Morphometric analysis of the C57BL/6J mouse brain

Magnetic resonance microscopy (MRM), when used in conjunction with active staining, can produce high-resolution, high-contrast images of the mouse brain. Using MRM, we imaged in situ the fixed, actively stained brains of C57BL/6J mice in order to characterize the neuroanatomical phenotype and produce a digital atlas. The brains were scanned within the cranium vault to preserve the brain morphology, avoid distortions, and to allow an unbiased shape analysis. The high-resolution imaging used a T1-weighted scan at 21.5 microm isotropic resolution, and an eight-echo multi-echo scan, post-processed to obtain an enhanced T2 image at 43 microm resolution. The two image sets were used to segment the brain into 33 anatomical structures. Volume, area, and shape characteristics were extracted for all segmented brain structures. We also analyzed the variability of volumes, areas, and shape characteristics. The coefficient of variation of volume had an average value of 7.0%. Average anatomical images of the brain for both the T1-weighted and T2 images were generated, together with an average shape atlas, and a probabilistic atlas for 33 major structures. These atlases, with their associated meta-data, will serve as baseline for identifying neuroanatomical phenotypes of additional strains, and mouse models now under study. Our efforts were directed toward creating a baseline for comparison with other mouse strains and models of neurodegenerative diseases.

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

[2]  Daniel Rueckert,et al.  Nonrigid registration using free-form deformations: application to breast MR images , 1999, IEEE Transactions on Medical Imaging.

[3]  G. Allan Johnson,et al.  High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology , 2007, NeuroImage.

[4]  Christos Davatzikos,et al.  Spatiotemporal maturation patterns of murine brain quantified by diffusion tensor MRI and deformation-based morphometry , 2005, Proc. Natl. Acad. Sci. USA.

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

[6]  R. Menzel,et al.  Bee brains, B-splines and computational democracy: generating an average shape atlas , 2001, Proceedings IEEE Workshop on Mathematical Methods in Biomedical Image Analysis (MMBIA 2001).

[7]  Alejandro F Frangi,et al.  Automatic construction of 3-D statistical deformation models of the brain using nonrigid registration , 2003, IEEE Transactions on Medical Imaging.

[8]  Scott T. Grafton,et al.  Automated image registration: I. General methods and intrasubject, intramodality validation. , 1998, Journal of computer assisted tomography.

[9]  G. Allan Johnson,et al.  Neuroanatomical phenotypes in the Reeler mouse , 2007, NeuroImage.

[10]  Alain Pitiot,et al.  A multimodal, multidimensional atlas of the C57BL/6J mouse brain , 2004, Journal of anatomy.

[11]  W. A. Hanson,et al.  Interactive 3D segmentation of MRI and CT volumes using morphological operations. , 1992, Journal of computer assisted tomography.

[12]  Mark Ellisman,et al.  e-Neuroscience: challenges and triumphs in integrating distributed data from molecules to brains , 2004, Nature Neuroscience.

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

[14]  A. Barabasi,et al.  Fractal concepts in surface growth , 1995 .

[15]  M. Solaiyappan,et al.  Diffusion tensor imaging of the developing mouse brain , 2001, Magnetic resonance in medicine.

[16]  Congwu Du,et al.  Anatomical and Functional Phenotyping of Mice Models of Alzheimer's Disease by MR Microscopy , 2007, Annals of the New York Academy of Sciences.

[17]  Andreas A. Ioannides,et al.  Surface visualization of electromagnetic brain activity , 2003, Journal of Neuroscience Methods.

[18]  L. Hedlund,et al.  Morphologic phenotyping with MR microscopy: the visible mouse. , 2002, Radiology.

[19]  Anjum A. Sharief,et al.  Enhanced T2 contrast for MR histology of the mouse brain , 2006, Magnetic resonance in medicine.

[20]  Richard M. Leahy,et al.  BrainSuite: An Automated Cortical Surface Identification Tool , 2000, MICCAI.

[21]  Michael Ian Shamos,et al.  Computational geometry: an introduction , 1985 .

[22]  S. Strich ATLAS OF THE MOUSE BRAIN AND SPINAL CORD , 1972 .

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

[24]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[25]  R. Murray,et al.  Fractal analysis of the boundary between white matter and cerebral cortex in magnetic resonance images: a controlled study of schizophrenic and manic-depressive patients , 1994, Psychological Medicine.

[26]  R Mark Henkelman,et al.  Anatomical phenotyping in the brain and skull of a mutant mouse by magnetic resonance imaging and computed tomography. , 2006, Physiological genomics.

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

[28]  Anders M. Dale,et al.  Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain , 2005, NeuroImage.