Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors

Abstract Maximal safe tumor resection remains the key prognostic factor for improved prognosis in brain tumor patients. Despite 5-aminolevulinic acid-based fluorescence guidance the neurosurgeon is, however, not able to visualize most low-grade gliomas (LGG) and infiltration zone of high-grade gliom...

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Autores principales:	Mikael T. Erkkilä, David Reichert, Johanna Gesperger, Barbara Kiesel, Thomas Roetzer, Petra A. Mercea, Wolfgang Drexler, Angelika Unterhuber, Rainer A. Leitgeb, Adelheid Woehrer, Angelika Rueck, Marco Andreana, Georg Widhalm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3db3992c1c224e26a3d16b40e28f6931
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spelling	oai:doaj.org-article:3db3992c1c224e26a3d16b40e28f69312021-12-02T11:41:41ZMacroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors10.1038/s41598-020-77268-82045-2322https://doaj.org/article/3db3992c1c224e26a3d16b40e28f69312020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77268-8https://doaj.org/toc/2045-2322Abstract Maximal safe tumor resection remains the key prognostic factor for improved prognosis in brain tumor patients. Despite 5-aminolevulinic acid-based fluorescence guidance the neurosurgeon is, however, not able to visualize most low-grade gliomas (LGG) and infiltration zone of high-grade gliomas (HGG). To overcome the need for a more sensitive visualization, we investigated the potential of macroscopic, wide-field fluorescence lifetime imaging of nicotinamide adenine dinucleotide (NADH) and protoporphyrin IX (PPIX) in selected human brain tumors. For future intraoperative use, the imaging system offered a square field of view of 11 mm at 250 mm free working distance. We performed imaging of tumor tissue ex vivo, including LGG and HGG as well as brain metastases obtained from 21 patients undergoing fluorescence-guided surgery. Half of all samples showed visible fluorescence during surgery, which was associated with significant increase in PPIX fluorescence lifetime. While the PPIX lifetime was significantly different between specific tumor tissue types, the NADH lifetimes did not differ significantly among them. However, mainly necrotic areas exhibited significantly lower NADH lifetimes compared to compact tumor in HGG. Our pilot study indicates that combined fluorescence lifetime imaging of NADH/PPIX represents a sensitive tool to visualize brain tumor tissue not detectable with conventional 5-ALA fluorescence.Mikael T. ErkkiläDavid ReichertJohanna GespergerBarbara KieselThomas RoetzerPetra A. MerceaWolfgang DrexlerAngelika UnterhuberRainer A. LeitgebAdelheid WoehrerAngelika RueckMarco AndreanaGeorg WidhalmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mikael T. Erkkilä David Reichert Johanna Gesperger Barbara Kiesel Thomas Roetzer Petra A. Mercea Wolfgang Drexler Angelika Unterhuber Rainer A. Leitgeb Adelheid Woehrer Angelika Rueck Marco Andreana Georg Widhalm Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
description	Abstract Maximal safe tumor resection remains the key prognostic factor for improved prognosis in brain tumor patients. Despite 5-aminolevulinic acid-based fluorescence guidance the neurosurgeon is, however, not able to visualize most low-grade gliomas (LGG) and infiltration zone of high-grade gliomas (HGG). To overcome the need for a more sensitive visualization, we investigated the potential of macroscopic, wide-field fluorescence lifetime imaging of nicotinamide adenine dinucleotide (NADH) and protoporphyrin IX (PPIX) in selected human brain tumors. For future intraoperative use, the imaging system offered a square field of view of 11 mm at 250 mm free working distance. We performed imaging of tumor tissue ex vivo, including LGG and HGG as well as brain metastases obtained from 21 patients undergoing fluorescence-guided surgery. Half of all samples showed visible fluorescence during surgery, which was associated with significant increase in PPIX fluorescence lifetime. While the PPIX lifetime was significantly different between specific tumor tissue types, the NADH lifetimes did not differ significantly among them. However, mainly necrotic areas exhibited significantly lower NADH lifetimes compared to compact tumor in HGG. Our pilot study indicates that combined fluorescence lifetime imaging of NADH/PPIX represents a sensitive tool to visualize brain tumor tissue not detectable with conventional 5-ALA fluorescence.
format	article
author	Mikael T. Erkkilä David Reichert Johanna Gesperger Barbara Kiesel Thomas Roetzer Petra A. Mercea Wolfgang Drexler Angelika Unterhuber Rainer A. Leitgeb Adelheid Woehrer Angelika Rueck Marco Andreana Georg Widhalm
author_facet	Mikael T. Erkkilä David Reichert Johanna Gesperger Barbara Kiesel Thomas Roetzer Petra A. Mercea Wolfgang Drexler Angelika Unterhuber Rainer A. Leitgeb Adelheid Woehrer Angelika Rueck Marco Andreana Georg Widhalm
author_sort	Mikael T. Erkkilä
title	Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
title_short	Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
title_full	Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
title_fullStr	Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
title_full_unstemmed	Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
title_sort	macroscopic fluorescence-lifetime imaging of nadh and protoporphyrin ix improves the detection and grading of 5-aminolevulinic acid-stained brain tumors
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/3db3992c1c224e26a3d16b40e28f6931
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Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors

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