Diffusion and diffusive exchange are sensitive to the structure of cartilage as measured by nuclear magnetic resonance

Abstract

Osteoarthritis (OA) is the deterioration of the tissue on the surface of the articulating joints in mammals. OA is the progression loss of articular cartilage. OA affects 50% of people over age 65 and is the leading cause of workplace disability. There is no cure for OA and the state of the art treatment is joint replacement. One limitation for treating OA is the difficulty of diagnosing OA before tissue failure. Magnetic Resonance Imaging (MRI) is capable of detecting early pathologic changes to cartilage but challenges remain. The goal of this work is to evaluate how parameters, specifically relaxation and diffusion, used for creating imaging contrast in MRI are affected by disease in naturally occurring human osteoarthritis. Nuclear Magnetic Resonance (NMR) is utilized to measure the diffusion and magnetic relaxation in human OA cartilage samples. Diffusion Weighted Imaging (DWI) is a proposed imaging mechanism for diagnosing OA. The hypothesis is that fluid diffusion is faster in diseased tissue than in healthy tissue. We show that diffusion of fluid increases when cartilage is damaged by enzymes, such as during OA. We also show that the diffusion of fluid is donor specific in human OA cartilage. Diffusion of proteins in cartilage is also sensitive to enzyme degradation and donor as well as to the size and structure of the proteins in cartilage. These are complementary measures of the fluid and solid phase of cartilage. Relaxation weighted imaging is the most common way to image cartilage and is capable of measuring small structure changes due to OA. One limitation of this method is that reported relaxation rates vary between studies. We show that exchange, or motion of fluid, between the two sites of relaxation in cartilage alters the observed relaxation. Further, we show that the exchange rate is sensitive to donor and enzyme degradation. The results suggest that exchange rate is a sensitive measure of structure in cartilage and that relaxation should be cautiously interpreted when exchange occurs. Overall, this work shows that NMR and MRI are sensitive to the structure of cartilage and capable of detecting pathological damage to cartilage.