Intervertebral Disc Mechanics Measured by dualMRI In Vivo

通过体内双核磁共振成像测量椎间盘力学

• 批准号: 9034951
• 负责人: Corey P Neu
• 金额: $ 19.57万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-03 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9034951
• 关键词: Algorithms; Animals; Autologous; Back Pain; Biological Assay; Biological Response Modifier Therapy; Biomechanics; Cells; Cervical; Clinical; Clinical Research; Communities; Custom; Data; Denervation; Devices; Diagnostic; Enzymes; Extracellular Matrix Proteins; Frequencies; Functional disorder; Future; Healed; Health; Human; Human Volunteers; Image; Imaging Phantoms; Imaging Techniques; Inflammatory; Injection of therapeutic agent; Intervertebral disc structure; Joints; Ligaments; Lower Back Injury; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mechanics; Meniscus structure of joint; Methods; Monitor; Musculoskeletal; Operative Surgical Procedures; Orthopedics; Pathologic; Pattern; Pharmacologic Substance; Physiologic pulse; Protein Biosynthesis; Proteoglycan; Protocols documentation; Reproducibility; Research; Specimen; Spinal Fusion; Spine surgery; Staging; Statistical Models; System; Techniques; Technology; Testing; Therapeutic Agents; Tissues; Torsion; Translating; United States; Vertebral column; Walking; Water; Weight-Bearing state; Work; articular cartilage; clinically relevant; cytokine; elastography; gene therapy; healing; healthy volunteer; imaging biomarker; implantation; improved; in vivo; intervertebral disk degeneration; joint destruction; nucleus pulposus; prophylactic; repaired; stem; therapeutic target; therapy development; tool; validation studies; volunteer

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.

项目概要/摘要 该提案的目的是将双磁共振成像（dualMRI）转化为测量椎间盘的新无创方法 椎间盘（IVD）生物力学，对人类。 IVD 变性是一种常见的骨科问题，困扰着数百万人 在美国的人。 IVD 病理生理学涉及破坏正常的退行性级联反应。 细胞外基质蛋白合成并增加炎症细胞因子和酶的表达。 IVD 生物力学功能对退化敏感，三维内部模式发生改变 (3D)与髓核(NP)中水分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，退化级联引起 许多潜在的治疗靶点。在终末期治疗（例如脊柱融合）之前，有多种可能 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 去神经术。理想的治疗最终会 恢复 IVD 的生物力学功能，其特征是内部应变场揭示局部修复和 损伤后愈合。目前没有可用于测量 3D 生物力学的体内方法 整个 IVD 内部的功能。努力开发一种非侵入性的成像生物标志物 为了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 （MRI 施加载荷下的位移）用于测量内部机械应变 关节软骨和 IVD。我们现在准备实施双MRI来进行体内测量 具有健康和退化腰椎 IVD 的志愿者的生物力学。我们将制定一个工作协议 人类志愿者体内双 MRI，包括定制机械加载方法和 MRI 脉冲 序列，在未来的应用中将很容易扩展到更大规模的病理和临床研究。我们 将追求两个目标。在目标 1 中，我们将实施 DualMRI 来测量人体椎间盘的 3D 模式 拉紧。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 如果成功的话，我们将为IVD的无创和体内功能评估提供一种新工具。这 这项工作将为肌肉骨骼、制药和整形外科界提供（a）临床 评估治疗剂针对动物和人类早期退化的功效的诊断工具 试验，(b) 使用新兴生物疗法对 IVD 愈合和修复进行功能评估的能力，(c) 描述人类 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（例如半月板、韧带）的机械功能。