Functional Magnetic Resonance Imaging Dynamic Study Of Ischemia-reperfusion Injury And Prognosis In Rats With Acute Cerebral Ischemia

PART Ⅰ Dynamic changes of Blood-Brain Barrier Permeability after Acute Cerebral Ischemia in RatsObjective The purpose of the present study was to apply Dynamic contrast-enhanced (DCE) Magnetic resonance imaging (MRI) to investigate the dynamic changes of Blood-brain barrier (BBB) permeability after acute cerebral ischemia in a rat model of Middle cerebral artery occlusion (MCAO). Material and Methods Sixty Sprague-Dawley (SD) rats were subjected to MCAO with the intraluminal suture occlusion model. According to the different ischemia duration, all rats were divided randomly into three groups of twenty rats each, including ischemia 3 hours group, ischemia 6 hours group and permanent ischemia group. According to the different reperfusion duration (2,6,12 and 24 hours), every group were further divided randomly into four subgroups, with five rats in each subgroup. All MRI experiments were performed using a 3.0 T Siemens scanner at different time points. The BBB permeability parameters, rKtrans, rKep and rVe, were calculated on a workstation. The changes of BBB permeability parameters were observed and compared to the pathological gold-standard (Evans blue) EB extravasation. Results BBB permeability following reperfusion were present biphasic changes in the two ischemia-reperfusion groups. BBB permeability increased at 2 and 6 hours after reperfusion, decrease at 12 hours and increased again at 24 hours after reperfusion. BBB permeability peaked at 6 hours after reperfusion in ischemia 3 hours group and ischemia 6 hours group both. At all reperfusion time points, BBB permeability of ischemia 6 hours group was larger than ischemia 3 hours group. However, BBB permeability of permanent ischemia group present uniphasic changes. BBB permeability increased only slightly with prolongation of ischemia duration in permanent ischemia group. The increase of BBB permeability in corpus striatum was larger than cortex in all groups. The MRI findings were consistent with the EB extravasation. Mean rKtrans, rKep, rVe values were statistically significant difference in and between groups (P<0.05). Ktrans values were significantly positively correlated with Ve values (r=0.93, P<0.01). Ktrans values were significantly negatively correlated with Kep values (r=-0.84, P<0.01) and Ve values were significantly negatively correlated with Kep values (r=-0.8, P<0.01). Conclusions The present results demonstrate that DCE-MRI is a useful method to evaluate the BBB permeability over time following ischemia and reperfusion. The BBB permeability was affected by two main factors: ischemia and reperfusion duration. With prolongation of the isehemia duration, injury of the BBB after ischemia need less time and more severe. BBB permeability of ischemia-reperfusion groups present biphasic changes.However, BBB permeability of permanent ischemia group present uniphasic changes.PART Ⅱ Prediction of Hemorrhagic Transformation in Acute Ischemic Stroke using Dynamic Contrast Enhanced Magnetic Resonance ImagingObjective The purpose of the present study was to estimate the incidence of hemorrhagic transformation caused by ischemia-reperfusion injury and apply DCE-MRI to evaluate the predictive power in terms of HT. Material and Methods Fifty male Sprague-Dawley rats were divided randomly into five groups of ten rats each:3h,4.5h,6h, 7.5h and 9h ischemia-reperfusion group. All rats were subjected to MCAO with the intraluminal suture occlusion model. An MRI scan was obtained immediately before and 6 hours after reperfusion. MRI protocols included Diffusion weighted imaging (DWI), DCE and Susceptibility weighted imaging (SWI). HT was evaluated with follow-up SWI and histopathological examination. All rats were divided into two groups according to the presence of HT (HT group and non-HT group). Mean rKtrans, rKep, rVe value of the two groups were investigated retrospectively. Binary logistic regression analysis and Receiver operating characteristic (ROC) curves were computed for predicting HT from DCE parameter. Results 8 rats (16%) showed HT, which of 0 in 3h group,0 in 4.5h group,1 rat in 6h group,3 rats in 7.5h group and 4 rats in 9h group respectively. Mean Ktrans and rKtrans value in corpus striatum and cortex were both higher in the HT group than in the non-HT group, which revealed statistically significant differences (P<0.01). Mean Ve and rVe values in corpus striatum and cortex were both higher in the HT group than in the non-HT group, which revealed statistically differences (P<0.05). Mean Kep and rKep values in corpus striatum and cortex revealed no statistically difference (P>0.05). Binary logistic regression analysis revealed that rKtrans of corpus striatum was independent factors associated with HT (OR=263.614). ROC analysis indicated rKtrans of corpus striatum threshold of 1.565, with a sensitivity of 91.4% and a specificity of 73.9%. Conclusions The results of this study indicate that rKtrans of corpus striatum is able to identify patients at higher risk of HT and may allow use of physiologic imaging associate with time from onset of symptoms (>6 hours) to guide treatment decision.PART Ⅲ Prediction Prognosis Ischemia-Reperfusion Injury using Dynamic Contrast Enhanced Magnetic Resonance Imaging in RatsObjective The purpose of the present study was to observe dynamic changes of imaging and neurobiological behavior before and after reperfusion of acute cerebral ischemia at different reperfusion time points and to evaluate the predictive power in terms of prognosis using DCE-MRI. Material and Methods Fifty Sprague-Dawley rats were divided randomly into five groups of ten rats each:3h,4.5h,6h,7.5h,9h ischemia-reperfusion groups. All rats were subjected to MCAO with the intraluminal suture occlusion model. An MR1 scan was obtained immediately before and 6 hours after reperfusion. MRI protocols included DWI, DCE and SWI. Those who present HT were rejected according to the findings of SWI and histopathologicl examination. Ktrans, Kep and Ve values in corpus striatum and cortex were calculated by DCE raw date proceed on a workstation. Difference values of Ktrans, Kep and Ve between pre and after reperfusion were obtained further. Neurobiological behavior test were performed immediately before and 24 hours after ischemia. Positive different value of neurobiological behavior test was considered as benign prognosis and negative or zero different value of neurobiological behavior test was considered as poor prognosis. Comparisons of prognosis and the DCE parameters representing BBB permeability were carried out by statistic methods. Results RKtrans values in corpus striatum between pre and after treatment revealed statistically significant difference in all groups (F=64.94, P=0.000). ΔrKtrans values in corpus striatum revealed statistically significant difference in all groups. RKtrans values in cortex between pre and after treatment revealed statistically significant difference in all groups (F=6.973, P=0.000).ΔrKtrans values in cortex in group 3h,4.5h and 6h were higher than group 7.5h and 9h (P<0.05). However, there were no statistically difference among 3h,4.5h and 6h groups, the same as 7.5h and 9h groups (P>0.05). RVe values in corpus striatum between pre and after treatment revealed statistically significant difference in all groups (F=67.935, P=0.000).ΔrVe in corpus striatum revealed no significant difference among 4.5h and 6h group (P>0.05), and the rest of groups revealed statistically difference (P<0.05). RVe values in cortex between pre and after treatment revealed statistically significant difference in all groups (F=70.352, P=0.000). ΔrVe in cortex revealed no significant difference among 4.5h and 6h group (P>0.05), and the rest of groups revealed statistically difference (P<0.05). RKep values in corpus striatum between pre and after treatment revealed statistically significant difference in all groups (F=67.935, P=0.000). ΔrKep in corpus striatum revealed no significant difference among 3h and 4.5h group (P>0.05),and the rest of groups revealed statistically difference (P<0.05).RKep values in cortex between pre and after treatment revealed statistically significant difference in all groups (F=67.935,P=000). ArKep in cortex revealed no significant difference among 3h and 4.5h group (P>0.05), and the rest of groups revealed statistically difference (P<0.05). Binary logistic regression analysis revealed that ArKtrans of corpus striatum and ArVe of cortex were independent factors associated with prognosis (OR=35.42, OR=19.13). ROC analysis indicated ArKtrans of corpus striatum threshold of 1.020, with a sensitivity of 93.3% and a specificity of 88.9%, and ArVe of cortex threshold of 1.036, with a sensitivity of 86.7% and a specificity of 88.9%. Conclusions The results of this study indicate that ArKtrans of corpus striatum and ArVe of cortex is able to identify ischemia-reperfusion injury early and guide further treatment.