Osteoarthritis (OA) leads to a compromised quality of life and places an enormous burden on the healthcare system. Current clinically available treatment methods mainly offer symptomatic relief but are unable to alter its natural course. Research and development of effective disease modifying therapies is hampered by lack of sensitive noninvasive tools to characterize and monitor the disease longitudinally. Ideally, the noninvasive technique should enable the quantitation of biochemical changes that are associated with the disease initiation process. Animal models serve as a bridge between tissue culture and human disease. Animal models are ideal for research in developing, optimizing, and validating therapies, stimulating repair of damaged tissues, understanding the disease process as well as developing noninvasive diagnostic tools to detect early OA. However, current magnetic resonance imaging (MRI) methods that are capable of quantitation of biochemical (specifically PG) changes have severe limitations in applying for small animal imaging. In this proposal, we will assess the potential capability of a novel MRI method in quantifying early biochemical and structural changes in a well studied, Guinea pig model that develops spontaneous OA. First, we will optimize this method for small animal imaging and then measure proton relaxation rates in vivo, and macromolecular content of cartilage biochemically. We will then be able to determine a correlation between the relaxation rate and macromolecular content of healthy cartilage. Finally, these studies will be performed on animals studied temporally with varying degrees of disease and we will establish a relationship between relaxation rate and changes in macromolecular content and extracellular matrix degradation. Once accomplished, results from this project will enable one to use the relaxation rate as a quantitative, surrogate marker for biochemical changes that occur before the onset of morphological changes in the small model under investigation. A major advantage of this approach is that it does not require any additional hardware modification or administration of exogenous contrast agent. Successful completion of the proposed work, has the potential to profoundly affect our ability to study OA process and to evaluate the efficacy of disease modifying therapies in animal models of osteoarthritis.
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