Optimization of near-infrared fluorescence cholangiography for open and laparoscopic surgery

Abstract

Background: During laparoscopic cholecystectomy, common bile duct (CBD) injury is a rare but severe complication. To reduce the risk of injury, near-infrared (NIR) fluorescent cholangiography using indocyanine green (ICG) has recently been introduced as a novel method of visualizing the biliary system during surgery. To date, several studies have shown feasibility of this technique; however, liver background fluorescence remains a major problem during fluorescent cholangiography. The aim of the current study was to optimize ICG dose and timing for NIR cholangiography using a quantitative intraoperative camera system during open hepatopancreatobiliary (HPB) surgery. Subsequently, these results were validated during laparoscopic cholecystectomy using a laparoscopic fluorescence imaging system.

Methods: Twenty-seven patients who underwent NIR imaging using the Mini-FLARE image-guided surgery system during open HPB surgery were analyzed to assess optimal dosage and timing of ICG administration. ICG was intravenously injected preoperatively at doses of 5, 10, and 20 mg, and imaged at either 30 min (early) or 24 h (delayed) post-injection. Next, the optimal doses found for early and delayed imaging were applied to two groups of seven patients (n = 14) undergoing laparoscopic NIR fluorescent cholangiography during laparoscopic cholecystectomy.

Results: Median liver-to-background contrast was 23.5 (range 22.1–35.0), 16.8 (range 11.3–25.1), 1.3 (range 0.7–7.8), and 2.5 (range 1.3–3.6) for 5 mg/30 min, 10 mg/30 min, 10 mg/24 h, and 20 mg/24 h, respectively. Fluorescence intensity of the liver was significantly lower in the 10 mg delayed-imaging dose group compared with the early imaging 5 and 10 mg dose groups (p = 0.001), which resulted in a significant increase in CBD-to-liver contrast ratio compared with the early administration groups (p < 0.002). These findings were qualitatively confirmed during laparoscopic cholecystectomy.

Conclusion: This study shows that a prolonged interval between ICG administration and surgery permits optimal NIR cholangiography with minimal liver background fluorescence.

Figure 1. NIR fluorescence imaging of the common bile ducts

Color video (left panel), NIR fluorescence (middle panel), and a color-NIR overlay (right panel) of intraoperative bile duct imaging. Upper row shows a patient undergoing pancreatoduodenectomy, 30 min after administration of 10 mg ICG. Bottom row shows a patient who underwent liver resection for colorectal metastases, 24 h after administration of 10 mg ICG. Arrows indicate the position of the common bile duct; “L” indicates the position of the liver and “Ad” indicates the localization of adipose tissue surrounding the biliary three. Circles are shown to give an example of the region-of-interests of liver, CBD and surrounding adipose tissue.

Figure 2. Evaluation of the effect of ICG dose and post-injection imaging time

Effect of dose and timing was determined by comparing contrast ratios between concentration groups. Signal-to-background ratios (SBR) for the liver and CBD were calculated. A background region-of-interest was drawn on surrounding (fatty) tissue. Figure A shows the effect on liver contrast ratio per dose group. Fluorescence intensity of the liver was significantly lower in the 10 mg delayed imaging dose group compared to the early imaging 5 mg and 10 mg dose groups (P = 0.001), while CBD signal remains the same (Figure B). Points represent individual patient values and the line indicates the median.

Figure 3. Contrast ratio of CBD versus liver background

Signal-to-background ratios (SBR) for the CBD versus the liver were calculated. A significant increase in contrast ratio was found in the delayed imaging 10 mg dose group compared to the early imaging 5 and 10 mg dose groups (P < 0.002). Points represent individual patient values and the line indicates the median.

Figure 4. Laparoscopic fluorescence imaging of the biliary anatomy

Color video (left panel) and NIR fluorescence (right panel; pseudocolored in blue) of laparoscopic bile duct imaging in two patients undergoing laparoscopic cholecystectomy. 5 or 10 mg ICG was injected respectively 30 min or 24 h before surgery. The arrow indicates localization of the cystic duct; “L” indicates the position of the liver. There is clearly less liver signal observed in the 10 mg/24 h group.