Theranostics 2020; 10(8):3636-3651. doi:10.7150/thno.41127

Research Paper

Extrahepatic cholangiography in near-infrared II window with the clinically approved fluorescence agent indocyanine green: a promising imaging technology for intraoperative diagnosis

Di Wu1, Dingwei Xue4, Jing Zhou2, Yifan Wang1, Zhe Feng2, Junjie Xu1, Hui Lin1✉, Jun Qian2✉, Xiujun Cai1,3✉

1. Department of General Surgery, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
2. State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research, College of Optical Science and Engineering, Zhejiang University, Hangzhou, 310058, China.
3. Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Hangzhou, 310016, China.
4. Department of Urology, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.

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Citation:
Wu D, Xue D, Zhou J, Wang Y, Feng Z, Xu J, Lin H, Qian J, Cai X. Extrahepatic cholangiography in near-infrared II window with the clinically approved fluorescence agent indocyanine green: a promising imaging technology for intraoperative diagnosis. Theranostics 2020; 10(8):3636-3651. doi:10.7150/thno.41127. Available from https://www.thno.org/v10p3636.htm

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Abstract

Rationale: Biliary tract injury remains the most dreaded complication during laparoscopic cholecystectomy. New intraoperative guidance technologies, including near-infrared (NIR) fluorescence cholangiography with indocyanine green (ICG), are under comprehensive evaluation. Previous studies had shown the limitations of traditional NIR light (NIR-I, 700-900 nm) in visualizing the biliary tract structures in specific clinical situations. The aim of this study was to evaluate the feasibility of performing the extrahepatic cholangiography in the second NIR window (NIR-II, 900-1700 nm) and compare it to the conventional NIR-I imaging.

Methods: The absorption and emission spectra, as well as fluorescence intensity and photostability of ICG-bile solution in the NIR-II window were recorded and measured. In vitro intralipid® phantom imaging was performed to evaluate tissue penetrating depth in NIR-I and NIR-II window. Different clinical scenarios were modeled by broadening the penetration distance or generating bile duct injuries, and bile duct visualization and lesion site diagnosis in the NIR-II window were evaluated and compared with NIR-I imaging.

Results: The fluorescence spectrum of ICG-bile solution extends well into the NIR-II region, exhibiting intense emission value and excellent photostability sufficient for NIR-II biliary tract imaging. Extrahepatic cholangiography using ICG in the NIR-II window obviously reduced background signal and enhanced penetration depth, providing more structural information and improved visualization of the bile duct or lesion location in simulated clinical scenarios, outperforming the NIR-I window imaging.

Conclusions: The conventional clinically approved agent ICG is an excellent fluorophore for NIR-II bile duct imaging. Fluorescence cholangiography with ICG in the NIR-II window could provide adequate visualization of the biliary tract structures with increased resolution and penetration depth and might be a valid option to increase the safety of cholecystectomy in difficult cases.

Keywords: bile duct injury, diagnosis, near-infrared II cholangiography, indocyanine green, fluorescence-guided surgery