Diffusion Tensor Imaging of White Matter Change in AD

描述(申请人提供)：AD患者脑白质改变的弥散张量成像。这项职业发展申请描述了一个具有两个主要目标的综合研究和培训阶段：(1)通过应用先进的神经成像技术和补充的神经病理学研究，将候选人发展成为阿尔茨海默病(AD)神经病理学研究的强大和独立的研究人员，以及(2)确定AD中白质(WM)变性对患者临床特征的独特贡献。应聘者热衷于继续AD相关研究，并在此研究计划中增加新的培训。近期的培训目标将集中在三个研究领域：(1)新的神经成像数据采集技术在研究神经病理学中的应用，(2)AD的神经病理评估和定量神经病理学技术，以及(3)临床研究和多变量数据的高级统计分析程序。这项提议的导师/顾问以及阿蒂努拉·A·马蒂诺斯生物医学成像中心和马萨诸塞州阿尔茨海默病研究中心(MADRC)的培训环境将确保在这三个领域提供一流的指导。候选人期望将这一基础应用于AD的高级成像方案和神经病理学，以开发一个强大的研究计划，旨在充分整合这些不同的领域，以更好地了解AD的病理生理学。 这项拟议的研究将把新的白质微结构扩散张量成像(DTI)测量方法与测量灰质形态特征的先进方法相结合，以确定与正常衰老相比，白质变性在AD中是否不同，以及当控制灰质退变时，WM退变是否对AD症状的特定方面有贡献。患者将通过MADRC招募。成像数据将与认知和临床测量(包括记忆和痴呆症严重程度)相关。本研究的具体目的是：目的1.确定AD患者WM变性模式与正常衰老模式的差异。目的2.明确白质退行性变与灰质退行性变的关系。目的3.确定西医变性对患者临床特征的独特贡献。因此，拟议的综合培训和研究计划可能会导致对WM变性对AD临床后遗症的独特贡献的新见解。

DESCRIPTION (provided by applicant): Diffusion Tensor Imaging of White Matter Change in AD. This Career Development application describes an integrated research and training period with two primary goals: (1) the development of the candidate into a strong and independent researcher in the study of the neuropathology of Alzheimer's disease (AD) through the application of advanced neuroimaging techniques and complementary neuropathology studies and (2) to determine the unique contribution of white matter (WM) degeneration in AD to the clinical profile of patients. The candidate is enthusiastic to continue AD-related research and to add new training to this research program. Immediate training goals will focus on three domains of study: (1) the application of novel neuroimaging data acquisition techniques to study neuropathology, (2) neuropathological assessment of AD and quantitative neuropathology techniques, and (3) advanced statistical analysis procedures for clinical research and multivariate data. The Mentors/Advisors on this proposal and the training environment of the Athinoula A. Martinos Center for Biomedical Imaging and the Massachusetts Alzheimer's Disease Research Center (MADRC) will assure superb instruction in the three fields. The candidate expects to apply the foundation in advanced imaging protocols and neuropathology of AD to develop a strong research program aimed at fully integrating these disparate domains to better understand AD pathophysioiogy. The proposed research will integrate novel diffusion tensor imaging (DTI) measures of WM microstructure with advanced methods for measuring morphological properties of gray matter to determine whether WM degeneration differs in AD compared to normal aging, and whether WM degeneration contributes to specific aspects of AD symptomology when controlling for gray matter degeneration. Patients will be recruited through the MADRC. Imaging data will be related to cognitive and clinical measures (including memory and dementia severity). The Specific Aims of this research are to: Aim 1. Identify differences in the patterns of WM degeneration in AD compared to normal aging. Aim 2. Identify the relation between WM degeneration and gray matter degeneration. Aim 3. Identify the unique contribution of WM degeneration to the patient's clinical profile. Thus, the proposed integrated training and research program could lead to novel insights about the unique contribution of WM degeneration to the clinical sequel of AD.