【作者】 王娟；

【导师】 周义成；

【作者基本信息】 华中科技大学 ， 影像医学与核医学， 2007， 博士

【摘要】 第一部分:急性脑静脉闭塞动物模型的建立目的:建立一个稳定的模拟临床疾病的急性脑静脉闭塞动物模型。方法:新西兰大白兔28只,随机分为2组(实验组24只,对照组4只)。一侧颈内静脉注入醋酸纤维素聚合物(CAP)合并双侧颈外静脉结扎术后1、3、6、12、24和48h行T2WI和扩散加权成像(DWI)检查,观察脑实质损害的动态变化,并与病理学对照研究。结果:实验组21只造模成功。由于手术操作失误及麻醉意外等原因,6、12和48h组各有1只动物实验失败。1h、3h及12h组各有1只在DWI及T2WI序列上均无明显异常表现。DWI在术后1h即能早期显示脑实质病变,术后3h DWI和T2WI均能显示病变。脑实质损害病变主要位于皮层及皮层下白质。显微病理学示病变以血管源性水肿为主,12h后出现脑组织大量坏死。对照组未见上述各种异常表现。结论:一侧颈内静脉注入醋酸纤维素聚合物(CAP)合并双侧颈外静脉结扎制备急性脑静脉闭塞模型的方法可行,该模型适合用于急性脑静脉闭塞疾病的病理生理机制和影像学研究。第二部分:急性脑静脉闭塞扩散加权成像与病理学相关性的对比实验研究目的:观察脑静脉闭塞模型脑实质损害区MR扩散加权成像(DWI)、扩散张量成像(DTI)及病理学的变化规律,探讨该模型在该病研究中的价值。方法:新西兰大白兔28只,随机分为2组(实验组24只,对照组4只)。一侧颈内静脉注入醋酸纤维素聚合物(CAP)合并双侧颈外静脉结扎术后1、3、6、12、24和48h行T2WI、DWI和DTI检查,观察扩散异常容积、ADC值、部分各向异性值(FA)和血流动力学变化规律,其结果与病理学对照研究。结果:DWI能早期显示脑实质病变,术后3hDWI和T2WI均能显示病变。术后6h前DWI上扩散异常容积明显大于T2WI上异常高信号区的容积(t=13.69,P<0.01);术后12h、24h及48h T2WI病变容积与DWI上的扩散异常容积无显著差异(t值分别为1.467、0.996及2.017,P值均>0.05)。ADC值早期下降随后逐渐回升,1h与12 h、48h时间点的ADCR相比较,其差异有统计学意义(t值分别为11.46和8.43,P值均<0.01)。术后1h FA值轻度升高,3h后则开始出现不可逆的持续减低。病理学检查示术后早期(1～3h)出现细胞毒性水肿,3h后血管源性水肿持续发展并占优势,12h后出现脑组织大量坏死。对照组未见上述各种异常表现。结论:DWI和DTI可准确评价急性脑静脉闭塞模型脑实质损害程度和血流动力学改变,指导临床治疗和预后判定。第三部分:急性脑静脉闭塞CT灌注成像与病理学对照研究目的:用CT灌注成像(CTP)和病理学方法对急性脑静脉闭塞动物模型进行评价。方法:新西兰大白兔28只,随机分为2组(实验组24只,对照组4只)。一侧颈内静脉注入醋酸纤维素聚合物(CAP)合并双侧颈外静脉结扎术后1、3、6、12、24和48h行CTP检查对各组模型的脑血流动力学改变进行观察,并将其结果与病理学行对照研究。结果:实验组21只造模成功,其中3h及12h组各有1只在CTP上无明显异常表现,有19只CTP检查示脑血流灌注异常。术后1～3h,病变区CBV轻度增加或正常, CBF轻度降低,MTT稍延长;6～12h后病变中心区主要表现为CBV和CBF降低,MTT延长,而病变边缘区CBV增加或正常或轻度降低,CBF降低,MTT缩短;12~24h后病变中心区和边缘区CBV和CBF均明显降低,MTT明显延长。各时间点病变中心区和边缘区的CBV%、CBF%、MTT%的差异均有统计学意义(P值均<0.05)。术后1h、3h和6h,CBF图上灌注异常区域的容积明显大于DWI上扩散异常容积,二者具有显著统计学差异(t值分别为3.707、4.029及4.015,P值均<0.01)。术后12h、24h及48h,CBF图上灌注异常区的容积与DWI上的扩散异常容积的差别无统计学意义(t值分别为0.676、1.356及2.306,P值均>0.05)。病理学示以血管源性水肿为主,12h后出现脑组织大量坏死。对照组未见上述各种异常表现。结论:CT灌注成像可准确、敏感的反映急性脑静脉闭塞模型的血流动力学改变,早期评价脑实质损害的程度和范围,进而指导临床治疗和预后判定。第四部分:急性脑静脉闭塞脑损伤治疗时间窗初探: DWI与病理学对照实验研究目的:探讨急性脑静脉闭塞模型脑实质损伤治疗时间窗的存在及其意义。方法:选择新西兰大白兔28只,随机分为2组(实验组24只,对照组4只)。一侧颈内静脉注入醋酸纤维素聚合物(CAP)合并双侧颈外静脉结扎术后1、3、6、12、24和48h行扩散加权成像(DWI)检查。各时间点MR扫描后取兔脑组织并做胶质纤维酸性蛋白(GFAP)、c-fos和神经元特异性烯醇化酶(NSE)表达的免疫组化研究。结果:DWI和GFAP、c-fos、NSE的表达均能显示急性脑静脉闭塞模型脑实质损伤的发生发展过程。DWI在术后1h即能早期显示脑实质病变。术后6h前ADC值下降;术后12、24和48h ADC值回升。术后1h病变区GFAP、c-fos阳性细胞增多,染色加深,术后3～6h变化更明显。NSE在术后1～6h呈波动状态。对照组未见上述各种异常表现。结果显示,静脉闭塞后脑实质损伤是渐进性过程。GFAP、c-fos、NSE的表达与DWI结果具有一致性。在ADC值早期降低时,脑细胞的代偿机制充分发挥,损伤具有可逆性,此期为可获得较好临床疗效的关键治疗时期。结论:DWI可准确评价急性脑静脉闭塞模型脑实质损伤程度,结合GFAP、c-fos、NSE的表达,在探讨急性脑静脉闭塞脑损伤的治疗时间窗的存在及其意义中具有重要价值,在其发生发展过程中确实存在潜在的治疗时间窗。更多还原

【Abstract】 PartⅠ: Modeling of an acute experimental cerebral venous occlusionObjective: To establish a stable animal model of an acute experimental cerebral venous occlusion to be similar to clinical disease.Methods: 28 New Zealand white rabbits were randomly divided into 2 groups, including experiment group (n=24) and control group (n=4). T2WI and DWI were performed at an interval of 1, 3, 6, 12, 24 and 48h after operation which injected CAP solution into left or right internal jugular vein and by ligation of the bilateral external jugular veins. Brain parenchymal lesions were observed dynamically and compared with pathological changes.Results:21 rabbits in experiment group were operated successfully. The operation of 3 rabbits failed because of misoperation and anesthesia. No abnormal appearance was observed in 3 rabbits on T2WI and DWI sequences. Brain parenchymal lesions were demonstrated by MRI in cortical and sub-cortical areas. The early pathological changes were only detected with DWI (within 1h), and then the lesions were also detected with T2WI after 3h. Brain parenchymal lesions in microscopically were mainly vasogenic edema and followed by necrosis after 12h. No abnormal changes were observed in control group.Conclusion: Modeling of injection of CAP solution into left or right internal jugular vein and ligation of the bilateral external jugular veins in rabbits is feasible. The model is suitable for pathophysiological and radiological studies of acute cerebral venous occlusion. PartⅡ: Comparison of diffusion weighted imaging and histopathology in experimental study of acute cerebral venous occlusionObjective: To observe the evolution of lesion on animal model of acute cerebral venous occlusion by diffusion weighted imaging (DWI), diffusion tensor imaging (DTI) and histopathology, and investigate the value of this kind of model in the disease’s study.Methods: 28 New Zealand white rabbits were randomly divided into 2 groups, including experiment group (n=24) and control group (n=4). T2WI, DWI and DTI were performed at an interval of 1, 3, 6, 12, 24 and 48h after operation which injected CAP solution into left or right internal jugular vein and by ligation of the bilateral external jugular veins. The evolution of the volume of DWI abnormality, apparent diffusion coeffient (ADC) values, fractional anisotropy (FA) values and hemodynamic changes were observed in each group. The data were compared with pathological findings.Results:The early pathological changes were only detected with DWI (within 1h), and then the lesions were also detected with T2WI after 3h. The volume of DWI abnormality was bigger than T2WI abnormality before 6h (P<0.01). No obvious difference of the volume on T2WI abnormality and DWI was found after 12h, 24h and 48h (t=1.467, 0.996, 2.017 respectively; P>0.05). The ADC values of the brain parenchymal lesions decreased at the early stage and increased subsequently. At 1h after operation, FA values of the brain parenchymal lesions slightly increased and subsequently decreased gradually after 3h. Cytotoxic edema emerged after 1h and 3h, then vasogenic edema emerged after 3h and gradually became the main patho-histology findings. Large amount of necrosis was found after 12h. No abnormal changes were observed in control group.Conclusion: DWI and DTI are accurate in evaluating brain parenchymal lesions and hemodynamics of acute cerebral venous occlusion, and are useful for early clinic treatment and prognosis assessment. PartⅢ: Correlation study between CT perfusion imaging and histopathology of acute experimental cerebral venous occlusionObjective: To evaluate model of acute cerebral venous occlusion with computed tomography perfusion (CTP) and histopathological.Methods: 28 New Zealand white rabbits were randomly divided into 2 groups, including experiment group (n=24) and control group (n=4). CTP was performed at an interval of 1, 3, 6, 12, 24 and 48h after operation which injected CAP solution into left or right internal jugular vein and by ligation of the bilateral external jugular veins. The hemodynamic changes were observed in each group. The CTP data were compared with pathological findings.Results:21 rabbits in experiment group were operated successfully. The operation of 3 rabbits failed because of misoperation and anesthesia. No abnormal appearance was observed in 2 rabbits on CT perfusion imagings. Cerebral blood volume (CBV) slightly increased or noral, cerebral blood flow (CBF) slightly decreased and mean transit time (MTT) prolonged slightly in the lesions after 1~3h. Both CBV and CBF decreased in the center of the lesions, while CBV increased, normal or decreased, CBF decreased in the marginal zone after 6~12h. CBV and CBF decreased obviously both in the center and marginal zone after 12~24h. There was obvious difference among CBV%, CBF% and MTT% in the center and marginal zone of the lesions at each time interval (P<0.05). The volume of CBF abnormality was bigger than DWI abnormality after 1h, 3h and 6h (t=3.707, 4.029, 4.015 respectively; P<0.01). No obvious difference of the volume on CBF abnormality and DWI was found after 12h, 24h and 48h (t=0.676, 1.356, 2.306 respectively; P>0.05). Brain parenchymal lesions in microscopically were mainly vasogenic edema and followed by necrosis after 12h. No abnormal changes were observed in control group.Conclusion: CT perfusion imaging is accurate and sensitive in evaluation hemodynamics of acute cerebral venous occlusion and is useful in the early evaluation of the consequences for brain parenchymal lesions. Moreover, CT perfusion imaging is favourable for early clinic treatment and prognosis assessment. PartⅣ: Preliminary research of the therapeutic widow in brain parenchymal lesion of acute cerebral venous occlusion: a comparison of diffusion weighted imaging and histopathology in experimental studyObjective: To discuss the existence and significance of therapeutic window in brain parenchymal lesions on animal model of acute cerebral venous occlusion.Methods: 28 New Zealand white rabbits were randomly divided into 2 groups, including experiment group (n=24) and control group (n=4). DWI was performed at an interval of 1, 3, 6, 12, 24 and 48h after operation which injected CAP in left or right internal jugular vein and by ligation of the bilateral external jugular veins. The specimen was analyzed at different time points by immunohistochemistry.Results:DWI and expression of GFAP, c-fos and NSE can show the process of occurrence and development in brain parenchymal lesions of acute cerebral venous occlusion. The early pathological changes were only detected with DWI (within 1h). The ADC values of the brain parenchymal lesions decreased before 6h. And the ADC values of the brain parenchymal lesions increased subsequently after 12, 24, and 48h. At the 1th hour after operation, the number of GFAP and c-fos immunopositive cells enhanced, the cell bodies enlarged. These changes became obvious after 3h and 6h. No abnormal changes were observed in control group. The process of brain parenchymal lesions in acute cerebral venous occlusion was progressive. The expression of GFAP, c-fos and NSE was consistent with the results of DWI. During the early stage of ADC values’s decrease, compensatory mechanism was sufficiently educed in brain cells and the brain lesions had reversibility. And it was possible to get satisfied therapeutic effect through timely treatment.Conclusion: In combination with the expression of GFAP, c-fos and NSE, DWI is accurate in evaluating brain parenchymal lesions. Therapeutic window truly exists in the process of occurrence and development in brain parenchymal lesions of acute cerebral venous occlusion.更多还原