Development of imaging probes for surgery

手术用成像探头的开发

• 批准号: 10702805
• 负责人: Ingrid Schroeder
• 金额: $ 3.33万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702805
• 关键词: Address; American; Cancer Patient; Chemicals; Clinical; Contrast Media; Cystine; Development; Disease; Excision; Fresh Tissue; Harvest; Histologic; Human; Image; Intuition; Label; Medical; Modification; Mus; Nerve; Neurons; Noise; Operative Surgical Procedures; Palpation; Patients; Peptides; Peripheral; Peripheral Nerves; Peripheral Nervous System; Peripheral nerve injury; Plant Roots; Signal Transduction; Sodium Channel; Surgeon; Tissues; Tracer; Trauma; Traumatic injury; Visual; clinical practice; fluorescence microscope; imaging probe; improved; nerve injury; preservation; prevent; sciatic nerve; sensor; side effect; standard of care; surgery outcome; tumor; vector; voltage

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.

2000万美国人患有由创伤引起的外周神经损伤， 医学疾病，导致广泛的潜在衰弱副作用。在 四分之一的病人认为手术是他们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，组织变形和不良 可见性可以挑战外科医生精确定位和保留外周血管的能力， 神经直觉上，如果神经能够被修复， 使用外源性造影剂突出显示。在临床实践中，目前 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问题， 根据临床需要，我们探索了电压门控钠通道Nav1.7的表达， 周围神经系统的术中标记物。我们发现Nav1.7的表达是 从人类和小鼠组织中获取的外周神经中含量都很高。我们进一步表明， Nav1.7选择性肽Hsp 1a的修饰可以作为靶向载体， 将荧光传感器递送到外周神经系统。离体，我们观察到高的 在组织学制备的和 新鲜的组织使用手术荧光显微镜，我们在模拟临床 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和它们的神经细胞。 在常规临床环境中观察周围组织。