Intraoperative Near‐Infrared Fluorescent Cholangiography (NIRFC) in Mouse Models of Bile Duct Injury

Abstract

Accidental injury to the common bile duct is a rare but serious complication of laparoscopic cholecystectomy. Accurate visualization of the biliary ducts may prevent injury or allow its early detection. Conventional X-ray cholangiography is often used and can mitigate the severity of injury when correctly interpreted. However, it may be useful to have an imaging method that could provide real-time extrahepatic bile duct visualization without changing the field of view from the laparoscope. The purpose of the present study was to test a new near-infrared (NIR) fluorescent agent that is rapidly excreted via the biliary route in preclinical models to evaluate intraoperative real-time near infrared fluorescent cholangiography (NIRFC). To investigate probe function and excretion, a lipophilic near-infrared fluorescent agent with hepatobiliary excretion was injected intravenously into one group of C57/BL6 control mice and four groups of C57/BL6 mice under the following experimentally induced conditions: (1) chronic biliary obstruction, (2) acute biliary obstruction (3) bile duct perforation, and (4) choledocholithiasis, respectively. The biliary system was imaged intravitally for 1 h with near-infrared fluorescence (NIRF) with an intraoperative small animal imaging system (excitation 649 nm, emission 675 nm). The extrahepatic ducts and extraluminal bile were clearly visible due to the robust fluorescence of the excreted fluorochrome. Twenty-five minutes after intravenous injection, the target-to-background ratio peaked at 6.40 +/- 0.83 but signal was clearly visible for ~60 min. The agent facilitated rapid identification of biliary obstruction and bile duct perforation. Implanted beads simulating choledocholithiasis were promptly identifiable within the common bile duct lumen. Near-infrared fluorescent agents with hepatobiliary excretion may be used intraoperatively to visualize extrahepatic biliary anatomy and physiology. Used in conjunction with laparoscopic imaging technologies, the use of this technique should enhance hepatobiliary surgery.