多发性硬化的磁共振成像研究

【作者】 王芳；

【导师】 金征宇； 陆菁菁； 冯逢；

【作者基本信息】 中国协和医科大学 ， 影像医学与核医学， 2009， 博士

【摘要】 目的建立实验性变态反应性脑脊髓炎(Experimental Allergic Encephalomyelitis,EAE)大鼠模型,为进一步研究多发性硬化(Multiple Sclerosis,MS)奠定基础。方法雌性Lewis大鼠44只随机分为模型组27只和对照组17只。采用免疫诱导法,模型组注射豚鼠脑脊髓匀浆和完全福氏佐剂(Complete Freund’s adjuvant,CFA)。对照组注射生理盐水和CFA。每天观察两组大鼠体重变化和临床症状。在不同时间点取大鼠脑组织,行HE染色及髓鞘染色,光镜下观察炎症细胞浸润及髓鞘脱失情况。结果EAE组大鼠免疫后15-30天出现临床症状,发病率为22/27。组织病理学证实大鼠脑组织内出现炎细胞浸润和脱髓鞘改变。对照组大鼠未出现临床症状,组织病理学未见异常。结论以豚鼠脑脊髓匀浆免疫雌性Lewis大鼠,可成功诱导EAE模型,发病率高、模型稳定,可作为研究MS的理想动物模型。目的探讨磁共振对比剂超小型超顺磁性氧化铁粒子(USPIO)增强磁共振(MR)检出实验性变态反应性脑脊髓炎(EAE)动物模型病变的敏感性及其增强病灶的磁化传递率(MTR)的变化。方法11只EAE组大鼠及10只对照组大鼠行常规T1加权像(T1WI)、T2加权像(T2WI)、三维T1磁化传递(3D T1 MT)、三维T1非磁化传递(3D T1 no MT)、钆喷酸葡胺注射液(Gadopentetate Dimeglumine Injection)增强T1WI及USPIO增强T2WI扫描。计算USPIO及Gd增强检出EAE病变的敏感性、EAE组大鼠第1次出现USPIO异常强化的区域及前一次扫描相应区域的MTR。大鼠脑组织行HE、髓鞘及普鲁士蓝铁染色。结果Gd对比剂增强扫描未能发现EAE大鼠脑内异常对比增强灶,USPIO增强扫描显示11只大鼠脑内均有异常沉积。EAE组大鼠USPIO异常强化区的MTR值与出现强化前同一区域的MTR值相比差异具有显著性(P<0.05)。USPIO强化区可见炎细胞浸润及脱髓鞘改变,普鲁士蓝铁染色结果阳性。对照组大鼠MR平扫及增强扫描无阳性显示。结论USPIO增强MR检出EAE病变的敏感性高。与USPIO增强扫描相结合,磁化传递成像能够提示EAE病变的性质。目的比较双翻转恢复序列(Double Inversion Recovery,DIR)、液体衰减翻转恢复序列(Fluid-Attenuated Inversion Recovery,FLAIR)、T2快速自旋回波序列(T2-weighted Spin Echo,T2 FSE)检测多发性硬化(Multiple Sclerosis,MS)病变的敏感性。方法MS患者13例,男性2例,女性11例,年龄范围20-62岁,平均36岁。与之年龄、性别匹配,无神经系统相关疾病的志愿者13例,男性2例,女性11例,年龄范围22-60岁,平均36岁。患者及对照组分别行DIR、FLAIR、T2 FSE序列扫描。根据皮质内、皮质旁、深部灰质、灰白质混合区、脑室周围白质、深部白质、幕下7个部位来分类和计数病变。将DIR检测病变的数目同FLAIR、T2 FSE比较。在3个序列上测量病变和看似正常灰质、看似正常白质及脑脊液间的对比。使用配对t检验进行统计学分析。P<0.05有统计学意义。结果DIR、FLAIR、T2 FSE检出病变总数分别为709、627、535。DIR较FLAIR增加82个(P=0.003),较T2 FSE增加174个(P=0.001)。DIR检出幕下病变的数目为58个,DIR较FLAIR增加48个(P=0.001),较T2 FSE增加20个(P=0.140)。在幕上,DIR检出皮质内、皮质旁、灰白质混合区、脑室周围白质、深部灰质及深部白质病变数目为82、4、151、103、9、302;DIR较FLAIR分别增加67(P=0.004)、-225(P=0.031)、149(P=0.022)、-41(P=0.176)、-16(P=0.251)、100(P=0.292);DIR较T2 FSE分别增加82(P=0.002)、-119(P=0.104)、141(P=0.019)、15(P=0.092)、-11(P=0.497)、46(P=0.419)。DIR病变和看似正常灰质、病变和看似正常白质间的对比较FLAIR高(P=0.000;P=0.000)、DIR病变和脑脊液间对比较FLAIR低(P=0.109);DIR病变和看似正常白质、病变和脑脊液间对比较T2 FSE高(P=0.000;P=0.000)、DIR病变和看似正常灰质间对比较T2 FSE低(P=0.145)。结论DIR增加幕下及皮质内病变的检出率,更好地区分皮质内、皮质旁及灰白质混合区病变。DIR病变对比高,是检出MS脑部病变的敏感MR序列。目的研究多发性硬化(Multiple sclerosis,MS)病人脑组织部分各向异性(fractionalanisotropy,FA)值的变化。方法MS患者13例,男性2例,女性11例,年龄范围20-62岁,平均36岁。年龄、性别与之匹配,无神经系统相关疾病的志愿者13例,男性2例,女性11例,年龄范围22-60岁,平均36岁。患者及志愿者均行MR检查,包括MR常规序列及扩散张量成像(Diffusion Tensor Imaging,DTI)序列。将感兴趣区分别放在斑块、斑块边缘、斑块周围看似正常白质及对照组白质测量FA值.将感兴趣区分别放在MS及对照组看似正常胼胝体膝部、体前部、体后部、压部测量FA值。统计学分析使用独立样本t检验,p<0.05有统计学意义。结果MS病人42个斑块平均FA值为0.21,斑块边缘平均FA值为0.35,斑块周围看似正常白质平均FA值为0.49,对照组白质平均FA值为0.61。与对照组白质比较,斑块(P=0.000)、斑块边缘(P=0.000)及斑块周围看似正常白质(P=0.000)FA值减低。MS病人胼胝体膝部(0.65±0.05)、体前部(0.48±0.03)、体后部(0.52±0.03)和压部(0.73±0.05)FA值较对照组相应部位(0.75±0.04、0.71±0.05、0.74±0.04、0.80±0.03)减低(p值均为0.000)。结论DTI能早期检出MS病人看似正常白质(Normal-Appearing White Matter,NAWM)、看似正常胼胝体的隐匿性损伤,对MS的研究比常规MR成像序列更有效。更多还原

【Abstract】 ObjectiveTo establish rats model of experimental allergic encephalomyelitis for further study of multiple sclerosis.Methods44 female Lewis rats were randomly divided into experimental allergic encephalomyelitis group(27) and control group(17).The experimental allergic encephalomyelitis model was established by immunization with guinea pig cerebrospinal homogenate and Complete Freund’s adjuvant.The control group rats were injected normal saline and Complete Freund’s adjuvant.The change of weight and clinical symptom of both groups rats were observed everyday.The samples of brain tissue in both group rats were taken at different time points.Hematoxylin and Eosin(HE) staining and myelin staining were performed.Inflammatory cells infiltration and demyelination were observed under light microscope.ResultsThe clinical symptoms appeared in experimental allergic encephalomyelitis group rats from 15 to 30 day after immunization.The incidence was 22/27.The infiltration of inflammatory cells and demyelination of brain tissue in experimental allergic encephalomyelitis rats were observed histopathologically.No clinical symptoms appeared and no histopathological abnormality were observed in control rats.ConclusionThe animal model of experimental allergic encephalomyelitis was successfully established with guinea pig cerebrospinal homogenate in Lewis rats.The model is stable and high in incidence and can be used to study multiple sclerosis. ObjectiveTo explore the sensitivity of magnetic resonance contrast agent ultrasmall superparamagnetic iron oxide(USPIO) enhancement scan in detecting experimental allergic encephalomyelitis lesions and the change of magnetization transfer of USPIO enhancement lesions in the animal model of experimental allergic encephalomyelitis (EAE).MethodsThe routine T1-weighted imaging,T2-weighted imaging,three dimensional T1 magnetization transfer,three dimensional T1 No magnetization transfer,Gd-DTPA (Gadopentetate Dimeglumine Injection) enhancement,and USPIO enhancement scan were performed in 11 EAE rats and 10 control rats respectively.The sensitivity of USPIO and Gd-DTPA enhancement in detecting the lesions in EAE rats was calculated. Magnetization transfer ratio(MTR) of USPIO enhancement area for the first time in EAE rats and MTR of the same area of the last scan were calculated respectively.HE, myelin and prussian Fe staining of brain tissues were performed.ResultsNo abnormally enhanced lesions were showed in EAE rats’ brain in Gd-DTPA enhancement scan,while abnormally enhanced lesions were showed in 11 EAE rats’ brain in USPIO enhancement scan.The MTR value of USPIO enhancement area for the first time was significantly different from MTR of the same area of the last scan in EAE rats(P<0.05).Inflammation cells and demyelination lesions were found in USPIO enhancement area histopathologically.The result of prussian Fe staining were positive. There were no positive findings in control rats.ConclusionThe sensitivity of USPIO enhancement scan in detecting EAE lesions was high.MT imaging,together with USPIO enhancement scan,was helpful to determine the features of the EAE lesions. ObjectiveTo compare the sensitivity of double inversion recovery with fluid-attenuated inversion recovery and T2-weighted Fast Spin Echo imaging in detecting multiple sclerosis lesions.MethodsMR examination including DIR,FLAIR and T2 FSE sequences was performed in 13 patients with MS(11 females,2 males,age ranged from 20 to 62 years,average age 36 years) and 13 age and gender-matched healthy volunteers(11 females,2 males,age ranged from 22 to 60 years,average age 36 years).Lesions were categorized on the basis of 7 anatomic regions:intracortical,juxtacortical,deep gray matter,mixed white-gray matter,periventricular white matter,deep white matter and infratentorial brain tissue and the number of lesions was calculated accordingly.The numbers of lesions detected by DIR in different regions was compared with those detected by FLAIR and T2 FSE sequences.The contrasts between lesions and normal-appearing gray matter, normal-appearing white matter and CSF in patient group were measured in 3 sequences respectively.The statistical differences were assessed using the t test for matched pairs.P values < 0.05 were considered as statistically significant.ResultsThe total numbers of lesions shown by DIR,FLAIR and T2 FSE were 709,627 and 535 respectively.There were gains of 82 and 174 in DIR compared with the FLAIR(P= 0.003)and T2 FSE(P=0.001) respectively.DIR depicted 58 infratentorial lesions, increasing 48 and 20 compared with the FLAIR(P=0.001) and T2 FSE(P=0.140).In the supratentorial brain,DIR detected 82 intracortical lesions,4 juxtacortical lesions,151 mixed gray-white matter lesions,103 periventricular lesions,9 deep gray matter lesions and 302 deep white matter lesions.There were gains of 67(P=0.004)、-225(P=0.031)、 149(P=0.022)、-41(P=0.176)、-16(P=0.251)、100(P=0.292) than FLAIR and 82(P =0.002)、-119(P=0.104)、141(P=0.019)、15(P=0.092)、-11(P=0.497)、46(P=0.419) than T2 FSE accordingly.The contrasts between lesions and normal-appearing gray matter and between lesions and normal-appearing white matter in DIR were higher than FLAIR(P=0.000;P=0.000).The contrast between lesions and CSF in DIR was lower than FLAIR(P=0.109).The contrasts between lesions and normal-appearing white matter and between lesions and CSF in DIR were higher than T2 FSE(P=0.000;P= 0.000).The contrast between lesions and normal-appearing gray matter in DIR was lower than T2 FSE(P=0.145).ConclusionDIR was able to increase the detection of infratentorial and intracortical lesions and improved categorization of intracortical,juxtacortical and mixed white-gray matter lesions.With higher lesions contrast ratio,DIR was more sensitive MR sequence in detecting MS lesions in brain. ObjectivesTo investigate the change of fractional anisotropy values of brain in patients with multiple sclerosis.Methods13 patients with MS(11 females,2 males,age ranged from 20 to 62 years,average age 36 years) and 13 age and gender-matched controls(11 females,2 males,age ranged from 22 to 60 years,average age 36 years) without nervous system disease were studied. Conventional MR imaging protocols and diffusion tensor imaging were performed.The regions of interest were placed on the plaques,peri-plaque regions,normal-appearing white matter around the plaques in MS patients and in white matter around lateral ventricle in control group.The FA values of both MS patients and the controls were measured.The regions of interest were placed on four different portions of the normal-appearing corpus callosum,namely genu,anterior and posterior portion of the body and splenium in both groups.The FA values of both MS patients and the controls were measured respectively.The statistical analysis was performed with independent sample t test and p<0.05 was considered significant statistically.ResultsThe average FA value of 42 plaques,peri-plaque regions and NAWM in MS patients was 0.21,0.35 and 0.49 respectively.The average FA value of white matter of control was 0.61.There were significant differences of FA values in plaques(p=0.000), peri-plaque regions(p=0.000),NAWM near the plaques(p=0.000) compared with the white matter in the control group.The FA values in the genu(0.65±0.05),anterior body(0.48±0.03),posterior body (0.52±0.03) and splenium of corpus callosum(0.73±0.05) were lower in the MS patients in comparison with the FA value(0.75±0.04、0.71±0.05、0.74±0.04、0.80±0.03) in corresponding areas of corpus callosum in controls(p=0.000、0.000、0.000、0.000,respectively). ConclusionDTI could show the occult injury of the NAWM and normal-appearing corpus callosum of MS patients in the early phase of disease and was considered more effective than conventional MR imaging sequences in studying MS patients.更多还原