| SECTION ONE: Combined application of permeability and perfusion parameters to evaluate acute ischemic stroke in an optimized modelOBJECTIVETo determine whether Ktrans maps, a permeability parameter indicating BBB dysfunction, combining with perfusion parameters, can identify the really infarct volume and predict the clinical outcome in acute ischemic stroke.METHODS98 consecutive patients were recruited in this study. Inclusion criteria 1) acute hemispheric stroke patients admitted within 9 hours since signs and symptoms started. 2) treated with arterial thrombolysis and / or mechanical thrombectomy. Ktrans maps were calculated from PCT data using prototype software, which uses the Patlak model to assess their BBBP. Then Ktrans maps were then loaded into Image J 1.47 for Mac OS to draw the Regions of interest. Combining with perfusion parameters, Ktrans map was a new strategy to predict final infarction volume. PCT- predict final infarction volume(PCT-FIV) and Ktranspredict final infarction volume(Ktrans-FIV) were calculated respectivly depending on recanalization. The agreements between different groups were calculated using Chi-square tests. The radiological calculated both perfusion and Ktrans maps. Multiple logistic regression analyses and multiple linear regression analyses were conducted to determine independent predictors of 90-day m RS and follow up final infarction volume(FIV) respectively. Finally, all patients were divided into two groups based on whether the ipsilateral carotid stenotic rate was above 75% or not. PCT-PIV/FIV and Ktrans-PIV/FIV were compared between the two groups.RESULTSOf 98 patients, 46 were female. 50 patients had a good outcome. Mean age of all patients was 65.03±14.1 years. Patients with good outcome had less mean age, NIHSS, PCT-FIV, Ktrans-FIV, and FIV(P<0.001). Patients with poor outcome had higher mean SBP on admission(P=0.003) and less opportunity of successful recanalization(P=0.003). In multivariate logistic regression analysis, Ktrans-FIV was the most powerful predictor of clinical outcome(P=0.009, OR=1.097),followed by age(P= 0.027; OR =1.243) and NIHSS on adimission(P= 0.029; OR = 1.085); In linear regression analysis, Ktrans-FIV was also the best positive predictor for FIV(F=75.590, P<0.0001), followed by hemorrhagic transformation(F = 11.650, P = 0.001). Patients with early hemorrhagic transformation tended to have a larger FIV. As for PCT-PIV versus FUP- FIV, there was a difference between the group with the ipsilateral carotid stenotic rate above 75% and the other within 75%.(p= 0.0063). As for the ratio of Ktrans-PIV over FIV, there was no difference between the two groups(p= 0.7565).INTERPRETATIONPerfusion paramters alone always exaggerated penumbra volume, especially in those patients with severe chronic carotid artery stenosis. Chronic hypoperfusion induced precondition which can protect tissue at risk could be an reasonable explaination. Combining PCT and Ktrans maps derived from first-pass of PCT can identify cerebral ischemic tissue at risk more precisely.SECTION TWO: Using permeability imaging to evaluate neurovascular unit in rats with cerebral chronic hypoperfusionOBJECTIVECerebral chronic hypoperfusion may trigger a series of pathological changes in NVU. It is the first time in vivo to use permeability imaging to evaluate neurovascular unit in rats with cerebral chronic hypoperfusion. This study aimed to compare permeability parameters with pathological findings and explored a new noninvasive imaging marker to evaluate neurovascular unit in cerebral chronic hypoperfusion.METHODSExperimental animals were divided into three groups( each group n= 12), rats in group 1 were normal SD rats, in group 2 were normal SHRs and group 3 were chronic hypoperfusion SHRs(ligations of bilateral carotid artery for 3 months).Frontal lobe, temporal lobe and hippocampal CA1 region were set as the region of interest(ROI) and evaluated by permeability imaging. Vascular dissociation index(VDI)and neuron counting of ROIs were accessed with confocal microscope. Finally, the correlation between the VDI and the permeability imagings was statistically analyzed using SPSS12.0 software.RESULTSWhen compared with the SD group, the VDI and neuron counting in the chronic hypoperfusion SHR group showed significant differences(P<0.0001 and P=0.0390). There was not statistically difference between normal SD group and normal SHR group. However,in normal SHR group, the average VDI was higher and the average neuron counting was lower, while compared with normal SD group. It is suggested that there was an increasing trend for VDI whereas a decreasing trend for neuron counting. Of note, permeability parameters Ktrans had a high coherence with vascular dissociation index(P=0.0015, R=0.827, 95% CI: 0.466- 0.952);followed by Kep(P=0.0163, R=0.686, 95% CI: 0.167- 0.908).INTERPRETATIONDuring chronic hypoperfusion, NVU was significanttly impaired with BBB permeability opened slightly and neuronal apoptosis started subsequently. Both Ktrans and Kep showed a good correlation with the pathological changes in NVU, which suggested Ktrans and Kep might be noninvasive imagings parameters for quantitative evaluation of neurovascular unit in cerebral chronic hypoperfusion.SECTION THREE: Using permeability imaging to evaluate neurovascular unit in rats with acute ischemic stroke under the cerebral chronic hypoperfusionOBJECTIVEThis study will continue to evaluate the changes of neurovascular unit suffered ischemic stroke under chronic hypoperfusion status. The correlation analysis was then conducted between Ktrans or Kep and VEGF or Caspase 3 protein.We aimed to determine whether the permeability parameters are correlated with changes of neurovascular unit in acute ischemic condition.METHODSExperimental animals were divided into two groups(each group n = 12). Rats in group 1 were SHR with ligations of bilateral carotid artery for 3 months, and then proceed to occlude their left middle cerebral artery. In group 2 were SHR made the left middle cerebral artery occlusion only. Between the 2 groups, we compared the infarct volume, the value of VEGF and Caspase 3 proteins around the infarction area, as well as the ischemic hemisphere. We observed the difference of the neurovascular unit by electron microscope and detected the expressions of VEGF and Caspase 3 proteins. Finally, we correlated Ktrans and Kep with the expressions of VEGF and Caspase 3 proteins.RESULTS1 Imaging results 1)Infarction volume(mm2):the infarction volume in group 1 was, 79.15± 13.97 and in group 2 was 106.6 ±11.43. There was a significant difference between the group 1 and group 2,(P<0.0001). 2) Ktrans calculated from the lesion side and the infarction core. Ktrans in group 1 were 0.788±0.397 and 1.232±0.455 respectively. Ktrans in group 2 were 1.513±0.561 and 1.938±0.636 respectively. There was a significant difference between between the group 1 and group 2,(P<0.0001). 3) Kep calculated from the lesion side and the infarction core. Kep in group 1 were 0.643±0.190 and 0.895±0.350 respectively. Kep in group 2 were 0.954±0.360 and 1.473±0.570 respectively. There was a difference between the group 1 and group 2(P=0.0145 and 0.0066). 2 Immunohistochemical results: the expression of VEGF and Caspase 3 in group 1 were 86.42 ±19.67 and 37.64 ±12.71; in group 2 were 66.52±19.44 and 53.28±19.05 respectively. There were significant differences between the two groups about the the expression of VEGF and Caspase 3(P<0.05). 3 The correlation of imagings with pathological changes in neurovascular unit. Ktrans had a strong correlation with the expression of VEGF protein. Kep had a good correlation with Caspase 3 as well.INTERPRETATIONBBB permeability showed a positive correlation with the degree of ischemic damage. Finally, we found that Ktrans had a strong correlation with the expression of VEGF protein which was the most powerful factor promoting angiogenesis.However, Kep showed a good correlation with Caspase 3,which might reflect neuronal apoptosis. |
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