Danique Heuvelings

113 Simultaneous fluorescence imaging of bowel perfusion and ureter delineation using methylene blue DISCUSSION This study demonstrated that simultaneous ureteral and bowel perfusion imaging in the same surgical procedure using a single commercially available NIRF imaging system and with the use of FDA-approved fluorescent dyes is feasible. The current findings provide surgeons with a potentially powerful tool to enhance the visibility of the ureter and assess bowel perfusion during colorectal procedures. With MB, clear identification of the ureters was achieved under NIRF imaging in all animals, as well as assessment of intestinal perfusion. The pigs were allocated to 3 different dose groups to determine the optimal dose of MB. Although no significant differences in TBR values were found among groups, the dose of 0.50 mg/kg MB appeared to be the most optimal with the highest TBR values in this animal study. A previously described optimal dose in the first human study using MB to identify the ureter was 0.25 mg/kg 18. Additionally, we found the ideal time to administer MB to be 10 minutes prior to requiring ureter delineation and that ureteral imaging remains possible at least until 240 minutes after a single bolus of MB dye administration. Bowel perfusion assessment was successful in all pigs with ICG. A key finding is that we have demonstrated that bowel perfusion can be visualized with MB as well. Cwalinski et al. created an overview of the role of MB as a fluorophore in a surgical setting 19; however, bowel perfusion assessment was not mentioned. The latter suggests that MB may represent a versatile substitute for ICG in intestinal perfusion imaging, especially in cases where there is also a need for intraoperative ureteral identification or when ICG is contraindicated. Another clinically relevant finding of this study is that there was no interference between ICG and MB in bowel perfusion assessment. As a result, MB alone may enable us to clearly assess intestinal perfusion in combination with ureteral imaging without the need for ICG. In several studies 5, 17, 20, our groups have thoroughly explored the potential of novel dyes for the purpose of intraoperative ureteral imaging. Although showing promising results, such novel dyes are still in an experimental phase and it is expected that it will take several years before they will be available for clinical use. A previous pre-clinical study by our group has demonstrated the simultaneous assessment of bowel perfusion and ureteral delineation with a single dye 12. However, the dye used in that study (IRDye® 800BK) is not yet approved for clinical use. In contrast, MB has been widely used in humans with a good safety profile. It is cheap and clinically available. In addition, MB is approved by the US Food and Drug Administration (FDA) for many indications 21. We believe that the use of a single dye for bowel perfusion assessment and ureteral imaging has several advantages. Most importantly, it reduces the potential risk of adverse reactions as only one dye is administered and contributes to the efficiency of the procedure. One point 5

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