Characterizing Magnetic Resonance Relaxation Times in the Extracellular Matrix in Osteoarthritis and Degenerative Disc Disease

The extracellular matrix (ECM) is a network of extracellular macromolecules that is present in both cartilage and intervertebral disc tissues. Osteoarthritis (OA) is a debilitating disease causing pain and stiffness in approximately 14% of adults. Intervertebral disc degeneration (IVDD) is the leading cause of pain and disability in adults in the United States. Despite the high prevalence of OA and IVDD worldwide, diagnosis in the early stages of symptomatic disease is elusive in clinical practice. Certain quantitative MRI methods including T1rho and T2 relaxation time mapping are sensitive to biochemical changes in the ECM, and thus may be valuable for early diagnosis of OA and IVDD. The purpose of this dissertation is to develop a methodology for the quantification of T1rho and T2 magnetic resonance relaxation times in the intervertebral disc and knee cartilage, and characterize the spatial distribution of T1rho and T2 in the extracellular matrix in IVDD and OA. This study evaluated the impact of signal to noise ratio and T2 fitting algorithms on the T2 quantification. Simulations were performed determine the minimum signal to noise ratio that can be used to distinguish healthy cartilage from degenerative cartilage. In addition, the mean and spatial distribution of cartilage T2 in subjects with and without OA was evaluated. The mean T2 values and their entropy were greater in OA patients than in controls, indicating that the T2 values in osteoarthritic cartilage are not only elevated, but also more heterogeneous than those in healthy cartilage. In addition, the entropy of cartilage T2 at baseline was associated with an increase in pain scores over two years. MRI T1rho relaxation time was investigated in subjects with IVDD. The results demonstrated positive correlations between T1rho and pain scores and negative correlations between T1rho and degenerative grade. This study suggests that T1rho may be sensitive to early degenerative changes and clinical symptoms in IVDD. The results of this project suggest that quantifying the spatial distribution of MRI relaxation times improves the clinical assessment of OA and IVDD, by providing a non-invasive evaluation of biochemical composition in cartilage and intervertebral disc tissues