The extracellular matrix (ECM) is a network of extracellular macromolecules that is present in both cartilage and intervertebral disc tissues. While both cartilage and intervertebral disc tissues are comprised of an ECM, their form and structure vary. Likewise, each tissue has unique characteristics during degeneration. This project will investigate the non-invasive detection of early degenerative changes of cartilage and disc tissues in osteoarthritis (OA) and intervertebral disc degeneration (IVDD) using novel magnetic resonance imaging methods.

OA is a debilitating disease causing pain, stiffness, and loss of mobility to approximately 14% of the adult population. 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, prior to morphologic degradation, is elusive in clinical practice. Certain quantitative MRI methods, including T_1ρ and T₂ relaxation time mapping, are sensitive to biochemical changes in the ECM, and thus may be valuable for early diagnosis of intervertebral disc and cartilage degeneration.

The overall purpose of my dissertation is to develop a methodology for the quantification of T_1ρ and T₂ magnetic resonance relaxation times in the intervertebral disc and knee cartilage, and characterize the spatial distribution of T_1ρ and T₂ in the extracellular matrix in IVDD and OA.

The first portion of this dissertation focuses on the methodology for MR relaxation time mapping. This study evaluated the impact of signal to noise ratio and T₂ fitting algorithms on the T₂ quantification. Simulations were performed determine the minimum SNR that can be used to distinguish healthy cartilage from degenerative cartilage. In addition, various fitting algorithms (noise correction vs. no noise correction) were assessed to determine whether their impact on the accuracy of T₂ quantification.

The second dissertation study examined the relationship between structural changes of trabecular bone and cartilage in patients with varying degrees of OA over two years, using MR imaging. A positive relationship was established between cartilage changes and localized bone changes closest to the joint line, while a negative relationship was established between cartilage changes and global bone changes farthest from the joint line. This study demonstrated a longitudinal relationship between the changes in bone and cartilage structure in patients with varying degrees of OA.

The third dissertation study evaluated the mean and spatial distribution of cartilage T₂ in subjects with and without OA. The mean T₂ values, their standard deviation, 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. The longitudinal results demonstrate that changes in texture parameters of cartilage T₂ may precede morphological changes in thickness and volume in the progression of OA.

The fourth dissertation study focused on the longitudinal changes in the spatial distribution of cartilage T₂ values in subjects with OA. This study evaluated both the morphologic and biochemical changes in cartilage using MR imaging as well as clinical data from the OAI. Entropy of cartilage T₂ at baseline (all compartments combined except the lateral tibia) was associated with an increase in WOMAC pain score over 2 years. This study demonstrated that the baseline heterogeneity of cartilage T₂ is associated with changes in clinical pain scores.

The fifth dissertation study assessed the feasibility of quantifying T_1ρ relaxation time for the non-invasive detection of disc degeneration. The in vivo results indicated that the median T_1ρ value of the nucleus is significantly greater than that of the annulus. The results of this study suggest that in vivo T_1ρ quantification is feasible and may potentially be a clinical tool to identify early degenerative changes in the intervertebral disc.

The sixth dissertation study built upon the results from the fifth study by evaluating T_1ρ and T₂ in subjects with varying degrees of disc degeneration. A positive relationship was evident between MR parameters and clinical questionnaire scores and a negative relationship was evident between degenerative grade and relaxation time. This study suggests that T_1ρ relaxation time may be sensitive to early degenerative changes and clinical symptoms in intervertebral disc degeneration.

The results of this project suggest that quantifying the spatial distribution of MRI relaxation times improves the clinical assessment of IVDD and OA, by providing a noninvasive evaluation of biochemical composition in the intervertebral disc and cartilage tissues. T_1ρ and T₂ relaxation times are not only sensitive to biochemical changes in OA and IVDD, they are also related to the clinical assessment of pain.