实验性自身免疫性脑脊髓炎的MRI研究进展

实验性自身免疫性脑脊髓炎(EAE)是公认的研究人类多发性硬化(MS)的动物模型。MRI能提供大鼠中枢神经系统的高分辨率图像,在活体上动态监测EAE病变的演变过程。随着MR设备及MRI新技术的不断研发及应用,EAE大鼠的MRI研究将更好的诠释EAE病灶的病理生理演变过程,为探索MS病因、发病机制和评估疗效提供了一种重要的研究手段。     

依达拉奉对实验性小鼠自身免疫性脑脊髓炎的抑制作用

目的：研究依达拉奉对实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis , EAE）小鼠的抑制作用。方法将60只雌性C57BL/6小鼠随机分为3组：正常对照组、EAE组、EAE＋依达拉奉组,每组20只。正常对照组用PBS作为对照。后两组应用髓鞘少突胶质细胞糖蛋白35-55、完全福氏佐剂（ CFA）、结核分枝杆菌,制成的抗原乳剂进行造模。免疫2 d后,EAE＋依达拉奉组腹腔注射依达拉奉5 mg/（ kg· d）。3组均监测20 d,每日称重,观察小鼠的摄食和发病情况,并进行神经功能评分。20 d后取小鼠脊髓组织,进行病理学观察。结果 EAE组小鼠的发病率（80％）高于EAE＋依达拉奉组（45％）,差异有统计学意义（P＜0．05）。 EAE＋依达拉奉组神经功能评分各个时间点都低于EAE组,差异有统计学意义（P＜0．05）,其中,监测10 d后,EAE组神经功能评分（3．6±0．4）级;而EAE＋依达拉奉组评分为（1．3±0．5）级。 HE染色后发现,EAE组小鼠的脊髓内有大量的炎性细胞浸润,白质脱髓鞘改变明显。而EAE＋依达拉奉组小鼠有较少的炎性细胞浸润,且没有白质脱髓鞘改变。结论依达拉奉对EAE的保护作用可能与其清除自由基、减轻炎性反应有关。     

电针对实验性自身免疫性脑脊髓炎大鼠急性期脑组织IFN-γ、IL-4含量的影响

 目的 探讨电针治疗急性期实验性自身免疫性脑脊髓炎(EAE)的有效性及其作用机制.方法 采用豚鼠脊髓匀浆(GPSCH)与完全福氏佐剂(CFA)制成混合乳剂免疫Wistar雌性大鼠制备EAE模型,研究电针对急性期EAE大鼠脑组织IFN-γ、IL-4含量的影响,并通过神经功能评分观察电针治疗EAE的有效性.结果 电针组及激素组均能明显改善急性期EAE的临床症状,脑组织中IFN-γ的含量较模型组显著降低(P<0.05),IL-4的含量较模型组明显升高(P<0.05),且电针组和激素组之间没有差异.结论 电针治疗通过干预Th0细胞向Th2细胞分化,促进脑组织中IL-4含量提高,抑制了IFN-γ的含量,调节Th1/ Th2细胞的平衡.     

重组人粒细胞集落刺激因子对实验性自身免疫性脑脊髓炎小鼠的治疗作用

目的观察重组人粒细胞集落刺激因子（recombinant human granulocyte colony stimulating factor,rhG CSF）对实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis,EAE）小鼠的治疗效果并探讨相关机制。方法将40只小鼠随机分为2组,对照组10只不作处理,30只用髓鞘少突胶质细胞糖蛋白35-55（纯度＞95%）多肽诱发建立EAE小鼠模型,死亡6只,剩余24只随机分为模型组和治疗组,各组12只,治疗组皮下注射rhG-CSF,模型组给予同等量的生理盐水。治疗期间对3组小鼠进行神经功能评分和体重检测;治疗2周后,取脑和脊髓制作标本行病理观察,劳克坚劳蓝染色进行脱髓鞘评分;流式细胞仪检测调节性T细胞和自然杀伤细胞比例的变化;蛋白质印迹法检测EAE小鼠胶质纤维酸性蛋白和髓鞘碱性蛋白的表达。结果与模型组相比,治疗组小鼠神经功能评分显著降低,髓炎性细胞浸润评分和脱髓鞘评分降低;调节性T细胞显著增加,自然杀伤细胞显著减少;蛋白质印迹法的结果提示治疗组小鼠胶质纤维酸性蛋白表达量下降,而髓鞘碱性蛋白表达量明显高于模型组。结论rhG-CSF对EAE具有显著治疗效果。     

3.0T临床型MR多发性硬化大鼠颅脑成像的初步研究

目的：探索应用3.0T临床型MR设备进行多发性硬化（MS）大鼠颅脑成像的可行性。方法：用髓鞘少突胶质细胞糖蛋白多肽35-55（MOG35-55）致敏Lewis大鼠制备MS动物模型实验性自身免疫性脑脊髓炎（EAE）大鼠10只,正常对照组大鼠4只。3.0T临床型MR（Siemens Trio Tim）扫描仪配用正交腕关节线圈,行T2W、T1W和Gd-DTPA增强T1W的三维容积扫描,体素0.06mm3。结果：大鼠脑T2WI和T1WI具有较高的空间分辨率和对比度。胼胝体、小脑、新皮质和脑室等解剖结构显示清晰。MOG35-55-EAE大鼠病灶出现在脑和上段颈髓,呈斑片状,T2高信号、T1低信号,部分出现Gd-DTPA强化。结论：应用3.0T临床型MR设备可以获得高质量的大鼠颅脑MR图像,为小动物中枢神经系统疾病的实验研究提供了一种能广泛应用的无创性的活体体外监测手段。     

3.0T临床型MR多发性硬化大鼠脊髓成像的初步研究

目的：探索应用3.0T临床型MR设备进行多发性硬化（MS）大鼠脊髓成像的可行性。方法：用髓鞘少突胶质细胞糖蛋白多肽35-55（MOG35-55）致敏Lewis大鼠制备MS动物模型实验性自身免疫性脑脊髓炎（EAE）大鼠10只,正常对照组大鼠4只。3.0T临床型MR（Siemens Trio Tim）扫描仪配用正交腕关节线圈,行T2W、T1W和Gd-DTPA增强T1W的三维容积扫描,体素0.06-0.08mm3。结果：大鼠脊髓T2WI具有较高的空间分辨率,颈髓、胸髓和腰髓等节段显示清晰。脊髓灰质和白质的对比度较弱。MOG35-55-EAE大鼠病灶出现在颈髓和胸髓,矢状位重组图像显示病灶细节清晰,呈条片状,T2高信号,T1等信号,4个脊髓病灶均未见Gd-DTPA强化。结论：应用3.0T临床型MR扫描仪配备小正交腕关节线圈进行MOG35-55-EAE大鼠脊髓MR成像是可行的,为小动物脊髓疾病的活体体外监测提供了一种能广泛应用的无创性手段。     

USPIOs在动脉粥样硬化MR成像中的应用

超微型超顺磁性氧化铁颗粒（ultrasmall superparamagnetic iron oxides,USPIOs）是一种新型的磁共振对比剂,它具有两个非常重要的特性：即血中停留时间较长和被组织中巨噬细胞进一步地吞噬摄取。前者因能在数小时内使血管一直保持较高的信号强度而成为一种理想的磁共振血管成像（MRA）对比剂;后者特性使巨噬细胞显像成为可能。由于诸多疾病的病理改变中均富含巨噬细胞（包括中枢神经系统的吞噬性小胶质细胞）,研究者们应用USPIOs作为单核巨噬细胞系统特异性的MRI对比剂,对动脉粥样硬化斑块、脑中风、多发性硬化、脊髓损伤、脑肿瘤等病变做了大量深入的研究。笔者就USPIOs的生物学特性及其目前应用于动脉粥样硬化斑块MR成像的现状进行综述。     

恒河猴实验性变态反应性脑脊髓炎MR波谱与组织病理及超微结构改变的对照研究

目的　研究非人类灵长类实验性变态反应性脑脊髓炎 (EAE)磁共振波谱 (MRS)改变的组织病理学基础。方法　 9只恒河猴 ,用同源猴脑白质或纯牛髓鞘碱性蛋白 (MBP)与完全福氏佐剂(CFA)的混合剂皮下注射诱导EAE ,对其发病前后进行自身配对对照研究 ,定量分析N 乙酰天门冬氨酸 /肌酸 (NAA/Cr)、胆碱复合物 /肌酸 (Cho/Cr)的参数变化 ,通过光学显微镜及透射电镜观察相对应组织的病理及超微结构改变。结果　急、慢性EAE的MRS测定均有NAA/Cr下降 (t值分别为 68 66和5 69,P值均 <0 0 5) ,统计学上差异有显著性意义。两者超微结构均观察到了轴索的空泡样变性及脂褐素颗粒的增加 ;急性EAE组织学表现为明显的炎性反应、严重区域髓鞘破坏和消失。慢性EAE炎性反应较轻 ,以脱髓鞘改变为主。慢性EAE同时伴有Cho/Cr的增高 (t=3 48,P <0 0 5) ,统计学上差异也有显著性意义 ,超微结构具有明显的脱髓鞘改变。结论　MRS定量分析可用于判定EAE脑部病变分期及预测组织病理学改变特征     

磁化传递成像观察多发性硬化大鼠中枢神经系统病灶

目的：探索应用3.0T临床型MR设备进行磁化传递成像（MTI）观察多发性硬化（MS）大鼠中枢神经系统病灶的可行性。方法：用髓鞘少突胶质细胞糖蛋白多肽35-55（MOG35-55）致敏Lewis大鼠制备MS动物模型实验性自身免疫性脑脊髓炎（EAE）大鼠10只,正常对照组大鼠4只。3.0T临床型MR扫描仪配备小正交腕关节线圈,分别对大鼠脑和脊髓行T2W、T1磁化传递和T1非磁化传递三维容积扫描。利用工作站专业软件获得磁化传递率（MTR）图像。结果：成功建立MOG35-55-EAE模型大鼠10只。大鼠脑和脊髓的MTR图像具有较高的空间分辨率和对比度。MOG35-55-EAE病灶在T2WI上呈高信号,在MTR图像上表现为MTR值下降,呈低信号,在T1WI上呈低信号或者等信号。MTR图像对MOG35-55-EAE病灶检出率高,病灶显示清晰。对照组大鼠MR扫描未见异常。结论：应用3.0T临床型MR设备可以获得高质量的MOG35-55-EAE大鼠脑和脊髓MTR图像。MTI有望成为小动物中枢神经系统脱髓鞘疾病实验研究的体外监测手段。     

Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

Purpose Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4-iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with ¹²³I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated.Methods EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freunds adjuvant containing Mycobacterium butyricum. Biodistribution studies with ¹²³I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores.Results ¹²³I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1⁺ cells representing macrophages and microglia.Conclusion These results demonstrate the ability of ¹²³I-CLINDE to measure in vivo inflammatory events represented by increased density of PBRs and suggest that ¹²³I-CLINDE warrants further investigation as a potential SPECT marker for imaging of CNS inflammation.     

LAC-HSA-SPIO增强磁共振成像检测大鼠肝癌的实验研究

目的 :探讨利用肝细胞去唾液酸糖蛋白受体 (ASG受体 )介导的LAC HSA SPIO对比剂检测肝癌的可能性。方法 :建立二乙基亚硝胺诱导的大鼠肝癌模型 ( 8例 ) ,获平扫及注射LAC HSA SPIO ( 1.2mgFe/10 0g体重 )后大鼠肝脏双回波SE像 ( 2 0 0 0 /30～ 80 ) ,测定肝实质强化率 (PCE)和肝癌灶信号对比度 /噪声比 (CNR)。结果 :①注药后在T2 WI肝实质PCE为 71.8%± 16.3% ,癌结节为 10 .2 %± 4.8% (P <0 .0 1) ;②增强后PD WI上瘤结节CNR由平扫时 1.6± 0 .3上升至 8.2± 4.6(P <0 .0 1) ,T2 WI癌结节CNR由 4.7± 3.1上升至 8.9± 4.0 ( 0 .0 1

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Database for serial magnetic resonance imaging in multiple sclerosis

The unique sensitivity of magnetic resonance imaging (MRI) in detecting disease activity in multiple sclerosis (MS) and the objective nature of the information obtained suggest that MRI will be a useful and reliable way of monitoring treatment trials. There is a need to develop an appropriate database which would provide a standardised means of assessment, not only of MRI, but also of essential clinical information. As part of the program of Concerted Action in Multiple Sclerosis, funded by the Commission of the European Community (CEC), we have developed a database for recording serial brain MRI results. The database consists of core, entry and follow-up sections. Both entry and follow-up parts are subdivided into clinical, MR system and MRI data. We expect that the use of this database will maximise efficiency of MRI monitoring in MS treatment trials, particularly in multicentre studies.     

3.0T MR磁敏感加权成像对多发性硬化患者脑静脉的研究

目的 探讨磁敏感加权成像(SWI)在检查多发性硬化(MS)患者大脑内静脉及属支和深部髓静脉改变中的价值.方法 对43例MS患者和年龄、性别相匹配的43名健康志愿者行常规了MRI和SWI,在43例MS患者中,5例病程<0.5年,17例病程0.5-2.0年,21例病程>2.0年.SWI所得静脉图像应用MinIP处理后,南2名有经验的医师双盲法评定MS患者大脑内静脉及其主要属支和深部髓静脉的改变,并与对照组比较.统计学分析采用Kruskal Wallis H 检验和Wilcoxon秩和检验.结果 43例MS患者中,23例为活动期,20例为稳定期.(1)大脑内静脉及其主要属支评分:23例活动期、20例稳定期MS患者及43名健康志愿者分别为(1.96±0.71)、(1.25±0.44)及(3.00±0.00)分,三者间差异均有统计学意义(H=67.65,P<0.01);活动期和稳定期MS患者均较对照组降低,差异有统计学意义(Z值分别为-6.67、-7.76,P值均<0.01),而活动期与稳定期MS患者比较差异也有统计学意义(Z=-3.35,P<0.01).(2)侧脑室体旁深部髓静脉改变:38例病程>0.5年的MS患者(17例病程0.5～2.0年、20例病程>2.0年)侧脑室体旁深部髓静脉减少、变短;5例病程<0.5年的MS患者侧脑室体旁深部髓静脉增多、延长.(3)"穿通静脉"表现:23例活动期MS患者中,35个侧脑室体旁强化病灶内"穿通静脉"明显扩张、延长;20例稳定期MS患者中,80个侧脑室体旁末强化病灶内"穿通静脉"变细、变短,但在3例患者中,6个侧脑室体旁未强化病灶内"穿通静脉"扩张、延长.结论 SWI能显示MS患者人脑内静脉及其属支和深部髓静脉改变,对了解MS的发病机制及病理改变具有重要价值.

Abstract：

Objective To explore the value of susceptibility weighted imaging (SWI) in detecting the changes of cerebral internal veins and their tributaries.especially the deep medullary veins,in the patients with multiple sclerosis(MS).Methods Conventional MRI and SWI were performed in 43 MS patients and 43 healthy volunteers(control group).Two groups were matched on gender and age.In the MS patients.the course of disease was less than 0.5 year in 5 paticnts,between 0.5 year and 2.0 years in 17 patients and more than 2.0 years in 21 patients.SWI venograms were obtained by performing minimum intensity projection(MinIP)reconstruction.Comparing with the control group,the changes of the cerebral internal veins,their main tributaries and the deep medullar veins in the MS patients were evaluated by 2 experienced radiologists with double blind methods.Kruskal Wallis H analysis and Wilcoxon rank test were used for statistics.Results In the 43 patients,23 had active MS(active group),20 had chronic MS (chronic group).(1)The mean score of the cerebral internal veins and their main tributaries was(1.96±0.71)for 23 active MS patients,(1.25±0.44)for 20 chronic MS patients and(3.00±0.00)for the control group,respectively.There were significant differences among the three groups(H=67.65,P<0.01).And the mean scores in the active and chronic MS patients were lower than that in the control group (1.96±0.71 vs 3.00±0.00,Z=-6.67.P<0.01:1.25±0.44 vs 3.00±0.00,Z=-7.76,P<0.01),the mean score in the active MS patients was higher than that in the chronic MS patients(Z=-3.35,P<0.01).(2)The deep medullar veins were shortened or diminished in 38 MS patients whose course of disease were more than 0. 5 year, and increased and prolonged in 5 MS patients whose course of disease were less than 0.5 year. (3) The " penetrating veins " were dilated and prolonged in 35 periventricular enhanced lesions in the 23 active MS patients, and thin and short in 80 periventricular non-enhanced lesions in the 20 chronic MS patients. However, in 3 chronic MS patients, slightly expanded and prolonged "penetrating veins" were detected in 6 periventricular non-enhanced lesions. Conclusion SWI can reveal the changes of the cerebral internal veins and their tributaries, especially the deep medullary veins, in different stages of MS patients, providing important information for pathogenesis and pathological study for MS patients.