ArticlePloS one2013
5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 6 of them syntheses that pooled it.
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86 citing papers in PubMed, 6 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions-A Systematic Review and Meta-Analysis.Tomography (Ann Arbor, Mich.) · 2023Pooled it
- Resection of the contrast-enhancing tumor in diffuse gliomas bordering eloquent areas using electrophysiology and 5-ALA fluorescence: evaluation of resection rates and neurological outcome-a systematic review and meta-analysis.Neurosurgical review · 2023Pooled it
- Intraoperative fluorescence diagnosis in the brain: a systematic review and suggestions for future standards on reporting diagnostic accuracy and clinical utility.Acta neurochirurgica · 2019Pooled it
- Various shades of red-a systematic analysis of qualitative estimation of ALA-derived fluorescence in neurosurgery.Neurosurgical review · 2018Pooled it
- Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results.Acta neurochirurgica · 2017Pooled it
- The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review.Neurosurgical review · 2016Pooled it
- Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.Journal of neurosurgery · 2018Trial
- Preoperative prediction of 5-ALA fluorescence in gliomas: comparison of 7-Tesla magnetic resonance spectroscopic imaging, contrast-enhancement on MRI, and positron emission tomography.European radiology · 2026Article
- Tunable Technologies for the Glioma Tumor Microenvironment: A Comprehensive Review on Bench-to-Bedside Neurosurgical Advances.Brain sciences · 2026Review
- Image-Guided Brain Tumor Surgery.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026Review
- Emerging uses of 5-aminolevulinic-acid-induced protoporphyrin IX in medicine: a review of multifaceted, ubiquitous, molecular diagnostic, therapeutic, and theranostic opportunities.Journal of biomedical optics · 2025Review
- EndoSCell: A portable intraoperative histopathological microscopy device for enhanced glioma resection and prognosis in animal models.APL bioengineering · 2025Article
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- Combined use of 5-ALA-induced protoporphyrin IX and chlorin e6 for fluorescence diagnostics and photodynamic therapy of skin tumors.Lasers in medical science · 2024Article
- Review
- Fluorescence guidance in skull base surgery: Applications and limitations - A systematic review.Brain & spine · 2024Review
- Advances in Intraoperative Glioma Tissue Sampling and Infiltration Assessment.Brain sciences · 2023Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria.
methodsWe prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status.
resultsA total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%.
conclusionsOur study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.
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