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Published in: Acta Neurochirurgica 4/2020

Open Access 01-04-2020 | Glioma | Original Article - Tumor - Glioma

Validating a new generation filter system for visualizing 5-ALA-induced PpIX fluorescence in malignant glioma surgery: a proof of principle study

Authors: Eric Suero Molina, Louise Stögbauer, Astrid Jeibmann, Nils Warneke, Walter Stummer

Published in: Acta Neurochirurgica | Issue 4/2020

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Abstract

Background

The BLUE 400 filter system (Carl Zeiss Meditec, Oberkochen, Germany) has provided visualization of 5-ALA-induced fluorescence-guided surgery for more than 20 years. Nevertheless, constraints, e.g., limited background discrimination during hemostasis, obstruct fluency of surgery. A novel filter with improved background visualization was developed, requiring validation regarding fluorescence discrimination. The aim of this article is to determine diagnostic accuracy and perception of protoporphyrin IX (PpIX) discrimination of a novel filter system with higher background illumination (BLUE 400 AR) compared with the gold standard, BLUE 400.

Methods

A surgical microscope equipped with both BLUE 400 and BLUE 400 AR was used. Comparisons were performed on a biological basis and on the visual perception of margins. High-resolution images were compared during and after surgery by senior neurosurgeons. In a predefined biopsy algorithm, four biopsies per patient at tumor margins of PpIX fluorescence and adjacent brain were acquired using BLUE 400 AR only from regions intended for resection and assessed for cell count and density.

Results

Thirty-two patients with malignant gliomas were included in this study. BLUE 400 AR markedly enhanced the brightness of the surgical field, allowing superior discrimination of brain anatomy. A total of 128 biopsies from fluorescence margins were collected. Positive predictive value (PPV) was 98.44% (95% CI, 90.06–99.77%) for malignant glioma. Residual median cell density in non-fluorescent tissue was 13% (IQR 13 to 31). Perception of the location of fluorescent margins on HD images was equivalent for both filter combinations.

Conclusions

BLUE 400 AR demonstrated superior background compared with conventional BLUE 400 in malignant glioma surgery but comparable fluorescence margins and PPV. Therefore, BLUE 400 AR can be considered safe and effective in supporting malignant glioma surgery.
Appendix
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Literature
2.
go back to reference Erkkila MT, Bauer B, Hecker-Denschlag N, Madera Medina MJ, Leitgeb RA, Unterhuber A, Gesperger J, Roetzer T, Hauger C, Drexler W, Widhalm G, Andreana M (2019) Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence-guided neurosurgery: an ex vivo feasibility study. J Biophotonics. https://doi.org/10.1002/jbio.201800378 Erkkila MT, Bauer B, Hecker-Denschlag N, Madera Medina MJ, Leitgeb RA, Unterhuber A, Gesperger J, Roetzer T, Hauger C, Drexler W, Widhalm G, Andreana M (2019) Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence-guided neurosurgery: an ex vivo feasibility study. J Biophotonics. https://​doi.​org/​10.​1002/​jbio.​201800378
5.
go back to reference Roberts DW, Valdes PA, Harris BT, Fontaine KM, Hartov A, Fan X, Ji S, Lollis SS, Pogue BW, Leblond F, Tosteson TD, Wilson BC, Paulsen KD (2011) Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between delta-aminolevulinic acid-induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters. Clinical article J Neurosurg 114:595–603. https://doi.org/10.3171/2010.2.JNS091322 CrossRefPubMed Roberts DW, Valdes PA, Harris BT, Fontaine KM, Hartov A, Fan X, Ji S, Lollis SS, Pogue BW, Leblond F, Tosteson TD, Wilson BC, Paulsen KD (2011) Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between delta-aminolevulinic acid-induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters. Clinical article J Neurosurg 114:595–603. https://​doi.​org/​10.​3171/​2010.​2.​JNS091322 CrossRefPubMed
10.
go back to reference Stummer W, Stepp H, Moller G, Ehrhardt A, Leonhard M, Reulen HJ (1998) Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir 140:995–1000CrossRef Stummer W, Stepp H, Moller G, Ehrhardt A, Leonhard M, Reulen HJ (1998) Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir 140:995–1000CrossRef
11.
go back to reference Stummer W, Stocker S, Novotny A, Heimann A, Sauer O, Kempski O, Plesnila N, Wietzorrek J, Reulen HJ (1998) In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B 45:160–169CrossRef Stummer W, Stocker S, Novotny A, Heimann A, Sauer O, Kempski O, Plesnila N, Wietzorrek J, Reulen HJ (1998) In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B 45:160–169CrossRef
12.
go back to reference Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, Goetz AE, Kiefmann R, Reulen HJ (1998) Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42:518–525 discussion 525-516 CrossRef Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, Goetz AE, Kiefmann R, Reulen HJ (1998) Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42:518–525 discussion 525-516 CrossRef
14.
go back to reference Stummer W, Tonn JC, Goetz C, Ullrich W, Stepp H, Bink A, Pietsch T, Pichlmeier U (2014) 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Neurosurgery 74:310–319; discussion 319-320. https://doi.org/10.1227/NEU.0000000000000267 CrossRefPubMed Stummer W, Tonn JC, Goetz C, Ullrich W, Stepp H, Bink A, Pietsch T, Pichlmeier U (2014) 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Neurosurgery 74:310–319; discussion 319-320. https://​doi.​org/​10.​1227/​NEU.​0000000000000267​ CrossRefPubMed
15.
go back to reference Suero Molina E, Ewelt C, Warneke N, Schwake M, Muther M, Schipmann S, Stummer W (2019) Dual labeling with 5-aminolevulinic acid and fluorescein in high-grade glioma surgery with a prototype filter system built into a neurosurgical microscope: technical note. J Neurosurg:1–7. https://doi.org/10.3171/2018.12.JNS182422 Suero Molina E, Ewelt C, Warneke N, Schwake M, Muther M, Schipmann S, Stummer W (2019) Dual labeling with 5-aminolevulinic acid and fluorescein in high-grade glioma surgery with a prototype filter system built into a neurosurgical microscope: technical note. J Neurosurg:1–7. https://​doi.​org/​10.​3171/​2018.​12.​JNS182422
Metadata
Title
Validating a new generation filter system for visualizing 5-ALA-induced PpIX fluorescence in malignant glioma surgery: a proof of principle study
Authors
Eric Suero Molina
Louise Stögbauer
Astrid Jeibmann
Nils Warneke
Walter Stummer
Publication date
01-04-2020
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 4/2020
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-020-04227-7

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