Document Detail

Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping.
MedLine Citation:
PMID:  20656039     Owner:  NLM     Status:  MEDLINE    
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. 39.1mm(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.
Jon O Cleary; Marc Modat; Francesca C Norris; Anthony N Price; Sujatha A Jayakody; Juan Pedro Martinez-Barbera; Nicholas D E Greene; David J Hawkes; Roger J Ordidge; Peter J Scambler; Sebastien Ourselin; Mark F Lythgoe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-23
Journal Detail:
Title:  NeuroImage     Volume:  54     ISSN:  1095-9572     ISO Abbreviation:  Neuroimage     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-04-05     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9215515     Medline TA:  Neuroimage     Country:  United States    
Other Details:
Languages:  eng     Pagination:  769-78     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Atlases as Topic*
DNA-Binding Proteins / deficiency,  genetics
Embryo, Mammalian / anatomy & histology*
High-Throughput Screening Assays / methods*
Histological Techniques
Imaging, Three-Dimensional / methods*
Magnetic Resonance Imaging / methods*
Mice, Inbred C57BL
Mice, Knockout
User-Computer Interface*
Grant Support
G0601546//Medical Research Council; PG/10/32/28333//British Heart Foundation; //Biotechnology and Biological Sciences Research Council; //British Heart Foundation
Reg. No./Substance:
0/Chd7 protein, mouse; 0/DNA-Binding Proteins

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