Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis
Michael O Breckwoldt,
Julia Bode,
Felix T Kurz,
Angelika Hoffmann,
Katharina Ochs,
Martina Ott,
Katrin Deumelandt,
Thomas Krüwel,
Daniel Schwarz,
Manuel Fischer,
Xavier Helluy,
David Milford,
Klara Kirschbaum,
Gergely Solecki,
Sara Chiblak,
Amir Abdollahi,
Frank Winkler,
Wolfgang Wick,
Michael Platten,
Sabine Heiland,
Martin Bendszus,
Björn Tews
Affiliations
Michael O Breckwoldt
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany
Julia Bode
Schaller Research Group, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany; Molecular Mechanisms of Tumor Invasion, German Cancer Research Center, Heidelberg, Germany
Felix T Kurz
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Angelika Hoffmann
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Katharina Ochs
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
Martina Ott
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
Katrin Deumelandt
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
Thomas Krüwel
Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, Germany
Daniel Schwarz
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Manuel Fischer
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Xavier Helluy
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany; NeuroImaging Centre, Research Department of Neuroscience, Ruhr-University Bochum, Bochum, Germany
David Milford
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Klara Kirschbaum
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Gergely Solecki
Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
Sara Chiblak
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
Amir Abdollahi
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
Frank Winkler
Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
Wolfgang Wick
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
Michael Platten
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
Sabine Heiland
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Martin Bendszus
Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany
Björn Tews
Schaller Research Group, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany; Molecular Mechanisms of Tumor Invasion, German Cancer Research Center, Heidelberg, Germany
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.
