Diffusion MRI Biomarkers of Peripheral Nerve Trauma

项目总结 如果不及时治疗，创伤后周围神经损伤会导致灾难性的感觉运动功能丧失 以及时的方式。在严重情况下，需要手术修复以恢复功能，但结果仍不佳。 MAL(失败率达到40%)。虽然电诊断是神经功能和 肌肉失神经，通常很难解释损伤后的早期，限制了我们确定 手术干预是必要的。手术后，电诊断也可能需要数月时间才能显示 轴突是否在修复部位萌发，并朝着它们的运动或感觉目标再生。在……里面 在这两种情况下，这往往会导致依赖于Rin-Rin的临床表现的“等待和观察”方法。 神经功能(例如，感觉运动功能的恢复)，最终延迟临床决策和治疗。 增加永久性肌肉萎缩、感觉丧失和痛性神经瘤形成的可能性。赠送- 在这些限制下，在整个恢复过程中监测神经再生的生物标记物将注入- 通过允许更早地识别i)需要手术的神经和ii)来证明感觉运动结果 手术后修复失败，甚至在后一种情况下指导重新手术(必要时)。扩散张量IM- 老化(DTI)是一种MRI方法，可产生对神经病理敏感的指数(如分数各向异性，FA)。 我们先前证明：1)大鼠离体神经的FA值与轴突密度和行为学有关 创伤和手术修复后的结果和ii)来自人类神经的FA值报告手术失败， 二次手术成功，伤情严重。虽然前景看好，但还需要更大规模的研究来进行临床验证。 考虑到创伤性神经损伤的异质性，这是一种不同的评估方法。此外，我们知道DTI缺乏特异性- 在创伤后早期出现并发的水肿和退化/再生。为了配合这些挑战- ES，我们的首要目标是通过i)开发将神经扩散生物标记物推向临床试验准备 先进的扩散方法，增强了再生的病理特异性；ii)展示了 跨MRI供应商/站点的一致性；iii)并通过扩展到更大规模的多站点来提供临床验证 一项评估手术前后磁共振扩散成像是否能预测临床结果的研究。这个多元PI项目 代表着在高级周围神经核磁共振方面拥有专业知识的科学家和 世界级的周围神经外科医生。我们将利用技术和临床上的互补专业知识 团队将基于球面平均技术(SMT)和Opti-Net确定基于扩散的新型生物标志物。 调整/评估绩效。我们假设SMT参数以更高的水平预测手术结果 其灵敏度和特异度均高于DTI和标准临床方法。如果成功，这些基于SMT的双 征兆标志将允许医生建议手术干预，并在治愈前更早发现失败的修复。 最近很有可能。一旦确定，这些方法也可能对近端损伤有临床实用价值，其中 由于检测再生失败所需的时间较长，目前恢复的预后很差。

PROJECT SUMMARY Peripheral nerve damage following trauma results in catastrophic loss of sensorimotor function if not treated in a timely manner. In severe cases, surgical repair is required to regain function, but outcomes remain subopti- mal (with a failure rate reaching 40%). While electrodiagnostics are valuable indicators of nerve function and muscle denervation, they are often challenging to interpret early post-injury, limiting our ability to determine if surgical intervention is warranted. After surgery, it can also take many months for electrodiagnostics to indicate whether axons are sprouting across the repair site and regenerating toward their motor or sensory target. In both cases, this often results in a “wait and watch” approach that relies on the clinical manifestations of rein- nervation (e.g., the return of sensorimotor function), which ultimately delays clinical decision-making and in- creases the likelihood of permanent muscle atrophy, sensory loss, and the formation of painful neuromas. Giv- en these limitations, a biomarker that monitors nerve regeneration throughout the recovery process would im- prove sensorimotor outcomes by allowing for the earlier identification of i) nerves that require surgery and ii) failed repairs after surgery, even guiding re-operation (when necessary) in the latter case. Diffusion tensor im- aging (DTI) is an MRI method that yields indices (e.g., fractional anisotropy, FA) sensitive to nerve pathologies. We previously demonstrated that i) FA values from ex vivo rat nerves relate to axon density and behavioral outcomes following trauma and surgical repair and ii) FA values from human nerves report on failed surgeries, successful reoperations, and injury severity. While promising, larger-scale studies are required for clinical vali- dation given the heterogeneous nature of traumatic nerve injuries. Furthermore, we know that DTI lacks speci- ficity in the presence of concurrent edema and de/regeneration early after trauma. In line with these challeng- es, our overarching goal is to move nerve diffusion biomarkers toward clinical trial readiness by i) developing advanced diffusion methods with increased pathological specificity to regeneration; ii) demonstrating con- sistency across MRI vendors/sites; iii) and providing clinical validation by expanding to a larger-scale, multi-site study to evaluate whether pre- and post-surgical diffusion MRI predicts clinical outcomes. This multi-PI project represents a unique collaboration between scientists with expertise in advanced peripheral nerve MRI and world-class peripheral nerve surgeons. We will use the complementary technical and clinical expertise of the team to identify novel diffusion-based biomarkers based on the spherical mean technique (SMT) and opti- mize/evaluate performance. We hypothesize that SMT parameters predict surgical outcomes with higher levels of sensitivity and specificity than both DTI and standard clinical methods. If successful, these SMT-based bi- omarkers will allow physicians to recommend surgical interventions and detect failed repairs earlier than is cur- rently possible. Once established, these methods will also likely be of clinical utility in proximal injuries, where the prognosis for recovery is currently poor due to the prolonged time required to detect failed regeneration.