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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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National Institute on Aging Initial Review Group (NIA)
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Hsiao, John
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Massachusetts General Hospital
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