Current trends and emerging future of indocyanine green usage in surgery and oncology

Abstract

Ever since Kitai first performed fluorescent navigation of sentinel lymph nodes (SLNs) using indocyanine green (ICG) dye with a charge-couple device and light emitting diodes, the intraoperative use of near infrared fluorescence has served a critical role in increasing our understanding in various fields of surgical oncology. Here the authors review the emerging role of the ICG fluorophore in the development of our comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers. In addition, they introduce the novel role of ICG-guided video angiography as a new intraoperative method of assessing microvascular circulation. The authors attempt to discuss the promising potential in addition to assessing several challenges and limitations in the context of specific surgical procedures and ICG as a whole. PubMed and Medline literature databases were searched for ICG use in clinical surgical settings. Despite ICG's significant impact in various fields of surgical oncology, ICG is still in its nascent stages, and more in-depth studies need to be carried out to fully evaluate its potential and limitations. Cancer 2011;117:4812-22. V C 2011 American Cancer Society.KEYWORDS: sentinel lymph node, indocyanine green, lymphedema, free flaps, axillary reverse mapping, sentinel lymph node biopsy.Near infrared (NIR; emission spectra of $700-850 nm) 1 fluorophores are probes that have gained immense interest in various fields of biomedicine because of their minimal interfering absorption and fluorescence from biological samples, inexpensive laser diode excitation, reduced scattering, and enhanced tissue penetration depth. 2 However, to date, only 1 NIR probe, indocyanine green (ICG) has been approved by the US Food and Drug Administration (FDA); methylene blue is another FDA-approved probe that displays NIR properties, however, it is not considered a pure NIR probe. The former, ICG, is a water-soluble, anionic, amphiphilic tricarbocyanine probe 3 with a hydrodynamic diameter of 1.2 nm, and excitation and emission wavelengths in serum at 778 and 830, respectively. 4,5 For several years, it has been used in ophthalmic angiography 6 and for determining cardiac output 7 and hepatic function. 8 However, it has only recently shown real practicability and feasibility in the field of surgical oncology. Three major domains where NIR-guided ICG fluorophores have appeared most promising are: 1) sentinel lymph node (SLN) detection, 2) evaluation of lymphedema, and 3) assessment of microvascular circulation of free flaps in reconstructive surgery. Although several reviews have discussed the importance of NIR fluorophores (including ICG), 9-13 in this review we limit our discussion specifically to ICG in an attempt to attain a better understanding of its impact and challenges it presents in the field of surgical oncology.Intraoperative SLN Mapping and Biopsy Using ICG The significance of cancer treatment management in relation to first lymphatic drainage from the tumor site, the SLN, was first proposed by Cabanas...

Different ways to manage indocyanine green fluorescence to different purposes in liver surgery: A systematic review

“…for hepatic function or for not-hepatic surgery (n=750), or being irrelevant to our topic (n=371).Congress presentation and letters to the editor (150) were excluded from the analysis. Of the remaning 35 articles, 16 of which were excluded after full text examination, either for being narrative review (n=4, these have been cited in Discussion section [29,31,32,33]), or being irrelevant as comments to other papers (n=7), or only available in abstract form (n=5).…”

“…31 Possible uses in oncological surgery are summarized in two reviews. 32,33 Many articles has been published about the staining of biliary tree during cholecystectomy as described by Boni et al 34 but it was not the goal of our review.…”

Emerging lymphatic imaging technologies for mouse and man

“…Upon illumination of tissue surfaces with NIR excitation light, ICG fluorescence is collected using charge-coupled device (CCD) cameras and can be used to visualize the initial lymphatics, collecting and conducting lymphatics, and draining LNs across wide fields of view that can encompass entire limbs (Figure 2, E and F). The majority of studies that employ NIRF imaging with ICG focus on pre-surgical and intraoperative sentinel LNM (SLNM) and dissection (31)(32)(33). While investigational camera designs have widely varying sensitivity (34,35), non-invasive NIRF imaging can detect the lymphatic vasculature located as deep as 3-4 cm beneath the tissue surface with as little as 10 μg of ICG in 0.1 ml in humans (36) using intensified camera technologies, and up to 5 μg of ICG in 10 μl in mice using electron multiplier CCD technology (37)(38)(39).…”

“…The lymph pump is thought be controlled by the autonomic nervous system and is critical to tissue fluid homeostasis and immune cell transport. The identification of factors that affect lymphatic pumping is an active area of research that will contribute to the development of (31,35,37) new pharmacologic strategies to correct lymphatic insufficiency. Lymphatic dysfunction is generally diagnosed based upon onset of late-stage, irresolvable symptoms of edema, chylous ascites, and chylothorax.…”

Photons across medicine: relating optical and nuclear imaging

“…ICG may make an excellent surrogate for qualification of near-infrared fluorescence devices, and most recently, it is used as a non-specific fluorescent imaging in lymph node mapping in cancer staging, intraoperative angiography, among other uses [36][37][38][39]. For over 50 years, ICG has been used as a blood pooling dye used on the basis of its dark green color for assessing hepatic function and retinopathy, but as an near infrared fluorescence imaging agent, it is a poor fluorophore, unstable, and has no functional group to attach molecularly targeting entities.…”