Kenneth A. McKusick

Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201.

Myocardial 201TI uptake and regional blood flow by the microsphere technique were determined in anesthetized dogs undergoing either 20 min of coronary occlusion and 100 min of reperfusion (N = 10) or 120 min of occlusion (N = 4). In both groups, 201TI was injected intravenously after 10 min of occlusion. In transiently occluded dogs, regional flow at the time of 201TI administration was reduced to 8 ± 3% of normal flow in endocardial layers of the central ischemic zone. After 100 min of reperfusion, flow values were not significantly different from normal. 201TI activity after reperfusion rose to 56 ± 5% of normal, demonstrating that redistribution of the radionuclide occurred during the reflow period. In animals with persistent occlusion, there was a significant relationship between 201TI uptake and flow (r = 0.95) and no evidence of redistribution of 2lTl during the two hour occlusion period. In another five dogs receiving 201TI, serial gamma camera images obtained during reperfusion showed increasing uptake of the tracer in apical defects which returned to normal by 4 hours of reflow.Thirteen patients with stable angina received 2 mCi of 201TI intravenously at peak exercise, and multiple gamma camera images obtained serially. All demonstrated zones of diminished 201TI uptake 10 min after exercise. Defects which partially or completely disappeared within 1–6 hours postexercise corresponded to areas supplied by coronary arteries with significant stenoses. Persistent defects were present in regions of old myocardial infarction. Six additional patients with acute myocardial infarction demonstrated 201TI myocardial defects which showed no significant change over 6 hours.Thus, redistribution of 201TI into ischemic myocardium was demonstrated during transient coronary occlusion in dogs and after exercise stress in man. Sequential imaging after a single dose of 201TI at the time of exercise may provide a means for distinguishing between transient perfusion abnormalities or ischemia and myocardial infarction or scar.

Increased lung uptake of thallium-201 during exercise myocardial imaging: Clinical, hemodynamic and angiographic implications in patients with coronary artery disease☆

Abstract To determine the clinical significance of increased thallium-201 activity in the lung immediately after exercise stress, the thallium-201 scans in 227 patients undergoing cardiac catheterization were reviewed. Thallium lung activity on the Initial anterior view images were graded qualitatively as follows: 0 (none) in 175 patients (77 percent); 1+ (moderate—increased activity in the lungs but less intense than that in left ventricular myocardium) in 37 patients (16 percent); and 2+ (severe—activity equal to or greater in intensity than left ventricular myocardlal activity) in 15 patients (7 percent). Increased (1+ or 2+) lung activity was related to (1) a greater number of myocardial segmental thallium defects (probability [p]

Transient defects of resting thallium scans in patients with coronary artery disease.

Defects on resting thallium-201 (201T1) scans in patients who do not have evidence of acute myocardial ischemia have been thought to represent myocardial scar. Our study of 20 patients with stable but severe coronary artery disease (CAD), including nine with ECG evidence of myocardial scar, was undertaken to reexamine the significance of such defects. Imaging was performed in two views, beginning within 10 minutes after Tl administration and repeated over a 2-4-hour period. Images in each of the two projections were divided into three zones, for a total of 120 zones in 20 patients. An initial defect was present in 43 zones in 15 patients, while five patients demonstrated totally normal studies. On later scans 18 defects persisted while 25 filled in. Twelve of 18 persistent defects were associated with ECG evidence of infarction, compared with only six of 25 transient defects (p>0.01). Correlation with angiographic left ventricular wall motion was possible for 12 of 18 persistent defects and 18 of 25 transient defects. Six of 12 persistent defects, compared with only one of 18 transient defects, were associated with akinesia/dyskinesia (p>0.01). In addition, 17 of 18 transient defects were associated with either normal left ventricular wall motion (12 defects) or hypokinesia (five defects). Finally, 23 of 25 transient defects, compared with only 41 of 77 normal zones, were associated with severe CAD (p>0.001).Thus, in resting patients with stable CAD: 1) serial imaging reveals that many initial defects fill in over time; 2) initial resting defects on TI scans may not indicate myocardial scar; and 3) transient defects are usually associated with severe CAD, but normal or only mildly abnormal left ventricular wall motion.

Comparison of thallium redistribution with rest “reinjection” imaging for the detection of viable myocardium

To determine the incidence of incomplete redistribution on conventional delayed thallium images, 41 patients with persistent perfusion defects on myocardial images recorded 3 to 4 hours after thallium injection during exercise were studied. At the conclusion of their delayed images the patients were reinjected at rest with approximately 1 mCi of thallium-201 and a third set of images was recorded. The images were presented at random in pairs (initial:delayed, initial:reinjection) to 2 experienced observers for qualitative scoring of 9 segments/patient. Of the 360 segments analyzed, concordance between the delayed and reinjected images occurred in 307 (85%). Of 141 segments that demonstrated a persistent perfusion abnormality on 3- to 4-hour delayed images, 44 (31%) were reassigned to a redistribution score after reinjection. In 9 patients, reinjection images provided the only evidence of ischemia from the scintigraphic data. In 13 of 14 vascular territories that demonstrated redistribution after reinjection, intact perfusion (either anterograde or via collaterals) was detected at coronary angiography. These data suggest that rest reinjection imaging may provide a means of detecting viable myocardium in segments that demonstrate a fixed perfusion abnormality on conventional 3- to 4-hour delayed thallium images.

Influence of coronary artery disease on pulmonary uptake of thallium-201

An increased pulmonary thallium-201 concentration has been observed in exercise stress thallium perfusion imaging in patients with coronary artery disease. To understand the cause of this lung uptake, studies were performed in experimental animals and in patients undergoing stress thallium perfusion imaging. The extraction fraction of thallium-201 by the lungs was measured in a group of eight dogs using a dual isotope technique. Basal thallium-201 extraction fraction at rest was 0.09 +/- 0.009. After administration of isoproterenol, it decreased to 0.06 +/- 0.02 (difference not significant). After balloon obstruction of the left atrium (which increased mean left atrial pressure and pulmonary transit time) and after administration of acetylcholine as a bolus injection (which prolonged pulmonary transit time only) it increased to 0.19 +/- 0.02 (p < 0.01). Lung thallium-201 activity was measured in 86 patients who had undergone cardiac catheterization and stress-redistribution myocardial perfusion imaging. The initial/final lung activity ratio was 1.41 +/- 0.03 in patients with no significant coronary artery disease, 1.52 +/- 0.03 (difference not significant) in patients with single vessel coronary disease, 1.60 +/- 0.05 (p < 0.05) in those with two vessel disease and 1.59 +/- 0.05 (p < 0.05) in those with triple vessel disease. Quantitation of lung activity in 30 of these patients indicated that the increased ratio in patients with multivessel coronary artery disease was due to a transient absolute increase in the thallium-201 concentration immediately after maximal exercise. The data imply that increased pulmonary concentration of thallium-201 during exercise is a consequence of left ventricular failure.

Improved diagnostic accuracy of thallium-201 stress test using multiple observers and criteria derived from interobserver analysis of variance.

Abstract This study was performed to determine the interobserver variance for the interpretation of segmental thallium-201 image scores and the changes in such scores between the exercise and delayed images. Fifty patients, 40 with and 10 without significant coronary artery disease, underwent thallium imaging immediately after exercise and 2 hours later in the anterior and 50 ° left anterior oblique projections. The left ventricle was divided into six segments and graded by four independent observers on a scale of 0 (minimal activity) to +2 (normal activity). Interobserver variance was determined for each segment. For a change in thallium activity between exercise and delayed images, the interobserver variance was greatest for the apical and apical-inferior segments, intermediate for the inferior and septal segments and least for the anterolateral and posterior segments. When segmental thallium scores were interpreted by an individual observer using a standard method employing one set of arbitrary criteria (method 1), the thallium stress test had a sensitivity of 77 percent and a specificity of 75 percent for coronary artery disease. When the scores were interpreted by an individual observer using criteria derived from interobserver variance analysis (method 2), the sensitivity increased to 86 percent (probability [p]

Usefulness of oral dipyridamole suspension for stress thallium imaging without exercise in the detection of coronary artery disease

Stress thallium imaging with intravenous dipyridamole permits assessment of coronary artery disease (CAD) without the need for exercise. However, intravenous dipyridamole is available in the United States only on an experimental basis. To study the use of oral dipyridamole as a clinically available alternative to intravenous dipyridamole for this purpose, 100 patients underwent thallium imaging with oral dipyridamole. Each patient received 300 mg of pulverized tablets in a 30-ml suspension. Maximal increase in mean heart rate and decrease in mean blood pressure occurred 30 minutes after ingestion. At 45 minutes, 2 mCi of thallium was given intravenously and serial imaging was begun within 7 minutes. The serum dipyridamole level (mean +/- standard deviation) 45 minutes after 300 mg was administered orally (3.7 +/- 2.2 micrograms/ml) was similar to that 5 minutes after 0.56 mg/kg was given intravenously (4.6 +/- 1.3 micrograms/ml). Fifty-five patients had some adverse effects between 15 and 75 minutes after oral ingestion, including nausea, headache, dizziness, chest pain (25 patients) and electrocardiographic changes (14 patients). Intravenous aminophylline was used to resolve these adverse effects in 21 patients. There were no severe arrhythmias, myocardial infarctions or deaths. Of the 43 patients with angiographically documented CAD, 39 had an initial perfusion defect that redistributed on the delayed images. When the results in patients who had undergone catheterization were analyzed by individual segment, the presence of thallium redistribution was associated with normal or hypokinetic contrast left ventriculographic wall motion of that segment, whereas the presence of a persistent defect was associated with akinesia or dyskinesia (Fishers standardized Z = 9.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of gastrointestinal bleeding with 99mTc-labeled red blood cells

Using a modified in vivo Tc-99M red cell labeling technique, gastrointestinal bleeding scintigraphy was performed in 100 patients with GI bleeding. Sixty-two patients with melena or bright red blood per rectum had positive scintiscans. In comparison to results of angiography, endoscopy, surgery and contrast radiography, radionuclide scintigraphy correctly located the site of bleeding in 83% of patients. The procedures could be performed over a 24 hr period which increased the sensitivity of the test since 85% of the scintiscans were positive at one hr or greater after the onset of imaging. The procedure was more sensitive than angiography in detecting sources of GI bleeding. We conclude that GI bleeding scintigraphy 99mTc-red cells in an accurate and effective method to detect upper and lower GI bleeding in patients with acute intermittent gastrointestinal bleeding.

Right ventricular function in adult atrial septal defect: Preoperative and postoperative assessment and clinical implications

Abstract Right ventricular function was assessed with gated cardiac blood pool scanning in 20 adult patients with an atrlal septal defect. All patients had scans both before and 6 or more months after surgical repair of the defect. Clinical findings, pre- and postoperative course and cardiac catheterization data were correlated with scan findings. In all 20 patients, the right ventricle was dilated preoperatively. In nine patients (aged 18 to 42 years, mean 25), right ventricular wall motion was normal preoperatively. All nine were asymptomatic and had normal sinus rhythm. Their pulmonary to systemic flow ratio ranged between 2:1 and 5:1, pulmonary arterial systolic pressure between 18 and 30 mm Hg and right ventricular end-diastolic pressure between 0 and 8 mm Hg. After repair of the atrlal septal defect, all nine remained asymptomatic, right ventricular size decreased dramatically and wall motion was normal. In the remaining 11 patients (aged 36 to 63 years, mean 52), there was moderate to severe preoperatlve right ventricular hypokinesia. All had preoperatlve symptoms (functional class II and III, New York Heart Association); six had atrial fibrillation and five had normal sinus rhythm; seven had clinical heart failure. Pulmonary to systemic flow ratio ranged between 1.7:1 and 5.0:1, pulmonary arterial pressure between 26 and 70 mm Hg and right ventricular end-diastolic pressure between 4 and 16 mm Hg. Symptoms were lessened and right ventricular size and function improved postoperatively in these 11 patients. Unlike those with normal preoperatlve right ventricular wall motion, however, only 1 of the 11 had normal postoperative right ventricular function and became asymptomatic.

An ambulatory ventricular function monitor: Validation and preliminary clinical results

A device for the continuous measurement of left ventricular (LV) function was tested in a series of 34 subjects. The instrument consisted of 2 arrays of radiation sensitive cadmium telluride detectors held in place over the region of the left ventricle and lung by a vest-like garment (hence the name VEST). The VEST electronic instrumentation included analog-to-digital converters, a battery pack, microprocessor and gating device, which were worn in a back pack. Data generated by the VEST, including the digitized average electrocardiogram, RR interval, counts/13 ms in each radiation detector, and time since commencement of data recording, were recorded on a cassette tape recorder every 2 minutes for subsequent analysis. At the conclusion of conventional multigated blood pool imaging, the VEST was positioned and worn by the subjects while supine, standing in place and walking. The correlation of ejection fraction calculated independently from the VEST and scintillation camera data was greater than 0.95. The inter-record reproducibility of the ejection fraction measured by the VEST in sedentary subjects was less than 3%.