Fluorescent Angiography

Fluorescent angiography is a simple and effective real-time tool for measurement of tissue perfusion both in and out of the operating room. It has multiple uses including: (1) identifying perforating vessels during flap planning; (2) locating primary and secondary angiosomes within a prepared flap; (3) as an aid in decision making for tissue debridement and flap creation; (4) intraoperative evaluation of microanastomoses; (5) postoperative flap monitoring, and (6) documentation of perfusion. The technology is easy to use in the hands of the operating surgeon and is safe for the patient, as it requires no radiation exposure.

Fluorescent angiography is a simple and effective real-time tool for measurement of tissue perfusion both in and out of the operating room. The technology is based on indocyanine green (ICG) dye that absorbs light in the near-infrared (NIR) spectrum. Advances in technology have allowed the surgeon to use fluorescent angiography in the operating room in real time, under complete control of the surgeon. Although used experimentally in the late 1990s, by the mid 2000s the technology was already in regular use by some plastic surgeons. For the first time, surgeons could immediately see perfusion in the operated tissues multiple times throughout a procedure as needs changed. Most importantly, use of the dye and the laser has been proved to be safe in humans. The true impact of the technology on the understanding of our specialty is only beginning to be felt.

ICG dye is a water-soluble tricarbocyanine dye that was originally developed by the Eastman Kodak company for use in infrared photography. It was introduced into clinical use when, as a token of appreciation for his treatment at the Mayo Clinic, an executive with the Eastman Kodak Company sent a variety of dyes to a clinician who was looking for suitable dyes that could be safely administered to patients and easily measured in blood. The clinically useful formulation of the dye, a stable lyophilized powder, was developed. For a time ICG was referred to as “Fox Green” after the cardiologist Dr Irwin Fox, who was responsible for its introduction into clinical practice. Initially ICG was used to assess cardiac output by means of a dye-dilution technique. It was later also used to assess arteriovenous fistulae and renal blood flow. The observation that ICG is excreted exclusively via the liver led to its use in assessing liver function and blood flow. The near-infrared absorption and emission of light by ICG makes it particularly well suited to visualizing small blood vessels. In the early 1970s, Flower developed techniques for acquisition of fluorescence angiograms of the choroid using ICG. All current fluorescence imaging using ICG is in essence adaptation of the principles developed by Flower, with the benefit of improvement in NIR-sensitive cameras and light sources.

One of the biggest advantages of ICG over other dyes such as fluorescein is its rapid clearance from the tissues. Following intravascular administration, ICG is rapidly and extensively bound to plasma proteins, with α-lipoproteins being the major carrier in humans. The ICG is thus confined to the intravascular compartment with little leakage into the interstitium, making it an ideal blood pool contrast agent. By contrast, fluorescein remains in the interstitium and therefore can only be used once, and gives no information about dynamic perfusion. The plasma half-life of ICG is very short, approximately 3 to 5 minutes in humans, with the dye being taken up by the liver and being excreted into the bile without any further metabolism. There is no renal excretion of ICG and so there is no contraindication for use in patients with renal insufficiency. Since its introduction into clinical practice, ICG has shown an excellent safety profile with a low incidence of adverse events of about 1 in 42,000 patients. Anaphylactic reactions are rare. The ICG contains iodide, so patients sensitive to iodides should undergo have this study. Most reactions if any are usually mild in nature, for example, feeling of warmth or sore throat.

A typical intraoperative imaging system comprises an imaging camera that houses an 806-nm diode laser to provide near-infrared illumination. This low-level laser does not require the use of protective goggles by operating room staff or the operating surgeon. Optics within the camera can provide even NIR illumination over fields as large as 20 × 20 cm or as small as a centimeter in an operating microscope. Cameras have also been adopted for use in robotic surgery and endoscopic surgery. Image sequences are usually captured at 30 frames per second, and the image sequences are displayed on a monitor in real time for the surgeon to assess. Most systems have a computer for further analysis, review, and archival of the data.

The SPY system (Novadaq, Mississauga, ON, USA; Canada/LifeCell, Branchburg, NJ, USA) is the most commonly used system in plastic and reconstructive surgery ( Fig. 1 ). It was originally developed for use in coronary artery bypass graft surgery to confirm the patency of bypass grafts and was cleared for this indication in Canada, Europe, and Japan in 2001. Several publications reported that SPY imaging detected nonfunctioning grafts in 4% to 8% of patients, and this finding was consistent across sites and surgical procedures that is, on-pump or off-pump. The use of SPY imaging was subsequently expanded to solid organ transplantation including, liver and kidney and pancreas. The SPY system received regulatory clearance from the US Food and Drug Administration for use in coronary artery bypass procedures grafting procedures in 2005, and subsequently clearance for use during plastic and reconstructive and microsurgical procedures was received in 2007.

Technique

Once the surgeon is ready to image, the camera is positioned and anesthesia gives a 5-mL bolus containing 2.5 mg ICG. No toxicity has been seen with total doses of 5 g/kg (400 mg in an 80-kg patient). Typical acquisition times are around 1 minute. If one is attempting to visualize and localize perforating blood vessels, the camera is turned on immediately to record the first blush. If perfusion is the goal, the camera is switched on 15 seconds after injection to maximize time for full tissue evaluation. As technology progresses these parameters may change, so one must check this with the particular vendor. If a second scan is desired, one should wait 5 minutes to allow washout of the ICG for optimal scanning. Some software development is under way to eliminate this wait by subtracting any background ICG still present. Current software, such as the SPY-Q (Novadaq/LifeCell) allows the data to be seen with colorimetric analysis for easier interpretation ( Fig. 2 ). This software can analyze data and plot areas of maximal intensity, which correlates with best perfusion or perforator location.