The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in perforator flap breast reconstruction

Abstract

Background: The ability to determine flap perfusion in reconstructive surgery is still primarily based on clinical examination. In this study, the authors demonstrate the use of an intraoperative, near-infrared fluorescence imaging system for evaluation of perforator location and flap perfusion.

Methods: Indocyanine green was injected intravenously in six breast cancer patients undergoing a deep inferior epigastric perforator flap breast reconstruction after mastectomy. Three dose levels of indocyanine green were assessed using the fluorescence-assisted resection and exploration (FLARE) imaging system. This system uses light-emitting diodes for fluorescence excitation, which is different from current commercially available systems. In this pilot study, the operating surgeons were blinded to the imaging results.

Results: Use of the FLARE system was successful in all six study subjects, with no complications or sequelae. Among the three dose levels, 4 mg per injection resulted in the highest observed contrast-to-background ratio, signal-to-background ratio, and signal-to-noise ratio. However, because of small sample size, the authors did not have sufficient power to detect statistical significance for these pairwise comparisons at the multiple-comparison adjusted type I error of 0.017. Six milligrams per injection provided a similar contrast-to-background ratio but also a higher residual background signal.

Conclusion: Based on this pilot study, the authors conclude that near-infrared assessment of perforator flap breast reconstruction is feasible with a light-emitting diode-based system, and that a dose of 4 mg of indocyanine green per injection yields the best observed contrast-to-background ratio compared with a dose of 2 or 6 mg for assessment of flap perfusion.

Trial registration: ClinicalTrials.gov NCT00952107.

Figure 1. The FLARE™ Imaging System

The cart-based imaging system is shown with major parts identified. A satellite monitor and footswitch are also available to the surgeon (not shown).

Figure 2. NIR Fluorescence Imaging after ICG Injection

A. Identification of perforating vessel (dashed circle) after injection of 2 mg (top), 4 mg (middle), or 6 mg (bottom) ICG on transferred skin flaps. Contrast was quantified using fluorescence intensity of the perforating vessel and background (solid circle). B. Typical CBR curve after ICG injection. Signal peaks shortly after injection and gradually declines.

Figure 3. NIR Fluorescence Contrast per Dose ICG

A. Contrast-to-Background ratio (CBR), Signal-to-Background ratio (SBR), and Signal-to-Noise ratio (SNR) in each dose group. CBR was defined as (I_perforator – I_background) / I_noise, where I = fluorescence intensity. The 2-mg dose group differed significantly from the 4-mg and 6-mg dose groups on all measures (2 mg vs. 4 mg: CBR, p = .001; SBR, p = .006; SNR, p = .001. 2 mg vs. 6 mg: CBR, p = .005; SBR, p = .025; SNR, p = .004). B. Effect of ICG dose on contrast after repeated injections. C. Effect of ICG dose on background intensity after injection 2. After repeat injection of 6 mg ICG, the background intensity remains increased in comparison with 2-mg (p = .009) and 4-mg (p = .008) dose groups.

Figure 4. Selected perforator is not the NIR fluorescence dominant perforator

A. Quantification of the signal confirms the increase in fluorescence intensity of the selected perforator and decrease in intensity of the perforator that was not chosen. B. Left and right sides of the abdomen are assessed before perforator dissection (two top rows) and the right side is chosen. Since the surgeon was blinded, NIR fluorescence information was not available for perforator selection. The perforator with the highest intensity (small arrow) was not selected in favor of a less fluorescent perforator (large arrow). After perforator dissection (third row) and subsequent transfer (bottom row) the chosen perforator appears to gain intensity.

Figure 4. Selected perforator is not the NIR fluorescence dominant perforator

A. Quantification of the signal confirms the increase in fluorescence intensity of the selected perforator and decrease in intensity of the perforator that was not chosen. B. Left and right sides of the abdomen are assessed before perforator dissection (two top rows) and the right side is chosen. Since the surgeon was blinded, NIR fluorescence information was not available for perforator selection. The perforator with the highest intensity (small arrow) was not selected in favor of a less fluorescent perforator (large arrow). After perforator dissection (third row) and subsequent transfer (bottom row) the chosen perforator appears to gain intensity.