Comprehensive Confocal Microscopy for Image Guided Biopsy

描述（由申请人提供）：明确需要指导活检程序，特别是上皮异型增生和早期癌症，这些疾病通常发生在大的组织区域内，肉眼无法识别。内窥镜光学显微镜技术是这种图像引导活检的有前途的候选者，因为它们提供的信息与病理学家用于当前护理标准的信息相似。不幸的是，如当前配置的，这些显微镜具有小的视场并且是“点采样”方法，使得它们不适合活检引导所需的大面积成像。我们已经开发了一种反射共聚焦显微镜技术，称为SECM，它通过以非常高的速度获取显微图像数据来自动和全面地筛选非常大的组织区域来解决这个问题。此外，我们还开发了一种激光方法，用于标记与SECM识别的感兴趣图像相对应的组织上的位置。总之，这些技术为基于显微形态学信息的新图像引导活检平台提供了基础。在本提案中，我们将通过制造一个包含这些技术的内窥镜探头，并通过测试其在20名患者的队列中引导活检的能力，将这项技术从实验室带到床边。由于相当需要更好的方法来诊断巴雷特食管（BE）和我们在食管成像方面的专业知识，该补助金的临床重点将是开发一种用于改善BE患者监测的设备。虽然目标是降低食管腺癌的死亡率，但该技术也将作为其他器官系统（如结肠，肺和膀胱）中大面积显微镜筛查的平台，现有的诊断模式无法很好地筛查大组织区域的异型增生和早期癌症。 公共卫生相关性：该提案将根据在大上皮表面获得的显微图像开发活检引导系统。使用该器械，我们将在20例Barrett食管患者的队列中确定显微图像引导活检的安全性和可行性。

DESCRIPTION (provided by applicant): There is a clear need for guiding biopsy procedures, especially for epithelial dysplasia and early cancer that commonly arise focally within large tissue areas and cannot be identified by the naked eye. Endoscopic optical microscopy technologies are promising candidates for such image-guided biopsy as they provide information that is similar to that used by pathologists for the current standard of care. Unfortunately, as currently configured, these microscopies have small fields of view and are "point sampling" methods, making them unsuitable for the large area imaging required for biopsy guidance. We have developed a reflectance confocal microscopy technique, termed SECM that solves this problem by acquiring microscopic image data at very high speeds to automatically and comprehensively screen extremely large tissue areas. In addition, we have developed a laser method for marking locations on the tissue that correspond to images of interest identified by SECM. Taken together, these technologies provide a foundation for a new image-guided biopsy platform that is based on microscopic morphologic information. In this proposal, we will take this technology from the bench to the bedside by fabricating an endoscopic probe that incorporates these technologies and by testing its capability to guide biopsy in a cohort of 20 patients. Due to the considerable need for better methods to diagnose Barrett's esophagus (BE) and our expertise in esophageal imaging, the clinical focus of this grant will be the development of a device for improving surveillance of BE patients. While targeted to reduce the mortality of esophageal adenocarcinoma, this technology will also serve as a platform for large-area microscopic screening in other organ systems, such as the colon, lung, and bladder, where screening large tissue areas for dysplasia and early cancer is not well served by existing diagnostic paradigms. PUBLIC HEALTH RELEVANCE: This proposal will develop a biopsy guidance system based on microscopic images obtained over large epithelial surfaces. Using this device, we will determine the safety and feasibility of microscopic image guided biopsy in a cohort of 20 patients with Barrett's esophagus.