Validation and commercialization of a/LCI for detection of esophageal neoplasia

描述（由申请人提供）：本研究的目的是将一种器械（Oncoscope Panocyte系统）商业化，该器械用于在早期食管癌的标准内镜监测期间指导Barrett食管（BE）患者的活检选择。巴雷特食管最常发生在慢性酸反流患者中，是食管腺癌发生的最强风险因素。目前的监测标准，即白光内窥镜引导的随机活检，受到严重限制，因为早期病变在成像过程中不可见，并且在单次手术中只能筛选少量的风险组织。Panocyte”系统利用基于角度分辨低相干干涉测量（a/LCI）的技术。它提供了一个高度敏感的癌症筛查工具，通过它的能力，使定量测量的细胞特征，如核大小，这是已知的高度相关的癌症进展。Panocyte系统的非侵入性和实时性使临床医生能够检查更大部分的高危组织，并且其选择性探测组织基底层的能力，疾病首先出现，使他们能够在癌症前阶段检测食管癌，当它是有效治疗的。有了这些功能，在食管内窥镜检查过程中使用Panocyte来指导活检选择，最终可以通过更彻底的检查实现更早的检测，通过最大限度地减少非异型增生组织的活检来降低医疗成本，并全面改善患者的预后和生活质量。在NIH SBIR计划的I期，Oncoscope成功开发了一种商业原型a/LCI设备，能够在大鼠Barrett食管模型中区分非发育异常和发育异常组织。在第二阶段，我们通过改进Panocyte系统的设计来扩大第一阶段的工作，以提高商业和临床可行性，同时还作为175名患者试点试验的一部分在体内展示其临床操作特性。基于以下具体目标，我们的IIB期研究计划将通过对食管a/LCI临床系统进行产品验证和确认，进一步实现全面商业化，最终向FDA提交我们的监管申请，用于食管a/LCI引导切除活检：（1）完成产品开发并进行初始制造和组装，以完成食管a/LCI临床系统的设计验证，（2）进行关键临床试验和用户界面研究，以进行使用a/LCI引导食管切除活检的设计确认;（3）完成食管a/LCI临床系统的制造过程确认和设计转移。 公共卫生相关性：本研究的目的是商业化的一种新的仪器，用于检测早期食管癌的基础上，一种新的光学技术，角度分辨低相干干涉（a/LCI）。所提出的a/LCI仪器将作为Barrett食管患者内窥镜检查期间活检选择的指南，从而能够在组织去除之前对原位组织健康进行实时非侵入性评估，并大大改善当前的护理标准，随机活检。使用a/LCI靶向活检有可能大大提高食管癌的监测，在早期发现它，而它仍然是可治疗的。

DESCRIPTION (provided by applicant): The objective of this research is to commercialize a device (the Oncoscope Panocyte" system) used to guide biopsy selection in patients with Barrett's esophagus (BE) during standard endoscopy surveillance for early- stage esophageal cancer. Barrett's esophagus most often develops in patients with chronic acid reflux and is the strongest risk factor for development of esophageal adenocarcinoma. The current standard of care for surveillance, random biopsy guided by white-light endoscopy, is severely limited, since early-stage lesions are not visible during imaging and only a small amount of at-risk tissue can be screened during a single procedure. The Panocyte" system utilizes technology based on angle-resolved low coherence interferometry (a/LCI). It provides a highly sensitive tool for cancer screening through its ability to make quantitative measurements of cellular characteristics, such as nuclear size, that are known to be highly correlated to cancer progression. The non-invasive and real-time nature of the Panocyte" system allows clinicians to examine a greater portion of at-risk tissue, and its ability to selectively probe the basal layer of tissue, where disease first manifests, allows them to detect esophageal cancer in its pre-cancer stages when it is effectively treatable. With these capabilities, using Panocyte" to guide biopsy selection during esophageal endoscopy procedures could ultimately deliver earlier detection via more thorough examination, a reduction in health-care costs by minimizing biopsy of non-dysplastic tissue, and overall improvement in patient outcomes and quality of life. In Phase I of the NIH SBIR program, Oncoscope successfully developed a commercial prototype a/LCI device capable of discriminating between non-dysplastic and dysplastic tissues in a rat Barrett's esophagus model. In Phase II, we expanded on the Phase I work by improving the Panocyte" system design for enhanced commercial and clinical viability, while also demonstrating its clinical operating characteristics in vivo as part of a 175-patient pilot trial. With the following specific aims, our research plan for Phase IIB will build further toward full commercialization by conducting product verification and validation of the esophageal a/LCI clinical system, culminating in the submission of our regulatory application to the FDA for a/LCI-guided excisional biopsy in the esophagus: (1) Finalize product development and perform initial manufacturing and assembly in order to complete design verification of the esophageal a/LCI clinical system, (2) Conduct pivotal clinical trial and user interface study for design validation of using a/LCI to guide excisional biopsy in the esophagus, and (3) Complete manufacturing process validation and design transfer of the esophageal a/LCI clinical system. PUBLIC HEALTH RELEVANCE: The objective of this research is to commercialize a new instrument for detecting early-stage esophageal cancer based on a novel optical technique, angle-resolved low coherence interferometry (a/LCI). The proposed a/LCI instrument will serve as a guide to biopsy selection during endoscopy in patients with Barrett's esophagus, enabling real-time non-invasive evaluation of tissue health in situ prior to tissue removal and greatly improving upon the current standard of care, random biopsy. Using a/LCI to target biopsies has the potential to greatly improve surveillance of esophageal cancer by detecting it in its early stages while it is still treatable.