Enn-Ling Chen

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.

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.

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.

Fast 23Na Magnetic Resonance Imaging of Acute Reperfused Myocardial Infarction Potential to Assess Myocardial Viability

BACKGROUND The ability of the myocyte to maintain an ionic concentration gradient is perhaps the best indication of myocardial viability. We studied the relationship of 23Na MRI intensity to viability and explored the potential of fast-imaging techniques to reduce 23Na imaging times in rabbits and dogs. METHODS AND RESULTS Eighteen rabbits underwent in situ coronary artery occlusion and reperfusion. The hearts were then either imaged following isolation and perfusion with cardioplegic solution (n = 6), imaged in vivo (n = 6), or analyzed for 23Na content and relaxation times (n = 12). Normal rabbits (n = 6) and dogs (n = 4) were imaged to examine the effect of animal size on 23Na image quality. 23Na imaging times were 7, 11, and 4 minutes for isolated rabbits, in vivo rabbits, and in vivo dogs, respectively. Infarcted, reperfused regions, identified by triphenyltetrazolium chloride staining, showed a significant elevation in 23Na image intensity compared with viable regions (isolated, 42 +/- 5%, P < .02; in vivo, 95 +/- 6%, P < .001), consistent with increased tissue sodium content. Similarly, 23Na MR spectroscopy showed that [Na+] was higher in nonviable than viable myocardium (isolated, 99 +/- 4 versus 61 +/- 2 mmol/L; in vivo, 91 +/- 2 versus 38 +/- 1 mmol/L; P < .001 for both). Image signal-to-noise ratios were higher in dogs than rabbits despite shorter imaging times, primarily due to larger voxels. CONCLUSIONS Following acute infarction with reperfusion, a regional increase in 23Na MR image intensity is associated with nonviable myocardium. Fast gradient-echo imaging techniques reduce 23Na imaging times to a few minutes, suggesting that 23Na MR imaging has the potential to become a useful experimental and clinical tool.

Relationship of elevated 23Na magnetic resonance image intensity to infarct size after acute reperfused myocardial infarction.

BACKGROUND Elevated 23Na MR image intensity after acute myocardial infarction has previously been shown to correspond to high tissue [Na+] and loss of myocardial viability. In this study, we explored the potential of in vivo 23Na MRI to assess infarct size and investigated possible mechanisms for elevated 23Na image intensity. METHODS AND RESULTS Thirteen dogs and 8 rabbits underwent in situ coronary artery occlusion and reperfusion and were imaged by 23Na MRI. For anatomically matched left ventricular short-axis cross sections (n=46), infarct size measured by in vivo 23Na MRI correlated well with triphenyltetrazolium chloride staining (r=0.87, y=0.92x+3.37, P<0.001). Elevated 23Na image intensity was observed in infarcted myocardium (206+/-37% of remote in dogs, P<0.001; 215+/-58% in rabbits, P<0.002) but was not observed after severe but reversible ischemic injury (101+/-11% of baseline, P=NS). High-resolution ex vivo imaging revealed that regions of elevated 23Na image intensity appeared to be identical to those of infarcted regions (r=0.97, y=0.92x+1.52, P<0.001). In infarcted regions, total tissue [Na+] was elevated (89+/-12 versus 37+/-9 mmol/L in control tissue, 156+/-60% increase, P<0.001) and was associated with increased intracellular sodium (254+/-68% of control, P<0.005) and an increased intracellular sodium/potassium ratio (868+/-512% of control, P<0.002). Morphometric analysis demonstrated only a minor increase in extracellular volume (17+/-8% versus 14+/-5%, P<0.05) in the infarcted territory. CONCLUSIONS Elevated 23Na MR image intensity in vivo measures infarct size after reperfused infarction in both a large and a small animal model. The mechanism of elevated 23Na image intensity is probably intracellular sodium accumulation secondary to loss of myocyte ionic homeostasis.

Microvascular Integrity and the Time Course of Myocardial Sodium Accumulation After Acute Infarction

Loss of membrane permeability caused by ischemia leads to cellular sodium accumulation and myocardial edema. This phenomenon has important implications to left ventricular structure and function in the first hours after myocardial infarction. We hypothesized that during this period of time, after prolonged coronary occlusion and complete reflow, the rate of myocardial sodium accumulation is governed by microvascular integrity. We used 3-dimensional 23Na MRI to monitor myocardial sodium content changes over time in an in vivo closed-chest canine model (n=13) of myocardial infarction and reperfusion. Infarcts with microvascular obstruction (MO) defined by both radioactive microspheres and contrast-enhanced 1H MRI showed a slower rate of sodium accumulation as well as lower blood flow at 20 minutes and 6 hours after reperfusion. Conversely, the absence of MO was associated with faster rates of sodium accumulation and greater blood flow restoration. In addition, infarct size by 23Na MRI correlated best with infarct size by triphenyltetrazolium chloride and contrast-enhanced 1H MRI at 9 hours after reperfusion. We conclude that in reperfused myocardial infarction, sodium accumulation is dependent on microvascular integrity and is slower in regions of MO compared with those with patent microvasculature. Finally, 23Na MRI can be a useful tool for monitoring in vivo myocardial sodium content in acute myocardial infarction.

Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk

RATIONALE After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. OBJECTIVE To determine whether T2-weighted MRI delineates the AAR. METHODS AND RESULTS Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis demonstrated a fingerprint match of T2-hyperintense regions with the intricate contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients there was a close correspondence between contours of T2-hyperintense and infarcted regions, and the transmural-extent of these regions were highly correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001). CONCLUSION T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI should not be used to measure myocardial salvage, either to inform patient management decisions or to evaluate novel therapies for acute MI.

Motion and flow insensitive adiabatic T2 -preparation module for cardiac MR imaging at 3 Tesla.

A versatile method for generating T2‐weighting is a T2‐preparation module, which has been used successfully for cardiac imaging at 1.5T. Although it has been applied at 3T, higher fields (B0 ≥ 3T) can degrade B0 and B1 homogeneity and result in nonuniform magnetization preparation. For cardiac imaging, blood flow and cardiac motion may further impair magnetization preparation. In this study, a novel T2‐preparation module containing multiple adiabatic B1‐insensitive refocusing pulses is introduced and compared with three previously described modules [(a) composite MLEV4, (b) modified BIR‐4 (mBIR‐4), and (c) Silver‐Hoult–pair]. In the static phantom, the proposed module provided similar or better B0 and B1 insensitivity than the other modules. In human subjects (n = 21), quantitative measurement of image signal coefficient of variation, reflecting overall image inhomogeneity, was lower for the proposed module (0.10) than for MLEV4 (0.15, P < 0.0001), mBIR‐4 (0.27, P < 0.0001), and Silver‐Hoult–pair (0.14, P = 0.001) modules. Similarly, qualitative analysis revealed that the proposed module had the best image quality scores and ranking (both, P < 0.0001). In conclusion, we present a new T2‐preparation module, which is shown to be robust for cardiac imaging at 3T in comparison with existing methods. Magn Reson Med 70:1360–1368, 2013.

Noninvasive Assessment of Blood Flow Based on Magnetic Resonance Global Coherent Free Precession

Background—Magnetic resonance global coherent free precession (GCFP) is a new technique that produces cine projection angiograms directly analogous to those of x-ray angiography noninvasively and without a contrast agent. In this study, we compared GCFP blood flow with “gold standards” to determine the accuracy of noninvasive GCFP blood flow measurements. Methods and Results—The relationship between GCFP blood flow and true blood flow defined by invasive ultrasonic flow probe and by phase contrast velocity encoded MRI (VENC) was studied in anesthetized dogs (n=6). Blood flow was controlled by use of a hydraulic occluder around the left iliac artery. GCFP images were acquired by selectively exciting the abdominal aorta and visualizing temporal blood flow into the iliac arteries. GCFP flow was similar to ultrasonic blood flow at baseline (131.3±44.8 versus 114.8±34.2 mL/min), during occlusion (10.8±5.1 versus 6.5±7.2 mL/min), during reactive hyperemia (191.4±100.7 versus 260.3±138.7 mL/min), during the new resting state (135.5±52.4 versus 117.8±24.1 mL/min), and during partial occlusion (61.4±36.4 versus 49.3±13.1 mL/min, P=NS for all). Results comparing GCFP flow with VENC were similar. Statistical analysis revealed that GCFP flow was related to mean blood flow assessed by the flow probe (P<0.0001) and by VENC (P<0.0001). In the control right iliac artery, conversely, GCFP measurements were unaffected throughout all left iliac interventions (P=NS). Conclusions—GCFP blood flow is linearly related to true blood flow for a straight, cylindrical blood vessel without branches. Although more complex geometries imply a qualitative rather than a quantitative relationship, the data nevertheless suggest that GCFP may serve as the basis for a new form of noninvasive stress testing.