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，该计划有两个基本目标：(1)将候选人发展成为新型高分辨率磁共振成像技术和阿尔茨海默病（AD）神经病理学的强大独立研究者；(2)定义体外磁共振成像和伴随神经病理学的参数，并将两种不同的介质联系起来。候选人渴望继续进行广告相关的研究，并在她的培训计划中增加一种新的方法。主要培训目标将集中在三个方面：(1)应用新的离体神经成像数据采集技术；(2)阿尔茨海默病病例的神经病理评估和神经病理标志物和细胞死亡的定量分析；(3)将离体成像应用于3D重建和纤维束造影。该提案的导师和顾问以及Athinoula A. Martinos生物医学工程中心和马萨诸塞州阿尔茨海默病研究中心的培训环境将在这些领域提供出色的指导。该候选人希望发展先进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大的神经病理学和定量分析，以发展针对老龄化人口的持久研究项目，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。本研究拟将新型超高场、高分辨率离体成像与阿尔茨海默病的神经病理评估相结合，以确定阿尔茨海默病病例的离体成像参数，并确定离体图像是否遵循阿尔茨海默病神经病理中的严重程度分期，以及弥散张量成像（DTI）指标是否反映颞叶神经退行性变，特别是穿透通路。样本将从马萨诸塞州阿尔茨海默病研究中心接收。神经影像学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：在临床和神经病理诊断的AD病例中，利用组织学确定离体MRI的层次。目的2：利用DTI确定白质变性对穿孔通路的影响。目的3：确定T2*序列在离体成像中的作用及其与神经病理标志物的关系。拟议的研究和培训计划将在阿尔茨海默病的诊断和治疗方面产生新的应用。

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.