Applications of indocyanine green in brain tumor surgery: review of clinical evidence and emerging technologies

Indocyanine green (ICG) is a water-soluble dye that was approved by the FDA for biomedical purposes in 1956. Initially used to measure cardiocirculatory and hepatic functions, ICG's fluorescent properties in the near-infrared (NIR) spectrum soon led to its application in ophthalmic angiography. In the early 2000s, ICG was formally introduced in neurosurgery as an angiographic tool. In 2016, the authors' group pioneered a novel technique with ICG named second-window ICG (SWIG), which involves infusion of a high dose of ICG (5.0 mg/kg) in patients 24 hours prior to surgery. To date, applications of SWIG have been reported in patients with high-grade gliomas, meningiomas, brain metastases, pituitary adenomas, craniopharyngiomas, chordomas, and pinealomas. The applications of ICG have clearly expanded rapidly across different specialties since its initial development. As an NIR fluorophore, ICG has advantages over other FDA-approved fluorophores, all of which are currently in the visible-light spectrum, because of NIR fluorescence's increased tissue penetration and decreased autofluorescence. Recently, interest in the latest applications of ICG in brain tumor surgery has grown beyond its role as an NIR fluorophore, extending into shortwave infrared imaging and integration into nanotechnology. This review aims to summarize reported clinical studies on ICG fluorescence-guided surgery of intracranial tumors, as well as to provide an overview of the literature on emerging technologies related to the utility of ICG in neuro-oncological surgeries, including the following aspects: 1) ICG fluorescence in the NIR-II window; 2) ICG for photoacoustic imaging; and 3) ICG nanoparticles for combined diagnostic imaging and therapy (theranostic) applications.