High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

  • Johnson G
  • Ali-Sharief A
  • Badea A
 et al. 
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The Mouse Biomedical Informatics Research Network (MBIRN) has been established to integrate imaging studies of the mouse brain ranging from three-dimensional (3D) studies of the whole brain to focused regions at a sub-cellular scale. Magnetic resonance (MR) histology provides the entry point for many morphologic comparisons of the whole brain. We describe a standardized protocol that allows acquisition of 3D MR histology (43-μm resolution) images of the fixed, stained mouse brain with acquisition times < 30 min. A higher resolution protocol with isotropic spatial resolution of 21.5 μm can be executed in 2 h. A third acquisition protocol provides an alternative image contrast (at 43-μm isotropic resolution), which is exploited in a statistically driven algorithm that segments 33 of the most critical structures in the brain. The entire process, from specimen perfusion, fixation and staining, image acquisition and reconstruction, post-processing, segmentation, archiving, and analysis, is integrated through a structured workflow. This yields a searchable database for archive and query of the very large (1.2 GB) images acquired with this standardized protocol. These methods have been applied to a collection of both male and female adult murine brains ranging over 4 strains and 6 neurologic knockout models. These collection and acquisition methods are now available to the neuroscience community as a standard web-deliverable service. © 2007 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Autosegmentation
  • Brain
  • MR
  • Magnetic resonance histology
  • Mouse

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  • Alexandra BadeaDuke University

  • G. Allan Johnson

  • Anjum Ali-Sharief

  • Jeffrey Brandenburg

  • Gary Cofer

  • Boma Fubara

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