This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Knee osteoarthritis (OA) affects roughly 27 million Americans and accounts for a significant number of visits to primary care physicians. For mild symptoms, treatment consists of weight loss, activity modification, physical therapy, and injections. Viscosupplementation (VS) is now routinely offered to patients with mild to moderate disease, usually after response failure to steroid injections. Pain relief following VS can last upwards of six months in some individuals. As of yet, no therapeutic agent has been shown to modify the disease progression of osteoarthritis;however, well-designed studies analyzing agents effects on articular cartilage are lacking. It is unclear whether some component of the clinical response to treatment is due to a structural and physiological effect on degenerative cartilage by restoring its matrix, in addition to a mechanical effect on joint contact surfaces and anti-inflammatory effect within the joint. Most current studies of the effects of VS on human cartilage use synovial fluid analysis for markers of cartilage degeneration, synovial tissue biopsy, and other indirect means of analysis. We propose the use of advanced MRI imaging to serially analyze articular cartilage following VS for changes in proteoglycan and water content. In vitro analysis suggests that these markers are correlates of the mechanical integrity of the tissue, and as such, can provide sensitive markers of disease progression and/or reversion. Having insight into cartilage biochemistry using imaging techniques will greatly advance investigations into the mechanism of VS. We propose T1? MRI imaging modalities to evaluate knee cartilage before and after injections to document the effect of hyalumonic acid on the proteoglycan content and character of articular cartilage in patients with mild to moderate OA of the knee (Kellgren-Lawrence Grades I and II). Using the T1? relaxation constant, detailed images of cartilage can be obtained, giving volumetric measurements and information on changes in proteoglycan content of the cartilage matrix. This study will attempt to apply these techniques to assess the effect of VS on knee cartilage.
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