Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic

描述（由申请人提供）：平民和战斗创伤肢体往往导致周围神经严重损伤，导致显著发病率。创伤管理的进步显著降低了总死亡率；然而，由于周围神经损伤，患者会留下严重的残疾和发病率。迫切需要可靠的措施来监测神经损伤和修复，以便在临床做出明智的管理决策。目前，用于早期评估外伤性神经损伤再生的无创技术在临床实践中尚不可用。我们建议发展和验证基于非侵入性磁共振（MR）的弥散张量成像（DTI）技术，以监测创伤后神经的退行性和再生反应。我们假设DTI参数的改变可以检测神经纤维变性和再生。我们在动物身上的初步研究支持了我们的假设，即这种技术可以测量受损神经的沃勒氏样变性和再生。我们的研究表明，正常的人类神经可以用这种技术成像，支持这个项目的可行性。这方面的知识缺口包括：a)不同周围神经的规范DTI参数的缺乏；b)研究表明DTI技术在检测人类周围神经变性和再生方面的效用。我们的具体目标是：1)建立基于活体dti的人类完整周围神经成像技术；2)建立基于dti的人体外伤性周围神经病变周围神经退化与再生成像技术。拟议研究的目标是收集对照组的规范数据，并将其应用于接受神经修复的完全性神经损伤（Sunderland grade V）患者。在本初步评估DTI技术的项目中，重点关注完全神经损伤和神经修复的患者，主要原因是在这种临床情况下，由于远端神经残端完全去神经并随后再神经化，DTI参数变化最大，从而可以建立单个神经的DTI参数阈值。DTI参数将与目前使用的临床、电诊断和组织学（如果可用）措施相关联，以评估神经再生。DTI技术在完全性神经损伤患者中的验证，将使该技术在临床不同程度的创伤性神经损伤患者中得到更广泛的应用。我们预计这项技术将有助于这些患者的医疗管理决策。这些研究可能为对照和完全失神经节段的不同DTI参数建立阈值，这将提供重要的比较数据范围，并可能适用于非创伤性神经性疾病监测神经变性和再生。

DESCRIPTION (provided by applicant): Civilian and combat trauma to limbs often results in serious injuries to the peripheral nerves that cause significant morbidity. Advances in trauma management have significantly reduced overall mortality; however, patients are left with significant disability and morbidity due to peripheral nerve injuries. There is an acute need for reliable measures to monitor nerve injury and repair to make informed management decisions in clinic. Currently, noninvasive techniques that allow early assessment of regeneration in traumatic nerve injuries are not available in clinical practice. We propose to develop and validate non-invasive magnetic resonance (MR) based diffusion tensor imaging (DTI) technology, to monitor the degenerative and regenerative response in the nerves after traumatic injuries. We hypothesize that alterations in DTI parameters can detect nerve fiber degeneration and regeneration. Our preliminary studies in animals support our hypothesis that this technique can measure Wallerian-like degeneration and regeneration in the injured nerves. We show that normal human nerves can be imaged with this technology supporting the feasibility of this project. The gaps in knowledge in this area include lack of: a) normative DTI parameters for different peripheral nerves; and b) studies demonstrating utility of DTI technology to detect peripheral nerve degeneration and regeneration in humans. Our specific Aims are: 1) To establish in vivo DTI-based techniques of imaging intact peripheral nerves in humans; and 2) To establish in vivo DTI-based techniques of imaging peripheral nerve degeneration and regeneration in traumatic peripheral nerve disorders in humans. The goals of the proposed studies are to collect normative data in controls and apply it to patients with complete nerve injuries (Sunderland grade V) undergoing nerve repairs. The principle reason to focus on patients with complete nerve injury and nerve repair in this initial project evaluating DTI technology is that in this clinical situation maximal change in DTI parameters is expected because of complete denervation and subsequent reinnervation of the distal nerve stumps, which will allow setting up thresholds of DTI parameters in individual nerves. DTI parameters will be correlated with currently used clinical, electrodiagnostic, and histological (when available) measures to assess nerve regeneration. Validation of DTI technology in patients with complete nerve injuries will allow broader application of this modality in patients with different grades of traumatic nerve injuries in clinic. We anticipate that this technology will facilitate medical management decisions in these patients. These studies are likely to establish thresholds for different DTI parameters in controls and completely denervated nerve segments, which will provide important range of comparative data with potential applicability to non-traumatic neuropathic conditions to monitor nerve degeneration and regeneration.