Sarcopenia, a condition characterized by loss of muscle mass and function in the elderly, is of increasing relevance in the United States due to its aging population. It is generally agreed that the weakening of the muscle in sarcopenia cannot be explained by loss of muscle mass alone, but the mechanisms behind this remain poorly understood. This is partly due to the lack of non-invasive techniques for observing muscle structure and composition in high detail. We propose to develop MRI techniques to measure muscle morphology, microstructure, and fat content to get a detailed view of the changes in muscle quantity and quality in patients with sarcopenia and how they relate to more easily attainable measurements of muscle function such as grip strength and gait speed. This would provide an important contribution to the ongoing debate about how such measurements could be used to define sarcopenia, which would pave the way for treatment development.
We aim to develop novel methods to investigate the structure and composition of muscle using ultra-high-field MRI. Specifically, we aim to (1) obtain water-based images of skeletal muscle macro- and microstructure with unparalleled efficiency, image quality, and resolution; (2) obtain images of the spatial distribution of intramyocellular lipids in skeletal muscle, measuring both methyl and methylene to estimate saturation; and (3) to conduct a study comparing skeletal muscle structure and quality by looking at MR measurements of T2 relaxation rates, diffusivity (as proxies for inflammation and fiber size, respectively), fat fraction, and lipid composition, in subjects with sarcopenia and healthy controls and see how these quantities correlate to muscle function. This project has several innovative aspects. First, we will develop a method to estimate muscle morphology, T2 relaxation rates, and diffusivity with a single MRI sequence. Importantly, this will make the developed method easy to run at other MRI sites. Second, we will devise methods to perform robust, efficient imaging of intramyocellular lipid droplet distribution and saturation in human skeletal muscle in vivo at high field. Both of these methods will have unparalleled signal-to-noise ratio and robustness against image artifacts. The significance of this work is the investigation of the role of inflammation, fiber size, and lipid distribution in the weakening of muscle in sarcopenia and how these measurements are related to muscle function. The resulting conclusions and techniques may help establish a common standard for the definition of sarcopenia and aid in the development of future treatments for this condition.

Public Health Relevance

Sarcopenia, the loss of muscle mass and function with age, is a condition bound to increase in prevalence with an aging population. The muscle changes involved include not only reduction in mass but also changes in muscle quality not easily visualized with current methods. This work aims to develop efficient MRI techniques to investigate these changes in better detail, improving scientific understanding of the mechanisms of sarcopenia and how they relate to muscle function.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Career Transition Award (K99)
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Neuroscience of Aging Review Committee (NIA)
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Williams, John
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Massachusetts General Hospital
United States
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