[unreadable] Barrett's esophagus, also termed specialized intestinal metaplasia (SIM) of the esophagus, is the precursor to esophageal adenocarcinoma, a lethal cancer that is rising in incidence at an alarming rate. The long-term objective of this proposal is to decrease the mortality associated with esophageal adenocarcinoma. Evidence supports screening a large percentage of the adult population to identify patients with SIM. Regular surveillance of patients with Barrett's can then identify dysplasia and adenocarcinoma at an earlier, more treatable stage. The only accepted method for screening for SIM is biopsy through endoscopic guidance. Although this approach is well established, the vast majority (96-98%) of adenocarcinomas are found in patients without prior diagnosis of SIM. Important factors that contribute to the inadequacy of endoscopic biopsy for screening are cost and accuracy. The first goal of this work is to develop and test an accurate, less expensive screening method for Barrett's esophagus. We have previously demonstrated that optical coherence tomography (OCT) can accurately distinguish esophageal SIM from normal squamous epithelium in patients undergoing endoscopy. In the proposed research we will develop methods for comprehensively screening the entire distal esophagus with OCT without requiring endoscopy or patient sedation. Current surveillance protocols consist of upper endoscopy with multiple random biopsies. Since dysplasia and adenocarcinoma are focal diseases, random biopsy is subject to sampling errors and high rates of false negative diagnoses. The second goal of this research is to develop and test a more sensitive method for surveillance in patients with Barrett's esophagus based on optically guided biopsy. Preliminary studies suggest that OCT can further differentiate SIM to identify dysplasia and adenocarcinoma. We propose to systematically image the entire Barrett's region and direct biopsy to locations that contain the most severe disease. The proposed work will expand the current diagnostic capabilities of OCT, develop a standalone imaging method for systematically evaluating the distal esophagus, and test these new methods for screening and surveillance in patients. This program will provide physicians with an improved diagnostic tool that will impact clinical practice as well as be used for future studies to address unresolved controversies regarding the natural history and treatment of patients with this disease. [unreadable] [unreadable]