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AJR 2005; 185:95-102
© American Roentgen Ray Society

Original Research

Diagnostic Accuracy of Stress First-Pass Contrast-Enhanced Myocardial Perfusion MRI Compared with Stress Myocardial Perfusion Scintigraphy

Hajime Sakuma1, Naohisa Suzawa2, Yasutaka Ichikawa2, Katsutoshi Makino3, Tadanori Hirano2, Kakuya Kitagawa1 and Kan Takeda1

1 Department of Radiology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
2 Department of Radiology, Matsusaka Central Hospital, Matsusaka, Mie, Japan.
3 Department of Internal Medicine, Matsusaka Central Hospital, Matsusaka, Mie, Japan.

Received January 21, 2004; accepted after revision October 6, 2004.

 
Address correspondence to H. Sakuma (sakuma{at}clin.medic.mie-u.ac.jp).


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The purpose of this study was to determine the diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery prepared turbo fast low-angle shot (turbo FLASH) compared with stress myocardial perfusion scintigraphy. Recent studies show that first-pass contrast-enhanced myocardial perfusion MRI can provide noninvasive detection of low-limiting stenosis in the coronary artery.

MATERIALS AND METHODS. First-pass contrast-enhanced MR images were acquired at rest and during stress in 40 patients with suspected coronary artery disease. All patients underwent thallium-201 SPECT without attenuation correction and coronary angiography. Two reviewers independently assigned one of five confidence grades without knowing the results of coronary angiography for receiver operating characteristic (ROC) analysis. Luminal stenosis >70% on coronary angiography was used as a reference standard.

RESULTS. On coronary angiography, 70% or greater diameter stenosis of the coronary artery was observed in 21 (52.5%) of 40 patients. The areas under the ROC curve for detection of significant stenosis in the individual coronary artery were 0.86 (observer 1) and 0.84 (observer 2) for MRI. These values were 0.79 (observer 1, p = not significant) and 0.72 (observer 2, p = not significant) for 201Tl SPECT.

CONCLUSION. The diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery-prepared turbo FLASH was comparable with that of stress 201Tl SPECT. Stress first-pass contrast-enhanced MRI is a noninvasive technique that can be used as an alternative to stress myocardial perfusion scintigraphy.


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Accurate assessment of myocardial ischemia caused by flow-limiting stenosis in the epicardial coronary artery is important in evaluating patients with chest-pain syndromes and in managing patients after therapeutic interventions [1, 2]. Stress myocardial perfusion scintigraphy has been widely used for demonstrating altered regional myocardial perfusion in patients with coronary artery disease [3-7].

Dynamic MRI with a bolus injection of contrast material enables assessment of first-pass myocardial enhancement during pharmacologic stress, which can provide information regarding the presence and extent of coronary artery disease [8-12]. In recent studies using hybrid echo-planar MRI sequences [13, 14], stress perfusion MRI showed a sensitivity of 87-90% and specificity of approximately 85% when coronary angiography was used as a gold standard. In addition, the enhancement at dynamic MRI during stress correlated more closely with coronary angiographic results than stress SPECT findings in patients without myocardial infarction [14].

Although excellent diagnostic performance of MRI was documented in the recent studies, these results were obtained with a myocardial perfusion MRI sequence with echo-planar readout. The purpose of this study was to determine the diagnostic performance of stress perfusion MRI compared with stress myocardial perfusion scintigraphy by using a saturation-recovery turbo fast low-angle shot (turbo FLASH) MRI sequence that is widely available.


Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
We retrospectively evaluated MR and SPECT images in 40 patients with suspected coronary artery disease (28 men and 12 women; mean age, 64.6 years ± 9.0 [SD]; age range, 48-78 years) who underwent stress first-pass contrast-enhanced MRI, stress thallium-201 SPECT scintigraphy, and coronary angiography within 4 weeks. The study protocol of rest and stress perfusion MRI was approved by the institutional review board and all patients gave informed consent for the MRI study. Exclusion criteria for the current retrospective assessment were previous myocardial infarction, abnormal Q-wave on ECG, chest pain at rest, abnormal myocardial wall motion, severe arrhythmia, and coronary event between the imaging studies. Patients with myocardial infarction were excluded [15-17] because the major objective of this study was to determine the diagnostic accuracy of stress first-pass contrast-enhanced MRI in depicting flow-limiting stenosis of the coronary artery. Coronary angiography was performed by cardiologists as a diagnostic procedure, and stenosis of 70% or more of the luminal diameter on quantitative coronary angiography was considered significant.

First-pass contrast-enhanced MR images of the heart were obtained at rest and during stress using a 1.5 T MR imager (Magnetom Vision, Siemens). The maximum slew rate was 40 T/m/sec and the maximal gradient strength was 25 mT/m. MR image acquisitions were gated to the ECG. The body array coil consisted of four circulatory polarized radiofrequency coils. Two circulatory polarized coil elements were equipped in a housing that was put on the patient table, and two other coil elements were placed on the patient. All four elements were always active and each coil had its own receiver channel. First-pass contrast-enhanced MR images were obtained with a saturation-recovery turbo FLASH sequence (2 R-R intervals/1.2 ms/58 ms [repetition time msec/TE msec/inversion time msec], 32 x 32 cm field of view, 84 x 128 matrix, 10-mm section thickness, 5-mm intersection gap). Acquisition of five to six short-axis images of the left ventricle was continuously repeated every other heartbeat. Thirty dynamic MR images were acquired for each slice location. After dynamic MR image acquisition was started, 0.03 mmol/kg of gadolinium contrast material (gadopentetate dimeglumine, Magnevist; Schering) was rapidly injected in the antecubital vein and was followed by a 20-mL saline flush. 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 first-pass contrast-enhanced MR images in the resting state were acquired, the patients were injected with IV 0.56 mg of dipyridamole (Persantine injection, Boehringer Ingelheim) per kilogram of body weight for 4 min. Blood pressure and heart rate were monitored while the patients were in the magnet, and any serious adverse reaction caused by the pharmacologic stress was recorded throughout the MRI examination. Two minutes after dipyridamole was administered, the acquisition of first-pass contrast-enhanced MR images with stress were initiated using the same imaging parameters and imaging locations as used in the resting study. Delayed contrast-enhanced MR images were obtained with a segmented inversion recovery FLASH sequence on contiguous short-axis imaging planes 15 min after stress-perfusion MR images. Immediately after acquiring stress perfusion MRI, 0.09 mmol/kg of gadopentetate dimeglumine was injected to achieve a total dose of 0.15 mmol/kg. MRI parameters for delayed contrast-enhanced MR images included a repetition time of 6.0 msec, a TE of 3.4 msec, an inversion time of 200-250 msec, a section thickness of 10 mm, a field of view of 240 x 320 mm, and an image matrix of 192 x 256. Inversion time was adjusted by acquiring several test images with different inversion times.

Thallium-201 myocardial SPECT scintigraphy was performed by exercise stress or pharmacologic stress. The maximum tolerated exercise on a treadmill was performed according to the standard Bruce protocol. Twenty-six patients completed the exercise stress test by reaching one of the exercise end points, which included greater than 85% of the maximum 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 was injected IV and the patients exercised for an additional minute before the test was terminated. Stress was induced with dipyridamole administration [18-22] in 14 patients who could not complete the exercise study. Two minutes after the end of the dipyridamole infusion (0.56 mg/kg IV for 4 min), 74 MBq of thallium chloride was injected. Scintigraphic imaging started 15 min after the injection. The at-rest injection of radioactive tracer was performed 4 hr after completion of the stress image acquisitions by exercise or pharmacologic stress. Thirty-seven MBq of 201Tl chloride were reinjected before the rest SPECT data were obtained. SPECT data were acquired using a triple-head camera (GCA9300A, Toshiba) equipped with lower-energy high-resolution collimators. The acquisition parameters were as follows: 128 x 128 matrix, 3.2-mm pixel size, 6.4-mm section thickness, three heads with a clockwise rotation of 120° each (total rotation of 360°), and a continuous acquisition mode with 6° angular steps at 18 sec/step. The full width at half maximum of SPECT was approximately 12 mm. The SPECT images were reconstructed at a workstation (GMS-5500PI, Toshiba) using a Butterworth filter with a cutoff frequency of 0.45 cycles per pixel and a triple-energy-window scatter compensation method. Transverse images were reconstructed in the short, horizontal-long, and vertical-long axes.

To evaluate the sensitivity and specificity, two experienced investigators qualitatively evaluated MR images by consensus without knowing the clinical or angiographic findings. Rest and stress perfusion MR images were displayed side by side on a workstation. Perfusion MR images were evaluated by manually paging the images. Semiquantitative analysis was not performed in this study. 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. Perfusion defect on MR images was defined as focal region of myocardium that had diminished contrast enhancement compared with normal myocardium on first-pass contrast-enhanced MR images [23]. Stenotic coronary artery disease was considered present if a myocardial perfusion defect was present during stress that was not observed at rest in the area that did not exhibit abnormal enhancement on delayed enhanced MR images. SPECT images were also assessed visually by two experienced investigators by consensus. Patient cases were randomized and presented in a different order for SPECT. Slices were displayed sequentially in all three cardiac planes. Stenotic coronary artery disease was considered to be present if redistribution was observed on the 4-hr images.

Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic performances of MRI and SPECT. After the order of the patient cases was randomized, MR and SPECT images were presented for interpretation. Two reviewers evaluated the images independently for ROC analysis, and each reviewer 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 was definitely absent; grade 2, probably absent; grade 3, equivocal; grade 4, probably present; and grade 5, definitely present. The diagnostic accuracy of each imaging technique was estimated by calculating the area under ROC curve for each reviewer using computer software (ROCKIT, Charles E. Metz; University of Chicago). Stenosis of 70% or more of the luminal diameter on coronary angiography was used as the reference standard.

Results were expressed as the mean ± SD. The statistical significance of difference in areas under the ROC curve between stress MRI and stress SPECT was evaluated by using the univariate Z score test. Two-tailed p values of less than 0.05 were considered to be statistically significant.


Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
On selective coronary angiography, 70% or greater diameter stenosis of the coronary artery was observed in 21 (52.5%) of the 40 patients, including nine patients with single-vessel disease, nine patients with double-vessel disease, and two patients with triple-vessel disease. First-pass contrast-enhanced MR images were of adequate quality for image interpretation in all patients (Figs. 1A, 1B, 2A, and 2B). No patient experienced life-threatening or serious adverse reactions during pharmacologic stress. The sensitivities and specificities of stress first-pass contrast-enhanced MRI and stress 201Tl SPECT in detecting patients with significant stenosis in the coronary artery are summarized in Table 1. The sensitivity for identifying patients with significant stenosis in at least one coronary artery was 81.0% (17 of 21 patients) for MRI and 81.0% (17 of 21 patients) for SPECT. The specificity in detecting patients with significant stenosis in the coronary artery was 68.4% (13 of 19 patients) for MRI and 63.2% (12 of 19 patients) for SPECT. Table 2 summarizes the sensitivities and specificities for depicting significant stenosis in the individual coronary artery. The sensitivity and specificity of stress first-pass contrast-enhanced MRI in detecting stenosis in the individual coronary artery was 69.7% (23 of 33 arteries) and 87.6% (76 of 87 arteries), respectively. These values were 60.6% (20 of 33 arteries) and 80.5% (70 of 87 arteries), respectively, for SPECT.



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  		Fig. 1A —58-year-old woman with chest pain during exercise. First-pass contrast-enhanced MR images (2 R-R intervals/1.2 ms/58 ms [repetition time msec/TE msec/inversion time msec]) obtained during stress and at rest. First row shows stress images and second row shows rest images.

 


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  		Fig. 1B —58-year-old woman with chest pain during exercise. Thallium-201 SPECT images obtained during stress and at rest in patient with significant stenosis in left anterior descending artery. In A, hypoperfused region (white arrows) in anterior wall is depicted as region of lower enhancement during stress. In B, stress-induced ischemia (arrows) is depicted in anterior wall.

 


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  		Fig. 2A —60-year-old man with chest pain during exercise. First-pass contrast-enhanced MR images (2 R-R intervals/1.2/58 [repetition time msec/TE msec/inversion time msec]) obtained during stress and at rest. First row shows stress images and second row shows rest images.

 


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  		Fig. 2B —60-year-old man with chest pain during exercise. Thallium-201 SPECT images obtained during stress and at rest in patient with significant stenosis in right coronary artery. In A, hypoperfused region (white arrows) in inferior wall is depicted as region of lower enhancement during stress. In B, stress-induced ischemia (arrows) is depicted in inferior wall.

 

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  		TABLE 1 : Diagnostic Accuracy of Stress Perfusion MRI and SPECT for Detecting Patients with Significant Stenosis (70%) in at Least One Coronary Artery

 

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  		TABLE 2 : Sensitivity and Specificity of MRI and SPECT for Detecting Significant Stenosis in the Individual Coronary Artery

 

ROC curves for detecting significant stenoses in the individual coronary artery with MRI and SPECT are shown in Figure 3. The areas under the ROC curves for stress first-pass contrast-enhanced MRI were 0.86 for observer 1 and 0.84 for observer 2. The areas under the ROC curves for stress SPECT were 0.79 (p = not significant) for observer 1 and 0.72 (p = not significant) for observer 2.




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  		Fig. 3 —Receiver operating characteristic curves of stress first-pass contrast-enhanced MRI and thallium-201 SPECT in detecting significant stenoses in individual coronary arteries revealed by selective coronary artery angiography in 40 patients. No statistically significant difference was observed between stress first-pass contrast-enhanced MRI and 201Tl SPECT for both observers. A shows results from observer 1 and B, from observer 2. n.s. = not significant.

 

Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The results in the current study showed that stress first-pass contrast-enhanced MRI acquired with saturation-recovery turbo FLASH can provide the detection of significant stenosis in the coronary artery with a diagnostic accuracy comparable with that of stress 201Tl SPECT without attenuation correction [3-7]. In patients with coronary artery disease, decisions regarding the need for the angioplasty and coronary artery bypass graft surgery are ideally made by determining functional significance of the stenosis and assessing morphology of the lesion. Impaired augmentation of myocardial blood flow with pharmacologic stress is a sensitive indicator of myocardial ischemia caused by flow-limiting stenosis in the coronary artery.

Myocardial perfusion has been evaluated most frequently with SPECT, and excellent sensitivity of stress myocardial perfusion SPECT has been reported in previous studies [3-7, 24-28]. Dynamic MRI with a bolus injection of an MR contrast medium can provide assessment of myocardial perfusion with high spatial resolution. Recent studies showed that first-pass contrast-enhanced MRI with pharmacologic stress allows the detection of hemodynamically significant coronary artery disease with high diagnostic accuracy. Schwitter et al. [8] evaluated first-pass kinetics of an MR contrast medium during dipyridamole stress in 48 patients and 18 healthy volunteers using a multislice hybrid echo-planar MR pulse sequence. Stress perfusion MRI showed a sensitivity of 91% and specificity of 94% in detecting coronary artery disease as defined by PET, and a sensitivity of 87% and specificity of 85% compared with quantitative coronary angiography. In a more recent study, Nagel et al. [29] obtained first-pass contrast-enhanced MR images in 84 patients by using a turbo gradient-echo/echo-planar hybrid sequence. By assessing myocardial perfusion reserve index, MRI yielded a sensitivity of 88%, specificity of 90%, and accuracy of 89%. Ishida et al. [9] evaluated first-pass contrast-enhanced MR images in 104 patients using a multislice hybrid echo-planar MR pulse sequence with an interleaved notched saturation. The sensitivity and specificity of stress first-pass contrast-enhanced MRI in detecting patients with significant coronary artery disease was 90% and 85%, respectively.

Although relatively good sensitivity was observed in the current study, the specificity of stress myocardial perfusion MRI was not as good as those found in recent studies that used higher-speed MR imagers and multishot echo-planar sequences [8, 9, 30]. One of the factors associated with a limited specificity is a hypointensity artifact that occurs along the endocardial border of the left ventricular myocardium during first-pass transit of MR contrast medium. To differentiate hypoenhancement caused by coronary arterial stenosis and artifact, we compared rest and stress first-pass contrast-enhanced MR images in all subjects (Fig. 4). However, differentiation between artifact and subendocardial ischemia was difficult in several cases, resulting in a reduced specificity.



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  		Fig. 4 —First-pass contrast-enhanced MR images (2 R-R intervals/1.2 ms/58 ms [repetition time msec/TE msec/inversion time msec]) obtained during stress and at rest in patient with normal coronary artery. Subendocardial hypointensity was observed around circumference (arrows) of left ventricle on stress perfusion MR images. However, subendocardial hypointensity was observed to similar extent on rest perfusion MR images. Therefore, hypointensity area was considered to be artifact. First row shows stress images and second row shows rest images.

 
Several limitations should be acknowledged in this study. First, the results were retrospectively analyzed in a relatively limited number of subjects with a high prevalence of coronary artery disease. The small number of subjects prevented an accurate determination of the sensitivity and specificity in predicting coronary artery disease. Second, 201Tl SPECT images were acquired without attenuation correction in this study. Previous studies have shown that attenuation correction improved the normalcy rate of myocardial perfusion SPECT [30, 31], and the higher diagnostic accuracy has been reported with use of technetium-99m myocardial perfusion tracers [32-34]. Therefore, the diagnostic performance of stress myocardial perfusion SPECT can be improved with use of 99mTc myocardial perfusion tracers, attenuation correction, and ECG gating. Third, SPECT images were acquired in 26 patients during exercise-induced stress and in the remaining patients, during dipyridamole-induced stress. Although previous studies show that myocardial perfusion scintigraphy in combination with pharmacologic stress provide imaging data equivalent to those with exercise in the assessment of coronary artery disease [18-22], further study is required to determine the comparative diagnostic accuracy of pharmacologic stress perfusion MRI compared with exercise-induced or pharmacologic stress perfusion scintigraphy. Fourth, since coronary angiography was used as a gold standard in this study, the diagnostic accuracy of MRI and SPECT relied on the morphologic cutoff value to define significant disease. Although quantitative coronary angiography can minimize the interobserver and intraobserver variabilities of interpretations, angiographic approaches cannot precisely evaluate the physiologic impact of coronary artery stenoses on coronary blood flow, especially in patients with intermediate stenosis of the coronary artery. Fifth, patients with myocardial infarction were excluded in this study. We focused on evaluation of the diagnostic value of stress myocardial perfusion MRI and SPECT for the detection of flow-limiting stenosis in the coronary artery. However, the differentiation between ischemic, viable myocardium, and infarction is important in managing patients with coronary artery disease. Further study is required to determine the diagnostic performances of MRI and SPECT for detecting flow-limiting stenosis in the coronary artery in patients with prior myocardial infarction.

In conclusion, the diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery-prepared turbo FLASH was comparable with that of stress 201Tl SPECT without attenuation correction. Stress first-pass contrast-enhanced MRI is a noninvasive technique that can be used as an alternative to stress myocardial perfusion scintigraphy.


References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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