Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis

Marc Cicero Schubert, Stella Judith Soyka, Amr Tamimi, Emanuel Maus, Julian Schroers, Niklas Wißmann, Ekin Reyhan, Svenja Kristin Tetzlaff, Yvonne Yang, Robert Denninger, Robin Peretzke, Carlo Beretta, Michael Drumm, Alina Heuer, Verena Buchert, Alicia Steffens, Jordain Walshon, Kathleen McCortney, Sabine Heiland, Martin Bendszus, Peter Neher, Anna Golebiewska, Wolfgang Wick, Frank Winkler, Michael O. Breckwoldt, Anna Kreshuk, Thomas Kuner, Craig Horbinski, Felix Tobias Kurz, Robert Prevedel () and Varun Venkataramani ()
Additional contact information
Marc Cicero Schubert: University Hospital Heidelberg
Stella Judith Soyka: University Hospital Heidelberg
Amr Tamimi: European Molecular Biology Laboratory (EMBL)
Emanuel Maus: European Molecular Biology Laboratory (EMBL)
Julian Schroers: University Hospital Heidelberg
Niklas Wißmann: University Hospital Heidelberg
Ekin Reyhan: University Hospital Heidelberg
Svenja Kristin Tetzlaff: University Hospital Heidelberg
Yvonne Yang: University Hospital Heidelberg
Robert Denninger: University Hospital Heidelberg
Robin Peretzke: German Cancer Research Center (DKFZ)
Carlo Beretta: Heidelberg University
Michael Drumm: Northwestern University
Alina Heuer: University Hospital Heidelberg
Verena Buchert: University Hospital Heidelberg
Alicia Steffens: Northwestern University
Jordain Walshon: Northwestern University
Kathleen McCortney: Northwestern University
Sabine Heiland: University Hospital Heidelberg
Martin Bendszus: University Hospital Heidelberg
Peter Neher: German Cancer Research Center (DKFZ)
Anna Golebiewska: Department of Cancer Research, Luxembourg Institute of Health
Wolfgang Wick: University Hospital Heidelberg
Frank Winkler: University Hospital Heidelberg
Michael O. Breckwoldt: University Hospital Heidelberg
Anna Kreshuk: European Molecular Biology Laboratory (EMBL)
Thomas Kuner: Heidelberg University
Craig Horbinski: Northwestern University
Felix Tobias Kurz: Division of Radiology
Robert Prevedel: European Molecular Biology Laboratory (EMBL)
Varun Venkataramani: University Hospital Heidelberg

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems.

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51432-4

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DOI: 10.1038/s41467-024-51432-4

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