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Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery

Maximal safe resection is a key strategy for improving patient prognosis in the management of brain tumors. Intraoperative fluorescence guidance has emerged as a standard in the surgery of high-grade gliomas. The administration of 5-aminolevulinic acid prior to surgery induces tumor-specific accumul...

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Autores principales: Reichert, David, Erkkilae, Mikael T., Gesperger, Johanna, Wadiura, Lisa I., Lang, Alexandra, Roetzer, Thomas, Woehrer, Adelheid, Andreana, Marco, Unterhuber, Angelika, Wilzbach, Marco, Hauger, Christoph, Drexler, Wolfgang, Kiesel, Barbara, Widhalm, Georg, Leitgeb, Rainer A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476921/
https://www.ncbi.nlm.nih.gov/pubmed/34595120
http://dx.doi.org/10.3389/fonc.2021.741303
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author Reichert, David
Erkkilae, Mikael T.
Gesperger, Johanna
Wadiura, Lisa I.
Lang, Alexandra
Roetzer, Thomas
Woehrer, Adelheid
Andreana, Marco
Unterhuber, Angelika
Wilzbach, Marco
Hauger, Christoph
Drexler, Wolfgang
Kiesel, Barbara
Widhalm, Georg
Leitgeb, Rainer A.
author_facet Reichert, David
Erkkilae, Mikael T.
Gesperger, Johanna
Wadiura, Lisa I.
Lang, Alexandra
Roetzer, Thomas
Woehrer, Adelheid
Andreana, Marco
Unterhuber, Angelika
Wilzbach, Marco
Hauger, Christoph
Drexler, Wolfgang
Kiesel, Barbara
Widhalm, Georg
Leitgeb, Rainer A.
author_sort Reichert, David
collection PubMed
description Maximal safe resection is a key strategy for improving patient prognosis in the management of brain tumors. Intraoperative fluorescence guidance has emerged as a standard in the surgery of high-grade gliomas. The administration of 5-aminolevulinic acid prior to surgery induces tumor-specific accumulation of protoporphyrin IX, which emits red fluorescence under blue-light illumination. The technology, however, is substantially limited for low-grade gliomas and weakly tumor-infiltrated brain, where low protoporphyrin IX concentrations are outweighed by tissue autofluorescence. In this context, fluorescence lifetime imaging has shown promise to distinguish spectrally overlapping fluorophores. We integrated frequency-domain fluorescence lifetime imaging in a surgical microscope and combined it with spatially registered fluorescence spectroscopy, which can be considered a research benchmark for sensitive protoporphyrin IX detection. Fluorescence lifetime maps and spectra were acquired for a representative set of fresh ex-vivo brain tumor specimens (low-grade gliomas n = 15, high-grade gliomas n = 80, meningiomas n = 41, and metastases n = 35). Combining the fluorescence lifetime with fluorescence spectra unveiled how weak protoporphyrin IX accumulations increased the lifetime respective to tissue autofluorescence. Infiltration zones (4.1ns ± 1.8ns, p = 0.017) and core tumor areas (4.8ns ± 1.3ns, p = 0.040) of low-grade gliomas were significantly distinguishable from non-pathologic tissue (1.6ns ± 0.5ns). Similarly, fluorescence lifetimes for infiltrated and reactive tissue as well as necrotic and core tumor areas were increased for high-grade gliomas and metastasis. Meningioma tumor specimens showed strongly increased lifetimes (12.2ns ± 2.5ns, p = 0.005). Our results emphasize the potential of fluorescence lifetime imaging to optimize maximal safe resection in brain tumors in future and highlight its potential toward clinical translation.
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spelling pubmed-84769212021-09-29 Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery Reichert, David Erkkilae, Mikael T. Gesperger, Johanna Wadiura, Lisa I. Lang, Alexandra Roetzer, Thomas Woehrer, Adelheid Andreana, Marco Unterhuber, Angelika Wilzbach, Marco Hauger, Christoph Drexler, Wolfgang Kiesel, Barbara Widhalm, Georg Leitgeb, Rainer A. Front Oncol Oncology Maximal safe resection is a key strategy for improving patient prognosis in the management of brain tumors. Intraoperative fluorescence guidance has emerged as a standard in the surgery of high-grade gliomas. The administration of 5-aminolevulinic acid prior to surgery induces tumor-specific accumulation of protoporphyrin IX, which emits red fluorescence under blue-light illumination. The technology, however, is substantially limited for low-grade gliomas and weakly tumor-infiltrated brain, where low protoporphyrin IX concentrations are outweighed by tissue autofluorescence. In this context, fluorescence lifetime imaging has shown promise to distinguish spectrally overlapping fluorophores. We integrated frequency-domain fluorescence lifetime imaging in a surgical microscope and combined it with spatially registered fluorescence spectroscopy, which can be considered a research benchmark for sensitive protoporphyrin IX detection. Fluorescence lifetime maps and spectra were acquired for a representative set of fresh ex-vivo brain tumor specimens (low-grade gliomas n = 15, high-grade gliomas n = 80, meningiomas n = 41, and metastases n = 35). Combining the fluorescence lifetime with fluorescence spectra unveiled how weak protoporphyrin IX accumulations increased the lifetime respective to tissue autofluorescence. Infiltration zones (4.1ns ± 1.8ns, p = 0.017) and core tumor areas (4.8ns ± 1.3ns, p = 0.040) of low-grade gliomas were significantly distinguishable from non-pathologic tissue (1.6ns ± 0.5ns). Similarly, fluorescence lifetimes for infiltrated and reactive tissue as well as necrotic and core tumor areas were increased for high-grade gliomas and metastasis. Meningioma tumor specimens showed strongly increased lifetimes (12.2ns ± 2.5ns, p = 0.005). Our results emphasize the potential of fluorescence lifetime imaging to optimize maximal safe resection in brain tumors in future and highlight its potential toward clinical translation. Frontiers Media S.A. 2021-09-14 /pmc/articles/PMC8476921/ /pubmed/34595120 http://dx.doi.org/10.3389/fonc.2021.741303 Text en Copyright © 2021 Reichert, Erkkilae, Gesperger, Wadiura, Lang, Roetzer, Woehrer, Andreana, Unterhuber, Wilzbach, Hauger, Drexler, Kiesel, Widhalm and Leitgeb https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Reichert, David
Erkkilae, Mikael T.
Gesperger, Johanna
Wadiura, Lisa I.
Lang, Alexandra
Roetzer, Thomas
Woehrer, Adelheid
Andreana, Marco
Unterhuber, Angelika
Wilzbach, Marco
Hauger, Christoph
Drexler, Wolfgang
Kiesel, Barbara
Widhalm, Georg
Leitgeb, Rainer A.
Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery
title Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery
title_full Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery
title_fullStr Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery
title_full_unstemmed Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery
title_short Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery
title_sort fluorescence lifetime imaging and spectroscopic co-validation for protoporphyrin ix-guided tumor visualization in neurosurgery
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476921/
https://www.ncbi.nlm.nih.gov/pubmed/34595120
http://dx.doi.org/10.3389/fonc.2021.741303
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