MRI of reperfused myocardial infarct in dogs

The current study evaluated the capability of magnetic resonance imaging (MRI) to detect acutely injured myocardium in the first 5 hr after a 1-hr period of occlusion followed by reperfusion of the coronary artery and to determine if magnetic relaxation times could be used to differentiate injured from normal myocardium. Fourteen dogs underwent left anterior descending coronary arterial occlusion for 1 hr, followed by reperfusion. Electrocardiographic gated MRI was performed before and during coronary artery occlusion and immediately after reperfusion, and serially up to 5 hr postreperfusion. In all dogs with postmortem evidence of myocardial infarction (n = 7), regional increase of signal intensity was observed in the anterior wall of the left ventricle as early as 30 min after reestablishing blood flow to the jeopardized myocardium. The area of increased signal intensity in the myocardium conformed to the site of myocardial infarction found at autopsy. The signal intensities of the jeopardized myocardium were significantly (p less than 0.01) greater than those of normal myocardium at 30 to 300 min postreperfusion. The T2 (spin-spin) relaxation time was significantly (p less than 0.05-p less than 0.01) prolonged in the region of the reperfused myocardial infarct at 30 min (59.6 +/- 13.1 msec) and remained prolonged up to 300 min (62.6 +/- 12 msec) postreperfusion compared with the T2 of normal myocardium (40.6 +/- 5.2 msec). Of the remaining seven dogs, four developed fatal arrhythmias during the reperfusion procedure and three dogs had no evidence of myocardial infarction at pathologic examination. Signal intensities and T2 relaxation times in these three dogs did not change during the experiment. Thus, acutely infarcted and reperfused myocardium can be detected by in vivo gated MRI, using the spin-echo technique, as early as 30 min after reperfusion. The jeopardized myocardium is characterized by a prolonged T2 relaxation time and, therefore, best visualized on T2-weighted images.     

Value of t2-weighted magnetic resonance imaging early after myocardial infarction in dogs: comparison with bis-gadolinium-mesoporphyrin enhanced T1-weighted magnetic resonance imaging and functional data from cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Magnetic Resonance Imaging (MRI) has proved to provide noninvasive methods to investigate the functional repercussion of myocardial infarction and to measure infarct size with specific contrast agents. In this study, we evaluate whether the combination of T2-weighted and contrast-enhanced T1-weighted MRI could detect and discern necrotic and ischemic, but salvageable, myocardium. METHODS: Reperfused myocardial infarction was surgically induced in 14 dogs. T1- and T2-weighted MRI was performed 6 hours after administration of the necrosis avid contrast agent Gadophrin-2 at 0.05 mmol/kg. Gradient-echo cine MRI series were performed at baseline and at 6 hours. Quantification of myocardial infarction was performed with triphenyltetrazolium chloride staining. RESULTS: There was a strong correlation between of postcontrast T1-weighted MRI and histomorphometry (r2 = 0.98, P < 0.01). T2-weighted MRI overestimated the infarct size by 10.5% +/- 4.3% of left ventricular area. A good correlation was found between hyperintense areas on T2-weighted images and the percentage of dysfunctional areas on cine MRI (r2 = 0.84, P < 0.01). In regions with increased signal intensity on T2-weighted MRI, a decreased maximal systolic thickening (11.8% +/- 4.9%, P = 0.043) was found. CONCLUSION: In this study, the difference between the hyperintense areas on T2-weighted and enhanced T1-weighted images after myocardial infarction likely represents viable myocardium.     

MR imaging of reperfused myocardial infarction: comparison of necrosis-specific and intravascular contrast agents in a cat model

PURPOSE: To compare T2-weighted and Gadomer-17- and bis-gadolinium mesoporphyrins-enhanced magnetic resonance (MR) images for distinguishing reversibly from irreversibly damaged myocardium in a cat model of reperfused myocardial infarction. MATERIALS AND METHODS: Twelve cats underwent 90 minutes of occlusion and 90 minutes of reperfusion of the left anterior descending coronary artery. After baseline T1- and T2-weighted MR images were obtained, Gadomer-17-enhanced and bis-gadolinium mesoporphyrins-enhanced T1-weighted images were sequentially obtained for 6 hours and 2 hours, respectively. After MR imaging, all cats were sacrificed for 2,3,5-triphenyltetrazolium chloride (TTC) histochemical tissue staining. Areas of abnormal signal intensity on T2-weighted and Gadomer-17-enhanced and bis-gadolinium mesoporphyrins-enhanced T1-weighted MR images were compared with the areas of infarction seen at TTC histochemical staining by using repeated-measures two-way analysis of variance, linear regression analysis, and Bland-Altman analysis. RESULTS: Mean areas of abnormally high signal intensity on T2-weighted and Gadomer-17-enhanced T1-weighted MR images (43.9% of the left ventricular surface area +/- 11.9 [SD] and 37.7% +/- 10.1, respectively) were significantly larger than the mean area of myocardial infarction at TTC staining (25.7% +/- 12.5) (P <.001). However, there was excellent correlation between the size of an enhancing area on bis-gadolinium mesoporphyrins-enhanced T1-weighted MR images and that of myocardial infarction at TTC staining (r = 0.916, P <.001). CONCLUSION: bis-Gadolinium mesoporphyrins-enhanced T1-weighted MR images accurately reflect the area of infarction, whereas the size of infarction is overestimated on T2-weighted and Gadomer-17-enhanced T1-weighted MR images, which seem to depict the periinfarct area as well as the infarct area.     

Factors influencing myocardial salvage with primary angioplasty

Background

The purpose of this study was to evaluate the factors influencing the salvage of jeopardized myocardium in patients treated with primary angioplasty for acute myocardial infarction.

Methods and Results

This multicenter study involved 59 patients with acute myocardial infarction who underwent primary angioplasty without antecedent thrombolytic therapy and paired baseline (before angioplasty) and predischarge tomographic perfusion imaging by quantitative ^99mTc-labeled sestamibi techniques for assessing the initial area at risk and eventual infarct size. Of the 59 patients who underwent primary angioplasty, Thrombolysis In Myocardial Infarction (TIMI) level 3 perfusion was restored in the infarct vessel in 54 patients (92%). On average, approximately one third of the left ventricular myocardial mass was initially jeopardized by the infarction in progress; eventual infarct size was 18%±15% of the left ventricle; myocardial salvage was 16%±17% of the left ventricle. Primary angioplasty salvaged 46%±50% of initially jeopardized myocardium. Factors correlated with myocardial salvage included elapsed time from onset of pain to reperfusion, infarct location (anterior infarcts had more myocardial salvage than inferior infarcts), and residual flow to the infarct zone at preangioplasty baseline levels. In the five patients reperfused less than 2 hours from onset of pain, 80% of the jeopardized myocardium was salvaged. Myocardial salvage beyond 2 hours was much more variable.

Conclusion

Primary angioplasty was highly effective at restoring normal perfusion in the infarct vessel and salvaging jeopardized myocardium. The myocardial salvage was highly variable and correlated with elapsed time to reperfusion, baseline residual flow to the infarct zone, and infarct location.     

Early-phase myocardial infarction: evaluation by MR imaging

In vivo gated magnetic resonance (MR) imaging was performed in 12 dogs immediately after occlusion of the left anterior descending coronary artery and serially up to 5 hours and again between 4 and 14 days. This was done to evaluate the appearance of acute myocardial infarcts and to determine how soon after coronary artery occlusion MR imaging can demonstrate the site of acute myocardial ischemia. In nine dogs with postmortem evidence of myocardial infarction, regional increase of signal intensity of the myocardium was present by 3 hours after coronary artery occlusion and conformed to the site of myocardial infarct found at autopsy. The signal intensity on T2-weighted images of the infarcted myocardium was significantly greater than that of normal myocardium at 3, 4, and 5 hours after occlusion. The T2 (spin-spin) relaxation time was significantly prolonged in the region of myocardial infarct at 3, 4, and 5 hours postocclusion compared with normal myocardium. Myocardial wall thinning and increased intracavitary flow signal were found in six dogs with comparable pre- and postocclusion images in late systole.     

23Na MRI combined with contrast-enhanced 1H MRI provides in vivo characterization of infarct healing.

Although (23)Na MRI has been shown to delineate acute myocardial infarction (MI), the time course of in vivo (23)Na MRI during infarct healing remains unknown. In this study (23)Na MRI was combined with contrast-enhanced (CE) (1)H MRI to noninvasively characterize infarct healing in vivo. Serial in vivo 3D (23)Na MRI and (1)H MRI were performed for up to 9 weeks postinfarction in 10 dogs. Radioactive microspheres were used to measure myocardial perfusion, and Hematoxylin-Eosin (H&E) and Masson's trichrome (MT) staining were used to assess interstitial cell infiltrate and collagen content. In vivo (23)Na MRI accurately delineated infarct size up to day 5 postinfarction in comparison with (1)H MRI (8.9% +/- 8.1% vs. 8.6% +/- 7.9% on day 1 postinfarction, P = NS; and 6.3% +/- 6.2% vs. 6.2% +/- 6.2% on days 4/5 postinfarction, P = NS). The in vivo (23)Na MRI signal intensity, expressed as the signal intensity ratio of infarcted tissue vs. noninfarcted tissue (MI/R) peaked on day 1 of infarction (2.04 +/- 0.23) but decreased significantly to 1.27 at 9 weeks postinfarction (P < 0.05) due to granulation tissue infiltrate and collagen deposition. To confirm the MI/R decrease during scar formation ex vivo, we performed (23)Na MRI in 12 rats on day 3 post-MI (N = 5) and after 6 weeks (N = 7). H&E and Picrosirius Red staining confirmed granulation tissue infiltrate on day 3 and scar formation after 6 weeks. MI/R decreased significantly from 1.91 +/- 0.45 on day 3 post-MI to 1.3 +/- 0.09 after 6 weeks. Thus, in vivo (23)Na MRI accurately delineates infarct size up to day 5 postinfarction. In vivo (23)Na MRI signal intensity decreases during infarct healing as a result of the underlying infarct healing process.     

The effect of postinfarction intramyocardial hemorrhage on transverse relaxation time.

1H NMR imaging has been used to define zones of myocardial infarction (MI), which appear as areas of relatively increased signal intensity (SI). However, zones of decreased SI have been observed within or around the areas of infarction in NMR images acquired at high magnetic fields. To determine the cause of these areas of reduced SI, ex vivo spin-echo 1H NMR imaging at 1.5 T was performed in eight dogs following 72 h of coronary artery occlusion. In all dogs, a zone of increased SI (122 +/- 7% compared to control myocardium; P less than 0.01) was observed in the territory of the occluded coronary artery. In seven of the dogs, additional zones were also seen, within or around the central zone of increased SI, which displayed SI that was reduced in comparison with the local enhanced intensity, but was similar to the intensity of normal myocardium (97 +/- 7% compared to control; P = NS). Gross inspection and histological assessment of sliced myocardium disclosed hemorrhage in these regions characterized by locally decreased NMR SI. Image-derived calculation of T2 in the various infarct regions revealed a significant shortening of T2 in the hemorrhagic infarct zones characterized by decreased SI, in comparison with the nonhemorrhagic infarct zones characterized by increased SI (59 +/- 7 ms vs 73 +/- 10 ms, P less than 0.05). No difference was found, however, between the observed T2's of hemorrhagic infarct and of control tissue (57 +/- 4 ms). Using a biexponential analysis of T2 from the hemorrhagic infarct zones, the intrinsic T2 of water protons affected by hemorrhage was determined to be 43 +/- 9 ms, significantly reduced in comparison with the values obtained with the standard monoexponential fit. The reduction in T2 in the hemorrhagic zone is consistent with the paramagnetic effects of deoxyhemoglobin associated with intramyocardial hemorrhage. Thus the apparent T2, measured in hemorrhagic infarct tissue, represents the result of an averaging effect of infarct and hemorrhage on T2 relaxation times. These observations improve our understanding of the changes in NMR SI within the infarcted regions, and may provide a noninvasive method for the detection and quantitative assessment of intramyocardial hemorrhage.     

MRI of acute myocardial infarction with injection of Gd-DOTA (15 patients)

We studied 15 patients 4 to 8 days after myocardial infarction by using ECG gated MR before and after administration of 0.2 mmol/kg Gd-DOTA. The diagnosis in each patient was confirmed by electrocardiographic criteria, elevated levels of fractionated creatine kinase (CK) isoenzyme, thallium scintigraphy, ventriculography and coronarography. T1-weighted, spin-echo images, were obtained before and immediately after injection of Gd-DOTA and were repeated 15 min later. The site of infarction was visualised in 10 patients as an area of high signal intensity after the injection of Gd-DOTA. Contrast between normal and infarcted myocardium was greatest 15 min after injection. Three patients were excluded because of failure to acquire adequate MR studies. In 2 other patients, the infarct were not detected. Before injection of Gd-DOTA, only 2 infarcts were detected. These results suggest that Gd-DOTA can improve MR visualisation and detection of acute myocardial infarction.     

Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field.

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium.     

Myocardial infarct size quantification by MR imaging early after coronary artery occlusion in dogs

The feasibility of using magnetic resonance (MR) imaging to estimate myocardial infarct size was explored in an in vitro model using only the inherent differences in contrast between infarcted and noninfarcted myocardium. Eight dogs underwent coronary occlusion; their hearts were removed 6 hours later. Estimates of T2 for normal and infarcted myocardium were derived from MR images. Infarct size was quantified anatomically using triphenyltetrazolium-chloride (TTC) staining and compared with MR estimates. The T2 values derived from the images clearly discriminated between infarcted (126 +/- 22 msec) and normal myocardium (88 +/- 10 msec, P less than .05), providing images with good contrast between normal and infarcted myocardium. Comparable differences in T2 values were also noted from spectrometric determinations. Estimates of infarct size by MR imaging compared well with TTC estimates (r = 0.98) over a wide range of infarct sizes from 3% to 29% of the left ventricular mass. These results suggest the potential for in vivo quantification of infarct size based on the inherent contrast difference between infarcted and normal myocardium.     

Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats.

PURPOSE: To measure the difference in size of reperfused myocardial infarction with necrosis-specific (bis-gadolinium-mesoporphyrin [hereafter, mesoporphyrin]) and standard extracellular (gadopentetate dimeglumine) magnetic resonance (MR) contrast media. MATERIALS AND METHODS: Echo-planar (for T1 measurement) and spin-echo (for infarction size) MR imaging were conducted in 32 rats subjected to reperfused reversible (n = 16) and irreversible (n = 16) myocardial injuries. All animals received gadopentetate dimeglumine 1 hour after reperfusion and underwent imaging. Sixteen rats received mesoporphyrin at 2 hours, the other 16 rats received gadopentetate dimeglumine at 24 hours, and all animals underwent imaging at 24 hours. RESULTS: Mesoporphyrin produced prolonged (22 hours) reduction in T1 in irreversibly, but not in reversibly, injured myocardium. The size of the mesoporphyrin-enhanced region (37% +/- 4 [SEM] of left ventricular surface area) closely correlated with the true infarction size as measured by means of histomorphometry (36% +/- 3, r = 0.90). The size of the gadolinium-enhanced region overestimated (48% +/- 2 and 43% +/- 1 at 1 and 24 hours of reperfusion, respectively) the size of true infarction (36% +/- 3, P < .05, r = 0.02), but it was close to the size of the area at risk (r = 0.93). CONCLUSION: The sizes of hyperenhanced regions displayed by using mesoporphyrin and gadopentetate dimeglumine differed from each other. The difference in size of the hyperenhanced region demarcated by mesoporphyrin and gadopentetate dimeglumine may provide an estimation of potentially salvageable myocardium.     

Myocardial "low reflow" assessed by Dy-DTPA-BMA-enhanced first-pass MR imaging in a dog model.

The aim of this study was to determine whether the use of a magnetic resonance (MR) susceptibility contrast medium, dysprosium diethylenetriamine pentaacetic acid-bismethylamide (Dy DTPA-BMA; Sprodiamide), may characterize myocardial perfusion abnormalities in a dog model of 90 minutes of coronary occlusion followed by 24 hours of reperfusion (no-reflow phenomenon installed). First-pass MR imaging after an intravenous bolus administration of the contrast agent was performed at the end of reperfusion. Signal intensity analysis on MR imaging, planimetry of pathological data, and blood flow determination were obtained by reference methods for comparison. Dogs were separated into two groups according to the level of collateral blood flow level (group I, <22.5 % of the flow in the non-ischemic zone; group II, >22.5 % of the flow in the non-ischemic zone). Signal intensity-time curves in the ischemic and non-ischemic left ventricle walls were extracted. Mean collateral blood flow was lower during occlusion in group I (9.8 +/- 5.4%, n = 5) than in group II (38 +/- 12.5%, n = 7, P < 0.05). Mean infarct size (expressed as a percentage of the area at risk) was significantly larger in group I (low collateral blood flow; 25.3 +/- 14.6%) than in group II (high collateral blood flow; 5.8 +/- 1.1%, P < 0.05). After rapid injection, a transient decrease of signal intensity induced by Dy DTPA-BMA was observed in both remote and ischemic myocardium but more markedly in remote normally perfused myocardium. Hence, during the transit of a susceptibility-type contrast agent, ischemic myocardium after ischemia and reperfusion appeared as a relative high signal intensity area. First-pass MR imaging with susceptibility contrast agent demonstrated the no- or low-reflow phenomenon. However, the behavior of the myocardial signal intensity-time-related curves did not allow distinction between the two groups of dogs.     

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs positive predictive value (PPV) of strain determination of infarction = (66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.     

Detection of myocardial viability based on measurement of sodium content: A (23)Na-NMR study.

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content post-myocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in buffer-perfused rat hearts, infarct scar can be differentiated from intact myocardium by (23)Na-MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post-MI (N = 6-8 each), Na content was determined by (23)Na-NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083 vs. control). In Protocol 2, (23)Na-MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, (23)Na-MRI revealed a mean increase in signal intensity, to 142 +/- 6% of control values, in scar tissue. A threshold of 2 standard deviations of the image intensity allowed determination of infarct size, correlating with histologically determined infarct size (r = 0.91, P < 0.0001).     

Evaluation by Contrast-Enhanced MR Imaging of the Lateral Border Zone in Reperfused Myocardial Infarction in a Cat Model

Objective

To identify and evaluate the lateral border zone by comparing the size and distribution of the abnormal signal area demonstrated by MR imaging with the infarct area revealed by pathological examination in a reperfused myocardial infarction cat model.

Materials and Methods

In eight cats, the left anterior descending coronary artery was occluded for 90 minutes, and this was followed by 90 minutes of reperfusion. ECG-triggered breath-hold turbo spin-echo T2-weighted MR images were initially obtained along the short axis of the heart before the administration of contrast media. After the injection of Gadomer-17 and Gadophrin-2, contrast-enhanced T1-weighted MR images were obtained for three hours. The size of the abnormal signal area seen on each image was compared with that of the infarct area after TTC staining. To assess ultrastructural changes in the myocardium at the infarct area, lateral border zone and normal myocardium, electron microscopic examination was performed.

Results

The high signal area seen on T2-weighted images and the enhanced area seen on Gadomer-17-enhanced T1WI were larger than the enhanced area on Gadophrin-2-enhanced T1WI and the infarct area revealed by TTC staining; the difference was expressed as a percentage of the size of the total left ventricle mass (T2= 39.2%; Gadomer-17 =37.25% vs Gadophrin-2 = 29.6%; TTC staining = 28.2%; p < 0.05). The ultrastructural changes seen at the lateral border zone were compatible with reversible myocardial damage.

Conclusion

In a reperfused myocardial infarction cat model, the presence and size of the lateral border zone can be determined by means of Gadomer-17- and Gadophrin-2-enhanced MR imaging.     

Molecular imaging identifies regions with microthromboemboli during primary angioplasty in acute coronary thrombosis.

Microthromboemboli (MTE) may contribute to the no-reflow phenomenon in acute myocardial infarction (AMI) either spontaneously or after primary percutaneous transluminal coronary angioplasty (PTCA). We hypothesized that myocardial MTE in acute coronary syndromes can be identified on imaging by in vivo (99m)Tc labeling of the coronary thrombus with a compound that binds to the glycoprotein IIb/IIIa present on activated platelets (DMP-444). METHODS: Fifteen dogs underwent left anterior descending coronary artery (LAD) injury in to produce thrombus, whereas 5 control dogs had LAD ligation. Before recanalization, the risk area (RA) and myocardial blood flow (MBF) were measured, and in vivo thrombus labeling was performed using (99m)Tc-labeled DMP-444. Nine of the 15 LAD injury dogs had occlusive thrombus on angiography and underwent PTCA. MBF measurements were repeated 30 and 60 min after recanalization, and (99m)Tc autoradiography (hot spot imaging) was performed ex vivo to determine the extent and magnitude of MTE. RESULTS: The ratio of hot spot size to RA size was higher in the 9 LAD injury dogs with thrombus compared with the 6 dogs with no thrombus (90% +/- 22% vs. 42% +/- 16%; P = 0.005). In control dogs, this ratio was significantly lower (29% +/- 11%; P = 0.05). (99m)Tc activity within the RA was higher in 8 of the 15 coronary injury dogs with AMI compared with those without AMI (1.8 +/- 0.48 vs. 1.24 +/- 0.22; P = 0.02). CONCLUSION: MTE can be detected and quantified after primary PTCA. The infarct size is proportional to the magnitude and extent of MTE, indicating that MTE may contribute to the AMI. Thus, in vivo thrombus labeling during reperfusion may provide important information in patients with AMI that may lead to better adjuvant therapy during PTCA.     

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.     

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.     

Improved evaluation of myocardial perfusion and viability with the magnetic resonance blood pool contrast agent p792 in a nonreperfused porcine infarction model

OBJECTIVES: To investigate whether a magnetic resonance (MR) blood pool contrast agent enables both evaluation of myocardial perfusion and viability in nonreperfused infarction in pigs. MATERIALS AND METHODS: An optimized MR protocol using the blood pool contrast agent P792 (0.026 mmol/kg, twice the clinical dose, Guerbet, France) was investigated to evaluate nonreperfused myocardial infarction in an animal model. P792 was compared with the extracellular contrast agent Gd-DOTA (0.1 mmol/kg). The MRI findings were compared with histomorphometry performed with microspheres to evaluate perfusion and triphenyltetrazolium chloride (TTC) to evaluate viability. Contrast-enhanced MR imaging of the heart was performed on a 1.5-Tesla scanner 2 days after instrumentation in 6 minipigs. A saturation recovery steady-state free precession sequence was used for perfusion imaging and an inversion recovery fast low-angle shot sequence for evaluation of myocardial viability. RESULTS: P792 tended to depict areas of reduced perfusion more accurately than Gd-DOTA (17.2% +/- 11.1% versus 13.7% +/- 8.0%) in comparison to the gold standard of histomorphometry with microspheres (18.2% +/- 9.8%). Moreover, P792, but not Gd-DOTA, depicted ischemic areas for 30 minutes after intravenous injection. The change in myocardial signal intensity during first pass was not significantly different after P792 compared with Gd-DOTA (140.3% +/- 64.4% versus 123.3% +/- 22.5%, P = 0.56). P792 was highly accurate in depicting infarcted areas (11.1% +/- 7.1%) compared with Gd-DOTA (12.1% +/- 8.2%, r = 0.98, P < 0.001) and histomorphometry with TTC (12.2% +/- 8.0%, r = 0.99, P < 0.001). CONCLUSIONS: Unlike Gd-DOTA, the blood pool contrast agent P792 allows evaluation of myocardial perfusion for a period of 30 minutes and shows good agreement with histomorphometry. P792 must be examined in further studies to evaluate its potential in evaluating early myocardial lesions and reperfusion. In addition, P792 also allows for evaluation of myocardial viability.     

Stunned,infarcted, and normal myocardium in dogs: simultaneous differentiation by using gadolinium-enhanced cine MR imaging with magnetization transfer contrast

PURPOSE: To simultaneously differentiate stunned, infarcted, and normal myocardial regions by using gadolinium-enhanced cine magnetic resonance (MR) imaging with magnetization transfer contrast. MATERIALS AND METHODS: Twelve dogs were imaged on days 1 and 8 after transient 90-minute coronary artery occlusion. A magnetization transfer contrast with echo-train readout (MTET) MR sequence was performed before and 30 minutes after gadolinium contrast enhancement. Ex vivo analysis consisted of MR imaging, microsphere blood flow analysis, and triphenyltetrazolium chloride (TTC) staining. A paired two-tailed t test was used to compare wall thickening from day 1 to day 8. Linear regression and Bland-Altman analyses were used to compare infarct size depicted with MTET imaging with that seen on TTC-stained tissue. RESULTS: Severe wall motion abnormalities were detected in all dogs. At TTC analysis, seven dogs had evidence of myocardial infarction and five had evidence of stunned myocardium. The mean percentages of left ventricular wall thickening in infarcted, stunned, and remote myocardial regions were 2% +/- 4 (SD), 4% +/- 8, and 33% +/- 5, respectively. Wall thickening did not improve in the infarcted zones, but it improved to nearly normal levels in the stunned region 1 week after induced occlusion (mean, 40% +/- 8; P <.02). MTET images clearly depicted infarcted myocardium as brighter than both the normal and stunned myocardial regions but darker than the blood pool. In vivo MTET infarct volume correlated with ex vivo TTC analysis data (y = 1.01x + 0.00, R = 0.98, standard error of the estimate = 0.019). CONCLUSION: One day after myocardial ischemia, MTET during one MR imaging examination enabled simultaneous differentiation of infarcted, stunned, and normal myocardial regions on the basis of gadolinium enhancement and regional function.