Biomechanics of Human Articular Cartilage Measured In Vivo

描述（由申请人提供）：本提案的目的是将一种新的，无创的测量关节软骨生物力学的方法，双磁共振成像，转化为人类。骨关节炎（OA）是一种关节退行性疾病，也是一种常见的骨科问题，折磨着近20%的美国人口。骨性关节炎的病理生理学涉及关节软骨的退行性级联，破坏正常的细胞外基质蛋白合成，增加炎症细胞因子和酶的表达。关节软骨是一种带状组织，其生物力学功能对退变非常敏感。具体来说，蛋白聚糖的分解和结构完整性的丧失改变了内部的三维（3D）应变模式

DESCRIPTION (provided by applicant): 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.