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. .
Peripheral nerve injuries are a major cause of disability and societal cost that is currently undertreated due to an inability to accurately predict injury severity and outcomes. We seek to develop a non-invasive technique that determines the injury severity of peripheral nerve trauma, and importantly its regenerative potential, by quantifying microcirculation and microstructure within the nerve. We believe our findings will improve prediction of outcomes, and create a paradigm shift in the treatment of nerve injuries from observational delay to early action.