脑干白质纤维连接的概率性图谱

The small and compact both structurally and functionally brainstem contains many critical structures but is a challenging area to study with neuroimaging and in neurosurgery. Fiber pathways in the brainstem are critically important for sensory and motor functions as well as consciousness and cognition, and connect nuclei implicated in the pathogenesis of a wide spectrum of neurological disorders including Alzheimer’s disease(AD), Parkinson’s disease(PD) and multiple sclerosis. The exploration of white matter fibers connectivity of brainstem is considered as an important scientific issues to be solved urgently in present. However, with the limitation of data quality and imaging process methods, there are few studies about quantitive analysis of the brainstem white matter fibers in vivo.. A total of 200 healthy young subjects (100 males and 100 females) will be included in this study. High resolution three-dimensional structural MR images and multi-shell high angular resolution diffusion imaging (HARDI) data will be acquired on a 3.0Tesla SIEMENS MRI scanner. After image preprocessing, the fiber orientation distribution (FODs) will be computed using a novel algorithm and the precise and higher resolution tract density images (TDI) will be reconstructed. The region of interest (ROIs) of the brainstem tracts will be labeled referenced with the histological staining sections data. Some advanced techniques and well-validated image analysis methods e.g. 3D computer visualization, tractography and tract reconstruction based on the ROIs will be performed to explore the three-dimensional anatomical locations of individual tracts and their spatial positions relative to adjacent structures. And some ideal methods of image registration, probability distribution calculation of fibers and brain atlas construction will be used to construct a comprehensive population-based probabilistic atlas of brainstem connectivity. Our results will be a novel tool in the neuroimaging studies and neurosurgery navigation, and will be useful for us to understand the complicated structure and function of the brainstem and the pathogenesis of implicated neurological disorders. It also will provide detailed anatomical basis for the diagnosis and treatment of the brainstem disease.

脑干结构功能紧凑，是脑科学研究与神经外科手术中最具挑战性的区域，其白质纤维束不仅对人的感觉、运动、意识、认知等功能非常重要，亦与许多神经疾病的发病机理密切相关。脑干白质纤维连接是当前亟需解决的重要科学问题，但由于数据质量和图像处理技术等限制，活体脑干纤维束的定量研究甚少。. 课题选用200例（男女各半）健康青年的3.0T结构MRI和多球壳高角分辨率扩散成像(multi-shell HARDI)数据，计算纤维方向分布(FODs)，以组织学染色数据为参照，利用计算机三维可视化、基于ROIs的纤维束成像和重建等技术研究脑干纤维束的空间位置和毗邻关系；用图像配准、概率性分布计算和图谱构建等方法建立脑干白质纤维连接的概率性图谱并进行验证。以期为神经影像学研究提供工具，帮助我们深入探索脑干复杂的结构和功能，探明相关神经精神疾病的发病机理，为涉及脑干疾病的诊治提供详实的解剖学依据。

脑干是脑科学研究与临床手术中最具挑战性的区域，弄清其结构和功能是脑计划的重要组成部分。脑干白质纤维对人的感觉、运动、认知等功能非常重要，而且与许多神经疾病的发病机理密切相关。目前关于人脑干结构与功能，尤其是纤维连接的研究极度缺乏。. 本研究选用高分辨率多模态影像学数据，以组织学染色图像为参照，利用纤维束成像和形态学分析的技术，构建脑干纤维束的概率性分布图谱，探索脑干内核团与大脑结构的纤维连接，以及脑干在老化过程中的形态学改变。我们利用Freesurfer等软件对三维结构MRI数据进行处理，利用球谐函数计算DTI图像的纤维方向分布（FODs），对FODs进行纤维束追踪，获得高分辨率、高结构对照的纤维密度图（TDIs），以基于ROI的纤维追踪技术对脑干内的主要纤维束进行概率性追踪和三维重建，并建立概率性白质纤维图谱。以蓝斑与内侧内嗅皮质为感兴趣区，利用MRTrix软件对纤维束进行概率性追踪和三维重建，建立蓝斑和内侧内嗅皮质纤维连接的概率性图谱。以此为模板计算并分析阿尔茨海默病人的相关纤维环路，发现随着AD病情的加重，纤维的完整性逐渐下降。. 除此之外，扩展的内容还有：1，利用结构MRI数据和形态分析方法探索老化过程中脑干形态的变化规律；2，利用冰冻切片和染色技术获取脑干连续组织学切片数据；3，利用结构MRI数据探索中外人脑不对称性的差异；4. 利用多模态影像学数据探索参与恋爱的脑区以及恋爱对大脑结构和功能的影响；5. 利用神经突定向弥散和密度成像（NODDI）方法对新生儿DTI数据进行分析并检测皮层微结构改变；6. 利用DTI数据探索上纵束三条分支的纤维形态和连接特征。本课题发表论文9篇，其中高质量SCI论文8篇，参加国际会议并作报告2次，参加国内会议并作报告5次，申请国家专利1项；累计培养博士后和研究生10人次。 . 本项目的研究成果能够帮助科研人员和临床医生深入了解脑干复杂的结构和功能，探索相关神经精神疾病的发病机理，为涉及脑干疾病的诊断和治疗提供详实的解剖学依据。

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