Experimental Study Of Acute Severe Hypoxic Ischemic Encephalopathy In Piglet Model: Diffusion Weighted MR Imaging Appearances And Pathologic Findings

Objective To study the value of the diagnosis of super acute Hypoxic Ischemic Encephalopathy (HIE), the differential diagnosis of reversible and irreversible cerebral ischemia regions, and the existence of therapeutic window in HIE piglet model with Diffusion-Weighted MR Imaging (DWI) and verified by pathology. Methods Seven days old piglets (n=50) were divided into 3 groups by random: group A (normal control group, n=5), group B (sham operation group, n=5) and group C (HIE group, n=40, perform by bilateral common carotid artery occlusion and then inspirited 4% oxygen about 1 hour). According to the time of sacrifice after hypoxic ischemic, Group C was divided into 7 groups more: group C1 (Oh, n=5), group C2 (lh, n=5), group C3 (3h, n=5), group C4 (6h, n=5), group C5 (12h, n=5), group C6 (18h, n=5), group C7 (24h, n=10). Group C1^C7 were undergone MRI scan before sacrificed, and the data was compared with pathologic findings; Group C7 was scanned at 0,1, 3, 6, 12, 18, 24 hours after hypoxic ischemic, and the data was used to study the dynamic changes of MRI appearances in HIE. All piglets were scan with GE Signa Hi-Speed 1.5T MRI scanner, scan series including T1WI, T2WI, FLAIR and DWI; DWI data was processing by functool in GE Advantage workstation AW4.0₀5 to get ADC maps and ADC values. HE Stain and HSP70 Immunohistochemistry were done in all cerebral samples (including frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia and corona radiata). On ADC maps, 4 regions of interest (ROI) were set from the minimum ADC values point to the normal ADC values area, and named ROI , ROI , ROI , ROI in order. The ADC values of 4 ROIs and the quantity of HSP70 positive cells in corresponding regions were analyzed by Independent-Samples T test, and their relationships with hypoxic ischemic time were analyzed by Spearman Correlate. Results No abnormalities were found in MRI nor pathology in group A and group B. Dynamic changes found in MRI and pathology ingroup C were presented regularly. (1) Small patchy region of long T1WI and long T2WI were found in bilateral cerebrum at 18 hour after hypoxic ischemic. (2) Widespread hyperintensity were found in bilateral cerebrum at 0 hour after hypoxic ischemic in DWI. And the lesions became more and more localized gradually with the time passing on. (3) ADC maps show that the range and time course of the abnormal ADC values in ROI were quite different. The ADC values of ROI drop first and then rise, and it drop most seriously at 12-18 hour after hypoxic ischemic. The ADC values of ROI and ROI drop less seriously when compare with ROI I and rise gradually just after hypoxic ischemic. The ADC values of ROI IV was normal. (4) HE Stain and HSP70 Immunohistochemistry show that the pathologic appearances of ROI I were quite different too. The pathological changes of ROI I were the most serious, and became more and more serious with the time passing on. The pathological changes of ROI were less serious when compare with ROI I and reconverted gradually just after hypoxic ischemic. The pathological changes of ROI IV were the slightest and reconverted gradually just after hypoxic ischemic too. It was a nearly normal region. The quantity of HSP70 positive cells in ROI I was very small and it did not increase with the time passing on. The quantity of HSP70 positive cells in ROI were large and it increase obviously with the time passing on. Conclusions (1) The focus of hypoxic ischemic can be found by DWI, ADC maps and ADC values in super acute HIE. (2) The range and the time course of ADC values can distinguish reversible and irreversible cerebral ischemia regions. (3) Combining DWI, ADC maps and ADC values with conventional MRI can diagnose HIE more exactly. ?The existence of therapeutic window in HIE is possible, but further research is needed.