In Vivo Magnetic Resonance Imaging and Semiautomated Image Analysis Extend the Brain Phenotype for cdf/cdf Mice

Magnetic resonance imaging and computer image analysis in human clinical studies effectively identify abnormal neuroanatomy in disease populations. As more mouse models of neurological disorders are discovered, such an approach may prove useful for translational studies. Here, we demonstrate the effectiveness of a similar strategy for mouse neuroscience studies by phenotyping mice with the cerebellar deficient folia (cdf) mutation. Using in vivo multiple-mouse magnetic resonance imaging for increased throughput, we imaged groups of cdf mutant, heterozygous, and wild-type mice and made an atlas-based segmentation of the structures in 15 individual brains. We then performed computer automated volume measurements on the structures. We found a reduced cerebellar volume in the cdf mutants, which was expected, but we also found a new phenotype in the inferior colliculus and the olfactory bulbs. Subsequent local histology revealed additional cytoarchitectural abnormalities in the olfactory bulbs. This demonstrates the utility of anatomical magnetic resonance imaging and semiautomated image analysis for detecting abnormal neuroarchitecture in mutant mice.

[1]  J. Mazziotta,et al.  Automated image registration , 1993 .

[2]  D. Louis Collins,et al.  Animal: Validation and Applications of Nonlinear Registration-Based Segmentation , 1997, Int. J. Pattern Recognit. Artif. Intell..

[3]  A. Koretsky,et al.  Manganese ion enhances T1‐weighted MRI during brain activation: An approach to direct imaging of brain function , 1997, Magnetic resonance in medicine.

[4]  Scott T. Grafton,et al.  Automated image registration: II. Intersubject validation of linear and nonlinear models. , 1998, Journal of computer assisted tomography.

[5]  Alan C. Evans,et al.  Enhancement of MR Images Using Registration for Signal Averaging , 1998, Journal of Computer Assisted Tomography.

[6]  P. Hof Comparative cytoarchitectonic atlas of the C57BL/6 and 129/Sv mouse brains , 2000 .

[7]  R. Hawkes,et al.  Abnormal dispersion of a purkinje cell subset in the mouse mutant cerebellar deficient folia (cdf) , 2001, The Journal of comparative neurology.

[8]  Alan C. Evans,et al.  Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. , 2001, Cerebral cortex.

[9]  D. Dubowitz,et al.  Peripheral somatosensory fMRI in mouse at 11.7 T , 2001, NMR in biomedicine.

[10]  Jacqueline H. Finger,et al.  Deletion in Catna2, encoding αN-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation , 2002, Nature Genetics.

[11]  Jacqueline H. Finger,et al.  The cerebellar deficient folia (cdf) gene acts intrinsically in Purkinje cell migrations , 2002, Genesis.

[12]  M. Bucan,et al.  The mouse: genetics meets behaviour , 2002, Nature Reviews Genetics.

[13]  J. Frahm,et al.  High-resolution 3D MRI of mouse brain reveals small cerebral structures in vivo , 2002, Journal of Neuroscience Methods.

[14]  Russell E Jacobs,et al.  Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Douglas W. Jones,et al.  Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[16]  P. Hof,et al.  A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy , 2005, Neuroscience.

[17]  Alan C. Evans,et al.  A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability. , 2005, Cerebral cortex.

[18]  Marco Weiergräber,et al.  Electrocorticographic and deep intracerebral EEG recording in mice using a telemetry system. , 2005, Brain research. Brain research protocols.

[19]  R. Mark Henkelman,et al.  Fast spin‐echo for multiple mouse magnetic resonance phenotyping , 2005, Magnetic resonance in medicine.

[20]  G. Allan Johnson,et al.  Magnetic resonance imaging at microscopic resolution reveals subtle morphological changes in a mouse model of dopaminergic hyperfunction , 2005, NeuroImage.

[21]  Jimmy D Bell,et al.  In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride , 2005, Journal of magnetic resonance imaging : JMRI.

[22]  R. Mark Henkelman,et al.  In vivo multiple‐mouse MRI at 7 Tesla , 2005, Magnetic resonance in medicine.

[23]  Natasa Kovacevic,et al.  Neuroanatomical differences between mouse strains as shown by high-resolution 3D MRI , 2006, NeuroImage.