Prognostic Perfusion Imaging for Nerve Injury

摘要/摘要 周围神经损伤会导致严重的残疾和功能丧失，尽管 神经在受伤后会再生。一个关键的挑战来自建议干预的临床指南。 只有在自发再生失败后。神经显示出最大再生的时间窗 受伤后两周的能力；然而，由于以下原因，确定故障需要3-6个月的延迟 较长距离的神经再生速度较慢。因此，许多伤病注定要失败，因为 缺乏评估损伤严重程度和预测再生能力的非侵入性技术。 我们有证据表明，拉伸损伤是造成毁灭性神经损伤的最常见原因， 主要影响周围神经的血管层以及破坏神经的微结构。 越来越多的证据表明，血管新生是神经再生的关键步骤。然而，非- 有创性血流灌注数据，特别是确定的损伤严重程度和预测再生潜力， 目前很稀缺。我们认为，基于病理生理学的周围神经损伤评估是有效的 在实践中开展这样的评估手段，可以从根本上改变对所有神经损伤的管理。 基于中心假设，即MR灌注将提供对再生的预测洞察力 对于创伤性神经损伤后的潜在风险，目前提案的目的有两个。首先，用理论上的 框架，我们将开发和验证快速磁共振 适用于同时评估神经微循环和微结构的成像方案。 其次，我们将对可复制的、渐变的和生物逼真的组织进行磁共振灌注成像和微结构成像。 神经牵拉损伤模型，以评估我们提出的方法的有效性并开发MRI测量方法 作为损伤严重程度和临床恢复潜力的生物标志物。 。

Summary/Abstract Peripheral nerve injuries cause severe disability and loss of function, despite an inherent capacity for the nerves to regenerate after injury. A key challenge arises from clinical guidelines that recommend intervention only after failure of spontaneous regeneration. Nerves demonstrate a temporal window of maximal regenerative capacity at two weeks following injury; however, determination of failure requires 3-6 months of delay due to slow regeneration rates of nerves over longer distances. Thus, many injuries are doomed to failure due to the lack of noninvasive techniques to assess injury severity and predict regenerative capacity. We have evidence that stretch injury, which is the most common cause of devastating nerve injury, predominantly affects the vascular layer of peripheral nerves as well as destroying nerve microarchitecture. Accumulating evidence indicates that vascular neogenesis is a critical step in nerve regeneration. However, non- invasive perfusion data, especially for identified injury severity and prognosticating regeneration potential, is currently scarce. We believe a pathophysiologic-based assessment of peripheral nerve injuries, and effective means to carry out such assessment in practice, can fundamentally change management of all nerve injuries. Based on the central hypothesis that MR perfusion will provide prognostic insight into the regenerative potential after traumatic nerve injury, the aims of the current proposal are two-fold. First, using the theoretical framework describing anisotropic perfusion we recently introduced, we will develop and validate rapid MR imaging protocols suitable for simultaneous assessments of microcirculation and microstructure in the nerve. Second, we will perform MR perfusion and microstructure imaging on a reproducible, graduated, and biofidelic nerve stretch injury model in order to evaluate the efficacy of our proposed approach and develop MRI metrics as biomarkers for injury severity and potential for clinical recovery. .