Biomechanics of Human Articular Cartilage Measured In Vivo

描述(申请人提供)：这项提议的目标是将一种测量关节软骨生物力学的新的、非侵入性的方法，即双磁共振成像，移植到人类身上。骨关节炎是一种关节退行性疾病，也是一种常见的骨科问题，困扰着近20%的美国人口。OA的病理生理学涉及关节软骨的退行性级联反应，破坏正常的细胞外基质蛋白合成，增加炎性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敏感。具体地说，蛋白多糖的破坏和结构完整性的丧失会改变体内的三维(3D)应变模式 在机械加载过程中的组织。目前，包括基因治疗、预防性蛋白注射、干细胞和自体细胞移植在内的新兴生物疗法和管理策略的发展受到了限制，因为缺乏一种合适的、非侵入性的方法来测量人类软骨的生物力学功能。我们开发了DualMRI(外加载荷下的位移)，作为对成像生物标记物的需求的解决方案，该成像生物标记物非侵入性地表征治疗后肌肉骨骼组织的生物力学功能。我们建议在人类志愿者体内建立一个使用定制机械加载方法和MRI脉冲序列的双核磁共振工作规程。我们将追求两个相关的具体目标。在目标1中，我们将利用双磁共振成像技术对人类志愿者关节软骨应变的三维图像进行量化。在目标2中，我们将在关节软骨中将双MRI应变和定量MRI(QMRI)测量相关联。如果成功，我们将为关节软骨的无创性、在体、功能性生物力学评估建立一个新的工具。这 这项工作将为肌肉骨骼研究界提供：(A)在动物和人体试验中评估针对早期退行性变的治疗药物的疗效的临床诊断工具，(B)通过新兴疗法对软骨愈合和修复进行功能性评估的能力，(C)描述人体软骨在体内的健康功能的基线数据，以及(D)更广泛地研究承载组织(如半月板、韧带)在体内的生物力学功能的平台技术。

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.