Clinical validation of a/LCI for detecting pre-cancerous lesions in the esophagus

描述（由申请人提供）：本研究的目的是创建基于角度分辨低相干干涉测量（a/LCI）的新型光学活检系统的临床原型。a/LCI是一种新的光学技术，其使用弹性散射光的干涉检测来探测食管上皮的核形态。α/LCI获得细胞特征（如核大小和光密度）的定量测量而不需要外源性染色剂或固定剂的能力，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 m的基底细胞层的变化是组织健康的最重要诊断。本研究的长期目标是创建一种新的基于a/LCI的生物医学诊断产品，用于内窥镜识别和监测人类肿瘤转化。研究计划将通过实现以下里程碑来创建和测试临床可行的a/LCI系统：（1）进行多点人体临床试验以定量评估α/LCI用于食管发育不良的监测和治疗监测的临床效用，（2）继续I期硬件和探头设计的创新，以优化a/LCI系统的临床应用，以及（3）开发基于a/LCI成像的组织诊断软件。公共卫生相关性：本研究的目的是开发一种新的仪器，用于检测人类上皮组织中的早期癌症的基础上一种新的光学光谱技术，角度分辨低相干干涉（a/LCI）。拟议的a/LCI仪器将作为临床医生活检和治疗监测的指南，在组织切除前能够原位评估组织健康。这项技术有可能大大改善目前的随机活检方法，用于筛查和监测早期上皮癌。

DESCRIPTION (provided by applicant): The objective of this research is to create a clinical prototype of a new optical biopsy system based on angle-resolved low coherence interferometry (a/LCI). a/LCI is a novel optical technique that uses interferometric detection of elastically scattered light to probe the nuclear morphology of esophageal epithelium. The ability of a/LCI to obtain quantitative measurements of cellular characteristics, such as nuclear size and optical density, without the need for either exogenous stains or 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 5m beneath the surface are the most important diagnostic of tissue health. The long-range goal of this research is to create a new a/LCI-based biomedical diagnostic product for the purpose of endoscopically identifying and monitoring neoplastic transformations in humans. The research plan will create and test a clinically viable a/LCI system by achieving the following milestones: (1) conducting multi-site human clinical trials to quantitatively assess clinical utility of a/LCI for surveillance and treatment monitoring of esophageal dysplasia, (2) continuing the innovation of the Phase I hardware and probe design to optimize clinical utility of the a/LCI system and (3) developing software for tissue diagnosis based on a/LCI imaging. PUBLIC HEALTH RELEVANCE: The objective of this research is to develop a new instrument for detecting early stage cancer in human epithelial tissues based on a novel optical spectroscopic technique, angle-resolved low coherence interferometry (a/LCI). The proposed a/LCI instrument will serve as a guide to biopsy and treatment monitoring for clinicians, enabling evaluation of tissue health in situ, prior to tissue removal. This technique has the potential to greatly improve upon the current method of random biopsy for screening and surveillance of early stage epithelial cancers.