Near-infrared fluorescence laparoscopy of the ureter with three preclinical dyes in a pig model

Abstract

Background Ureteric injury is reported to occur in 1–7.6% of colorectal surgeries. To reduce the incidence of ureteral injury, it is essential to identify the ureters. The use of near-infrared fluorescence (NIRF) imaging with intravenously administered dyes might be of added value for ureteral visualization during laparoscopy. The aim of this study is to assess the performance of three preclinical dyes; IRDye ® 800BK, IRDye ® 800NOS and IRDye ® 800CW, for near-infrared fluorescence laparoscopy of the ureter in pigs. Methods In three female Dutch landrace pigs, the new dyes were evaluated. In each pig, 1 dye was tested using a 6-mg intravenous dose in a concentration of 1 mg/ml. Imaging was performed in fluorescence mode and white light mode with a laparoscopic imaging system. In order to further evaluate the dyes, an ex vivo imaging experiment was performed, in which 8 decreasing concentrations per dye, diluted in PBS, were evaluated in a transparent test tube with NIRF mode at a distance of 1, 5 and 10 cm from the laparoscope. Results All three dyes were effective in allowing the identification of the ureter with NIRF imaging. The ureter became fluorescent after 35, 45 and 10 min, respectively, for IRDye ® 800BK, IRDye ® 800NOS and IRDye ® 800CW with a maximum target-to-background ratio (TBR) of 2.14, 0.66 and 1.44, respectively. In the ex vivo imaging experiment, all three dyes produced a strong fluorescence signal at all concentrations and all distances evaluated. Conclusions Intravenous administration of the preclinical dyes IRDye ® 800CW, IRDye ® 800 BK and IRDye ® 800NOS facilitated successful identification of the anatomical course of the ureter in living pig models. The highest measured TBR occurred with the use of IRDye ® 800BK. Ex vivo, a correlation was observed between the fluorescence intensities of the signal with the concentration of the dye and with the distance to the object.

Intraoperative ureter identification with a novel fluorescent catheter

“…Certainly, the IRDye 800BK allows for a totally non-invasive ureter visualization whereas the NICE-coated stent requires a cystoscopic placement. However, the performance of this promising dye has been described only in animal studies so far 18 , 19 , 26 . As pigs have less visceral adipose tissue than humans, their peritoneum is subsequently thinner.…”

“…The IRDye 800BK powder was diluted in a sterile phosphate-buffered saline (PBS) solution to a concentration of 1 mg/mL (as per the manufacturer’s instructions). Based on earlier studies 18 , 19 , 26 , which have achieved optimal ureteral visualization, the concentration of 0.15 mg/kg was chosen.…”

Currently available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters: a systematic review

“…CW800-BK is specifically developed for visualizing the ureters, but the initial results seem comparable or even inferior to CW800-CA as lower SBRs are found. However, a recent paper found higher SBRs for CW800-BK in comparison with CW800 and newly developed 800NOS in pigs [ 40 ]. Fluorescein has a good safety profile, but its fluorescent emission is within the visible spectrum and thus high autofluorescence and low tissue penetration can be expected.…”

Key clinical applications for indocyanine green fluorescence imaging in minimally invasive colorectal surgery

“…[ 40 ] Consequently, fluorophores that are renally excreted but have similar emission wavelengths to ICG at the same time are in development work is currently done preclinically in animal models. [ 41 ]…”