Relation Between Signal Intensity on T2-Weighted MR Images and Presence of Microvascular Obstruction in Patients With Acute Myocardial Infarction

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1 Cardiopulmonary Imaging Original Research Mikami et al. MRI of Myocardial Infarction Cardiopulmonary Imaging Original Research Yoko Mikami 1,2 Hajime Sakuma 1 Motonori Nagata 1 Masaki Ishida 1 Tairo Kurita 3 Issei Komuro 2 Masaaki Ito 3 Mikami Y, Sakuma H, Nagata M, et al. Keywords: cardiac MRI, microvascular obstruction, myocardial infarction, T2-weighted MRI DOI: /AJR Received January 3, 2009; accepted after revision March 24, Department of Radiology, Mie University Hospital, Edobashi, Tsu, Mie , Japan. Address correspondence to Y. Mikami (yokomikami@gmail.com). 2 Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. 3 Department of Cardiology, Mie University Hospital, Mie, Japan. WEB This is a Web exclusive article. AJR 2009; 193:W321 W X/09/1934 W321 American Roentgen Ray Society Relation Between Signal Intensity on T2-Weighted MR Images and Presence of Microvascular Obstruction in Patients With Acute Myocardial Infarction OBJECTIVE. In experimental animal models and human autopsy studies, hemorrhagic infarction caused by microvascular injury has been detected after coronary reperfusion. The purpose of this study was to determine whether detection of myocardial edema with T2- weighted MRI is influenced by the presence of microvascular obstruction. SUBJECTS AND METHODS. Thirty-seven patients underwent black-blood fat-suppressed T2-weighted, rest perfusion, and late gadolinium-enhanced MRI 5.4 ± 3.1 days after the onset of acute myocardial infarction. On T2-weighted MR images, the signal intensity in relation to that of remote myocardium was determined in the late gadolinium-enhanced and periinfarction areas. Segment-based analysis was performed to determine whether the presence of microvascular obstruction influences the detection of myocardial edema. RESULTS. The averaged signal intensity in the late gadolinium-enhanced area without microvascular obstruction was significantly higher than the signal intensity in remote normal myocardium (relative signal intensity, 1.83 ± 0.50; p < 0.001). In contrast, the signal intensity in the microvascular obstruction area on T2-weighted images was not significantly different from the signal intensity in remote myocardium (relative signal intensity, 1.14 ± 0.26). The percentages of late gadolinium-enhanced segments with high signal intensity on T2-weighted MR images were 95% (73/77) without microvascular obstruction and 30% (22/73) with microvascular obstruction. CONCLUSION. With T2-weighted MRI, infarction-associated edema can be reliably detected in infarct lesions without microvascular obstruction. Microvascular obstruction, however, does not necessarily exhibit high signal intensity on T2-weighted MRI. Careful attention is required in interpretation of cardiac MR images of patients who have experienced acute myocardial infarction and undergone percutaneous coronary intervention. The findings on T2-weighted MR images can be substantial underestimates of the extent of acute myocardial infarction. E arly and accurate diagnosis of acute myocardial infarction (MI) is necessary for optimizing the pharmacologic and interventional treatment of patients with acute MI and for improving outcome [1]. Late gadolinium-enhanced MRI can be used to differentiate infarcted myocardium from normal myocardium [2, 3] and is useful for predicting recovery of impaired contractile function in patients with MI [4 6]. Although differentiation between acute MI and chronic MI is frequently required in the care of patients with MI, both acute and chronic infarcts exhibit late gadolinium enhancement and thus cannot be differentiated with late gadolinium-enhanced MRI alone [6 8]. Cardiac MRI that combines late gadolinium enhancement and T2- weighted imaging has been found useful in differentiating acute from chronic MI because T2-weighted MRI depicts the infarctassociated myocardial edema found only in acute MI [8 10]. At the center of the infarcted segment, both myocytes and capillaries may undergo necrosis. In that situation, despite reopening of the epicardial coronary arteries with successful reperfusion therapy, capillaries in myocardial tissue continue to be occluded and are not reperfused [11]. The absence of tissue perfusion is called microvascular obstruction and can be evaluated noninvasively with contrast-enhanced MRI [12, 13]. In experimental studies of animal models and in autopsy studies of humans, hemorrhagic infarction caused by microvascular injury has been observed after coronary reperfusion [14 17]. Lotan et al. [18, 19] studied AJR:193, October 2009 W321

2 Mikami et al. canine models of acute MI and found that the signal intensity (SI) on T2-weighted MR images was significantly lower in MI lesions with hemorrhage. Those findings with animal models indicated that SI on T2-weighted MR images might be altered substantially in patients with acute MI, particularly in patients with microvascular obstruction [12, 13, 20 22]. The purpose of this study was to determine whether detection of myocardial edema with T2-weighted MRI is influenced by the presence or absence of microvascular obstruction in patients with acute MI. Subjects and Methods Patients The institutional review board approved this study protocol. All patients gave written informed consent. A total of 37 patients (31 men, six women; mean age, 64 ± 13 years) were enrolled. They had been admitted to the coronary care units at our hospital with the diagnosis of acute MI, which was defined as persistent typical chest pain, characteristic abnormal ECG findings, and presence of enzymatic criteria. The exclusion criteria were any contraindication to MRI and a history of previous MI. The patient characteristics are presented in Table 1. All patients underwent primary percutaneous coronary revascularization before MRI, and reperfusion was successful in all cases. TABLE 1: Patient Characteristics (n = 37) Characteristic Protocol for MRI MRI was performed a mean of 5.4 ± 3.1 days after the onset of MI. The patient was placed supine in a 1.5-T imager (Achieva 1.5T Nova Dual, Philips Healthcare) with 5-channel cardiac coils around the chest. All cardiac MR images were gated to ECG and were obtained during repeated breath-holds. After acquisition of initial survey images, ECG-gated black-blood T2-weighted MR images were acquired in three short-axis imaging planes (basal, midventricular, and apical) of the left ventricle that corresponded to 16 myocardial segments based on the American Heart Association 17-segment model (the apical segment was not used). We used double-inversion recovery pulses for blood suppression with the following parameters: TR, two cardiac cycles; TE, 90 milliseconds; inversion time, 940 milliseconds; inversion recovery fat saturation pulse inversion time, 180 milliseconds; slice thickness, 8 mm; field of view, cm; acquisition matrix size, ; number of signals averaged, 2. Cine MR images encompassing the entire left ventricle were acquired in short-axis imaging planes with a steady-state free precession sequence; TR/TE, 3.2/1.6; flip angle, 55 ; slice thickness, 10 mm; slice gap, 0 mm; field of view, cm; acquisition matrix size, ; sensitivity encoding parallel imaging (SENSE) factor, 2. First-pass contrast-enhanced myocardial perfusion MR images were obtained in the resting state in short-axis imaging planes of the left ventricle that corresponded to the slice locations of T2-weighted MRI. A saturation recovery steady-state free precession sequence was used with the following parameters: 3.0/1.5; flip angle, 40 ; time between saturation preparation pulse and center of k-space acquisition, 150 milliseconds; slice thickness, 8 mm; field of view, cm; acquisition matrix size, ; SENSE factor, 2. Gadopentetate dimeglumine (Magnevist, Bayer Schering Pharma) was administered IV at a dose of 0.05 mmol/kg and injection rate of 4 ml/s and followed by a saline flush of 20 ml at the same injection rate. Dynamic acquisitions were repeated every two cardiac cycles, 30 dynamic MR images being obtained for each slice location. The patients were instructed to begin the breath-hold at the start of image acquisition and to maintain the breath-hold as long as possible. Immediately after rest myocardial perfusion MRI, an additional gadolinium dose of 0.1 mmol/ kg was injected to achieve a cumulative dose of 0.15 mmol/kg. After 10 minutes, late gadolinium-enhanced MR images were obtained with an inversion Value Age (y) 64 ± 13 Sex Men 31 (84) Women 6 (16) Maximum total creatine kinase concentration (IU/L) 1,970 ± 2,045 Time between onset of myocardial infarction and MRI (d) 5.4 ± 3.1 Left ventricular ejection fraction (%) 49 ± 12 Diabetes mellitus 19 (51) Hypertension 20 (54) Smoking 18 (49) Hypercholesterolemia 22 (59) Obesity 11 (30) Family history of coronary artery disease 7 (19) Time between pain and balloon inflation (min) 294 ± 282 Infarct-related artery Left anterior descending 18 (49) Left circumflex 3 (8) Right coronary 16 (43) ST segment elevation myocardial infarction 21 (57) Stent implantation 33 (89) Heart rate during MRI (beats/min) 72 ± 13 Note Values are number of patients with percentage in parentheses or mean ± SD. recovery 3D gradient-echo sequence with short-axis imaging slices covering the entire left ventricle. The MRI parameters were 3.7/1.2; inversion time, milliseconds; field of view, cm; acquisition matrix size, ; SENSE factor, 2. The late gadolinium-enhanced images were reconstructed with a slice thickness of 10 mm and increment of slice location of 5 mm. A Look-Locker sequence was used to adjust the inversion time to minimize the SI of normal myocardium. To ensure matching slice position between sequences, the midventricular slice was placed at the midpoint between the apex and the mitral valve. T2-weighted MR images and rest myocardial perfusion MR images were acquired in three shortaxis imaging planes (basal, midventricular, and apical), care being taken to obtain the same slice position for the different pulse sequences. Cine MR and late gadolinium-enhanced MR images were obtained in the short-axis imaging planes covering the entire left ventricle and containing the same slice position for T2-weighted MR images and rest perfusion MR images. Image Analysis The T2-weighted, first-pass myocardial perfusion, and late gadolinium-enhanced MR images W322 AJR:193, October 2009

3 MRI of Myocardial Infarction A Fig. 1 Graph shows relative signal intensity compared with remote normal myocardium in area of microvascular obstruction, infarction area without microvascular obstruction, and periinfarction area on T2-weighted MRI. Relative signal intensity in area of microvascular obstruction is significantly lower than that in infarction area without microvascular obstruction and periinfarction area. were evaluated in consensus by two readers with 19 and 3 years of experience in cardiac MRI. We displayed T2-weighted, rest perfusion, and late gadolinium-enhanced MR images side by side. Late gadolinium-enhanced and T2-weighted MR images were analyzed on a workstation (Virtual Place, AZE). To exclude the effect of variation in SI due to surface coil sensitivity variations, we measured regional SI in the anterior wall, septum, inferior wall, and lateral wall on T2-weighted images in eight healthy volunteers without risk factors for coronary artery disease. We then calculated the relative SI in the anterior wall, septum, inferior wall, and lateral wall compared with the mean SI of these four areas. We defined the late gadolinium-enhanced area as the area showing the SI greater than the mean plus twice the SD of remote myocardium on late gadolinium-enhanced images [5, 23]. According to the definition of microvascular obstruction in previous studies [24, 25], we defined areas of microvascular obstruction as areas that did not have an SI greater than the mean plus twice the SD of remote myocardium surrounded by abnormal enhancement on late gadoliniumenhanced images and that showed low or no enhancement on rest myocardial perfusion MR images. Areas of microvascular obstruction and late gadolinium enhancement were measured and expressed as percentages of left ventricular area. Areas of abnormal late gadolinium enhancement and microvascular obstruction defined on late gadolinium-enhanced images were then copied to corresponding T2-weighted images. T2-weighted MRI findings were considered abnormal when myocardial SI was greater than the mean plus twice the SD of the SI in remote myocardium [8]. The periinfarction area was defined as the area without late gadolinium enhancement adjacent to the area of late gadolinium enhancement and exhibited an SI greater than the mean plus twice the SD of the SI in remote myocardium on T2-weighted MR images. We placed 5-mmdiameter regions of interest on T2-weighted MR images to measure the SI in the area of microvascular obstruction, SI in the late gadoliniumenhanced area without microvascular obstruction, and SI in the periinfarction area. To exclude high SI due to the presence of nonsuppressed slowly flowing blood in the left ventricular cavity, we discerned the endocardial border of the left ventricular wall by performing cine MRI on the same slice and at the same cardiac phase of T2-weighted MRI. The SI of area of microvascular obstruction, SI in the late gadoliniumenhanced area without microvascular obstruction, and SI in the periinfarction area on T2-weighted cardiac MR images were presented as relative SI ratios compared with the SI in remote normal myocardium [19]. Segment-based analysis was performed with a 16-segment model in which the left ventricular myocardium was divided into six basal, six midventricular, and four apical segments. The presence or absence of late gadolinium enhancement, TABLE 2: Relative Signal Intensity on T2-Weighted MR Images Microvascular Obstruction No. of Segments Relative Signal Intensity a a Mean ± SD. Relative Signal Intensity Compared With Remote Area Microvascular Obstruction Present p < 0.01 Infarction Area Microvascular Obstruction Absent p < 0.01 Present ± 0.26 Absent ± 0.50 Periinfarction Area Fig year-old man without microvascular obstruction. Emergency percutaneous coronary intervention was performed for management of occlusion of left anterior descending coronary artery, and successful reperfusion was achieved. A, Late gadolinium-enhanced MR image shows high signal intensity (arrows) in anteroseptal wall of left ventricle. B, Rest perfusion MR image shows no perfusion defect. C, T2-weighted MR image shows transmural high intensity (arrowheads). B C AJR:193, October 2009 W323

4 Mikami et al. microvascular obstruction, and myocardial edema were recorded for each myocardial segment. Data analysis was performed by a researcher blinded to clinical data and to interpretations made by the readers of the cardiac MR images. Statistical Analysis All values were expressed as mean ± SD. We confirmed that our data were normally distributed. A two-tailed Student s t test was used to compare the SI of the late gadolinium-enhanced area, SI of the area of microvascular obstruction, and SI of the periinfarction area with the SI in remote myocardium. In a segment-based analysis, the chi-square test was used to determine the statistical significance of differences in percentages A Fig year-old man with microvascular obstruction. Emergency percutaneous coronary intervention was performed for management of occlusion of left circumflex artery. A, Late gadolinium-enhanced MR image shows microvascular obstruction (arrow) in inferolateral wall of left ventricle. B, Rest perfusion MR image shows microvascular obstruction (arrowhead). C, T2-weighted MR image shows signal intensity in microvascular obstruction area is similar to that in remote myocardium. A of segments with high SI on T2-weighted cardiac MR images. A value of p < 0.05 was inferred to be statistically significant. Results In healthy volunteers, the relative SIs in the anterior wall, septum, inferior wall, and lateral wall on T2-weighted images compared with the mean SI of those four areas were 1.04 ± 0.06, 0.97 ± 0.07, 0.97 ± 0.08, and 1.01 ± 0.03 (p not significant). Figure 1 shows the relative SI of the area of microvascular obstruction, the late gadolinium-enhanced area without microvascular obstruction, and the periinfarction area compared with the SI of remote normal myocardium on B T2-weighted MR images. Table 2 summarizes the number of segments analyzed and the average SI. Myocardial edema was revealed as an area of high SI area on T2-weighted MR images of patients without microvascular obstruction (Fig. 2). The averaged SI in late gadoliniumenhanced areas without microvascular obstruction was significantly higher than the SI in remote normal myocardium, the relative SI being 1.83 ± 0.50 (p < 0.001). The SI in the periinfarction area also was significantly higher, the relative SI being 1.66 ± 0.17 (p < 0.001). In the area of microvascular obstruction, however, increased SI caused by myocardial edema was not seen on T2-weighted Fig year-old man with microvascular obstruction. Emergency percutaneous coronary intervention was performed for management of occlusion of left anterior descending coronary artery. A, Late gadolinium-enhanced MR image shows microvascular obstruction (arrows) in anteroseptal wall of left ventricle. B, Rest perfusion MR image shows microvascular obstruction (arrowhead). C, T2-weighted MR image shows signal intensity in microvascular obstruction area is not altered compared with signal intensity in remote myocardium. B C C W324 AJR:193, October 2009

5 MRI of Myocardial Infarction MR images (Figs. 3 and 4). The SI in the area of microvascular obstruction on T2-weighted images was not significantly different from the SI in remote myocardium (relative SI, 1.14 ± 0.26). The percentage of infarcted myocardium compared with the total area of left ventricular wall on three short-axis imaging slices was 16.8% ± 13.5%. The percentage area of microvascular obstruction was 10.0% ± 10.3%, and the percentage periinfarction area was 11.0% ± 4.3%. In segment-based analyses, late gadolinium enhancement was observed in all 37 patients and in 150 of 592 segments (25%). Microvascular obstruction was found in 19 of 37 patients (51%) and in 73 of 592 segments (12%). In all patients, on late gadolinium-enhanced MR images, areas that did not exhibit an SI greater than the mean plus twice the SD of remote myocardium and were surrounded by late gadolinium enhancement exhibited perfusion defects on rest myocardial perfusion MRI. Seventy-three of 77 (95%) late gadolinium-enhanced segments without microvascular obstruction had high SI on T2- weighted MR images. However, increased SI on T2-weighted cardiac MR images was observed in only 22 of 73 (30%) segments with microvascular obstruction (p < 0.05). The percentage of segments with high SI on T2-weighted MR images was not significantly different among the major coronary arteries. The percentages of segments with high SI in patients without microvascular obstruction were 93% (42/45) for the left anterior descending coronary artery, 100% (4/4) for the left circumflex artery, and 96% (27/28) for the right coronary artery (p not significant). The percentages of segments that showed high SI in patients with microvascular obstruction were 32% (12/38) for the left anterior descending coronary artery, 25% (1/4) for the left circumflex artery, and 29% (9/31) for the right coronary artery (p not significant). In a patient-based analysis, infarct-related myocardial edema on T2- weighted cardiac MR images was detected in at least one of 16 segments in 35 of 37 patients (95%). In the other two patients, however, both with microvascular obstruction, myocardial edema was not detected in any of 16 segments on T2-weighted MR images. Discussion In this study, we obtained cardiac MR images of patients with acute MI who underwent percutaneous coronary intervention dur ing the acute phase. A substantial number of left ventricular myocardial segments with microvascular obstruction did not exhibit high signal intensity on T2-weighted MR images. This finding is important in interpretation of MR images of patients with acute MI, particularly those who have undergone percutaneous coronary intervention, because of the risk of underestimation of the extent of acute MI on T2-weighted MR images. A study by Abdel-Aty et al. [8] showed that high transmural SI on T2-weighted MR images accurately represents the area of acute MI. Several studies of animal models, however, showed that SI on T2-weighted MR images was significantly lower in hemorrhagic areas of reperfusion after MI than in areas without hemorrhage [18, 19]. In a study in which 16 dogs were subjected to 3 hours of coronary occlusion followed by 1 hour of reperfusion, Lotan et al. [19] observed areas of decreased SI on T2-weighted MR images of 13 of the dogs. The area of decreased SI on T2-weighted MR images correlated well with the hemorrhage size calculated from a tissue slice. Good agreement also was found between areas of decreased SI on T2-weighted MR images and the distribution of tissue RBCs, as assessed with 51 Cr labeling. The results of our study show that the SI on T2-weighted images was significantly lower in areas of microvascular obstruction than in late gadolinium-enhanced areas without microvascular obstruction. A previous study with dogs [19] showed that the T2 relaxation time of infarcted tissue with hemorrhage (58 ± 9 milliseconds) was significantly shorter than that in the absence of hemorrhage (98 ± 13 milliseconds). Although no histopathologic data were available to confirm the presence of hemorrhage in areas of microvascular obstruction in patients with acute MI, the presence of erythrocytes with paramagnetic characteristics of deoxyhemoglobin that have leaked from capillaries to the tissue is most likely related to the reduced SI on T2-weighted MR images. Although edema leads to increased T2 relaxation time in zones of MI, hemorrhage can reduce the T2 relaxation time. The opposing effects of infarction and hemorrhage on T2 relaxation time can result in averaged T2 values not significantly different from those of normal myocardium [19]. The prevalence of microvascular obstruction and the severity of myocardial damage are strongly influenced by infarct size. In our study, the percentage of late gadolinium-enhanced area was 16.8% ± 13.5% and that of microvascular obstruction area was 10.0% ± 10.3%. This percentage of late gadoliniumenhanced area is similar to that in previous studies (11.5% ± 2.5% [6] and 20.7% ± 11.5% [23]). The percentage of area of microvascular obstruction in our study also is in accordance with that in a previous study [23] (13.5% ± 5.7%). We also measured periinfarction area in this study because the periinfarction area with edema corresponds to salvaged myocardium in patients with acute MI who have undergone primary percutaneous coronary revascularization. The prevalence of microvascular obstruction was 51% in the group of patients with acute MI who underwent coronary intervention. This prevalence of microvascular obstruction shows good agreement with results of previous studies. In a study by Stork et al. [10], microvascular obstruction was found in 29 of 50 patients (58%) who underwent reperfusion therapy with angioplasty or thrombolysis. Hombach et al. [25] studied the cases of 110 patients with acute MI and detected microvascular obstruction in 51 patients (46%). We defined area of microvascular obstruction as the area that did not exhibit SI greater than the mean plus twice the SD of remote myocardium surrounded by abnormal enhancement on late gadolinium-enhanced images and showed low or no enhancement on rest myocardial perfusion MR images. Lund et al. [23] found high concordance between areas of microvascular obstruction identified as hypoenhanced zones on rest myocardial perfusion MR images and areas of microvascular obstruction identified as persistent hypoenhancement on late gadolinium-enhanced MR images. In our study, areas of microvascular obstruction identified on late gadolinium-enhanced MR images consistently exhibited perfusion defects on rest myocardial perfusion MR images. We acquired late gadolinium-enhanced MR images 10 minutes after administration of gadolinium contrast medium because the peripheral aspect of areas of microvascular obstruction can gradually exhibit late enhancement if the images are acquired 15 minutes or more after contrast administration [26, 27]. Several potential limitations of our study should be acknowledged. The number of patients was relatively small. In addition, no histopathologic confirmation was obtained for evaluation of the relation between the presence of hemorrhage and altered SI on T2-weighted MR images. Interpretation of T2-weighted MR images of the heart can be AJR:193, October 2009 W325

6 Mikami et al. subjective. Therefore, in this study, myocardium on T2-weighted MR images was considered abnormal when we observed high SI greater than the mean plus twice the SD of the SI in remote normal myocardium. This approach is in accordance with the method used in a previous study by Abdel-Aty et al. [8]. The microvascular obstruction observed at contrast-enhanced MRI does not necessarily indicate the presence of hemorrhage in infarcted myocardium. Although previous results in the literature [28] have indicated that the presence of macroscopic hemorrhage correlates well with the area of no reflow, further studies are necessary to determine the relation between areas of microvascular obstruction and those of hemorrhage. We conclude that infarct-associated edema in infarct lesions without microvascular obstruction can be reliably detected with T2- weighted MRI. Microvascular obstruction, however, does not necessarily exhibit high signal intensity on T2-weighted MR images. 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