Enhancing Perfusion Assessment of Chronic Wounds Through the Utilization of Fluorescence Angiography

  One of the biggest challenges today in wound care clinics is the assessment of the vascularity of the wound and the ability of the patient to heal. For many years, there has not been a surefire way to assess overall blood flow to any tissue that may be ischemic or compromised by a lack of vascularity, such as with diabetic neuropathy. The ability to influence and gain information regarding the inflow and outflow to any wound bed is of great value to the wound clinician and staff. Historically, injection of fluorescence dye and a Woods lamp have been used in surgery (as is laser Doppler) in an attempt to assess blood flow. These modalities can be confusing and cumbersome, however, and are associated with potential side effects.   This article examines the use of fluorescence angiography in wound care and considerations that should be made for those clinicians seeking to incorporate it into practice.

Covering The Basics

  Fluorescence angiography is an effective, real-time imaging tool for measuring blood flow in vessels and micro-vessels as well as for tissue and organ perfusion during medical procedures. The technology is based on a fluorescence agent known as indocyanine green (ICG) that absorbs light in the near-infrared (NIR) spectrum. Advances in technology have allowed the use of fluorescence angiography in open, robotic, and endoscopic surgical procedures in the operating room under complete control of the surgeon and without the ionizing radiation and contrast potential nephrotoxicity safety concerns associated with traditional X-ray in certain patient populations such as those living with diabetes, renal insufficiency, or congestive heart failure. Although used experimentally in the late 1990s, this technology was being used by the mid-2000s by cardiac and plastic surgeons.^1,12,13 For the first time, surgeons could immediately visualize perfusion in the operated tissues multiple times throughout a procedure as their needs changed. Most importantly, use of the dye and the laser has been proven to be safe in humans.^{7, 12-26}   ICG is a water-soluble tricarbocyanine dye originally developed by the Eastman Kodak Company for use in infrared photography and was first approved by the FDA for use in the US in 1959. Introduced into clinical practice in the form of a stable lyophilized powder at the Mayo Clinic, ICG was once referred to as “Fox Green” after the cardiologist Dr. Irwin Fox, who was responsible for its initial use to assess cardiac output by means of a dye-dilution technique.² ICG was also later used to assess arteriovenous fistulae³ and renal blood flow.⁴ The observation that ICG is metabolized exclusively via the liver and excreted completely into bile led to its use in assessing liver function and blood flow.^5,6 Near-infrared absorption and emission of light ICG makes it particularly well suited to visualizing small blood vessels. In the early 1970s, Dr. Robert Flower leveraged the near infrared absorption and emission of light properties of ICG to develop techniques for acquisition of fluorescence angiograms of the microvasculature in the retinal choroid in the eye.^7,8 Use of fluorescence-imaging technologies and techniques today continues to be based on the angiography principles developed by Flower.   Fluorescence angiography systems are comprised of an imaging camera, which houses a laser (806-nm diode) that provides near-infrared illumination. During a procedure, the operator positions the camera above the area of interest and (following administration of ICG) activates the NIR laser light source and camera. Real-time moving images are then displayed instantly onto a computer screen. Because ICG remains within the vascular space and has the benefit of a short half-life, multiple images may be taken within a single procedure. The ability to view and evaluate blood flow in or around any open wound and assess real-time fluorescence angiography to gauge the status of the lower extremity or other area of concern is invaluable in assessing whether a treatment modality such as hyperbaric oxygen or negative pressure wound therapy are providing necessary healing. Fluorescence angiography has become a vital part of the author’s practice in the wound care center.

Launch of Fluorescence Angiography

  The first fluorescence angiography system (SPY® by Novadaq® Technologies, Mississauga, ON) was developed for use during coronary artery bypass graft (CABG) surgery to confirm the patency of bypass grafts. Initially approved for use during CABG in Canada, Europe, and Japan in 2001 and in the US by the FDA in January 2005, SPY has been compared to X-ray angiography through multiple reports in that its use resulted in the detection of nonfunctioning bypass grafts in 4-8% of patients.^12–22 SPY fluorescence angiographic technologies have also subsequently been cleared by regulatory authorities to include other cardiovascular and peripheral vascular procedures, solid organ transplantation (including liver and kidney^23,24 and pancreas²⁵), gastrointestinal procedures, general surgery, and robotic and minimally invasive surgery. In late 2007, SPY technology was then cleared for use during plastic and reconstructive as well as microsurgical procedures. Today, the use of the SPY Elite® system for perfusion assessment in plastic reconstructive surgery is rapidly expanding. Several peer-reviewed journal articles have shown that the use of SPY imaging in breast and other reconstruction procedures results in significantly lower rates of tissue necrosis compared to historical necrosis rates.^25,26 More recently, in part because of the increase in the number of medical practitioners who treat chronic, nonhealing wounds and have used this technology in other parts of their plastic or general surgery practice, application of fluorescence angiography has organically expanded to include perfusion assessment in the wound-healing environment. Introduced in March 2013, the latest generation of fluorescence angiography technology — LUNA™ (Novadaq Technologies) — has also been embraced by wound care specialists for the treatment of patients who live with chronic, nonhealing wounds.^27,28

Addressing Advantages, Precautions for ICG

  One of the more notable advantages of ICG over other fluorescent agents, such as fluorescein, is its rapid clearance from the tissues and its confinement to the intravascular compartment — making it an ideal blood pool contrast agent that can be used multiple times in the same patient during a single treatment setting. By contrast, fluorescein leaks into the interstitial space, causing staining, and therefore can only be used once in a single setting. Fluorescein, unlike ICG, which travels in circulation, gives no information about dynamic perfusion. Following intravascular administration, ICG is rapidly and extensively bound to plasma proteins, with a-lipoproteins being the major carrier in humans.⁹ The plasma half-life of ICG is very short, approximately 3-5 minutes in humans. ICG is taken up by the liver and excreted completely into the bile without any further metabolism, making it an ideal agent for use in patients whose renal function is of concern.¹⁰ Since its introduction into clinical practice, ICG has shown an excellent safety profile, including a low incidence of adverse reactions (about 1 in 42,000 patients). However, ICG contains iodide, so it should be used with caution or in combination with pre-treatment regimens in patients who have sensitivity to iodides. Most reported reactions, if any, have been called mild in nature, such as experiencing a feeling of warmth or sore throat. Reports of anaphylaxis are extremely rare.¹¹ C. Andrew Salzberg is associate professor of plastic surgery, New York Medical College, Valhalla.

References

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