title: Three-dimensional imaging of the mouse neurovasculature with magnetic resonance microscopy.
abstract: Knowledge of the three-dimensional (3D) architecture of blood vessels in the brain is crucial because the progression of various neuropathologies ranging from Alzheimer's disease to brain tumors involves anomalous blood vessels. The challenges in obtaining such data from patients, in conjunction with development of mouse models of neuropathology, have made the murine brain indispensable for investigating disease induced neurovascular changes. Here we describe a novel method for "whole brain" 3D mapping of murine neurovasculature using magnetic resonance microscopy (μMRI). This approach preserves the vascular and white matter tract architecture, and can be combined with complementary MRI contrast mechanisms such as diffusion tensor imaging (DTI) to examine the interplay between the vasculature and white matter reorganization that often characterizes neuropathologies. Following validation with micro computed tomography (μCT) and optical microscopy, we demonstrate the utility of this method by: (i) combined 3D imaging of angiogenesis and white matter reorganization in both, invasive and non-invasive brain tumor models; (ii) characterizing the morphological heterogeneity of the vascular phenotype in the murine brain; and (iii) conducting "multi-scale" imaging of brain tumor angiogenesis, wherein we directly compared in vivo MRI blood volume measurements with ex vivo vasculature data.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. pathak@mri.jhu.edu
authors.forename: Arvind P
authors.initials: AP
authors.lastname: Pathak
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Melina V
authors.initials: MV
authors.lastname: Jones
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008853:Microscopy / Q000379:methods*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology; D015203:Reproducibility of Results; D055114:X-Ray Microtomography