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

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 incor...

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Autores principales: Powell, Nick M., Modat, Marc, Cardoso, M. Jorge, Ma, Da, Holmes, Holly E., Yu, Yichao, O’Callaghan, James, Cleary, Jon O., Sinclair, Ben, Wiseman, Frances K., Tybulewicz, Victor L. J., Fisher, Elizabeth M. C., Lythgoe, Mark F., Ourselin, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033246/
https://www.ncbi.nlm.nih.gov/pubmed/27658297
http://dx.doi.org/10.1371/journal.pone.0162974
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author Powell, Nick M.
Modat, Marc
Cardoso, M. Jorge
Ma, Da
Holmes, Holly E.
Yu, Yichao
O’Callaghan, James
Cleary, Jon O.
Sinclair, Ben
Wiseman, Frances K.
Tybulewicz, Victor L. J.
Fisher, Elizabeth M. C.
Lythgoe, Mark F.
Ourselin, Sébastien
author_facet Powell, Nick M.
Modat, Marc
Cardoso, M. Jorge
Ma, Da
Holmes, Holly E.
Yu, Yichao
O’Callaghan, James
Cleary, Jon O.
Sinclair, Ben
Wiseman, Frances K.
Tybulewicz, Victor L. J.
Fisher, Elizabeth M. C.
Lythgoe, Mark F.
Ourselin, Sébastien
author_sort Powell, Nick M.
collection PubMed
description 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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spelling pubmed-50332462016-10-10 Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome Powell, Nick M. Modat, Marc Cardoso, M. Jorge Ma, Da Holmes, Holly E. Yu, Yichao O’Callaghan, James Cleary, Jon O. Sinclair, Ben Wiseman, Frances K. Tybulewicz, Victor L. J. Fisher, Elizabeth M. C. Lythgoe, Mark F. Ourselin, Sébastien PLoS One Research Article 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. Public Library of Science 2016-09-22 /pmc/articles/PMC5033246/ /pubmed/27658297 http://dx.doi.org/10.1371/journal.pone.0162974 Text en © 2016 Powell et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Powell, Nick M.
Modat, Marc
Cardoso, M. Jorge
Ma, Da
Holmes, Holly E.
Yu, Yichao
O’Callaghan, James
Cleary, Jon O.
Sinclair, Ben
Wiseman, Frances K.
Tybulewicz, Victor L. J.
Fisher, Elizabeth M. C.
Lythgoe, Mark F.
Ourselin, Sébastien
Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
title Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
title_full Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
title_fullStr Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
title_full_unstemmed Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
title_short Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
title_sort fully-automated μmri morphometric phenotyping of the tc1 mouse model of down syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033246/
https://www.ncbi.nlm.nih.gov/pubmed/27658297
http://dx.doi.org/10.1371/journal.pone.0162974
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