MULTIPARAMETRIC STUDIES OF CARTILAGE INTEGRITY

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DESCRIPTION: (Adapted From Investigator's Abstract) Osteoarthritis and rheumatoid arthritis are relatively prevalent diseases in which articular cartilages become progressively destroyed. The ability to fully understand these disease states and to formulate sensible diagnostic, preventive, and therapeutic strategies has been hampered by the inability to assess the functional state of cartilage in vivo. The applicants' long term goal is to establish magnetic resonance (MR) techniques for the compositional and functional evaluation of cartilage and to apply these techniques for the study of cartilage physiology and pathophysiology. Their approach is to develop a multiparametric protocol grounded in a basic understanding of the MR sensitivity to specific functionally relevant features of cartilage. The ability of cartilage to function as a load bearing tissue is directly related to the composition and structure of the extracellular matrix. Glycosaminoglycans (GAGs) and collagen are the predominant constituents of cartilage matrix, and are responsible in large part for the compressive and tensile strength of the tissue, respectively. The transport of water through the tissue is a measure of matrix structural integrity and is a direct indicator of how drugs, nutrients and other solutes may reach the cartilage cells. The investigators have recently shown that the glycosaminoglycan content of cartilage can be measured with sodium MR. Collagen is the predominant cartilage constituent which contributes to an MR effect referred to as magnetization transfer. They have recently demonstrated that the diffusivity of small solutes in cartilage can be measured by MR. The specific aims for this project are the following: (1) To combine the three magnetic resonance (MR) experiments (sodium, magnetization transfer, and diffusion) for a multiparametric evaluation of samples of living cartilage in culture. The techniques will be applied to the study of the physiologic and pathologic perturbations of compression and interleukin-1 degradation. (2) To establish magnetic resonance imaging (MRI) protocols for the multiparametric evaluation of cartilage in intact heterogeneous samples, and to apply the techniques to the study of human cartilage samples in various stages of disease. A combined measure of glycosaminoglycans, collagen, and transport (diffusivity) properties of cartilage should provide the unique opportunity to non-destructively study and monitor the progression of matrix destruction during the early stages of arthritis and to evaluate the efficacy of therapeutic endeavors in terms of replenishing matrix constituents both in vitro and in vivo systems. The nondestructive nature of the MR studies provides the powerful capability of conducting kinetic or sequential studies on the same specimen (or patient). This combination of nondestructive, functionally relevant studies of living cartilage is currently not feasible in an experimental or clinical setting.