title: 4D MEMRI atlas of neonatal FVB/N mouse brain development.
abstract: The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-μm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases.
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA; Biomedical Imaging, New York University School of Medicine, New York, NY, USA.
authors.forename: Kamila U
authors.initials: KU
authors.lastname: Szulc
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nieman
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA; Molecular Biophysics Graduate Programs, New York University School of Medicine, New York, NY, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Bartelle
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Miriam
authors.initials: M
authors.lastname: Friedel
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA; Biomedical Imaging, New York University School of Medicine, New York, NY, USA.
authors.forename: Giselle A
authors.initials: GA
authors.lastname: Suero-Abreu
authors.affiliation: Health Sciences, Curtin University, Perth, Western Australia, Australia.
authors.forename: Charles
authors.initials: C
authors.lastname: Watson
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY, USA.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Joyner
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA; Biomedical Imaging, New York University School of Medicine, New York, NY, USA; Molecular Biophysics Graduate Programs, New York University School of Medicine, New York, NY, USA; Department of Radiology, New York University School of Medicine, New York, NY, USA; Department of Pathology, New York University School of Medicine, New York, NY, USA. Electronic address: daniel.turnbull@med.nyu.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Turnbull
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001271:Atlases as Topic; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development*; D003287:Contrast Media; D007089:Image Enhancement / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese; D051379:Mice; D013997:Time Factors
chemical_list: D003287:Contrast Media; D008345:Manganese
keywords: Brain nuclei; Cerebellum; Image registration; Mn-enhanced MRI