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

描述（由申请人提供）：四肢的平民和战斗创伤通常会导致周围神经严重受伤，从而导致严重的发病率。创伤管理的进步显着降低了总体死亡率；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，以便在临床上做出明智的管理决策。目前，临床实践中还没有能够早期评估创伤性神经损伤再生的非侵入性技术。我们建议开发和验证基于扩散张量成像（DTI）的非侵入性磁共振（MR）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。我们对动物的初步研究支持了我们的假设，即该技术可以测量受损神经的沃勒样变性和再生。我们证明，可以使用该技术对正常人类神经进行成像，支持该项目的可行性。该领域的知识差距包括缺乏： a) 不同周围神经的标准化 DTI 参数； b) 研究证明 DTI 技术可用于检测人类周围神经变性和再生。我们的具体目标是： 1) 建立基于 DTI 的体内技术，对人体完整的周围神经进行成像； 2) 建立基于 DTI 的体内技术，对人类创伤性周围神经疾病的周围神经变性和再生进行成像。拟议研究的目标是收集对照的规范数据，并将其应用于接受神经修复的完全神经损伤（桑德兰 V 级）的患者。在这个评估 DTI 技术的初始项目中，重点关注完全神经损伤和神经修复的患者的主要原因是，在这种临床情况下，由于远端神经残端的完全去神经支配和随后的神经支配，预计 DTI 参数会发生最大变化，这将允许在单个神经中设置 DTI 参数的阈值。 DTI 参数将与当前使用的临床、电诊断和组织学（如果可用）测量相关联，以评估神经再生。 DTI 技术在完全神经损伤患者中的验证将使该方法在临床上更广泛地应用于不同级别的创伤性神经损伤患者。我们预计这项技术将有助于这些患者的医疗管理决策。这些研究可能会为对照和完全去神经神经节段的不同 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​​神经病变条件，以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.