Intraoperative ureter visualization using a near-infrared imaging agent

Richard W Farnam, Richard G Arms, Alwin H Klaassen, Jonathan M Sorger, Richard W Farnam, Richard G Arms, Alwin H Klaassen, Jonathan M Sorger

Abstract

The fluorescent imaging agent IS-001 was determined to be well tolerated in all subjects and has the potential to provide ureter visualization throughout minimally invasive hysterectomy procedures. This study was conducted to evaluate clinical safety and efficacy of a real-time ureter visualization technique for use during hysterectomy surgery. The study drug appears safe, is renally excreted, and allows enhanced ureter visualization when imaged with a clinically approved near-infrared sensitive endoscope. This is a first-in-human study showing preliminary results that the drug is safe and effective during surgery for improved ureter visualization.

Trial registration: ClinicalTrials.gov NCT03006237.

Keywords: hysterectomy; near-infrared; robotic-assisted minimally invasive surgery; ureter imaging.

Figures

Fig. 1
Fig. 1
Disposition of study participants. Of the 50 subjects screened, 26 failed to meet serum chemistry or hematology inclusion criteria. The remaining 24 subjects were assigned to a drug dose-cohort in an escalating fashion based on their enrollment in the study.
Fig. 2
Fig. 2
Ureter near-infrared fluorescence following IV IS-001 injection. Intraoperative white light and near-infrared Firefly® images of the ureter during da Vinci® hysterectomy ∼20  min after IV IS-001 injection at 10, 20, or 40 mg per patient.
Fig. 3
Fig. 3
Intraoperative ureter fluorescence scores. Surgeon-assessed intraoperative ureter fluorescence scores. Assessments were made at 10, 30, and 60 min (or last possible time-point if surgery lasted less than 60 min) postinjection (n=8 for each dose-cohort at each time-point). Images in Firefly® mode scored for ureter fluorescence intensity scored on a 4-point scale from 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = strong fluorescence of the ureter.
Fig. 4
Fig. 4
Green pixels in regions of interest within the ureter and 5 cm away from the ureter were used to compute a ureter-to-background ratio. While the results were not statistically significant, trends generally indicate a drop off in signal beyond 30 min.

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