Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors

PurposeModern techniques for improved tumor visualization have the aim to maximize the extent of resection during brain tumor surgery and thus improve patient prognosis. Optical imaging of autofluorescence is a powerful and non-invasive tool to monitor metabolic changes and transformation in brain t...

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Main Authors: David Reichert, Lisa I. Wadiura, Mikael T. Erkkilae, Johanna Gesperger, Alexandra Lang, Thomas Roetzer-Pejrimovsky, Jessica Makolli, Adelheid Woehrer, Marco Wilzbach, Christoph Hauger, Barbara Kiesel, Marco Andreana, Angelika Unterhuber, Wolfgang Drexler, Georg Widhalm, Rainer A. Leitgeb
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1105648/full
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author David Reichert
David Reichert
Lisa I. Wadiura
Mikael T. Erkkilae
Johanna Gesperger
Johanna Gesperger
Alexandra Lang
Thomas Roetzer-Pejrimovsky
Jessica Makolli
Adelheid Woehrer
Marco Wilzbach
Christoph Hauger
Barbara Kiesel
Marco Andreana
Angelika Unterhuber
Wolfgang Drexler
Georg Widhalm
Rainer A. Leitgeb
Rainer A. Leitgeb
author_facet David Reichert
David Reichert
Lisa I. Wadiura
Mikael T. Erkkilae
Johanna Gesperger
Johanna Gesperger
Alexandra Lang
Thomas Roetzer-Pejrimovsky
Jessica Makolli
Adelheid Woehrer
Marco Wilzbach
Christoph Hauger
Barbara Kiesel
Marco Andreana
Angelika Unterhuber
Wolfgang Drexler
Georg Widhalm
Rainer A. Leitgeb
Rainer A. Leitgeb
author_sort David Reichert
collection DOAJ
description PurposeModern techniques for improved tumor visualization have the aim to maximize the extent of resection during brain tumor surgery and thus improve patient prognosis. Optical imaging of autofluorescence is a powerful and non-invasive tool to monitor metabolic changes and transformation in brain tumors. Cellular redox ratios can be retrieved from fluorescence emitted by the coenzymes reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). Recent studies point out that the influence of flavin mononucleotide (FMN) has been underestimated.Experimental designFluorescence lifetime imaging and fluorescence spectroscopy were performed through a modified surgical microscope. We acquired 361 flavin fluorescence lifetime (500-580 nm) and fluorescence spectra (430-740 nm) data points on freshly excised different brain tumors: low-grade gliomas (N=17), high-grade gliomas (N=42), meningiomas (N=23), metastases (N=26) and specimens from the non-tumorous brain (N=3).ResultsProtein-bound FMN fluorescence in brain tumors did increase with a shift toward a more glycolytic metabolism (R=-0.87). This increased the average flavin fluorescence lifetime in tumor entities with respect to the non-tumorous brain. Further, these metrics were characteristic for the different tumor entities and showed promise for machine learning based brain tumor classification.ConclusionsOur results shed light on FMN fluorescence in metabolic imaging and outline the potential for supporting the neurosurgeon in visualizing and classifying brain tumor tissue during surgery.
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spelling doaj.art-c2c599ad28d84f66a89f23773e63cad42023-02-20T07:24:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.11056481105648Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumorsDavid Reichert0David Reichert1Lisa I. Wadiura2Mikael T. Erkkilae3Johanna Gesperger4Johanna Gesperger5Alexandra Lang6Thomas Roetzer-Pejrimovsky7Jessica Makolli8Adelheid Woehrer9Marco Wilzbach10Christoph Hauger11Barbara Kiesel12Marco Andreana13Angelika Unterhuber14Wolfgang Drexler15Georg Widhalm16Rainer A. Leitgeb17Rainer A. Leitgeb18Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Innovative Optical Imaging and its Translation to Medicine (OPTRAMED), Medical University of Vienna, Vienna, AustriaDepartment of Neurosurgery, General Hospital and Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, AustriaDepartment of Neurosurgery, General Hospital and Medical University of Vienna, Vienna, AustriaDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, AustriaDepartment of Neurosurgery, General Hospital and Medical University of Vienna, Vienna, AustriaDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, AustriaAdvanced Development Microsurgery, Carl Zeiss Meditec AG, Oberkochen, GermanyAdvanced Development Microsurgery, Carl Zeiss Meditec AG, Oberkochen, GermanyDepartment of Neurosurgery, General Hospital and Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaDepartment of Neurosurgery, General Hospital and Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Innovative Optical Imaging and its Translation to Medicine (OPTRAMED), Medical University of Vienna, Vienna, AustriaPurposeModern techniques for improved tumor visualization have the aim to maximize the extent of resection during brain tumor surgery and thus improve patient prognosis. Optical imaging of autofluorescence is a powerful and non-invasive tool to monitor metabolic changes and transformation in brain tumors. Cellular redox ratios can be retrieved from fluorescence emitted by the coenzymes reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). Recent studies point out that the influence of flavin mononucleotide (FMN) has been underestimated.Experimental designFluorescence lifetime imaging and fluorescence spectroscopy were performed through a modified surgical microscope. We acquired 361 flavin fluorescence lifetime (500-580 nm) and fluorescence spectra (430-740 nm) data points on freshly excised different brain tumors: low-grade gliomas (N=17), high-grade gliomas (N=42), meningiomas (N=23), metastases (N=26) and specimens from the non-tumorous brain (N=3).ResultsProtein-bound FMN fluorescence in brain tumors did increase with a shift toward a more glycolytic metabolism (R=-0.87). This increased the average flavin fluorescence lifetime in tumor entities with respect to the non-tumorous brain. Further, these metrics were characteristic for the different tumor entities and showed promise for machine learning based brain tumor classification.ConclusionsOur results shed light on FMN fluorescence in metabolic imaging and outline the potential for supporting the neurosurgeon in visualizing and classifying brain tumor tissue during surgery.https://www.frontiersin.org/articles/10.3389/fonc.2023.1105648/fullfluorescence guided surgeryfluorescence lifetime imagingfluorescence spectroscopyoptical redox ratioflavin mononucleotide
spellingShingle David Reichert
David Reichert
Lisa I. Wadiura
Mikael T. Erkkilae
Johanna Gesperger
Johanna Gesperger
Alexandra Lang
Thomas Roetzer-Pejrimovsky
Jessica Makolli
Adelheid Woehrer
Marco Wilzbach
Christoph Hauger
Barbara Kiesel
Marco Andreana
Angelika Unterhuber
Wolfgang Drexler
Georg Widhalm
Rainer A. Leitgeb
Rainer A. Leitgeb
Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
Frontiers in Oncology
fluorescence guided surgery
fluorescence lifetime imaging
fluorescence spectroscopy
optical redox ratio
flavin mononucleotide
title Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
title_full Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
title_fullStr Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
title_full_unstemmed Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
title_short Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
title_sort flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors
topic fluorescence guided surgery
fluorescence lifetime imaging
fluorescence spectroscopy
optical redox ratio
flavin mononucleotide
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1105648/full
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