaging system of the Tl-201 tracer studied.

Thallium-201 myocardial imaging: a comparison of the redistribution and rest images.

Forty-one patients with chest pain and suspected coronary artery disease underwent thallium-201 myocardial imaging, performed immediately following maximal treadmill exercise, also at "redistribution" 4--5 hr after exercise, and at rest 1 wk later. All had coronary angiography. All images in seven patients without coronary artery disease were normal. Twenty-seven of the 34 (79%) patients with coronary artery disease had new, exercise-induced image defects. The redistribution and rest images were identical in 15/27 (56%) patients (complete redistribution). In 10/27 (37%) patients with exercise-induced defects, some redistribution occurred but defect size on the redistribution image was larger than that on the rest images (incomplete redistribution). In 2/27 (7%) of patients with exercise-induced defects, redistribution was absent. The presence of prior myocardial infarction, regional abnormalities of left-ventricular contraction or the severity of coronary stenoses did not correlate with the presence or absence of redistribution. Overall image quality between the two studies was similar, although image collection times for the redistribution study were prolonged. We conclude that some redistribution (complete or incomplete) occurs in most patients with exercise-induced image defects. When both fixed and reversible perfusion defects are present, defect size was often larger in the redistribution image and may thus overestimate the extent of prior myocardial infarction.

In vivo simulation of thallium-201 myocardial scintigraphy by seven-pinhole emission tomography.

Seven-pinhole emission tomography has been studied under conditions that simulate clinical myocardial imaging with thallium-201, and is compared with planar imaging with a heart phantom. The seven-pinhole technique produces reconstructed images that offer a tomographic presentation of the object but do not quantitatively represent true cross sections of the object's activity distribution. Tomography produces significantly greater image contrast than planar imaging, even when maximal background subtraction is used to enhance the planar images. Two quantitative limitations of seven-pinhole tomography are noted for a simulated 24-g, 1.5-cm-thick complete transmural infarct: (a) the defect's activity concentration is not accurately reconstructed, and (b) it propagates longitudinally into some reconstructed planes that do not contain it. The imaging limitations of seven-pinhole tomography under the conditions studied are shown to be consistent on several camera/computer/software configurations.

Thallium-201 myocardial imaging during coronary vasodilation induced by oral dipyridamole.

Myocardial perfusion imaging of 201TI injected during maximum exercise has been an important diagnostic tool for coronary artery disease. Pharmacologic coronary vasodilation by i.v. infusion of dipyridamole may be used in lieu of exercise stress for purposes of diagnostic perfusion imaging. However, i.v. dipyridamole is not currently available from commercial sources for widespread routine use. Accordingly, this study was carried out in order to determine whether high dose, oral dipyridamole would be useful as a coronary vasodilator for purposes of diagnostic perfusion imaging. Fifty-eight patients undergoing diagnostic coronary arteriography also had myocardial perfusion imaging with 201TI under conditions of rest, maximum exercise stress, and high dose oral dipyridamole. Of those patients who had a defect on exercise thallium images, 75% also had a perfusion defect on thallium images after high dose oral dipyridamole. These results indicate that oral dipyridamole causes sufficient coronary arteriolar vasodilation and increase of coronary flow in nonstenotic arteries to identify perfusion defects comparable to those seen on maximum exercise stress in at least 75% of cases. In 25% of patients with exercise defects, no perfusion defect was seen after oral dipyridamole. Thus, oral dipyridamole is a potent coronary vasodilator, comparable to exercise stress in most cases, but in a minority of patients may not be comparable to exercise stress.

Myocardial imaging with thallium-201: an experimental model for analysis of the true myocardial and background image components.

The true myocardial and background components of a resting thallium-201 myocardial image were determined in an experimental dog model. True background was determined by imaging after the heart had been removed and replaced with a water-filled balloon of equal size and shape. In all studies, the background estimated from the region surrounding the heart exceeded true background activity. Furthermore, the relationship between true myocardial background and that estimated from the pericardiac region was inconsistent. Background estimates based on the activity surrounding the heart were not accurate predictors of true background activity.

Performance characteristics of a commercial ECG gate.

A commercial ECG gate was tested to evaluate its ability to predict accurately the time of end-systole. The predicted times followed the manufacturer's specifications quite well. These times were compared with the actual times of end-systole as determined by computer-derived left-ventricular time-activity curves using Tc-99m-labeled red blood cells. Although there was moderate scatter, the predicted times of end-systole correlated well with the actual times (n = 59, r = 0.829). If the left-ventricular ejection fraction was calculated using the predicted time of end-systole, the error would be 0.03, or less, for 95% of the subjects.

Cardiac chamber imaging: a comparison of red blood cells labeled with Tc-99m in vitro and in vivo.

A detailed comparison was performed between the quality of cardiac images obtained using red blood cells labeled in vitro and in vivo. Both methods gave cardiac images of high quality. The in vitro method resulted in subjectively superior images, better intravascular retention of injected radioactivity, and a higher left-ventricle-to-background count ratio (p less than 0.05). The differences in image quality and left-ventricular blood-pool activity were not great, however, and the slight advantage of the in vitro method was offset by a somewhat more complicated preparative procedure. We believe that both agents are suitable for radionuclide imaging of the cardiac chambers.

A field procedure for the quantitative assessment of nuclear imaging cameras.

Techniques developed for the quantitative assessment of gamma cameras are described. The performance parameters discussed include energy resolution, intransic line spread function, uniformity, and extrinsic line spread function. In addition to describing the equipment used and indicating methods used in analyzing data, some of the potential problems in interfacing multichannel analyzers to gamma cameras are discussed.

The radionuclide ejection fraction: a comparison of three radionuclide techniques with contrast angiography.

Left-ventricular ejection fraction (EF) can be measured by several radionuclide methods. The EFs determined by three such methods (first-transit time-activity, equilibrium blood-pool time-activity, and equilibrium blood-pool area-length) were compared in 30 patients with EFs measured by area-length analysis of x-ray contrast angiograms. Both time-activity methods (first-transit and blood-pool) yielded EFs that correlated well with x-ray contrast EFs (r=0.86 and 0.84, respectively). Area-length analysis of blood-pool images yielded EFs that agreed less well with x-ray contrast EFs (r=0.73 in the RAO view, 0.70 in the LAO view). We conclude that first-transit and blood-pool techniques are equally accurate methods for determining EF when the time-activity method of analysis is employed.

Seven-pinhole emission tomography with thallium-201 in patients with prior myocardial infarction.

Thirty-six patients with prior myocardial infarction, and 14 patients without, had myocardial imaging at rest using both seven-pinhole emission tomography and planar imaging with thallium-201. The sensitivity and specificity of the two approaches for the detection of prior myocardial infarction were compared. Qualitatively, planar imaging yielded sensitivities of 69% (25 of 36) and 80% (29 of 36) with Polaroid and video display formats, respectively. A semiquantitative analysis gave a sensitivity of 75% (27 of 36). Specificities for these three planar approaches were, respectively, 100% (14 of 14), 93% (13 of 14), and 71% (10 of 14) for the Polaroid, video, and semiquantitative analyses. Seven-pinhole tomography had a sensitivity of 83% (30 of 36) by qualitative or visual inspection and 86% (31 of 36) by semiquantitative analysis. Specificities by these two techniques were 71% (10 of 14) and 57% (8 of 14). There were no statistically significant differences in either sensitivity or specificity between the planar and tomographic approaches. Repeat seven-pinhole images were identical in 95% (46 of 48) of patients, showing that reproducibility was satisfactory. We conclude that the seven-pinhole tomographic approach has no advantage over standard planar imaging in the detection of prior myocardial infarction.

Regional distribution of myocardial blood flow measured by single-photon emission tomography: comparison with in vitro counting.

An emission computed tomography system (SPECT), which uses a single large-field-of-view gamma camera, was evaluated for its ability to measure the relative distribution of myocardial blood flow and to assess the effect of attenuation, scatter, and cardiac motion on the tomographic images. Normalized regional myocardial counts from the SPECT images of the living dogs correlated closely with those from the anatomic slices and the samples counted at necropsy except for an over-estimate of tracer in the perfusion defect (SPECT) 57.7 compared to tissue count 32.1; p less than 0.05. The differences were less for the other imaging conditions. Heart and thorax motion, attenuation, and scatter contributed less than 25% to the over-estimate of defect counts. We conclude that the SPECT system accurately reflects regional distribution of myocardial blood flow except for overestimation of flow in regions of perfusion defects. Small perfusion defects might therefore be missed, but no artifactual defects are created.

Detection of left ventricular thrombi with radionuclide angiography.

Apparent filling defects compatible with left ventricular thrombus are occasionally noted in equilibrium radionuclide angiocardiograms. To define the usefulness of the radionuclide angiogram in detecting left ventricular thrombus, the anterior and left anterior oblique radionuclide angiograms of 39 patients with proved presence or absence of thrombus were blindly interpreted. The presence of thrombus was proved at autopsy in 5 patients, at cardiac operation in 2, or on indium-111 platelet imaging in 6; the absence of thrombus was proved at autopsy in 24 or at cardiac operation in 2. Overall, 13 radionuclide angiograms were interpreted as positive (n = 10) or equivocally positive (n = 3) for thrombus, and 26 studies were judged negative. The sensitivity of a positive or equivocally positive radionuclide angiogram for detection of thrombus was 77 percent (10 of 13 patients), the specificity 88 percent (23 of 26 patients), the positive predictive value 77 percent the negative predictive value 88 percent. If the three equivocal studies are instead considered negative for thrombus, the sensitivity was 62 percent, the specificity 92 percent, the positive predictive value 80 percent and the negative predictive value 93 percent. All thrombi were visualized in the anterior view in an area of akinetic or dyskinetic wall motion. A small group of 13 patients (8 with thrombus, 5 without) underwent two dimensional echocardiography, which was 100 percent sensitive and specific. The finding of a discrete filling defect or squared or cutoff ventricular apex in an area of abnormal wall motion in the anterior view of the radionuclide angiogram should suggest the diagnosis of ventricular thrombus, which may be confirmed by other noninvasive studies.

Left ventricular thrombi: in vivo detection by indium-111 platelet imaging and two dimensional echocardiography.

Indium-111 platelet imaging, which can identify sites of active intravascular platelet deposition, and two dimensional echocardiography, which can identify intracardiac masses, can both be used to detect left ventricular thrombi noninvasively. We compared these techniques in 44 men at risk for thrombi from remote transmural myocardial infarction (31 patients) or cardiomyopathy (13 patients). All 44 patients underwent platelet imaging; 35 underwent echocardiography. On platelet imaging nine patients had thrombi and one had a possible thrombus. Of these 10 studies, none were positive at 2 hours, 5 were positive at 24 hours and all were positive 48 or 72 hours after platelet labeling. Nine of these patients underwent echocardiography, and all had an intraventricular mass. The findings on platelet scanning were negative in six patients who had positive (four patients) or equivocally positive (two patients) findings on echocardiography. All patients with thrombi detected by either noninvasive method had transmural anterior myocardial infarction with ventricular aneurysm. Of the seven patients who underwent cardiac surgery or autopsy, three had thrombi. Platelet imaging failed to identify one thrombus in a patient in whom imaging was performed only at 24 hours after labeling. There were no false positive platelet images in this group. Five of these seven patients (two with thrombi, three without) underwent echocardiography; in all cases the echocardiographic findings agreed with the pathologic findings. Both platelet imaging and echocardiography detect ventricular thrombi. Platelet imaging may detect only the most hematologically active thrombi. Both techniques may help define patients at risk of embolization and may be useful for in vivo assessment of antithrombotic drugs.

Myocardial imaging and radionuclide angiography in survivors of sudden cardiac death due to to ventricular fibrillation: preliminary report.

Twenty-one long-term survivors of out of hospital sudden cardiac death due to ventricular fibrillation underwent radionuclide angiography and myocardial imaging with thallium-201. In 13 patients images were obtained at rest and after maximal treadmill exercise; 11 of these 13 (85 percent) had an image defect in one or both studies. Eleven of the 21 patients (52 percent) had a defect in the image obtained at rest. The magnitude of myocardial image defects was typically great; some patients had an image abnormality without other clinical evidence (angina, S-T depression) of ischemia. The mean ejection fraction, assessed in 16 patients with radionuclide angiography, was 0.41 +/- 0.15 (standard deviation); in 5 of the 16 ejection fraction was normal (more than 0.50) and in 3 it was severely abnormal (less than 0.25). Thus, noninvasive radionuclide studies defined a broad spectrum of ischemic and ventriculographic abnormalities in survivors of sudden cardiac death. Further application of these noninvasive studies may identify those at high risk.

Myocardial imaging with intravenously injected thallium-201 in patients with suspected coronary artery disease: analysis of technique and correlation with electrocardiographic, coronary anatomic and ventriculographic findings.

Myocardial imaging was performed after intravenous injection of thallium-201 at rest in 50 patients with suspected coronary artery disease and the results were compared with electrocardiographic, ventriculographic and coronary arteriographic findings. The thallium-201 myocardial images were of good quality and compared favorably with images previously obtained with intracoronary particle injection. Myocardial to background ratios averaged 2:1, a considerable improvement over ratios reported with potassium-43. There was complete intra- and interobserver agreement in the interpretation of images in 90 and 82 percent of cases, respectively. Major disagreement occurred in less than 5 percent of cases. Overall, 15 (30 percent) had an abnormal, 10 patients (20 percent) a borderline abnormal and 25 patients (50 percent) a normal myocardial image. Of patients with electrocardiographic Q waves, 91 percent had an image defect. Of 39 patients without Q waves, 13 percent had an image defect. All 30 patients with a normal or borderline abnormal thallium-201 image had a normal ventricular contraction pattern. All patients with a segmental ventriculographic abnormality had an image defect. In all cases, the area of electrocardiographic or ventriculographic abnormality corresponded to the area of the thallium-201 image defect. The systolic ejection fraction was depressed (0.49 +/- 0.18 [mean +/- standard deviation]) in patients with an image defect compared with that in patients with a normal image (0.64 +/- 0.06, P less than 0.005). Coronary arterial lesions were present and usually of high grade in all patients with an abnormal image; however, the presence of high grade coronary stenosis or occlusion as such correlated with image defects only to the extent that prior myocardial infraction was associated. Thus, satisfactory myocardial images at rest appear to be obtained with intravenously administered thallium-201 and electrocardiographic, ventriculographic and coronary arteriographic data suggest that image defects denote regions of prior myocardial infarction.

Myocardial imaging with indium- 113m- and technetium-99m-macroaggregated albumin. New procedure for identification of stress-induced regional ischemia.

Regional coronary blood flow distribution was studied by myocardial imaging after intracoronary injection of technetium-99m- and indium-113m-macroaggregated albumin at rest and during coronary hyperemia induced by intracoronary injection of Hypaque-M, 75 percent. The four- to five-fold increase in coronary flow after injection of radiographic contrast material was similar in magnitude to that occurring with maximal exercise stress. Experimentally, resting coronary blood flow and regional distribution of radioactive particles remains normal in spite of coronary stenosis of up to 85 percent. Less severe stenosis causes flow and distribution abnormalities only during periods of increased flow, and the degree of maldistribution is directly related to the physiologic severity of the stenosis. Of 49 patients with suspected coronary artery disease, 10 had no significant lesions by coronary arteriography and all had normal images at rest and during coronary hyperemia. Thirty-seven of 39 patients with significant obstructive coronary artery disease had abnormal images at rest or during contrast agent-induced hyperemia, or both. Patients with significant coronary artery disease without previous infarction usually demonstrated abnormalities in flow distribution only during coronary hyperemia. Patients with previous infarction demonstrated resting perfusion abnormalities that often became more abnormal during hyperemia. This technique provides a new method for assessing the physiologic effects of coronary stenosis in conjuntion with coronary arteriography.

Indium-111 platelet imaging for detection of platelet deposition in abdominal aneurysms and prosthetic arterial grafts.

Thirty-four platelet imaging studies were performed in 23 patients to determine whether platelet deposition could be detected in patients with vascular aneurysms (18 patients) or in patients in whom Dacron prosthetic grafts had been place (5 patients). In patients in whom abnormal platelet deposition was detected, the effect of administration of platelet-active drugs on platelet deposition was examined. Of the 18 patients with an aneurysm, 12 had positive studies on initial imaging and 2 had equivocally positive images. Of five patients with Dacron arterial grafts in place, four had diffuse platelet deposition in the grafts; the fifth patient had platelet deposition only in a pseudoaneurysm. Eight patients with an abdominal aneurysm and positive or equivocally positive baseline images were restudied during platelet-active drug therapy either with aspirin plus dipyridamole (seven patients) or with sulfinpyrazone (four patients). No patient studied during treatment with aspirin plus dipyridamole had detectably decreased platelet deposition compared with baseline determinations. In contrast, two of four patients studied while receiving sulfinpyrazone showed decreased platelet deposition. Thus, platelet imaging may be of value for studying platelet physiology in vivo and for assessing platelet-active drugs and the thrombogenicity of prosthetic graft materials in human beings.

Myocardial imaging with thallium-201: a multicenter study in patients with angina pectoris or acute myocardial infarction.

A multicenter study of rest and exercise thallium-201 myocardial imaging in 190 patients from five centers was performed. Exercise images were obtained after graded treadmill or bicycle stress with use of five different gamma camera models and were interpreted by the originating investigator without knowledge of other clinical data. Of 42 patients with less than 50 percent coronary stenosis, 4 (10 percent) had a resting image defect, 1 (2 percent) a new exercise defect and 5 (12 percent) either a resting or an exercise image defect, or both. Of 148 patients with coronary stenosis of 50 percent or greater, 64, (45 percent) had an image defect in the study at rest, 90 (61 percent) had new or increased defects after exercise, and 115 (78 percent) had resting or exercise defects, or both. New exercise image defects were more common than exercise S-T depression (90 of 148 [61 percent] versus 62 of 148[42 percent]; P less than 0.01). In a second group of 111 patients with acute myocardial infarction studied at three centers, 90 patients (81 percent) had image defects compared with 71 (64 percent) two had new electrocardiographic Q waves (P less than 0.01). Smaller infractions, as assessed with serum enzyme values, and diaphragmatic infarctions were less commonly detected than larger or anterior infarctions. These findings suggest that myocardial imaging complements the electrocardiographic identification of acute myocardial infarction of exericse-induced myocardial ischemia.

Myocardial imaging with 201thallium: an analysis of clinical usefulness based on Bayes' theorem.

Rest-exercise thallium-201 (201Tl) myocardial imaging and rest-exercise electrocardiography were performed in 137 patients with suspected coronary artery disease (CAD). The final diagnosis of coronary disease was made by arteriography. Sensitivity and specificity for the ECG and thallium studies alone or combined were then determined. Based on these data, the posttest probability of CAD with a normal or abnormal test was calculated using Bayes' theorem for disease prevalences ranging from 1%--99%. The difference between the probability of disease with a normal test and the probability of disease with an abnormal test was also calculated for each prevalence range. The results demonstrate that 201Tl imaging discriminates between disease absence or presence better than does the ECG. However, both the ECG and thallium studies provide rather poor discrimination between disease and no disease when the disease prevalence is low (less than 0.20) or high (greater than 0.70). Because of this characteristic, it is unlikely that screening tests for CAD will prove useful unless the disease prevalence in the group under study is in the moderate (0.20--0.70) range.