Magnetic Resonance Microscopy of Alzheimers Disease Pathology

描述（由申请人提供）：此职业发展申请描述了一个综合研究和培训计划，有两个基本目标：（1）将候选人培养成新型高分辨率磁共振成像技术和阿尔茨海默病（AD）神经病理学方面的强大而独立的研究者;（2）以定义离体磁共振成像和伴随的神经病理学中的参数，并将两种不同的介质相关联。候选人渴望继续AD相关的研究，并在她的培训计划中添加新的方法。主要培训目标将集中在三个组成部分：（1）新的离体神经成像数据采集技术的应用，（2）阿尔茨海默病病例的神经病理学评估和神经病理学标志物和细胞死亡的定量分析，以及（3）将离体成像应用于3D重建和纤维束成像。关于这个建议和Athinoula A培训环境的导师和顾问。马蒂诺斯生物医学工程中心和马萨诸塞州阿尔茨海默病研究中心将在这些领域提供出色的指导。候选人预计将发展先进的神经成像技术和数据分析的基础知识，并对阿尔茨海默病病例进行强有力的神经病理学和定量分析，以开发一个持久的研究计划，该计划针对我们的老龄化人口，并结合两种不同的技术，阿尔茨海默病的神经病理学和高分辨率神经成像。拟开展的研究将联合收割机新型超高场、高分辨率离体成像与AD的神经病理学评估相结合，以描述AD病例的离体成像参数，并确定离体图像是否遵循AD神经病理学中的严重程度分期，以及扩散张量成像（DTI）测量是否反映了颞叶神经变性，特别是穿通通路。将从马萨诸塞州阿尔茨海默病研究中心接收标本。神经成像数据将与临床和神经病理学数据相关联。本研究的具体目的是：目的1：在临床和神经病理学诊断的AD病例中，使用组织学识别离体MRI的层次结构。目的2：利用弥散张量成像（DTI）研究白色变性对穿支通路的影响。目的3：识别离体成像中的T2 * 序列并与神经病理学标记物相关。拟议的研究和培训计划将产生新的应用阿尔茨海默氏症的诊断和治疗。

DESCRIPTION (provided by applicant): This career development application describes a combined research and training program that has two fundamental goals: (1) the development of the candidate into a strong and independent investigator in novel high resolution magnetic resonance imaging techniques and neuropathology of Alzheimer's disease (AD) and (2) to define parameters in ex vivo magnetic resonance imaging and accompanying neuropathology and correlate the two different mediums. The candidate is eager to continue AD-related research and to add a new methodology to her training program. Primary training goals will concentrate on three components: (1) the application of novel ex vivo neuroimaging data acquisition techniques, (2) neuropathological assessment of Alzheimer's disease cases and quantitative analysis of neuropathological markers and cell death and (3) apply ex vivo imaging to 3D reconstruction and fiber tractography. The Mentors and Advisors on this proposal and the training setting of the Athinoula A. Martinos Center for Biomedical Engineering and the Massachusetts Alzheimer's Disease Research Center will provide excellent instruction in these areas. The candidate anticipates to develop the fundamentals in advanced neuroimaging techniques and data analysis and implement a strong neuropathological and quantitative analysis on Alzheimer's disease cases to develop an enduring research program that targets our aging population and incorporates the two diverse techniques, neuropathology of Alzheimer's disease and high resolution neuroimaging. The proposed research will combine novel ultra high field, high resolution ex vivo imaging with neuropathological assessment of AD to delineate the ex vivo imaging parameters in AD cases and to determine whether ex vivo images follow the staging of severity as in AD neuropathology and whether diffusion tensor imaging (DTI) measures reflect with the temporal lobe neurodegeneration, especially the perforant pathway. Specimens will be received from the Massachusetts Alzheimer's Disease Research Center. Neuroimaging data will be correlated to the clinical and neuropathological data. The Specific Aims of this research are: Aim 1: Identify the hierarchy in ex vivo MRI using histology in clinically and neuropathologically diagnosed AD cases. Aim 2: Identify the effect of white matter degeneration in the perforant pathway using DTI. Aim 3: Identify the T2* sequences in ex vivo imaging and relate to neuropathological markers. The proposed research and training program will yield novel applications to Alzheimer's diagnosis and treatment.