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

Cleary, JO; Modat, M; Norris, FC; Price, AN; Jayakody, SA; Martinez-Barbera, JP; Greene, NDE; ... Lythgoe, MF; + view all (2011) Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping. NEUROIMAGE , 54 (2) 769 - 778. 10.1016/j.neuroimage.2010.07.039.

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Abstract

Ambitious international efforts are underway to produce gene-knockout mice for each of the 25,000 mouse genes, providing a new platform to study mammalian development and disease. Robust, large-scale methods for morphological assessment of prenatal mice will be essential to this work. Embryo phenotyping currently relies on histological techniques but these are not well suited to large volume screening. The qualitative nature of these approaches also limits the potential for detailed group analysis. Advances in non-invasive imaging techniques such as magnetic resonance imaging (MRI) may surmount these barriers. We present a high-throughput approach to generate detailed virtual histology of the whole embryo, combined with the novel use of a whole-embryo atlas for automated phenotypic assessment. Using individual 3D embryo MRI histology, we identified new pituitary phenotypes in Hesx1 mutant mice. Subsequently, we used advanced computational techniques to produce a whole-body embryo atlas from 6 CD-1 embryos, creating an average image with greatly enhanced anatomical detail, particularly in CNS structures. This methodology enabled unsupervised assessment of morphological differences between CD-1 embryos and Chd7 knockout mice (n = 5 Chd7(+/+) and n = 8 Chd7(+/-), C57BL/6 background). Using a new atlas generated from these three groups, quantitative organ volumes were automatically measured. We demonstrated a difference in mean brain volumes between Chd7(+/+) and Chd7(+/-) mice (42.0 vs. 39.1 mm(3), p<0.05). Differences in whole-body, olfactory and normalised pituitary gland volumes were also found between CD-1 and Chd7(+/+) mice (C57BL/6 background). Our work demonstrates the feasibility of combining high-throughput embryo MRI with automated analysis techniques to distinguish novel mouse phenotypes. (C) 2010 Elsevier Inc. All rights reserved.

Type: Article
Title: Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping
DOI: 10.1016/j.neuroimage.2010.07.039
Keywords: Embryo atlas, Magnetic resonance microscopy, Mouse embryo phenotyping, Image registration, TRANSGENIC MOUSE EMBRYOS, VOXEL-BASED MORPHOMETRY, GRADIENT-ECHO SEQUENCE, SEPTO-OPTIC DYSPLASIA, HIGH-RESOLUTION, STAINING METHODS, CHARGE SYNDROME, MR-IMAGES, MICRO-CT, BRAIN
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
UCL > School of BEAMS
UCL > School of BEAMS > Faculty of Engineering Science
URI: http://discovery.ucl.ac.uk/id/eprint/166328
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