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，特别是上皮发育不良和早期癌症，通常在大组织区域局部发生，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希望的候选者，因为它们提供的信息与病理学家目前使用的标准护理相似。不幸的是，按照目前的配置，这些显微镜的视野很小，而且是“点采样”方法，不适合活检指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全面地筛选超大组织区域，从而解决了这个问题。此外，我们还开发了一种激光方法，用于标记组织上与SECM识别的感兴趣图像相对应的位置。总之，这些技术为基于微观形态信息的新的图像引导活检平台提供了基础。在这个提议中，我们将通过制造一个内窥镜探针，结合这些技术，并通过在20名患者中测试其指导活检的能力，将这项技术从实验室带到床边。由于需要更好的方法来诊断巴雷特食管（BE），以及我们在食管成像方面的专业知识，该资助的临床重点将是开发一种改善BE患者监测的设备。在降低食管癌死亡率的同时，这项技术也将为其他器官系统（如结肠、肺和膀胱）的大面积显微筛查提供平台，在这些器官系统中，现有的诊断模式无法很好地筛查大组织区域的不典型增生和早期癌症。

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.