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

描述(由申请人提供)： 这项研究的目的是开发一种基于光纤的角度分辨低相干干涉(a/LCI)技术，这是一种基于弹性散射光的干涉检测的新光学技术，用于探测人的食道上皮细胞的形态。A/LCI能够定量测量细胞核大小和染色质质地等细胞特征，不需要外源染色或固定剂，使其成为体内检测癌前组织状态(如上皮内瘤变)的极佳候选工具。顾名思义，a/lci使用低相干干涉仪检测散射光的角度分布。通过利用宽带光的相干特性，该技术能够选择性地检测从被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癌前病变的上皮组织尤其重要，在上皮组织中，基底细胞层的变化是最能诊断组织健康的，大约在表面下100亩/米。 这项研究的长期目标是创造一种新的基于a/lci的生物医学诊断技术，用于内窥镜下识别和监测人类上皮组织中的肿瘤转化。这里提出的研究计划将评估创建基于a/LCI的临床仪器的可行性，在R21(第1年)的初始阶段实现以下里程碑：(1)开发快速扫描a/LCI原型，建立通过光纤测量角度分布的可行性；(2)利用组织模体和体外细胞培养展示新原型系统的能力；以及(3)表征新原型系统在探测体外人体组织核形态方面的敏感性。在随后的研究计划R33阶段，我们将完善a/LCI作为临床技术，实现下列里程碑：(1)实现一个使用光纤探头的便携式快速扫描a/LCI系统，并将其应用于新鲜切除的人体组织；(2)开发一种与内窥镜兼容的便携式a/LCI系统，并通过对人体食道组织的体内核形态测量来验证其功能；(3)完善内窥镜下的a/LCI系统，以实现正向和侧向观察，并展示其在体内临床应用中的效用。

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.