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Christoph Klein

Publications and source records attributed to Christoph Klein.

At least 37 records · Page 2Linked to original sources

The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function.

The mechanisms controlling the differentiation of dendritic cells (DCs) remain largely unknown. Using a transcriptional profiling approach, we identified Gfi1 as a novel critical transcription factor in DC differentiation. Gfi1-/- mice showed a global reduction of myeloid and lymphoid DCs in all lymphoid organs whereas epidermal Langerhans cells were enhanced in number. In vivo, Gfi1-/- DCs showed striking phenotypic and functional alterations such as defective maturation and increased cytokine production. In vitro, Gfi1-/- hematopoietic progenitor cells were unable to develop into DCs. Instead, they differentiated into macrophages, suggesting that Gfi1 is a critical modulator of DC versus macrophage development. Analysis of hematopoietic chimeras and retrovirus-reconstituted hematopoietic progenitor cells established a cell autonomous and nonredundant role for Gfi1 in DC development. The developmental defect of Gfi1-/- progenitor cells was associated with decreased STAT3 activation. In conclusion, we have identified Gfi1 as a critical transcription factor that controls DC versus macrophage development and dissociates DC maturation and activation.

Animals↗

High-dose dobutamine-atropine stress cardiovascular MR imaging after coronary revascularization in patients with wall motion abnormalities at rest.

PURPOSE: To determine the value of high-dose dobutamine-atropine stress cardiovascular magnetic resonance (MR) imaging for diagnosis of ischemia in patients with coronary artery disease (CAD) who had undergone revascularization and have wall motion abnormalities at rest, with quantitative invasive coronary angiography serving as reference standard. MATERIALS AND METHODS: One hundred sixty consecutive patients (mean age, 59 years +/- 8 [standard deviation]) who had undergone revascularization for CAD and have wall motion abnormalities at rest underwent stress cardiovascular MR imaging prior to clinically indicated invasive coronary angiography. Turbo gradient-echo MR images were acquired at rest and during a standardized high-dose dobutamine-atropine protocol with three short-axis and two long-axis views. Regional wall motion was assessed by a blinded observer by using a 16-segment model and a four-point scoring system. New or worsening wall motion abnormality in at least one segment was considered positive for myocardial ischemia. RESULTS: Significant CAD (stenoses of at least 50% diameter at angiography) was found in 119 patients (74%). Target heart rate was not reached in nine patients (6%). Overall sensitivity and specificity for detection of significant CAD were 89% and 84%, respectively. Diagnostic accuracy was 88%, and positive and negative predictive values were 94% and 73%, respectively. Overall sensitivity for detection of significant CAD in patients with single-, double-, and triple-vessel disease was 87%, 88%, and 100%, respectively. CONCLUSION: High-dose stress cardiovascular MR imaging can be used for follow-up of patients after coronary revascularization procedures. Diagnostic accuracy is similar to stress cardiovascular MR imaging data for patients suspected of having CAD and compares favorably with that of other established noninvasive techniques.

Adult↗

Magnetic resonance low-dose dobutamine test is superior to SCAR quantification for the prediction of functional recovery.

BACKGROUND: Low-dose dobutamine challenge (DSMR) by MRI was compared with delayed enhancement imaging with Gd-DTPA (SCAR) as a predictor of improvement of wall motion after revascularization (RECOVERY). METHODS AND RESULTS: In 29 patients with coronary artery disease (68+/-7 years of age, 2 women, 32+/-8% ejection fraction), wall motion was evaluated semiquantitatively by MRI before and 3 months after revascularization. SCAR and DSMR were performed before revascularization. The transmural extent of scar was assessed semiquantitatively. Binary prediction of RECOVERY was performed by logistic regression in 288 segments with wall motion abnormalities at rest. Receiver operating characteristic-area under curve (AUC) statistics were used to compare different models. Low-dose DSMR (AUC 0.838) was superior to SCAR (AUC 0.728) in predicting RECOVERY. SCAR did not improve accuracy of prediction by DSMR. Subgroup analysis showed superiority of DSMR for 1% to 74% transmural extent of infarction. CONCLUSIONS: Low-dose DSMR is superior to SCAR in predicting RECOVERY. This advantage is largest in segments with a delayed enhancement of 1% to 74%.

Aged↗

Synthesis, structure and comparison of the DNA cleavage ability of metal complexes M(II)L with the N-(2-ethoxyethanol)-bis(2-picolyl)amine ligand L (M = Co, Ni, Cu and Zn).

Complexes of a N,N-bis(2-picolyl)amine (bpa) derivative with a pendant ethoxyethanol side chain (bpa(CH2)2O(CH2)2OH) (1) with late divalent transition metal ions Co(II), Ni(II), Cu(II) and Zn(II) have been studied. All complexes, [[bpa(CH2)2O(CH2)2OH]Co(NO3)](NO3) (1Co), [[bpa(CH2)2O(CH2)2OH]Ni(NO3)](NO3) (1Ni), [[bpa(CH2)2O(CH2)2OH]Cu(H2O)(NO3)](NO3) (1Cu) and [[bpa(CH2)2O(CH2)2OH]Zn(NO3)](NO3) (1Zn), were comprehensively characterized and their X-ray single crystal structures have been determined. The complexes show hexacoordinated geometries, in which 1 acts as a tetradentate (1Cu) or pentadentate (1Co, 1Ni and 1Zn) ligand. DNA cleavage experiments have been performed on supercoiled double stranded DNA plasmids in order to compare the cleavage efficiency of all four metals in the same ligand environment of 1. In this assay, 1Co and 1Cu showed the highest cleavage efficiency, whereas 1Ni and 1Zn were virtually inactive. Quantification of the gel electrophoresis bands showed that more than 80% of the plasmid has suffered at least one single strand cut in the case of 1Cu, and about 50% of the plasmid was nicked by 1Co. The differential cleavage activity is discussed in relation to the structural findings and a mechanism is proposed for 1Cu.

Amines↗

The influence of myocardial blood flow and volume of distribution on late Gd-DTPA kinetics in ischemic heart failure.

PURPOSE: To determine the mechanism of enhancement of contrast-enhanced MRI (ceMRI) in chronic ischemic myocardium. While ceMRI can identify scar tissue in chronic ischemic myocardium, the mechanism of enhancement is not completely understood. MATERIALS AND METHODS: A total of 11 patients with ischemic heart failure (ejection fraction [EF] 28 +/- 9%) were imaged with ceMRI and positron emission tomography (PET) to measure myocardial blood flow (MBF). Longitudinal relaxation rate (T1) of blood, normal tissue, and scar tissue defined by ceMRI was determined before and two to 50 minutes after contrast (Look Locker technique), and the partition coefficient (lambda) and volume of distribution (VD) were calculated. RESULTS: In scar and viable tissue, T1 was significantly different over the whole period after contrast, but not before contrast. However, T1 of scar and blood were similar five to 15 minutes post contrast, making the detection of subendocardial defects difficult. lambda reached an initial steady state in viable tissue, but was delayed (20 minutes) in scar tissue. VD in scar was double that of viable tissue (0.54 +/- 0.01 vs. 0.29 +/- 0.02, respectively) indicating an increased interstitial space. Contrast wash-in kinetics correlated moderately with MBF (r = -0.36), but well with the combination of MBF and VD (r = 0.59). CONCLUSION: Late myocardial contrast kinetics depend on both MBF and VD; however the increased VD seems to be the main mechanism for the late enhancement effect.

Blood Volume↗

Safety and feasibility of high-dose dobutamine-atropine stress cardiovascular magnetic resonance for diagnosis of myocardial ischaemia: experience in 1000 consecutive cases.

AIMS: To determine the safety of high-dose dobutamine-atropine stress cardiovascular magnetic resonance (stress-CMR), which recently emerged as a highly accurate modality for diagnosis of inducible myocardial ischaemia. METHOD AND RESULTS: From 1997 to 2002, 1000 consecutive stress-CMR examinations were performed. Images were acquired at rest and during a high-dose dobutamine-atropine protocol in 3 short-axis, a 4- and a 2-chamber view. Stress testing was discontinued when > or =85% of age-predicted heart rate was reached, on patient request, maximum pharmacologic infusion, or when new or worsening wall motion abnormalities, severe angina, dyspnoea, increase or decrease in blood pressure, or severe arrhythmias occurred. Stress-CMR was successfully performed in all but four patients (0.4%; insufficient ECG-triggering). Target heart rate was not reached in 95 cases (9.5%), due to maximum pharmacologic infusion in submaximal negative examinations in 21 cases (2.1%), and limiting side effects in 74 (7.4%). Side effects included one case (0.1%) of sustained and four cases (0.4%) of non-sustained ventricular tachycardia, 16 cases (1.6%) of atrial fibrillation, and two cases (0.2%) of transient second degree AV block. CONCLUSION: The safety profile of stress-CMR is similar to other methodologies using dobutamine infusions. Patients must be closely monitored, and resuscitation equipment and trained personnel must be available.

Adult↗

Gene therapy for inherited disorders of haematopoietic cells.

Over the last decade, the majority of inborn errors of haematopoiesis has been elucidated on a molecular level. For some of these diseases, gene transfer into transplantable cells offers new therapeutic perspectives. Improved retroviral or lentiviral techniques allow stable gene transfer in >10% of repopulating cells cultured in vitro. However, severe impediments are still encountered with respect to achieving sufficient and long-lasting transgene expression levels and appropriate numbers of transgenic cells in vivo. Improving the techniques for manipulation of stem cells in vitro, and the development of regimens promoting engraftment and selection of gene-modified cells are important areas of current research. Further activities address the level and persistence of transgene expression within individual cell clones, and the functional characteristics of progeny cells in vivo. Promises with respect to the potential impact of gene therapy for patients suffering from inherited disorders are often triggered by 'proof of concept' in preclinical disease models. However, recent observations of side effects related to random vector insertion or transgene expression indicate that even more careful quantitative and qualitative investigations of efficiency and toxicity may be needed for individual transgenes before approaching clinical trials.

Animals↗

Myocardial perfusion imaging using OMNISCAN: a dose finding study for visual assessment of stress-induced regional perfusion abnormalities.

BACKGROUND: Different doses of contrast agent are applied for magnetic resonance perfusion studies and mainly semiquantitative approaches have been reported for analysis. We aimed to determine the optimal dose for a visual detection of perfusion defects. METHODS: 49 patients (59+/-8 years; 33 male) scheduled for invasive angiography were examined at stress (0.14 mg adenosine/kg body weight/minute) and rest using a TFE-EPI hybrid sequence (Philips ACS NT; 1.5 T). Patients were assigned to three different dose groups of gadodiamide (0.05, 0.1, and 0.15 mmol/kg body weight) injected as a bolus via a peripheral vein. Visual assessment was used to detect a regional reduction of peak signal intensity or speed of contrast agent inflow at stress in comparison to rest. RESULTS: Prevalence for coronary artery disease was 67%. The highest diagnostic accuracy was reached for a dose of 0.1 mmol gadodiamide/kg body weight (86% p=nonsignificant vs. 0.15 and 0.05 mmol gadodiamide/kg). At this dose, no major artifacts related to the contrast agent were found. CONCLUSIONS: Visual assessment of myocardial perfusion using a high-flow rate contrast agent bolus injection and a TFE-EPI sequence can be best achieved with a dose of gadodiamide 0.1 mmol/kg bodyweight.

Aged↗

Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration.

We have investigated the contribution of intrasplenic bone marrow transplants or in vivo mobilized hematopoietic stem cells to the formation of hepatocytes in normal and injured liver. Direct intrasplenic injections of bone marrow mononuclear cells (5 x 10(5) cells), Scal+/lin- hematopoietic stem cells (5 x 10(3)) cells, and highly purified "side population" hematopoietic stem cells (5 x 10(3)) derived from enhanced green fluorescent protein (EGFP)-transgenic mice [C57Bl/6-TgN(ActbEGFP)1Osb] were performed in normal C57Bl/6 mice (n = 6) and in C57Bl/6 mice following two thirds hepatectomy (n = 8). To test the effect of mobilized stem cells on transdifferentiation, C57Bl/6 mice (n = 12) were lethally irradiated and reconstituted with EGFP-positive bone marrow mononuclear cells in a second series of experiments. Eight to 12 weeks after bone marrow transplantation a subset of mice (n = 3 in each group) received either rhG-CSF for hematopoietic stem cell mobilization, rhG-CSF combined with an intraperitoneal application of carbon tetrachloride (CCl4) as hepatocyte regeneration stimulus, or CCl4 alone. All mice were completely perfused with PBS to remove circulating nonorgan cells for analyses 4 weeks later. Liver as well as heart, intestine, spleen, and kidney tissue was analyzed for the presence of EGFP-transgenic cells. In 100 sections (2.3 x 10(7) cells) of any recipient mouse no EGFP-positive hepatocytes were detected either by analysis of native EGFP fluorescence or by immunofluorescence analysis with anti-EGFP and antidipeptidyl peptidase (DPP) IV antibodies. EGFP-transgenic cells resembling heart, kidney, or intestinal cells could also not be proven. The results demonstrate that there is little or no contribution of bone marrow-derived cells to the regeneration of normal and injured liver in the animal models used. Thus, potential therapeutic prospects of hematopoietic stem cell therapy for liver disease have to be critically reassessed.

Animals↗

Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease.

BACKGROUND: With MRI, an index of myocardial perfusion reserve (MPRI) can be determined. We assessed the value of this technique for the noninvasive detection of coronary artery disease (CAD) in patients with suspected CAD. METHODS AND RESULTS: Eighty-four patients referred for a primary diagnostic coronary angiography were examined with a 1.5 T MRI tomograph (Philips-ACS). For each heartbeat, 5 slices were acquired during the first pass of 0.025 mmol gadolinium-diethylenetriamine pentaacetic acid/kg body weight before and during adenosine vasodilation by using a turbo-gradient echo/echo-planar imaging-hybrid sequence. MPRI was determined from the alteration of the upslope of the myocardial signal intensity curves for 6 equiangular segments per slice. Receiver operating characteristics were performed for different criteria to differentiate ischemic and nonischemic segments. Prevalence of CAD was 51%. Best results were achieved when only the 3 inner slices were assessed and a threshold value of 1.1 was used for the second smallest value as a marker for significant CAD. This approach yielded a sensitivity of 88%, specificity of 90%, and accuracy of 89%. CONCLUSIONS: The determination of MPRI with MRI yields a high diagnostic accuracy in patients with suspected CAD.

Coronary Angiography↗

Noninvasive determination of coronary blood flow velocity with cardiovascular magnetic resonance in patients after stent deployment.

BACKGROUND: In patients with coronary artery stents, no direct noninvasive coronary artery imaging is possible with magnetic resonance (MR). A well-established method for the assessment of the functional significance of a coronary lesion is the measurement of coronary flow reserve by invasive intracoronary Doppler. The purpose of the study was to determine coronary flow velocity reserve (CFVR) with MR after stent deployment. METHODS AND RESULTS: Thirty-eight patients after successful PTCA and stent deployment were included. CFVR was measured perpendicular to the artery distal to the stent using phase-contrast velocity quantification at rest and during adenosine-stimulated hyperemia with a 1.5T MR tomograph (ACS NT, Philips). Measurements were repeated after 3 months and compared with invasive coronary angiography. In 18 patients, additional invasive Doppler flow measurements were obtained. CFVR could be determined in 29 of 38 (76%) of the patients. After 3 months, significant differences were obtained between coronary arteries with and without restenosis. Using a threshold of 1.2, a sensitivity of 83% with a specificity of 94% was achieved for > or =75% stenoses. CFVR with CMR was similar to Doppler results (r=0.87), with a mean relative difference of 7.5%. CONCLUSIONS: In patients with preserved coronary microcirculating vasoreactivity that are suitable for MR coronary angiography and flow assessments, CMR measures of coronary blood flow velocities reserve may be used to detect in-stent restenosis.

Blood Flow Velocity↗

Prognostic impact of matrix metalloproteinase-9 in operable non-small cell lung cancer.

We assessed the clinical impact of MMP-9 expression on long-term survival in patients with operable non-small cell lung cancer (NSCLC). Primary tumors of 143 consecutive patients with NSCLC resected completely and without overt distant metastases (pT1-4, pN0-2, M0, R0) were examined for MMP-9 expression using immunohistochemistry with a polyclonal, affinity-purified rabbit antibody that recognizes both latent and active MMP-9. Immunohistochemical staining of tumor cells was evaluated in comparison to normal bronchiolar epithelium that served as an internal positive control. MMP-9 expression was categorized into negative, 5% and <95% tumor cells stained; and homogeneous, >or=95% tumor cells stained at least as intensively as bronchiolar epithelium. The median follow-up period was 72 months (range = 12-144 months). Homogeneous expression of MMP-9 was observed in 26 of 143 patients (18.2%) and did not correlate with clinicopathological parameters. Relapse defined as diagnosis of distant metastasis or local recurrence was observed in 78 of the 130 (60%) patients eligible for clinical follow up analysis. Relapse led to cancer-related death in all of the 78 patients within the observation period. Kaplan-Meier analysis showed a significant association between homogeneous MMP-9 expression and shortened cancer-related survival (log-rank p = 0.016). Multivariate regression analysis including pT-status, pN-status, tumor histology and tumor grading showed an independence of this prognostic impact of homogeneous MMP-9 expression (p = 0.045). Thus, immunohistochemical evaluation of MMP-9 expression may provide a basis for the preselection of patients to be included in trials investigating specific protease inhibitor therapy after surgical resection of NSCLC.

Adult↗

Improvement of image quality of non-invasive coronary artery imaging with magnetic resonance by the use of the intravascular contrast agent Clariscan (NC100150 injection) in patients with coronary artery disease.

PURPOSE: To assess the feasibility of Clariscan, an intravascular contrast agent, for free breathing, navigator assisted, high resolution, three-dimensional-magnetic resonance coronary angiography (MRCA) in patients, as extracellular contrast agents are unfavorable for the improvement of image quality. MATERIALS AND METHODS: MRCA was performed in 10 patients with known coronary artery disease (CAD) with (1-5 mg Fe/kg body weight) and without contrast agent. RESULTS: Compared to unenhanced images, Clariscan did not improve signal-to-noise (SNR) or contrast-to-noise ratios (CNR) compared to fat or myocardium in the proximal parts of the coronary arteries. However, when analyzing the peripheral parts (>4 cm from origin), CNR(fat) and CNR(myo) improved up to a factor of 1.81 and 5.85, respectively, at a dose of 3 mg Fe/kg body weight, while SNR did not reach statistical significance. The visible length of the coronary arteries was improved from 49 +/- 18 mm to 73 +/- 33 mm. The proximal diameter was reduced from 3.6 +/- 0.8mm to 3.2 +/- 0.8 mm, representing more closely the diameter of 3.1 +/- 0.7 mm measured by quantitative coronary angiography. Of 11 significant stenoses (>50%), eight were identified in the enhanced compared to six in the unenhanced images. CONCLUSION: The use of Clariscan at a dose of 2-3 mg Fe/kg body weight improves image quality of three-dimensional-MRCA, especially in the peripheral segments, and, thus, the diagnostic accuracy for the detection of CAD.

Analysis of Variance↗

Cardiac oxidative metabolism, function, and metabolic performance in mild hyperthyroidism: a noninvasive study using positron emission tomography and magnetic resonance imaging.

Using noninvasive imaging, we have previously demonstrated that myocardial efficiency is impaired in hypothyroidism and improves after establishing euthyroid conditions. Little is known about the effects of abnormally elevated thyroid hormone exposure on cardiac metabolic performance. We studied 10 patients without evidence of heart disease in mild hyperthyroidism, and after therapy under euthyroid conditions. Cardiac oxidative metabolism was quantified by positron emission tomography with [(11)C]acetate. Left ventricular geometry was determined by cine magnetic resonance imaging. Myocardial efficiency, defined by the relation between work and oxygen consumption, was estimated using the work metabolic index [WMI = stroke volume * systolic blood pressure * heart rate/(oxidative metabolism * ventricular mass)]. In hyperthyroidism, heart rate and cardiac output were expectedly higher. Peripheral vascular resistance was reduced. Differences of blood pressure, stroke volume, and ventricular mass were not observed. Oxidative metabolism was significantly higher, but WMI was not different from the euthyroid state. In summary, while improvement of efficiency through thyroid hormone substitution was observed previously in hypothyroidism, our data in mild hyperthyroidism suggest an increase of oxygen consumption, paralleled by an increase of work. Thus, moderately elevated thyroid hormone levels neither result in further increase nor in reduction of cardiac metabolic performance.

Acetates↗

Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice.

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency that is caused by mutations in the recently identified WASP gene. WASP plays an important role in T-cell receptor-mediated signaling to the actin cytoskeleton. In these studies we assessed the feasibility of using retroviral gene transfer into WASP-deficient hematopoietic stem cells (HSCs) to rescue the T-cell signaling defect that is characteristic of WAS. Upon transplantation of WASP-deficient (WKO) HSCs that have been transduced with WASP-expressing retroviruses, mature B and T cells developed in normal numbers. Most importantly, the defect in antigen receptor-induced proliferation was significantly improved in T cells. Moreover, the susceptibility of colitis by WKO HSCs was prevented or ameliorated in recipient bone marrow chimeras by retrovirus-mediated expression of WASP. A partial reversal of the T-cell signaling defect could also be achieved following transplantation of WASP-deficient HSCs expressing the WASP-homologous protein N-WASP. Furthermore, we have documented a selective advantage of WT over WKO cells in lymphoid tissue using competitive repopulation experiments and Southern blot analysis. Our results provide proof of principle that the WAS-associated T-cell signaling defects can be improved upon transplantation of retrovirally transduced HSCs without overt toxicity and may encourage clinical gene therapy trials.

Animals↗

Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10-15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype-phenotype relationship among the various clinical forms of CHS.

Adolescent↗

Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography.

BACKGROUND: Recent studies indicate that MRI, after administration of gadolinium-diethylenetriamine pentaacetic acid, can identify nonviable areas in dysfunctional myocardium. We compared MRI hyperenhancement with PET as a gold standard for detection and quantification of myocardial scar tissue. METHODS AND RESULTS: Thirty-one patients with ischemic heart failure (ejection fraction, 28+/-9%) were imaged with PET and MRI. Scar was defined as regionally increased MRI signal intensity 20 minutes after injection of 0.2 mmol/kg gadolinium-diethylenetriamine pentaacetic acid and as concordantly reduced perfusion and glucose metabolism as defined by PET. Sensitivity and specificity of MRI in identifying patients and segments (n=1023) with matched flow/metabolism defects was 0.96 of 1.0 and 0.86 of 0.94, respectively. Eleven percent of segments defined as viable by PET showed some degree of MRI hyperenhancement. Defect severity score based on visual analysis was 44.3+/-9.1 for PET and 47.6+/-11.1 for MRI (r=0.91, P<0.0001). Quantitatively assessed relative MRI infarct mass correlated well with PET infarct size (r=0.81, P<0.0001). Furthermore, MRI hyperenhancement was a better predictor of scar tissue than end-diastolic and end-systolic wall thickness or thickening. CONCLUSIONS: In severe ischemic heart failure, MRI hyperenhancement as a marker of myocardial scar closely agrees with PET data. Although hyperenhancement correlated with areas of decreased flow and metabolism, it seems to identify scar tissue more frequently than PET, reflecting the higher spatial resolution. Additional functional studies after revascularization are required to define the significance of small islands of scar detected by MRI.

Cell Survival↗