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While neurodegenerative conditions represent a rapidly growing medical and social problem worldwide, the definite diagnosis of the most common neurodegenerative pathologies such as Parkinson's disease (PD), Progressive Supranuclear Palsy (PSP), Lewy body disorders (LBD) and Alzheimer's disease (AD) generally is confirmed only by postmortem histological studies. Although each disorder presents with different symptoms histopathologically, characterization and differentiation of these conditions are difficult due to considerable overlap in clinical symptoms. To rule out other treatable causes, magnetic resonance imaging (MRI) at clinical field strengths is employed routinely in the evaluation of these conditions. MRI can provide three dimensional digital datasets based solely on endogenous contrast mechanisms that are sensitive to factors such as iron content, cellular density and white/gray matter ratios. However, the lack of disease-specific biomarkers and relatively low spatial resolutions than are achieved with clinical scanners have prevented successful detection and monitoring of disease progression in living subjects. With the aim to develop an approach that potentially can be translated to clinical field strengths and establish hallmarks to indicate pathology, this work employs ex vivo MRI at 21.1 T to assess and quantify MR contrast. This ultra-high field strength provides improved sensitivity and enhanced contrast, particularly for those mechanisms that exploit differences in magnetic susceptibility between tissues and pathologies. As verified by histological staining for iron, ferritin and microglia and standard histology for neuron count and vacuoolation, the findings of this work suggest that by employing high resolution MR microscopy at 21.1 T and quantifying contrast, relaxation and diffusion properties, it is possible to differentiate successfully between neurologically healthy brain tissue and pathological specimens diagnosed with PSP, AD or DLBD. In addition, this approach identified significant distinctions between dementing pathologies (i.e. AD and DLBD). The ramifications of these findings, the potential sources for MR contrast and their correlation to disease specific features are discussed in this work.
A Dissertation submitted to the Department of Chemical and Biomedical Engineering in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Includes bibliographical references.
Samuel C. Grant, Professor Directing Dissertation; Cathy Levenson, University Representative; Teng Ma, Committee Member; Jingjiao Guan, Committee Member.
Florida State University
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