Evaluation of Noninvasive Muscle Imaging Biomarkers for Knee Osteoarthritis in Older Adults

Project Summary Knee osteoarthritis is a leading cause of disability among older adults. Patients suffer from weakness and functional deficits that extend beyond articular cartilage erosion, with degenerative pathology in quadriceps muscles including weakness, atrophy, and fibrosis. Recent reports underscore reductions in quadriceps muscle quality, with poor muscle quality an important predictor of pain trajectory in patients. Prior studies have not identified the specific deficits in muscle quality, and the identification of specific cellular and acellular source(s) of poor muscle quality would directly lead to new therapeutic targets unique to this muscle phenotype. A critical first step to advance patient care step is the development of non-invasive muscle biomarkers to define muscle dysfunction unique to this population. Recent advances in T1 rho magnetic resonance imaging (MRI) and diffusion tensor imaging have enabled an ability to estimate indices of muscle quality and size, respectively, and offer novel and non-invasive assessments of muscle morphology. The proposed clinical observation grant is a crucial step to establish potential non-invasive magnetic imaging biomarkers for the identification of altered muscle quality in people with knee osteoarthritis. The overarching objective of the current proposal is to validate non-invasive MRI measurements with validated assessment of muscle quality and fiber size obtained from aligned quadriceps biopsies. Further, this proposal will determine the relationship between non-invasive measures of muscle quality to strength and physical performance in persons with knee osteoarthritis. This critical first step is necessary define non-invasive biomarkers in patients with knee osteoarthritis so that future studies can test new treatments that are specifically targeted to the underlying muscle biology deficits contributing to quadriceps muscle dysfunction. The results of this work will provide critical translational between cellular and acellular effectors of muscle quality to function known to limit quality of life in persons with knee osteoarthritis.