Project Summary Bile duct cancer, also known as cholangiocarcinoma, is the second most common primary liver cancer. It is considered to be an incurable cancer with no identifiable risk factors, that can rapidly become lethal, unless it can be detected early enough to be fully resected. Cross-sectional imaging lacks sensitivity to cellular structure and biochemical properties of the bile duct wall. While a combination of endoscopic retrograde cholangiopancreatography (ERCP) based brush cytology and trans-papillary endobiliary forceps biopsy, which is often considered the gold standard, has a high specificity, it offers only low sensitivity. Another very significant challenge with the current standard of care approaches is difficulty in acquiring tissue samples adequate for the histopathologic examination. Because of the poor prognosis, a technique capable of reliably detecting pre-cancer of the bile duct is urgently needed. We recently introduced a new diagnostic technology that combines light scattering spectroscopy and diffuse reflectance spectroscopy to identify biliary duct pre-cancer and early cancer during routine diagnostic ERCP procedures. It employs a single-point forward looking ultraminiature spatial gating fiber optic probe. To ensure clinical acceptance of the technique and improve accuracy, scanning the entire internal surface of the bile duct in a shorter time using an ERCP catheter-compatible probe, without the requirement for a cholangioscope, would be a major advance. Therefore, we propose to develop a side looking spatial gating fiber optic probe capable of parallel data collection at multiple locations on the bile duct wall to significantly simplify and speed up the operation of the clinical system. We will test the performance of the new endoscopic instrument in detecting bile duct pre-cancerous and early cancerous lesions in patients undergoing ERCP for potential malignancies as well as inflammatory strictures and gallstones.