An Experimental Research Of Hyperacute Cerebral Infarction By Multi-slice CT Perfusion Imaging

Background and Purpose: Stroke is the third leading cause of death, and one of the leading causes of adult disability. Hyperacute cerebral infarction refers to ischemic stroke which occurs within 6 hours after the onset. During the hyperacute stage, there is ischemic penumbra (IP) of hypoperfusion between the severely hypoperfused areas and normal brain tissue. If thrombolytic therapy is performed in time to restore blood flow, IP may be salvageble, otherwise, it may be irreversibly damaged. Moreover, reperfusion may cause additional damage to the ischemic brain by inducing hemorrhagic complications if thrombolysis is applied to large severely hypoperfused regions. Therefore the identification of IP and its extent as well as the extent of severely hypoperfused regions is of great importance guiding early therapy of infarction.Nonenhancement CT (NECT) can identify early signs of acute ischemic and hemorrhagic stroke according to morphological changes. However, it provides no information about IP and oligemic extent of irreversibly damaged regions. Recently, with the advent and application of computed tomography perfusion (CTP), CT technique has evaluated from morphological diagnosis to functional diagnosis. Perfusion CT can evaluate cerebral blood ?ow and perfusion of ischemic tissues effectively and can identify the infarction and the penumbra tissue. Our research was to establish a middle cerebral artery occlusion model (MCAO) in rat, the purpose was to explore the CTP imaging findings of hyperacute infarction and IP, and by comparing with pathomorphological results of TTC staining and microscopy to evaluate the CTP diagnostic value of hyperacute infarction.Objects and methods: Fifty SD male rats were randomly divided into 2 groups, 40 rats were included in the experimental group, 10 rats were classified as control group. For the experimental group, a thread was inserted into middle cerebral artery (MCA) via external carotid artery to make a rat MCAO model, whereas there was no thread occluding MCA for the control group. CT perfusion imaging was performed by GE LightSpeed 16-slice CT scanner at 0.5h, 1h, 2h, 3h, and 6h interval after the onset of occlusion, respectively. 8 rats of each experimental group and 2 rat of each control group were classified as above time point. The scan sequences included: scout image, coronal plain CT and fixed 8 slices continuous dynamic scan (cine mode). After CT perfusion imaging, the rats were rapidly decapitated. Specimens of the brain tissue in each time point which were obtained correspondently to CT scan were cut with slice thickness 2.5mm for TTC staining. Subsequently, the stained slices were photographed by a digital camera. Automatic image analysis system was applied to measure the extent of the infracted area. After immersing in 10% buffered formalin, specimens of the brain tissue in each time point were observed by microscopy after HE staining.All of the perfusion CT images were processed by CT Perfusion 3 in the GE Sun Advantage Workstation 4.2. 3 kinds of artifact colour images were obtained, including CBF map, CBV map, and MTT map. Volumes of ischemic cores and peri-ischemic areas on CBF map, hypoperfusion regions on CBV map and MTT map were calculated, each parameter including absolute and relative value was also measured.The statistical analysis was executed by SPSS 10.0 software; statistical methods were t-test, analysis of variance as well as analysis of Pearson correlation, a =0.05 was deemed significant level.Results: (1)There was no significant difference between bilateral CBF, CBV, and MTT of the control groups(P>0.05), and no difference was found between the cortex and basal ganglia region on MTT map, while there was difference between the cortex and basal ganglia region on CBF and CBV maps(P<0.05). (2)0.5h after MCAO, source CTP images showed perfusion defect, CBF maps showed areas of green staining involving the basal ganglia region, frontal, temporal, and parietal regions, mixed with punctuate and patch blue staining areas; the green staining band were located in the medial aspect of the ischemic cores and the upperportion of the frontal and parietal cortex. According to CBV map, the ischemic region showed blue staining without transitional region between the lesion and the normal region. From MTT maps, the lesion showed extensive green staining region, mixed with patchy red and yellow areas. With the time coursing after MCAO, there were involvement of the frontal, temporal, and parietal cortex, showing blue staining areas on CBF and CBV maps. ?There was significant difference between the ischemic core and the correspondent region of the unaffected side on CBF map, between the ischemic region and the correspondent region of the unaffected side on CBV, MTT map (P<0.001). The CBF value in the ischemic core didn't show a tendency of decreasing over time, and there was no significant difference between different time points (P>0.05). And for the CBV, MTT value in the ischemic regions of different time points no significant difference was found, either (P>0.05). ?After MCAO, the volumes of perfusion defect areas on source CTP images, ischemic core on CBF maps, and ischemic regions on CBV, MTT maps during l-3h fluctuated, and they showed a tendency to enlarge, but there was no significant difference between different time points (P>0.05). After MCAO, no significant difference was seen as to the infarction volumes by TTC staining between different time points (P>0.05). There was no difference between the volumes of perfusion defect areas on source CTP images, ischemic core on CBF maps, and ischemic regions on CBV maps(P>0.05). However, significant difference was observed between the volumes of ischemic regions on MTT maps and perfusion defect areas on source CTP images, between the volumes of ischemic regions on MTT maps and ischemic core on CBF maps, or ischemic regions on CBV (P<0.0001). Close correlation was found between ischemic core on CBF maps, ischemic regions on CBV maps and infarction volumes by TTC staining (rcb*=0.959, P<0.01; rcbv=0.911, P<0.01). And ischemic regions on MTT maps as well as perfusion defect areas on source CTP images were positively linear correlated with infarction volumes shown by TTC staining (rmtt=0.800, P<0.01; rsoUrce =0.713, P<0.0l). ?The extent of peri-ischemic region on CBF maps of different time points showed no significant difference (P>0.05). And no significant difference was found between CBV value of peri-ischemic region and the corresponding part on the unaffected side at 0.5h, while significant difference was seen at other time points. And there was significant difference between CBF value of peri-ischemic region and the corresponding part on the unaffected side, between MTT valueof peri-ischemic region and the corresponding part on the unaffected side at each time points. Significant difference was observed between CBF value of peri-ischemic region at 2h and other time points, and CBF value of peri-ischemic region at 2h was the lowest, which was 9.11±2.05ml/100g/min. There was significant difference between CBV value of peri-ischemic region at 0.5h, 6h and other time points, the CBV value was lowest at 0.5h and highest at 6h. Significant difference was seen between MTT value of peri-ischemic region of different time points, the MTT value were higher at 2h, 3h than at other time points. There was no significant difference between each parameter from and the corresponding part on the unaffected side at each time points. ?No significant difference was found between rCBFc of the ischemic core on CBF map of each time point, and there was no significant difference between rCB Va, rMTTa of the ischemic regions on CBV, MTT map of each time point, either. While there was significant difference between rCBFp, rCBVp, rMTTp of the peri-ischemic region of each time point. And significant difference was observed between rCBFc and rCBFp, rCBVa and rCBVp at each time point. There was no significant difference between rMTTa and rMTTp at 1, 2h, while significant difference was seen between rMTTa and rMTTp at other time points.? On CBF maps, there were2, 7,13,13, 5cases involving 1, 2,3, 4, 5 cuts as to the ischemic core, respectively; 2, 6,15, 15, 2 cases affecting 2, 3, 4, 5, 6 cuts as to the peri-ischemic region, respectively. ? The brain tissue of the control group and the non-thrombosed side of the experimental group showed red by TTC staining, the core regions on CBF maps showed white, which mainly were located in the cortex of frontal, temporal, and parietal lobes as well as lateral aspect of the new corpus striatum. The peri-ischemic region on CBF maps showed pink or red staining. ? In the ischemic core on CBF maps, microscopy showed no abnormal evidence at 0.5h, loose of neuronal nuclear chromatin and edema of gliocytes at lh, nuclear hyperchromatism and ballooning degeneration of some neural cells, obvious edema of gliocytes at 2h, karyopyknosis and karyoklasis in neural cells as well as ballooning degeneration of gliocytes at 3h, neuronal clasmatosis and vacuolar degeneration of gliocytic nuclei at 6h. During 0.5~3h, there was no abnormal evidence in the peri-ischemic region on CBF maps by microscopy. At 6h, there were still no abnormal changes of neuron, while there was vacuolar degeneration surrounding neurons.Conclusion: (Dl.The source MS-CTP images can identify potentially irreversible ischemia and show its extent to some degrees; ?The ischemic core on the CBF maps and ischemic regions on the CBV maps are infarcted areas which were pathologically proven. MTT map is highly sensitive to identify ischemia, but it always overevaluate the extent of the ischemia. (3)IP locates between the ischemic core and normal brain tissue, CBF maps can reveal the IP, which is the peri-ischemic region; @The volumes of infarction and the focal CBF, CBV values as well as the volumes of IP at different time points within 6h show no significant difference, while there is significant difference as to CBF, CBV values of IP. And there is high individual variability in the amount of infarction volume at the same time point after MCAO. Therefore, the therapeutic window should be established according to CBF, IP showed by perfusion imaging and vary from patient to patient; ?MS-CTP is superior to SS-CTP since the former can reveal the perfusion situation and extent of hyperacute cerebral infarction and IP more correctly; ?MS-CTP is an effective imaging modality for diagnosis of hyperacute cerebral infarction and identification of IP.