The utilization of fluorescein in brain tumor surgery: a systematic review

J Neurosurg Sci. 2018 Dec;62(6):690-703. doi: 10.23736/S0390-5616.18.04480-6. Epub 2018 May 22.


Introduction: Sodium fluorescein (SF) is a green, water-soluble dye with the capacity to accumulate in cerebral areas as a result of damaged blood-brain barrier (BBB); this property allows SF to concentrate specifically at the tumor site of various types of brain neoplasms, making the tumor tissue more clearly visible.

Evidence acquisition: A literature search (1947-2018) was conducted with the keywords "fluorescein neurosurgery," "YELLOW neurosurgery," "fluorescein brain tumor," "YELLOW brain tumor." We included clinical studies, clinical trials, observational studies, only conducted on humans and concerning surgery; in addition, we have included 3 articles derived from the analysis of the references of other papers. Ultimately, 57 articles were included for further analysis.

Evidence synthesis: Fluorescein as a fluorescent tracer in neuro-oncology is gaining a wider acceptance in the neurosurgical literature: until February 1st, 2018, at least 1099 neuro-oncological patients have been operated through fluorescein-assistance, mostly only after 2012. The most important application remains the aim to improve tumor visualization and extent of resection for high-grade gliomas (HGG), but the nonspecific mechanism of action is the theoretical base for its use also for tumors different from HGG. Nevertheless, no homogenous protocol of fluorescein utilization in neurosurgical oncology can be found in literature.

Conclusions: Fluorescein-guided surgery is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration, with a growing evidence-based background.

Publication types

  • Systematic Review

MeSH terms

  • Blood-Brain Barrier / physiopathology*
  • Brain Neoplasms / surgery*
  • Extracellular Space*
  • Fluorescein*
  • Fluorescent Dyes*
  • Humans
  • Microscopy / methods*
  • Neurosurgical Procedures / methods*


  • Fluorescent Dyes
  • Fluorescein