Intervertebral Disc Mechanics Measured by dualMRI In Vivo

项目总结/摘要 该提案的目的是将双MRI，一种新的非侵入性测量椎间融合器的方法， 椎间盘（IVD）生物力学，人类。IVD变性是一种常见的骨科问题， 在美国的人。IVD病理生理学涉及破坏正常 细胞外基质蛋白质的合成，并增加炎性细胞因子和酶的表达。 IVD生物力学功能对退行性变敏感，三维结构的内部模式改变 (3D)与髓核（NP）中水含量损失和蛋白聚糖分解相关的菌株， 以及纤维环（AF）结构完整性的丧失。幸运的是，退化级联产生了 许多潜在的治疗靶点。在终末期治疗（例如脊柱融合术）之前， 用于IVD变性的生物疗法和管理策略包括干细胞和自体细胞 植入、基因治疗、预防性注射和IVD去神经。一个理想的疗法最终会 恢复IVD的生物力学功能，其特征在于内部应变场显示局部修复， 损伤后愈合。目前没有体内方法可用于测量3D生物力学 在整个IVD内部发挥作用。为了开发一种成像生物标志物， 跟踪治疗后肌肉骨骼组织的生物力学功能，我们开发了双MRI （通过MRI在施加载荷下的位移），用于测量 关节软骨和体外诊断我们现在准备实施双MRI，用于体内测量 健康和退行性腰椎IVD志愿者的生物力学。我们将建立一个工作协议， 人体志愿者体内双MRI，包括定制机械加载方法和MRI脉冲 序列，这将很容易扩展到更大规模的病理和临床研究在未来的应用。我们 我们将追求两个目标。在目标1中，我们将实现双MRI来测量人类椎间盘的3D图案 株在目标2中，我们将在体内证明健康和异常IVD之间的菌株差异。如果 成功的，我们将提供一个新的工具，非侵入性和体内功能评估的IVD。这 工作将提供肌肉骨骼，制药，和骨科社区（a）临床 评估治疗剂靶向动物和人早期变性的功效的诊断工具 试验，（B）使用新兴生物疗法功能性评价IVD愈合和修复的能力，（c） 描述人体IVD体内健康功能的基线数据，以及（d）平台技术， 广泛研究体内承重组织（如半月板、韧带）的力学功能。

PROJECT SUMMARY / ABSTRACT The objective of this proposal is to translate dualMRI, a new noninvasive method of measuring intervertebral disc (IVD) biomechanics, to humans. IVD degeneration is a common orthopaedic problem, afflicting millions of people in the United States. The IVD pathophysiology involves a degenerative cascade that disrupts normal extracellular matrix protein synthesis and increases the expression of inflammatory cytokines and enzymes. IVD biomechanical function is sensitive to degeneration, with altered internal patterns of three dimensional (3D) strains related to the loss of water content and proteoglycan breakdown in the nucleus pulposus (NP), and loss of structural integrity of the annulus fibrosus (AF). Fortunately, the degenerative cascade gives rise to many potential therapeutic targets. Prior to end-stage treatment (e.g. spinal fusion), numerous possible biological therapies and management strategies for IVD degeneration include stem and autologous cell implantation, gene therapy, prophylactic injection, and IVD denervation. An ideal therapy would ultimately restore the biomechanical function of the IVD, characterized by internal strain fields that reveal local repair and healing following damage. There are currently no in vivo methods available to measure 3D biomechanical function throughout the interior of the IVD. In an effort to develop an imaging biomarker that noninvasively tracks the biomechanical functional of musculoskeletal tissues following therapy, we developed dualMRI (displacements under applied loading by MRI) for the measurement of mechanical strain in the interior of articular cartilage and IVDs. We are now poised to implement dualMRI for the in vivo measurement of biomechanics in volunteers with healthy and degenerated lumbar IVDs. We will establish a working protocol for in vivo dualMRI in human volunteers, including custom mechanical loading methods and MRI pulse sequences, which will readily expand to larger scale pathologic and clinical studies in future applications. We will pursue two Aims. In Aim 1, we will implement dualMRI to measure 3D patterns of human intervertebral disc strain. In Aim 2, we will demonstrate strain differences between healthy and abnormal IVDs in vivo. If successful, we will provide a new tool for the noninvasive and in vivo functional assessment of the IVD. This work will provide musculoskeletal, pharmaceutical, and othopaedic surgery communities 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 IVD healing and repair with emerging biological therapies, (c) baseline data describing the healthy function of human IVDs in vivo, and (d) a platform technology to more broadly study mechanical function of load-bearing tissues (e.g. meniscus, ligament) in vivo.