Ex-vivo analysis of quantitative 5-ALA fluorescence intensity in diffusely infiltrating gliomas using a handheld spectroscopic probe: Correlation with histopathology, proliferation and microvascular density.


Journal

Photodiagnosis and photodynamic therapy
ISSN: 1873-1597
Titre abrégé: Photodiagnosis Photodyn Ther
Pays: Netherlands
ID NLM: 101226123

Informations de publication

Date de publication:
Sep 2019
Historique:
received: 09 01 2019
revised: 02 05 2019
accepted: 13 05 2019
pubmed: 19 5 2019
medline: 11 2 2020
entrez: 19 5 2019
Statut: ppublish

Résumé

Intraoperative semiquantitative classification of different visible 5-aminolevulinic acid (5-ALA) fluorescence levels by the neurosurgeon is subjective. Recently, handheld spectroscopic probes were introduced enabling quantitative analysis of 5-ALA induced fluorescence intensity (FI). The aim of this ex-vivo study was to correlate the FI in gliomas of different grades with histopathology, proliferation and microvasular density (MVD). Patients with suspected World Health Organization (WHO) grade II-IV gliomas were included and tissue samples from different visible fluorescence levels (strong, vague or none) were intraoperatively collected. After resection, the FI of each sample was investigated ex-vivo by a handheld spectroscopic probe. The FI values were correlated with visible fluorescence, histopathology (WHO grade, quality of tissue, histopathological parameters of anaplasia), proliferation (MIB-1) and MVD. Altogether, 143 tumor samples with strong (n = 61), vague (n = 21) and no fluorescence (n = 61) were collected in 68 patients. We found significantly different median FI values between all three visible fluorescence levels. Moreover, the median FI value was significantly higher in WHO grade III/IV samples and compact tumor tissue compared to WHO grade II samples and infiltrated tumor tissue. Further, significant differences in median FI values were observed in specific histopathological parameters of anaplasia (mitotic rate, cell density, nuclear pleomorphism and microvascular proliferation) in multivariable analysis. Finally, a significant correlation between the proliferation rate and FI, but not between MVD and FI was noted. Our data indicate that handheld spectroscopic probes are capable of visualizing intratumoral glioma heterogeneity by objective assessment of fluorescence and may thus optimize future glioma surgery.

Sections du résumé

BACKGROUND BACKGROUND
Intraoperative semiquantitative classification of different visible 5-aminolevulinic acid (5-ALA) fluorescence levels by the neurosurgeon is subjective. Recently, handheld spectroscopic probes were introduced enabling quantitative analysis of 5-ALA induced fluorescence intensity (FI). The aim of this ex-vivo study was to correlate the FI in gliomas of different grades with histopathology, proliferation and microvasular density (MVD).
PATIENTS AND METHODS METHODS
Patients with suspected World Health Organization (WHO) grade II-IV gliomas were included and tissue samples from different visible fluorescence levels (strong, vague or none) were intraoperatively collected. After resection, the FI of each sample was investigated ex-vivo by a handheld spectroscopic probe. The FI values were correlated with visible fluorescence, histopathology (WHO grade, quality of tissue, histopathological parameters of anaplasia), proliferation (MIB-1) and MVD.
RESULTS RESULTS
Altogether, 143 tumor samples with strong (n = 61), vague (n = 21) and no fluorescence (n = 61) were collected in 68 patients. We found significantly different median FI values between all three visible fluorescence levels. Moreover, the median FI value was significantly higher in WHO grade III/IV samples and compact tumor tissue compared to WHO grade II samples and infiltrated tumor tissue. Further, significant differences in median FI values were observed in specific histopathological parameters of anaplasia (mitotic rate, cell density, nuclear pleomorphism and microvascular proliferation) in multivariable analysis. Finally, a significant correlation between the proliferation rate and FI, but not between MVD and FI was noted.
CONCLUSION CONCLUSIONS
Our data indicate that handheld spectroscopic probes are capable of visualizing intratumoral glioma heterogeneity by objective assessment of fluorescence and may thus optimize future glioma surgery.

Identifiants

pubmed: 31102691
pii: S1572-1000(19)30015-8
doi: 10.1016/j.pdpdt.2019.05.013
pii:
doi:

Substances chimiques

Photosensitizing Agents 0
Aminolevulinic Acid 88755TAZ87

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

354-361

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Mauricio Martínez-Moreno (M)

Department of Neurosurgery, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: mauricio.martinezmoreno@helios-gesundheit.de.

Barbara Kiesel (B)

Department of Neurosurgery, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: barbara.kiesel@meduniwien.ac.at.

Adelheid Woehrer (A)

Institute of Neurology, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: adelheid.woehrer@meduniwien.ac.at.

Mario Mischkulnig (M)

Department of Neurosurgery, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: mario.mischkulnig@meduniwien.ac.at.

Julia Furtner (J)

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: julia.furtner@meduniwien.ac.at.

Gerald Timelthaler (G)

Institute of Cancer Research, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: gerald.timelthaler@meduniwien.ac.at.

Walter Berger (W)

Institute of Cancer Research, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: walter.berger@meduniwien.ac.at.

Engelbert Knosp (E)

Department of Neurosurgery, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: engelbert.knosp@meduniwien.ac.at.

Johannes A Hainfellner (JA)

Institute of Neurology, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: johannes.hainfellner@meduniwien.ac.at.

Stefan Wolfsberger (S)

Department of Neurosurgery, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria.

Georg Widhalm (G)

Department of Neurosurgery, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria; Institute of Cancer Research, Medical University of Vienna Waehringer Guertel 18 - 20, 1090 Vienna, Austria. Electronic address: georg.widhalm@meduniwien.ac.at.

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Classifications MeSH