Comprehensive Confocal Microscopy for Image Guided Biopsy

描述(申请人提供)：显然有必要指导活检程序，特别是对于上皮异常增生和早期癌症，这些通常发生在大组织区域内，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技术，因为它们提供的信息类似于病理学家在目前的护理标准中使用的信息。不幸的是，按照目前的配置，这些显微镜的视场很小，属于“点抽样”方法，不适合活检引导所需的大面积成像。我们开发了一种反射式共聚焦显微镜技术，称为SECM，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极大的组织区域，从而解决了这一问题。此外，我们还开发了一种激光方法，用于在组织上标记与SECM识别的感兴趣图像相对应的位置。综上所述，这些技术为基于显微形态信息的新的图像引导活检平台提供了基础。在这项提案中，我们将通过制造一种结合了这些技术的内窥镜探头，并通过测试其在20名患者队列中指导活检的能力，将这项技术从工作台带到床边。由于需要更好的方法来诊断巴雷特食道(BE)，以及我们在食道成像方面的专业知识，这笔赠款的临床重点将是开发一种用于改善对BE患者的监测的设备。虽然这项技术的目标是降低食管腺癌的死亡率，但它也将成为其他器官系统(如结肠、肺和膀胱)大面积显微筛查的平台，在这些系统中，现有的诊断范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：这项提案将开发一种基于大型上皮表面获得的显微图像的活检指导系统。使用该设备，我们将确定显微图像引导下对20例Barrett‘s食管病患者进行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.