Optical imaging using near-infrared (NIR) fluorescence provides new prospects for general and oncologic surgery. ICG is currently utilised in NIR fluorescence cancer-related surgery for three indications: sentinel lymph node (SLN) mapping, intraoperative identification of solid tumours, and angiography during reconstructive surgery. Therefore, understanding its advantages and limitations is of significant importance. Although non-targeted and non-conjugatable, ICG appears to be laying the foundation for more widespread use of NIR fluorescence-guided surgery.

BACKGROUND The fundamental principle of oncologic surgery is the complete resection of malignant cells. However, small tumors are often difficult to find during surgery using conventional techniques. Our objectives were to determine if optical imaging, using a contrast agent already approved for other indications, could improve hepatic metastasectomy with curative intent, to optimize dose and timing, and to determine the mechanism of contrast agent accumulation. METHODS We exploited the high tissue penetration of near-infrared (NIR) light using the FLARE™ image-guided surgery system and the NIR fluorophore indocyanine green (ICG) in a clinical trial of 40 patients undergoing hepatic resection for colorectal cancer metastases. RESULTS A total of 71 superficially located (< 6.2 mm beneath the liver capsule) colorectal liver metastases were identified and resected using NIR fluorescence imaging. Median tumor-to-liver ratio (TLR) was 7.0 (range 1.9–18.7) and no significant differences between time-points or doses were found. ICG fluorescence was seen as a rim around the tumor, which we show to be entrapment around CK7-positive hepatocytes compressed by the tumor. Importantly, in 5 of 40 patients (12.5%, 95% CI: 5.0–26.6), additional small and superficially located lesions were detected using NIR fluorescence, and were otherwise undetectable by preoperative computed tomography (CT), intraoperative ultrasound (IOUS), visual inspection, and palpation. CONCLUSION We conclude that NIR fluorescence imaging, even when utilizing a non-targeted, clinically available NIR fluorophore, is complementary to conventional imaging and able to identify missed lesions by other modalities.

Purpose Near-infrared (NIR) fluorescence imaging is a promising technique that offers, real-time, visual information during surgery. The current study reports the first clinical results of ureter imaging using NIR fluorescence after a simple peripheral infusion of methylene blue (MB). Furthermore, optimal timing and dose of MB were assessed. Materials and Methods A total of 12 patients that underwent lower abdominal surgery were included in this prospective feasibility study. NIR fluorescence imaging was performed using the Mini-FLARE™ imaging system. To determine optimal timing and dose, MB was injected intravenously at doses of 0.25, 0.5 or 1 mg/kg, after exposure of the ureters. Subsequently imaging was performed for up to 60 min following injection. Results In all patients both ureters could be clearly visualized within 10 minutes after infusion of MB. Signal lasted at least up to 60 minutes after injection. The mean signal-to-background ratio (SBR) of the ureter was 2.27 ± 1.22 (N = 4), 2.61 ± 1.88 (N = 4) and 3.58 ± 3.36 (N = 4) for the 0.25, 0.5 and 1 mg/kg groups, respectively. A mixed model analysis was used to compare SBRs between dose groups and time points and to assess the relation between dose and time. A significant difference between time points (P < 0.001) was found. However no difference between dose groups was observed (P = 0.811). Conclusions This study demonstrates the first successful use of NIR fluorescence using low-dose MB for the identification of the ureters during lower abdominal surgery.

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 to visualize 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 27 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 2 groups of 7 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 the 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 to the early imaging 5 mg and 10 mg dose groups (P = 0.001), which resulted in a significant increase in CBD-to-liver contrast ratio compared to 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.