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(Circulation. 1998;98:2687-2694.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Contrast Magnetic Resonance Imaging in the Assessment of Myocardial Viability in Patients With Stable Coronary Artery Disease and Left Ventricular Dysfunction

Kishin Ramani, MD; Robert M. Judd, PhD; Thomas A. Holly, MD; Todd B. Parrish, PhD; Vera H. Rigolin, MD; Michele A. Parker, MS; Cathy Callahan; Steven W. Fitzgerald, MD; Robert O. Bonow, MD; Francis J. Klocke, MD

From the Departments of Medicine, Radiology, and Biomedical Engineering and the Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Ill.

Correspondence to Robert O. Bonow, MD, Wesley 524, Northwestern University Medical School, 250 E Superior St, Chicago, IL 60611-3008. E-mail r-bonow{at}nwu.edu

	Abstract

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Background—The utility of contrast MRI for assessing myocardial viability in stable coronary artery disease (CAD) with left ventricular dysfunction is uncertain. We therefore performed cine and contrast MRI in 24 stable patients with CAD and regional contractile abnormalities and compared MRI findings with rest-redistribution ²⁰¹Tl imaging and dobutamine echocardiography.

Methods and Results—Delayed MRI contrast enhancement patterns were examined from 3 to 15 minutes after injection of 0.1 mmol/kg IV gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Comparable MRI and ²⁰¹Tl basal and midventricular short-axis images were subdivided into 6 segments. Segments judged nonviable by quantitative and qualitative assessment of ²⁰¹Tl scans showed persistent, systematically greater MRI contrast signal intensity than segments judged viable (P0.002). Delayed contrast hyperenhancement also occurred in segments judged nonviable by dobutamine echocardiography (P0.03). The presence or absence of hyperenhancement correlated most closely with nonviability and viability, respectively, in segments that were akinetic or dyskinetic under resting conditions (83% concordance with ²⁰¹Tl in both cases). In segments with resting hypokinesis, 58% of segments showing hyperenhancement were judged viable by ²⁰¹Tl and may have represented an admixture of scar tissue and viable myocardium.

Conclusions—Delayed (by 3 to 15 minutes) hyperenhancement of Gd-DTPA contrast–enhanced MRI images occurs frequently in dysfunctional areas of the left ventricle in patients with stable CAD. Hyperenhancement is associated with nonviability by rest-redistribution ²⁰¹Tl scintigraphy and dobutamine echocardiography, particularly in regions exhibiting resting akinesis/dyskinesis. The absence of hyperenhancement correlates with radionuclide and echocardiographic determinations of viability, regardless of resting contractile function.

Key Words: coronary disease • echocardiography • heart failure • magnetic resonance imaging

	Introduction

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The identification of patients with coronary artery disease (CAD) who have viable but hypocontractile myocardium that is likely to benefit from revascularization continues to be based on assessments of regional contractile function (dobutamine echocardiography) or perfusion and metabolism (PET and radionuclide imaging). MRI can in principle address function and perfusion in a single setting, with excellent spatial resolution and the potential for in vivo spectroscopic assessment of metabolism. However, its value for assessing the viability of chronically dysfunctional myocardium is not yet clear.

The present study was undertaken to define the behavior of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), a commonly used paramagnetic contrast agent, in chronically dysfunctional areas of the left ventricle (LV) in patients with stable CAD. To place MRI findings in context with other imaging approaches used to assess myocardial viability, patients were also studied with rest-redistribution ²⁰¹Tl imaging and dobutamine echocardiography.

	Methods

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Patient Population
We prospectively studied 24 ambulatory patients with stable CAD and LV dysfunction (identified by previous angiographic, echocardiographic, and/or radionuclide studies). The group included 22 men and 2 women ranging from 35 to 75 years (mean, 64 years) of age. Ten were diabetic, 13 had a history of hypertension, 13 had a history of hypercholesterolemia, and 16 had a history of cigarette smoking. CAD was confirmed in all patients by coronary arteriography; 14 showed 70% reduction in the luminal diameters of 2 major coronary arteries, whereas 10 had triple-vessel disease. Seven had undergone CABG, and 3 had had coronary angioplasty. Twenty-two patients had a history of myocardial infarction. In 18 patients, the infarction occurred >6 months before study. One patient was studied 4 months after infarction. The remaining 3 patients had infarctions producing persistent wall motion abnormalities >6 months before study and were studied 1, 2, and 4 weeks after recurrent ischemic episodes associated with minor elevations in creatine kinase and/or no demonstrable change in wall motion. Fifteen patients had abnormal Q waves on ECGs. All patients were in NYHA functional class II or III at the time of study. LV ejection fraction averaged 0.33 (range, 0.15 to 0.45). No patient had a hemodynamically significant valvular abnormality.

Of the 24 patients, 21 underwent rest–4-hour redistribution ²⁰¹Tl single photon emission computed tomography (SPECT) and contrast-enhanced MRI; 1 additional patient had only a rest ²⁰¹Tl study. Eighteen patients also underwent dobutamine echocardiography. MRI, ²⁰¹Tl SPECT, and echocardiographic studies were performed within an interval of 12±2 days (mean±SEM).

Imaging Protocols
Magnetic Resonance Imaging
All images were acquired on a 1.5T MRI unit (Siemens Vision, Siemens Medical Systems) with patients in the supine position with a flexible torso surface radiofrequency coil for signal reception. ECG-gated cine MRI images were acquired at 6 to 8 base-apex short-axis locations during repeated breath-holds (15 seconds). From the cine images, 4 short-axis locations exhibiting regional myocardial dysfunction were selected for further study. Delayed contrast enhancement patterns were examined by imaging at all 4 locations every 2 minutes from 3 to 15 minutes after bolus injection of Gd-DTPA (0.1 mmol/kg IV). Imaging parameters included image data acquisition gated to end diastole, 3 cardiac cycles per image, 60 nonselective 30° radiofrequency pulses before image acquisition, repetition time of 6 ms, echo time of 2 ms, and voxels of 1.1x2.8x10 mm.¹

²⁰¹Tl Imaging and Dobutamine Echocardiography
Patients underwent SPECT imaging after the administration of 3 mCi ²⁰¹Tl IV under resting conditions. Rest images were acquired 15 minutes after ²⁰¹Tl administration; redistribution images were acquired 4 hours after ²⁰¹Tl injection.

Transthoracic echocardiographic images were acquired at rest and during dobutamine infusion by use of a standard clinical protocol.²

Registration of Images for Comparative Analyses
MRI and ²⁰¹Tl images were displayed side by side on a Macintosh computer with the software package NIH Image 1.60 (National Institutes of Health). The entire series of contrast-enhanced short-axis MRI images at 4 base-apex levels, the cine short-axis MRI images at 6 to 8 levels, and ²⁰¹Tl short-axis images at 12 to 13 levels were examined. MRI short-axis images, 1 at the midventricular level and 1 at the base of the heart, were selected for further study by consensus of 2 observers. (Apical images were not analyzed because they were not obtained in all patients.) Two short-axis ²⁰¹Tl images corresponding to the basal and midventricular short-axis MRI locations were then selected (at rest and at redistribution). Each MRI and ²⁰¹Tl image was subdivided into six 60^o segments, yielding a total of 264 segments in the 22 patients evaluated with both techniques. MRI images could not be assessed further in 7% of segments because the patient began to breathe during the scan, resulting in image artifacts.

Short-axis MRI and echocardiographic images were compared by use of the midventricular MRI image and the echocardiographic parasternal short-axis view at the level of the papillary muscles. Echocardiographic images were rotated counterclockwise so that anterior, anteroseptal, septal, inferior, posterior, and lateral segments³ were matched to MRI and ²⁰¹Tl anterior, anteroseptal, inferoseptal, inferior, inferolateral, and anterolateral segments. Only 1 of the 108 segments in the 18 patients studied with MRI and echocardiography was unsuitable for analysis.

Data Analysis
Magnetic Resonance Images
MRI Quantitative Analysis of Contrast Enhancement
MRI image intensity was measured in each segment at 2-minute intervals from 3 to 15 minutes after contrast administration by use of manually drawn regions of interest encompassing each segment. Care was taken to avoid endocardial and epicardial pixels that might have been affected by partial volume effects. MRI image intensity was expressed as a percent of baseline (precontrast) image intensity.

MRI Qualitative Analysis of Contrast Enhancement
By consensus of 2 observers, each segment was independently classified as becoming hyperenhanced or not becoming hyperenhanced by examination of all postcontrast images (3 to 15 minutes).

Cine MRI
Regional wall motion for each segment analyzed for contrast enhancement was characterized by examining the cine MRI images at the same location. Each segment was rated by consensus of 2 observers as showing normal, hypokinetic, or akinetic/dyskinetic wall motion.

²⁰¹Tl Images
²⁰¹Tl Quantitative Analysis
Analogous to the MRI quantitative analysis of contrast enhancement, regions of interest were manually drawn to encompass each segment, and ²⁰¹Tl image intensity was measured. The myocardium within each segment was considered viable if segmental ²⁰¹Tl activity was 50% of activity in the segment (of any slice) with greatest ²⁰¹Tl activity. Because of inadvertent erasure of raw data in 2 patients, quantitative analyses of ²⁰¹Tl activity were derived from 20 rather than 22 patients.

²⁰¹Tl Qualitative Analysis
For qualitative assessment of myocardial viability, rest and redistribution ²⁰¹Tl images were examined by consensus of 2 experienced nuclear cardiologists blinded to the clinical and other imaging data. Each segment was scored as viable or nonviable, with the severity of any resting defect and the presence or absence of redistribution at 4 hours taken into account.

Echocardiographic Images
Echocardiographic images were analyzed off-line from videotape and digitized cine-loop playback by 2 experienced echocardiographers unaware of the ²⁰¹Tl and MRI results. LV regional wall motion was analyzed and graded semiquantitatively.³ A segment with a baseline wall motion abnormality was considered viable if it showed improvement in wall motion score by at least 1 grade during dobutamine infusion or if ischemia became evident (wall motion deteriorated). Segments with normal resting wall motion were also categorized as viable.

Statistical Analyses
Comparisons of MRI image intensity between segments exhibiting viability and segments exhibiting nonviability by the various modalities were made by use of 2-sample t tests. Comparisons of MRI image intensity between viable and nonviable segments within patients were made by use of paired t tests. Agreement between MRI hyperenhancement and nonviability by ²⁰¹Tl or dobutamine echocardiography was assessed using K values and McNemar's test. Differences in categorical variables were assessed by use of the ² test statistic. All statistical tests were 2 tailed; P<0.05 was regarded as statistically significant.

	Results

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Comparison of Regional MRI Signal Intensity and Regional ²⁰¹Tl Activity
Regional MRI signal intensity after contrast administration was evaluated relative to baseline signal intensity, and the signal intensity in each region was compared with the ²⁰¹Tl activity in that region. Figure 1 presents images from an illustrative case. Figures 2 and 3 show pooled MRI data compared with 3 different approaches for assessing ²⁰¹Tl activity: measured activity at rest (Figure 2, top), measured activity on redistribution images (Figure 2, bottom), and visual assessment of regional viability or nonviability (Figure 3).

View larger version (71K): [in this window] [in a new window]   Figure 1. Short-axis MRI images obtained after contrast administration compared with corresponding short-axis 201Tl tomograms at rest and after redistribution (REDIST). Persistent MRI hyperenhancement develops in inferolateral wall, corresponding to severe irreversible 201Tl defect in same region. Inferior wall also demonstrates substantial perfusion defect at rest but shows redistribution, indicating myocardial viability; MRI images in this area show lesser degree of hyperenhancement than in area of irreversible injury.

View larger version (17K): [in this window] [in a new window]   Figure 2. MRI signal intensity as a function of time after contrast administration in myocardial regions subgrouped on basis of quantitative 201Tl analysis. Top, Regions with 201Tl activity <50% on initial resting images are compared with those with resting activity >50%. Bottom, Segments with 201Tl activity <50% on redistribution images are compared with those with redistribution activity >50%. In each panel, regions with greater 201Tl evidence for nonviability have significantly greater MRI enhancement; this effect persists throughout 15-minute MRI imaging period. Values shown are mean±SEM. Numbers of segments included in each value are shown at bottom of each panel. For segments with 201Tl activity <50% on initial resting images, 17% were located anteriorly, 46% inferiorly, and 37% laterally. For segments with 201Tl activity <50% on redistribution images, 23% were located anteriorly, 44% inferiorly, and 33% laterally.

View larger version (18K): [in this window] [in a new window]   Figure 3. MRI signal intensity as function of time after contrast administration in myocardial regions subgrouped on basis of qualitative 201Tl analysis. Segments considered viable by visual assessment of 201Tl rest-redistribution images are compared with segments considered nonviable. Values shown are mean±SEM. Numbers of segments included in each value are shown at bottom. Of segments considered nonviable, 17% were located anteriorly, 46% inferiorly, and 37% laterally.

In segments with severely reduced ²⁰¹Tl activity on initial resting images (<50% of normal as defined by maximum segment activity), MRI signal intensity was significantly greater than in segments with ²⁰¹Tl activity >50% at rest (Figure 2, top). This difference in the degree of MRI enhancement persisted throughout the 15-minute MRI acquisition period. MRI signal intensity was also greater in segments with severely reduced ²⁰¹Tl activity (<50% of normal) on redistribution images (Figure 2, bottom), an effect that again lasted throughout the MRI imaging period. A somewhat greater separation of the MRI enhancement data between regions with <50% and >50% ²⁰¹Tl activities was apparent on redistribution images than on rest images. This resulted from a greater degree of contrast enhancement in segments with ²⁰¹Tl activity <50% on redistribution and rest images. Similar results were observed when the ²⁰¹Tl data were analyzed by visual assessment of viability versus nonviability (Figure 3), with greater contrast enhancement in regions judged to be nonviable than in those judged to be viable. Table 1 compares the visual assessment of ²⁰¹Tl viability and qualitative MRI analysis of contrast enhancement.

View this table: [in this window] [in a new window]   Table 1. 201T1 Nonviability Versus MR Hyperenhancement in Individual Segments

Because the mean data in Figures 2 and 3 do not represent paired data, this analysis could conceivably obscure individual responses and individual variability. Thus, a paired analysis was performed in individual patients comparing MRI signal intensity in regions considered viable or nonviable by qualitative ²⁰¹Tl imaging (Figure 4). At each point in time after contrast administration, there was significantly greater MRI enhancement in regions in which ²⁰¹Tl imaging suggested nonviability.

View larger version (23K): [in this window] [in a new window]   Figure 4. Paired data comparing MRI signal intensity in individual patients in segments considered viable and nonviable by 201Tl imaging (qualitative). Image intensities for viable and nonviable segments within same patient were averaged. Nonviable regions by 201Tl have significantly greater MRI enhancement at each point in time after contrast administration. (Not shown are 6 patients without nonviable regions at short-axis levels of LV chosen for analysis.)

MRI Signal Intensity, Regional Wall Motion, and ²⁰¹Tl Activity
The relation between MRI signal enhancement and regional ²⁰¹Tl activity was further analyzed in relation to regional wall motion assessed by cine MRI (Figure 5). The likelihood of increased MRI signal intensity was significantly greater in akinetic or dyskinetic (43%) than in hypokinetic (22%) or normal (9%) segments (P<0.0001). Among myocardial regions with normal systolic function, 95% had evidence of myocardial viability by ²⁰¹Tl imaging regardless of the presence or absence of hyperenhancement (Figure 5, left). In hypokinetic regions, 58% of regions with MRI hyperenhancement were considered viable on the basis of ²⁰¹Tl imaging compared with 91% of hypokinetic regions without hyperenhancement (Figure 5, middle). In regions with akinetic or dyskinetic wall motion, 83% of segments not showing MRI hyperenhancement were viable by ²⁰¹Tl criteria compared with only 17% of segments with MRI hyperenhancement (Figure 5, right).

View larger version (30K): [in this window] [in a new window]   Figure 5. Relationship of MRI contrast hyperenhancement (qualitative analysis) to regional wall motion and evidence of viable or nonviable myocardium by 201Tl imaging (also qualitative analysis). Likelihood of MRI hyperenhancement increases from 9% in segments with normal wall motion (left) to 22% in segments with hypokinetic wall motion (middle) to 43% in segments with akinetic or dyskinetic wall motion (right) (P<0.0001 for relationship between worsening wall motion and hyperenhancement). In akinetic/dyskinetic segments showing hyperenhancement, 83% are nonviable by 201Tl criteria. Although >50% of regions with akinesis or dyskinesis did not manifest MRI hyperenhancement, most (83%) are considered viable by 201Tl criteria. Regardless of severity of wall motion disturbance, segments failing to show MRI hyperenhancement have 201Tl findings indicating myocardial viability.

Comparison of Regional MRI Signal Intensity and Dobutamine Echocardiography
The relation between MRI hyperenhancement and nonviable myocardium identified by dobutamine echocardiography was similar to that observed in comparisons of MRI hyperenhancement and ²⁰¹Tl data. Segments assessed as nonviable during dobutamine administration showed significantly greater MRI contrast enhancement than those segments judged to be viable (Figure 6). The difference was observed when all myocardial regions were analyzed together (Figure 6, top) and when only regions with baseline wall motion abnormalities were analyzed (Figure 6, bottom). In both cases, the difference again persisted throughout the 15-minute MRI acquisition period. Figure 7 shows a paired analysis in individual patients comparing MRI signal intensity in regions considered viable and nonviable by dobutamine echocardiography. Table 2 compares the qualitative MRI analysis of contrast enhancement with the dobutamine echocardiography assessment of viability.

View larger version (17K): [in this window] [in a new window]   Figure 6. MRI signal intensity as function of time related to myocardial viability as determined by dobutamine echocardiography. Regions without echocardiographic evidence of viability have greater MRI signal intensity, whether all segments (top) or only segments with resting wall motion abnormalities (bottom) are analyzed. Values shown are mean±SEM. Numbers of segments included in each value are shown below each panel. Of viable segments with resting wall motion abnormalities, 34% demonstrated sustained improvement in wall thickening with dobutamine; 55%, initial improvement followed by deterioration; and 11%, only deterioration.

View larger version (22K): [in this window] [in a new window]   Figure 7. Paired data comparing MRI signal intensity in individual patients in segments considered viable and nonviable by dobutamine echocardiography. Image intensities for viable and nonviable segments within same patient were again averaged.

View this table: [in this window] [in a new window]   Table 2. Dobutamine Echocardiography Nonviability Versus MR Hyperenhancement in Individual Segments

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
MRI Assessment of Myocardial Viability
Van der Wall and colleagues⁴ have recently reviewed MRI studies in acute myocardial ischemia and infarction. Prolongation of T₁ and T₂ relaxation times without contrast infusion has been suggested to indicate loss of viability after myocardial infarction. Because of the excellent spatial resolution of MRI, measurements of regional wall thickness have also been of interest in assessing myocardial viability in chronic ischemic heart disease. Baer et al⁵ found excellent concordance between segment viability graded by end-diastolic wall thickness and SPECT ^99mTc–methoxyisobutyl-isonitrile uptake. Although thin, asynergic myocardium can represent irreversibly scarred tissue, Perrone-Filardi et al⁶ found many thin, akinetic segments on spin-echo–gated MRI to be metabolically active by fluorodeoxyglucose-PET imaging. That study underscored the need for further refinement of MRI techniques for predicting myocardial viability.

Use of contrast agents has enhanced the ability of MRI to distinguish infarcted from viable myocardium. Intravenous administration of Gd-DTPA and other paramagnetic compounds results in a shortening of both T₁ and T₂ relaxation times, with the former predominating. The signal enhancement caused by these agents is proportional to the tissue concentration.⁷ Tissue contrast depends on differences in tissue perfusion, blood content, size of extracellular space, and myocardial contrast agent distribution. Gd-DTPA diffuses into the extracellular fluid with 50% clearance from the intravascular space on initial capillary transit.^{7 8} Areas of edema and inflammation have greater accumulation and slower clearance of Gd-DTPA because of increased capillary permeability and expansion of the interstitial space.^{9 10} The signal enhancement in an area of infarct is probably related to increased uptake of Gd-DTPA and/or delayed washout.¹¹

Early studies using contrast-enhanced MRI were limited by spin-echo imaging, which required several minutes to obtain each cardiac image. Nevertheless, hyperenhancement of acutely injured myocardium was sometimes described, both clinically^{12 13} and experimentally.^{14 15 16 17 18} More recently, the advent of fast MRI methods has permitted acquisition of MRI tomograms during a breath-hold. This allows study of the influence of paramagnetic contrast agents on myocardial signal intensity with much greater temporal resolution.¹⁹ In a study of recent infarction in humans, Lima et al²⁰ showed that in the first few minutes after contrast administration, large infarcts were characterized by central dark zones surrounded by regions of hyperenhancement, whereas smaller infarcts were characterized by hyperenhancement alone. In both cases, hyperenhanced regions correlated with a fixed ²⁰¹Tl scintigraphic defect. In a related study of dogs subjected to 2-day-old reperfused infarction, dark regions were shown to relate to the "no-reflow" phenomenon, whereas hyperenhanced regions correlated with nonviable areas histologically.²¹

Few other studies of contrast MRI have been performed in nonacute settings. Those using spin-echo technology^{12 13} reported that regional contrast enhancement abates within the first few weeks after acute infarction. A recent experimental fast MRI study²² also noted a decreasing pattern of contrast enhancement in the first few weeks after acute infarction. Conversely, Fedele et al²³ have reported that chronically infarcted areas judged to be "necrotic" on the basis of ¹²³I-phenylpentadecanoic acid scintigraphy show relatively enhanced MRI signal intensity 8 to 30 minutes after contrast administration. A preliminary report from Roberts et al²⁴ also indicates that hyperenhancement can persist for up to 6 months after Q-wave myocardial infarction.

Limitations of MRI Analysis in This Study
The choice of a surface radiofrequency receiver coil rather than a body coil represented a compromise between improved image signal-to-noise ratio and homogeneity of the radiofrequency field. Although the surface coil introduces inhomogeneities resulting in higher image intensities closer to the coil, they are expected to be similar before and after contrast administration. Normalization of MRI signal intensity after contrast administration to the precontrast image intensity in the same segment should correct, at least to the first order, for radiofrequency inhomogeneities. Pooling of data from multiple patients implies that all patients received the same amount of contrast agent, that hemodynamics were similar in all patients, and that the slope of the relationship of MRI image intensity to contrast concentration was similar in all cases. To minimize these variables, all patients received the same contrast dosage on a body mass basis, and care was taken to choose identical MRI imaging parameters such as flip angle. Despite these procedures, it remains likely that patient-to-patient variation increased the variability of MRI image intensity after contrast administration. Because patient-to-patient variability would tend to mask differences in MRI image intensity between viable and nonviable myocardium, this study cannot provide a specific cutoff point between normal and irreversibly damaged tissue. In addition, the acquisition of postcontrast images at 2-minute intervals permitted only 4 short-axis views, and apical segments were not studied. Nonetheless, this study does demonstrate a systematically greater elevation in MRI image intensity in nonviable segments than in other areas.

Relationship of Delayed Contrast Enhancement to Rest-Redistribution ²⁰¹Tl SPECT and Dobutamine Echocardiography Assessments of Myocardial Viability
As shown in Figure 5, the absence of MRI hyperenhancement appears to be a specific finding for viable myocardium with the ²⁰¹Tl criteria, regardless of the severity of regional dysfunction. The presence of MRI hyperenhancement correlates with ²⁰¹Tl evidence of nonviable myocardium when regional systolic function is severely depressed (Figure 5, right) but correlates less well when systolic function is only mildly abnormal (Figure 5, center). MRI hyperenhancement is an uncommon finding in regions with normal wall motion (Figure 5, left) and may not be an accurate marker of nonviable tissue in such regions. Several previous studies have validated the use of rest-redistribution ²⁰¹Tl imaging for predicting myocardial viability by use of a cutoff of 50% to 60% of maximal ²⁰¹Tl activity to define nonviable tissue.^{25 26}

Our echocardiographic criteria for viability were intended to separate living myocardium from scar tissue and therefore included segments with resting wall abnormalities that responded to dobutamine with sustained improvement, initial improvement followed by deterioration, or deterioration alone. As with ²⁰¹Tl imaging, Gd-DTPA contrast enhancement was systematically greater in segments failing to show viability by echocardiography.

Recent studies have compared ²⁰¹T1 rest-redistribution scintigraphy and dobutamine echocardiography in patients with chronic CAD and LV dysfunction.^{27 28} Perrone-Filardi et al²⁷ and Qureshi et al²⁸ have found that dobutamine echocardiography has a greater positive predictive accuracy for functional recovery after revascularization, whereas negative predictive accuracy is superior with ²⁰¹Tl. Although information concerning functional responses to revascularization in hypocontractile segments studied with MRI contrast enhancement is not yet available, the present findings suggest that the predictive characteristics of hyperenhancement correspond more closely to those of ²⁰¹Tl than dobutamine. Information about other end points, eg, improved exercise tolerance, a reduction in ischemic events, or improved survival, remains limited for all technologies being used to assess viability.

Mechanism(s) of MRI Hyperenhancement
The mechanism(s) responsible for delayed hyperenhancement on MRI remain unclear. As discussed previously, there is considerable evidence that the concentration of Gd-DTPA is increased in regions showing hyperenhancement during acute injury. It is often argued that this increase reflects an increased volume of distribution, resulting from Gd-DTPA (molecular weight, 800 Da) entry into the intracellular space after myocyte membrane rupture. However, in a study of isolated acutely infarcted rabbit hearts subjected to step changes in contrast concentration, the primary mechanism of hyperenhancement appeared to be prolonged washout of Gd-DTPA.¹¹ In a long-term setting, myocardium that has been irreversibly injured in the past is presumably replaced by scar tissue. The present findings suggest that delayed contrast enhancement may have special value in evaluating fibrotic or scar tissue. Delayed enhancement correlated closely with fixed ²⁰¹Tl defects in akinetic segments and was infrequent in akinetic segments judged viable by ²⁰¹Tl. The somewhat poorer concordance of delayed enhancement and ²⁰¹Tl nonviability in hypocontractile segments could reflect an admixture of viable myocardium and scar tissue. The potential importance of scar tissue is highlighted by studies demonstrating an inverse relationship between magnitude of fibrosis and chances of functional recovery after revascularization in coronary patients with regional ventricular dysfunction.^{29 30} It is possible that hyperenhancement results, at least in part, from a relatively larger extracellular space (and therefore a larger volume of distribution for Gd-DTPA) in scar tissue than viable myocardium.

Conclusions
In patients with stable CAD, delayed (3 to 15 minutes) hyperenhancement of Gd-DTPA contrast–enhanced MRI images occurs frequently in LV regions showing contractile dysfunction. The presence of hyperenhancement is associated with evidence of nonviability by rest-redistribution ²⁰¹Tl imaging and dobutamine echocardiography, particularly in regions exhibiting akinesis/dyskinesis under resting conditions. The absence of hyperenhancement correlates closely with evidence of viability, regardless of resting contractile function. Delayed hyperenhancement may be useful in evaluating scar tissue in stable CAD.

Received June 26, 1998; revision received August 24, 1998; accepted September 2, 1998.

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