PROJECT SUMMARY Osteoarthritis (OA) is a degenerative joint disease, affecting more than 27 million people in the United States alone. This large affected population and the severe consequent debility of OA lead to significant expenses to the health care system. OA is characterized by biochemical, structural and morphologic degradation of components of the extracellular matrix (ECM) of articular cartilage. The ECM is composed of primarily two groups of macromolecules including proteoglycan (PG) and collagen fibers. Early diagnosis of cartilage degeneration would require the ability to non-invasively detect changes in PG concentration and collagen integrity before morphological changes occur. T1ρ and T2 relaxation times are affected by these pathological processes and are the most widely used biochemical cartilage MRI sequences worldwide. . The overarching goal of this proposal is to develop, optimize, and translate high spatial resolution 3D-isotropic- MRI sequence (700µmX700µmX700µm) for simultaneous assessment of morphometry and biexponential 3D- T1ρ (T2) mapping sequences (each protocol under 10 minutes) for improved quantitative assessment of morphological (cartilage thickness and volume) and biochemical characterization of cartilage on a standard clinical 3T scanner employing combinations of compressed sensing (CS) and parallel imaging (PI). The proposed accelerated, isotropic, high spatial resolution, multicomponent 3D-T1ρ (T2) mapping techniques can be easily incorporated into routine clinical protocols for biochemical assessment of cartilage in addition to standard morphological evaluation and could serve as future imaging biomarkers for disease modifying therapies for OA. The outcome of this proposed study will significantly impact our ability for personalized treatment regimens and possibly prevent the development of premature OA.