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

描述(申请人提供)：四肢的平民和战斗创伤往往会导致周围神经的严重损伤，导致严重的发病率。创伤处理的进步显著降低了总体死亡率；然而，由于周围神经损伤，患者留下了显著的残疾和发病率。迫切需要可靠的措施来监测神经损伤和修复，以便在临床上做出知情的管理决策。目前，可以早期评估创伤性神经损伤再生的非侵入性技术在临床上还不可用。我们建议开发和验证基于无创磁共振(MR)的扩散张量成像(DTI)技术，以监测创伤后神经的退行性和再生性反应。我们假设DTI参数的改变可以检测神经纤维的退化和再生。我们在动物身上的初步研究支持了我们的假设，即这项技术可以测量受损神经中的沃勒样退化和再生。结果表明，利用该技术可以对正常的人体神经进行成像，从而支持了该项目的可行性。这一领域的知识空白包括：a)不同周围神经的标准DTI参数；以及b)证明DTI技术在检测人类周围神经退化和再生方面的有效性的研究。我们的具体目标是：1)建立基于体内DTI的人体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疾病周围神经变性和再生的体内成像技术。这项拟议研究的目标是收集对照的标准数据，并将其应用于接受神经修复的完全性神经损伤(桑德兰V级)患者。在这个评估DTI技术的初始项目中，将重点放在完全神经损伤和神经修复的患者身上的主要原因是，在这种临床情况下，由于完全去神经和随后的神经残端再神经支配，DTI参数预计会有最大的变化，这将允许在个别神经中设置DTI参数的阈值。DTI参数将与目前用于评估神经再生的临床、电诊断和组织学(如果可用)措施相关联。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，这项技术将促进这些患者的医疗管理决策。这些研究可能为对照组和完全失神经的神经节段建立不同DTI参数的阈值，这将提供重要的比较数据范围，具有潜在的可应用于非创伤性神经病变的情况，以监测神经退化和再生。

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.