NIR-Ⅱ Fluorescence Imaging For Extrahepatic Cholangiography

Disorders of the gallbladder are quite common among the adult population,making cholecystectomy one of the most frequent operations worldwide.Iatrogenic injuries tobiliary tract remain the most dreaded complication during cholecystectomy.Aberrant biliary tract structure,obesity,inflammation and misrecognition of biliary anatomy are the main etiologies responsible for injury incidence.Intraoperative biliary tract imaging is of vital importance toreduce the incidence of injury and the related complications.Conventional X-ray based intraoperative cholangiography shows drawbacks including radiation exposure and manpower requirement.Recently,with the rapid development of technology,fluorescence imaging has emerged as a promising method for intraoperative diagnosis and surgical guidance.Moreover,improvement in sensor fabrication and development in bright NIR fluorophores synthesis have greatly broadened the detectable wavelength region and extended the fluorescence imaging from the conventional nearinfrared window(NIR-I;700 nm-900 nm)intothe second near-infrared window(NIRⅡ;900 nm-1700 nm),showing advantages of deeper tissue penetrating depth and higher spatial resolution.Herein,we conducted the research about applying NIR-Ⅱ imaging technology in cholangiography.Twomainly sections are as follows:In the first section,we applied the clinically approved agent indocyanine green as the fluorophore for NIR-Ⅱ extrahepatic cholangiography.The fluorescence signal of indocyanine green-bile solution in the NIR-Ⅱ window was measured which exhibited intense and stable NIR-Ⅱ signal,outperforming that measured from the aqueous solution.A series of experiments at in vivolevel were conducted tofurther compare the performance of biliary tract imaging in the NIR-Ⅱ window and NIR-I window,the result of which showed that bile duct imaging performed in the NIR-Ⅱ window exhibited the advantages in deeper penetrating ability,higher signal-to-background ratioand better diagnosis of the biliary injuries,outperforming those performed in the NIR-I window.In the second section,we applied the novel aggregation-induced emission material TT3-oB as the fluorophore for the following bile duct imaging.Benefiting from the largeπ-conjugated planar blocks and the twisted molecular skeletons,the TT3-oB nanoparticles exhibited bright fluorescent signal in the near-infrared Ⅱb window(NIRⅡb,1500 nm-1700 nm).By intrabiliary injection of the fluorophore,we have successfully performed the cholangiography in the NIR-Ⅱb window with much higher signal-tobackground ratioand better spatial resolution,which could be applied for the precise diagnosis of the tiny biliary injury and gallstone disease.Moreover,intrabiliary injection method maximally reduces the risk of long-term nanoparticles retention,which is a safe imaging approach with great feasibility.