Bringing Light to Neurosurgical Tumors - Fluorescence Guided Surgery

Fluorescence guided surgery (FGS) is an intraoperative technology aimed at aiding surgeons in performing more complete and safer resection of brain tumors through improving visualization of tumor tissue. This technology brings clarity to neurosurgeons, allowing them to clearly and easily differentiate the tumor and surrounding healthy brain tissue. But how does this work? Prior to the surgery, patients are administered the 5-ALA oral drug, also known as Gleolan. This metabolic precursor agent is preferentially taken up by the tumor cells of the brain, causing the cells to become fluorescent and photosensitive. During surgery, a blue light is shone upon the brain: tumor cells absorb this blue light and emit a distinct red-pink fluorescence, clearly deviating from healthy tissue. This then allows the neurosurgeon to precisely identify and operate on the tumor without harming the healthy cells, optimizing patient outcomes. This has led to the improvement of gross total resection rates to 81% for fluorescein-guided surgery and rates of up to 100% with adjuncts such as intraoperative MRI.

FGS is no longer a newfound technology. On the contrary, it was first integrated into medical sciences over 2 centuries ago, with the first fluorescent stain, fluorescein, being invented in 1871. However, it was only in 1947 when the discovery that fluorescein could be used to differentiate neoplastic and normal tissue during brain tumor surgery took place, and neurosurgery became the first surgical field to explore the utility of intraoperative fluorescence. Since then, a variety of fluorophores have been developed and studied for application in FGS, the most popular today being 5-aminolevulinic acid hydrochloride (5-ALA), indocyanine-green (ICG), and fluorescein. In the United States, Dr. Costas Hadjipanayis, MD, PhD played an enormous role in advancing FGS. His team completed a number of clinical studies with 5-ALA, confirming it to be safe and effective in the removal of malignant gliomas. This led to the United States FDA approval of  5-ALA (Gleolan) for use during glioma surgery in 2017. He also became the first neurosurgeon in the U.S. to utilize the agent Gleolan following his removal of a glioblastoma tumor in 2011. 

As of today, FGS is combined with other rising technologies, such as robotic-assisted exoscopes, to further maximize safety and precision. Ongoing clinical trials and technological refinements continue to take place regarding FGS– it is a technology requiring persistent update and advancements. With dedicated researchers, scientists, and medics rising up for the cause, novel fluorophores, quantitative imaging, and therapeutic applications are all possible promises to further optimize tumor visualization and treatment in the future.

Written by Renee Wang at Incisionary

References

McCracken, D. J., Schupper, A. J., Lakomkin, N., Malcolm, J., Painton Bray, D., & Hadjipanayis, C. G. (2022). Turning on the light for brain tumor surgery: A 5-aminolevulinic acid story. Neuro-oncology, 24(Suppl 6), S52–S61. https://doi.org/10.1093/neuonc/noac191

Rodriguez, B., Brown, C. S., Colan, J. A., Zhang, J. Y., Huq, S., Rivera, D., Young, T., Williams, T., Subramaniam, V., & Hadjipanayis, C. (2025). Fluorescence-Guided Surgery for Gliomas: Past, Present, and Future. Cancers, 17(11), 1837. https://doi.org/10.3390/cancers17111837