Osteoarthritis is a major cause of morbidity in the population over 50, affecting more than 40 million Americans. It also imposes considerable expense on the health care system. There is currently no cure for this debilitating disease and the effective treatment is, at best, focused on symptomatic relief. Cartilage degeneration is thought to be the primary pathology associated with the disease. Recent developments in chondro-protective drugs and gene therapy have generated substantial demand for noninvasive techniques for detecting changes in cartilage. These developments and any other potential therapies can effectively work only if the disease is detected early. Among the most significant early changes in articular cartilage in osteoarthritis is the loss of proteoglycans (PG). However, currently there is no reliable quantitative noninvasive method available for detecting and evaluating these early changes. The applicants proposed to quantitatively evaluate the potential of sodium magnetic resonance imaging (MRI) for detecting and quantifying proteoglycan (PG) changes in an in vivo model of early osteoarthritis. To accomplish this task, the applicants proposed to first characterize the technique in bovine cartilage specimens treated with a known mediator of extracellular matrix degradation. Secondly, they would inject to cytokine injection based model of PG degradation in the dog knee to create artificial osteoarthritic condition and measure dose dependent changes in cartilage degeneration. Specifically, they proposed to inject the cytokine into the intra-articular space of the hind limb knee, using the contralateral knee as control. After the appropriate time interval, the applicants proposed to perform sodium MR on both the treated and control knee to measure changes in sodium content. After the MRI experiments, harvested cartilage tissue would be subjected to spectrophotometric, histologic, and immunohistochemistry determination of PG content and its spatial distribution. The changes in sodium content as measured from MRI and the changes in PG content (measured by spectrophotometry, histology and immunohistochemistry) would be correlated. These measurements would establish the capability of sodium MR in determining the changes that occur during early degeneration of cartilage in vivo. Since it is possible to perform sodium MR in a noninvasive clinical setting, this method can be immediately exploited in human studies for detecting early changes due to QA. Once developed, this method would have a major impact on the ability to make an early and appropriate therapeutic intervention, monitor the clinical outcome, and aid in evaluating new treatment modalities.
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