(Micro)structural Biomarkers of Skeletal Muscle Health Across the Lifespan

About This Grant

Project Summary Sarcopenia is a leading cause of disability and mortality the aging population worldwide, and poses a societal burden, resulting in $18 billion in annual costs in the United States alone. The management of patients with sarcopenia remains challenging, given that diagnosis often occurs at late stages of the disease, when the treatment strategy available are mostly ineffective. Thus, there is a pressing need for non-invasive biomarkers capable of distinguishing normal aging from early-stage sarcopenia, and correlating to functional outcomes such as muscle strength. To address this need we propose the development of innovative tools for the analysis of Magnetic Resonance Imaging (MRI) data. This project aims to explore the feasibility of using MRI, in combination with novel data analysis and modeling technique, to study key features of muscle tissue affected by aging, and that might play a role in the age-related loss of muscle strength. Our specific aims are to (1) investigate the impact of age on shape and structure in thigh muscles, and their contribution to muscle strength, and to (2) develop a novel diffusion MRI framework with heightened sensitivity and specificity to cellular atrophy. This framework can increase the predictive values of muscle strength from diffusion MRI data. The innovation of this project lies in the development of analysis tools that make use of shape information to predict strength. This approach can facilitate the retrospective analysis of existing data and “opportunistic screening” of sarcopenia. Additionally, we propose the development of an innovative framework for the analysis of diffusion MRI data, capable of non-invasive quantification of muscle atrophy. The outcome of this proposal is a set of quantitative MRI tool to investigate muscle quality and structure, and its connection to patient strength and functional status. These tools will be openly shared with the research community, maximizing their impact, and allowing for the detection of early signs of sarcopenia. This, in turn, will facilitate the implementation of targeted and timely interventions that can halt or slow the progression of sarcopenia.