ORIGINAL ARTICLE 
Annals of Nuclear Medicine Vol. 10, No. 1,  119-126, 1996 

Comparative accuracy of various Tl-201 reinjection imaging protocols to detect myocardial viability 

Hitoshi NARUSE, Tomohiro KONDO, Tohru ARII, Masato MORITA, Mitsumasa OHYANAGI, Tadaaki IWASAKI and Minoru FUKUCHI 

First Department of Internal Medicine and Department of Nuclear Medicine, Hyogo College of Medicine 

The conventional exercise-3 hours-redistribution thallium-201 [201-Tl] imaging protocol has been recognized to be suboptimal for reliable detection of myocardial viability. Although 201-Tl rest-reinjection after exercise has improved detection of viable myocardium, it is still underestimated in some patients. The present study was designed to compare detection of viable myocardium in five separate imaging steps: step 1 : initial-exercise imaging, step 2: delayed-exercise imaging, step 3: Tl-201 reinjection imaging after delayed-exercise imaging, step 4: separate day rest-reinjection imaging, and step 5: separate day delayed-rest imaging. The study group consisted of 22 patients scheduled for coronary revascularization (either percutaneous transluminal coronary angioplasty or coronary bypass surgery). Pre- and postintervention echocardiographic wall motion and thickness served as independent markers of myocardial viability. Results: Accuracy in identifying myocardial viability gradually improved incrementally from 201-Tl imaging step 1 to step 5. The positive predictive value, negative predictive value and overall accuracy were best for the separate day delayed-rest study (step 5) at 90%, 33% and 78%, respectively. Myocardial segments had fixed defects on separate day delayed-rest 201-Tl imaging (step 5), but nevertheless echocardiographic evidence of myocardial viability indicated less severe defects than segments judged nonviable by echocardiography (p = 0.021). The overall accuracy of separate day delayed-rest imaging (step 5) in predicting viability improved to 88% when segments with moderate or mild defects were considered viable. In conclusion, the most reliable predictor of myocardial viability with 201-Tl imaging is defect severity on separate day delayed-rest images. 

Key words: 201-Tl exercise-reinjection study, 201-Tl rest-injection study, myocardial infarction, coronary revascularization, myocardial viability 

INTRODUCTION 

THALLIUM-201 [201-Tl] redistribution, i.e. complete or partial reversiblity of a myocardial perfusion defect, is generally accepted to indicate the presence of viable myocardium,1-3 but some apparently fixed 201-Tl defects on delayed redistribution imaging after exercise may nevertheless show improvement after coronary revascularization.4.5 Conventional redistribution 201-Tl imaging may therefore underestimate myocardial viability in some patients.6.7 
 In recent years, various protocols using rest reinjection of 201-Tl have been shown to improve the accuracy of detection of viable myocardium. A multitude of 201-TI rest-reinjection protocols have been proposed,8-22 none of which appears to detect myocardial viability with complete accuracy. 
 The purpose of the present study was to systematically evaluate the increasing value of various steps in a Tl-201 exercise-redistribution-rest-reinjection imaging protocol to identify viable myocardium. 

MATERIALS AND METHODS 

Patients The study population consisted of 22 patients with previous myocardial infarction (21 men and 1 woman, mean age 60 +- 11 years), who had coronary revascularization 2 to 6 months after the infarction. The diagnosis of acute myocardial infarction was based on all of the following criteria: acute chest pain lasting longer than 30 min, serum creatine kinase > 1,OOO IU and development of abnormal Q-waves on electrocardiography. 
 All patients underwent 201-Tl exercise and rest imaging prior to revascularization. The infarct related artery was the right coronary artery in 5 patients and the left anterior descending coronary arteries in 17 patients. Coronary artery bypass surgery was performed in 5 patients (2-vessel bypass in 4 patients and 3-vessel bypass in 1 patient), and single-vessel percutaneous transluminal angioplasty (PTCA) was performed in the remaining 17 patients. All patients had repeat coronary (or graft) angiography 6 months after revascularization to confirm patency in the target vessels. 

201-Tl SPECT imaging 
Symptom-limited exercise testing was performed on an upright bicycle ergometer. The workload was increased with 25 Watts in 3 minute increments until an exercise end point was reached i.e. fatigue, severe angina, ST segment depression more than 2 mm, decrease in blood pressure more than 20 mmHg or ventricular tachycardia. At the end point of the exercise, 74 MBq (2.0 mCi) of 201-Tl-chloride was administered intravenously, followed by a 10 ml saline flush. Preoperative 201-Tl SPECT imaging was performed in 5 "steps" (Fig. l). An initial-exercise image (step l) was acquired within 10 minutes after injection; a delayed (redistribution)-postexercise image (step 2) was acquired 3 hours later. Immediately thereafter 37 MBq ( 1.O mCi) of 201-Tl-chloride was injected, and a reinjection-exercise image (step 3) was acquired within 10 minutes of the injection. Approximately I week later, 111 MBq (3.0 mCi) of 201-Tl-chloride was injected at rest, and an initial-rest image (step 4) was acquired within 10 minutes after the injection. A delayed-rest (step 5) image was acquired 3 hours later. 
 A StarCam SPECT gamma camera (General Electric, Milwaukee) was used for single-photon emission computed tomography (SPECT) data acquisition and analysis. From the 45deg. right-anterior oblique to the 45deg. left-posterior oblique projection, 32 acquisitions (30 seconds each) were taken over a 180deg. arc. By filtered back-projection, 6-mm thick short axis and vertical and horizontal long axes slices of the left ventricle were constructed. 
 The SPECT images were evaluated qualitatively as the consensus of three experienced observers who were not informed of the patient's history or echocardiographic findings. The left ventricle was divided into 9 segments for analysis of reconstructed slices. Myocardial segments judged to be abnormal were classified according to the severity of myocardial perfusion defects as one of three grades: mild, moderate or severe (Fig. 2). 
 Thallium-201 redistribution (radiotracer fill-in of per-fusion defects) was considered to be present if defect severity on delayed images improved by more than one grade (e.g., from severe to mild or normal or from moderate to normal). 

Echocacardiography 
 All patients underwent 2-dimensional echocardiography before and after revascularization, in a semi-reclining position, by means of Toshiba SSH-60A or SSH-160A ultrasonic equipment. The locations of the short-axis echocardiographic slices were selected to correlate with the short-axis SPECT images. 
 The left ventricle was divided into 9 segments for analysis. Regional wall motion of the left ventricle was evaluated qualitatively by three experienced observers who were unaware of the 201-Tl findings. In segments with abnormal wall motion, the severity of abnormality was classified as one of four grades: mild hypokinesis, severe hypokinesis, akinesis or dyskinesis (Fig. 2). The change in wall motion was considered to be significant and to be evidence of myocardial viability if postoperative wall motion improved by one or more grades compared with the preoperative assessment (e.g., from dyskinesis to severe hypokinesis and from akinesis to normal). Wall thickness, measured on the end-diastolic short-axis echocardiogram, was judged to be normal if it measured > 10 mm. 

Echocardiographic evidence of myocardial viability The myocardium was judged to be viable if the postoperative echocardiogram showed one or more of the following: l) normal wall thickness, 2) normal wall motion or 3) improved wall motion as defined above by comparing pre- and post-revascularization wall motion. 

Data analysis 
The following 201-Tl imaging patterns were prospectively hypothesized to predict postintervention myocardial viability: 1) Normal 201-Tl uptake at initial-exercise (step 1); 2) Filling-in of a defect at any of the subsequent imaging steps (step 2 to step 5); 3) Defect severity on 201-Tl images with fixed defects on step 5 images. Predictive values are defined as follows: 

Positive predictive value = TP/(TP + FP), negative predictive value = TN/(TN + FN) and overall accuracy = (TP + TN)/(TP + FP + TN + FN). (TP: true positive, FP: false positive, TN: true negative and FN: false negative). 

Statistics 
Mann-Whitney U tests were used to compare defect severity. Differences were considered statistically significant when p < 0.05. 

RESULTS 

Angiographic and echocardiographic findings after revascularization 
All bypass grafts and recanalized arteries were patent at the time of post-revascularization coronary angiography. In 22 patients, 198 segments were available for analysis. Of a total of 198 available myocardial segments, 121 segments showed both normal wall motion and normal wall thickness, and 48 segments satisfied one of three echocardiographic criteria for myocardial viability. The remaining 29 segments did not show echocardiographic evidence of myocardial viability. 

Stepwise 201-Tl imaging 
Figure 3 shows a representative example of a patient who had the 5-step imaging protocol. Initial-exercise studies showed normal myocardial perfusion in 78 segments and myocardial perfusion defects in 120 segments. Figure 4 displays the occurence of 201-Tl filling-in at each of the subsequent imaging steps. Of 120 initially abnormal segments, filling-in of defects was observed in 36 on delayed-exercise imaging (step 2), in 21 on reinjection-exercise imaging (step 3), in 14 on initial-rest imaging (step 4) and in 7 on delayed-rest imaging (step 5). The remaining 42 segments had fixed myocardial perfusion defects throughout all imaging steps. 

201-Tl imaging and echocardiographic evidence of viable myocardium 
Echocardiographic evidence of myocardial viability was present in 77 of 78 (99%) normal segments in step I ; in 3l of 36 (86%) segments with reversible defects in step 2; in 15 of 21 (71 %) segments with reversible defects in step 3; in 12 of 14 (86%) segments with reversible defects in step 4; and in 6 of 7 (86%) segments with reversible defects in step 5. Overall 141 of 156 (90%) segments that were normal or filled-in had echocardiographic evidence of viability, but 28 of 42 (67%) segments with fixed 201-Tl defects on step 5 had apparent echocardiographic evidence of viability. 
 Figure 5 shows predictive values and overall accuracies for myocardial viability for each step. The accuracies increased from step 1 to step 5. The positive predictive value, negative predictive value, and accuracy of step 5 were 90%, 33% and 78%, respectively. 

Defect severity in segments with discordant 201-TI and echocardiography results 
In 28 segments, 201-Tl defects remained fixed (suggesting scar) on step 5 imaging. Nevertheless echocardiography indicated myocardial viability in these segments. Defect severity in these discordant segments was significantly less severe (p < 0.021 ) than in concordant segments (Fig. 6). 
 In 15 segments, 201-Tl defects showed filling-in at any of the separate steps (suggesting viability), but echocardiography nevertheless indicated scar in these segments. Analyzing the severity in these segments, defect severity (after partial filling-in) was greater (p < 0.0001) in these l5 discordant segments than in concordant segments. 
 When segments with moderate or mild defects were assumed to be viable, the overall accuracy of delayed-rest (step 5) images increased to 88% (Fig. 7). 
 Although the overall accuracy of reinjection-exercise (step 3) and initial-rest images (step 4) were equivalent, the negative predictive value of step 5 was higher than that of step 3 and step 4 (Fig. 8). 

DISCUSSION 

Although the "gold standard" for myocardial viability remains somewhat controversial, in the present study we used echocardiographic normal or improved wall motion, and/or normal wall thickness, as evidence of myocardial viability. 
 Our results show that additional rest 201-Tl imaging increases the accuracy of detecting myocardial viability. In this study, the accuracy increased from step 1 to step 5 (Fig. 4), primarily due to the increase in negative predictive values with a small decrease in positive predictive values. The delayed-rest (step 5) 201-Tl images provided the most accurate assessment of myocardial viability. 
 Exercise-induced myocardial perfusion defects that fill in with 201-TI redistribution represent myocardial ischemia, and thus myocardial viability, but some ischemic defects take longer to fill in, and are not identified in typical 201-Tl stress/delayed protocols.23.24 The 201-TI reinjection protocol was designed to address this limitation. Compared with positron emission tomography (PET), however, 201-Tl reinjection SPECT still may underestimate myocardial viability. 17-19 Despite the importance of identifying myocardial viability in patients with fixed defects, there have been only a few studies that compared all possible variations in 201-Tl reinjection protocols in the same patients, as 25-27 evaluated in the present study. 
 After our extensive reinjection protocol involving 5 imaging steps, there were still 28/198 false-negative segments ( 14%) for myocardial viability. Some investigators suggested that defect severity is useful in distinguishing viable from necrotic (scar) tissue in fixed defects.28-30 Our analysis validates this approach. When fixed defects with moderate or mild severity were considered viable, overall accuracy improved to 88%, matching the best reported accuracy based on defect severity.29 
Our results show that defect severity on delayed-rest imaging (step 5) is the best overall predictor of myocardial viability. Using this criterion, myocardial viability was underestimated in only 6 of 198 (3.0%) segments. 

CONCLUSION 

Separate-day delayed-rest 201-Tl imaging (step 5) provides optimal accuracy for detecting myocardial viability, but this protocol is not practical for routine clinical use, because of the camera time required, the increased cost and patient dosimetry. For most patients, a two-step protocol, initial-exercise/delayed-exercise, is the method of choice for determining viable myocardium. When the delayed-exercise study shows fixed defects, additional separate day delayed-rest 201-Tl imaging is optimal to determine myocardial viability. 

ACKNOWLEDGMENTS 

We would like to thank Professor Frans J. Th. Wackers (Yale University) for reviewing the manuscript and making a number of helpful suggestions. 

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