Joshua H. Winer

Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents

BACKGROUND Iatrogenic bile duct injuries are serious complications with patient morbidity. We hypothesized that the invisible near-infrared (NIR) fluorescence properties of methylene blue (MB) and indocyanine green (ICG) could be exploited for real-time, intraoperative imaging of the extrahepatic bile ducts during open and laparoscopic surgeries. METHODS In all, 2.0 mg/kg of MB and 0.05 mg/kg of ICG were injected intravenously into 35-kg female Yorkshire pigs and the extrahepatic bile ducts were imaged over time using either the Fluorescence-Assisted Resection and Exploration (FLARE) image-guided surgery system (open surgery) or a custom NIR fluorescence laparoscopy system. Surgical anatomy was confirmed using x-ray cholangiography. The contrast-to-background ratio (CBR), contrast-to-liver ratio (CLR), and chemical concentrations in the cystic duct (CD) and common bile duct (CBD) were measured, and the performance of each agent was quantified. RESULTS Using NIR fluorescence of MB, the CD and CBD could be identified with good sensitivity (CBR and CLR > or =4), during both open and laparoscopic surgeries, from 10 to 120 min postinjection. Functional impairment of the ducts, including constriction and injury were immediately identifiable. Using NIR fluorescence of ICG, extrahepatic bile ducts did not become visible until 90 min postinjection because of strong residual liver retention; however, between 90 and 240 min, ICG provided exquisitely high sensitivity for both CD and CBD, with CBR > or =8 and CLR > or =4. CONCLUSION We demonstrate that 2 clinically available NIR fluorophores, MB fluorescing at 700 nm and ICG fluorescing at 800 nm, provide sensitive, prolonged identification of the extrahepatic bile ducts and assessment of their functional status.

Intraoperative near-infrared fluorescence imaging in perforator flap reconstruction: current research and early clinical experience.

Despite recent advances in perforator flap reconstruction, there can be significant variability in vessel size and location. Although preoperative evaluation may provide valuable information, real-time intraoperative methods have the potential to provide the greatest benefit. Our laboratory has developed the Fluorescence-Assisted Resection and Exploration (FLARE) near-infrared (NIR) fluorescence imaging system for intraoperative visualization of details of the underlying vasculature. The FLARE system uses indocyanine green, a safe and reliable NIR fluorophore already FDA-approved for other indications. The system has been optimized in large-animal models for the identification of perforator size, location, and perfusion and has also been translated to the clinic for use during breast reconstruction after mastectomy. In this article, we review our preclinical and clinical data, as well as literature describing the use of similar NIR fluorescence imaging systems in plastic and reconstructive surgery.

Quantitative assessment of perfusion and vascular compromise in perforator flaps using a near-infrared fluorescence-guided imaging system.

Background: Techniques currently used to determine flap perfusion are mainly subjective, with the majority of reconstructive surgeons still relying on clinical examination. In this study, the authors demonstrate the use of near-infrared fluorescence angiography to directly quantify normal and abnormal perfusion in perforator flaps. Methods: Indocyanine green was injected intravenously into anesthetized adult pigs (n = 38). A custom near-infrared fluorescence imaging system was used for image acquisition and quantitation. Thirty-nine flaps were designed based on identified perforators, and postoperative imaging was performed for comparison. In select flaps, isolated occlusion of the arterial and venous pedicle was performed. In select flaps, vascular spasm was induced by local irrigation of the vessels with epinephrine. The fluorescence intensities of select regions of interest were quantified. From these data, the authors defined two indices for abnormal perfusion: the Tmax ratio and the drainage ratio. Results: The authors identified a normal pattern of perfusion before flap elevation, composed of a distinct fluorescence intensity peak at maximal arterial inflow followed by a smooth drop representing venous drainage. Delay of this peak after flap elevation, as indicated by the Tmax ratio, identified vascular spasm and arterial occlusion (p < 0.0001). Abnormal fall of fluorescence intensities after this peak, as indicated by the drainage ratio, identified venous occlusion (p < 0.0001). Conclusions: Quantitation of fluorescence intensities by near-infrared angiography accurately characterizes arterial and venous compromise. The authors’ technique can assess perfusion characteristics during the intraoperative and postoperative periods and therefore complements clinically based subjective criteria now used for flap assessment.

Image-Guided Perforator Flap Design Using Invisible Near- Infrared Light and Validation with X-Ray Angiography

Although perforator flaps mark an important conceptual change in reconstructive surgery, individual perforator vessels show a high degree of variability with respect to anatomic landmarks. We have developed an intraoperative imaging system that simultaneously displays surgical anatomy and otherwise invisible near-infrared images. In 22 adult pigs, perforating vessels were identified within seconds using this optical imaging system and systemic injection of indocyanine green. Perforator flaps were then designed based on these results, and vessel location confirmed by direct visualization and anatomic dissection. Since x-ray angiography remains the gold standard for identification of underlying vessels, conventional x-ray angiography was also performed in 8 pigs to verify the location of perforators. There was full correlation of all the perforators identified among near-infrared fluorescence angiography, x-ray angiography, and anatomic dissection. The technology we describe provides high-sensitivity real-time image guidance throughout perforator dissection, and permits patient-specific flap design.

Predicting the survival of experimental ischaemic small bowel using intraoperative near-infrared fluorescence angiography

Predicting the long‐term viability of ischaemic bowel during surgery is challenging. The aim was to determine whether intraoperative near‐infrared angiography (NIR‐AG) of ischaemic bowel might provide metrics that were predictive of long‐term outcome.

Submental perforator flap design with a near-infrared fluorescence imaging system: the relationship among number of perforators, flap perfusion, and venous drainage.

Background: The submental flap is a reliable alternative to microsurgical reconstruction of facial deformities, providing an excellent cosmetic match with the contour and color of the face. In this study, the authors evaluated submental flap design by using near-infrared fluorescence angiography to identify perforator arteries. The impact of the number of preserved perforator arteries on flap perfusion and venous drainage was quantified. Methods: Indocyanine green was injected intravenously into 18 pigs. Three groups of six animals each had one, two, or three perforator arteries preserved. The fluorescence-assisted resection and exploration near-infrared fluorescence imaging system was used for image acquisition. Images were recorded before and after flap creation, and every hour, for 6 hours. The time to maximum perfusion, the drainage ratio (an indicator of venous drainage), and the percentage of perfused flap area were analyzed statistically at each time point. Results: Flaps with a single dominant perforator artery had an initial mean perfused area of 80 percent, which improved to 97 percent at 6 hours. For flaps with two and three preserved perforator arteries, perfused area at 6 hours was 99.8 percent and 100 percent, respectively. A significant increase was observed in all three metrics as more vessels were preserved. Regardless of the number of perforator arteries preserved, though, all three metrics improved over 6 hours. Conclusions: Near-infrared fluorescence angiography can reliably identify submental perforator arteries for flap design and can be used to assess flap perfusion and venous drainage in real time. Flap metrics at 6 hours were equivalent when either one or multiple perforator arteries were preserved.