Magnetic Resonance Microscopy of Alzheimers Disease Pathology

描述(由申请者提供)：这份职业发展申请描述了一项研究和培训相结合的计划，该计划有两个基本目标：(1)将候选人发展成为新的高分辨率磁共振成像技术和阿尔茨海默病(AD)神经病理学的强大和独立的研究员，以及(2)定义体外磁共振成像和伴随的神经病理学的参数，并将这两种不同的媒介联系起来。这位候选人渴望继续与AD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部分：(1)新的体外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评估，以及神经病理标记物和细胞死亡的定量分析，以及(3)将体外成像应用于3D重建和纤维束成像。这项提议的导师和顾问以及阿蒂努拉·A·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的培训环境将在这些领域提供出色的指导。候选人希望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大的神经病理学和量化分析，以开发针对我们老龄化人口的持久研究计划，并将阿尔茨海默病的神经病理学和高分辨率神经成像这两种不同的技术结合在一起。这项研究将结合新的超高场、高分辨率的体外成像与AD的神经病理学评估，以描绘AD患者的体外成像参数，并确定体外成像是否遵循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，特别是穿孔通路。样本将从马萨诸塞州阿尔茨海默病研究中心收到。神经影像数据将与临床和神经病理数据相关联。本研究的具体目的是：目的1：在临床和神经病理诊断为AD的病例中，利用组织学确定体外MRI的层级。目的2：应用弥散张量成像(DTI)确定穿支通路中白质变性的影响。目的3：确定体外成像中的T2*序列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氏症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.