Abstract
The laboratory mouse, with its genetic similarity to humans and rich set of tools for manipulating its genome, has emerged as one of the key models for experimental investigation of the genotype/phenotype relationships in mammals. Recent innovations have made MRI an increasingly popular tool for examining the phenotype of genetically altered mice. Advances in field strengths, mouse handling, image analysis and statistics have contributed greatly in this regard. In this chapter, we illustrate the methods necessary to achieve high-throughput phenotyping of genetically altered mice using multiple-mouse MRI combined with advanced image analysis techniques and statistics.
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References
Waterston, R. H., Lindblad-Toh, K., Birney, E. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 2002;420:520–562.
Henkelman, R., Dazai, J., Lifschitz, N. et al. High throughput microimaging of the mouse brain. Proc Int Soc Magn Reson Med 2006.
Nieman, B., Bishop, J., Dazai, J. et al. MR technology for biological studies in mice. NMR Biomed 2007;20:291–303.
Bock, N., Nieman, B., Bishop, J., Mark Henkelman, R. In vivo multiple-mouse MRI at 7 tesla. Magn Reson Med 2005;54:1311–1316.
Spring, S., Lerch, J., Henkelman, R. Sexual dimorphism revealed in the structure of the mouse brain using three-dimensional magnetic resonance imaging. Neuroimage 2007;35:1424–1433.
Dazai, J., Bock, N. A., Nieman, B. J., Davidson, L. M., Henkelman, R. M., Chen, X. J. Multiple mouse biological loading and monitoring system for MRI. Magn Reson Med 2004;52:709–715.
Collins, D. L., Neelin, P., Peters, T. M., Evans, A. C. Automatic 3d intersubject registration of MR volumetric data in standardized talairach space. J Comput Assist Tomogr 1994;18:192–205.
Collins, D., Holmes, C., Peters, T. M., Evans, A. Automatic 3-D model-based neuroanatomical segmentation. Hum Brain Mapp 1995;3:190–208.
Kale, S. C., Lerch, J., Henkelman, R. M., Chen, X. J. Optimization of the SNR-resolution tradeoff for registration of magnetic resonance images. Hum Brain Mapp 2008;29:1147–1158.
Sled, J. G., Zijdenbos, A. P., Evans, A. C. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 1998;17:87–97.
Chung, M. K., Worsley, K. J., Paus, T. et al. A unified statistical approach to deformation-based morphometry. Neuroimage 2001;14:595–606.
Dorr, A., Lerch, J., Spring, S., Kabani, N., Henkelman, R. High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6j mice. Neuroimage 2008;42:60–69.
Genovese, C. R., Lazar, N. A., Nichols, T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 2002;15:870–878.
Nichols, T., Hayasaka, S. Controlling the familywise error rate in functional neuroimaging: A comparative review. Stat Methods Med Res 2003;12:419–446.
Nichols, T. E., Holmes, A. P. Nonparametric permutation tests for functional neuroimaging: A primer with examples. Hum Brain Mapp 2002;15:1–25.
Worsley, K. J., Taylor, J. E., Tomaiuolo, F., Lerch, J. Unified univariate and multivariate random field theory. Neuroimage 2004;23(Suppl 1):S189–S195.
Acknowledgments
Many of the present and previous members of the Mouse Imaging Centre (MICe) in Toronto have contributed to the development of these techniques. Many developmental biologists and mouse geneticists from around the world have provided mutant mice for imaging and improved the analysis methods. Funding from the Canadian Foundation for Innovation, the Ontario Research and Development Challenge Fund, the US National Institutes of Health and the Canadian Institutes of Health Research is gratefully acknowledged.
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Lerch, J.P., Sled, J.G., Henkelman, R.M. (2011). MRI Phenotyping of Genetically Altered Mice. In: Modo, M., Bulte, J. (eds) Magnetic Resonance Neuroimaging. Methods in Molecular Biology, vol 711. Humana Press. https://doi.org/10.1007/978-1-61737-992-5_17
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DOI: https://doi.org/10.1007/978-1-61737-992-5_17
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