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Radionuclide assessment of regional myocardial perfusion with thallium-201
Fundamentals Radionuclide myocardial
of clinical assessment
perfusion
cardiology
of regional
with
thallium-201
Robert A. Corne M.D., F.R.C.P.(C), F.A.C.C.* Mervyn S. Gotsman M.D., F.R.C.P., F.A.C.C. Henri Atlan M.D., Ph.D. Winnipeg,
Manitoba,
Canada,
and
Jerusalem,
Israel
The marked prevalence and alarming natural history of coronary atherosclerosis make it imperative that a thorough evaluation of the coronary circulation be obtained in patients with known or suspected ischemic heart disease. In addition, an assessment of regional myocardial perfusion is important in the evaluation of the medical and surgical management of patients with ischemic heart disease. The coronary arteriogram provides anatomic information of the site(s) and degree of coronary arterial narrowing. However, it does not provide functional information regarding regional myocardial flow at the capillary level; this information can be obtained with the use of radionuelides and a scintillation camera. Furthermore, this technique is noninvasive and safe. Radionuclide indicators available for assessment of regional myocardial perfusion include potassium analogues,’ particulate indicators,’ and diffusible inert gases (‘““Xe).:’ The latter two indicators require cardiac catheterization and will not be discussed in this review. The following discussion will be restricted to potassium analogues, with major emphasis on thallium-201 (‘“‘Tl). The approach of regional myocardial perfusion imaging with radioactive potassium or one of its analogues involves the intravenous injection of the radionuclide which is initially distributed to From the Department of Medicine, and the Departments of Medicine University of Jerusalem, Israel. Received Reprint Health Canada
for publication
May
requests: Robert Sciences Centre, R3E 023.
University of Manitoba, and Medical Biophysics,
22, 1978.
A. Corm, M.D., Section of Cardiology, 700 William Ave., Winnipeg, Manitoba.
*This work was performed while Dr. Corm was a Lady Professor of Medicine, Hebrew University of Jerusalem.
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and concentrated by cardiac muscle. The myocardial accumulation of radiopotassium and rubidium was first demonstrated by Love and colleagues in 1954.’ Carr and associates’. ‘) suggested the potential clinical application of this observation to imaging of the myocardium. They demonstrated, F that significant radioactivity could be detected and imaged in the normal myocardium using rubidium-86 and cesium-131, and that following experimental coronary ligation the zones of decreased or absent radioactivity (“cold spots”) could be visualized on the myocardial scan. Subsequently newer radionuclides have been developed, including potassium-43, cesium129, rubidium-81 and thallium-201. While none of these tracers possess ideal physical and biological properties, thallium-201 appears to be the best of the currently available cationic tracers for myocardial perfusion imaging.‘, ’ Physical and ZOl-thallium’.
biologic *
properties
of
Thallium-201 has a physical half-life of 73 hours. While this provides and adquate shelf-life, a longer time is required between sequential studies in the same patient. ‘“‘Tl decays by electron capture, emitting a small yield of gamma rays (135 to 167 keV). In addition the daughter nuclide 201-mercury emits x-rays with an energy of 65 to 82 keV; these x-rays occur in 95 per cent of ““Tl disintegrations. Although the energy spectrum of this radionuclide is less than optimal, ““Tl can be effectively imaged with a scintillation camera. ““Tl concentration in the blood decays exponentially with a half-time of less than 30 seconds. In comparison with other cationic tracers, ““Tl has a greater heart/blood and heart/
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liver ratio of activity. The concentration of ?“‘Tl initially in the myocardium is between 2 and 5 per cent of the administered dose. This myocardial concentration of tracer at any particular time after injection is influenced by the rate of turnover of the intracellular pool of these tracers in the myocardium. The myocardial half-life of thallium is longer than that of potassium; therefore, myocardial imaging may be performed at least up to one hour after administration of ““Tl and still reflect myocardial perfusion at the time of administration. The initial distribution of ““Tl in the myocardium is dependent on both coronary blood flow and cellular extraction. Strauss and associates” compared the regional distribution of ““‘Tl with that of radioactive microspheres (administered into the left atrium of dogs) as an indicator of blood flow and demonstrated excellent correlations under conditions of normal flow, and partial and total coronary artery occlusion. These data suggest that the major determinant of ““Tl distribution is blood flow. Myocardial extraction of ““Tl is dependent on an active transport mechanism involving ths sodium-potassium membrane ATP-ase system. Extraction efficiency by the heart approximates 85 to 90 per cent.“’ This may be reduced by hypoxia and acidosis; the effects of digitalis, propranolol, and insulin on ““Tl extraction are conflicting.“‘, I’ Normal
201Tl scan
(Fig.
1)
The appearance of the normal myocardial perfusion image after intravenous injection of ““Tl at rest and exercise has been described by Cook and co-workers.‘” At rest, the only portion of the heart normally visualized is left ventricular myocardium; the right ventricular myocardium is not visualized, due to its thinner wall and lower blood supply. When injection of ““IT1 occurs at the time of maximal exercise stress, lung, hepatic, and splanchnic activity diminish, and the right ventricular myocardium is visible on the scintigram, best seen in the 45 degree left anterior oblique view. In the anterior view, the anterolateral wall, apex, and inferior wall of the left ventricle can be visualized. The apex frequently has less activity than the remainder of the myocardium, due to anatomic thinning in this zone. In the 45 degree left anterior oblique view, the septum, posterolatera1 and inferior walls are detected; if the heart
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Fig. 1. Normal thallium-201 myocardial perfusion .scintigram at rest (upper panels) and exercise (lower panels) in a patient with normal coronary arteries on selective coronary arteriography. ANT = anterior view; LAO = left anterior oblique view; LL = left lateral view.
has a vertical position in the chest, the apex makes up the inferior border.“’ In the left lateral view the anterior wall, apex, inferior and posterior walls are identified.lA It has been suggested that there are physiologic areas of decreased perfusion in the normal myocardium and, therefore, that if lesions are to be considered significant, their radioactivity must vary by more than 20 per cent from adjacent areas.‘” Myocardial
infarction
The major application of the assessment of regional myocardial perfusion with ?“‘Tl has been in patients with known or suspected ischemic heart disease. When myocardial imaging is performed at rest, ‘“‘Tl is injected intravenously with the patient standing, after a 12 hour fast, in order to decrease hepatic and splanchnic blood flow. Regions of recent or old myocardial infarction appear as areas of reduced tracer uptake at rest which do not change with exercise (vide infra)‘. Ii (Fig. 2). This is due to reduced blood flow to the infarct area and a reduction in myocardial cellular mass. The sensitivity of the procedure for acute myocardial infarction is approximately 80 per cent.‘” The frequency of positive scintigrams was significantly higher in patients studied within 24 hours after onset than in those studied later. Repeat scintigrams in the
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Fig. 2. Myocardial infarction showing a rest defect, Thallium-201 myocardial perfusion scintigram in a patient with 100 per cent obstruction of the left anterior descending and right coronary arteries. There is a focal defect involving the septum and inferior wall of the left ventricle at rest (upper panels) which is unchanged after exercise (lower panels), consistent with myocardial infarction without ischemia.
same patient demonstrated a reduction in the size of the defect with time; these observations suggest that during the acute stage of myocardial infarction the perfusion defect is due to a combination of myocardial necrosis, ischemia, and periinfarction edema. It is important to note that ““Tl perfusion scintigraphy does not differentiate between old and new infarction.‘“. Ii Ancillary clinical information and the use of infarct avid agents such as 99m technetium (99m Tc) pyrophosphate aid in this distinction. Abnormal resting ““Tl scintigrams have also been reported in patients with unstable angina pectoris,‘” and in patients with coronary spasm.‘!‘, “‘I Defects in the ““Tl scintigram at rest appear to be more sensitive than the 12-lead electrocardiogram or the ventriculogram.‘“, L”-yS Myocardial perfusion defects accurately localize the site of transmural infarction.“, .‘j However, the ability of the procedure to estimate the size of the infarct is presently limited”, “Ii; dual radionuclide studies with ““‘Tl combined with infarct avid agents such as 99m Tc pyrophosphate may improve results.‘!i. iti There are additional limitations with ““Tl rest imaging for myocardial infarction.‘:‘, (’ Lesions less than 2.5 cm. cannot usually be detected; inferior and posterior infarcts are more difficult to
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LAO Fig. 3. Myocardial ischemia with exercise-induced defect. A patient with myocardial ischemia and 95 per cent stenosis of the left anterior descending coronary artery. The thallium-201 scintigram is normal at rest (upperpanel). After exercise there is a perfusion defect involving the apex and lower portion of the septum (LAO view).
visualize than anterior infarcts. Furthermore, thallium myocardial perfusion imaging is unable to detect lesions that are limited to the subendocardium.‘:’ Myocardial
ischemia
When patients with angina pectoris without myocardial infarction are imaged at rest, regional perfusion is generally normal. In the resting nonischemic state, viable myocardial regions supplied by stenotic coronary arteries are usually adequately perfused in either an antegrade or retrograde fashion. Both resting coronary blood flow and regional distribution were normal in animals despite coronary stenosis of 85 per cent in diameter.“’ However, the ability to increase coronary flow in response to stress became progressively abnormal with coronary stenosis exceeding 45 per cent. Therefore, by combining a stress with the imaging procedure, one can image transiently ischemic myocardium which appears as a region of decreased radioactivity compared to a separate rest image (Fig. 3).R3.‘Ii Patients are exercised on a treadmill or bicycle until limited by angina, dyspnea, significant arrhythmias, or the attainment of 85 per cent of the maximum predicted heart rate. ““Tl is then injected intravenously, and the patient continues to exercise for 45 to 60 seconds
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Myocardial ischemia with defect at exercise disappearing 4 hours later. Thallium-201 myocardial perfusion scintigram 10 minutes after exercise (upperpanel) and 4 hours later (lower panel). The decreased tracer concentration 10 minutes after exercise is not present 4 hours later, indicative of myocardial ischemia. Coronary arteriography revealed 90 per cent obstruction of the left anterior descending coronary artery.
5. Myocardial infarction with additional ischemia. A patient with triple vessel coronary disease and a previous myocardial infarction. On the rest injected thallium scintigram (upperpanel), there is decreased tracer concentration in the inferior wall seen best in the LAO view. With injection at peak exercise (lower panel), the inferior defect becomes more marked and there is decreased perfusion of the apex (Ant view), septum and posterolateral walls (LAO uier.u), consistent with myocardial infarction and ischemia.
following injection. The ““Tl is rapidly cleared from the blood and distributed within the ventricular myocardium; the proportion distributed within the left ventricular myocardium remains essentially unchanged for at least one hour after injection and, therefore, reflects the physiological state at the time of the radionuclide injection. Thus, imaging from 10 to 60 minutes after injection reflects the distribution of the radioactive cation at the time of stress, even though the patient has returned to the resting state. Mechanisms responsible for the abnormal “‘IT1 uptake under stress include more ‘“IT1 being delivered to normal myocardium in comparison to that in the myocardium distal to the critical stenosis, and decreased extraction efficiency under conditions of hypoxia and acidosis. Recent reports”“-,” indicate that imaging repeated 4 hours after exercise demonstrate resolution of exercise-induced myocardial defects, thereby obviating the need for a separate rest study (Fig. 4). Rest defects associated with an increased perfusion defect with exercise are consistent with both previous infarction and myocardial ischemia (Fig. 5). Studies evaluating patients undergoing rest and exercise ““Tl imaging have demonstrated a
sensitivity of approximately 75 to 80 per cent in detecting significant coronary artery disease.“‘-‘“. :j”. ne Our current results confirm these findings.‘” This sensitivity is higher than that reported with either the resting or exercise ECG. When the results of rest and exercise ““Tl myocardial perfusion scintigrams are combined with the results of the rest and exercise ECG, the sensitivity increases to approximately 90 per cent. ‘“‘Tl imaging is particular helpful in patients with single vessel coronary artery disease, those with abnormal resting ECG’s and those with exercise ECG’s which are difficult to interpret because of conduction abnormal abnormalities or ventricular arrhythmias. Myocardial imaging with ““Tl is currently generally a qualitative study dependent on the demonstration of relative differences in radionuelide uptake. In the presence of global ischemia due to severe proximal triple vessel disease or bilateral coronary ostial stenosis, a normal homogenous appearing scan would be evident. Quantification of the ““Tl scintigram has demonstrated a reduction in total myocardial activity.“’ Falsenegative studies may also occur in single vessel
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finding of a perfusion defect on the exercise ““Tl scintigram would suggest coronary stenosis, whereas a normal exercise ‘“‘Tl scintigram would suggest that the exercise ECG was not indicative of hemodynamically significant coronary atherosclerosis.
PRE ANTERIOR
POST
Fig. 6. Effects of coronary artery bypass graft surgery. Preoperative (upper panels) and postoperative (lower panels) thallium-201 scintigrams at rest and exercise (anterior hew). The resting scintigrams are normal. The perfusion defect in the exercise scintigram preoperatively is not present after coronary bypass surgery. Preoperative coronary arteriography revealed 95 per cent stenosis of the left anterior descending coronary artery. Coronary arteriography 3 months postoperatively revealed a patent graft to the left anterior descending coronary artery.
disease involving either the right or the circumflex coronary artery. In addition, in the presence of a large myocardial infarction, an exercise defect may be difficult to demonstrate. We have found the specificity of ““Tl exercise scintigraphy to be 90 per cent,?” confirming recent reports by Ritchie and associates’” and by Botvinick and colleagues.‘” However, since these results were obtained from selected populations, more experience is necessary before the specificity of ““Tl scintigraphy is definitively established. An extension of the use of myocardial perfusion imaging has been employed in the evaluation of patients who have had coronary bypass surgery. The post-surgical studies by Zaret and co-worker+’ using potassium-43 have been confirmed recently with ““Tl.“-“’ Comparison of pre- and postoperative rest and exercise scintigrams have provided information regarding graft pate’ncy, status of the distal native circulation, and perioperative infarction” (Fig. 6). An additional application of the exercise ““Tl myocardial perfusion scintigram has been advocated in asymptomatic patients or patients with atypical chest pain and ST segment depression 1 mm. or greater on exercise testing.‘?, 1X,” The
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“‘IT1 perfusion imaging has also been used to evaluate patients without coronary disease. Patients with tetralogy of Fallot have been differentiated from patients with single ventricle by the appearance of the septum on the scintigram.“’ An increase in septal thickness relative to the left ventricular free wall with a ““Tl perfusion scintigram has been demonstrated in idiopathic hypertrophic subaortic stenosis.“’ Furthermore, patients with the obstructive form of the disease have a thicker basal posterior free wall than patients with the nonobstructive form of this disease. In idiopathic congestive cardiomyopathy, thallium uptake is generally uniform, whereas in ischemic cardiomyopathy focal defects in uptake are apparent.“’ While left ventricular dilatation was found in both conditions, right ventricular dilatation was more common in idiopathic congestive cardiomyopathy. Cardiomyopathy due to infiltrative systemic disease such as sarcoidosis” are associated with focal decreases in ‘“‘Tl concentration. The scintigram is not specific, however, and coronary artery disease must be differentiated on clinical grounds. Finally, thallium perfusion imaging has been reported to be a useful technique for the diagnosis of right ventricular (RV) hypertrophy?’ On low contrast ‘“‘Tl scintigrams at rest, Cohen and colleagues”” visualized the RV in all patients with RV hypertrophy; in addition, there was apparent thickness of the RV free wall. This technique was more sensitive than the ECG. Future
developments
While ““Tl is the best of the currently available potassium analogues, the optimal gammaemitting radioactive potassium analogue has not become available. It is anticipated that the future will see the development of more optimal radionuclides as well as improvements in imaging techniques and development of quantitative approaches to myocardial imaging with improved computer data processing. Methods for accurately sizing acute myocardial infarction, with or
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without the concomitant use of infarct avid agents, and for providing sequential follow-up information are needed. Finally, the use of positron-emitting potassium analogues and the positron camera promise improved spatial resolution in perfusion scintigraphy and the potential for three-dimensional reconstruction.54
11.
Conclusions
14.
In conclusion, assessment of regional myocardial perfusion with ‘“‘Tl rest and exercise provides useful information employing a technique that is non-invasive and safe. It can be performed on acutely ill patients and can be repeated for re-evaluation. The reproducibility of repeat ‘“IT1 myocardial imaging”i enables this diagnostic study to be employed in longitudinal follow-up studies. Since the myocardial perfusion scintigram provides functional information regarding regional tissue perfusion whereas the coronary arteriogram provides anatomic information, these two procedures are complementary and not competitive.
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1979,
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of clinical assessment
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Robert A. Corne M.D., F.R.C.P.(C), F.A.C.C.* Mervyn S. Gotsman M.D., F.R.C.P., F.A.C.C. Henri Atlan M.D., Ph.D. Winnipeg,
Manitoba,
Canada,
and
Jerusalem,
Israel
The marked prevalence and alarming natural history of coronary atherosclerosis make it imperative that a thorough evaluation of the coronary circulation be obtained in patients with known or suspected ischemic heart disease. In addition, an assessment of regional myocardial perfusion is important in the evaluation of the medical and surgical management of patients with ischemic heart disease. The coronary arteriogram provides anatomic information of the site(s) and degree of coronary arterial narrowing. However, it does not provide functional information regarding regional myocardial flow at the capillary level; this information can be obtained with the use of radionuelides and a scintillation camera. Furthermore, this technique is noninvasive and safe. Radionuclide indicators available for assessment of regional myocardial perfusion include potassium analogues,’ particulate indicators,’ and diffusible inert gases (‘““Xe).:’ The latter two indicators require cardiac catheterization and will not be discussed in this review. The following discussion will be restricted to potassium analogues, with major emphasis on thallium-201 (‘“‘Tl). The approach of regional myocardial perfusion imaging with radioactive potassium or one of its analogues involves the intravenous injection of the radionuclide which is initially distributed to From the Department of Medicine, and the Departments of Medicine University of Jerusalem, Israel. Received Reprint Health Canada
for publication
May
requests: Robert Sciences Centre, R3E 023.
University of Manitoba, and Medical Biophysics,
22, 1978.
A. Corm, M.D., Section of Cardiology, 700 William Ave., Winnipeg, Manitoba.
*This work was performed while Dr. Corm was a Lady Professor of Medicine, Hebrew University of Jerusalem.
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and concentrated by cardiac muscle. The myocardial accumulation of radiopotassium and rubidium was first demonstrated by Love and colleagues in 1954.’ Carr and associates’. ‘) suggested the potential clinical application of this observation to imaging of the myocardium. They demonstrated, F that significant radioactivity could be detected and imaged in the normal myocardium using rubidium-86 and cesium-131, and that following experimental coronary ligation the zones of decreased or absent radioactivity (“cold spots”) could be visualized on the myocardial scan. Subsequently newer radionuclides have been developed, including potassium-43, cesium129, rubidium-81 and thallium-201. While none of these tracers possess ideal physical and biological properties, thallium-201 appears to be the best of the currently available cationic tracers for myocardial perfusion imaging.‘, ’ Physical and ZOl-thallium’.
biologic *
properties
of
Thallium-201 has a physical half-life of 73 hours. While this provides and adquate shelf-life, a longer time is required between sequential studies in the same patient. ‘“‘Tl decays by electron capture, emitting a small yield of gamma rays (135 to 167 keV). In addition the daughter nuclide 201-mercury emits x-rays with an energy of 65 to 82 keV; these x-rays occur in 95 per cent of ““Tl disintegrations. Although the energy spectrum of this radionuclide is less than optimal, ““Tl can be effectively imaged with a scintillation camera. ““Tl concentration in the blood decays exponentially with a half-time of less than 30 seconds. In comparison with other cationic tracers, ““Tl has a greater heart/blood and heart/
0002~8703/79/010112
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C. V. Mosby
CO.
Myocardial
liver ratio of activity. The concentration of ?“‘Tl initially in the myocardium is between 2 and 5 per cent of the administered dose. This myocardial concentration of tracer at any particular time after injection is influenced by the rate of turnover of the intracellular pool of these tracers in the myocardium. The myocardial half-life of thallium is longer than that of potassium; therefore, myocardial imaging may be performed at least up to one hour after administration of ““Tl and still reflect myocardial perfusion at the time of administration. The initial distribution of ““Tl in the myocardium is dependent on both coronary blood flow and cellular extraction. Strauss and associates” compared the regional distribution of ““‘Tl with that of radioactive microspheres (administered into the left atrium of dogs) as an indicator of blood flow and demonstrated excellent correlations under conditions of normal flow, and partial and total coronary artery occlusion. These data suggest that the major determinant of ““Tl distribution is blood flow. Myocardial extraction of ““Tl is dependent on an active transport mechanism involving ths sodium-potassium membrane ATP-ase system. Extraction efficiency by the heart approximates 85 to 90 per cent.“’ This may be reduced by hypoxia and acidosis; the effects of digitalis, propranolol, and insulin on ““Tl extraction are conflicting.“‘, I’ Normal
201Tl scan
(Fig.
1)
The appearance of the normal myocardial perfusion image after intravenous injection of ““Tl at rest and exercise has been described by Cook and co-workers.‘” At rest, the only portion of the heart normally visualized is left ventricular myocardium; the right ventricular myocardium is not visualized, due to its thinner wall and lower blood supply. When injection of ““IT1 occurs at the time of maximal exercise stress, lung, hepatic, and splanchnic activity diminish, and the right ventricular myocardium is visible on the scintigram, best seen in the 45 degree left anterior oblique view. In the anterior view, the anterolateral wall, apex, and inferior wall of the left ventricle can be visualized. The apex frequently has less activity than the remainder of the myocardium, due to anatomic thinning in this zone. In the 45 degree left anterior oblique view, the septum, posterolatera1 and inferior walls are detected; if the heart
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perfusion
and thallium-201
LA
imaging
L
t 4..
Fig. 1. Normal thallium-201 myocardial perfusion .scintigram at rest (upper panels) and exercise (lower panels) in a patient with normal coronary arteries on selective coronary arteriography. ANT = anterior view; LAO = left anterior oblique view; LL = left lateral view.
has a vertical position in the chest, the apex makes up the inferior border.“’ In the left lateral view the anterior wall, apex, inferior and posterior walls are identified.lA It has been suggested that there are physiologic areas of decreased perfusion in the normal myocardium and, therefore, that if lesions are to be considered significant, their radioactivity must vary by more than 20 per cent from adjacent areas.‘” Myocardial
infarction
The major application of the assessment of regional myocardial perfusion with ?“‘Tl has been in patients with known or suspected ischemic heart disease. When myocardial imaging is performed at rest, ‘“‘Tl is injected intravenously with the patient standing, after a 12 hour fast, in order to decrease hepatic and splanchnic blood flow. Regions of recent or old myocardial infarction appear as areas of reduced tracer uptake at rest which do not change with exercise (vide infra)‘. Ii (Fig. 2). This is due to reduced blood flow to the infarct area and a reduction in myocardial cellular mass. The sensitivity of the procedure for acute myocardial infarction is approximately 80 per cent.‘” The frequency of positive scintigrams was significantly higher in patients studied within 24 hours after onset than in those studied later. Repeat scintigrams in the
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Fig. 2. Myocardial infarction showing a rest defect, Thallium-201 myocardial perfusion scintigram in a patient with 100 per cent obstruction of the left anterior descending and right coronary arteries. There is a focal defect involving the septum and inferior wall of the left ventricle at rest (upper panels) which is unchanged after exercise (lower panels), consistent with myocardial infarction without ischemia.
same patient demonstrated a reduction in the size of the defect with time; these observations suggest that during the acute stage of myocardial infarction the perfusion defect is due to a combination of myocardial necrosis, ischemia, and periinfarction edema. It is important to note that ““Tl perfusion scintigraphy does not differentiate between old and new infarction.‘“. Ii Ancillary clinical information and the use of infarct avid agents such as 99m technetium (99m Tc) pyrophosphate aid in this distinction. Abnormal resting ““Tl scintigrams have also been reported in patients with unstable angina pectoris,‘” and in patients with coronary spasm.‘!‘, “‘I Defects in the ““Tl scintigram at rest appear to be more sensitive than the 12-lead electrocardiogram or the ventriculogram.‘“, L”-yS Myocardial perfusion defects accurately localize the site of transmural infarction.“, .‘j However, the ability of the procedure to estimate the size of the infarct is presently limited”, “Ii; dual radionuclide studies with ““‘Tl combined with infarct avid agents such as 99m Tc pyrophosphate may improve results.‘!i. iti There are additional limitations with ““Tl rest imaging for myocardial infarction.‘:‘, (’ Lesions less than 2.5 cm. cannot usually be detected; inferior and posterior infarcts are more difficult to
114
LAO Fig. 3. Myocardial ischemia with exercise-induced defect. A patient with myocardial ischemia and 95 per cent stenosis of the left anterior descending coronary artery. The thallium-201 scintigram is normal at rest (upperpanel). After exercise there is a perfusion defect involving the apex and lower portion of the septum (LAO view).
visualize than anterior infarcts. Furthermore, thallium myocardial perfusion imaging is unable to detect lesions that are limited to the subendocardium.‘:’ Myocardial
ischemia
When patients with angina pectoris without myocardial infarction are imaged at rest, regional perfusion is generally normal. In the resting nonischemic state, viable myocardial regions supplied by stenotic coronary arteries are usually adequately perfused in either an antegrade or retrograde fashion. Both resting coronary blood flow and regional distribution were normal in animals despite coronary stenosis of 85 per cent in diameter.“’ However, the ability to increase coronary flow in response to stress became progressively abnormal with coronary stenosis exceeding 45 per cent. Therefore, by combining a stress with the imaging procedure, one can image transiently ischemic myocardium which appears as a region of decreased radioactivity compared to a separate rest image (Fig. 3).R3.‘Ii Patients are exercised on a treadmill or bicycle until limited by angina, dyspnea, significant arrhythmias, or the attainment of 85 per cent of the maximum predicted heart rate. ““Tl is then injected intravenously, and the patient continues to exercise for 45 to 60 seconds
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Myocardial ischemia with defect at exercise disappearing 4 hours later. Thallium-201 myocardial perfusion scintigram 10 minutes after exercise (upperpanel) and 4 hours later (lower panel). The decreased tracer concentration 10 minutes after exercise is not present 4 hours later, indicative of myocardial ischemia. Coronary arteriography revealed 90 per cent obstruction of the left anterior descending coronary artery.
5. Myocardial infarction with additional ischemia. A patient with triple vessel coronary disease and a previous myocardial infarction. On the rest injected thallium scintigram (upperpanel), there is decreased tracer concentration in the inferior wall seen best in the LAO view. With injection at peak exercise (lower panel), the inferior defect becomes more marked and there is decreased perfusion of the apex (Ant view), septum and posterolateral walls (LAO uier.u), consistent with myocardial infarction and ischemia.
following injection. The ““Tl is rapidly cleared from the blood and distributed within the ventricular myocardium; the proportion distributed within the left ventricular myocardium remains essentially unchanged for at least one hour after injection and, therefore, reflects the physiological state at the time of the radionuclide injection. Thus, imaging from 10 to 60 minutes after injection reflects the distribution of the radioactive cation at the time of stress, even though the patient has returned to the resting state. Mechanisms responsible for the abnormal “‘IT1 uptake under stress include more ‘“IT1 being delivered to normal myocardium in comparison to that in the myocardium distal to the critical stenosis, and decreased extraction efficiency under conditions of hypoxia and acidosis. Recent reports”“-,” indicate that imaging repeated 4 hours after exercise demonstrate resolution of exercise-induced myocardial defects, thereby obviating the need for a separate rest study (Fig. 4). Rest defects associated with an increased perfusion defect with exercise are consistent with both previous infarction and myocardial ischemia (Fig. 5). Studies evaluating patients undergoing rest and exercise ““Tl imaging have demonstrated a
sensitivity of approximately 75 to 80 per cent in detecting significant coronary artery disease.“‘-‘“. :j”. ne Our current results confirm these findings.‘” This sensitivity is higher than that reported with either the resting or exercise ECG. When the results of rest and exercise ““Tl myocardial perfusion scintigrams are combined with the results of the rest and exercise ECG, the sensitivity increases to approximately 90 per cent. ‘“‘Tl imaging is particular helpful in patients with single vessel coronary artery disease, those with abnormal resting ECG’s and those with exercise ECG’s which are difficult to interpret because of conduction abnormal abnormalities or ventricular arrhythmias. Myocardial imaging with ““Tl is currently generally a qualitative study dependent on the demonstration of relative differences in radionuelide uptake. In the presence of global ischemia due to severe proximal triple vessel disease or bilateral coronary ostial stenosis, a normal homogenous appearing scan would be evident. Quantification of the ““Tl scintigram has demonstrated a reduction in total myocardial activity.“’ Falsenegative studies may also occur in single vessel
Fig.
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finding of a perfusion defect on the exercise ““Tl scintigram would suggest coronary stenosis, whereas a normal exercise ‘“‘Tl scintigram would suggest that the exercise ECG was not indicative of hemodynamically significant coronary atherosclerosis.
PRE ANTERIOR
POST
Fig. 6. Effects of coronary artery bypass graft surgery. Preoperative (upper panels) and postoperative (lower panels) thallium-201 scintigrams at rest and exercise (anterior hew). The resting scintigrams are normal. The perfusion defect in the exercise scintigram preoperatively is not present after coronary bypass surgery. Preoperative coronary arteriography revealed 95 per cent stenosis of the left anterior descending coronary artery. Coronary arteriography 3 months postoperatively revealed a patent graft to the left anterior descending coronary artery.
disease involving either the right or the circumflex coronary artery. In addition, in the presence of a large myocardial infarction, an exercise defect may be difficult to demonstrate. We have found the specificity of ““Tl exercise scintigraphy to be 90 per cent,?” confirming recent reports by Ritchie and associates’” and by Botvinick and colleagues.‘” However, since these results were obtained from selected populations, more experience is necessary before the specificity of ““Tl scintigraphy is definitively established. An extension of the use of myocardial perfusion imaging has been employed in the evaluation of patients who have had coronary bypass surgery. The post-surgical studies by Zaret and co-worker+’ using potassium-43 have been confirmed recently with ““Tl.“-“’ Comparison of pre- and postoperative rest and exercise scintigrams have provided information regarding graft pate’ncy, status of the distal native circulation, and perioperative infarction” (Fig. 6). An additional application of the exercise ““Tl myocardial perfusion scintigram has been advocated in asymptomatic patients or patients with atypical chest pain and ST segment depression 1 mm. or greater on exercise testing.‘?, 1X,” The
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“‘IT1 perfusion imaging has also been used to evaluate patients without coronary disease. Patients with tetralogy of Fallot have been differentiated from patients with single ventricle by the appearance of the septum on the scintigram.“’ An increase in septal thickness relative to the left ventricular free wall with a ““Tl perfusion scintigram has been demonstrated in idiopathic hypertrophic subaortic stenosis.“’ Furthermore, patients with the obstructive form of the disease have a thicker basal posterior free wall than patients with the nonobstructive form of this disease. In idiopathic congestive cardiomyopathy, thallium uptake is generally uniform, whereas in ischemic cardiomyopathy focal defects in uptake are apparent.“’ While left ventricular dilatation was found in both conditions, right ventricular dilatation was more common in idiopathic congestive cardiomyopathy. Cardiomyopathy due to infiltrative systemic disease such as sarcoidosis” are associated with focal decreases in ‘“‘Tl concentration. The scintigram is not specific, however, and coronary artery disease must be differentiated on clinical grounds. Finally, thallium perfusion imaging has been reported to be a useful technique for the diagnosis of right ventricular (RV) hypertrophy?’ On low contrast ‘“‘Tl scintigrams at rest, Cohen and colleagues”” visualized the RV in all patients with RV hypertrophy; in addition, there was apparent thickness of the RV free wall. This technique was more sensitive than the ECG. Future
developments
While ““Tl is the best of the currently available potassium analogues, the optimal gammaemitting radioactive potassium analogue has not become available. It is anticipated that the future will see the development of more optimal radionuclides as well as improvements in imaging techniques and development of quantitative approaches to myocardial imaging with improved computer data processing. Methods for accurately sizing acute myocardial infarction, with or
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without the concomitant use of infarct avid agents, and for providing sequential follow-up information are needed. Finally, the use of positron-emitting potassium analogues and the positron camera promise improved spatial resolution in perfusion scintigraphy and the potential for three-dimensional reconstruction.54
11.
Conclusions
14.
In conclusion, assessment of regional myocardial perfusion with ‘“‘Tl rest and exercise provides useful information employing a technique that is non-invasive and safe. It can be performed on acutely ill patients and can be repeated for re-evaluation. The reproducibility of repeat ‘“IT1 myocardial imaging”i enables this diagnostic study to be employed in longitudinal follow-up studies. Since the myocardial perfusion scintigram provides functional information regarding regional tissue perfusion whereas the coronary arteriogram provides anatomic information, these two procedures are complementary and not competitive.
15.
12.
13.
16.
17.
18.
19.
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