Quantitative Assessment of Peripheral Nerve Injury and Repair via Multi-Parametric MRI

通过多参数 MRI 定量评估周围神经损伤和修复

• 批准号: 10057154
• 负责人: Richard Dortch
• 金额: $ 21.61万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057154
• 关键词: Quantitative; Assessment; Peripheral; Nerve; Injury

PROJECT SUMMARY The overall goal of this proposal is to develop and evaluate a multi-parametric set of quantitative MRI (qMRI) tools for monitoring the microstructural changes associated with traumatic peripheral nerve injury (TPNI) and subsequent surgical repair. Up to 5% of all admissions to level I trauma centers have a TPNI; and a significant increase in the incidence of TPNI has been noted in recent military missions. Common etiologies include trauma to limbs from penetrating injury, crush, stretch, and ischemia. Clinical management of TPNI faces two limitations: i) the inability to acutely identify injuries that require surgery (e.g., nerve lacerations) and ii) the inability to detect failed nerve surgeries prior to muscle re-innervation—may take months or years depending on the injury site. Due to these limitations, physicians are required to a “wait and watch” using qualitative measures obtained from patient history and physical exam. This results in delayed management and increased instances of permanent motor/sensory loss. Quantitative MRI (qMRI) techniques may provide a non-invasive, quantitative characterization of nerve microstructure in vivo following trauma and throughout the recovery process (i.e., prior to muscle re-innervation). We propose to develop and evaluate qMRI techniques for this purpose. If successful, these strategies could improve outcomes by i) identifying patients that require surgery and ii) identifying surgical failures earlier than current techniques, even guiding re-operation. The proposed qMRI methods will be developed and evaluated as potential biomarkers of nerve recovery via human studies in the median/ulnar nerves of the forearm and wrist. We will first develop and optimize qMRI methods of these nerves (Aim 1). MRI of peripheral nerves is challenging due a number of factors, including the need for fast, high-resolution imaging and the influence of fat. The PI has previously shown success in developing and optimizing qMRI methods to evaluate inherited neuropathies. Here, we will build upon these previous developments and employ quantitative magnetization transfer and diffusion imaging to assay Wallerian degeneration and axonal outgrowth following injury/repair, respectively. We have shown that inflammation confounds diffusion-based assessments of nerve recovery in a rat model of trauma. As a result, we will also evaluate models the account for the influence of inflammation. Once optimized, we will perform cross-sectional studies (Aim 2) in patients with nerve injuries of varying severity to evaluate the ability of qMRI to identify injuries that require surgery. We will also perform longitudinal studies (Aim 3) following surgery to evaluate the ability of qMRI to monitor nerve regeneration, with results compared to EMG/NCS and function (e.g., grip strength). Finally, we will explore MRI methods to monitor the downstream effects of TPNI on skeletal muscle, as this information may improve future revisional surgery recommendations when failed repairs are detected. Specifically, we will measure T2/fat-fraction (reports on acute/chronic denervation) in muscles innervated by the median/ulnar nerves (e.g., muscles of the hand) to assess their viability after nerve repair.

项目摘要 本提案的总体目标是开发和评价定量MRI（qMRI）的多参数集 用于监测与创伤性周围神经损伤（TPNI）相关的微结构变化的工具， 随后进行手术修复。一级创伤中心的所有入院者中，高达5%的人患有TPNI; 在最近的军事任务中，注意到TPNI的发生率有所增加。常见病因包括 穿透性损伤、挤压、拉伸和局部缺血对四肢造成的创伤。TPNI的临床管理面临两个问题 局限性：i）不能精确地识别需要手术的损伤（例如，神经撕裂）和ii） 在肌肉神经重建之前无法检测到失败的神经手术-可能需要数月或数年的时间，具体取决于 受伤部位。由于这些限制，医生需要使用定性测量方法进行“等待和观察” 从病人的病史和身体检查中获得。这导致延迟管理和增加的情况 永久性运动/感觉丧失定量MRI（qMRI）技术可以提供非侵入性的， 创伤后和整个恢复过程中体内神经微观结构的定量表征 (i.e.,在肌肉神经再支配之前）。为此，我们建议开发和评估qMRI技术。如果 如果成功，这些策略可以通过i）识别需要手术的患者和ii） 比现有技术更早识别手术失败，甚至指导再次手术。拟议的qMRI 方法将通过人体研究开发和评估神经恢复的潜在生物标志物， 前臂和手腕的正中/尺神经。我们将首先开发和优化这些神经的qMRI方法 (Aim 1）。 周围神经的MRI由于许多因素而具有挑战性，包括需要快速， 高分辨率成像和脂肪的影响。PI以前在开发和 优化qMRI方法以评估遗传性神经病。在这里，我们将在这些先前发展的基础上 并采用定量磁化传递和扩散成像来测定沃勒变性， 损伤/修复后轴突生长。 我们已经证明，炎症 基于扩散的创伤大鼠模型中神经恢复的评估。因此，我们还将评估模型 解释炎症的影响。一旦优化，我们将进行横断面研究（目标2） 在不同严重程度的神经损伤患者中，评估qMRI识别损伤的能力， 需要手术 我们还将在手术后进行纵向研究（目标3），以评估 qMRI监测神经再生，结果与EMG/NCS和功能（例如， 握力）。 最后，我们将探索MRI方法来监测TPNI对骨骼肌的下游影响，因为这 当检测到失败的修复时，该信息可以改进未来的修正手术建议。 具体来说，我们将测量T2/脂肪分数（关于急性/慢性去神经支配的报告）， 正中/尺神经（例如，手的肌肉）以评估它们在神经修复后的生存能力。