Genes into geometry: imaging for mouse development in 3D

Nieman, Brian J.; Wong, Michael D.; Henkelman, R. Mark

doi:10.1016/j.gde.2011.08.009

Cited by 25 publications

(24 citation statements)

References 63 publications

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“…This has created a need for effective phenotype analysis in the developing mouse brain, from molecular and cellular changes (Sillitoe and Joyner, 2007), to 3D morphological changes (Nieman et al, 2011), and ultimately to changes in behavior (Crawley, 2012; Silverman et al, 2010) associated with defined genetic modifications. Among neuroimaging methods available for phenotype analysis in mice, MRI offers relatively high spatial resolution over the entire brain, with an acquisition time compatible with most morphological processes (Nieman and Turnbull, 2010; Turnbull and Mori, 2007).…”

Section: Introductionmentioning

confidence: 99%

4D MEMRI atlas of neonatal FVB/N mouse brain development

et al. 2015

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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 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, position and signal intensity 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.

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Section: Introductionmentioning

confidence: 99%

4D MEMRI atlas of neonatal FVB/N mouse brain development

et al. 2015

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“…Three-dimensional (3D) volumetric imaging is an attractive option for analyzing mouse embryo morphological phenotypes (Nieman et al, 2011), particularly when used as a primary phenotypic screen, because of its whole embryo coverage. Single gene mutations can cause multi-organ abnormalities that single tissue or two-dimensional (2D) sections can easily miss.…”

Section: Introductionmentioning

confidence: 99%

A novel 3D mouse embryo atlas based on micro-CT

et al. 2012

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SUMMARYThe goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype targeted knockout mouse strains throughout the whole mouse genome (23,000 genes) by 2021. A significant percentage of the generated mice will be embryonic lethal; therefore, phenotyping methods tuned to the mouse embryo are needed. Methods that are robust, quantitative, automated and high-throughput are attractive owing to the numbers of mice involved. Three-dimensional (3D) imaging is a useful method for characterizing morphological phenotypes. However, tools to automatically quantify morphological information of mouse embryos from 3D imaging have not been fully developed. We present a representative mouse embryo average 3D atlas comprising micro-CT images of 35 individual C57BL/6J mouse embryos at 15.5 days post-coitum. The 35 micro-CT images were registered into a consensus average image with our automated image registration software and 48 anatomical structures were segmented manually. We report the mean and variation in volumes for each of the 48 segmented structures. Mouse organ volumes vary by 2.6-4.2% on a linear scale when normalized to whole body volume. A power analysis of the volume data reports that a 9-14% volume difference can be detected between two classes of mice with sample sizes of eight. This resource will be crucial in establishing baseline anatomical phenotypic measurements for the assessment of mutant mouse phenotypes, as any future mutant embryo image can be registered to the atlas and subsequent organ volumes calculated automatically.

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“…For these reasons, morphometric analysis of craniofacial morphogenesis have not to date employed μMRI. Instead, efforts have focused on atlas construction or (Petiet et al 2008) or automated organism-wide detection of abnormalities (Nieman et al 2011). …”

Section: D Imaging For Morphometricsmentioning

confidence: 99%

Morphometrics, 3D Imaging, and Craniofacial Development

Hallgrímsson

Percival

Green

et al. 2015

Current Topics in Developmental Biology

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Recent studies have shown how volumetric imaging and morphometrics can add significantly to our understanding of morphogenesis, the developmental basis for variation and the etiology of structural birth defects. On the other hand, the complex questions and diverse imaging data in developmental biology present morphometrics with more complex challenges than applications in virtually any other field. Meeting these challenges is necessary in order to understand the mechanistic basis for variation in complex morphologies. This chapter reviews the methods and theory that enable the application of modern landmark-based morphometrics to developmental biology and craniofacial development, in particular. We discuss the theoretical foundations of morphometrics as applied to development and review the basic approaches to the quantification of morphology. Focusing on geometric morphometrics, we discuss the principal statistical methods for quantifying and comparing morphological variation and covariation structure within and among groups. Finally, we discuss the future directions for morphometrics in developmental biology that will be required for approaches that enable quantitative integration across the genotype-phenotype map.

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Genes into geometry: imaging for mouse development in 3D

Cited by 25 publications

References 63 publications

4D MEMRI atlas of neonatal FVB/N mouse brain development

4D MEMRI atlas of neonatal FVB/N mouse brain development

A novel 3D mouse embryo atlas based on micro-CT

Morphometrics, 3D Imaging, and Craniofacial Development

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