Near‐infrared (NIR) fluorescence imaging is gaining clinical acceptance over the last years and has been used for detection of lymph nodes, several tumor types, vital structures and tissue perfusion. This review focuses on NIR fluorescence imaging with indocyanine green and methylene blue for different clinical applications in abdominal surgery with an emphasis on oncology, based on a systematic literature search. Furthermore, practical information on doses, injection times, and intraoperative use are provided.

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The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible create tissue-specific near-infrared fluorophores using the inherent chemical structure. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head/neck surgery, the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake in the specific glands after a single intravenous injection of only 0.06 mg kg−1 in a pig. Using a dual-channel near-infrared imaging system, we demonstrate the real-time, high-sensitivity, unambiguous identification of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays the foundation for head/neck surgery performed with increased precision and efficiency, and potentially lowers morbidity, and a general strategy for targeted near-infrared fluorophore development.

Background Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver. Methods Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard-of-care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered one day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard. Results Twenty-two patients suspected to have hepatocellular carcinoma (n=4), cholangiocarcinoma (n=2) or liver metastases from colorectal carcinoma (n=12), uveal melanoma (n=2) and breast cancer (n=2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80% (CT), 84% (MRI), 62% (inspection), 86% (LUS) and 92% (FI), respectively. Three metastases (12%) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100% sensitivity). Conclusion This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance.

Background: Fluorescence cholangiography using indocyanine green (ICG) can enhance orientation of bile duct anatomy during laparoscopic cholecystectomy. To ensure clear discrimination between bile ducts and liver, the fluorescence ratio between both should be sufficient. This ratio is influenced by the ICG dose and timing of fluorescence imaging. We first systematically identified all strategies for fluorescence cholangiography. Second, we aimed to optimize the dose of ICG and dosing time in a prospective clinical trial. Methods: PubMed was searched for clinical trials studying fluorescence cholangiography. Furthermore, 28 patients planned to undergo laparoscopic cholecystectomy were divided into 7 groups, receiving different intravenous doses (5 or 10 mg ICG) at different time points (0.5, 2, 4, 6, or 24 hours prior to surgery). Results: The systematic review revealed 27 trials including 1057 patients. The majority of studies used 2.5 mg administered within 1 hour before imaging. Imaging 3 to 24 hours after ICG administration was never studied. The clinical trial demonstrated that the highest bile duct-to-liver ratio was achieved 3 to 7 hours after administration of 5 mg and 5 to 25 hours after administration of 10 mg ICG. Up to 3 hours after administration of 5 mg and up to 5 hours after administration of 10 mg ICG, the liver was equally or more fluorescent than the cystic duct, resulting in a ratio ≤1.0. Conclusion: This study shows for the first time that the interval between ICG administration and intraoperative fluorescence cholangiography should be extended. Administering 5 mg ICG at least 3 hours before imaging is easy to implement in everyday clinical practice and results in bile duct-to-liver ratios >1.0.