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ABSTRACT: It is not known whether deeper or longer hypothermia (HT) can achieve better neuroprotection against hypoxic ischemic encephalopathy (HIE) in neonates. To compare the neuroprotective effects of different durations and temperatures of postischemic HT in neonatal rats with severe HIE, 7-d-old rats were subjected to the Rice-Vannucci model for 150 min hypoxia. Only the rats with identified brain lesions in diffusion-weighted MRI were assigned to normothermia (NT, 36° C/48 h) or four HT (HT-30° C/48 h; HT-30° C/24 h; HT-33° C/48 h; and HT-33° C/24 h) groups. H-magnetic resonance spectroscopy (H-MRS) and T2-weighted MRI were obtained serially, and functional studies were performed. HT groups showed significantly greater residual hemispheric volume and better rotarod and cylinder tests than did the NT group at 5 wk postischemia. HT groups also showed lower lactate-plus-lipid level in H-MRS than did the NT group at 7 d postischemia. All of these outcome variables, however, did not differ among the 4 HT subgroups, despite a trend toward greater residual brain volume in the 48-h HT versus 24-h HT subgroups. In conclusion, neither reducing the target temperature from 33 to 30° C nor prolonging the duration from 24 to 48 h produced further improvements in neurologic outcomes in neonatal rat with HIE.
Pediatric Research 10/2010; 68(4):303-8. · 2.70 Impact Factor
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ABSTRACT: The objective of this study was to determine whether long-term exercise training will improve age-related cardiac metabolic derangement using proton magnetic resonance (MR) spectroscopy.
Young and old male Fischer 344 rats were assigned to sedentary controls groups {young control (YC) group-3 months of age: YC, n=10; old control (OC) group-22 months of age: OC, n=10}, and an exercise training group (OT, n=5). After 12-week of treadmill exercise training, MR spectroscopy at 4.7 T was performed to assess myocardial energy metabolism: measurements of myocardial creatine-to-water ratio (Scr/Sw) were performed using the XWIN-NMR software.
Exercise capacity was 14.7 minutes greater in OT than that in OC (20.1±1.9 minutes in OT, 5.4±2.3 minutes in OC; p<0.001). The 12-week exercise training rendered the old rats a maximum exercise capacity matching that of untrained YC rats (17.9±1.5 minutes in YC, 20.1±1.9 minutes in OT; p>0.05). The creatine-to-water ratios in the interventricular septa of YC did not differ significantly from that of OT (0.00131±0.00025 vs. 0.00127±0.00031; p=0.37). However, OC showed significant reduction in creatine-to-water ratio compared to OT (0.00096±0.00025 vs. 0.00127±0.00031; p<0.001). Mean total creatine concentrations in the myocardium were similar between YC and OT (13.3±3.6 vs. 11.5±4.1 mmol/kg wet weight; p=0.29). In contrast, the mean total creatine concentration of OC was significantly reduced compared to OT (6.8±3.2 vs. 11.5±4.1 mmol/kg wet weight; p=0.03).
Our findings suggest that long-term exercise training in old rats induced prevention of age-related deterioration in myocardial metabolism.
Korean Circulation Journal 09/2010; 40(9):454-8.
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ABSTRACT: To evaluate the feasibility of MR imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to aid diagnosis of graft rejection in kidney transplantation.
This study was approved by the institution's committee on animal research. Eighteen male Lewis rats received a kidney transplant; 12 had an F344 rat donor and six had a Lewis rat donor. Peritoneal macrophages were harvested from thioglycollate-treated Lewis rats, cultured, and labeled with SPIO. After resuspension of macrophages in a concentration of 1 x 10(7) cells per milliliter of Hanks balanced salt solution, 5 x 10(6) of SPIO-labeled macrophages was administered through the tail vein 2 or 5 days after transplantation in each group. The transplanted kidneys were imaged on a 4.7-T MR imager 24 hours after macrophage administration. The Wilcoxon signed rank test was performed for evaluating the differences between the relative signal intensity (SI) before and after SPIO-labeled macrophage administration.
A low-SI zone was predominantly noted in the medulla of the transplanted kidneys, and the relative SI decreased significantly from 1.40 to 0.53 (P < .001) in the allogeneic transplants following SPIO-labeled macrophage administration 5 days after the allogeneic transplantation. In the syngeneic group, the lower-SI zone was not noted in the grafts. At histopathologic examination, the lower-SI zone corresponded to the distribution of the SPIO-labeled macrophages.
This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored in the allograft rejection model on in vivo MR images.
Radiology 09/2010; 256(3):847-54. · 5.73 Impact Factor
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ABSTRACT: Increased levels of lactate are observed by (1)H magnetic resonance spectroscopy ((1)H-MRS) in rat brains after stroke. However, it is not known whether the changes in lactate levels are predictive of the degree of neuronal damage.
To investigate the correlation between changes in lactate and lipid levels measured by (1)H-MRS and neuronal cell damage in the rat brain.
A middle cerebral artery occlusion (MCAO) model was used to evaluate focal ischemia in rats (n=36). After MCAO for 90 min T2-weighted images (T2WIs), diffusion-weighted images (DWIs), and (1)H-MRS data were obtained from brains immediately, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 3 days, and 7 days after reperfusion. Infarct volumes were measured in T2WIs obtained 4 weeks after reperfusion. The degree of neuronal damage was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining in three rats from each group at the same time as brain images were collected.
Creatine (Cr)-normalized lactate + lipid levels ([Lac+Lip]/Cr) were negatively correlated with Cr-normalized N-acetyl-L-aspartate levels (NAA/Cr) and positively correlated with TUNEL-positive cell numbers up to 24 hours after reperfusion. (Lac+Lip)/Cr at 6 hours and 9 hours was significantly correlated with NAA/Cr at 7 days, but there was no significant correlation between (Lac+Lip)/Cr during the first 24 hours and infarct volume at 4 weeks.
Up to 24 hours after reperfusion, (Lac+Lip)/Cr was strongly negatively correlated with NAA/Cr, and was a good predictor of neuronal damage at 7 days; however, it was not predictive of final infarct volume at 4 weeks.
Acta Radiologica 02/2010; 51(3):344-50. · 1.37 Impact Factor
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ABSTRACT: To assess the signal pattern in T2-weighted images (T2WI) and determine its relation to persistent microvascular obstruction (PMO) and intramyocardial hemorrhage in a porcine model with reperfused acute myocardial infarction. Left anterior descending artery was occluded (90 or 180 min) and reperfused (90 min). T2WI and delayed-enhanced magnetic resonance images (DE-MRI) were acquired. The T2WI signal pattern, T2WI contrast ratio, PMO, and intramyocardial hemorrhage were evaluated, and their interrelationships were analyzed. The infarct area on T2WI was recorded as a homogeneous high-intensity signal or as low- or iso-intensity signals. The contrast ratio of the T2WI in the cases with PMO was significantly lower than that in those without PMO (1.38 +/- 0.25 vs. 1.89 +/- 0.31, P < 0.05), and it showed significant inverse correlation with the extent of PMO observed in DE-MRI images (r =-0.8, P < 0.05). The extent of PMO correlated strongly with that of intramyocardial hemorrhage (r = 0.97, P < 0.05). The abnormal signal area in the T2WI was larger than the infarct area in the DE-MRI images (47.0 +/- 9.9% vs. 37.8 +/- 9.9%, P < 0.05) and the infarct area observed after TTC staining (47.0 +/- 9.9% vs. 37.4 +/- 8.4%, P < 0.05). We observed variable T2WI signal patterns for the infarcted myocardium. Lower T2WI contrast ratios significantly correlated with the extent of PMO in DE-MRI and intramyocardial hemorrhage in the gross specimen.
The international journal of cardiovascular imaging 01/2009; 25 Suppl 1:111-9. · 2.15 Impact Factor
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ABSTRACT: We describe the pace of recruitment of iron-oxide-labeled macrophages to the site of different stages of infection by in vivo magnetic resonance (MR) imaging. Peritoneal macrophages were labeled with superparamagnetic iron oxide ex vivo and administered through the tail vein 6 (acute) or 48 (subacute) h after bacterial inoculation. The legs of the mice were imaged sequentially on a 4.7-T MR unit before and 3, 6, 12, 18, 24, 48 and 72 h after macrophage administration. The band-shaped lower signal intensity zone around the abscess on T2*-weighted GRE images became more obvious due to recruited macrophages up until 24 h after injection in the subacute and 48 h after injection in the acute group, indicating that the relative SI of the abscess wall decreased more rapidly and the pace of recruitment of macrophages was faster in the subacute than in the acute group. Chemokine antibody arrays of mouse sera detected increased concentration of granulocyte-colony-stimulating factor and tissue inhibitor of metalloproteinase-1 beginning at 12 h and increased interleukin-13 at 18 h. Monocyte chemoattractant protein-1 and macrophage-colony-stimulating factor began to increase at 96 h after infection. This difference in pace of recruitment may result from the release of chemokines.
European Radiology 06/2008; 18(10):2033-9. · 3.22 Impact Factor
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ABSTRACT: To evaluate the feasibility of magnetic resonance (MR) imaging in depicting in vivo recruitment of iron oxide-labeled macrophages in experimentally induced soft-tissue infection.
The study was performed according to the guidelines of the U.S. National Institutes of Health and recommendations of the committee on animal research. The protocol was approved by the local institutional review committee on animal care. Experimental soft-tissue infection in 12 mice was induced by inoculation with a 5 x 10(7) colony-forming units of Staphylococcus aureus into the left calf. Peritoneal macrophages were harvested from thioglycollate-treated mice, cultured, and labeled with iron oxide in vitro. The iron oxide-labeled macrophage (macrophage group, n = 6) or iron oxide solution (control group, n = 6) was administered through the tail vein. The left calf of the mice was imaged on days 2 and 3 with a 4.7-T MR unit. Changes in relative signal intensity (SI) and pattern of contrast material enhancement (macrophage distribution) were analyzed and compared with histopathologic findings. Statistical analysis was performed with the Wilcoxon matched-pairs signed rank test.
On MR images obtained 24 hours after administration of macrophage labeled with iron oxide, a band-shaped lower SI zone was noted in the abscess wall, which corresponded to the distribution of the iron oxide-labeled macrophages at histopathologic examination. The relative SI of the abscess wall significantly decreased after injection of iron oxide-labeled macrophages (median, 0.42) compared with that before injection (median, 1.23) (P = .031). In the control group, the SI change after administration of iron oxide solution was not significant (P = .688).
Homing of intravenously administered iron oxide-labeled macrophages can be monitored with MR imaging and may provide a tool to investigate interactions between macrophages and the invading pathogens.
Radiology 11/2006; 241(1):142-8. · 5.73 Impact Factor
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ABSTRACT: We report two infants with neonatal hypoglycaemic encephalopathy who were evaluated with diffusion-weighted imaging (DWI) and proton MR spectroscopy (MRS) as well as conventional MR. As in conventional MR, DWI and proton MRS revealed a predominance of abnormalities in the parieto-occipital lobes and underlying white matter including the splenium of the corpus callosum. In the acute phase of the disease, lesions on DWI showed restricted water diffusion and on DWI the characteristic lesions seemed to be more readily discernible than on conventional MRI. In the chronic phase, DWI demonstrated increased water diffusion in the affected areas showing atrophy on conventional MRI. Proton MRS revealed an increased lactate-lipid peak and a decreased NAA peak in the involved areas. DWI and proton MRS findings appear helpful in evaluating the extent and the presence of neuronal damage early in the course of neonatal hypoglycaemic encephalopathy.
Pediatric Radiology 03/2006; 36(2):144-8. · 1.67 Impact Factor
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ABSTRACT: To investigate the capacity of manganese dipyridoxyl diphosphate (MnDPDP)-enhanced magnetic resonance imaging (MRI) to discriminate the injured myocardium from the normal myocardium in a cat model.
Fourteen cats were prepared for acute myocardial infarction with 90-minute occlusion followed by 120-minute reperfusion. Inversion recovery gradient-recalled echo (IR-GRE) MR images were obtained at 60-minute intervals for 4 hours after the injection of MnDPDP, and ex vivo after the cats were killed. We evaluated the differences between the unenhanced area on the in vivo and ex vivo MR images and the unstained area on triphenyl tetrazolium chloride (TTC) staining.
The unenhanced area on the in vivo MR images was well correlated with that on the ex vivo MR images. The unenhanced area on the ex vivo MR images was significantly larger than the unstained area on TTC staining.
This study suggests that the MnDPDP-unenhanced area on the MR images includes not only the infarcted myocardium but also the stunned myocardium.
Investigative Radiology 02/2005; 40(1):49-55. · 4.59 Impact Factor
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ABSTRACT: To compare manganese dipyridoxyl diphosphate (MnDPDP)-enhanced magnetic resonance imaging (MRI) with cine MRI for distinguishing the dysfunctional myocardium from the normal myocardium.
Seventeen cats were prepared for acute myocardial infarction with 90 minutes of occlusion followed by 120 minutes of reperfusion. In vivo inversion-recovery gradient-recalled echo MRI and cine MRI were performed. Two radiologists independently analyzed the MR images and recorded the size of the unenhanced area on the MnDPDP-enhanced MR images as well as that of the dysfunctional area on the cine MR images. Agreement between these abnormal areas was evaluated using Bland-Altman analysis. Interobserver agreement was assessed using Bland-Altman analysis.
The sizes of the unenhanced area on the MnDPDP-enhanced MR images and the dysfunctional area on the cine MR images showed good agreement on Bland-Altman analysis (the limits of agreement: observer 1= 1.8% +/- 11.6, observer 2 = 0.1% +/- 9.9). The abnormal segments on both types of MR imaging showed a good interobserver agreement (the limits of agreement: MnDPDP-enhanced MRI = 0.3% +/- 7.6, cine MRI = -1.4% +/- 10.9).
The size of the dysfunctional area on the cine MR images was well correlated with that of the unenhanced area on the MnDPDP-enhanced MR images.
Investigative Radiology 02/2005; 40(1):56-61. · 4.59 Impact Factor
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ABSTRACT: To assess the usefulness of magnetic resonance (MR) imaging for detecting bowel ischemia with strangulation compared with histopathologic findings in an experimental cat model.
Fourteen cats were assigned to the normal control group (n = 3), acute ischemic group (induced by ligation of superior mesenteric vessels for 3 hours, n = 7), and subacute ischemic group (induced by ligation of superior mesenteric vessels for 10 hours, n = 4). Using a 4.7-T MR scanner, contrast-enhanced T1-weighted images were obtained at 0, 10, 20, 30, and 60 minutes after bolus injection of contrast media. T1- and T2-weighted images were obtained from the extracted bowel wall and compared with histopathologic findings.
On contrast-enhanced MR images, the target-like bowel wall layers were clearly demonstrated and the submucosal layer showed the most prominent enhancement. At 10 minutes after administration of contrast media, the subacute ischemic group showed significantly lower enhancement of the submucosal layer than the normal or acute ischemic group (P <0.05). On T1-weighted images, there were not significant differences between the normal and ischemic bowel groups (P >0.05). On T2-weighted images, the signal intensity of all layers of acute ischemic bowel wall was significantly higher than that of the normal control or subacute ischemic group (P <0.05).
Delayed contrast-enhanced MR images and T2-weighted images were helpful for detecting subacute and acute bowel ischemia with strangulation, respectively.
Journal of Computer Assisted Tomography 02/2004; 28(2):187-92. · 1.22 Impact Factor
