Sodium NMR: An noninvasive probe for proteoglycan macromolecules

Osteoarthritis (OA) is a progressive disease of cartilage that results in joint pain and inflammation. It is estimated that it affects over 40 million people in the United States alone. The early biochemical changes of OA are associated primarily with the loss of proteoglycan (PG) macromolecules from the extra-cellular matrix of cartilage. Identifying these early changes would allow efficient therapeutic intervention to halt the progress of the disease. Currently, there are no noninvasive techniques available for the detection of these early changes due to OA. The goal of this thesis is to develop MR methodologies targeted to design noninvasive diagnostic tools for the early detection of OA. We have demonstrated the efficacy of novel sodium magnetic resonance imaging and spectroscopy techniques for studying the biochemical properties of cartilage in a noninvasive and non-destructive manner. MRI has the potential to detect cartilage degeneration better than other imaging modalities. We used sodium MRI to validate the sensitivity of proton MR1 for detecting changes in PG concentration in bovine articular cartilage specimens. We found that proton density, and proton T1 and T 2 maps did not show any correlation to PG loss. We also demonstrated the feasibility of obtaining sodium MR images of the human wrist, in vivo. Contrast-enhanced proton MRI has shown great promise in quantifying PG loss. To evaluate the utility of this method, we quantified the sensitivity of Gd(DTPA)2−-enhanced proton MRI and sodium MRI in detecting small changes in PG content in intact bovine patellae following enzymatic degradation. We determined that, despite its lower NMR sensitivity, sodium MRI is more sensitive in detecting small changes (\u3c35% loss of total PG) in the PG concentration than Gd(DTPA)2−-enhanced proton MRI. We quantified the effect of interieukin-1 induced degradation of the extra cellular matrix of cartilage on the residual quadrupolar interaction in cartilage. We showed that, contrary to previously published results, PG also contributes to quadrupolar interactions and, hence, to the macroscopic order of the tissue. We also demonstrated that it is possible to obtain sodium MQF images in vivo with high signal to noise ratios and resolution in a reasonable time