title: Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis.
abstract: Neoangiogenesis is a pivotal therapeutic target in glioblastoma. Tumor monitoring requires imaging methods to assess treatment effects and disease progression. Until now mapping of the tumor vasculature has been difficult. We have developed a combined magnetic resonance and optical toolkit to study neoangiogenesis in glioma models. We use in vivo magnetic resonance imaging (MRI) and correlative ultramicroscopy (UM) of ex vivo cleared whole brains to track neovascularization. T2* imaging allows the identification of single vessels in glioma development and the quantification of neovessels over time. Pharmacological VEGF inhibition leads to partial vascular normalization with decreased vessel caliber, density, and permeability. To further resolve the tumor microvasculature, we performed correlated UM of fluorescently labeled microvessels in cleared brains. UM resolved typical features of neoangiogenesis and tumor cell invasion with a spatial resolution of ~5 µm. MR-UM can be used as a platform for three-dimensional mapping and high-resolution quantification of tumor angiogenesis.
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Breckwoldt
authors.affiliation: Schaller Research Group, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany.|Molecular Mechanisms of Tumor Invasion, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bode
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Felix T
authors.initials: FT
authors.lastname: Kurz
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.|Molecular Mechanisms of Tumor Invasion, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ochs
authors.affiliation: Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Ott
authors.affiliation: Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Deumelandt
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krüwel
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schwarz
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.|NeuroImaging Centre, Research Department of Neuroscience, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Xavier
authors.initials: X
authors.lastname: Helluy
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Milford
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Klara
authors.initials: K
authors.lastname: Kirschbaum
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Gergely
authors.initials: G
authors.lastname: Solecki
authors.affiliation: German Cancer Consortium and Heidelberg Institute of Radiation Oncology, National Center for Radiation Research in Oncology, Heidelberg, Germany.|Heidelberg University School of Medicine, Heidelberg University, Heidelberg, Germany.|Translational Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Chiblak
authors.affiliation: German Cancer Consortium and Heidelberg Institute of Radiation Oncology, National Center for Radiation Research in Oncology, Heidelberg, Germany.|Heidelberg University School of Medicine, Heidelberg University, Heidelberg, Germany.|Translational Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Abdollahi
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Winkler
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heiland
authors.affiliation: Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.affiliation: Schaller Research Group, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany.|Molecular Mechanisms of Tumor Invasion, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tews
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D005910:Glioma / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008810:Mice, Inbred C57BL; D008853:Microscopy / Q000379:methods*; D009389:Neovascularization, Pathologic; D013194:Staining and Labeling / Q000379:methods
chemical_list: D005456:Fluorescent Dyes
keywords: MRI; Tissue Clearing; Ultramicroscopy; angiogenesis; mouse; neuroscience
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