Minimally-invasive optical imaging is being advanced by molecular probes that enhance contrast using fluorescence. The applications in cancer imaging are very broad, ranging from early diagnosis of cancer to the guiding of interventions, such as biopsy. The high-sensitivity afforded by wide-field fluorescence imaging using scanning laser light is being developed for these broad applications. The platform technology is the SFE – Scanning Fiber Endoscope, which places a sub-1-mm scanner at the tip of a highly flexible shaft. Because several different laser wavelengths can be mixed and scanned together, full-color reflectance imaging will be combined with near infrared (NIR) fluorescence imaging in a 4-channel multimodal SFE. The goal of this project is to develop a prototype VerAvanti 4-channel multimodal SFE (mmSFE) for a specific cancer imaging application that can have significant impact in early detection and endoscopic treatment of esophageal cancer. VerAvanti is a start-up company located in Redmond, Washington and is founded and staffed with engineering graduates from the University of Washington (UW), where the SFE was invented and tested in pilot clinical trials. VerAvanti has exclusive license to commercialize the SFE technology for medical imaging and a 3- channel full color SFE (using red, green, and blue reflectance) is already in pilot manufacturing and testing. This project will rapidly translate the 4-channel mmSFE technology into a specific product for fluorescently guiding endoscopic interventions in the GI tract. Furthermore, the VerAvanti mmSFE will be designed for efficient manufacturing in a modular format with reduced part numbers and expected lower cost. The application is using NIR fluorescence molecular probes that were developed at the University of Michigan (UM) that bind to high grade dysplasia (HGD) and neoplastic cells of esophageal adenocarcinoma (EAC). The mmSFE product is introduced through the working channel of a conventional endoscope to identify regions of the lower esophagus that are over-expressing EGFR and ErbB2, which are transmembrane tyrosine kinase receptors that stimulate epithelial cell growth, proliferation, and differentiation. Overexpression of these targets reflects an increase in biological aggressiveness and higher risk for progression to Barrett's esophagus, HGD, and EAC. The design of the mmSFE diagnostic algorithm is based on the high correlation of the fluorescence lesion target-to-background measurement in collaboration with UW and UM. Additional mmSFE guided tools will be developed for more accurate endoscopic interventions using NIR fluorescence molecular probes. Both software and hardware will be fabricated and tested for the start of a multisite clinical trial using the mmSFE.