Evidence map›Paper›PMID 38987630›Full record

ArticleNature biomedical engineering2024

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy.

Mustafa Nasir-Moin, Lisa Irina Wadiura, Vlad Sacalean, Devin Juros, Misha Movahed-Ezazi, Emily K Lock, Andrew Smith, Matthew Lee, Hannah Weiss, Michael Müther and 28 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. 5-Aminolevulinic acid (5-ALA) in paediatric brain tumour surgery-a systematic review and exploration of fluorophore alternatives.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025
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  5. Contemporary surgical strategies for resection of intracranial gliomas.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors.

Mustafa Nasir-Moin *Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0389-1852
Lisa Irina Wadiura *Department of Neurosurgery, Medical University Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-9227-461X
Vlad SacaleanDepartment of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
Devin JurosDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-1151-0738
Misha Movahed-EzaziDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Emily K LockDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.
Andrew SmithDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-3990-2138
Matthew LeeDepartment of Radiology, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-8816-1076
Hannah WeissDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.
Michael MütherDepartment of Neurosurgery, Münster University Hospital, Münster, Germany.ORCID http://orcid.org/0000-0001-9427-5555
Daniel AlberDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-7957-5170
Sujay RatnaInvenio Imaging, Inc, Santa Clara, CA, USA.ORCID http://orcid.org/0000-0002-0939-3715
Camila FangDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-8477-1253
Eric Suero-MolinaDepartment of Neurosurgery, Münster University Hospital, Münster, Germany.ORCID http://orcid.org/0000-0001-5652-2105
Sönke HellwigDepartment of Neurosurgery, Münster University Hospital, Münster, Germany.
Walter StummerDepartment of Neurosurgery, Münster University Hospital, Münster, Germany.
Karl RösslerDepartment of Neurosurgery, Medical University Vienna, Vienna, Austria.
Johannes A HainfellnerDivision of Neuropathology and Neurochemistry (Obersteiner Institute), Department of Neurology, Medical University Vienna, Vienna, Austria.
Georg WidhalmDepartment of Neurosurgery, Medical University Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0001-6014-0273
Barbara KieselDepartment of Neurosurgery, Medical University Vienna, Vienna, Austria.
David ReichertCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
Mario MischkulnigDepartment of Neurosurgery, Medical University Vienna, Vienna, Austria.
Rajan JainDepartment of Radiology, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-4879-0457
Jakob StraehleDepartment of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-3063-8972
Nicolas NeidertDepartment of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-0299-1138
Oliver SchnellDepartment of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
Jürgen BeckDepartment of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-7687-6098
Jay TrautmanInvenio Imaging, Inc, Santa Clara, CA, USA.
Steve PastoreInvenio Imaging, Inc, Santa Clara, CA, USA.
Donato PacioneDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.
Dimitris PlacantonakisDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.
Eric Karl OermannDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-1876-5963
John G GolfinosDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA.
Todd C HollonDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5987-6531
Matija SnuderlDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Christian W FreudigerInvenio Imaging, Inc, Santa Clara, CA, USA.
Dieter Henrik HeilandDepartment of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany. dieter.henrik.heiland@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0002-9258-3033
Daniel A OrringerDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA. Daniel.Orringer@nyulangone.org.ORCID http://orcid.org/0000-0001-6427-8376

Funding

Transitioning Early Career Neurosurgeons to Scientific IndependenceK12NS080223 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ESKANDAR, EMAD N · 2012 to 2022
$9.2M
Clinical Translation of Stimulated Raman HistologyR01CA226527 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ORRINGER, DANIEL · 2018 to 2025
$4.4M
Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) J 4725-BU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) K12NS080223U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01-CA226527
6 · The paper itself

Abstract

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.

Indexed as

Brain NeoplasmsGliomaProtoporphyrinsSpectrum Analysis, RamanAminolevulinic AcidFemaleHumansMaleMicroscopy, FluorescenceAminolevulinic Acidprotoporphyrin IXProtoporphyrins

Identifiers

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.