title: Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome.
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.
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.|Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: Nick M
authors.identifier: http://orcid.org/0000-0003-4120-0642
authors.initials: NM
authors.lastname: Powell
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Modat
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.
authors.forename: M Jorge
authors.initials: MJ
authors.lastname: Cardoso
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.|Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: Da
authors.initials: D
authors.lastname: Ma
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Holmes
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: O'Callaghan
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.|Melbourne Brain Centre Imaging Unit, Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Cleary
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Sinclair
authors.affiliation: Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, United Kingdom.
authors.forename: Frances K
authors.initials: FK
authors.lastname: Wiseman
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.|Imperial College, London W12 0NN, United Kingdom.
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.affiliation: Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, United Kingdom.
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, United Kingdom.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, 3rd Floor, Wolfson House, 4 Stephenson Way, London NW1 2HE, United Kingdom.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ourselin