Fluorescence image-guided surgery (FIGS ) is a surgical technique that involves the use of indicator substances that absorb and emit light under specific wavelengths to allow for visualization of particular anatomic structures. Methylene blue, quinine, fluorescein, and indocyanine green (ICG) are examples of indicator substances, or fluorophores, that have been used for medical and surgical purposes. The field of immunofluorescence is based upon the action of fluorophores binding to target molecules such as plasma proteins or antibodies, absorbing light and then emitting a specific wavelength of light once excited. FIGS has been utilized in various surgical fields, including ophthalmology; urology; cardiothoracic, hepatobiliary, plastic, and reconstructive surgery; and, more recently, colon and rectal surgery [1–6]. Cutting edge technology pairing near-infrared imaging (NIR) with intravenous administration of ICG has been utilized in open and minimally invasive colorectal surgery to evaluate blood supply and anastomotic perfusion [7–14].

German physician and immunologist, Paul Ehrlich, is credited with the first in vivo use of fluorescence in 1882 when he intravenously injected uranin, the sodium salt of fluorescein, to follow the outflow of the aqueous humor of the eye. In the early 1900s, fluorescence microscopes were created by German physicists Otto Heimstadt and Heinrich Lehmann and allowed scientists to more closely evaluate the autofluorescence of bacteria, plants, and bioorganic substances such as albumin, elastin, and keratin. Quinine, a fluorophore found naturally in the bark of the South American cinchona tree, became an important compound to combat malaria in the Pacific theater during the World War II. Pharmacologists Bernard Brodie and Sidney Udenfriend (1943) developed a spectrophotofluorometer to evaluate the levels of quinine in the plasma of malaria patients, advancing the fields of immunofluorescence and targeted chemotherapy.

The first successful fluorescein angiogram in a human subject (1959) was performed by Indiana University medical students, Harold Novotny and David Alvis, and furthered the study of diabetic and hypertensive retinopathy. Another important fluorophore, indocyanine green (ICG), gained FDA approval in 1959 and soon found application in the assessment of ophthalmic circulation, cardiac output, and hepatic function and blood flow. Video fluorescence angiography utilizing fluorescein and ICG served as a precursor to FIGS as it allowed for real-time investigation of retinal and cardiac pathology and subsequent surgical interventions.

As video and digital technology advanced, FIGS expanded into such surgical fields as urology, hepatobiliary, plastic, and intestinal surgery. Fluorescence imaging has been reported in both open and minimally invasive surgery, with a developing subsector in the realm of robotic surgery [6, 8, 9, 11, 13].

Originally developed as a photographic dye, ICG has become the more utilized fluorophore for FIGS. It is a water-soluble, tricarbocyanine dye that absorbs light between 600 and 900 nm and emits fluorescence between 750 and 950 nm, with a peak spectral absorption at 800–810 nm in blood or plasma. When injected intravenously, ICG binds tightly to plasma proteins and remains exclusively in the vascular system. The affinity for the bloodstream allows for excellent evaluation of vascular anatomy and tissue perfusion. It is metabolized microsomally and solely excreted by the liver, with a half-life of approximately 3–4 min. The specific hepatic uptake and excretion also provide for enhanced visualization of the bile ducts. Although fluorescein has been similarly utilized in the past for assessment of intestinal perfusion, ICG is a more versatile agent given its short half-life, allowing for multiple administrations during a single operation [14].

The main applications of ICG fluorescence in general surgery have been visualization of vascular anatomy, assessment of anastomotic perfusion, examination of hepatobiliary anatomy, intraluminal tattooing, sentinel lymph node biopsying, and lymph node mapping [15–18].

ICG is a relatively safe imaging agent with very few reports of toxic or allergic reactions from its administration [19–21]. Rare cases of urticaria and anaphylaxis have been described [22]. Although ICG contains less than 5 % sodium iodide, caution should be exercised in patients with a history of an iodide or iodinated imaging agent allergy.

Since 2005, several companies have manufactured biomedical NIR imaging systems (i.e., Stryker Corporation, Karl Storz GmbH, Olympus Corporation, Pulsion Medical Systems, Novadaq Technologies). All of the systems are designed around the capability of deep photon penetration of NIR light into tissues (<1 cm) to provide imaging of ICG, which emits light between 700 and 900 nm [23]. The systems are comprised of a spectrally resolved light source (i.e., LED or laser diode) which is focused on the surgical field that excites the fluorophore . The light emitted from ICG is then filtered and imaged onto a charge-coupled device camera (CCD) . The images from the camera can then be displayed on the surgical monitor with or without the white light imaging background.

The surgeon can initiate Firefly mode with either the master finger switches while depressing the endoscope foot pedal or by toggling to “Firefly mode” in the settings section of the surgeon console. Alternatively, an assistant can switch to “Firefly mode” on the touchscreen of the vision cart. Ideally, Firefly mode is initiated immediately following the intravenous administration of ICG, producing a fluorescent image within 30–60 s. By manipulating the Firefly intensity slider on either the surgeon console or on the touchscreen of the vision cart, the intensity of the fluorescent image in relation to the black and white image can be adjusted.

The literature regarding the use of IF within the realm of minimally invasive colorectal surgery is growing. To best understand the application of IF for colorectal surgery with the robotic system, it is important to review the small body of literature involving IF and MIS for colorectal disease. To date, the focus of IF in colorectal surgery has largely been assessment of anastomotic perfusion and identification of vascular anatomy, with the goal of minimizing anastomotic complications.

Anastomotic leak (AL) can be a catastrophic complication following colorectal resection. Reports in the literature suggest that AL occurs in 1–3 % of ileocolic anastomoses and up to 10–20 % of colorectal anastomoses [24, 25]. Morbidity, mortality, and local recurrence rates are significantly increased by postoperative AL in the setting of colorectal cancer [7, 26].

Typically considered multifactorial in origin, AL has been associated with poor tissue perfusion, anastomotic tension, distal anastomoses, preoperative radiation, corticosteroid use, male sex, and smoking [7, 27–29]. Historically, assessment of anastomotic tissue perfusion has been a subjective evaluation by the surgeon based on unreliable parameters, such as active bleeding at the edges of the distal and proximal bowel, discoloration of the serosa at the resection margins, and the presence of a palpable pulse in the mesentery. In a study evaluating AL in 191 colorectal resections, Karliczek et al. concluded that these subjective parameters lack the predictive accuracy to determine if AL will occur and encouraged more objective tools to assess perfusion, such as visible light spectroscopy to measure anastomotic tissue oxygenation [30, 31].

In a systematic review of 37 studies detailing intraoperative colorectal anastomotic assessment techniques and their effect on postoperative anastomotic complications, Nachiappan et al. found that a wide range of mechanical patency tests, endoscopic visualization techniques, and microperfusion evaluations has been utilized [32]. Laser Doppler flowmetry, tissue oxygen tension, visible and NIR O2 spectroscopy, narrow band imaging, LFA, and NIR angiography have all been evaluated in non-randomized controlled studies [33–35]. The authors concluded that microperfusion techniques utilizing autofluorescent dyes were promising techniques, given the ease of performing the studies and the sensitivity of the information gathered.

Kudszus and colleagues performed the first clinical study utilizing laser fluorescence angiography (LFA) to evaluate tissue perfusion and its effect on the rate of colorectal anastomotic complications [7]. In a retrospective, case-matched study, 402 patients underwent either laparoscopic or conventional colorectal resection by experienced surgeons. Half of the patients received ICG (0.2–0.5 mg/kg) immediately following the construction of the anastomosis with subsequent LFA. The IC-View^® system (Pulsion Medical Systems), comprised of a digital video camera with an attached laser (λ = 780 nm) and an infrared filter, was utilized. Tissue perfusion was deemed suboptimal in 13.9 % (28/201) of patients who underwent LFA, resulting in an immediate revision of the colorectal anastomosis. AL occurred in 7 (3.5 %) patients in the LFA group and 15 (7.5 %) patients in the control group. Revisional surgery was required to address AL in all 22 patients.

Subgroup analysis demonstrated that the use of LFA significantly reduced AL in patients older than 70, those with hand-sewn anastomoses, and those performed under elective conditions. The authors concluded that the use of LFA reduced the risk of anastomotic leakage and subsequently decreased hospital length of stay.