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Powell NM, Modat M, Cardoso MJ, et al. Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome. PLoS One. 2016;11(9):e0162974doi: 10.1371/journal.pone.0162974.
Powell, N. M., Modat, M., Cardoso, M. J., Ma, D., Holmes, H. E., Yu, Y., O'Callaghan, J., Cleary, J. O., Sinclair, B., Wiseman, F. K., Tybulewicz, V. L., Fisher, E. M., Lythgoe, M. F., & Ourselin, S. (2016). Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome. PloS one, 11(9), e0162974. https://doi.org/10.1371/journal.pone.0162974
Powell, Nick M, et al. "Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome." PloS one vol. 11,9 (2016): e0162974. doi: https://doi.org/10.1371/journal.pone.0162974
Powell NM, Modat M, Cardoso MJ, Ma D, Holmes HE, Yu Y, O'Callaghan J, Cleary JO, Sinclair B, Wiseman FK, Tybulewicz VL, Fisher EM, Lythgoe MF, Ourselin S. Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome. PLoS One. 2016 Sep 22;11(9):e0162974. doi: 10.1371/journal.pone.0162974. eCollection 2016. PMID: 27658297; PMCID: PMC5033246.
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PLoS One. 2016 Sep 22;11(9):e0162974. doi: 10.1371/journal.pone.0162974. eCollection 2016.

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

PloS one

Nick M Powell, Marc Modat, M Jorge Cardoso, Da Ma, Holly E Holmes, Yichao Yu, James O'Callaghan, Jon O Cleary, Ben Sinclair, Frances K Wiseman, Victor L J Tybulewicz, Elizabeth M C Fisher, Mark F Lythgoe, Sébastien Ourselin

Affiliations

  1. Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.
  2. Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
  3. Melbourne Brain Centre Imaging Unit, Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria 3052, Australia.
  4. Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, United Kingdom.
  5. The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
  6. Imperial College, London W12 0NN, United Kingdom.

PMID: 27658297 PMCID: PMC5033246 DOI: 10.1371/journal.pone.0162974

Abstract

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

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