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测量关节软骨生物力学的新型无创方法（dualMRI）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，困扰着近20%的美国人口。OA的病理生理学涉及关节软骨中的退行性级联反应，其破坏正常的细胞外基质蛋白合成并增加炎性细胞因子和酶表达。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，蛋白聚糖分解和结构完整性的丧失改变了细胞内的三维（3D）应变模式。 在机械加载期间的组织。新兴的生物疗法和管理策略的发展，包括基因治疗，注射预防性蛋白质，干细胞和自体细胞植入，目前受到缺乏合适的，非侵入性的方法来测量人体软骨的生物力学功能的限制。我们开发了dualMRI（通过MRI施加载荷下的位移）作为对成像生物标志物的需求的解决方案，该成像生物标志物可无创地表征治疗后肌肉骨骼组织的生物力学功能。我们建议使用自定义机械加载方法和MRI脉冲序列在人类志愿者中建立体内dualMRI的工作协议。我们将追求两个相关的具体目标。在目标1中，我们将通过双MRI量化人类志愿者关节软骨应变的3D模式。在目标2中，我们将在关节软骨中关联双MRI应变和定量MRI（qMRI）测量。如果成功，我们将建立一个新的工具，非侵入性的，在体内，关节软骨的功能生物力学评估。这 工作将为肌肉骨骼研究团体提供（a）临床诊断工具，以评估治疗剂在动物和人体试验中针对早期退化的功效，（B）功能性评估软骨愈合和新兴疗法修复的能力，（c）描述人体软骨体内健康功能的基线数据，以及（d）更广泛地研究体内承重组织（例如半月板、韧带）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.