Magnetic resonance imaging (MRI) has emerged as a powerful tool for soft tissue imaging of static and time sensitive biological events in real time allowing the exploration of novel medical techniques. With the advancement of MRI technology the microimaging of tissue samples has become possible as a means to further enhance our understanding of disease processes and move forward testing and validation of innovative therapeutic strategies. The biological process associated with Alzheimer's disease (AD) is under constant scrutiny and as such the determination of disease therapeutic strategies has remained elusive. The histo-pathological basis of MR imaging techniques and their association to disease processes is not entirely understood in AD. This research focuses on the utilization of magnetic resonance imaging to pursue the underlying mechanism and histo-pathological basis of MR relaxation associated with neural tissue alterations in Alzheimer's disease. There is a body of evidence supporting the hypothesis that Alzheimer's disease is not only a cortical gray matter (i.e. neuronal) disease but also one of cortical and sub-cortical white matter integrity. Recent research has shown that white matter alterations are present in the AD brain and are found in regions known to form beta-amyloid plaques. Regions the myelinate later during neural development have been found to development beta-amyloid plaques early in the disease process while regions that myelinate earlier are largely spared until later in Alzheimer's progression. This phenomena is not currently understood and frameworks the involvement of myelin in the AD process. A gap exists within the imaging field in linking the cause and interpretation of structural and anatomical MRI metrics in relation to alterations in micro- and ultra-structural patterns due to disease state. Studies have ostensibly reported the relation of MRI image metrics to the Alzheimer's disease state, however the exact anatomic-pathologic correlates of MRI aberrations remains unclear. This results in a fundamental concern when using structural MRI findings in the clinical interpretation of disease processes without direct knowledge of the relationship between image contrast and cyto-architecture.
The aims of this research involve the microscopic magnetic resonance and subsequent histological evaluation of early and late myelinating cortical white matter composition and integrity in relation to Alzheimer's disease pathology. Alzheimer's and control tissue sections will be MR imaged with previously established histological methods along with the utilization of various histological examination techniques. The objective being to histologically MR image and microscopically evaluate white matter in AD cortical tissue, in support of the hypothesis that cortical white matte and related microstructure is altered in the AD process, reviewable with MR imaging, and can be utilized in early diagnosis determination and tracking of disease progression in support of a biomarker of disease progression.

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Utilizing structural MRI findings in the clinical interpretation of Alzheimer's disease processes requires the direct knowledge of the relationship between MR image metrics and cyto-architecture. This application will directly determine the cause of Alzheimer's white matter abnormalities visible on MR images to fill this fundamental gap and drive the creation of biomarkers for early AD detection that are currently unavailable.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
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Clinical Neuroscience and Neurodegeneration Study Section (CNN)
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Hsiao, John
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Pennsylvania State University
Schools of Medicine
United States
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