ORIGINAL ARTICLE 
Annals of Nuclear Medicine Vol. 8, No. 3, 171-176, 1994 
Thallium-201 reinjection images can identify the viable and necrotic myocardium similarly to metabolic imaging with glucose loading 18F-fluorodeoxyglucose (18FDG)-PET 
Naonori OGIU, Kenji NAKAI and Katsuhiko HIRAMORI 
Second Department of Internal Medicine, Iwate Medical University 
We compared the usefulness of 18F-fluorodeoxyglucose (18FDG)-PET with glucose loading and thallium-201 (201Tl) reinjection imaging for determining the viability of the myocardium in 21 patients with an old anterior myocardial infarction. We obtained transaxial views during 201Tl reinjection imaging performed 10 minutes after post-exercise injection of 37 MBq 201T1. PET imaging with 75 g oral glucose loading was performed 60 min after injection of 148 MBq of 18FDG. Wall motion was evaluated by echocardiography. Excellent 18FDG-PET images were obtained in 19 of 21 subjects in whom plasma glucose levels were below 25 1 mg/dl. The results of 201Tl reinjection imaging and 18FDG-PET imaging were in agreement in 20 of the 21 subjects. Echocardiography demonstrated hypokinesis or akinesis in segments identified as abnormal in imaging studies. Our results showed that 201Tl reinjection imaging identified the viable and necrotic myocardium similarly to metabolic imaging obtained by 18FDG-PET with glucose loading. 
Key words: myocardial infarction, myocardial viability, 201Tl reinjection, positron emission tomography, 18FDG 
INTRODUCTION 
IDENTIFICATION of the viable and necrotic myocardium is important for clinical and therapeutic decisions. The viability of the myocardium has been assessed in terms of coronary artery patency and preserved regional contractile function, but when certain conditions are present, such as hibernating myocardium or stunned myocardium, the prolonged regional left ventricular dysfunction may be completely reversible.1.2 
Myocardial imaging with thallium-201 chloride (201Tl) can be used to evaluate myocardial viability on the basis of myocardial perfusion, and cell membrane integrity. However, 4-hour 201Tl redistribution images have been found to underestimate myocardial viability in patients with coronary artery disease (CAD).3 Previous studies found that 31 to 52% of persistent defects identified by 201Tl redistribution images exhibited normal perfusion after revascularization on reinjection images.4-7 Recently, positron emission tomography with glucose analog 18F-deoxyglucose (18FDG-PET) during fasting has been used in evaluating the metabolic tissue activity in patients who have an indication for revascularization. Previous studies comparing the results of 18FDG-PET with 201Tl imaging found that 18FDG-PET during fasting identified myocardial viability in 25 to 50% of myocardial segments that showed fixed early defects on 201Tl images.8-10 However, it has been pointed out that 18FDG-PET during fasting might overestimate the myocardial viability.11,12 
We compared the usefulness of 18FDG-PET with glucose loading and 201Tl reinjection imaging in determining the viability of the myocardium in 21 patients with an old anterior myocardial infarction. 
MATERIALS AND METHODS 
Subjects 
We studied 21 subjects (19 men and 2 women, average age: 61.6+-9.0 years) with coronary artery disease diagnosed by coronary angiography (Table 1). All subjects had been treated for myocardial infarction. Angina pectoris was identified in 19 subjects. Fourteen subjects had Q waves and poor R progression in one or more precordial leads on a standard ECG. None had had an acute myocardial infarction within the 2 weeks before the study. Coronary angiography was performed by Judkins' method.13,14 Significant lesions were identified by the presence of stenosis greater than 75%. 
Study protocol 
We assessed myocardial viability in transaxia views obtained by 201Tl reinjection images and 18FDG-PET with glucose loading. Wall motion was assessed by echocardiography. 
Exercise 201Tl reinjection imaging 
A multistage exercise test with a bicycle ergometer was initiated at 25 watts with an increase of 25 watts every 3 min. Standard 12-lead electrocardiograms and blood pressure levels were monitored at 1-minute intervals during the exercise test. Exercise endpoints were defined as the appearance of chest pain, ST depression exceeding 0.2 mV, or achievement of the target heart rate (THR = 85% of maximum HR) . When subjects reached an endpoint, 74 MBq 201Tl was injected and an additional 1 minute of exercise was performed. Exercise 201Tl imaging was performed 10 minutes after the tracer injection. Reinjection images were obtained 10 minutes after the injection of 37 MBq 201Tl, 4 hours after the completion of the exercise. 
Single photon emission computed tomography (SPECT) images were obtained over a 180 arc with a gamma camera (Hitachi Gamma View-D [RC-135T]) and an online mini-computer (Harp) equipped with an all-purpose, low-energy, general-purpose collimator. Data aquisition times were 40 seconds per step for a total of 32 steps. Images on the short axis, vertical, horizontal, and transaxial planes were reconstructed with a Wiener filter. 
18FDG positron emission tomography (PET) 
PET was performed with a whole-body, multi-slice positron camera (Headtome IV, Shimadzu SET-1400W, Kyoto, Japan). 18FDG was synthesized from 18F2 by an automated synthesis system (FDG-CBB, Shimadzu, Kyoto. Japan) via the acetylhypofluorite method. Transmission scanning was performed with 68Ge/68Ga standard line source for correction of photon attenuation for 12 minutes. After transmission scanning for accurate collection of photon attenuation, 148 MBq (4 mCi) of 18FDG was injected. Images were recorded 60 minutes later for 10 minutes. We obtained 7 contiguous transverse myocardial slices at 13 mm intervals. Patients ingested a meal containing carbohydrate (approximately 2-hour before the PET study) and were given a 75 g glucose load l hour before tracer administration. Plasma glucose levels were measured before and 1 hour after 18FDG administration with a SPOTCHEM SP-4410 (Kyoto Daiichi Kagaku, Kyoto, Japan). Analysis of 201Tl reinjection images and 18FDG-PET images 
Three experienced nuclear cardiologists visually assessed 201Tl myocardial images in five segments: anteroseptum, anterior, apical, lateral, and posterolateral. In both the stress and reinjection studies, segmental activity was graded as normal, reduced, or defective. 18FDG-PET images were assessed in the same fashion as 201Tl images, and the 201Tl images were compared with those of 18FDG-PET. 
Echocardiography 
Echocardiography was performed with an Aloka SSD-9000 system (Tokyo, Japan). The left ventricular ejection fraction (EF) was measured in the M-mode or 2-chamber view, and LV wall motion was assessed in the 4-chamber view. Wall motion was classified as normal, hypokinetic, akinetic, or dyskinetic. 
RESULTS 
Coronary angiography showed coronary stenosis greater than 75% in all 21 cases. Single-vessel disease was identified in 5 subjects, double-vessel disease in 10 and triple-vessel disease in 6. 
Perfusion abnormalities of anterior wall were present in all subjects on the 201Tl stress images. Reinjection imaging showed that 12 of these abnormalities were fixed, 7 were partially reversible, and 2 were completely reversible. All 14 cases of Q wave myocardial infarction (MI) demonstrated abnormal 201Tl uptake on 201Tl reinjection images; 71% (10 of 14) of the subjects showed 201Tl defects on reinjection images. Of 7 non-Q wave MI, 2 had a fixed 201Tl defect, and the other subjects showed normal or reduced 201Tl uptake (Table 1). 
Images obtained by 18FDG-PET with glucose loading were more homogeneous than those obtained during fasting in a normal volunteer (Fig. 1). Plasma glucose levels were below 251 mg/dl in 19 subjects (average plasma glucose: 161 mg/dl); excellent 18FDG-PET images were obtained in these subjects. Plasma glucose levels were above 300 mg/dl (444 and 325 mg/dl) in the 2 subjects in whom inadequate 18FDG-PET images were obtained (Table 1). 
18FDG-PET images demonstrated complete defect in 71% (10 of 14) of Q wave MI and reduced or normal uptake in 86% (6 of 7) of non-Q wave MI. 
Relationship between 201Tl reinjection imaging and 18FDG-PET with glucose loading  
The results of the imaging studies were in agreement in 20 of the 21 subjects. Representative images in the patient (No. 11) with anterior MI and effort angina are shown in Figure 2. 
Relationship between imaging studies and echocardiography 
The relationship between imaging studies and echocardiography in assessing myocardial viability is shown in Figure 3 . Echocardiography showed normal wall motion in 2 segments that showed a normal uptake on 201Tl reinjection imaging and 18FDG imaging. Of the 7 segments that showed a reduced uptake on both imaging studies, echocardiography showed akinesis in 3 segments and hypokinesis in 4 segments. Both techniques showed defects in 11 segments. Echocardiography showed akinesis in 10 of those segments and hypokinesis in 1 segment. Echocardiography identified hypokinesis in 1 segment in which the results of imaging studies were inconsistent, as shown in Figure 3. 
DISCUSSION 
The results of 18FDG-PET with glucose loading and 201Tl reinjection imaging were consistent in 20 of the 21 cases of old anterior myocardial infarction. Echocardiography demonstrated hypokinetic or akinetic wall motion in the regions identified by both imaging techniques as abnormal. Our results showed that 201Tl reinjection images can be used to identify viable and necrotic myocardium with similar identification to metabolic imaging obtained by 18FDG-PET with glucose loading. 
201Tl reinjection
Methods of 201Tl reinjection have been developed for assessing myocardial viability.3,5 When 201Tl reinjection images were obtained immediately after the conventional 4-hour redistribution images, viable myocardium was detected in 34 to 49% of regions that were interpreted as having irreversible perfusion abnormalities on the conventional redistribution images.15 In the present study, fill in on the 201Tl reinjection images was found to be 43% (9 of 21) (Table 1). A possible explanation for these improved results is that the delivery of 201Tl may be delayed during the 3-to-4 hour period after exercise.16 
18FDG-PET 
PET, a noninvasive imaging method that uses a variety of tracers, can provide a qualitative as well as quantitative assessment of multiple physiologic and metabolic myocardial parameters. However, subsequent metabolism of these tracers can be severely affected by the metabolic milieu. The uptake of 18FDG is similar to that involved in glucose uptake. However, the terminal metabolic step of 18FDG uptake is phosphorylation by hexokinase which, unlike glucose, discontinues to be metabolized. Thus, 18FDG accurately traces the initial transport of glucose but not its eventual fate (i.e., Kreb's cycle, glycolysis, glycogen storage). Glucose loading and fasting alter the arterial concentrations of substrates (glucose, free-fatty acid and lactate) and hormones (insulin), altering myocardial substrate extraction and utilization. Fasting images are therefore not superior to glucose loading images. 
Tamaki et al.9 reported that uptake of 18FDG was observed in about 40% of myocardial areas that demonstrated reduced 201Tl uptake, indicating that these areas were viable. They also reported that cardiac contractile function improved after surgical revascularization in 78 % of segments with preserved 18FDG uptake, compared with 22% of segments without 18FDG uptake. Because myocardial uptake of 18FDG is affected by several metabolic factors,17 studies are perfomed when patients are in the fasting state, after glucose loading, or postprandially, depending on the issue to be resolved.18-20 Fasting improves the detection of increased 18FDG utilization caused by ischemia. However, Gropler et al.11 recently showed a significant heterogeneity in regional myocardial glucose utilization rates (rMGU) in fasting subjects, suggesting that the specificity of fasting 18FDG studies in detecting myocardial ischemia is limited. The myocardial uptake of 18FDG is more homogeneously distributed after glucose loading. This metabolic heterogeneity is unexplained to date but should be incorporated into the interpretation of clinical studies. 
We obtained homogeneous images in 19 of 21 subjects. Excellent images were obtained when the average plasma glucose level was 161 mg/dl. Inhomogeneous images were obtained in 2 subjects with plasma glucose levels of 444 and 325 mg/dl. Glucose loading is inappropriate in subjects with diabetes mellitus. In such cases, glucose loading should be performed with an insulin clamp to stabilize the plasma glucose level.21 However, the use of an insulin clamp is more complicated than glucose loading. 
Comparison of 18FDG-PET imaging with 201Tl reinjection SPECT imaging 
A recent study has compared thallium reinjection and fasting 18FDG-PET imaging in differentiating the viable from the scarred myocardium.22 There have been no comparative studies assessing myocardial viability by means of thallium reinjection and 18FDG-PET after glucose loading. Fasting 18FDG-PET identified 30 to 40% of 201Tl defect segments. However, fasting images were not homogeneous, because of unstable glucose or insulin levels, indicating that fasting images may overestimate the extent of viable myocardium. We found that 18FDG-PET images after glucose loading and perfusion 201Tl images were consistent in all but one case, indicating that 201Tl reinjection imaging identifies viable and necrotic myocardium similarly to 18FDG-PET with glucose loading. Bonow et al.23 also demonstrated that 201Tl reinjection identified the myocardial viability the same as 18FDG-PET imaging with glucose loading. 
Comparison of 18FDG-PET and 201Tl reinjection SPECT imagings with wall motion by echocardiography 
The assessment of myocardial viability was difficult in certain conditions such as hibernating myocardium or stunned myocardium. In this study, there were 3 of 7 cases identified as akinesis by echocardiography in whom 18FDG-PET images after loading and 201Tl reinjection imagings indicated reduced uptake. We considered that in these segments there is the possibility of the improvement in wall motion after revascularization. 
CONCLUSIONS 
Identification of the viable and necrotic myocardium is important in making clinical and therapeutic decisions. However the assessment of myocardial viability by regional wall motion is difficult in certain conditions such as hibernating myocardium or stunned myocardium. Our results showed that 201Tl reinjection imaging identified the viable and necrotic myocardium similarly to metabolic imaging obtained by 18FDG-PET with glucose loading. 
ACKNOWLEDGMENTS 
We thank Drs. Naoki Moriai, Tomohisa Miyakawa. Masataka Nasu, Tsuneo Takahashi and Toru Yanagisawa for their advice and Kentarou Hatano. Ph.D., and Toshiaki Sasaki of the Cyclotron Research Center of Iwate Medical University for the production of isotopes, and Hiroshi Gakumazawa and Masayuki Nagaoka for technical assistance with 201Tl SPECT. We would especially like to thank the Japan Isotope Association Nishina Memorial Cyclotron Center for permitting us to use its facilities. We also thank Dr. Paul Langman, Iwate Medical University, for assistance with English usage. 
REFERENCES 
1. Braunwald E, Kloner RA. The stunned myocardium: Prolonged, postischemic ventricular dysfunction. Circulation 66: 1146-1149, 1982. 
2. Braunwald E, Rutherford JD. Reversible ischemic left ventricular dysfunction: Evidence for the "Hibernating myocardium." J Am Coll Cardiol 8: 1467-1470, 1986. 
3. Dilsizian V, Rocco TP, Freedman NMT, Leon MB, Bonow RO. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging. N Engl J Med 323: 141-146, 1990. 
4. Gibson RS, Watson DD, Taylor GJ. Crosby IK, Wellons HL, Holt ND, et al. Prospective assessment of regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy. J Am Coll Cardiol 1: 804-815, 1983. 
5. Liu P, Kiess MC,Okada RD, Block PC, Strauss HW, Pohost GM, et al. The persistent defect on exercise thallium imaging and its fate after myocardial revascularization: does it represent scar or ischemia? Am Heart J 110: 996-1001, 1985. 
6. Rocco TP, Dilsizian V, Mckusick A, Fischman AJ, Boucher CA, Strauss HW. Comparison of thallium redistribution with rest "reinjection" imaging for the detection of viable myocardium. Am J Cardiol 66: 158-163, 1990. 
7. Ohtani H,Tamaki N, Yonekura Y,Mohiuddin IH,Hirata K, Ban T, et al. Value of thallium-201 reinjection after delayed SPECT imaging for predicting reversible ischemia after coronar bypass grafting. Am J Cardiol 66: 394-399, 1990. 
8. Bonow RO. Berman DS, Gibbons RJ, Johnson LL, Rumgerger JA, Schwaiger M, et al. Cardiac positron emission tomography. Circulation 84: 447-454, 1991. 
9. Tamaki N, Yonekura Y, Yamashita K, Senda M, Saji H, Hashimoto T, et al. Relation of left ventricular perfusion and wall motion with metabolic activity in persistant defects on thallium-201 tomography in healed myocardium infarction. Am J Cardiol 62: 202-208, 1988. 
10. Tarnaki N, Yonekura Y, Yamashita K. Mukai T, Magata Y, Hashimoto T, et al. SPECT thallium-201 tomography and positron tomograpy using N-13 ammonia and F-18 fluorodeoxyglucose in coronary artery disease. Am J Cardiac Imaging 3: 3-9, 1989. 
11. Gropler RJ, Sigel BA, Lee KJ, Moerlein SM, Perry DJ, Bergmann SR, et al. Nonuniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans. JNucl Med 31: 1749-1756, 1990. 
12. Schwaiger M, Hicks R. The clinical role of metabolic imaging of the heart by positron emission tomography. J Nucl Med 32: 565-578, 1991. 
13. Judkins MP. Selective coronary angiography-a percutaneous transfemoral technic. Radiol 89: 815-824, 1967 
14. Melvin P, Judkins MP. Percutaneous transfemoral coronary arteriography. Radiol Clin North Am 6: 467-492, 1968. 
15. Dilsizian V, Bonow RD. Current diagnostic techniques of assessing myocardial viability in patients with hibernating and stunned myocardium. Circulation 87: 1-20, 1993. 
16. Budinger TF, Pohost GM. Thallium 'redistribution': An explanation. J Nucl Med 27: 996, 1986 (abstract).
17. Camici P, Ferranini E, Opie LH. Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by positron emission tomography. Prog Cardiovasc Dis 32: 217-238, 1989. 
18. Fudo T, Kambara H, Hashimoto T, Hayashi M. Nohara R, Tamaki N, et al. F-18 deoxyglucose and stress N-13 ammonia positron emission tomography in anterior wall healed myocardial infarction. Am J Cardiol 60: 1191-1197, 1988. 
19. Marshall RC, Tillisch JH, Phelps ME, Huang SC. Carson R, Henze E, et al. Identification and differentiation of myocardial ischemia and infarction in man with positron computed tomography, F-18-labeled fluorodeoxyglucose and N-13 ammonia. Circulation 67: 766-788, 1983. 
20. Berry JJ, Schwaiger M. Metabolic imaging with positron emission tomography. Current Opinion in Cardiology 5: 803-812, 1990. 
21. Knuuti MJ, Nuutila P. Ruotsalainen U, Saraste M, Harkonen R, Ahonen A, et al. Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography. J Nucl Med 33: 1255-1262, 1992. 
22. Tamaki N, Ohtani H, Yamashita K, Magata Y. Yonekura Y, Nohara R, et al. Metabolic activity in the area of new fill-in after thallium-201 reinjection: comparison with positron emission tomography using fluorine-18-deoxyglucose. J Nucl Med 32: 673-678, 1991. 
23. Bonow RO, Dilsizian V, Cuocolo A, Bacharach SL. Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Circulation 83: 26-37, 1991.