title: Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents.
abstract: BACKGROUND
  Iatrogenic bile duct injuries are serious complications with patient morbidity. We hypothesized that the invisible near-infrared (NIR) fluorescence properties of methylene blue (MB) and indocyanine green (ICG) could be exploited for real-time, intraoperative imaging of the extrahepatic bile ducts during open and laparoscopic surgeries.
  
  
  METHODS
  In all, 2.0 mg/kg of MB and 0.05 mg/kg of ICG were injected intravenously into 35-kg female Yorkshire pigs and the extrahepatic bile ducts were imaged over time using either the Fluorescence-Assisted Resection and Exploration (FLARE) image-guided surgery system (open surgery) or a custom NIR fluorescence laparoscopy system. Surgical anatomy was confirmed using x-ray cholangiography. The contrast-to-background ratio (CBR), contrast-to-liver ratio (CLR), and chemical concentrations in the cystic duct (CD) and common bile duct (CBD) were measured, and the performance of each agent was quantified.
  
  
  RESULTS
  Using NIR fluorescence of MB, the CD and CBD could be identified with good sensitivity (CBR and CLR > or =4), during both open and laparoscopic surgeries, from 10 to 120 min postinjection. Functional impairment of the ducts, including constriction and injury were immediately identifiable. Using NIR fluorescence of ICG, extrahepatic bile ducts did not become visible until 90 min postinjection because of strong residual liver retention; however, between 90 and 240 min, ICG provided exquisitely high sensitivity for both CD and CBD, with CBR > or =8 and CLR > or =4.
  
  
  CONCLUSIONS
  We demonstrate that 2 clinically available NIR fluorophores, MB fluorescing at 700 nm and ICG fluorescing at 800 nm, provide sensitive, prolonged identification of the extrahepatic bile ducts and assessment of their functional status.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Matsui
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tanaka
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Winer
authors.forename: Vida
authors.initials: V
authors.lastname: Kianzad
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gioux
authors.forename: Rita G
authors.initials: RG
authors.lastname: Laurence
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D017734:Bile Ducts, Extrahepatic / Q000601:surgery*; D003287:Contrast Media; D005260:Female; D005453:Fluorescence; D010535:Laparoscopy / Q000379:methods*; D008751:Methylene Blue; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013552:Swine
chemical_list: D003287:Contrast Media; D008751:Methylene Blue