Frontiers in Neuroscience (Jan 2019)
Correlated MRI and Ultramicroscopy (MR-UM) of Brain Tumors Reveals Vast Heterogeneity of Tumor Infiltration and Neoangiogenesis in Preclinical Models and Human Disease
- Michael O. Breckwoldt,
- Michael O. Breckwoldt,
- Julia Bode,
- Felix Sahm,
- Felix Sahm,
- Thomas Krüwel,
- Gergely Solecki,
- Artur Hahn,
- Peter Wirthschaft,
- Anna S. Berghoff,
- Maximilian Haas,
- Varun Venkataramani,
- Varun Venkataramani,
- Andreas von Deimling,
- Andreas von Deimling,
- Wolfgang Wick,
- Wolfgang Wick,
- Christel Herold-Mende,
- Sabine Heiland,
- Michael Platten,
- Michael Platten,
- Martin Bendszus,
- Felix T. Kurz,
- Frank Winkler,
- Frank Winkler,
- Björn Tews
Affiliations
- Michael O. Breckwoldt
- Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany
- Michael O. Breckwoldt
- Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Julia Bode
- Schaller Research Group at the University of Heidelberg and the German Cancer Research Center (DKFZ), Molecular Mechanisms of Tumor Invasion, Heidelberg, Germany
- Felix Sahm
- Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
- Felix Sahm
- Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Thomas Krüwel
- Schaller Research Group at the University of Heidelberg and the German Cancer Research Center (DKFZ), Molecular Mechanisms of Tumor Invasion, Heidelberg, Germany
- Gergely Solecki
- Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) Within the DKFZ, Heidelberg, Germany
- Artur Hahn
- Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany
- Peter Wirthschaft
- Schaller Research Group at the University of Heidelberg and the German Cancer Research Center (DKFZ), Molecular Mechanisms of Tumor Invasion, Heidelberg, Germany
- Anna S. Berghoff
- Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) Within the DKFZ, Heidelberg, Germany
- Maximilian Haas
- Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany
- Varun Venkataramani
- Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) Within the DKFZ, Heidelberg, Germany
- Varun Venkataramani
- Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany
- Andreas von Deimling
- Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
- Andreas von Deimling
- Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Wolfgang Wick
- Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) Within the DKFZ, Heidelberg, Germany
- Wolfgang Wick
- Neurology Clinic and National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
- Christel Herold-Mende
- Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany
- Sabine Heiland
- Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany
- Michael Platten
- Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Michael Platten
- 0Department of Neurology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- Martin Bendszus
- Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany
- Felix T. Kurz
- Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany
- Frank Winkler
- Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) Within the DKFZ, Heidelberg, Germany
- Frank Winkler
- Neurology Clinic and National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
- Björn Tews
- Schaller Research Group at the University of Heidelberg and the German Cancer Research Center (DKFZ), Molecular Mechanisms of Tumor Invasion, Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fnins.2018.01004
- Journal volume & issue
-
Vol. 12
Abstract
Diffuse tumor infiltration into the adjacent parenchyma is an effective dissemination mechanism of brain tumors. We have previously developed correlated high field magnetic resonance imaging and ultramicroscopy (MR-UM) to study neonangiogenesis in a glioma model. In the present study we used MR-UM to investigate tumor infiltration and neoangiogenesis in a translational approach. We compare infiltration and neoangiogenesis patterns in four brain tumor models and the human disease: whereas the U87MG glioma model resembles brain metastases with an encapsulated growth and extensive neoangiogenesis, S24 experimental gliomas mimic IDH1 wildtype glioblastomas, exhibiting infiltration into the adjacent parenchyma and along white matter tracts to the contralateral hemisphere. MR-UM resolves tumor infiltration and neoangiogenesis longitudinally based on the expression of fluorescent proteins, intravital dyes or endogenous contrasts. Our study demonstrates the huge morphological diversity of brain tumor models regarding their infiltrative and neoangiogenic capacities and further establishes MR-UM as a platform for translational neuroimaging.
Keywords
- magnetic resonance microscopy
- ultramicroscopy
- brain tumor models
- tumor invasion
- brain clearing
- glioblastoma
