Development and Application of T1rho Dispersion Imaging of Aging Muscle

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Summary / Abstract This supplement aims to extend the goals and impact of research being undertaken by award #1K25AG076864-01 “Development and Application of T1rho Dispersion Imaging of Aging Muscle” to quantify degenerative changes in brain tissues associated with the progression of Alzheimer’s Disease (AD). The aims of our current parent grant are to adapt and validate magnetic resonance imaging (MRI) methods that exploit novel contrast mechanisms based on variations of R1ρ (R1ρ =1/T1ρ -the rotating frame spin-lattice relaxation rates) with changing the locking field frequencies, which provide new ways to detect changes in tissue, quantify intrinsic micro-structural features such as vascular spacing, and improve the ability to discriminate pathological processes. This supplement will specifically be used to quantify and validate changes in microvasculature and molecular composition associated with degenerative changes in brain tissues associated with the onset of dementia using animal models. To achieve these goals, we validate the interpretation of MRI parameters in terms of pathophysiological changes via gold-standard methods, including histology and imaging mass spectroscopy. The adapted T1ρ sequence and conventional MRI measurements also will be evaluated in a large cohort of older adults (+60 years), including patients with mild cognitive impairment (MCI), AD, and age- matched controls using a clinical 3T MR scanner. Clinical diagnosis and cognitive behavioral tests will be used to determine the cognitive level of each participant. We predict that application of this MRI protocol will characterize the changes in composition and microvasculature that accompany the progression towards AD in correlation with cognitive index scores, with special relevance to changes in white matter. Relevance to AD: The insights provided by these studies will provide new ways to extract information on tissue composition and microstructure using R1ρ weighted acquisitions with specific applications in AD. The supplement would support the extension of an exciting and highly innovative method of quantifying changes in brain structure and microvasculature in aging brains and provide new, quantitative biomarkers of the changes that occur during cognitive decline and the onset of Alzheimer’s Disease and transition to dementia.