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The Journal of Neuroscience, April 26, 2006, 26(17):4455-4459; doi:10.1523/JNEUROSCI.5438-05.2006

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

Nicholas A. Bock,¹ Natasa Kovacevic,¹ Tatiana V. Lipina,² John C. Roder,² Susan L. Ackerman,³ and R. Mark Henkelman¹

¹Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8, ²Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5, and ³Howard Hughes Medical Institute and The Jackson Laboratory, Bar Harbor, Maine 04609

Correspondence should be addressed to Nicholas A. Bock, Cerebral Microcirculation Unit/Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke–National Institutes of Health, 10 Center Drive, Building 10, Room B1D109, Bethesda, MD 20892-1065. Email: bockn{at}mail.nih.gov

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.

Key words: mice; imaging; cytoarchitecture; cerebellum; hippocampus; inferior colliculus

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Received Dec. 20, 2005; revised March 5, 2006; accepted March 12, 2006.

Correspondence should be addressed to Nicholas A. Bock, Cerebral Microcirculation Unit/Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke–National Institutes of Health, 10 Center Drive, Building 10, Room B1D109, Bethesda, MD 20892-1065. Email: bockn{at}mail.nih.gov

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