Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome.

PLoS One 2016;11(9):e0162974. Epub 2016 Sep 22.

Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033246PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162974PLOS
September 2016
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References

(Supplied by CrossRef)
Trends in Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register
J Morris et al.
British Medical Journal 2009
Down syndrome mouse models are looking up
RH Reeves et al.
Trends in molecular medicine 2006
Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome
F Carducci et al.
Functional Neurology 2013

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