Development of imaging probes for surgery

2000万美国人患有由创伤和医学疾病引起的外周神经损伤，导致广泛的潜在的使人衰弱的副作用。在四分之一的病例中，患者认为手术是神经损伤的根本原因。特别是在肿瘤切除术或创伤性损伤后，组织变形和可见性差可能会挑战外科医生精确定位和保护周围神经的能力。直观地说，如果可以使用外源性造影剂突出神经，手术结果将大大改善。然而，在临床实践中，目前的护理标准-视觉检查和触诊-保持不变。为了解决这一未满足的临床需求，我们探索了电压门控钠通道Nav1.7的表达作为外周神经系统的术中标记物。我们发现Nav1.7在从人和小鼠组织中收获的外周神经中表达很高。我们进一步表明，Nav1.7选择性肽Hsp 1a的修饰可以作为将荧光传感器递送到外周神经系统的靶向载体。离体，我们观察到一个高的信号-噪声比荧光标记的Hsp 1a在组织学准备和新鲜组织。使用手术荧光显微镜，我们在模拟的临床情况下，小鼠坐骨神经的识别是可能的，这表明荧光标记的Hsp 1a示踪剂可用于区分神经从其周围组织在常规的临床设置。

Twenty million Americans suffer from peripheral nerve injury caused by trauma and medical disorders, resulting in a broad spectrum of potentially debilitating side effects. In one out of four cases, patients identify surgery as the root cause of their nerve injury. Particularly during tumor resections or after traumatic injuries, tissue distortion and poor visibility can challenge a surgeon's ability to precisely locate and preserve peripheral nerves. Intuitively, surgical outcomes would improve tremendously if nerves could be highlighted using an exogeneous contrast agent. In clinical practice, however, the current standard of care-visual examination and palpation-remains unchanged. To address this unmet clinical need, we explored the expression of voltage-gated sodium channel Nav1.7 as an intraoperative marker for the peripheral nervous system. We show that expression of Nav1.7 is high in peripheral nerves harvested from both human and mouse tissue. We further show that modification of a Nav1.7-selective peptide, Hsp1a, can serve as a targeted vector for delivering a fluorescent sensor to the peripheral nervous system. Ex vivo, we observe a high signal-to-noise ratio for fluorescently labeled Hsp1a in both histologically prepared and fresh tissue. Using a surgical fluorescent microscope, we show in a simulated clinical scenario that the identification of mouse sciatic nerves is possible, suggesting that fluorescently labeled Hsp1a tracers could be used to discriminate nerves from their surrounding tissues in a routine clinical setting.