OA is a major cause of morbidity in the population over 50 and affects more than 40 million Americans. Although evidence implicates cartilage degeneration as the primary cause for OA, no cure exists as yet. Current treatments relieve symptoms but do not inhibit disease progression. However, if the disease is detected in early stages then appropriate therapeutic intervention may be possible. Currently, there are no noninvasive methods to detect early biochemical changes in cartilage. This lack of noninvasive diagnostic methods also hampered the research in the development of potential chondroprotective agents. To develop sensitive, noninvasive diagnostic tools that target early degenerative changes, one needs to understand the structural and biochemical changes that occur during degeneration and correlate these properties to measurable parameters obtained by a noninvasive method. In this application we propose to exploit proton magnetic resonance (MR) relaxation under spin-locking condition to develop a novel MR technique to monitor structural and biochemical changes in cartilage that occur during early OA. Both spectroscopic and imaging measurements will be performed on cartilage tissue models, normal bovine cartilage, on enzymatically degraded bovine cartilage (which are subjected to selective degradation of varying degrees of proteoglycans (PG) or collagen to mimic the structural and biochemical changes that occur in OA). The results obtained from the extracellular matrix (ECM) model systems will enable one to determine contributions from different components of ECM to the observed relaxation and dispersion behavior, and underlying mechanism. The data from the selective enzymatic degradation studies will provide the signal changes and contrast in spin-lock-weighted images and will help in developing optimal imaging parameters to measure changes induced by specific macromolecular degradation. Since the measured MR properties rely not only on tissue contrast, but are also dependent on structural and biochemical changes, this proposed research will aid in the development of a sensitive non-invasive technique for early diagnosis of OA as well as aid in the development/evaluation of potential chondroprotective drugs and treatment therapies.
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