What is the recommended dosing regimen, safety considerations, and contraindications for using indocyanine green (ICG) fluorescence imaging as an adjunct during adult liver resection for primary or metastatic tumors?

ICG Fluorescence Imaging in Hepatectomy

Indocyanine green (ICG) fluorescence imaging is a safe and effective adjunct during liver resection, administered intravenously at 0.5 mg/kg body weight 2-14 days preoperatively for tumor visualization, or intraoperatively for anatomical segment delineation and fluorescence cholangiography. 1, 2

Dosing Regimens

For Tumor Detection and Visualization

• Administer 0.5 mg/kg body weight intravenously 2-14 days before surgery to allow hepatocyte uptake and tumor accumulation, enabling fluorescence-guided identification of hepatocellular carcinoma (HCC), cholangiocarcinoma, and liver metastases during resection 1, 3, 4, 2
• This preoperative timing achieves sensitivity of 69-100% for tumor detection, with studies reporting identification of additional occult lesions in 27.8-40% of cases that were missed by preoperative imaging and intraoperative ultrasound 3, 4, 2
• The smallest detectable tumors measure as little as 2 mm in diameter 4

For Anatomical Resection and Fluorescence Angiography

• Inject ICG intravenously at the beginning of the operation for real-time fluorescence angiography to delineate hepatic segments, identify resection margins, and visualize portal vein anatomy 4, 2
• This intraoperative administration method enables direct or indirect tissue staining to identify anatomical liver segments and determine boundaries for hemihepatectomy or segmentectomy 4, 2

For Fluorescence Cholangiography

• ICG can be administered intravenously before surgery to visualize intra- and extrahepatic bile ducts without requiring X-ray imaging, particularly useful when intraoperative cholangiography cannot be performed 5, 2

Safety Profile and Contraindications

Absolute Contraindication

• History of allergy to iodides is the only absolute contraindication, as ICG contains sodium iodide 1

Safety Considerations

• ICG fluorescence imaging is simple, safe, and well-tolerated with minimal adverse events reported in hepatobiliary surgery 3, 4, 2, 6
• The technique does not interfere with standard surgical procedures and adds minimal operative time 4, 2

Clinical Applications and Technical Considerations

Tumor Identification

• ICG fluorescence demonstrates 100% sensitivity for HCC detection in cirrhotic livers when administered 2-14 days preoperatively, with clear delineation between tumor and normal tissue enabling complete resection with negative margins 3, 2
• The technique successfully identifies extrahepatic metastases including peritoneal implants and omental lesions, allowing intraoperative revision of tumor staging 7

False-Positive Signals: Critical Pitfall

• False-positive fluorescence occurs in approximately 39% of cases, predominantly in cirrhotic livers 2
• This represents the most significant limitation and occurs because ICG accumulates in areas of hepatic dysfunction, inflammation, or regenerative nodules, not just malignant tissue 2
• Surgeons must correlate fluorescence findings with preoperative imaging, intraoperative ultrasound, and frozen section pathology to avoid unnecessary resection of benign tissue 2
• False-positive rates can be reduced by considering tumor entity and degree of liver functional impairment when interpreting fluorescence signals 2

Anatomical Resection Guidance

• ICG fluorescence angiography enables precise identification of segmental boundaries in 9 of 15 patients (60%) by examining portal vein anatomy after injection 4
• This enhances surgical precision and oncological quality, particularly in minimally invasive (laparoscopic and robotic) hepatectomy where tactile feedback is limited 2, 6

Preoperative Liver Function Assessment

ICG Retention Test (ICG-R15)

• The ICG retention test at 15 minutes (ICG-R15) serves as a non-invasive predictor of portal hypertension and hepatic functional reserve, guiding the safe extent of liver resection 8
• Limit major hepatectomy to patients with ICG-R15 below 20-25%, and restrict segmentectomy to those with ICG-R15 below 30-35% 8
• ICG clearance correlates with perioperative mortality and should be combined with Child-Pugh classification, MELD score, and liver stiffness measurement to improve patient selection and reduce post-hepatectomy liver failure risk 8

Integration with Volumetric Assessment

• Combine ICG-R15 testing with CT volumetry to ensure future liver remnant (FLR) meets minimum thresholds: ≥20% for normal livers, ≥30-40% for chronic liver disease or Child-Pugh A cirrhosis 9
• When FLR falls below recommended thresholds, perform preoperative portal vein embolization to induce hypertrophy over 4-8 weeks before resection 9

Practical Implementation

Equipment Requirements

• Near-infrared fluorescence imaging system (such as photodynamic eye [PDE] or equivalent laparoscopic/robotic platforms) capable of detecting ICG fluorescence at 805 nm wavelength 3, 4, 2

Intraoperative Workflow

• After laparotomy or trocar placement, inspect the liver with intraoperative ultrasound first, then examine with the fluorescence imaging system 3, 4
• Use fluorescence guidance to identify tumor boundaries, determine resection margins in real-time, and detect additional occult lesions 4, 2
• Confirm negative margins by absence of fluorescence at the resection edge 3

Minimally Invasive Surgery

• ICG fluorescence imaging is particularly valuable in laparoscopic and robotic hepatectomy, where it compensates for loss of tactile feedback and enhances precision of anatomical resection 2, 6
• The technique has been successfully adopted by early users in Germany with demonstrated improvements in surgical precision and oncological quality 2

Evidence Quality and Future Directions

• Current evidence consists primarily of retrospective case series and small prospective cohorts 3, 7, 4, 2
• Phase II/III randomized controlled trials with standardized imaging protocols and long-term oncologic outcomes are urgently needed to demonstrate superiority over standard-of-care before widespread adoption 10
• Standardized protocols for ICG dosing, timing, data acquisition, and reporting are necessary to enable cross-study comparisons and regulatory approval 5, 10