Prognostic Perfusion Imaging for Nerve Injury

摘要/摘要 周围神经损伤导致严重的残疾和功能丧失，尽管有固有的能力， 神经损伤后再生。一个关键的挑战来自于建议干预的临床指南 只有在自发再生失败后。神经显示出一个最大的再生时间窗 在受伤后两周的能力;然而，由于以下原因， 长距离神经再生速度缓慢。因此，许多伤害是注定要失败的，由于 缺乏非侵入性技术来评估损伤严重程度和预测再生能力。 我们有证据表明，拉伸损伤，这是最常见的破坏性神经损伤的原因， 主要影响周围神经的血管层以及破坏神经微结构。 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- 有创灌注数据，特别是用于识别损伤严重程度和预测再生潜力的数据， 目前稀缺。我们认为，基于病理生理学的周围神经损伤评估， 在实践中进行这样的评估，可以从根本上改变所有神经损伤的管理。 基于MR灌注将提供再生性肿瘤的预后洞察力的中心假设， 潜在的创伤性神经损伤后，目前的建议的目的是双重的。首先，使用理论 框架描述各向异性灌注，我们最近介绍，我们将开发和验证快速MR 适合于同时评估神经中的微循环和微结构的成像协议。 第二，我们将在可重复的、分级的和生物相容性的MRI上进行MR灌注和显微结构成像。 神经牵张损伤模型，以评估我们提出的方法的有效性，并开发MRI指标 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. .