Nature Communications (Sep 2024)
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,
- Varun Venkataramani
Affiliations
- Marc Cicero Schubert
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Stella Judith Soyka
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Amr Tamimi
- Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL)
- Emanuel Maus
- Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL)
- Julian Schroers
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Niklas Wißmann
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Ekin Reyhan
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Svenja Kristin Tetzlaff
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Yvonne Yang
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Robert Denninger
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Robin Peretzke
- Division of Medical Image Computing (MIC), German Cancer Research Center (DKFZ)
- Carlo Beretta
- Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University
- Michael Drumm
- Department of Neurological Surgery, Northwestern University
- Alina Heuer
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Verena Buchert
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Alicia Steffens
- Department of Neurological Surgery, Northwestern University
- Jordain Walshon
- Department of Neurological Surgery, Northwestern University
- Kathleen McCortney
- Department of Neurological Surgery, Northwestern University
- Sabine Heiland
- Department of Neuroradiology, University Hospital Heidelberg
- Martin Bendszus
- Department of Neuroradiology, University Hospital Heidelberg
- Peter Neher
- Division of Medical Image Computing (MIC), German Cancer Research Center (DKFZ)
- Anna Golebiewska
- NORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health
- Wolfgang Wick
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Frank Winkler
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- Michael O. Breckwoldt
- Department of Neuroradiology, University Hospital Heidelberg
- Anna Kreshuk
- Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL)
- Thomas Kuner
- Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University
- Craig Horbinski
- Department of Neurological Surgery, Northwestern University
- Felix Tobias Kurz
- German Cancer Research Center (DKFZ), Division of Radiology
- Robert Prevedel
- Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL)
- Varun Venkataramani
- Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg
- DOI
- https://doi.org/10.1038/s41467-024-51432-4
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
