Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellar cortex of the Tc1 mouse model of down syndrome – a comprehensive morphometric analysis with active staining contrast-enhanced MRI
Da Ma,
Manuel J. Cardoso,
Maria A. Zuluaga,
Marc Modat,
Nick M. Powell,
Frances K. Wiseman,
Jon O. Cleary,
Benjamin Sinclair,
Ian F. Harrison,
Bernard Siow,
Karteek Popuri,
Sieun Lee,
Joanne A. Matsubara,
Marinko V. Sarunic,
Mirza Faisal Beg,
Victor L.J. Tybulewicz,
Elizabeth M.C. Fisher,
Mark F. Lythgoe,
Sebastien Ourselin
Affiliations
Da Ma
Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; Centre for Advanced Biomedical Imaging, University College London, United Kingdom; School of Engineering Science, Simon Fraser University, Burnaby, Canada; Corresponding author at: School of Engineering Science, Simon Fraser University, Canada.
Manuel J. Cardoso
Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom
Maria A. Zuluaga
Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; Data Science Department, EURECOM, France
Marc Modat
Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom
Nick M. Powell
Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; Centre for Advanced Biomedical Imaging, University College London, United Kingdom
Frances K. Wiseman
UK Dementia Research Institute at University College London, UK London; Down Syndrome Consortium (LonDownS), London, United Kingdom
Jon O. Cleary
Centre for Advanced Biomedical Imaging, University College London, United Kingdom; Department of Radiology, Guy´s and St Thomas’ NHS Foundation Trust, United Kingdom; Melbourne Brain Centre Imaging Unit, Department of Medicine and Radiology, University of Melbourne, Melbourne, Australia
Benjamin Sinclair
Centre for Advanced Biomedical Imaging, University College London, United Kingdom
Ian F. Harrison
Centre for Advanced Biomedical Imaging, University College London, United Kingdom
Bernard Siow
Centre for Advanced Biomedical Imaging, University College London, United Kingdom; The Francis Crick Institute, London, United Kingdom
Karteek Popuri
School of Engineering Science, Simon Fraser University, Burnaby, Canada
Sieun Lee
School of Engineering Science, Simon Fraser University, Burnaby, Canada
Joanne A. Matsubara
Department of Ophthalmology & Visual Science, University of British Columbia, Vancouver, Canada
Marinko V. Sarunic
School of Engineering Science, Simon Fraser University, Burnaby, Canada
Mirza Faisal Beg
School of Engineering Science, Simon Fraser University, Burnaby, Canada
Victor L.J. Tybulewicz
The Francis Crick Institute, London, United Kingdom; Department of Immunology and Inflammation, Imperial College, London, United Kingdom
Elizabeth M.C. Fisher
Institute of Neurology, University College London, United Kingdom
Mark F. Lythgoe
Centre for Advanced Biomedical Imaging, University College London, United Kingdom
Sebastien Ourselin
Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom
Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer.