Fluorescence-Guided Surgery: A Review on Timing and Use in Brain Tumor Surgery

Abstract

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery.

Keywords: 5-ALA; ICG; extent of resection; fluorescein; fluorescence-guided surgery; timing.

Figure 1

(A) Pre-operative T1 post-contrast MR, showing a left temporal lesion with surrounding vasogenic edema. Histological diagnosis showed a metastatic lung adenocarcinoma. (B) Intraoperative picture during the surgical removal of the same case depicted in (A), showing the ICG uptake by the tumor visualized with yellow-green excitation. (C) Intraoperative picture during the surgical removal of the same case depicted in (A), showing the ICG uptake by the tumor with blue excitation. (D) Intraoperative picture during the surgical removal of the same case depicted in (A), showing the ICG uptake by the tumor visualized with near-infrared excitation.

Figure 2

(A) Pre-operative T1 post-contrast MR, showing a large right temporal lesion (white arrow), with irregular enhancement and mass effect, compatible with the suspect of high-grade glioma. (B) Post-operative T1 post-contrast MR, performed 24 h after surgery, confirming a gross-total resection (GTR) of the lesion (histological diagnosis showed a Glioblastoma, IDH wild-type). (C–E) Intraoperative picture during the surgical removal of the same case depicted in (A), taken with the Y560 filter activated (Pentero 900 microscope, Carl Zeiss Meditec, Oberkochen, Germany): after a small corticectomy (C), the pathological tissue is clearly visible as a bright green-yellow fluorescent area (white arrow), while the non-pathological temporal cortex (dotted white arrow) anteriorly and posteriorly is non-fluorescent (for orientation, Ant is anterior and Post is posterior temporal lobe); during surgical removal with ultrasonic aspirator (Sonoca 300, Soring, Quickborn, Germany), subcortical tumoral tissue is clearly discernible from normal peri-tumoral parenchyma by its bright green-yellow fluorescence (white arrow in (D) at the posterior border and in (E) at the anterior border), compared to pinkish peritumoral parenchyma (dotted white arrow).

Figure 3

Intraoperative imaging for case demonstration patient. (A) Tumor bulk fluorescence after 5-ALA administration (asterisk). (B) Infiltrative margin fluorescence after 5-ALA administration (white arrows). Taken with permission from Maragkos et al. (53).