Robert M. Judd

The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction.

BACKGROUND Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischemic injury regardless of the extent of wall motion or the age of the infarct. We hypothesized that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with coronary artery disease. METHODS Gadolinium-enhanced MRI was performed in 50 patients with ventricular dysfunction before they underwent surgical or percutaneous revascularization. The transmural extent of hyperenhanced regions was postulated to represent the transmural extent of nonviable myocardium. The extent of regional contractility at the same locations was determined by cine MRI before and after revascularization in 41 patients. RESULTS Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularization. In all patients with hyperenhancement the difference in image intensity between hyperenhanced regions and regions without hyperenhancement was more than 6 SD. Before revascularization, 804 of the 2093 myocardial segments analyzed (38 percent) had abnormal contractility, and 694 segments (33 percent) had some areas of hyperenhancement. In an analysis of all 804 dysfunctional segments, the likelihood of improvement in regional contractility after revascularization decreased progressively as the transmural extent of hyperenhancement before revascularization increased (P<0.001). For instance, contractility increased in 256 of 329 segments (78 percent) with no hyperenhancement before revascularization, but in only 1 of 58 segments with hyperenhancement of more than 75 percent of tissue. The percentage of the left ventricle that was both dysfunctional and not hyperenhanced before revascularization was strongly related to the degree of improvement in the global mean wall-motion score (P<0.001) and the ejection fraction (P<0.001) after revascularization. CONCLUSIONS Reversible myocardial dysfunction can be identified by contrast-enhanced MRI before coronary revascularization.

Relationship of MRI Delayed Contrast Enhancement to Irreversible Injury, Infarct Age, and Contractile Function

BACKGROUND Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction. METHODS AND RESULTS In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001). CONCLUSIONS In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.

Prognostic Significance of Microvascular Obstruction by Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction

BACKGROUND The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contrast-enhanced MRI, regions of profound microvascular obstruction at the infarct core are hypoenhanced and correspond to greater myocardial damage acutely. We investigated whether profound microvascular obstruction after infarction predicts 2-year cardiovascular morbidity and mortality. METHODS AND RESULTS Forty-four patients underwent MRI 10 +/- 6 days after infarction. Microvascular obstruction was defined as hypoenhancement seen 1 to 2 minutes after contrast injection. Infarct size was assessed as percent left ventricular mass hyperenhanced 5 to 10 minutes after contrast. Patients were followed clinically for 16 +/- 5 months. Seventeen patients returned 6 months after infarction for repeat MRI. Patients with microvascular obstruction (n = 11) had more cardiovascular events than those without (45% versus 9%; P=.016). In fact, microvascular status predicted occurrence of cardiovascular complications (chi2 = 6.46, P<.01). The risk of adverse events increased with infarct extent (30%, 43%, and 71% for small [n = 10], midsized [n = 14], and large [n = 14] infarcts, P<.05). Even after infarct size was controlled for, the presence of microvascular obstruction remained a prognostic marker of postinfarction complications (chi2 = 5.17, P<.05). Among those returning for follow-up imaging, the presence of microvascular obstruction was associated with fibrous scar formation (chi2 = 10.0, P<.01) and left ventricular remodeling (P<.05). CONCLUSIONS After infarction, MRI-determined microvascular obstruction predicts more frequent cardiovascular complications. In addition, infarct size determined by MRI also relates directly to long-term prognosis in patients with acute myocardial infarction. Moreover, microvascular status remains a strong prognostic marker even after control for infarct size.

Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study

BACKGROUND Myocardial infarcts are routinely detected by nuclear imaging techniques such as single photon emission computed tomography (SPECT) myocardial perfusion imaging. A newly developed technique for infarct detection based on contrast-enhanced cardiovascular magnetic resonance (CMR) has higher spatial resolution than SPECT. We postulated that this technique would detect infarcts missed by SPECT. METHODS We did contrast-enhanced CMR and SPECT examinations in 91 patients with suspected or known coronary artery disease. All CMR and SPECT images were scored, using a 14-segment model, for the presence, location, and spatial extent of infarction. To compare each imaging modality to a gold standard, we also acquired contrast-enhanced CMR and SPECT images in 12 dogs with, and three dogs without, myocardial infarction as defined by histochemical staining. FINDINGS In animals, contrast-enhanced CMR and SPECT detected all segments with nearly transmural infarction (>75% transmural extent of the left-ventricular wall). CMR also identified 100 of the 109 segments (92%) with subendocardial infarction (<50% transmural extent of the left-ventricular wall), whereas SPECT identified only 31 (28%). SPECT and CMR showed high specificity for the detection of infarction (97% and 98%, respectively). In patients, all segments with nearly transmural infarction, as defined by contrast-enhanced CMR, were detected by SPECT. However, of the 181 segments with subendocardial infarction, 85 (47%) were not detected by SPECT. On a per patient basis, six (13%) individuals with subendocardial infarcts visible by CMR had no evidence of infarction by SPECT. INTERPRETATION SPECT and CMR detect transmural myocardial infarcts at similar rates. However, CMR systematically detects subendocardial infarcts that are missed by SPECT.

Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction

BACKGROUND A technical advance in contrast-enhanced magnetic resonance imaging (MRI) has significantly improved image quality. We investigated whether healed myocardial infarction can be visualised as hyperenhanced regions with this new technique, and whether assessment of the transmural extent of infarction yields new physiological data. METHODS 82 MRI examinations were carried out in three groups: patients with healed myocardial infarction; patients with non-ischaemic cardiomyopathy; and healthy volunteers. Patients with healed myocardial infarction were prospectively enrolled after enyzmatically proven necrosis and imaged 3 months (SD 1) or 14 months (7) later. The MRI procedure used a segmented inversion-recovery gradient-echo sequence after gadolinium administration. Findings were compared with those of coronary angiography, electrocardiography, cine MRI, and creatine kinase measurements. FINDINGS 29 (91%) of 32 patients with infarcts imaged at 3 months (13 non-Q-wave) and all of 19 imaged at 14 months (eight non-Q-wave) showed hyperenhancement. In patients in whom the infarct-related-artery was identified by angiography, 24 of 25 imaged at 3 months and all of 14 imaged at 14 months had hyperenhancement in the appropriate territory. None of the 20 patients with non-ischaemic cardiomyopathy or the 11 healthy volunteers showed hyperenhancement. Irrespective of the presence or absence of Q waves, the majority of patients with hyperenhancement had only non-transmural involvement. Normal left-ventricular contraction was shown in seven patients examined at 3 months and three examined at 14 months, but in these cases hyperenhancement was limited to the subendocardium. INTERPRETATION The presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction can be accurately determined by contrast-enhanced MRI.

Myocardial Gd-DTPA Kinetics Determine MRI Contrast Enhancement and Reflect the Extent and Severity of Myocardial Injury After Acute Reperfused Infarction

BACKGROUND Contrast medium-enhanced magnetic resonance images of acute, reperfused infarcts have shown hypoenhanced and hyperenhanced regions in areas of injured myocardium. The precise mechanisms that lead to these altered enhancement patterns are unknown. This study was designed to evaluate possible mechanisms and to relate altered enhancement patterns to myocardial perfusion and viability. METHODS AND RESULTS Thirteen rabbits underwent in situ coronary artery occlusion and reperfusion followed by isolated perfusion with cardioplegic solution. T1-weighted spin-echo images were acquired continuously during step changes in perfusate Gd-DTPA concentration. Regional blood flow was also measured by use of radioactive microspheres in all rabbits. There were marked differences in Gd-DTPA wash-in and washout time constants (wash-in, 0.8 +/- 0.1, 2.1 +/- 02, and 16.3 +/- 2.4 minutes, P < .001; washout, 1.6 +/- 0.1, 4.8 +/- 0.5, and 31.1 +/- 3.3 minutes, P < .001) in normal, infarct rim, and infarct core regions, respectively, resulting in differential enhancement of these regions. Microsphere flows in the infarct rim and core were 42.9 +/- 4.0% and 12.0 +/- 1.6% of normal myocardium and correlated well with washout time constants (r = .86, y = 0.77x - 0.002, P < .001), suggesting that these time constants index the severity of microvascular damage. In addition, spatial maps of washout time constants were produced. The extent of regions with abnormal time constants correlated well with triphenyltetrazolium chloride-determined infarct size (r = .94, y = 0.95x + 4.17, P < .001). CONCLUSIONS In contrast-enhanced magnetic resonance images of acute, reperfused rabbit infarcts, differential image intensity is primarily due to regional differences in contrast agent wash-in and washout time constants. These regional differences in time constants also indicate the extent and severity of myocardial injury.

Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy

OBJECTIVES We sought to ascertain whether myocardial scarring occurs in living unselected patients with hypertrophic cardiomyopathy (HCM). BACKGROUND Myocardial scarring is known to occur in select HCM patients, who were highly symptomatic prior to death or who died suddenly. The majority of HCM patients, however, are minimally symptomatic and have not suffered sudden death. METHODS Cine and gadolinium-enhanced magnetic resonance imaging was performed in 21 HCM patients who were predominantly asymptomatic. Gadolinium hyperenhancement was assumed to represent myocardial scar, and the extent of scar was compared to left ventricular (LV) morphology and function. RESULTS Scarring was present in 17 patients (81%). Scarring occurred only in hypertrophied regions (> or =10 mm), was patchy with multiple foci, and predominantly involved the middle third of the ventricular wall. All 17 patients had scarring at the junction of the interventricular septum and the right ventricular (RV) free wall. On a regional basis, the extent of scarring correlated positively with wall thickness (r = 0.36, p < 0.0001), and inversely with wall thickening (r = -0.21, p < 0.0001). On a per patient basis, the extent of scarring (mean, 8 +/- 9% of LV mass) was minimally related to maximum wall thickness (r = 0.40, p = 0.07) and LV mass (r = 0.33, p = 0.15), and correlated inversely with ejection fraction (r = -0.46, p = 0.04). CONCLUSIONS Myocardial scarring is common in asymptomatic or mildly symptomatic HCM patients who have not suffered sudden death. When present, scarring occurs in hypertrophied regions, is consistently localized to the junctions of the septum and RV free wall, and correlates positively with regional hypertrophy and inversely with regional contraction.

Contrast-enhanced magnetic resonance imaging of myocardium at risk ☆: Distinction between reversible and irreversible injury throughout infarct healing

OBJECTIVES We sought to determine the relationship of delayed hyperenhancement by contrast magnetic resonance imaging (MRI) to viable and nonviable myocardium within the region at risk throughout infarct healing. BACKGROUND The relationship of delayed MRI contrast enhancement patterns to injured but viable myocardium within the ischemic bed at risk has not been established. METHODS We compared in vivo and ex vivo MRI contrast enhancement to histopathologic tissue sections encompassing the entire left ventricle in dogs (n = 24) subjected to infarction with (n = 12) and without (n = 12) reperfusion at 4 h, 1 day, 3 days, 10 days, 4 weeks and 8 weeks. In vivo MR imaging was performed 30 min after contrast injection. RESULTS The sizes and shapes of in vivo myocardial regions of elevated image intensity (828+/-132% of remote) were the same as those observed ex vivo (241 slices, r = 0.99, bias = 0.05+/-1.6% of left ventricle [LV]). Comparison of ex vivo MRI to triphenyltetrazolim chloride-stained sections demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent ofinfarction at every stage of healing (510 slices, lowest r = 0.95, largest bias = 1.7+/-2.9% of LV). Conversely, hyperenhanced regions were smaller than the ischemic bed at risk defined by fluorescent microparticles at every stage of healing (239 slices, 35+/-24% of risk region, p<0.001). Image intensities of viable myocardium within the risk region were the same as those of remote, normal myocardium (102+/-9% of remote, p = NS). CONCLUSIONS Delayed contrast enhancement by MRI distinguishes between viable and nonviable regions within the myocardium at risk throughout infarct healing.

Physiological Basis of Myocardial Contrast Enhancement in Fast Magnetic Resonance Images of 2-Day-Old Reperfused Canine Infarcts

BACKGROUND Contrast-enhanced fast magnetic resonance (MR) images of acute, reperfused human infarcts demonstrate regions of hypoenhancement and hyperenhancement. The relations between the spatial extent and time course of these enhancement patterns to myocardial risk, infarct, and no-reflow regions have not been well characterized. METHODS AND RESULTS The proximal left anterior descending coronary artery was occluded in 11 closed-chest dogs for 90 minutes followed by 2 days of reperfusion. Regional blood flow was determined by use of radioactive microspheres. The animals were studied at the 2-day time point with contrast-enhanced fast MRI (Signa 1.5 T, General Electric). Thioflavin-S was administered to demarcate no-reflow regions. The hearts were then excised, sectioned into five base-to-apex slices, stained with 2,3,5-triphenyltetrazolium chloride (TTC), and photographed under room light (for TTC) and ultraviolet light (for thioflavin). The spatial extents of thioflavin-negative, TTC-negative, and risk regions were compared planimetrically with MRI hypoenhanced and hyperenhanced regions. The spatial locations of subendocardial hypoenhancement in MR images correlated closely with those of thioflavin-negative regions. Microsphere blood flow in these regions was significantly reduced compared with remote regions (0.37 +/- 0.09 versus 0.88 +/- 0.10 mL/min per gram, respectively, P < .001) and with baseline (0.37 +/- 0.09 versus 0.87 +/- 0.15 mL/min per gram, P < .01). The spatial extent of hyperenhancement was smaller than the risk region (r = .64, slope = 0.48, P < .001) but highly correlated with TTC-negative regions and were, on average, 12% larger (r = .93, slope = 1.12, P = .035). CONCLUSIONS In contrast-enhanced MR images of 2-day-old reperfused canine infarcts, myocardial regions of hypoenhancement are related to the no-reflow phenomenon. Approximately 90% of the myocardium within hyperenhanced regions is nonviable.

Regional Heterogeneity of Human Myocardial Infarcts Demonstrated by Contrast-Enhanced MRI Potential Mechanisms

BACKGROUND Myocardial reperfusion is pivotal to the prognosis of patients with acute myocardial infarction. In these patients, coronary flow is generally assessed by angiography and tissue perfusion by tracer scintigraphy. This study was designed to examine whether magnetic resonance imaging (MRI) provides information on myocardial perfusion and damage beyond that supplied by angiography and thallium scintigraphy after acute myocardial infarction. METHODS AND RESULTS Twenty-two patients with recent myocardial infarction had ECG, echocardiography, coronary angiography, and fast contrast-enhanced MRI. Twelve patients also had exercise thallium scintigraphy. Time-intensity curves obtained from infarcted and noninfarcted regions were correlated with coronary anatomy and left ventricular function. Two perfusion patterns were observed in infarcted regions by comparison with the normal myocardial pattern. All patients but 1 had persistent myocardial hyperenhancement within the infarcted region up to 10 minutes after contrast. In 10 patients, this hyperenhanced region surrounded a subendocardial area of decreased signal at the center of the infarcted region associated with coronary occlusion at angiography, Q waves on ECG, and greater regional dysfunction by echocardiography. Moreover, the extent and location of the MRI abnormalities correlated well with the extent and location of the fixed single-photon emission computed tomography thallium defects. CONCLUSIONS Large human infarcts, associated with prolonged obstruction of the infarct-related artery, are characterized by central dark zones surrounded by hyperenhanced regions on MRI. Conversely, reperfused infarcts with less regional dysfunction have uniform signal hyperenhancement. The MRI hyperenhanced segment correlates well with the fixed scintigraphic defect in patients with acute myocardial infarction.