This proposal seeks to acquire a Cellvizio confocal endomicroscopic imaging system for Yale Medical School. The ongoing renaissance in the use of light microscopy for cell and molecular biology and physiology has been driven in large part by the development of confocal fluorescence microscope systems, coupled with availability of specific fluorescent probes of cell structure and function, which together extend our abilities to visualize and quantify events in cells and tissues. Because of its ability to """"""""optically section"""""""" cells and tissues, laser scanning confocal microscopy provides a tool with the spatial resolution needed to define structure and function in live cells within intact tissues and organs. Until now, confocal microscopy has largely been a tool for laboratory- based research. The confocal imaging system that we seek to obtain will enable our investigators to perform confocal imaging directly in patients as well. The requested instrument is specifically designed for use with gastrointestinal endoscopes and bronchoscopes, and would be used to obtain confocal images in patients who are undergoing GI endoscopic, pancreatobiliary, or bronchoscopic procedures. Specific clinical research projects that would take immediate advantage of this equipment include investigation of submucosal immune cell trafficking in inflammatory bowel disease, progression of airway remodeling in asthma and chronic obstructive pulmonary disease, alterations in epithelial secretion and proliferation in disorders characterized by mucosal inflammation, and lymphangiogenesis in cholangiocarcinoma and in other biliary tract diseases. Scientific and administrative oversight for this new clinical research tool would be provided by an established imaging core facility, and additional institutional commitments would assure that proper technical support, service, and supplies would be available long-term. Together, the requested equipment and the support we will provide for it would enable our investigators to move their confocal imaging-based research from the bench to the bedside in order to expand their NIH-funded basic and translational research to include direct studies in humans.
