Development of imaging probes for surgery

2000万美国人因创伤和医疗疾病导致的周围神经损伤，导致了一系列潜在的削弱副作用。在四分之一的病例中，患者认为手术是他们神经损伤的根本原因。尤其是在肿瘤切除或创伤后，组织扭曲和能见度低可能会挑战外科医生精确定位和保护周围神经的能力。直觉上，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。为了解决这一未得到满足的临床需求，我们探索了电压门控钠通道Nav1.7的表达作为手术中周围神经系统的标志物。我们发现，Nav1.7在从人和小鼠组织中采集的周围神经中都有高表达。我们进一步证明，对Nav1.7选择性多肽Hsp1a的修饰可以作为靶向载体，将荧光传感器输送到周围神经系统。在体外，我们观察到荧光标记的Hsp1a在组织学准备和新鲜组织中的高信噪比。使用外科荧光显微镜，我们在模拟的临床场景中展示了识别小鼠坐骨神经的可能性，这表明荧光标记的Hsp1a示踪剂可以在常规的临床环境中用于区分神经及其周围组织。

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.