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Cardiac Imaging |
1 From the Department of Radiology (N. Ishida, H.S., K.T.) and First Department of Internal Medicine (M.M., T.O., N. Isaka, T.N.), Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. From the 2001 RSNA scientific assembly. Received September 5, 2002; revision requested November 7; final revision received February 13, 2003; accepted March 6. Address correspondence to H.S. (e-mail: sakuma@clin.medic.mie-u.ac.jp).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: First-pass contrast-enhanced MR images of the entire left ventricle were acquired in 104 patients at rest and during dipyridamole-induced stress by using an interleaved notched saturation technique. Coronary angiography was performed in all patients, and stress perfusion single photon emission computed tomography (SPECT) was performed in 69 patients. Receiver operating characteristic curve analysis was performed to compare the diagnostic accuracies of first-pass contrast-enhanced stress MR imaging and stress SPECT, with coronary angiography as the reference standard.
RESULTS: The overall sensitivity of MR imaging for depicting at least one coronary artery with significant stenosis was 90% (69 of 77 patients). The sensitivities of MR imaging for depiction of single-, double-, and triple-vessel stenoses were 85% (33 of 39 patients), 96% (22 of 23 patients), and 100% (15 of 15 patients), respectively. The specificity of MR imaging for identification of patients with significant coronary artery stenoses was 85% (23 of 27 patients). The areas under the receiver operating characteristic curve for detection of significant stenosis in individual coronary arteries were 0.888 (observer 1) and 0.911 (observer 2) for MR imaging and 0.707 (observer 1, P < .001) and 0.750 (observer 2, P < .001) for SPECT.
CONCLUSION: In patients without myocardial infarction, stress enhancement at dynamic MR imaging correlates more closely with quantitative coronary angiography results than does stress enhancement at SPECT.
© RSNA, 2003
Index terms: Coronary vessels, stenosis or obstruction, 54.76 • Magnetic resonance (MR), perfusion study, 54.121412, 54.121416, 54.12143, 54.12144 • Myocardium, ischemia, 54.1939, 54.76 • Myocardium, MR, 54.121412, 54.121416, 54.12143, 54.12144 • Myocardium, SPECT, 54.12162
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Dynamic magnetic resonance (MR) imaging with a bolus injection of contrast material enables assessment of first-pass myocardial enhancement, which can yield information regarding the extent and physiologic significance of coronary artery disease. Recent advances in cardiac MR imaging enable dynamic first-pass contrast material–enhanced imaging of the entire left-ventricular myocardium with improved image quality. However, to our knowledge, the diagnostic accuracy of multisection first-pass contrast-enhanced MR imaging in depicting coronary artery stenosis has not been evaluated in a study in which the findings are compared with SPECT results.
The purpose of this study was to determine the accuracy of first-pass contrast-enhanced stress MR imaging in depicting myocardial ischemia in patients without myocardial infarction.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Patients with myocardial infarction were excluded (3,4,10) because the major objective of this study was to determine the diagnostic accuracy of stress myocardial MR imaging in depicting flow-limiting stenosis of the coronary artery. Stress perfusion SPECT was performed in 69 of the 104 patients within 4 weeks before or after the MR imaging examinations. The study protocol was approved by the institutional ethics committee, and informed consent was obtained from all patients.
MR Imaging
First-pass contrast-enhanced myocardial MR images were obtained with the patient at rest and under stress by using a 1.5-T cardiac MR imaging unit (Signa CV/i; GE Medical Systems, Waukesha, Wis) equipped with high-performance gradients for cardiac MR imaging (maximum slew rate, 150 T/m/sec; gradient strength, 40 mT/m) and a four-element phased-array cardiac coil (GE Medical Systems). Two coil elements were placed on the anterior part of the chest, and two coil elements were placed on the posterior part.
Breath-hold cine MR images were obtained in contiguous short-axis planes from the apex to the base of the heart with the patient in a resting state. After the cine MR images were acquired, the patients were intravenously injected with 0.56 mg of dipyridamole (Persantin Injection; Boehringer Ingelheim, Ingelheim, Germany) per kilogram of body weight for 4 minutes. While under pharmacologic stress, all patients performed an isometric handgrip exercise, because previous study (11,12) results indicate that adjunctive handgrip exercises are useful for reducing the occurrence and severity of both noncardiac side effects and atrioventricular blockage.
The first-pass contrast-enhanced MR images (6.7/1.4/180 [repetition time msec/echo time msec/inversion time msec], 20° flip angle, echo train length of four, receiver bandwidth of ±125 kHz, 32 x 32-cm field of view, 128 x 128 matrix, 10-mm section thickness, 2-mm intersection gap, true pixel size of 2.5 x 2.5 mm in data acquisition) were acquired with a gradient-echo sequence by using fast echo-planar readouts and interleaved notched saturation (13). Seven to eight short-axis images of the left ventricle were acquired at every other heartbeat for approximately 1 minute.
After dynamic MR image acquisition was started, 0.075 mmol/kg of gadolinium-based contrast material (gadopentetate dimeglumine, Magnevist; Schering, Berlin, Germany) was injected into the antecubital vein at a rate of 4 mL/sec and followed by a 20-mL saline flush. Because we used visual analysis, we injected a relatively high dose (0.075 mmol/kg) of contrast material to achieve better contrast between the ischemic and normal myocardial regions. The patients were instructed to begin holding their breath at the start of the image acquisition and to maintain the breath hold as long as possible. After intravenous injection of aminophylline (Nipro Pharma, Osaka, Japan) and a 15-minute delay, 0.075 mmol/kg of the gadolinium-based contrast material was injected and first-pass contrast-enhanced MR images were obtained with the patient in a resting state. One author (N. Ishida) continuously monitored blood pressure, heart rate, and any serious adverse reactions caused by the pharmacologic stress throughout the MR imaging examination. The total MR imaging time was approximately 50 minutes.
Coronary Angiography
Coronary angiography was performed in all patients by using a biplane angiography system (Advantx ACT BP; GE Medical Systems). Cardiologists (M.M., T.O., N. Isaka) performed coronary angiography in multiple projections by using 5-F Judkins or Amplatz catheters (Clinical Supply, Gifu, Japan). Without knowing the results of the other imaging examinations, one of two authors (M.M., N. Ishida) used a workstation (Advantage CRS workstation and quantitative coronary angiography package; GE Medical Systems) to perform coronary angiography–based quantitative analysis to determine the severity of coronary stenoses in each patient. Stenosis of 70% or more of the luminal diameter of the coronary artery was considered to be significant.
Scintigraphic Examinations
In 69 patients, myocardial scintigraphy was performed within either 4 weeks before or 4 weeks after first-pass contrast-enhanced myocardial MR imaging. Forty-nine patients underwent thallium 201 (201Tl) SPECT, and 20 patients underwent SPECT with technetium 99m (99mTc) sestamibi or 99mTc tetrofosmin. Patients performed the maximal tolerated level of exercise on a treadmill according to the Bruce protocol. Thirty-five patients completed the exercise stress test by reaching one of the exercise end points, which included greater than 85% of the maximal predicted heart rate, greater than 2 mm of ST segment depression, and moderate to severe angina. At the peak exercise level, 74 MBq of thallium chloride or 555 MBq of one of the 99mTc myocardial perfusion agents (ie, sestamibi or tetrofosmin) was injected intravenously and the patients exercised for 1 additional minute before the test was terminated.
Stress was induced with dipyridamole and the handgrip exercise in 34 patients who could not complete the body exercise study. The radioactive tracer was injected within 2 minutes after the end of the dipyridamole infusion (0.56 mg/kg intravenously for 4 minutes). Scintigraphic imaging started 15 minutes after the injection. The at-rest injection of radioactive tracer was performed 3–4 hours after completion of the stress image acquisitions. Thirty-seven MBq of Tl chloride or 555 MBq of one of the 99mTc myocardial perfusion agents was reinjected before the at-rest SPECT data were obtained.
SPECT data were acquired with a triple-head camera (GCA-9300A; Toshiba, Tokyo, Japan). The acquisition parameters were as follows: 128 x 128 matrix, 3.2-mm pixel size, 6.4-mm section thickness, and three heads with a clockwise rotation of 120° each (total rotation of 360°). The actual spatial resolution of the SPECT images was substantially lower than the SPECT voxel size; the full width at half maximum was approximately 12 mm. The SPECT images were reconstructed at a workstation (GMS-5500PI; Toshiba) by using a Butterworth filter with a cutoff frequency of 0.45 cycle per pixel and a triple-energy-window scatter compensation method. Transverse images were reoriented in the short horizontal-long and vertical-long axes.
Assessment of MR and SPECT Images
Two readers (K.T., N. Ishida) evaluated MR image quality by consensus and determined the presence or absence of altered first-pass enhancement. K.T. has 20 years of subspecialist experience in nuclear cardiology and 15 years of experience in cardiac MR imaging. N. Ishida has 6 years of experience in cardiac MR imaging and 5 years of experience in nuclear cardiology. Images of the left ventricular myocardium were divided into three sections that corresponded to the locations of three major coronary arteries: the left anterior descending artery, circumflex artery, and right coronary artery. To evaluate sensitivity and specificity, the two readers, by consensus and blinded to the results of coronary angiography and the other imaging examination (ie, MR imaging or SPECT), recorded the presence or absence of altered first-pass contrast enhancement on the stress MR images and the presence or absence of reduced uptake on the stress SPECT images. Patient cases were randomized and presented in a different order for each modality.
Dynamic MR images depicting the up-slope segment of myocardial enhancement were evaluated. We compared the at-rest and stress first-pass contrast-enhanced MR images to differentiate low enhancement caused by coronary artery stenosis from artifact. Myocardial contrast enhancement was considered to be abnormal when persistent low enhancement was observed on at least three consecutive images obtained during the first pass of gadopentetate dimeglumine through the myocardium. SPECT images were considered to be abnormal when there was a decrease, at visual inspection, of radioactive tracer uptake in any myocardial segment compared with the uptake in the normal segments.
To generate receiver operating characteristic (ROC) curves, we performed additional image assessments after an interval of longer than 6 months. After the order of the patient cases was randomized, the MR and SPECT images were presented for interpretation. Two readers (N. Ishida, K.T.) evaluated the images independently for ROC analysis, and each reader assigned one of five confidence grades without knowing the results of coronary angiography and the other imaging examination. Grade 1 meant low enhancement caused by coronary artery stenosis definitely absent; grade 2, probably absent; grade 3, equivocal; grade 4, probably present; and grade 5, definitely present on the three myocardial sections corresponding to the three major coronary arteries.
The diagnostic accuracy of each imaging modality was estimated by calculating the area under the ROC curve for each reader by using computer software (ROKIT; Charles E. Metz, University of Chicago, Ill). Stenosis of 70% or more of the luminal diameter at coronary angiography was used as the reference standard.
Statistical Analysis
Results are expressed as the mean ± 1 SD. The statistical significance of differences in areas under the ROC curve between stress MR imaging and stress SPECT was evaluated by using the univariate z score test. Two-tailed P values of less than .05 were considered to be statistically significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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The sensitivities and specificities of first-pass contrast-enhanced stress myocardial MR imaging in the identification of patients with significant stenosis are summarized in Table 3. The overall sensitivity of MR imaging in the identification of patients with significant stenosis of at least one coronary artery was 90% (69 of 77 patients). Sensitivities were 85% (33 of 39 patients), 96% (22 of 23 patients), and 100% (15 of 15 patients), respectively, for the detection of single-, double-, and triple-vessel disease. The specificity of MR imaging in the identification of patients with significant stenosis of the coronary artery was 85% (23 of 27 patients).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Assessment of Myocardial Perfusion with MR Imaging
SPECT and PET have been used for the evaluation of myocardial perfusion (14–19). These techniques are limited by their dependency on radioactive tracers, attenuation artifacts (for SPECT), and a site cyclotron (for PET). Cardiac MR imaging has been used primarily to obtain anatomic information and assess left ventricular function. Myocardial perfusion abnormalities can be detected by using dynamic MR imaging with a bolus injection of contrast material (20). Since conventional MR contrast materials distribute to extracellular spaces during the first pass in the circulation (21), fast sequences are required to delineate myocardial perfusion.
The results of several previous studies (22–25) have demonstrated that alterations in myocardial perfusion can be assessed by using MR imaging. With recent advances in MR imaging techniques, including hybrid echo-planar imaging and interleaved notched saturation, the diagnostic capability of first-pass contrast-enhanced myocardial MR imaging may be substantially improved (26–28). In this study, the entire left ventricular myocardium was imaged during two cardiac cycles, which seemed to be sufficient to evaluate the first-pass dynamics of the contrast material through this region. Schwitter et al (29) recently reported that multisection MR assessment of myocardial perfusion with use of a hybrid echo-planar method has 91% sensitivity and 94% specificity in the detection of coronary artery disease, as defined at nitrogen 13 ammonia PET.
MR Imaging Performance in the Diagnosis of Myocardial Ischemia
In the current study, ROC analysis revealed significant improvements in the detection of myocardial ischemia with use of first-pass contrast-enhanced stress myocardial MR imaging, as compared with the detection at myocardial SPECT, which is widely used in the clinical assessment of coronary artery disease. A larger area under the ROC curve indicates a greater separation between disease and healthy coronary artery regions; this results in better discrimination between stenotic and nonstenotic coronary arteries. As demonstrated in Table 5, the overall sensitivity of first-pass contrast-enhanced myocardial MR imaging in depicting single-vessel disease was substantially higher than that of SPECT. The higher spatial resolution of MR imaging enables better delineation of small subendocardial ischemia and may explain the improved diagnostic performance in the detection of coronary artery disease.
Another advantage of MR imaging is excellent visualization of anatomic structures in the heart, such as the left ventricular and right ventricular myocardia and the major coronary arteries. Therefore, the distribution of myocardial ischemia in relation to the territories of the major coronary arteries can be easily identified with MR imaging.
Study Limitations
There were several limitations in this study: The study group had a high prevalence of coronary artery disease and a much higher proportion of male patients than female patients. The limited number of patients without significant coronary artery stenosis prevented a reliable assessment of the overall specificity of MR imaging and SPECT in depicting myocardial ischemia. In this study, patients who had had myocardial infarction were excluded, because the major objective of this study was to evaluate the diagnostic value of stress myocardial MR imaging in the detection of flow-limiting stenosis in the coronary artery. However, the differentiation between ischemic but viable myocardium and infarcted myocardium is important in managing the treatment of patients. The diagnostic performance of the combined first-pass stress MR imaging and delayed-enhancement MR imaging examination in patients with myocardial infarction remains to be determined.
In this study, SPECT images were acquired in 35 patients during exercise-induced stress and in the remaining 34 patients during dipyridamole-induced stress. Previous studies (30–33) have revealed that the sensitivities and specificities of myocardial perfusion scintigraphy performed with exercise-induced stress and of that performed with pharmacologic stress are similar in the assessment of coronary artery disease. In the present study, ROC analysis results indicated the high diagnostic performance of MR imaging as compared with the performance of perfusion SPECT, regardless of whether MR imaging was performed with exercise-induced or pharmacologic stress.
Although coronary artery disease involves a continuous spectrum of obstruction severities, the diagnostic accuracies of MR imaging and SPECT depend on the angiographic cutoff value used to define significant disease. This means that some stenoses that are physiologically nonsignificant may be classified as significant disease and that some physiologically significant stenoses may be classified as nonsignificant disease. The use of quantitative coronary angiography can minimize the interobserver and intraobserver variabilities in angiographic interpretations. However, angiographic approaches do not enable precise evaluation of the physiologic influences that coronary artery stenoses have on coronary artery blood flow, especially in patients who have intermediate-severity coronary artery stenoses.
In the current study, neither quantitative nor semiquantitative assessment of first-pass contrast-enhanced MR imaging was employed. Rather, we compared MR imaging and SPECT by using qualitative assessment. To minimize subjective bias during image interpretation, ROC analysis was used to assess the diagnostic accuracy of MR imaging and SPECT. Quantitative assessment of first-pass contrast-enhanced MR imaging with correction for inhomogeneous coil sensitivity may further improve the sensitivity and specificity of first-pass contrast-enhanced MR imaging and may be useful for eliminating interobserver variabilities.
In conclusion, enhancement at dynamic MR imaging during stress correlates more closely with quantitative coronary angiography results than do stress SPECT findings in patients without myocardial infarction. Multisection first-pass contrast-enhanced MR imaging performed with cardiac MR imaging units is a noninvasive technique that can enable assessment of the altered first-pass dynamics of gadolinium-based contrast material through the heart during stress in patients with coronary artery disease.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, N. Ishida, H.S.; study concepts, H.S.; study design, N. Ishida, H.S.; literature research, N. Ishida; clinical studies, M.M., T.O., N. Isaka; data acquisition, N. Ishida, H.S., M.M.; data analysis/interpretation, N. Ishida, H.S., K.T.; statistical analysis, N. Ishida, H.S.; manuscript preparation, N. Ishida; manuscript definition of intellectual content and editing, N. Ishida, H.S.; manuscript revision/review and final version approval, T.N., K.T.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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= observer 1 results, 
= observer 2 results.