Optical Spectroscopy for Minimally Invasive Pancreatic Cancer Risk-stratification

描述（由申请人提供）：本R21申请的主要目的是探索两种新型互补光学技术的潜力，四维弹性光散射指纹（4D-ELF）和低相干后向散射（LEBS）光谱，用于胰腺癌的微创诊断，而无需对胰腺进行检查。这项工作建立在我们开发的这两种光学技术的基础上，用于在癌变早期对组织纳米/微结构中细微的组织学上不可检测的变化进行原位传感，并成功完成了人体试验研究。胰腺癌是预后最差的疾病之一，5年总生存率<5%。这种不良预后的原因是，大多数胰腺癌只有在晚期才被诊断出来，无法治愈。目前的影像学技术，包括CT、MRI、超声和内窥镜胰胆管造影（ERCP）都不能可靠地检测胰腺癌前病变或早期病变。此外，尽管经过多年的研究，尚未发现临床上适当的分子标记物。重要的是，通过胰管检查（如ERCP）进行广泛的胰腺癌筛查是不可行的，因为严重并发症（约20%）的风险非常高，包括胰腺炎（约5%），这些并发症基本上是由胰管的任何检查引起的，包括活检、光纤评估和涂刷。我们的目标是开发一种生物光子学方法，用于胰腺癌的早期检测，而无需对胰腺进行检查。我们的策略是基于检测胰腺癌发生的“场效应”，即在特定组织部位导致肿瘤病变的遗传/环境环境也应该在该部位之外检测到。这为通过检查十二指肠壶腹周围粘膜来诊断胰腺肿瘤的风险提供了可能性，通过现有的上内镜技术可以很容易地到达十二指肠壶腹周围粘膜，而不会有胰腺炎的风险。我们已经获得了试点数据，支持这种方法在胰腺和其他器官中的可行性。

DESCRIPTION (provided by applicant): The major objective of this R21 application is to explore the potential of two novel complimentary optical techniques, four-dimensional elastic light scattering fingerprinting (4D-ELF) and low-coherence backscattering (LEBS) spectroscopy, for minimally invasive diagnosis of pancreatic cancer without the need for interrogation of the pancreas. The work builds upon our development of these two optical techniques for in situ sensing of subtle histologically-undetectable changes in tissue nano/micro-architecture in early stages of carcinogenesis and completion of successful pilot human studies. Pancreatic cancer has one of the worst prognoses with an overall 5-year survival rate of <5%. The reason for this poor prognosis is that most pancreatic cancers are diagnosed only at a late, incurable stage. No current imaging techniques including CT, MRI, ultrasound and endoscopic cholangiopancreatography (ERCP) can reliably detect pancreatic precancerous or early cancerous lesions. Moreover, despite years of research, no clinically adequate molecular markers have been identified. Importantly, widespread pancreatic cancer screening by means of examination of the pancreatic duct (e.g., ERCP) is not feasible due to a very high risk of serious complications (approximately 20%) including pancreatitis (approximately 5%) caused by essentially any interrogation of the pancreatic duct including biopsy, fiber-optic evaluation, and brushing. Our objective is to develop a biophotonics approach for the early detection of pancreatic cancer without the need for interrogation of the pancreas. Our strategy is based on detection of the "field-effect" of pancreatic carcinogenesis, the proposition that the genetic/environmental milieu that results in a neoplastic lesion in a particular tissue site should be also detectable outside this location. This opens up a possibility to diagnose the risk of pancreatic neoplasia by examination of the duodenal periampullary mucosa, which can be readily accessed by means of existing upper endoscopy techniques without the risk of pancreatitis. We have obtained pilot data supporting the feasibility of this approach in the pancreas and other organs.