International Journal of Cardiology, 34 (1992) 85-95 1992 Elsevier Science Publishers R .V . All rights reserved 0167-5273/92/$05 .00
85
CARDIO 01364
Quantification of antimyosin uptake and infarct size at various stages of myocardial infarction Tomoaki Nakata I , Mahiko Gotoh I , Tetsuya Noto l, Shigemichi Tanaka I , Tetsuro Shoji Masahiro Kubota 3 , Takatoshi Tsuda 3 and Osamu limura
2,
3
Second Department of Internal Medicine ; ' Division of Emergency and Critical Care ; 'Department of Radiology, Sapporo Medical College, Sapporo, Japan (Received 12 January 1991 ; second revision received 7 June 1991 ; accepted 22 July 1991)
Nakata T, Gotoh M, Noto T, Tanaka S, Shoji T, Kubota M, Tsuda r. limura 0 . Quantification of antimyosin uptake and infarct size at various stages of myocardial infarction . Int J Cardiol 1992 ;343 :85-95 . We studied with quantitative techniques the clinical efficacy of indium-111 antimyosin at a later stage of myocardial infarction in 18 patients at various stages after infarction . Antimyosin accumulation was detected irrespective of infarct age and size and quantified as an infarct weight with a tomographic technique . Higher intensities in a planar image were observed in anterior Q wave infarct group (36 ± 5 g) but not in inferior and non-Q wave anterior infarct groups because of the smaller infarct weights (8 ± 3 g, 13 ± 6 g, respectively) . Infarct area calculated from thallium-201 tomography significantly correlated with left ventricular ejection fraction in both recent (less than 2 weeks) and older (2-week- to 6-month-old) infarct groups (r = -0.969, P < 0.001 ; r = -0 .860, P < 0 .001, respectively), whereas there was a significant negative correlation between infarct weight and left ventricular ejection fraction in the recent infarct group (r = -0 .731, P < 0.05) but not in the older infarct group . Thus, antimyosin tomography can detect myocardial necrosis with a high sensitivity regardless of infarct age, size, and location. However, the accumulation might be affected by infarct age and correspond to necrotic mass but not necessarily to infarct volume itself at a later stage probably because of the presence of necrosed and scarred tissues in infarcted myocardium . Key words : Antimyosin Fab ; Thallium-201 ; Single photon emission computed tomography ; Myocardial infarction ; Infarct age ; Infarct size
Introduction
and acutely injured myocardium [1-3], indium-111 labeled antimyosin Fab (In-111) scintigraphy can
Since antimyosin monoclonal antibody Fab be used with a high degree of binds specifically to human myosin in irreversibly specificity to visualize myocardial ing from myocardial infarction, rejection, and viral myocarditis Correspondence to : T . Nakata . MD, Second Dept . of Internal Medicine . Sapporo Medical College . Sapporo 060, Japan .
sensitivity and necrosis resultheart transplant [4-91 . In-111 an-
timyosin Fab imaging appears to be able to detect acute myocardial infarction and the quantifica-
86 tion of myocardial necrosis by antimyosin Fab can reflect wall motion abnormality and infarct size when it is used during the first 72-96 h after the onset of infarction [4-6] . Recently, several reports in the literature [10-12] showed that an-
lished in all patients when at least 3 of the following criteria were present : (1) prolonged chest pain typical of acute myocardial infarction, (2) typical 12-lead electrocardiographic changes lasting several days after the onset of chest pain,
timyosin Fab can be taken up by infarcted myocardial tissue several days to months after the onset of infarction. Although precise identifica-
(3) serial increases in creatine kinase and MB isoenzyme levels, and (4) a fixed perfusion defect in thallium-201 myocardial scintigraphy or a defi-
tion of myocardial necrosis might contribute retrospectively to the diagnosis and selection of a therapeutic approach (since it is sometimes diffi-
nite uptake of technetium-99m pyrophosphate within several days after the onset of chest pain . Thallium-201 myocardial emission computed to-
cult to diagnose myocardial infarction at a later stage), the practice has not been widely accepted and the clinical implications of antimyosin Fab scintigraphy during the later stages of myocardial infarction have not been established . We speculate that several factors, such as the interval from onset to imaging (infarct age), type (Q wave or non-Q wave), size, and site of myocardial infarction, may influence myocardial uptake of antimyosin Fab during a remote phase of myocardial infarction . This study was designed to assess whether or not infarcted myocardium can take up antimyosin
mography was performed in all patients to assess the perfusion abnormality . Technetium-99m pyrophosphate scintigraphy was carried out in 8 of 20 patients . There were 14 patients with anteroseptal or extensive anterior infarction, 4 with inferior infarction, and 2 with posterolateral or lateral infarction . Sixteen patients had Q wave infarction and non-Q wave infarction was seen in 3 of 14 patients who had anterior infarction and in a patient with lateral infarction . Two patients in our study had a history of prior infarction . Three patients were treated with intracoronary urokinase infusion within the sixth hour after the onset of chest pain and reperfusion was confirmed angiographically in all 3 patients . Thirteen
Fab during a remote phase of myocardial infarction as well as during an acute phase and whether or not the age, size, and location of the infarct affect In-111 antimyosin Fab imaging . Furthermore, we have retrospectively tried to determine whether or not quantification of antimyosin Fab accumulation by single photon-emission computed tomography (SPECT) has clinical implications irrespective of infarct age by comparing it to infarct size determined by thallium-201 myocardial SPECT . Materials and Methods Study population We studied 20 consecutive patients with definite or strongly suspected myocardial infarction (15 men and 5 women with a mean age of 63 ± 2 years and range of 54-86 years) . All patients were admitted to the Division of Emergency and Critical Care or the Second Department of Internal Medicine, Sapporo Medical College Hospital . The diagnosis of myocardial infarction was estab-
of 20 patients underwent coronary angiography and the infarct-related arteries .were identified . Antibody preparation and In-ill antimyosin Fab scintigraphy The protocol was approved by the ethics committee for research involving human subjects at Sapporo Medical College Hospital and this study was performed as a part of a Phase III trial in Japan . After all patients had given informed consent, skin tests were performed using 0 .1 ml of a solution containing 0 .05 mg antimyosin murine monoclonal antibody (Fab) modified by conjugation with diethylene triamine pentaacetic acid (DTPA) . When a negative skin test was confirmed 15 minutes later, 74 MBq of In-Ill labeled antimyosin Fab-DTPA solution containing 0.5 mg murine monoclonal antimyosin Fab antibody (R11D10, Centocor Inc, Malvern) was injected intravenously . Infarct age, which was defined as the time interval from the onset of chest
87
pain to the injection of In-111 labeled antimyosin Fab. was 46 ± 13 days (range : 1-176 days ) (Table 1) . In-111 antimyosin Fab scans were recorded 48 hours after injection . Initially, planar scintigrams were obtained from anterior, left anterior oblique, and left lateral views using a large field of view scintillation camera (Searle LFOV) with a medium-energy, all-purpose, parallel-hole collimator . Approximately 2-3 x 10 5 counts for each projection were collected . In order to precisely assess the localization of myocardial uptake, single photon-emission computed tomography (SPECT) was subsequently performed using a large-field-of-view rotating gamma camera (Siemens ZLC 75) equipped with a high-resolution parallel-hole collimator . The data were acquired at 5-degree increments for 30 seconds per increment during a 180-degree rotation from the left posterior oblique to the right anterior oblique view . The information was stored in a 64 x 64 word matrix nuclear medicine computer system
(Shimadzu Scintipac 2400) . Serial transverse tomograms were reconstructed by a filtered backprojection algorithm with Shepp and Logan filter. Image analysis of In-111 antimyosin Fab scintigraphy Planar and SPECT antimyosin Fab images were reviewed by 2 experienced nuclear medicine physicians blinded to the clinical data . First, the presence or absence of tracer uptake was evaluated and then the localization was determined as anterior, septal, apical, lateral, inferior, and posterior. In the case of a disagreement, a third physician was asked to review the images . Final interpretation of all images was arrived at by discussion . In the planar antimyosin Fab images, myocardial activity was classified visually as follows : 0 = no or questionable activity which can not be distinguished from the background activity ; 1 + = definite but relatively faint activity (which is
TABLE 1 Summary of clinical and scintigraphic data in 18 patients with myocardial infarction Patient No .
Age/Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
86/F 61/M 61/M 81/M 73/F 63/M 58/M 56/M 57/F 70/M 55/M 55/M 56/F 61/M 59/M 54/M 69/F 57/M
ECG infarct location
Prior MI
AS extANT INF AS AS (post ICT) AS AS (non 0) INF (post ICT) AS AS ext ANT (non Q) INF (post ICT) ext ANT L(non Q) AS ext ANT AS (non Q) PL
no no no no no no no no yes no no yes no no no no no no
Infarctrelated artery
Infarct age (days)
LVEF (%)
T)-201 SPECT
In-I11 antimyosin Fab
Infarct area (cm 2)
Intensity
Infarct weight (g)
LAD RCA LAD LAD LCX LAD RCA LCX LAD LAD LCX
11 8 1 6 8 12 12 6 18 26 176 34 90 38 33 154 148 52
14 29 51 44 39 61 64 45 20 38 60 28 16 63 60 15 76 68
108 84 40 69 69 8 0 42 56 71 0 123 81 24 32 95 0 8
3 + 1 + 1 + 1 + 1 + 2 + 1+ 1 + 2 + 3 + 1+ 1 + 2 + 1 + 2 + 2 + 1 + 1+
42 46 12 18 32 24 8 2 38 55 9 59 41 2 34 20 32 9
ANT= anterior, AS = anteroseptal ; ICT = intracoronary thrombolysis ; INF = inferior ; ECG = electrocardiographic ; ext ANT = extensive anterior: L = lateral ; LAD = left anterior descending artery ; LCX = left circumflex artery ; MI = myocardial infarction ; non Q = non Q wave infarction ; PL= posterolateral; RCA = right coronary artery.
88
clearly distinguished from that of the background); 2 + = definite and increased activity but less than that in the liver; 3 + = equal or greater activity compared to that in the liver . Grades of 1 + to 3 + were considered to be positive in this study . In order to assess the influence of infarct age upon In-111 antimyosin Fab imaging, patients were divided into 3 subgroups : (1) within 14 days of infarction, (2) 14-30 days after, and (3) more than 30 days after infarction . The quantitative assessment of tracer uptake was performed using serial transverse tomograms . Infarct weight was calculated by multiplying the number of uptake-positive voxels in each slice (using a threshold of 60% of the overall maximum activity after a background subtraction) by the voxel volume (0 .216 cm') and the myocardial specific gravity (1 .05) . The values of the threshold and voxel volume were derived from SPECT phantom data with indium-111 . Infarct sizing by thallium-201 SPECT Myocardial SPECT with thallium-201 (148 MBq) was performed at rest in all patients in order to assess the location and size of the myocardial infarction . The mean time intervals between thallium-201 SPECT and the onset of myocardial infarction or the antimyosin injection were 55 ± 13 days (range : 11-180 days) and 9 ± I days (range : 3-19 days), respectively . Serial transverse tomograms were reconstructed first, followed by vertical long axis, horizontal long axis, and short axis images . Infarct size was calculated as an area of infarcted myocardium (cm') by the unfolded surface mapping method, as reported previously [13] . The method was briefly summarized as follows. Following maximum-counts circumferential profile analysis with each short axis slice, the distance from the center of a short axis tomogram to each profile point was measured to calculate the circumference (1). The profile data were plotted on each pixel line with the length (1) and one-pixel thickness to make an unfolded surface map by arranging the lines from apex to base . An infarct area was calculated by the number of pixels having the abnormal count defined as a value less than the lower normal limit (mean
value minus two standard deviations) determined from 8 normal control data with the following formula : Infarct area (cm') = 0.03 x (number of pixel with an abnormal count) where 0 .03 = area of one pixel (0 .1 cm x 0.3 cm) in this study . Thus, infarct size was quantified as an infarct area which contributed to a more accurate measurement of infarct size, compared to a percentage of infarct to left ventricle [13] . Technetium-99m pyrophosphate scintigraphy and measurement of left ventricular systolic function Pyrophosphate scintigraphy with technetium99m (740 MBq) was performed at rest within the first 7 days following the onset of myocardial infarction in 8 of 20 patients . Planar images from anterior, left anterior oblique, and left lateral views and transverse tomograms were obtained by the same methods as mentioned above . Radionuclide ventriculography with 99m-pertechnetate (740 MBq) was carried out in all patients to assess left ventricular systolic function . The mean time intervals between radionuclide ventriculography and the onset of myocardial infarction or the injection of antimyosin Fab were 52 ± 12 days (range: 15-176 days) and 9 ± 1 days (range : 1-15 days), respectively. The patient's red blood cells were labeled in vivo and after an equilibration period upon labeling data were collected from the 45-degree left anterior oblique view, with a 5- to 10-degree caudal tilt in a multiple gated mode of 500 cardiac cycles at a rate of 20-25 frames/cycle . The information obtained was then used to calculate the left ventricular ejection fraction . Statistical analysis All values are presented as group mean ± SEM. Statistical comparisons of group means were made with Student's unpaired t-test . Correlations were analyzed by linear regression computed by the least-squares method and the chisquare test was performed in order to compare individual groups. A probability of less than 0 .05 was considered significant .
89
Results In-111 labeled antimyosin Fab was injected in the 18 (of 20) patients that showed negative skin tests. Two patients showed a positive skin reaction (wheal and flare) and were therefore excluded from all subsequent analysis . Positive results in In-111 antimyosin Fab planar and tomographic images were obtained in all patients (Table 1). Fifteen of 18 planar scans were diagnostic and SPECT imaging was useful for evaluating the precise location of In-III antimyosin Fab accumulation . Furthermore, in the remaining 3 the tomographic scan was essential to identify the definite myocardial uptake by differentiating the latter from the persistent blood pool activity . The infarct sites assessed by In-111 antimyosin Fab scan correlated well with those determined by electrocardiograms and/or thallium-201 myocardial tomography . The sites of both antimyosin and pyrophosphate uptakes were relatively compatible in all 8 patients who received both tracers (Table 2) . The highest activity (3 + ) was observed in only 2 patients ; one (patient 1) from the youngest subgroup and one (patient 10) from the intermediately aged subgroup . However, there were no significant differences in left ventricular ejection fraction, infarct area, and infarct weight among the three subgroups (Table 3) . Planar and SPECT images of pyrophosphate and antimyosin Fab from a typical patient are presented in Fig . 1 . Compared with the increased activity of Tc-99m pyrophosphate on the third day after the onset of infarction, the antimyosin Fab scan performed 89 days later showed definite but relatively low myocardial uptake . On the other hand, the tracer activities were low (1 + ) in all 4 patients with non-Q wave infarction in which infarct sizes were small (i .e ., the mean infarct area was 6 ± 5 cm 2 and the mean infarct weight was 13 ± 6 g) . Antimyosin Fab scanning was used more than 30 days after onset in 3 of the 4 patients . In one of these, non-Q wave lateral infarction was delineated in the antimyosin images (Fig . 2) even though imaging was performed 40 days after the onset of infarction . There was a wide range of infarct size from 0
TA13LE 2 infarct locations determined by SPECT techniques with thatRum-201, Tc-99m pyrophosphate and In-Ill antimyosin Fab Patient infarct site No . Thallium-201 SPELT I 2
7 S 9 10 1l 12 13 14 15
ext ANT AS INF INF, SEP AS AS not detectable IMP AS AS not detectable AS, INF ext ANT L AS AS not detectable PL
In-111 AM Tc-99m PYP SPECT
Intensity Infarct site (planar) (SPECT)
ext ANT AS INF AS, INF AS not performed not performed INF not performed not performed not performed INF ext ANT not performed not performed not performed not performed not performed
3+ 1+ 1+ 1+ 1+ 2+ 1+ I231+ I+ 2+ I+ 2+ 2+ I+ I +
AS, L AS INF SEP, Ap AS AS AS, Ap INF ANT, INF AS AS INF AS . L PL AS, L, Ap AS . L AS, L PL
AL =anterolateral ; Ap =apical ; AS =anteroseptal ; ext ANT = extensive anterior ; IMP = inferior; In- Ill AM = indium-11 I labeled antimyosin Fab ; LVEF = left ventricular ejection traction ; SPECT = single photon emission computed tomography ; L = lateral ; PL = postcrolatcral : PYP = pyrophosphate ; SEP = septal .
non-Q wave infarction) to 123 cm' when infarct area was calculated by TI-201 SPECT and from 2 to 59 g when infarct weight was derived (i .e . .
TABLE 3 Comparisons of scintigraphic parameters among three patient subgroups Infarct age
85
CARDIO 01364
Quantification of antimyosin uptake and infarct size at various stages of myocardial infarction Tomoaki Nakata I , Mahiko Gotoh I , Tetsuya Noto l, Shigemichi Tanaka I , Tetsuro Shoji Masahiro Kubota 3 , Takatoshi Tsuda 3 and Osamu limura
2,
3
Second Department of Internal Medicine ; ' Division of Emergency and Critical Care ; 'Department of Radiology, Sapporo Medical College, Sapporo, Japan (Received 12 January 1991 ; second revision received 7 June 1991 ; accepted 22 July 1991)
Nakata T, Gotoh M, Noto T, Tanaka S, Shoji T, Kubota M, Tsuda r. limura 0 . Quantification of antimyosin uptake and infarct size at various stages of myocardial infarction . Int J Cardiol 1992 ;343 :85-95 . We studied with quantitative techniques the clinical efficacy of indium-111 antimyosin at a later stage of myocardial infarction in 18 patients at various stages after infarction . Antimyosin accumulation was detected irrespective of infarct age and size and quantified as an infarct weight with a tomographic technique . Higher intensities in a planar image were observed in anterior Q wave infarct group (36 ± 5 g) but not in inferior and non-Q wave anterior infarct groups because of the smaller infarct weights (8 ± 3 g, 13 ± 6 g, respectively) . Infarct area calculated from thallium-201 tomography significantly correlated with left ventricular ejection fraction in both recent (less than 2 weeks) and older (2-week- to 6-month-old) infarct groups (r = -0.969, P < 0.001 ; r = -0 .860, P < 0 .001, respectively), whereas there was a significant negative correlation between infarct weight and left ventricular ejection fraction in the recent infarct group (r = -0 .731, P < 0.05) but not in the older infarct group . Thus, antimyosin tomography can detect myocardial necrosis with a high sensitivity regardless of infarct age, size, and location. However, the accumulation might be affected by infarct age and correspond to necrotic mass but not necessarily to infarct volume itself at a later stage probably because of the presence of necrosed and scarred tissues in infarcted myocardium . Key words : Antimyosin Fab ; Thallium-201 ; Single photon emission computed tomography ; Myocardial infarction ; Infarct age ; Infarct size
Introduction
and acutely injured myocardium [1-3], indium-111 labeled antimyosin Fab (In-111) scintigraphy can
Since antimyosin monoclonal antibody Fab be used with a high degree of binds specifically to human myosin in irreversibly specificity to visualize myocardial ing from myocardial infarction, rejection, and viral myocarditis Correspondence to : T . Nakata . MD, Second Dept . of Internal Medicine . Sapporo Medical College . Sapporo 060, Japan .
sensitivity and necrosis resultheart transplant [4-91 . In-111 an-
timyosin Fab imaging appears to be able to detect acute myocardial infarction and the quantifica-
86 tion of myocardial necrosis by antimyosin Fab can reflect wall motion abnormality and infarct size when it is used during the first 72-96 h after the onset of infarction [4-6] . Recently, several reports in the literature [10-12] showed that an-
lished in all patients when at least 3 of the following criteria were present : (1) prolonged chest pain typical of acute myocardial infarction, (2) typical 12-lead electrocardiographic changes lasting several days after the onset of chest pain,
timyosin Fab can be taken up by infarcted myocardial tissue several days to months after the onset of infarction. Although precise identifica-
(3) serial increases in creatine kinase and MB isoenzyme levels, and (4) a fixed perfusion defect in thallium-201 myocardial scintigraphy or a defi-
tion of myocardial necrosis might contribute retrospectively to the diagnosis and selection of a therapeutic approach (since it is sometimes diffi-
nite uptake of technetium-99m pyrophosphate within several days after the onset of chest pain . Thallium-201 myocardial emission computed to-
cult to diagnose myocardial infarction at a later stage), the practice has not been widely accepted and the clinical implications of antimyosin Fab scintigraphy during the later stages of myocardial infarction have not been established . We speculate that several factors, such as the interval from onset to imaging (infarct age), type (Q wave or non-Q wave), size, and site of myocardial infarction, may influence myocardial uptake of antimyosin Fab during a remote phase of myocardial infarction . This study was designed to assess whether or not infarcted myocardium can take up antimyosin
mography was performed in all patients to assess the perfusion abnormality . Technetium-99m pyrophosphate scintigraphy was carried out in 8 of 20 patients . There were 14 patients with anteroseptal or extensive anterior infarction, 4 with inferior infarction, and 2 with posterolateral or lateral infarction . Sixteen patients had Q wave infarction and non-Q wave infarction was seen in 3 of 14 patients who had anterior infarction and in a patient with lateral infarction . Two patients in our study had a history of prior infarction . Three patients were treated with intracoronary urokinase infusion within the sixth hour after the onset of chest pain and reperfusion was confirmed angiographically in all 3 patients . Thirteen
Fab during a remote phase of myocardial infarction as well as during an acute phase and whether or not the age, size, and location of the infarct affect In-111 antimyosin Fab imaging . Furthermore, we have retrospectively tried to determine whether or not quantification of antimyosin Fab accumulation by single photon-emission computed tomography (SPECT) has clinical implications irrespective of infarct age by comparing it to infarct size determined by thallium-201 myocardial SPECT . Materials and Methods Study population We studied 20 consecutive patients with definite or strongly suspected myocardial infarction (15 men and 5 women with a mean age of 63 ± 2 years and range of 54-86 years) . All patients were admitted to the Division of Emergency and Critical Care or the Second Department of Internal Medicine, Sapporo Medical College Hospital . The diagnosis of myocardial infarction was estab-
of 20 patients underwent coronary angiography and the infarct-related arteries .were identified . Antibody preparation and In-ill antimyosin Fab scintigraphy The protocol was approved by the ethics committee for research involving human subjects at Sapporo Medical College Hospital and this study was performed as a part of a Phase III trial in Japan . After all patients had given informed consent, skin tests were performed using 0 .1 ml of a solution containing 0 .05 mg antimyosin murine monoclonal antibody (Fab) modified by conjugation with diethylene triamine pentaacetic acid (DTPA) . When a negative skin test was confirmed 15 minutes later, 74 MBq of In-Ill labeled antimyosin Fab-DTPA solution containing 0.5 mg murine monoclonal antimyosin Fab antibody (R11D10, Centocor Inc, Malvern) was injected intravenously . Infarct age, which was defined as the time interval from the onset of chest
87
pain to the injection of In-111 labeled antimyosin Fab. was 46 ± 13 days (range : 1-176 days ) (Table 1) . In-111 antimyosin Fab scans were recorded 48 hours after injection . Initially, planar scintigrams were obtained from anterior, left anterior oblique, and left lateral views using a large field of view scintillation camera (Searle LFOV) with a medium-energy, all-purpose, parallel-hole collimator . Approximately 2-3 x 10 5 counts for each projection were collected . In order to precisely assess the localization of myocardial uptake, single photon-emission computed tomography (SPECT) was subsequently performed using a large-field-of-view rotating gamma camera (Siemens ZLC 75) equipped with a high-resolution parallel-hole collimator . The data were acquired at 5-degree increments for 30 seconds per increment during a 180-degree rotation from the left posterior oblique to the right anterior oblique view . The information was stored in a 64 x 64 word matrix nuclear medicine computer system
(Shimadzu Scintipac 2400) . Serial transverse tomograms were reconstructed by a filtered backprojection algorithm with Shepp and Logan filter. Image analysis of In-111 antimyosin Fab scintigraphy Planar and SPECT antimyosin Fab images were reviewed by 2 experienced nuclear medicine physicians blinded to the clinical data . First, the presence or absence of tracer uptake was evaluated and then the localization was determined as anterior, septal, apical, lateral, inferior, and posterior. In the case of a disagreement, a third physician was asked to review the images . Final interpretation of all images was arrived at by discussion . In the planar antimyosin Fab images, myocardial activity was classified visually as follows : 0 = no or questionable activity which can not be distinguished from the background activity ; 1 + = definite but relatively faint activity (which is
TABLE 1 Summary of clinical and scintigraphic data in 18 patients with myocardial infarction Patient No .
Age/Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
86/F 61/M 61/M 81/M 73/F 63/M 58/M 56/M 57/F 70/M 55/M 55/M 56/F 61/M 59/M 54/M 69/F 57/M
ECG infarct location
Prior MI
AS extANT INF AS AS (post ICT) AS AS (non 0) INF (post ICT) AS AS ext ANT (non Q) INF (post ICT) ext ANT L(non Q) AS ext ANT AS (non Q) PL
no no no no no no no no yes no no yes no no no no no no
Infarctrelated artery
Infarct age (days)
LVEF (%)
T)-201 SPECT
In-I11 antimyosin Fab
Infarct area (cm 2)
Intensity
Infarct weight (g)
LAD RCA LAD LAD LCX LAD RCA LCX LAD LAD LCX
11 8 1 6 8 12 12 6 18 26 176 34 90 38 33 154 148 52
14 29 51 44 39 61 64 45 20 38 60 28 16 63 60 15 76 68
108 84 40 69 69 8 0 42 56 71 0 123 81 24 32 95 0 8
3 + 1 + 1 + 1 + 1 + 2 + 1+ 1 + 2 + 3 + 1+ 1 + 2 + 1 + 2 + 2 + 1 + 1+
42 46 12 18 32 24 8 2 38 55 9 59 41 2 34 20 32 9
ANT= anterior, AS = anteroseptal ; ICT = intracoronary thrombolysis ; INF = inferior ; ECG = electrocardiographic ; ext ANT = extensive anterior: L = lateral ; LAD = left anterior descending artery ; LCX = left circumflex artery ; MI = myocardial infarction ; non Q = non Q wave infarction ; PL= posterolateral; RCA = right coronary artery.
88
clearly distinguished from that of the background); 2 + = definite and increased activity but less than that in the liver; 3 + = equal or greater activity compared to that in the liver . Grades of 1 + to 3 + were considered to be positive in this study . In order to assess the influence of infarct age upon In-111 antimyosin Fab imaging, patients were divided into 3 subgroups : (1) within 14 days of infarction, (2) 14-30 days after, and (3) more than 30 days after infarction . The quantitative assessment of tracer uptake was performed using serial transverse tomograms . Infarct weight was calculated by multiplying the number of uptake-positive voxels in each slice (using a threshold of 60% of the overall maximum activity after a background subtraction) by the voxel volume (0 .216 cm') and the myocardial specific gravity (1 .05) . The values of the threshold and voxel volume were derived from SPECT phantom data with indium-111 . Infarct sizing by thallium-201 SPECT Myocardial SPECT with thallium-201 (148 MBq) was performed at rest in all patients in order to assess the location and size of the myocardial infarction . The mean time intervals between thallium-201 SPECT and the onset of myocardial infarction or the antimyosin injection were 55 ± 13 days (range : 11-180 days) and 9 ± I days (range : 3-19 days), respectively . Serial transverse tomograms were reconstructed first, followed by vertical long axis, horizontal long axis, and short axis images . Infarct size was calculated as an area of infarcted myocardium (cm') by the unfolded surface mapping method, as reported previously [13] . The method was briefly summarized as follows. Following maximum-counts circumferential profile analysis with each short axis slice, the distance from the center of a short axis tomogram to each profile point was measured to calculate the circumference (1). The profile data were plotted on each pixel line with the length (1) and one-pixel thickness to make an unfolded surface map by arranging the lines from apex to base . An infarct area was calculated by the number of pixels having the abnormal count defined as a value less than the lower normal limit (mean
value minus two standard deviations) determined from 8 normal control data with the following formula : Infarct area (cm') = 0.03 x (number of pixel with an abnormal count) where 0 .03 = area of one pixel (0 .1 cm x 0.3 cm) in this study . Thus, infarct size was quantified as an infarct area which contributed to a more accurate measurement of infarct size, compared to a percentage of infarct to left ventricle [13] . Technetium-99m pyrophosphate scintigraphy and measurement of left ventricular systolic function Pyrophosphate scintigraphy with technetium99m (740 MBq) was performed at rest within the first 7 days following the onset of myocardial infarction in 8 of 20 patients . Planar images from anterior, left anterior oblique, and left lateral views and transverse tomograms were obtained by the same methods as mentioned above . Radionuclide ventriculography with 99m-pertechnetate (740 MBq) was carried out in all patients to assess left ventricular systolic function . The mean time intervals between radionuclide ventriculography and the onset of myocardial infarction or the injection of antimyosin Fab were 52 ± 12 days (range: 15-176 days) and 9 ± 1 days (range : 1-15 days), respectively. The patient's red blood cells were labeled in vivo and after an equilibration period upon labeling data were collected from the 45-degree left anterior oblique view, with a 5- to 10-degree caudal tilt in a multiple gated mode of 500 cardiac cycles at a rate of 20-25 frames/cycle . The information obtained was then used to calculate the left ventricular ejection fraction . Statistical analysis All values are presented as group mean ± SEM. Statistical comparisons of group means were made with Student's unpaired t-test . Correlations were analyzed by linear regression computed by the least-squares method and the chisquare test was performed in order to compare individual groups. A probability of less than 0 .05 was considered significant .
89
Results In-111 labeled antimyosin Fab was injected in the 18 (of 20) patients that showed negative skin tests. Two patients showed a positive skin reaction (wheal and flare) and were therefore excluded from all subsequent analysis . Positive results in In-111 antimyosin Fab planar and tomographic images were obtained in all patients (Table 1). Fifteen of 18 planar scans were diagnostic and SPECT imaging was useful for evaluating the precise location of In-III antimyosin Fab accumulation . Furthermore, in the remaining 3 the tomographic scan was essential to identify the definite myocardial uptake by differentiating the latter from the persistent blood pool activity . The infarct sites assessed by In-111 antimyosin Fab scan correlated well with those determined by electrocardiograms and/or thallium-201 myocardial tomography . The sites of both antimyosin and pyrophosphate uptakes were relatively compatible in all 8 patients who received both tracers (Table 2) . The highest activity (3 + ) was observed in only 2 patients ; one (patient 1) from the youngest subgroup and one (patient 10) from the intermediately aged subgroup . However, there were no significant differences in left ventricular ejection fraction, infarct area, and infarct weight among the three subgroups (Table 3) . Planar and SPECT images of pyrophosphate and antimyosin Fab from a typical patient are presented in Fig . 1 . Compared with the increased activity of Tc-99m pyrophosphate on the third day after the onset of infarction, the antimyosin Fab scan performed 89 days later showed definite but relatively low myocardial uptake . On the other hand, the tracer activities were low (1 + ) in all 4 patients with non-Q wave infarction in which infarct sizes were small (i .e ., the mean infarct area was 6 ± 5 cm 2 and the mean infarct weight was 13 ± 6 g) . Antimyosin Fab scanning was used more than 30 days after onset in 3 of the 4 patients . In one of these, non-Q wave lateral infarction was delineated in the antimyosin images (Fig . 2) even though imaging was performed 40 days after the onset of infarction . There was a wide range of infarct size from 0
TA13LE 2 infarct locations determined by SPECT techniques with thatRum-201, Tc-99m pyrophosphate and In-Ill antimyosin Fab Patient infarct site No . Thallium-201 SPELT I 2
7 S 9 10 1l 12 13 14 15
ext ANT AS INF INF, SEP AS AS not detectable IMP AS AS not detectable AS, INF ext ANT L AS AS not detectable PL
In-111 AM Tc-99m PYP SPECT
Intensity Infarct site (planar) (SPECT)
ext ANT AS INF AS, INF AS not performed not performed INF not performed not performed not performed INF ext ANT not performed not performed not performed not performed not performed
3+ 1+ 1+ 1+ 1+ 2+ 1+ I231+ I+ 2+ I+ 2+ 2+ I+ I +
AS, L AS INF SEP, Ap AS AS AS, Ap INF ANT, INF AS AS INF AS . L PL AS, L, Ap AS . L AS, L PL
AL =anterolateral ; Ap =apical ; AS =anteroseptal ; ext ANT = extensive anterior ; IMP = inferior; In- Ill AM = indium-11 I labeled antimyosin Fab ; LVEF = left ventricular ejection traction ; SPECT = single photon emission computed tomography ; L = lateral ; PL = postcrolatcral : PYP = pyrophosphate ; SEP = septal .
non-Q wave infarction) to 123 cm' when infarct area was calculated by TI-201 SPECT and from 2 to 59 g when infarct weight was derived (i .e . .
TABLE 3 Comparisons of scintigraphic parameters among three patient subgroups Infarct age
