Myocardial perfusion imaging with ggmT~ or ‘13*In macroaggregated albumin: Correlation of the perfusion image with clinical, angiographic, surgical, and histologic findings Glen W. Hamilton, James L. Ritchie,
M.D. M.D.
David Allen, Ph.D. Eugene Lapin, M.D. John A. Murray, M.D. Seattle, Wash.
Precise definition of ischemic and scarred segments of left ventricular myocardium is of major clinical importance. Revascularization of ischemic segments may relieve ischemia and improve myocardial performance, while enhanced delivery of blood to areas of the ventricular myocardium which are predominantly scar tissue will do neither. This information regarding the state of the myocardium is not fully provided by current electrocardiographic (ECG), angiographic, or hemodynamic techniques.‘-” Myocardial perfusion imaging following the direct intracoronary injection of particulate radiopharmaceuticals allows external visualization of the relative distribution of coronary blood flow at the capillary level. Since the state of the myocardium is directly related to blood supply in patients with atherosclerotic disease, this technique potentially provides a method for assessing the presence of regional ischemia and scar due to infarction. This report compares the results of myocardial perfusion imaging with clinical history, ECG, left ventriculography, coronary angiography, and surgical and autopsy findings in 77 patients. Perfusion defects in the myocardial images will be shown to be related primarily to scar due to From the Divisions of Nuclear Veterans Administration Hospital, School of Medicine, Seattle. Received
for publication
July
Reprint Veterans 98108.
requests: Dr. Administration
Glen W. Hospital,
708
M&i&w and
and Cardiology, Seattle Uniyersity of Washington
16, 1974. Hamilton, Chief, Nuclear Medicine, 4435 Beacon Ave. S., Seattle, Wash.
previous infarction or, in a few cases, to regional ischemia in patients with the syndrome of preinfarction angina. Methods
A total of 77 myocardial perfusion images were performed in 76 supine resting patients undergoing diagnostic coronary arteriography. Patients with congenital or valvular heart disease were excluded from this study. The left coronary artery alone was imaged in 57 patients, the right coronary artery alone in seven patients, and both the left and right coronary arteries in 13 patients. All were fully informed of the investigative nature of the study. All patients had a complete history, physical examination, and ECG. ECG’s were interpreted as positive for myocardial infarction only if typical Q-waves of 0.04 second duration were present. Additionally, the probability of past myocardial infarction was assessed as follows: none-no clinical or ECG evidence of infarction; possible-episodes of prolonged, severe pain; no ECG Q-waves; probable-clinical history of infarction, negative or equivocal ECG, or ECG Qwaves alone; and definite-ECG Q-waves, appropriate clinical history, and enzyme documenta” tion. Coronary arteriography was performed using either the Sones or the Judkins technique. Coronary arteriograms were interpreted by at least two observers. The area of the most severe narrowing was measured and the severity of stenosis expressed as the per cent of diameter
June, 1975, Vol. 89, No. 6, pp. 708-715
Myocardial perfusion imaging wrth “‘CfY or ” ‘lliln
_ANT
LAO
L LAT
RIGHT 8 LEFT c ARY IMJECTHIN Fig. 1. Injection of the left coronary artery (top row) produces an elliptical (ANT or L LAT) or spherical (LAO) pattern; an inferior wedge of less activity is produced by perfusion of the inferior system from the right coronary artery. Injection of the right coronary artery (middle row) produces a “ball and tail” configuration, the former reflecting perfusion of the inferior left ventricle, the latter perfusion of the right ventricle. Injection of both arteries shows uniform perfusion of the left ventricle with a small right ventricular appendage. Abbreviations: ANT, anterior; L LAT, left lateral; and LAO, left anterior oblique.
narrowing as compared to the diameter of the most proximal normal area of vessel. Biplane left ventriculography was performed using 0.75 to 1.0 C.C. per kilogram of radiographic contrast material filmed at 12 frames per second (roll films) or 60 frames per second (tine filming). Left ventricular volumes and systolic ejection fraction (SEF) were determined by the length-area method of Dodge and co-workers.* The ventricular contraction pattern was assessed in both planes and graded as normal (I), borderline abnormal (II), localized akinesis or hypokinesis (III), localized dyskinesis (IV), or diffuse hypo- or akinesis (V), using the method of Hamilton, Murray, and
Kennedy.” High specific activity “gmTechnetium or llD”‘Indium macroaggregated albumin (TcMAA, InMAA) was prepared using stannous chloride.” The MAA contained 1.5 to 3.0 mCi of Y!‘mTc or ‘% on 30,000 to 60,000 particles of MAA. Ninety per cent of the particles were from 20 to 40 p in size with no particles exceeding 100 p in diameter. Following coronary angiography, the tagged MAA was injected directly into one or both coronaries, flushed in with 5 C.C. of saline, and the catheter position confirmed by angiography. A delay of two minutes was observed between the last injection of radiographic contrast media and
American Heart Journal
the injection of MAA to allow coronary flow to return to a near basal level.- Following completion of the catheterization procedure, patients were taken directly to the Nuclear Medicine Laboratory; imaging was usually started within 30 minutes of the time of MAA injection and required 3 to 10 minutes per view. One hundredthousand count Polaroid “scintiphotos” were obtained using a Nuclear-Chicago HP gamma camera in the right anterior oblique, anterior, left anterior oblique, left lateral, left posterior oblique, and posterior positions. Camera collimation varied depending on whether ‘+‘“‘Tc. i’~‘mIn, or both had been injected; in most cases a 4,000 parallel hole, medium energy collimator was employed. Two patients experienced transient angina at or near the time of MAA injection; there were no ECG or intracoronary pressure changes during or immediately following injection. Myocardial perfusion images were read by two independent observers without knowledge of the clinical history or laboratory data. The normal image was defined as uniform perfusion of the arterial bed injected-the abnormal image as a clearly discernible region of diminished activity. Intra-observer variation was minimal; in two studies only one observer described regions of slightly decreased perfusion. An additional three
709
Hamilton
et al.
Fig. 2. The anatomy of a dominant right coronary artery system (posterior descending artery arising from the right coronary) is overlaid with the three major perfusion image zones in the LAO view. The left anterior descending coronary (LAD) artery supplies the anteroseptal portion of the sphere, the circumflex coronary artery the posterolateral portion, the posterior descending artery (PDA) an inferior wedge.
studies were felt by both observers to be technically inadequate due to breakdown of the tagged MAA resulting in high background levels. These five studies were deleted from the initial 82 patients studied, leaving 77 patients for analysis. Statistical analyses were performed with the Student’s t-test for unpaired data and reported as the mean & one standard deviation of the series. * Results The normal myocardial image. Three normal resting images are presented in Fig. 1. The resul*Since, in most cases, only one coronary artery was injected, there were five cases in which the arterial bed involved by definite infarction was not imaged. Tha Ave cases (two patients with infarction in the left coronary system in whom only the right coronary artery was injected and three patients with inferior infarctions with dominant right coronary arteries in whom the left coronary artery was injected) were eliminated from the comparative analysis of image data versus ECG, history of infarction, and hemodynamic data since the area of known abnormality was not imaged.
710
tant image is dependent upon which coronary arteries are injected (Fig. 1) and the coronary anatomy. Injection of the left coronary artery (LCA) alone shows uniform distribution in the myocardium supplied by the LCA. Normally, the LCA injection appears much like the image of the left ventricle as seen by angiography, with a small inferior defect representing the right coronary artery (RCA) supply to the inferior diaphragmatic left ventricle. The RCA injection appears as a ball of activity representing flow to the inferior diaphragmatic left ventricle with a much less dense tail representing flow to the right ventricle. When both arteries are injected, the left ventricular myocardium appears uniformly active and there is a faint visualization of the right ventricular myocardium (lower images, Fig. 1). Fig. 2 illustrates the basic pattern of myocardial images in the left anterior oblique (LAO) view with the regions of arterial distribution overlaid on a diagram of the normal coronary arteriogram. It can be readily appreciated that in this view the left anterior descending (LAD) supplies an anterior-septal wedge, the circumflex a posterior lateral wedge, and the RCA a smaller inferior diaphragmatic wedge. The LAO view, which visualizes the heart from the apex toward the base, is the single best view for determining which areas of myocardium are abnormally perfused. The abnormal myocardial images. Abnormal myocardial images demonstrate areas of diminished activity corresponding to areas of decreased blood flow. Three typical examples are presented in Fig. 3. Fig. 3 (left) shows a patient with an anteroseptal infarction due to complete occlusion of the left anterior descending coronary artery. Fig. 3 (center) illustrates the image pattern resulting from an RCA occlusion with inferior infarction. An inferior defect is seen and intense activity in the right ventricle is also present due to the RCA occlusion. Fig. 3 (right) shows a posterior lateral defect due to complete circumflex occlusion with infarction. Myocardial image correlations. Overall, 41 patients had perfusion defects and 36 patients demonstrated normal, uniform myocardial perfusion. The majority of patients in both groups (401 41, 34/36) had angina pectoris. Three of five patients with the syndrome of pre-infarction angina had image defects. Twenty-two patients were classified as having no myocardial infarction, 17 as possible, 8 as June, 1975, Vol. 89, No. 6
Myocardial
LAO
LAO
perfusion
imaging
with
“!““Tr or l”“llln
LAO i p:’ y/
Anteroseptal defect
hf. diaphrugrnatlc defect
Posterior iaterai defect
I-CA inj Total owl. LAD
LCA 8 RCA inj Total occl. RCA
LCA inj Total occi. circ.
Fig. 3. Typical image defects in the LAO view; the left image showing decreased image showing decreased activity inferiorIy with hang up of activity in the proximal right image showing decreased activity posterolaterally. These defects corresponded inf., inferior: inj., lateral myocardial infarctions. Abbreviations: occl., occluded: artery; and RCA, right coronary artery.
probable, and 25 as definite. Ninety-six per cent of the patients (24/25) in the latter group had abnormal images, while only one of those without infarction had an abnormal image (Fig. 4). Electrocardiographic Q-waves were present in 28 patients; all but one of these had abnormal images. However, only 66 per cent of the group with abnormal images had Q-waves. The mean systolic ejection fraction (SEF) for the group with normal images with 63 f 11 per cent compared to 43 -+ 15 percent (p
M.D. M.D.
David Allen, Ph.D. Eugene Lapin, M.D. John A. Murray, M.D. Seattle, Wash.
Precise definition of ischemic and scarred segments of left ventricular myocardium is of major clinical importance. Revascularization of ischemic segments may relieve ischemia and improve myocardial performance, while enhanced delivery of blood to areas of the ventricular myocardium which are predominantly scar tissue will do neither. This information regarding the state of the myocardium is not fully provided by current electrocardiographic (ECG), angiographic, or hemodynamic techniques.‘-” Myocardial perfusion imaging following the direct intracoronary injection of particulate radiopharmaceuticals allows external visualization of the relative distribution of coronary blood flow at the capillary level. Since the state of the myocardium is directly related to blood supply in patients with atherosclerotic disease, this technique potentially provides a method for assessing the presence of regional ischemia and scar due to infarction. This report compares the results of myocardial perfusion imaging with clinical history, ECG, left ventriculography, coronary angiography, and surgical and autopsy findings in 77 patients. Perfusion defects in the myocardial images will be shown to be related primarily to scar due to From the Divisions of Nuclear Veterans Administration Hospital, School of Medicine, Seattle. Received
for publication
July
Reprint Veterans 98108.
requests: Dr. Administration
Glen W. Hospital,
708
M&i&w and
and Cardiology, Seattle Uniyersity of Washington
16, 1974. Hamilton, Chief, Nuclear Medicine, 4435 Beacon Ave. S., Seattle, Wash.
previous infarction or, in a few cases, to regional ischemia in patients with the syndrome of preinfarction angina. Methods
A total of 77 myocardial perfusion images were performed in 76 supine resting patients undergoing diagnostic coronary arteriography. Patients with congenital or valvular heart disease were excluded from this study. The left coronary artery alone was imaged in 57 patients, the right coronary artery alone in seven patients, and both the left and right coronary arteries in 13 patients. All were fully informed of the investigative nature of the study. All patients had a complete history, physical examination, and ECG. ECG’s were interpreted as positive for myocardial infarction only if typical Q-waves of 0.04 second duration were present. Additionally, the probability of past myocardial infarction was assessed as follows: none-no clinical or ECG evidence of infarction; possible-episodes of prolonged, severe pain; no ECG Q-waves; probable-clinical history of infarction, negative or equivocal ECG, or ECG Qwaves alone; and definite-ECG Q-waves, appropriate clinical history, and enzyme documenta” tion. Coronary arteriography was performed using either the Sones or the Judkins technique. Coronary arteriograms were interpreted by at least two observers. The area of the most severe narrowing was measured and the severity of stenosis expressed as the per cent of diameter
June, 1975, Vol. 89, No. 6, pp. 708-715
Myocardial perfusion imaging wrth “‘CfY or ” ‘lliln
_ANT
LAO
L LAT
RIGHT 8 LEFT c ARY IMJECTHIN Fig. 1. Injection of the left coronary artery (top row) produces an elliptical (ANT or L LAT) or spherical (LAO) pattern; an inferior wedge of less activity is produced by perfusion of the inferior system from the right coronary artery. Injection of the right coronary artery (middle row) produces a “ball and tail” configuration, the former reflecting perfusion of the inferior left ventricle, the latter perfusion of the right ventricle. Injection of both arteries shows uniform perfusion of the left ventricle with a small right ventricular appendage. Abbreviations: ANT, anterior; L LAT, left lateral; and LAO, left anterior oblique.
narrowing as compared to the diameter of the most proximal normal area of vessel. Biplane left ventriculography was performed using 0.75 to 1.0 C.C. per kilogram of radiographic contrast material filmed at 12 frames per second (roll films) or 60 frames per second (tine filming). Left ventricular volumes and systolic ejection fraction (SEF) were determined by the length-area method of Dodge and co-workers.* The ventricular contraction pattern was assessed in both planes and graded as normal (I), borderline abnormal (II), localized akinesis or hypokinesis (III), localized dyskinesis (IV), or diffuse hypo- or akinesis (V), using the method of Hamilton, Murray, and
Kennedy.” High specific activity “gmTechnetium or llD”‘Indium macroaggregated albumin (TcMAA, InMAA) was prepared using stannous chloride.” The MAA contained 1.5 to 3.0 mCi of Y!‘mTc or ‘% on 30,000 to 60,000 particles of MAA. Ninety per cent of the particles were from 20 to 40 p in size with no particles exceeding 100 p in diameter. Following coronary angiography, the tagged MAA was injected directly into one or both coronaries, flushed in with 5 C.C. of saline, and the catheter position confirmed by angiography. A delay of two minutes was observed between the last injection of radiographic contrast media and
American Heart Journal
the injection of MAA to allow coronary flow to return to a near basal level.- Following completion of the catheterization procedure, patients were taken directly to the Nuclear Medicine Laboratory; imaging was usually started within 30 minutes of the time of MAA injection and required 3 to 10 minutes per view. One hundredthousand count Polaroid “scintiphotos” were obtained using a Nuclear-Chicago HP gamma camera in the right anterior oblique, anterior, left anterior oblique, left lateral, left posterior oblique, and posterior positions. Camera collimation varied depending on whether ‘+‘“‘Tc. i’~‘mIn, or both had been injected; in most cases a 4,000 parallel hole, medium energy collimator was employed. Two patients experienced transient angina at or near the time of MAA injection; there were no ECG or intracoronary pressure changes during or immediately following injection. Myocardial perfusion images were read by two independent observers without knowledge of the clinical history or laboratory data. The normal image was defined as uniform perfusion of the arterial bed injected-the abnormal image as a clearly discernible region of diminished activity. Intra-observer variation was minimal; in two studies only one observer described regions of slightly decreased perfusion. An additional three
709
Hamilton
et al.
Fig. 2. The anatomy of a dominant right coronary artery system (posterior descending artery arising from the right coronary) is overlaid with the three major perfusion image zones in the LAO view. The left anterior descending coronary (LAD) artery supplies the anteroseptal portion of the sphere, the circumflex coronary artery the posterolateral portion, the posterior descending artery (PDA) an inferior wedge.
studies were felt by both observers to be technically inadequate due to breakdown of the tagged MAA resulting in high background levels. These five studies were deleted from the initial 82 patients studied, leaving 77 patients for analysis. Statistical analyses were performed with the Student’s t-test for unpaired data and reported as the mean & one standard deviation of the series. * Results The normal myocardial image. Three normal resting images are presented in Fig. 1. The resul*Since, in most cases, only one coronary artery was injected, there were five cases in which the arterial bed involved by definite infarction was not imaged. Tha Ave cases (two patients with infarction in the left coronary system in whom only the right coronary artery was injected and three patients with inferior infarctions with dominant right coronary arteries in whom the left coronary artery was injected) were eliminated from the comparative analysis of image data versus ECG, history of infarction, and hemodynamic data since the area of known abnormality was not imaged.
710
tant image is dependent upon which coronary arteries are injected (Fig. 1) and the coronary anatomy. Injection of the left coronary artery (LCA) alone shows uniform distribution in the myocardium supplied by the LCA. Normally, the LCA injection appears much like the image of the left ventricle as seen by angiography, with a small inferior defect representing the right coronary artery (RCA) supply to the inferior diaphragmatic left ventricle. The RCA injection appears as a ball of activity representing flow to the inferior diaphragmatic left ventricle with a much less dense tail representing flow to the right ventricle. When both arteries are injected, the left ventricular myocardium appears uniformly active and there is a faint visualization of the right ventricular myocardium (lower images, Fig. 1). Fig. 2 illustrates the basic pattern of myocardial images in the left anterior oblique (LAO) view with the regions of arterial distribution overlaid on a diagram of the normal coronary arteriogram. It can be readily appreciated that in this view the left anterior descending (LAD) supplies an anterior-septal wedge, the circumflex a posterior lateral wedge, and the RCA a smaller inferior diaphragmatic wedge. The LAO view, which visualizes the heart from the apex toward the base, is the single best view for determining which areas of myocardium are abnormally perfused. The abnormal myocardial images. Abnormal myocardial images demonstrate areas of diminished activity corresponding to areas of decreased blood flow. Three typical examples are presented in Fig. 3. Fig. 3 (left) shows a patient with an anteroseptal infarction due to complete occlusion of the left anterior descending coronary artery. Fig. 3 (center) illustrates the image pattern resulting from an RCA occlusion with inferior infarction. An inferior defect is seen and intense activity in the right ventricle is also present due to the RCA occlusion. Fig. 3 (right) shows a posterior lateral defect due to complete circumflex occlusion with infarction. Myocardial image correlations. Overall, 41 patients had perfusion defects and 36 patients demonstrated normal, uniform myocardial perfusion. The majority of patients in both groups (401 41, 34/36) had angina pectoris. Three of five patients with the syndrome of pre-infarction angina had image defects. Twenty-two patients were classified as having no myocardial infarction, 17 as possible, 8 as June, 1975, Vol. 89, No. 6
Myocardial
LAO
LAO
perfusion
imaging
with
“!““Tr or l”“llln
LAO i p:’ y/
Anteroseptal defect
hf. diaphrugrnatlc defect
Posterior iaterai defect
I-CA inj Total owl. LAD
LCA 8 RCA inj Total occl. RCA
LCA inj Total occi. circ.
Fig. 3. Typical image defects in the LAO view; the left image showing decreased image showing decreased activity inferiorIy with hang up of activity in the proximal right image showing decreased activity posterolaterally. These defects corresponded inf., inferior: inj., lateral myocardial infarctions. Abbreviations: occl., occluded: artery; and RCA, right coronary artery.
probable, and 25 as definite. Ninety-six per cent of the patients (24/25) in the latter group had abnormal images, while only one of those without infarction had an abnormal image (Fig. 4). Electrocardiographic Q-waves were present in 28 patients; all but one of these had abnormal images. However, only 66 per cent of the group with abnormal images had Q-waves. The mean systolic ejection fraction (SEF) for the group with normal images with 63 f 11 per cent compared to 43 -+ 15 percent (p
