Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping

Cleary, Jon O.; Modat, Marc; Norris, Francesca C.; Price, Anthony N.; Jayakody, Sujatha A.; Martinez-Barbera, Juan Pedro; Greene, Nicholas D. E.; Hawkes, David J.; Ordidge, Roger J.; Scambler, Peter J.; Ourselin, Sébastien; Lythgoe, Mark F.

doi:10.1016/j.neuroimage.2010.07.039

Cited by 56 publications

(52 citation statements)

References 48 publications

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“…Volumes of specific organs of mouse embryos have been calculated previously through image registration using MRI images (Zamyadi et al, 2010;Cleary et al, 2011). MRI is advantageous due to its ability to image soft tissue and also because the gadolinium contrast agents used do not distort or perturb the natural, fixed mouse embryo shape.…”

Section: Micro-ct Is a Viable Option For Mouse Embryo Phenotypingmentioning

confidence: 99%

“…Micro-CT systems are already readily available as stand-alone machines that can be installed in any laboratory and, if the demand is present, the engineering of new systems that are dedicated to imaging and phenotyping the mouse embryo will no doubt be considered. The MRI scan time required to reach an image resolution that rivals that of a dedicated micro-CT machine is usually overnight; however, groups have overcome this to some degree by imaging multiple samples at a time (Bock et al, 2003;Schneider et al, 2004;Cleary et al, 2011). This could also be done in micro-CT, with the fabrication of custom holders that arrange the embryos suitably for imaging multiple embryos at once.…”

Section: Micro-ct Is a Viable Option For Mouse Embryo Phenotypingmentioning

confidence: 99%

“…Image registration has been successfully performed on MR images of mouse embryos at 15.5 days post-coitum (dpc), demonstrating the feasibility of morphing these images (Zamyadi et al, 2010;Cleary et al, 2011). As a consequence, each homologous anatomical point resides in the same position in space, resulting in a high-quality consensus average image.…”

Section: Introductionmentioning

confidence: 96%

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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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Section: Micro-ct Is a Viable Option For Mouse Embryo Phenotypingmentioning

confidence: 99%

Section: Micro-ct Is a Viable Option For Mouse Embryo Phenotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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

et al. 2012

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“…Registration of 3D mouse embryo images acquired by MRI (Cleary et al, 2011;Sussman et al, 2013;Zamyadi et al, 2010), and OPT have previously been published (Anderson et al, 2013;Sussman et al, 2013). Another imaging modality performing image acquisition for the IMPC is high resolution episcopic microscopy (HREM), which generates images with resolution of the order of 1 µm isotropic (Weninger et al, 2006).…”

Section: Benefits Of the Phenotyping Image Registration Pipelinementioning

confidence: 99%

“…Image registration of mature mouse embryos images acquired by magnetic resonance imaging (MRI) and optical projection tomography (OPT) (Sharpe et al, 2002) has been previously described (Cleary et al, 2011;Sussman et al, 2013;Zamyadi et al, 2010). In these studies, structural volume differences were identified between viable strains of mice using image registration methods.…”

Section: Introductionmentioning

confidence: 99%

Automated pipeline for anatomical phenotyping of mouse embryos using micro-CT

et al. 2014

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The International Mouse Phenotyping Consortium (IMPC) plans to phenotype 20,000 single-gene knockout mice to gain an insight into gene function. Approximately 30% of these knockout mouse lines will be embryonic or perinatal lethal. The IMPC has selected threedimensional (3D) imaging to phenotype these mouse lines at relevant stages of embryonic development in an attempt to discover the cause of lethality using detailed anatomical information. Rate of throughput is paramount as IMPC production centers have been given the ambitious task of completing this phenotyping project by 2021. Sifting through the wealth of data within high-resolution 3D mouse embryo data sets by trained human experts is infeasible at this scale. Here, we present a phenotyping pipeline that identifies statistically significant anatomical differences in the knockout, in comparison with the wild type, through a computer-automated image registration algorithm. This phenotyping pipeline consists of three analyses (intensity, deformation, and atlas based) that can detect missing anatomical structures and differences in volume of whole organs as well as on the voxel level. This phenotyping pipeline was applied to micro-CT images of two perinatal lethal mouse lines: a hypomorphic mutation of the Tcf21 gene (Tcf21-hypo) and a knockout of the Satb2 gene. With the proposed pipeline we were able to identify the majority of morphological phenotypes previously published for both the Tcf21-hypo and Satb2 mutant mouse embryos in addition to novel phenotypes. This phenotyping pipeline is an unbiased, automated method that highlights only those structural abnormalities that survive statistical scrutiny and illustrates them in a straightforward fashion.

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Embryos, Placentas, and Neonates

Bolon¹,

Ward²

2021

Pathology of Genetically Engineered and Other Mutant Mice

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Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping

Cited by 56 publications

References 48 publications

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

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

Automated pipeline for anatomical phenotyping of mouse embryos using micro-CT

Embryos, Placentas, and Neonates

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