title: High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology.
abstract: 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-microm resolution) images of the fixed, stained mouse brain with acquisition times <30 min. A higher resolution protocol with isotropic spatial resolution of 21.5 microm can be executed in 2 h. A third acquisition protocol provides an alternative image contrast (at 43-microm 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.
authors.affiliation: Center for In Vivo Microscopy, Box 3302, Duke University Medical Center, Durham, NC 27710, USA. gaj@orion.duhs.duke.edu
authors.forename: G Allan
authors.initials: GA
authors.lastname: Johnson
authors.forename: Anjum
authors.initials: A
authors.lastname: Ali-Sharief
authors.forename: Alexandra
authors.initials: A
authors.lastname: Badea
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Brandenburg
authors.forename: Gary
authors.initials: G
authors.lastname: Cofer
authors.forename: Boma
authors.initials: B
authors.lastname: Fubara
authors.forename: Sally
authors.initials: S
authors.lastname: Gewalt
authors.forename: Laurence W
authors.initials: LW
authors.lastname: Hedlund
authors.forename: Lucy
authors.initials: L
authors.lastname: Upchurch
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology*; D019992:Databases as Topic; D004292:Dominance, Cerebral / Q000502:physiology; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012680:Sensitivity and Specificity; D012984:Software