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

Author

Listed:
  • Marc Cicero Schubert

    (University Hospital Heidelberg
    Heidelberg University)

  • Stella Judith Soyka

    (University Hospital Heidelberg
    Heidelberg University)

  • Amr Tamimi

    (European Molecular Biology Laboratory (EMBL))

  • Emanuel Maus

    (European Molecular Biology Laboratory (EMBL))

  • Julian Schroers

    (University Hospital Heidelberg
    Division of Radiology)

  • Niklas Wißmann

    (University Hospital Heidelberg
    Heidelberg University)

  • Ekin Reyhan

    (University Hospital Heidelberg
    German Cancer Research Center (DKFZ))

  • Svenja Kristin Tetzlaff

    (University Hospital Heidelberg
    Heidelberg University)

  • Yvonne Yang

    (University Hospital Heidelberg
    German Cancer Research Center (DKFZ))

  • Robert Denninger

    (University Hospital Heidelberg
    Heidelberg University)

  • 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)
    German Cancer Consortium (DKTK)
    National Center for Tumor Diseases (NCT))

  • Anna Golebiewska

    (Department of Cancer Research, Luxembourg Institute of Health)

  • Wolfgang Wick

    (University Hospital Heidelberg
    German Cancer Research Center (DKFZ))

  • Frank Winkler

    (University Hospital Heidelberg
    German Cancer Research Center (DKFZ))

  • Michael O. Breckwoldt

    (University Hospital Heidelberg)

  • Anna Kreshuk

    (European Molecular Biology Laboratory (EMBL))

  • Thomas Kuner

    (Heidelberg University)

  • Craig Horbinski

    (Northwestern University
    Northwestern University)

  • Felix Tobias Kurz

    (Division of Radiology
    University Hospital Heidelberg
    Geneva University Hospitals)

  • Robert Prevedel

    (European Molecular Biology Laboratory (EMBL)
    Developmental Biology Unit, European Molecular Biology Laboratory
    Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory
    Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory)

  • Varun Venkataramani

    (University Hospital Heidelberg
    Heidelberg University
    European Molecular Biology Laboratory (EMBL)
    German Cancer Research Center (DKFZ))

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.

Suggested Citation

  • 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 & Ca, 2024. "Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51432-4
    DOI: 10.1038/s41467-024-51432-4
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