Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis

• DOI: 10.7554/elife.11712
• Publication Date: 2016-02-02T00:05:06Z
• Authors: 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
• Keywords: 0301 basic medicine; QH301-705.5; Science; 610; angiogenesis; 03 medical and health sciences; Animals; Ultramicroscopy; Biology (General); Fluorescent Dyes; Microscopy; Neovascularization, Pathologic; Staining and Labeling; Brain Neoplasms; Q; R; Glioma; Magnetic Resonance Imaging; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Tissue Clearing; Medicine; MRI; Neuroscience

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.