【作者】 郭大静；

【导师】 孔祥泉； 王志刚；

【作者基本信息】 华中科技大学 ， 影像医学与核医学， 2006， 博士

【摘要】 第一部份急性脑静脉闭塞动物模型的建立及磁共振扩散、灌注成像研究目的对急性脑静脉闭塞动物模型加以改进，拟建立一个稳定的类似临床疾病的动物模型；用磁共振扩散和灌注成像（DWI、PWI）对模型进行评价，观察脑实质损害的变化规律。方法家猫28只，随机分为3组（栓塞组18只，结扎组6只，假手术组4只），栓塞组和结扎组分别采用开颅上矢状窦穿刺注射醋酸纤维素聚合物（CAP）和上矢状窦（SSS）后份结扎制备急性脑静脉闭塞动物模型，假手术组仅行开颅上矢状窦暴露。术后1、3、6、12、24、48h对各组模型行DWI、PWI检查，观察脑实质损害的动态变化，并和病理结果作对照研究。结果栓塞组16只猫造模成功。DWI发现栓塞组10只猫脑实质出现19个异常信号，指数化表观扩散系数（eADC）图以低信号为主，1～3h可呈高信号或高、低混杂信号改变，12h后信号复杂多变。PWI发现13只猫脑实质内23个异常灌注区，表现为平均通过时间（MTE）延长，局部脑血容量（rCBV）增加、正常或降低。病变中心区和边缘区的相对平均通过时间比率（rMTE）1、3、6h稍延长，12h后明显延长。6h后病变中心区相对脑血容量比率（rrCBV）降低明显，12h后病变边缘区rrCBV逐渐降低，24h降低明显。6、12、24h病变中心区和边缘区rrCBV差异均有统计学意义(t₆=-5.73，t₁₂=-3.22，t₂₄=-4.22，P＜0.05)。大体病理学16只猫上矢状窦、桥静脉及皮层静脉内见CAP凝固呈铸型改变。显微病理学见病灶以血管源性水肿为主，12h后出现静脉性脑梗塞、脑出血。结扎组和假手术组脑实质未见异常改变。结论上矢状窦穿刺注射CAP制备急性脑静脉闭塞模型方法可行，该模型适合于病理生理基础及影像学研究；DWI结合PWI对急性脑静脉闭塞脑实质损害的动态变化、发病机理的判断具有重要价值。第二部份急性脑静脉闭塞CT灌注成像及其与MR扩散、灌注成像对比研究目的用CT灌注成像（CTPI）对急性脑静脉闭塞动物模型进行评价；对比CTPI和磁共振扩散加权成像（DWI）、灌注加权成像（PWI）评价急性脑静脉闭塞脑实质损害的价值。方法家猫22只，随机分为2组（手术组18只，假手术组4只）。手术组采用开颅上矢状窦穿刺注射醋酸纤维素聚合物（CAP）制备急性脑静脉闭塞动物模型，假手术组仅行开颅上矢状窦暴露。术后1、3、6、12、24、48h用CTPI对各组模型的脑血流动力学改变进行观察，对比CT、MR对病灶检出率、脑实质损害容积及程度判断的一致性。结果手术组12只猫CTPI出现脑血流异常灌注区。术后1h，病变表现为局部脑血容量（regional Cerebral Blood Volume，rCBV）轻度增加，局部脑血流量（regional Cerebral Blood Flow，rCBF）轻度降低，平均通过时间（Mean Transit Time，MTT）稍延长；3～6h后病变中心区主要表现为rCBV和rCBF降低，而病变边缘区rCBV增加或正常或轻度降低，rCBF降低；12～24h后病变中心区和边缘区rCBV和rCBF均明显降低。假手术组4只猫均未见上述各种异常表现。与MR结果对比：CTPI发现12只猫脑实质内20个异常血流灌注区，DWI发现10只猫脑实质内19个异常信号，PWI发现13只猫脑实质内23个异常灌注区。PWI平均通过时间（Mean time to enhance，MTE）参数图与CTPI-rCBF参数图对病灶容积的测量差异无统计学意义（t=1.54，P＞0.05）。PWI和CTPI-rCBV图对脑实质损害程度判断一致性好（Kappa=0.69，P＜0.01）。结论功能CT灌注成像是评价急性脑静脉闭塞动物模型血流动力学改变的一种准确、敏感的方法，可早期评价脑实质损害的程度。CTPI与DWI、PWI对急性脑静脉闭塞脑实质损害的判断均能提供重要信息，具有较好的一致性。第三部份急性脑静脉闭塞脑实质损害质子波谱分析的实验研究目的用磁共振波谱（MRS）连续观察急性脑静脉闭塞模型脑实质损害的代谢规律，评价MRS的应用价值。方法家猫30只，随机分为2组（手术组24只，假手术组6只）。手术组采用开颅上矢状窦穿刺注射醋酸纤维素聚合物（CAP）制备急性脑静脉闭塞动物模型，假手术组仅行开颅上矢状窦暴露。术后1、3、6、12、24、48h用MRS对各组模型脑实质损害进行连续动态观察，分析代谢物为氮-乙酰天门冬氨酸（NAA）、胆碱类复合物（Cho）、肌酸（Cr）、乳酸和脂质（LL）及NAA／Cr、Cho／Cr、LL／Cr。测量病变中心区、边缘区、周围相对正常区及其对侧镜像区脑组织的代谢物浓度并做统计分析。结果手术组常规MRI及DWI发现15只猫脑实质出现异常信号，病变中心区NAA、Cho及Cr于术后3h开始降低，边缘区NAA、Cho术后6h开始降低，Cr术后12h降低，病变中心区和边缘区LL术后1h升高明显，以后逐渐降低。术后各时间点病变中心区和边缘区的NAA／Cr、Cho／Cr、LL／Cr差异均有统计学意义（F值分别为5.14和3.09，9.90和5.62，9.16和3.35，P＜0.05）。术后1、3h病变周围相对正常区LL／Cr明显升高。术后3、6、12h病变中心区及边缘区NAA／Cr差异有统计学意义（t值分别为-3.15，-3.66，-2.75，P＜0.05）。术后1、3、6h病变中心区及边缘区LL／Cr差异有统计学意义（t值分别为5.37，4.47，2.40，P＜0.05）。手术组9只猫常规MRI及DWI检查结果均为阴性，术后各时间点MRS检查见双侧MRS曲线对称，无明显LL峰出现。病理学检查见病变以血管源性水肿为主，12h后出现坏死，伴有出血性脑梗塞。假手术组未见上述各种异常表现。结论NAA、Cho、Cr降低及LL明显升高是急性脑静脉闭塞脑实质损害的主要特点，MRS对其代谢变化、发病机理的判断具有重要价值。第四部份磁共振弥散张量成像及纤维示踪技术在急性脑静脉闭塞中的初步应用研究目的用磁共振弥散张量成像（DTI）对急性脑静脉闭塞模型进行评价，观察脑实质损害病灶的弥散规律及白质纤维束的完整性，评价DTI的应用价值。方法家猫30只，随机分为2组（手术组24只，假手术组6只）。手术组采用开颅上矢状窦穿刺注射醋酸纤维素聚合物（CAP）制备急性脑静脉闭塞动物模型，假手术组仅行开颅上矢状窦暴露。术后1、3、6、12、24、48h用常规MRI和DTI对各组模型脑实质损害进行连续动态观察，重建参数图并测量病变区的平均弥散系数（AvgDC）和各向异性分数（FA）值，计算与健侧镜像区的AvgDC、FA比值，用纤维示踪技术（FT）立体显示脑白质纤维束的完整性和连贯性，并和病理学对照研究。结果手术组15只猫脑实质出现异常信号。术后1h，AvgDC值较健侧镜像区降低，3h后，AvgDC值较健侧逐渐增高，12h后，增高明显。FA值于术后各时间点均降低。各时间点病变区与健侧镜像区AvgDC、FA值差异有统计学意义（P＜0.05）。各时间点AvgDC、FA比值差异有统计学意义（F值分别为62.07，9.37，P＜0.05）。术后1h，FT显示脑白质纤维束出现移位和穿过病灶区，6h后，脑白质纤维束断裂、破坏，12h后，脑白质纤维束于病变边缘处中断。病理学检查，术后1h，病变区出现细胞毒性脑水肿，3h后以血管源性水肿为主，12h后出现静脉性脑梗塞、脑出血。假手术组未见上述各种异常表现。结论DTI能清楚显示并定量判断急性脑静脉闭塞脑实质损害的动态变化规律，FT能更好地显示脑白质纤维束的受损和移位。更多还原

【Abstract】 Part Ⅰ Modeling of acute experimental cerebral venous occlusion and evaluation with MR diffusion and perfusion weighted imagingObjective To improve the model of acute cerebral venous occlusion and establish a stable animal model to be similar to clinical disease; To evaluate the model with MR diffusion and perfusion weighted imaging （DWI and PWI） in observing the changing regularity of the brain parenchymal lesions. Methods Twenty-eight cats were randomly divided into 3 groups, including embolism group （n=18）, ligation group （n=6） and sham operation group （n=4）. Embolism group and ligation group were performed respectively by injection of the cellulose acetate polymer （CAP） solution into the superior sagittal sinus （SSS） and by ligation of the posterior part of the SSS. DWI and PWI were performed at an interval of 1, 3, 6, 12, 24 and 48h after operation. Brain parenchymal lesions were observed dynamically and compared with pathological changes. Results Sixteen cats in embolism group were operated successfully. In embolism group, nineteen lesions were detected on DWI mainly with hypointensity on exponential Apparent Diffusion Coefficient （eADC） maps in 10 cats. Lesions with hyperintensity or mixed with both hyperintensity and hypointensity were observed in 1 to 3 hours. The signal intensity was complicated in 12 hours; twenty-three abnormal perfusion regions were detected on PWI in 13 cats. Mean time to enhance （MTE） is prolonged, while regional cerebral blood volume （rCBV） could be increased, normal or decreased. Relative MTE （rMTE） of the central and marginal region prolonged slightly in 1、3、6h and prolonged obviously in 12h. Relative rCBV （rrCBV） of the central region in lesions decreased obviously in 6h, while rrCBV of marginal region decreased gradually in 12h and obviously in 24h. Relative rCBV of the central and marginal region in 6, 12, 24h showed significant difference (t₆=-5.73, t₁₂=-3.22, t₂₄=-4.22 respectively, P<0. 05). There were cast-like materials formed by CAP within SSS, bridging veins and cortical veins in 16 cats. The microscopic changes were mainly vasogenic edema and followed by venous hemorrhagic infarction in 12h. No abnormal findings were observed in ligation group and sham operation group. Conclusion Modeling of acute cerebral venous occlusion by injection of CAP solution into SSS is feasible. The model is suitable for pathophysiological and radiological studies of acute cerebral venous occlusion. DWI combined PWI has great value in judging the dynamic changes and the etiopathogenesis of brain parenchymal lesions in acute cerebral venous occlusion. Part Ⅱ CT perfusion imaging in acute experimental cerebral venous occlusion: Comparison with diffusion and perfusion MR imagingObjective To evaluate a model of acute cerebral venous occlusion with CT perfusion imaging （CTPI） and to compare the value of CTPI with MR diffusion weighted imaging （DWI） and perfusion weighted imaging （PWI） in evaluating the brain parenchymal lesions. Methods Twenty-two cats were randomly divided into 2 groups, including operation group （n=18） and sham operation group （n=4）. Acute cerebral venous occlusion was induced by injection of the cellulose acetate polymer （CAP） solution into the superior sagittal sinus （SSS）. CTPI were performed at an interval of 1, 3, 6, 12, 24 and 48h after operation. The hemodynamic changes were observed in each group. Detection ratios of lesions, lesion volumes and the degree of brain parenchymal injury were compared with DWI and PWI. Results Abnormal cerebral blood flow perfusion regions were detected in 12 cats in operation group by CTPI. Regional cerebral blood volume （rCBV） increased, regional cerebral blood flow（rCBF） decreased and mean transit time （MTT） prolonged slightly in the lesions in 1h. Both rCBV and rCBF decreased in the center of the lesions, while rCBV increased, normal or decreased, rCBF decreased in the marginal region in 3-6h. rCBV and rCBF decreased obviously both in the central and marginal regions in 12²4h. No abnormal changes were observed in sham operation group. CTPI detected 20 lesions in 12 cats, while DWI detected 19 lesions in 10 cats, PWI detected 23 abnormal perfusion regions in 13 cats. The lesion volumes on PWI mean time to enhance （MTE） maps showed no significant difference with that on CTPI-rCBF （t=1.54, P>0.05）. The evaluation of the degree of brain parenchymal injury on PWI and CTPI-rCBV showed good consistency （Kappa=0.69, P<0.01）. Conclusion CT perfusion imaging is accurate and sensitive in evaluating hemodynamics of acute cerebral venous occlusion and is useful in the early evaluation of the consequences for brain parenchymal lesions. DWI and PWI have good consistency with CTPI in judging the brain parenchymal lesions in acute cerebral venous occlusion.Part Ⅲ Experimental study of the brain parenchymal lesions in acute cerebral venous occlusion with magnetic resonance spectroscopyObjective To evaluate the value of magnetic resonance spectroscopy （MRS） in observing the dynamic metabolic changes of the brain parenchymal lesions in acute experimental cerebral venous occlusion. Methods Thirty cats were randomly divided into 2 groups, including operation group （n=24） and sham operation group （n=6）. The modeling of acute cerebral venous occlusion in operation group was performed by injection of the cellulose acetate polymer （CAP） solution into the superior sagittal sinus （SSS）. MRS was continually performed at an interval of 1, 3, 6, 12, 24 and 48h after operation for each group to observe the brain parenchymal lesions. The metabolic concentrations of N-acetylaspartate （NAA）, Choline （Cho）, Creatine （Cr）, Lactate and Lipid （LL） and their ratios of NAA/Cr, Cho/Cr, LL/Cr were analyzed. The metabolite in the central, marginal regions of the lesions, peripheral regions adjacent to the lesions and the contralateral normal side were measured and the statistical results were analyzed. Results In operation group, abnormal signal regions were detected on conventional MRI and DWI in 15 cats, NAA, Cho, Cr in the center of the lesions were decreased in 3h, while NAA, Cho in the marginal regions were decreased in 6h, Cr decreased in 12h, LL in the center and marginal regions increased obviously in 1h and decreased gradually later. NAA/Cr, Cho/Cr, LL/Cr in the center and marginal regions showed statistical difference over the time period of measurement （F=5.14 and 3.09, 9.90 and 5.62, 9.16 and 3.35, P<0.05）. LL/Cr in the peripheral regions adjacent to the lesions increased obviously in 1h and 3h. NAA/Cr between the center and marginal regions showed statistical difference in 3, 6, 12h （t=-3.15, -3.66, -2.75 respectively, P<0.05）. LL/Cr between the center and marginal regions showed statistical difference in 1, 3, 6h （t=5.37, 4.47, 2.40 respectively, P<0.05）. No abnormal findings were detected on conventional MRI and DWI in 9 cats in operation group. MRS curve showed symmetry both sides and no obvious LL peak observed in all time point. Pathologic examination showed the lesions were mainly vasogenic edema, followed by necrosis with venous hemorrhagic infarction in 12h. No abnormal changes were observed in sham operation group. Conclusion A reduction of NAA, Cho, Cr and significant increase of LL are the main characteristic of the brain parenchymal lesions and MRS has great value in investigating the changes of the metabolites and the pathogenesis of the brain parenchymal lesions in cerebral venous occlusion.Part Ⅳ The preliminary application of MR diffusion tensor imaging and fiber tractography in acute experimental cerebral venous occlusionObjective To evaluate a model of acute cerebral venous occlusion with MR diffusion tensor imaging （DTI）, and to evaluate the value of DTI in observing diffusion regularity of the brain parenchymal lesions and the integrity of white matter fiber tracts. Methods Thirty cats were randomly divided into 2 groups, including operation group （n=24） and sham operation group （n=6）. Operation group were performed by injection of the cellulose acetate polymer （CAP） solution into the superior sagittal sinus （SSS）. Conventional MRI and DTI were continually performed at an interval of 1, 3, 6, 12, 24 and 48h after operation for each group to observe the brain parenchymal lesions, parametric maps were reconstructed, average diffusion coefficient （AvgDC） and fractional anisotropy （FA） were measured in the lesions and calculated the ratio to the contralateral corresponding regions, the integrity and connectivity of white matter tracts were showed by fiber tractography （FT）. Pathology examination were compared with MR data. Results In operation group, the brain parenchymal lesions were detected in 15 cats. Compared with contralateral corresponding regions, AvgDC values decreased in 1h, increased in 3h and increased obviously in 12h. FA values were decreased in all time point after operationon. AvgDC and FA of the lesions and the contralateral corresponding regions showed significant difference （P<0.005）. The AvgDC ratio and FA ratio showed significant difference （F=62.07 and 9.37 respectively, P<0. 05）. FT showed displayment of white matter fiber tracts and running through the lesions in 1h, damage or disruption in 6h and breaking in the edge of the lesions in 12h. Pathologic examination showed the lesions were cytotoxic edema in 1h, mainly vasogenic edema in 3h, followed by necrosis with venous hemorrhagic infarction in 12h. No abnormal changes were observed in sham operation group. Conclusion DTI can clearly depict and assess quantitatively the dynamic changes of brain parenchymal lesions in acute cerebral venous occlusion, FT is better in displaying damage or displacement of white matter fiber tracts than conventional MRI.更多还原