In vivo detection of pre-cancerous lesions using a/LCL

描述（由申请人提供）： 本研究的目的是开发一种基于光纤的角度分辨低相干干涉测量（a/LCI），一种基于弹性散射光干涉检测的新型光学技术，用于探测人类食管上皮细胞形态。a/LCI获得细胞特征（如核大小和染色质质地）的定量测量的能力，而不需要外源性染色剂或固定剂，使其成为用于癌前组织状态（如上皮内瘤形成）的体内检测的筛选工具的优秀候选者。顾名思义，a/LCI使用低相干干涉仪检测散射光的角分布。该技术能够通过利用宽带光的相干特性来选择性地检测从探测组织内的小区域散射的光场。探测亚表面细胞形态的能力对于检测上皮组织中的癌前变化特别重要，其中表面下约100 μ/m2的基底细胞层的变化是组织健康的最佳诊断。 本研究的长期目标是创建一种新的基于a/LCI的生物医学诊断技术，用于内窥镜识别和监测人类上皮组织中的肿瘤转化。本文提出的研究计划将通过在初始R21（第1年）阶段实现以下里程碑来评估创建基于a/LCI的临床仪器的可行性：（1）开发快速扫描a/LCI原型，该原型建立了通过光纤测量角分布的可行性;（2）使用组织模型和体外细胞培养来展示新原型系统的能力;和（3）表征新原型系统在探测离体人组织中的核形态学中的灵敏度。在研究计划的后续R33阶段，我们将通过实现以下里程碑来完善a/LCI作为临床技术：（1）实现使用光纤探针的便携式快速扫描a/LCI系统并将其应用于新鲜切除的人体组织，（2）开发一种兼容内窥镜的便携式a/LCI系统，并通过人体食管组织的体内核形态学测量验证其功能;（3）完善内镜a/LCI系统，以实现前视图和侧视图，并证明其在体内临床应用中的实用性。

DESCRIPTION (provided by applicant): The objective of this research is to develop a fiber optic-based implementation of Angle-resolved Low Coherence Interferometry (a/LCI), a novel optical technique based on interferometric detection of elastically scattered light, for the purpose of probing the cellular morphology of human esophageal epithelium. The ability of a/LCI to obtain quantitative measurements of cellular characteristics such as nuclear size and chromatin texture, without the need for neither exogenous stains nor fixatives, makes it an excellent candidate to become a screening tool for in vivo detection of pre-cancerous tissue states such as intraepithelial neoplasia. As its name implies, a/LCI detects the angular distribution of scattered light using a low-coherence interferometer. The technique enables selective detection of the optical field scattered from a small region within probed tissue by exploiting the coherence properties of broadband light. The ability to probe sub-surface cellular morphology is especially important for detecting pre-cancerous changes in epithelial tissues, where changes in the basal cell layer, approximately 100 mu/m beneath the surface, are most diagnostic of tissue health. The long-range goal of this research is to create a new a/LCI-based biomedical diagnostic technique for the purpose of endoscopically identifying and monitoring neoplastic transformation in human epithelial tissues. The research plan proposed here will evaluate the feasibility of creating clinical instrumentation based on a/LCI by achieving the following milestones during the initial R21 (year 1) phase: (1) development of a rapid scanning a/LCI prototype which establishes the feasibility of measuring angular distributions via optical fiber; (2) demonstration of the capabilities of the new prototype system using tissue phantoms and in vitro cell cultures; and (3) characterization of the sensitivity of the new prototype system in probing nuclear morphology in ex vivo human tissues. During the subsequent R33 phase of the research plan, we will refine a/LCI as a clinical technique by achieving the following milestones: (1) implement a portable rapid scanning a/LCI system which uses an optical fiber probe and apply it to freshly excised human tissues, (2) develop an endoscope-compatible version of the portable a/LCI system and validate its functionality with in vivo nuclear morphology measurements of human esophageal tissues and (3) refine the endoscopic a/LCI system to enable forward and sideways views and demonstrate its utility with in vivo clinical application.