Comparison of albumin-(Gd-DTPA)30 and Gd-DTPA-24-cascade-polymer for measurements of normal and abnormal microvascular permeability

The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). T1-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)₃₀ or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)₃₀ demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.     

Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA

To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction.     

Acute myocardial infarction: MR evaluation in 29 patients

This study evaluated the ability of MR to identify and characterize the region of myocardial infarction in humans. Twenty-nine patients, all with ECG and enzyme rises consistent with an acute myocardial infarction, were studied by MR 3-17 days from the onset of acute chest pain. Four patients were excluded because of inability to acquire adequate MR studies. For comparison, 20 normal subjects were studied who also had gated MR examinations. The site of infarction was visualized in 23 patients as an area of high signal intensity in relation to the normal myocardium, a contrast that increased on the second-echo image. The regions of abnormal signal intensity corresponded to the anatomic site of infarction as defined by the ECG changes. The mean T2 relaxation time of the infarcted myocardium (79 +/- 22 msec) was significantly prolonged in comparison with the mean T2 (43.9 +/- 9 msec) of normal myocardium (p less than .01). The mean percentage of contrast (intensity difference) between normal and infarcted myocardium was much greater on the second-echo images (65.6 +/- 34.0%) than the first-echo images (27.5 +/- 18.7%). In the normal subjects there was no difference in T2 between the anterolateral (40.3 +/- 5.7 msec) and septal (39.5 +/- 7.4 msec) regions, and percentages of contrast between these two regions of myocardium on the first-echo (9.1 +/- 7.4%) and second-echo (15.0 +/- 13.3%) images were similar. Thus, MR can be used to directly visualize acute infarcts. However, it has several pitfalls, including the necessity to differentiate signal from slowly flowing blood in the ventricle, from increased signal from a region of infarction and artifactual variation of signal intensity in the myocardium due to respiratory motion or residual cardiac motion.     

Occlusive myocardial infarction: investigation of bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging in a cat model

PURPOSE: To test whether bis-gadolinium mesoporphyrins-enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2'3'5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity-enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time. In one of the two remaining cats, a doughnut pattern of signal intensity enhancement was noted. The other cat showed intensely homogeneous enhancement of infarcted myocardium at MR imaging. The size of the area of signal intensity enhancement at MR imaging in these two cats was accurately mapped to that of the infarction on the TTC-stained specimens. CONCLUSION: Occlusive myocardial infarction cannot be accurately detected at bis-gadolinium mesoporphyrins-enhanced MR imaging.     

Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats.

PURPOSE: To measure the fractional distribution volume of gadopentetate dimeglumine in normal and reperfused infarcted myocardium at magnetic resonance (MR) imaging by using the fractional distribution volume of technetium 99m-diethylenetriaminepentaacetic acid (DTPA) as an independent reference. MATERIALS AND METHODS: Rats were subjected to 1 hour of coronary artery occlusion and 1 hour of reperfusion before inversion-recovery echo-planar imaging or autoradiography. Regional change in relaxation rate (delta R1) ratios for myocardium over blood were compared with radioactivity ratios for myocardium over blood after the injection of 99mTc-DTPA. RESULTS: Both delta R1 and radioactivity ratios demonstrated equilibrium distribution and hence represent partition coefficients (lambda). The fractional distribution volumes were greater in infarcted myocardium (0.90 +/- 0.05 for gadopentetate dimeglumine and 0.89 +/- 0.04 for 99mTc-DTPA) than in normal myocardium (0.23 +/- 0.02 for gadopentetate dimeglumine and 0.16 +/- 0.01 for 99mTc-DTPA). Area at risk at autoradiography was not significantly different from that at histomorphometry. The infarction size defined by using triphenyltetrazolium chloride was 13% +/- 4 smaller than that defined by using autoradiography. CONCLUSION: The fractional distribution volumes of gadopentetate dimeglumine and 99mTc-DTPA are similar and indicate extracellular distribution in normal myocardium and intracellular as well as extracellular distribution in reperfused infarction. Because the failure of cells to exclude these agents is indicative of necrosis, contrast medium-enhanced MR imaging may be useful to quantify myocardial infarction.     

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). ΔR1 was repeatedly measured over 30 min. Gd-BOPTA caused greater ΔR1 for blood and myocardium than did Gd-DTPA clearance of both agents from normal and infarcted myocardium was similar to blood clearance; plots of ΔR1myocardium/ΔR1blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater ΔR1 than Gd-DTPA in regions which contain serum albumin.     

Differentiation of reversible and irreversible myocardial injury by MR imaging with and without gadolinium-DTPA

The current study evaluated the capability of magnetic resonance (MR) imaging to distinguish myocardium subjected to reversible and irreversible ischemic injury. Nine dogs underwent left anterior descending coronary arterial occlusion for 15 minutes (reversible injury) and nine for 1 hour (irreversible injury), followed by reperfusion for 24 hours in both groups. Six dogs from each group received 0.5 mmol/kg of gadolinium-DTPA intravenously; the remaining dogs received no contrast media. In the dogs with irreversible injury but no contrast media, there were prolonged T1 and T2 of the infarcted myocardium and adequate visualization of the infarct. The percentage of contrast between normal and infarcted myocardium was greatest on T2-weighted images. In the group with irreversible injury and contrast media, Gd-DTPA produced significant T1 shortening of injured myocardium, with resultant high signal intensity of the infarct, and significantly enhanced contrast compared with the group that did not receive Gd-DTPA. In the dogs with reversible injury, there were no regional differences in intensity or relaxation times. MR has the capability to distinguish myocardium with irreversible injury from that with reversible injury. The difference of T1 between normal and reperfused infarcted myocardium is increased by Gd-DTPA; thus, contrast between these two is enhanced on MR images.     

MR imaging of spatial extent of microvascular injury in reperfused ischemically injured rat myocardium: value of blood pool ultrasmall superparamagnetic particles of iron oxide

PURPOSE: To (a) assess the value of a blood pool magnetic resonance (MR) imaging contrast agent (Clariscan) for characterizing microvascular injury in ischemically injured rat myocardium and (b) compare the extent of microvascular injury at Clariscan-enhanced MR imaging with infarction and areas at risk seen with histochemical staining. MATERIALS AND METHODS: Twenty rats underwent 45 minutes of coronary artery occlusion and 3 hours of reperfusion. Sequential T1-weighted spin-echo MR images were acquired in 10 rats to assess leakage of Clariscan into myocardium over time. Ten other rats underwent the same duration of occlusion and reperfusion (3 hours) so that the extent of microvascular injury in the entire heart could be measured and correlated with infarction and area at risk at necropsy. The Student t test and Bland-Altman method were used for data analysis. RESULTS: Clariscan improved visualization of regions with transmural and nontransmural microvascular injury. Accumulation of Clariscan was best reflected by the mean ratios of signal intensity in injured myocardium to that in normal myocardium measured before (0.98 +/- 0.01 [standard error of the mean]) and after (1.34 +/- 0.04) injection. At 15 minutes after injection, the size of the enhanced region remained constant over the course of observation. The mean size of the hyperenhanced region (44% of the left ventricle +/- 2) was significantly (P <.001) larger than the mean size of true infarction at necropsy (29% +/- 3) but smaller than the mean size of the area at risk (50% +/- 2). CONCLUSION: Clariscan has potential for estimating the spatial extent of microvascular injury in ischemically injured myocardium and may be useful as a marker of microvascular injury after thrombolytic therapy.     

Infarcted myocardium in pigs: MR imaging enhanced with slow-interstitial-diffusion gadolinium compound P760.

PURPOSE: To assess the value of P760, a gadolinium chelate with slow interstitial diffusion and high relaxivity, for magnetic resonance (MR) imaging of acute myocardial infarction in pigs. MATERIALS AND METHODS: First-pass gradient-echo MR imaging and spin-echo MR imaging were performed with P760 and then with gadoterate meglumine in eight pigs with occlusive acute myocardial infarction. P760 signal intensity enhancement and clearance were compared with those of gadoterate meglumine. RESULTS: The first-pass enhancement ratio of P760 in normal myocardium was higher than that in infarcted myocardium (1.37 +/- 0.06 [SEM] vs 1.05 +/- 0.03, P = .03). The myocardial first pass showed a blood pool-like curve for P760. The blood pool enhancement ratio 40 seconds after injection was higher for P760 than for gadoterate meglumine (left ventricular cavity, 1.75 +/- 0.06 vs 1.45 +/- 0.06, P = .009). Spin-echo MR imaging showed improved contrast between normal and infarcted myocardium after P760 administration: The ratio before contrast material administration was 0.21 +/- 0.03, that at 15 minutes was 0.48 +/- 0.05 (P = .002), and that at 25 minutes was 0.47 +/- 0.07 (P = .003). CONCLUSION: P760 is an MR imaging contrast agent characterized by low diffusion, a blood pool effect soon after low-dose administration, and fast elimination. This agent is useful for improved myocardial perfusion MR imaging of acute myocardial infarction.     

Gd—DTPA增强MRI诊断心肌梗塞

15例心脏作Gd-DTPA增强前后MRI检查,增强后为连续动态观察。其中7例为正常对照;7例为心肌梗塞(包括5例亚急性和2例慢性心肌梗塞);1例为陈旧性心肌梗塞。结果显示:增强前正常心肌信号率与梗塞心肌信号率无差别。增强后梗塞心肌信号率既高于增强前也明显高于其周围的正常心肌。无论肉眼观察还是信号测量均发现Gd-DTPA增强MRI能诊断心肌梗塞,改善心肌梗塞的显示。作者对增强后心肌信号率的系列变化作了描述。     

Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: Evidence for loss of compartmentalization of contrast media

The purpose of this study was to characterize the contrast caused by a susceptibility MRI contrast agents, on spin echo T₂-weighted imaging of reperfused myocardial infarction. Our interest in this model focused on the expected requirement that such agents be compartmentalized in the tissue to cause signal loss on spin echo images, a condition which may not be present in reperfused infarcted myocardium. Accordingly, nine rats were subjected to 2 h of left coronary artery occlusion followed by 3 ± 0.5 h of reperfusion prior to administration of contrast media. Three sets of MR images were acquired: (a) baseline axial images at the midventricle, both T₁-weighted (TR/TE = 300/20) and T₂-weighted (TR/TE = 1500/60); (b) T₁-weighted images after administering a T₁-enhancing agent, Gd-DTPA-BMA (0.2 mmol/kg), to document that contrast media is delivered to the reperfused infarction; and (c) T₂-weighted images after administering the susceptibility agent, Dy-DTPA-BMA (1.0 mmol/kg). Gadolinium-enhanced T₁ images depicted reperfused infarction as regions with greatly enhanced signal intensity compared with unin-farcted myocardium, indicating that contrast agent was delivered to the infarcted zone. Dysprosium-enhanced T₁ images depicted the injury as a region of persistent signal intensity relative to depletion of signal in normal myocardium, consistent with failure of the contrast agent to cause signal loss. Similar infarction sizes were observed for unenhanced T₂-weighted images (33 ± 5%), gadolinium-enhanced T₁ weighted images (36 ± 5%) and postmortem staining (30 ± 6%); strong correlations (r > 0.9) were noted in comparisons of these data. Dysprosium-enhanced images exhibited a smaller region of differential signal presumed to be infarction (20 ± 5%, P < 0.05) and weak correlations (r < 0.75) with the other measurements. We conclude that the smaller infarction depicted on dysprosium-enhanced images is a subregion of the true infarction in which myocardial necrosis is sufficiently advanced that the agent is homogeneously distributed throughout all tissue compartments, preventing T₂*-dependent phase loss on spin echo images.     

Contrast enhancement for the myocardium.

The potential of MR imaging and spectroscopy in ischemic heart disease is substantial. MR contrast media have the potential to improve the differential tissue characterization among normal, ischemic, and infarcted myocardium. Several reports in animals and patients have revealed that MR contrast media can improve the delineation of acute myocardial infarctions (1–7). Studies from several centers in Europe and Asia have demonstrated that the contrast between the normal and acutely infarcted myocardium substantially increased with the use of gadolinium-DTPA administered intravenously (1, 2, 4, 5). In these studies, the acutely infarcted myocardium on delayed MR scans demonstrated greater enhancement with the paramagnetic contrast media than normal myocardium, producing a greater percentage contrast between the two regions. These studies are consistent with previous reports using gadolinium-DTPA contrast media to enhance the differential in signal intensity between the normal and infarcted myocardium in animal models (3, 6, 7). The expanded use of MR in ischemic heart disease will likely depend upon employing contrast media to enhance regional myocardial signal in proportion to regional blood flow. Such contrast media are needed for using MRI to demonstrate regions of myocardial ischemia and to depict reperfusion of a myocardial region after an ischemic event. © 1991 Academic Press, Inc.     

Optimal use of contrast medium in contrast enhanced MR imaging of the heart

With the recent development of fast MR imaging techniques, the diagnostic value of contrast enhanced MR imaging of the heart has been substantially improved. Since no tissue-specific contrast medium is available for clinical cardiac MR imaging at this point, both the early and late dynamics of extracellular MR contrast medium should be carefully evaluated for assessing the multiple aspects of cardiac function, including myocardial blood flow, myocardial, viability, and left ventricular function. Myocardial blood flow can be assessed by monitoring the first-pass passage of MR contrast medium. Quantitative assessments of arterial input function and output function in the regional myocardium can provide more accurate detection of altered myocardial blood flow in patients with coronary artery disease. Excellent contrast between infarcted myocardium and normal tissue can be obtained with delayed contrast enhanced MR imaging. Myocardial infarction, including small subendocardial infarction and chronic scar, is demonstrated as an area of "hyperenhancement" on delayed enhanced MR images, while the signal from normal myocardium is nearly null. This review paper describes the optimal dose and injection rate of MR contrast material for functional cardiac MR imaging studies. In addition, practical suggestions for obtaining good cardiac MR images and interpreting contrast enhanced MR images are given and are explained in detail.     

Myocardial infarction: optimization of inversion times at delayed contrast-enhanced MR imaging

Seventeen patients underwent magnetic resonance (MR) imaging for myocardial viability with a protocol approved by the institutional review board and gave written informed consent. Breath-hold cine inversion-recovery segmented k-space true fast imaging with steady-state precession sequence, referred to as inversion time (TI) mapping, was performed to determine optimal TI for myocardial infarction inversion-recovery imaging. From TI mapping, optimal TI was 180-315 msec 10-15 minutes after administration of 0.15 mmol/kg of gadolinium-based contrast material. At that optimal TI, relative signal intensity of infarcted myocardium compared with uninfarcted myocardium was maximal (mean +/- standard deviation, 297.8% +/- 86.5), whereas signal-to-noise ratio of uninfarcted myocardium was minimal (4.5 +/- 1.2). When applied to conventional myocardial infarction inversion-recovery imaging, optimal TI resulted in nulling of signal intensity of uninfarcted myocardium in all patients and in excellent conspicuity of infarcted myocardium in all nine patients with visible infarction.     

Irreversibly damaged myocardium at MR imaging with a necrotic tissue-specific contrast agent in a cat model

PURPOSE: To investigate the capability of a necrosis-avid magnetic resonance (MR) contrast agent, bis-gadolinium mesoporphyrins, for assessment of irreversibly damaged myocardium and to evaluate the time course of signal enhancement in the reperfused myocardium. MATERIALS AND METHODS: Nine cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery followed by 90 minutes of reperfusion. Contrast material-enhanced T1-weighted spin-echo images were obtained for 12 hours in five cats and 6 hours in four cats. Pathologic examinations of the resected specimens were performed with 2'3'5-triphenyl tetrazolium chloride (TTC) histochemical staining and electron microscopy. The size of enhanced area on MR images was compared with that of irreversibly damaged myocardium with TTC staining. The time course of signal enhancement was evaluated. RESULTS: The size of enhanced area on MR images was well correlated with that of irreversibly damaged myocardium with TTC staining. Maximum enhancement occurred 1-3 hours after administration of the contrast material, with mean enhancement of 171% that of normal myocardium. Electron microscopic examinations showed severe myocardial damage in the irreversibly damaged myocardium but only mild edematous changes in the reversibly damaged myocardium. CONCLUSION: MR images enhanced with bis-gadolinium mesoporphyrins provide accurate sizing of irreversibly damaged myocardium with a strong and persistent signal enhancement in the reperfused myocardium.     

Reperfused and nonreperfused myocardial infarction: diagnostic potential of Gd-DTPA--enhanced MR imaging

Forty-five patients with suspected acute myocardial infarction were examined with magnetic resonance (MR) imaging before and serially up to 30 minutes after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (DTPA), 0.1 mmol/kg of body weight. Coronary angiography after thrombolytic therapy was performed in all patients to assess reperfusion. Intensity ratios between both reperfused and nonreperfused infarcted areas and normal myocardium increased significantly up to 15-20 minutes after administration of Gd-DTPA and were still elevated 30 minutes after injection (P less than .0001). In accordance with the findings in experimental studies, four distribution patterns of infarct enhancement were observed. The overlap in enhancement patterns and similar maximal intensity ratios after Gd-DTPA administration for both reperfused and nonreperfused infarcts preclude a reliable differentiation on the basis of these factors alone. Significant enhancement of both reperfused and nonreperfused infarcts allows adequate infarct imaging up to at least 30 minutes after administration of Gd-DTPA.     

MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of liver infarction

RATIONALE AND OBJECTIVES: The mechanisms of action leading to specific localization of necrosis-avid contrast agents (NACAs) such as gadophrin-2 are not well defined. It has been suggested recently that agents with a high degree of serum albumin binding may also serve as NACAs by virtue of nonspecific hydrophobic interactions. The present MRI-histomorphology correlation study was conducted to verify the likelihood of the proposed albumin-binding mechanism by comparing an albumin-binding blood pool agent, MP-2269, with gadophrin-2 in a rat model of reperfused liver infarction. METHODS: Reperfused infarction in the right liver lobe was surgically induced in six rats. Serial T1-weighted MRI was performed before and after intravenous injection of MP-2269 at 0.05 mmol/kg and repeated in the same rats 24 hours later after intravenous injection of gadophrin-2 at the same dosage (0.05 mmol/kg). The MR images were matched with corresponding histomorphological findings. The signal intensity and contrast ratio of infarcted and normal hepatic lobes were quantified and compared between the two agents during the postcontrast course. RESULTS: Before contrast, the infarcted lobe was indiscernible from normal liver on T1-weighted MRI. Shortly after injection of both MP-2269 and gadophrin-2, a negative contrast occurred between infarcted and normal liver because of a strong liver signal intensity enhancement and an inferior uptake in the necrotic liver. On delayed phase (>60 minutes), a necrosis-specific contrast enhancement (contrast ratio 1.6) developed with gadophrin-2 but not with MP-2269. The MR images matched well with corresponding histomorphological findings. CONCLUSIONS: Although both MP-2269 and gadophrin-2 feature an albumin-binding capacity, only gadophrin-2 displayed a persistent necrosis-specific contrast enhancement in the rat model of reperfused liver infarction. Therefore, the role of albumin binding in the mechanisms of NACAs should be reevaluated.     

Contrast media for MR imaging of the heart

The role of contrast media for quantitative characterization of ischemic myocardial events with magnetic resonance (MR) imaging has advanced considerably in the past few years. Contrast material-enhanced MR imaging is useful for identifying and sizing myocardial infarcts and for distinguishing between occlusive and reperfused myocardial infarcts. Recent results suggest that contrast-enhanced MR imaging can also be used to identify areas of cell death in regions of reperfused myocardial infarction. With the aid of MR contrast media, fast MR imaging techniques may be useful in estimating regional myocardial perfusion. Although no simple relationship between signal intensity and concentration exists, contrast-enhanced MR perfusion imaging can demonstrate the presence and relative severity of hypoperfused myocardium. Combining myocardial perfusion imaging with the anatomic and functional information provided by other MR imaging techniques could make MR imaging a comprehensive noninvasive means of evaluating ischemic cardiac disease.     

An improved MR imaging technique for the visualization of myocardial infarction

PURPOSE: To design a segmented inversion-recovery turbo fast low-angle shot (turboFLASH) magnetic resonance (MR) imaging pulse sequence for the visualization of myocardial infarction, compare this technique with other MR imaging approaches in a canine model of ischemic injury, and evaluate its utility in patients with coronary artery disease. MATERIALS AND METHODS: Six dogs and 18 patients were examined. In dogs, infarction was produced and images were acquired by using 10 different pulse sequences. In patients, the segmented turboFLASH technique was used to acquire contrast material-enhanced images 19 days +/- 7 (SD) after myocardial infarction. RESULTS: Myocardial regions of increased signal intensity were observed in all animals and patients at imaging. With the postcontrast segmented turboFLASH sequence, the signal intensity of the infarcted myocardium was 1,080% +/- 214 higher than that of the normal myocardium in dogs-nearly twice that of the next best sequence tested and approximately 10-fold greater than that in previous reports. All 18 patients with myocardial infarction demonstrated high signal intensity at imaging. On average, the signal intensity of the high-signal-intensity regions in patients was 485% +/- 43 higher than that of the normal myocardium. CONCLUSION: The segmented inversion-recovery turboFLASH sequence produced the greatest differences in regional myocardial signal intensity in animals. Application of this technique in patients with infarction substantially improved differentiation between injured and normal regions.     

Blood pool contrast-enhanced MRI detects suppression of microvascular permeability in early postinfarction reperfusion after nicorandil therapy.

Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with a nitrate-like effect. It is approved for clinical use in Europe and Japan as an antianginal drug. The purpose of this investigation was to assess the acute effects of nicorandil therapy on microvascular injury using the blood pool MR contrast medium, NC100150 injection (Clariscan). Microvascular injury was produced in 24 rats using 45 min of coronary occlusion / 3 hr reperfusion. Nicorandil was infused at 15 min of occlusion and during reperfusion. Control animals received a saline solution. MR imaging was used to characterize microvascular permeability, quantify the extent of microvascular injury, LV volume, and wall thickness. Hyperenhancement at 30 min after administration of 0.05 mmol/kg Clariscan mapped the extent of ischemia-induced loss of microvascular integrity. The accumulation of Clariscan in the injured region was significantly suppressed in nicorandil compared to control rats. Nicorandil reduced the extent of microvascular injury from 44 +/- 2% to 18 +/- 2% (P < 0.01) and true infarction size from 29 +/- 2% to 12 +/- 1%. The extent of the hyperenhanced region correlated with the true size of area at risk at autopsy. On spin-echo MRI during end-diastole, nicorandil reduced LV end-diastolic volume and preserved wall thickness in remote myocardium; both parameters are markers of LV dilatation caused by acute infarction (remodeling). In conclusion, blood pool contrast-enhanced MRI has the potential to depict and quantify the extent of microvascular permeability and injury. Nicorandil suppressed microvascular permeability, reduced infarction size, and improved LV function in early postinfarction reperfusion.