The objective of this proposal is to translate a novel, noninvasive method of measuring articular cartilage biomechanics, dualMRI, to humans. Osteoarthritis (OA) is a degenerative disease of the joint and a common orthopaedic problem, afflicting nearly 20% of the US population. The pathophysiology of OA involves a degenerative cascade in articular cartilage that disrupts normal extracellular matrix protein synthesis and increases inflammatory cytokine and enzyme expression. Articular cartilage is a zonal tissue whose biomechanical function is sensitive to degeneration. Specifically, proteoglycan breakdown and loss of structural integrity alters the three dimensional (3D) strain patterns within the tissue during mechanical loading. The development of emerging biological therapies and management strategies, including gene therapy, injection of prophylactic proteins, and stem and autologous cell implantation, are currently limited by a lack of a suitable, noninvasive method of measuring the biomechanical function of cartilage in humans. We developed dualMRI (displacements under applied loading by MRI) as a solution to the need for an imaging biomarker that noninvasively characterizes the biomechanical functional of musculoskeletal tissues following therapy. We propose to establish a working protocol for in vivo dualMRI in human volunteers using custom mechanical loading methods and MRI pulse sequences. We will pursue two related specific aims.
In Aim 1, we will quantify 3D patterns of articular cartilag strain by dualMRI in human volunteers.
In Aim 2, we will correlate dualMRI strains and quantitative MRI (qMRI) measures in articular cartilage. If successful, we will establish a new tool for the noninvasive, in vivo, functional biomechanical assessment of articular cartilage. This work will provide the musculoskeletal research community with (a) a clinical diagnostic tool to evaluate efficacy of therapeutic agents to target early degeneration in animal and human trials, (b) the ability to functionally evaluate cartilage healing and repair with emerging therapies, (c) baseline data describing the healthy function of human cartilage in vivo, and (d) a platform technology to more broadly study biomechanical function of load-bearing tissues (e.g. meniscus, ligament) in vivo.
The impact of osteoarthritis on human health is enormous. The proposed research will likely improve our ability to monitor degenerative changes in cartilage following injury and repair by using novel noninvasive magnetic resonance imaging techniques and human populations. We aim to establish a foundational and clinically- relevant imaging technique to quantify damage and repair through noninvasive strain measures, and compare the technique to conventional imaging assays.
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