Development and Application of T1rho Dispersion Imaging of Aging Muscle

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Project Summary: The overall goals of the research proposed are to develop, validate and apply innovative magnetic resonance imaging (MRI) biomarkers that can be used to improve our understanding of the processes involved in muscle deterioration that occurs with aging. MRI can provide not only superb depiction of soft tissue anatomy, but appropriate MRI images can be analyzed to provide quantitative parametric maps that report intrinsic pathological changes in tissue composition, microstructure, and function. We propose to develop novel parametric images based on quantifying changes in R1ρ, the spin-lock relaxation rate, and its variation with the locking field amplitude, which we term R1ρ dispersion imaging. We hypothesize this novel methodology can be used to quantify degenerative changes in microvasculature as well as the abnormal accumulation of macromolecules in the membranes of muscle fiber. The specific aims of this proposal are to refine and implement novel methods of MRI data acquisition and analysis to derive quantitative parametric images based on R1ρ dispersion and validate their interpretation in terms of pathophysiological changes via gold-standard methods including histology, and imaging mass spectroscopy. To achieve these goals, we will perform longitudinal MRI imaging studies of rodent models of skeletal muscle deterioration with aging. Optimized methods will then be evaluated in a cohort of human subjects on a clinical 3T MR scanner. The quantitative measures of microvascular changes along with macromolecular deposition will provide new information on the progression of the characteristic changes that occur with aging and provide a new tool that may catalyze new hypotheses and therapeutic strategies to ameliorate the effects of tissue degeneration. During this career development award, the awardee will gain crucial training in geriatric, the biology of aging, advanced MRI sequence development, quantitative methods of histology, and how to translate methodological innovations into human studies. A comprehensive didactic training and career mentorship program will provide the knowledge and experiences needed to accomplish the career goal of becoming an independent researcher at the interface of imaging and aging study. The institutional environment at Vanderbilt University Institute of Imaging Science is exceptional and will provide an exemplary opportunity to build a strong foundation in developing imaging biomarkers for translational applications.