Peripheral nerve damage is a debilitating consequence of both traumatic injury to the extremities of soldiers, and a secondary outcome following spinal cord injury (SCI). Equally devastating, for both the Veteran and general population, is nerve damage during excision of surrounding tissue, disease, or iatrogenic injury. Functional recovery from nerve damage is often incomplete, resulting in impaired motor function, sensory loss, and pain. Recovery is especially poor for chronic nerve injuries, which can result from unrepaired nerves or from delayed or failed primary repair. A major challenge in treating nerve injury is the current lack of effective methods to medically image nerves. As a consequence, surgeons are unable to accurately assess the extent of nerve injury, plan surgical intervention in an informed and data-driven manner, or assess the success of nerve repair at early time points, to predict long-term recovery. We have developed innovative quantitative strategies for nerve imaging, which overcome challenges created by the complex structure and architecture of nerves. Our approach employs two widely deployed clinical modalities, ultrasound (US) and magnetic resonance imaging (MRI). Our imaging approach is motivated by strong preliminary data demonstrating that quantitative US (qUS) and MRI (qMRI) are powerful and clinically feasible strategies for monitoring nerve structure and composition at high-resolution and with high sensitivity. These approaches are also intended to provide non-invasive surrogates for biological changes that occur during nerve degeneration and regeneration, but which cannot be evaluated in patients. To establish the validity and utility of qUS and qMRI in evaluating nerve structure and composition in a clinical setting, we will address the following specific aims in rat (Aim 1) and human (Aim 2) models of acute and chronic nerve injury: 1) To test the efficacy of quantitative US and MR imaging strategies in assessing neuromuscular morphology and composition during peripheral nerve degeneration and following repair of acute and chronic models of rat sciatic nerve injury. 2) To test the clinical efficacy of quantitative US and MR imaging strategies in assessing neuromuscular morphology and composition in acute and chronic models of human median and ulnar nerve injury immediately prior to surgical repair. Our approach has the potential to transform the diagnosis and treatment of nerve injury. Immediate clinical impacts include: (i) objective guidance on deciding whether to perform nerve repair or nerve transfer surgery; (ii) predicting and monitoring the efficacy of nerve repair; (iii) guidance for post-op rehabilitation protocols. This work will also set the stage for a prospective study in which imaging strategies will be deployed as prognostic tools for predicting the efficacy of neuromuscular recovery following nerve repair, towards improved treatment of nerve injury in Veteran and general populations. More br...