In-vivo characterization of pancreatic field carcinogenesis using spatially resolved reflectance measurements via a fiber optic probe

 描述(申请人提供)：胰腺癌(PC)是最致命的癌症，在过去的十年中总的5年生存率约为7%。这主要是因为PC倾向于在几十年的过程中秘密发展(即从开始到转移超过20年)，直到癌症进展的最后阶段才出现明显的症状。目前尚无适用于PC全人群筛查的技术。该项目的目标是开发和测试一种新的光学技术 PC的检测。这项技术将针对癌症发生的现场效应(FC)中呈现的超微结构变化。FC是一种现象，通过这种现象，组织结构的许多物理变化在整个受累器官的早期时间点发生，远在转移之前。这些物理变化发生在亚衍射(纳米)长度尺度上。光散射技术已经显示出在多种癌症类型的体内和体外研究中检测和表征这些超微结构变化的能力。本项目的目的是在以前工作的基础上扩展和开发一种非侵入性光纤探头，用于在上消化道内窥镜检查过程中探测十二指肠壶腹周围区域的超微结构变化。十二指肠壶腹周围区域可以作为评估癌症风险状况的替代部位，因为它暴露在与胰管(胰液和微生物组)相同的环境中，而胰管不适合进行探查。这个项目的方法将大致分为两个阶段：1)工程阶段和2)临床测试阶段。首先，我将开发模拟以准确地模拟探头设计。我将使用模体来构建、测试和验证探测器设计。然后，该探针将在人体受试者中进行测试，以开发出检测胰腺癌的预测规则，最后，该预测规则将在一组独立的患者中得到验证。

 DESCRIPTION (provided by applicant): Pancreatic cancer (PC) is the most deadly cancer with an overall 5-year survival rate of ~7% over the last decade. This is primarily because PC tends to develop surreptitiously over the course of multiple decades (i.e., over 20 years from initiation to metastasis) with no appreciable symptoms presenting until the very final stages of cancer progression. There are no techniques available which are suitable for population- wide screening of PC. The goal of this project is to develop and test a novel optical technology for the detection of PC. This technology will target the ultrastructural alterations presenting in Field Effect of Carcinogenesis (FC). FC is the phenomenon by which a number of physical alterations in tissue structure occur throughout an entire affected organ at an early time- point, long before metastasis. These physical alterations happen at subdiffractional (nano) length-scales. Light scattering techniques have shown the ability to detect and characterize these ultrastructural alterations in both in-vivo and ex-vivo studies for multiple cancer types. The purpose of this project is to extend on previous work and develop a noninvasive fiber optic probe for use during an upper endoscopy procedure to probe the periampullary region of the duodenum for ultrastructural alterations. The periampullary region of the duodenum serves as a surrogate site from which cancer risk status can be assessed, since it is exposed to the same milieu as the pancreatic duct (pancreatic juices and microbiome) and the pancreatic duct is not practical for probing. The approach of this project will be divided into roughly two phases: 1) an engineering phase and 2) a clinical testing phase. First I will develop simulations to accurately model the probe design. I will build, test, and validate the probe design with phantoms. The probe will then be tested with human subjects to develop a prediction rule for detecting pancreatic cancer, and finally the prediction rule will be validate with an independent set of patients.