Extrahepatic biliary tract visualization using near-infrared fluorescence imaging with indocyanine green: optimization of dose and dosing time

Abstract

Background The dose and dosing time of indocyanine green (ICG) vary among fluorescence cholangiography (FC) studies. The purpose of this prospective, randomized, exploratory clinical trial was to optimize the dose and dosing time of ICG. Methods PubMed was searched to determine the optimal dose. To optimize the dosing time of ICG, a clinical trial was designed with two parts. The first part included patients with T tubes for more than 1 month. After the patient was injected with ICG, bile was collected at 10 time points to explore the change and trends of bile fluorescence intensity (FI). In addition, the results of the first experiment were used to setup a randomized controlled trial (RCT) that aimed to find the optimal dosing timing for ICG injections for laparoscopic cholecystectomy (LC). During surgery, imaging data were collected for analysis. Results After performing a systematic review, the ICG injection dose for each patient in the clinical trial was 10 mg. Five patients were included in the first part of the study. Bile collected 8 h after ICG injection had a higher FI than bile collected at other time points (p < 0.05), and the FI of bile collected 20 h after ICG injection was nearly zero. In the second part of the experiment, 4 groups of patients (6 patients per group) were injected with 10 mg ICG at 8, 10, 12 and 14 h prior to surgery. The distribution of bile duct FI (p = 0.001), liver FI (p < 0.001), and common bile duct (CBD)-to-liver contrast (p = 0.001) were not the same in each group. Further analysis with the Bonferroni method revealed the following: (1) the FI of the CBD in the 8 h group was significantly different from that in the 14 h group (adjusted p < 0.001); (2) the liver FI of the 8 h group was higher than that of the 10 h group (adjusted p = 0.042) and the 14 h group (adjusted p < 0.001); and (3) the CBD-to-liver contrast of the 8 h group was lower than that of the 10 h group (adjusted p = 0.013) and the 14 h group (adjusted p = 0.001). Conclusion ICG FC enables the real-time identification of extrahepatic bile ducts. The optimal effect of FC can be achieved by performing 10 mg ICG injections 10 to 12 h prior to surgery.

Intraoperative indocyanine green-visualization in a difficult to localize central cholangiocarcinoma – A case report

“…There is an ongoing debate about the exact mode of application of ICG. To support current research we present a case in which intraoperative ICG was used to localize a central intrahepatic cholangiocarcinoma in accordance to the recommendation by Chen et al [ 7 ]…”

“…According to most recent recommendations by Chen et al [ 7 ] 10 mg ICG (VERDYE®, Diagnostic green GmbH, Aschheim-Dornach, Germany) was administered intravenously 12 h before surgery. A standard open right hepatectomy with lymph node dissection of the hepatoduodenal ligament was performed, the intraoperative course was uneventful.…”

“…ICG emits light at a wave length of around 835 nm when illuminated with near-infrared light and can therefore be used in fluorescence guided imaging with a tissue penetration up to 1 cm [ 5 ]. Combining these properties ICG has been established in hepatic surgery to help visualizing intrahepatic tumours and biliary structures intraoperatively [ [6] , [7] , [8] , [9] ]. This technique has shown to improve the outcome after resection of both primary and metastatic liver tumours [ 10 ].…”

Feasibility and educational value of fluorescence cholangiography in laparoscopic cholecystectomy

“…Another goal of the procedure using near‐infrared fluorescence cholangiography with indocyanine green dye has been to determine the optimal dose and dosing time of the indocyanine green administration for distinguishing bile ducts from adjacent liver tissue. Liver background fluorescence remains a major problem during fluorescence cholangiography with the conventional method, 5 in which the dye is usually administered within 60 minutes prior to surgery 6 . There have been five investigations of the optimal interval between the administration of indocyanine green and the performance of fluorescence cholangiography by adjusting the different doses.…”

“…There have been five investigations of the optimal interval between the administration of indocyanine green and the performance of fluorescence cholangiography by adjusting the different doses. According to the results of those studies, the contrast between bile ducts and liver tissue was better when a longer time interval was used after the administration of higher doses of indocyanine green 3,5‐8 . However, the visualization of the extrahepatic biliary structures by means of the longer interval method has not yet been fully evaluated.…”