Project Summary/Abstract Sarcopenia is a leading cause of death and disability for the aging population and creates a societal burden resulting in $18 billion in annual costs in the United States alone. While new treatments have shown promise to improve functional outcomes, they have been hampered by the lack of non-invasive biomarkers sensitive to the early stages of the disease. In particular, non-invasive assessment of muscle atrophy is a long-recognized but unmet need in the sarcopenia community, and we propose to use magnetic resonance imaging (MRI) to address this need. This project develops a clinically feasible toolset to noninvasively image early atrophic changes in skeletal muscle using Magnetic Resonance Imaging (MRI). Our specific aims are (1) to develop new MRI techniques that utilize a novel pulse sequence to quantify muscle cell size and changes thereof due to atrophy; (2) to validate MR atrophy imaging with histological evaluation of muscle biopsies from young and older subjects, and correlate with muscle strength; and (3) to apply MRI atrophy methods to study longitudinal changes in sarcopenic patients and in pre-frail subjects, which are at high risk of developing sarcopenia. The innovation of this work lies in the development of a novel imaging technique to quantify atrophy in muscle tissue non-invasively. The outcome of this proposal is a validated and quantitative MRI tool to image muscle quality, and its relationship to patient strength and functional status. The significance of this work is a robust clinical MRI protocol to image early degenerative changes associated to sarcopenia that is transferrable to any clinical site. The reproducible and robust tool will allow the sarcopenia imaging community to identify subject at risk, and implement targeted and timely interventions that can stop or slow the progression of sarcopenia.