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

项目摘要 这项研究的目标是将一种用于引导 Barrett‘s食道(BE)患者在标准内窥镜监测中的活检选择 食道癌分期。Barrett‘s食道最常发生在慢性胃酸反流患者中， 食管腺癌发生的最大危险因素。目前的护理标准是 监测，白光内窥镜引导的随机活检，是严重有限的，因为早期病变 在成像过程中看不到，在一次手术中只有少量有风险的组织可以进行筛查。 Pancell“系统采用了基于角度分辨低相干干涉(a/LCI)的技术。它 为癌症筛查提供了一个高度敏感的工具，因为它能够对 细胞特征，如核大小，已知与癌症进展高度相关。这个 全血细胞系统的非侵入性和实时特性使临床医生能够检查更多的 处于危险状态的组织，以及它选择性地探测疾病最初显现的组织的基底层的能力，允许 当食道癌可以有效治疗时，它们可以检测出处于癌前阶段的食道癌。有了这些 在食道内窥镜检查过程中，使用全血细胞来指导活检选择的能力可能 最终通过更彻底的检查提供更早的检测，通过以下方式降低医疗成本 最大限度地减少非发育不良组织的活检，并全面改善患者的预后和生活质量。 在NIH SBIR计划的第一阶段，OnCoscope成功地开发了一种商业原型a/LCI设备 能够在大鼠Barrett‘s食道模型中区分非发育不良组织和发育不良组织。在……里面 第二阶段，我们对第一阶段的工作进行了扩展，改进了Pancell的系统设计，以增强 商业和临床可行性，同时还在体内展示了其临床操作特征，作为 一项有175名患者参加的飞行员试验。有了以下具体目标，我们的第二阶段B研究计划将进一步 通过对食道a/LCI临床进行产品验证和确认，实现完全商业化 系统，最终向FDA提交了我们的监管申请，要求/LCI指导的切除 食道活组织检查：(1)完成产品开发并进行初步制造和组装 为完成食道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，用于使用a/LCI指导食道切除活检的设计验证，以及 (3)完成食道a/LCI临床系统的制造工艺验证和设计移交。

Project Summary 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.