Near-infrared fluorescence imaging of liver metastases in rats using indocyanine green

J Surg Res. 2012 May 15;174(2):266-71. doi: 10.1016/j.jss.2011.01.009. Epub 2011 Feb 2.

Abstract

Background: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is a promising technique to obtain real-time assessment of the extent and number of colorectal liver metastases during surgery. The current study aims to optimize dosage and timing of ICG administration.

Materials and methods: Liver tumors were induced in 18 male WAG/Rij rats by subcapsular inoculation of CC531 rat colorectal cancer cells into three distinct liver lobes. Rats were divided in two groups: imaging after 24 and 48 h or 72 and 96 h after intravenous ICG administration. In each time group, rats were allocated to three dose groups: 0.04, 0.08, or 0.16 mg ICG. Intraoperative imaging and ex vivo measurements were performed using the Mini-FLARE imaging system and confirmed by fluorescence microscopy. Fluorescence intensity was quantified using the Mini-FLARE software and the difference between tumor signal and liver signal (tumor-to-liver ratio; TLR) was calculated.

Results: In all 18 rats, all colorectal liver metastases (n = 34), some as small as 1.2 mm, were identified using ICG and the Mini-FLARE imaging system. Average tumor-to-liver ratio (TLR) over all groups was 3.0 ± 1.2. TLR was significantly higher in the 72 h time group compared with other time points. ICG dose did not significantly influence TLR, but a trend was found favoring the 0.08 mg dose group. Fluorescence microscopy demonstrated a clear fluorescent rim around the tumor.

Conclusions: This study demonstrates that colorectal cancer liver metastases can be clearly identified during surgery using ICG and the Mini-FLARE imaging system, with optimal timing of 72 h post-injection and an optimal dose of 0.08 mg (0.25 mg/kg) ICG. NIR fluorescence imaging has the potential to improve intraoperative detection of micrometastases and, thus, the completeness of resection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / diagnosis*
  • Carcinoma / secondary
  • Cell Line, Tumor
  • Colorectal Neoplasms / pathology*
  • Coloring Agents* / administration & dosage
  • Diagnostic Imaging / methods
  • Indocyanine Green* / administration & dosage
  • Intraoperative Period
  • Liver Neoplasms, Experimental / diagnosis*
  • Liver Neoplasms, Experimental / secondary
  • Male
  • Rats

Substances

  • Coloring Agents
  • Indocyanine Green