Optical Imaging Perspective on the Use of Indocyanine Green in Endoscopic Skull Base Neurosurgery

Background: Fluorescence-guided surgery (FGS) has become a cornerstone in modern neurosurgery. Indocyanine green (ICG) stands out given its optical profile: excitation/emission in the near-infrared (NIR) spectrum (780 and 805 nm, respectively), deeper tissue penetration, favorable signal-to-noise ratios (SNR), and excellent safety profiles. While ICG has long been used for cerebrovascular cases and for tumor visualization via “second-window ICG (SWIG)” (i.e., 5 mg/kg dose 24 hrs before imaging), its potential in endoscopic, endonasal skull base surgery (EES) is beginning to be realized. Innovation: ICG is effective for neurosurgical applications due to its optical and pharmacokinetic properties underlying its performance. First, when illuminated with near-infrared (NIR) light (~780 nm), ICG absorbs photons and re-emits fluorescence at slightly longer NIR wavelengths (~805 nm), allowing deeper imaging compared to visible light. Second, tissue autofluorescence is almost nonexistent in NIR, thereby optimizing the signal-to-background ratio (SBR). Third, ICG rapidly binds to plasma proteins, keeping it confined within the intravascular compartment; ensuring that the measured fluorescence signal directly maps perfused blood vessels, and the intensity and dynamics of the signal reflect both vascular anatomy and blood flow in real time. The mechanistic combination of plasma protein binding, NIR excitation/emission, and intravascular confinement underlies ICG’s reliability and precision for intraoperative vascular imaging. In SWIG, patients receive a high-dose ICG infusion 24 hours before surgery, allowing dye accumulation in tumors through the enhanced permeability and retention (EPR) effect caused by leaky tumor vasculature and impaired lymphatic drainage. This enables tumor margin visualization with deeper tissue penetration and higher contrast that persists even in vascularly dense or optically heterogeneous tumor regions. Furthermore, endoscope-based optics delivers excitation light directly into deep or narrow surgical corridors and captures emitted fluorescence with high-sensitivity detectors next to target tissue. This reduces background scatter and signal loss, enhancing contrast and enabling detection of low fluorophore signals; unlike operating microscopes, which rely on longer optical paths and wider fields of view that can decrease fluorescence intensity. By integrating the advantages of ICG with endoscope optics, neurosurgeons exploit ICG fluorescence to navigate complex anatomy otherwise obscured by bone, dura, or tumor. Institutional Experience: We exemplify ICG’s advantage in our ESS cases, discuss comparative fluorophore performance, and frame ICG’s promise in the broader context of fluorescence-guided skull base neurosurgery. Significance: The integration of ICG into routine ESS workflows could redefine the boundaries of what is considered safe and feasible in skull base surgery. Emerging optical technologies—such as quantitative fluorescence, mapping, and hyperspectral imaging—promise to extend ICG’s applications beyond qualitative visualization, enabling objective assessment of tissue perfusion, tumor margins, and endocrine preservation. In this presentation, we exemplify ICG’s advantage in ESS cases, discuss comparative fluorophore performance, and frame ICG’s promise in the broader context of fluorescence-guided skull base neurosurgery. Fig. 1 ICG illumination of internal carotid arteries bilaterally, as well as pituitary gland centrally, through the sellar floor Fig. 2 ICG illumination of pituitary gland, distinctly separating it from the pathology Fig. 3 ICG illumination of pituitary and perforator vessel to the optic chiasm Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany