【作者】 左传涛；

【导师】 林祥通；

【作者基本信息】 复旦大学 ， 影像医学与核医学， 2004， 博士

【摘要】 大脑可塑性的研究是目前神经科学研究的前沿之一，医学研究发现神经细胞损伤后在一定条件下是可以再生，在这种“脑可塑性理论”基础上建立的“技能恢复神经学”证实：经过神经康复，残存的神经功能可以复活、重组，病人可因此获得最大限度的功能恢复，PET这种脑功能成像技术的应用使我们能够从活体和整体水平来研究脑，好比窥探脑的窗口，可以在无创伤条件下了解到人的思维、行为活动时脑的功能活动，从整体阐明疾病状态下脑功能区的重建，不仅从理论方面提高对脑自主功能的认识，更有助于采取相应的措施促进疾病状态下脑功能最大限度的恢复，又例如在神经变性疾病的研究中（例如Alzheimer’s病），在早期阶段，即使CT和MRI未出现特异性异常改变，¹⁸F-FDG PET脑代谢显像都有可能出现与正常老龄化不同的表现，从而为早期药物介入干预、预防疾病的发展提供了客观依据。美国FDA已批准了治疗和干预AD的胆碱酯酶抑制物作为一个重大医药产业，这为脑功能变化检测（Brain Function Alteration Detection）技术平台提供了广阔的应用前景。本课题的主要目的是：（1） 以双侧丘脑底核（STN）慢性电刺激术（DBS）对帕金森病（PD）患者脑局部糖代谢影响为研究对象，建立脑PET功能影像学研究技术平台；（2） 以臂丛根性撕脱伤健侧C7移位术后的患者为研究对象，初步探讨周围神经损伤后脑的跨大脑半球重塑和可能机制；（3） 强迫症（OCD）内囊前肢毁损术后相关脑区葡萄糖代谢变化的研究；（4） 为本总课题后续的AD分题研究奠定方法学基础。 一、脑PET功能影像学研究技术平台的建立 目的：（本研究于2001年12月开始进行）根据病例来源实际情况，以双侧STN DBS对PD患者脑局部糖代谢变化为研究对象，开发相关软件建立脑PET功能影像学技术平台。方法：具有双侧肢体症状的晚期原发性PD患者10例，其中5例患者接受双侧STN DBS手术。10例PD患者和10例正常人均进行静止期FDG-PET检查，同时进行双侧STN DBS手术的5例患者，亦在术后1个月电刺激条件下，进行静止期FDG-PET检查，通过SPM统计学软件进行数据分析，比较晚期PD脑代谢的变化及STN DBS对脑内代谢的变化。结果：经Realign模块校正后，将DBS“开”状态下脑PET图像的空间位置调整与未DBS手术前的脑PET图脑PET功能影像学技术平台的建立及脑功能重塑研究中的应用像一致;经少I一化模块处理后，脑PET图像与rf:，lairach的空间坐标相对应;与正常对照组10例相比，晚期即患者脑内双侧海马、豆状核、丘脑以及中央前回代谢增加，前额时一运动区以及双侧顶枕部代谢减低:双侧STN DBS使PD患者左侧苍白球，右侧中脑以及双侧顶枕部、右侧前额叶辅助运动区的脑代谢明显增加，而双侧前额叶底部的代谢明显减少。结论:FD(i一PE1’图像的SPM分析可以显示晚期PD患者脑内异常代谢的脑区，并初步探讨双侧STN DBS治疗晚期PD的可能机制，本研究通过方法学各种条件的实验和质量控制、模型测试以及SPM方法学验证，提出脑PET图像的SPM分析可以作为脑功能变化研究的可靠、客观方法。二、全臂从撕脱伤健侧C7移位术后脑功能重塑研究（一）」E常人与全臂丛撕脱伤健侧C了移位术后未转型的患者脑葡萄糖代谢的比较 目的:应用FDG一PET可以显示左侧全臂丛撕脱伤患者脑内葡萄糖代谢减低的区域，在活体上显示周围神经损伤后脑内葡萄糖代谢变化的特点，为脑重塑研究提供基准的脑内功能区分布状态。方法:左侧个臂从C7移位术后男性患者6例 （未转型），}下常健康男性6例，分别行FDG一PET显像，应用SPM比较左侧全臂丛C7移位术后患者与正常对照组脑局部糖代一谢的变化。结果:与年龄、性别匹配的正常人相比，在左侧全臂丛撕脱伤患者脑内，右侧第工体感运动区（SMC，BA4）、右侧运动辅助区（SMA，BA6）、右侧感觉皮层（BA4O）、右侧基底节区（尾状核头和壳核）的葡萄糖代谢明显降低。结论:左侧全臂丛撕脱伤患者因为缺少感觉的传入和运动的传出，相应脑内的感觉和运动皮层葡萄糖代谢降低。（二）正常人运动一侧上肢后脑葡萄糖代谢发生变化的相关脑区 目的:局部糖代谢率反映了神经网络传入突触的活动，FDG一PET可以用来研究脑部的生理生化过程，本研究通过FDG一PET显像发现各功能脑区在上肢内夹动作时的葡萄糖代谢变化，从而显示脑内运动所涉及的相关脑区。方法:正常健康男性6例，先进行正常人静息脑FDG一PET显像，隔4个半衰期（约8小时）后行运动右侧上肢后脑FDG一PET显像，应用SPM对正常人静息状态下和运动上肢后的脑F’DG PET图像进行配对、检验统计分析，观察运动后脑内葡萄糖代谢增加的区域。结果:运动右侧上肢后脑内左侧大脑半球SMc（BAZ、队3和BA4）、BAS、左侧壳外白质、左侧丘脑、左侧脑干、双侧SMA（BA6），右侧SMC（BA4）、右侧BA了的葡萄糖代谢代谢增加，葡萄糖代谢增加以左侧相关脑区为明显。结论:运动右侧上肢可一以引起双侧脑功能相关皮层的变化，但仍以左侧脑皮层功能区为主，与其神经纤维投射双侧性（以对侧为主）解剖学基础相符。（三）全臂从撕脱伤患者健侧C7移位术后脑重塑机制的初步探讨 目的:本研究主要对左侧全臂丛撕脱伤(汀移位术后患者（未转型）患者进行更多还原

【Abstract】 Nowadays, the study on the plasticity of the brain is one of the hotspots in nerve scientific research. But the mechanism of the brain plasticity is not clear at present. A subject with significant meanings is how to make the use of brain plasticity to obtain the largest entent of functional recovery after nerve injury. The application of brain FDG-PET imaging tecnique makes it possible to study a whole and live brain and to understand the brain plasticity. Our study concentrates FDG-PET imaging of brain plasticity after nerve injury, which involves 3 parts as follows.Part I. Establishment of technical methods to study brain functionObjective Through establishing the technical methods to study the abnormal glucose metabolism in parkinson’ s disease, and the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism of advanced Parkinson’ s disease. Methods Ten advanced Parkinson’ s diseases patients and 10 age-matched healthy subjects underwent 18F~FDG/PET examinations at res ting-state . Five in the ten advanced Parkinson’ s disease patients with bilateral STN DBS underwent 2 times ’"F-FDG/PET examinations at resting-state preoperatively and one month postoperatively with STN stimulation respectively. Statistical parametric mapping (SPM) was used to investigate regional cerebral metabolism during STN stimulation in comparison with metabolism preoperatively. Results Compared to age-matched healthy subjects, the regional glucose metabolism increased in both hippocampus , thalamus, precentral cortex(BA6) and lentiform and decreased in both prefrontal motor area (BA46), parietal area in advanced PD cases. STN stimulation improved the clinical symptoms obviously for each patient and changedPETsignificantly: cerebral metabolism increased in left globus pallidus, upper brainst em (right midbrain), bilateral parietal -occipital cortex , and decreased in the bottom of both prefrontal cortex. Conclusion The SPM analysis of PET images can show the abnormal metabolism brain regions, and can investigate the mechanism of DBS. The SPM analysis of PET images can be used as standard methods of brain function study.Part II. The study of brain plascitity after peripheral nerve injury(?The brain metabolic differnce between the normal and the contra lateral C7 nerve root transfer after the peripheral nerve injury Objective To show The brain metabolic differnce between the normal and the contralateral C7 nerve root transfer after the peripheral nerve injury with 18FDG-PET imaging. Methods Six contralateral C7 nerve root transfer patients and sixth healthy subjects underwent 1SFDG PET examinations at resting state separately. SPM was used to investigate regional cerebral metabolic rate of glucose. Results SPM show the regional glucose metabolism decreased in right SMC(BA4), right parietal (BA40, right SMA (BA6), right caudate and putamen. Conclusion Because lack of the input nerve and output nerve fiber, the decreased brain regions were showed by FDG-PET in the contralateral C7 nerve root transfer patients. () Cerebral structures participating in upper limb movement in health subjectsObjective To show the brain functional regions participating in the upper limb movement in health subjects with 1SFDG~PET imaging. Methods Six healthy subjects underwent ISFDG PET examinations at resting state and activated state separately. SPM was used to investigate regional cerebral metabolic rate of glucose. Results SPM show the regional glucose metabolism increased in bilateral Brodmann6, bilateral Brodmann4, left Brodmann2, left BrodmannS, left BrodmannS, left extra-nucleus white matter, left thalamus, left brainstem and right Brodmann? after right upper limb movement, obviously in left brain region. Conclusion SPM can show the activated brain regions after upper limb movement in accord with the nerve transfer, and this is helpful to investigates brain functionPETreorganization.Cri)The mechanism of brain plasticity in the the contralateral C7 nerve root transfer after the peripheral n更多还原