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      Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment

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          Highlights

          • DS fetal and neonatal brains show deviations from typical development.

          • Whole brain and cerebellar volumes are smaller in DS from 21 weeks gestation.

          • Cortical volumes in DS appear to deviate around the third trimester.

          • Structural abnormalities are likely substrates for later neurocognitive impairment.

          Abstract

          Down Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify the development of the fetal and neonatal brain in DS participants, with and without a congenital cardiac defect compared with a control population using dedicated, optimised and motion-corrected in vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks’ gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, we believe that the results of this study will assist counselling for prospective parents.

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          Most cited references57

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          Down's syndrome

          The sequencing of chromosome 21 and the use of models of Down's syndrome in mice have allowed us to relate genes and sets of genes to the neuropathogenesis of this syndrome, and to better understand its phenotype. Research in prenatal screening and diagnosis aims to find methods to identify fetuses with Down's syndrome, and reduce or eliminate the need for amniocentesis. Other areas of active research and clinical interest include the association of Down's syndrome with coeliac disease and Alzheimer's disease, and improved median age of death. Medical management of the syndrome requires an organised approach of assessment, monitoring, prevention, and vigilance. Improvements in quality of life of individuals with Down's syndrome have resulted from improvements in medical care, identification and treatment of psychiatric disorders (such as depression, disruptive behaviour disorders, and autism), and early educational interventions with support in typical educational settings. Approaches and outcomes differ throughout the world.
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            Controlling the false discovery rate: a practical and powerful approach to multiple testing

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              Automatic whole brain MRI segmentation of the developing neonatal brain.

              Magnetic resonance (MR) imaging is increasingly being used to assess brain growth and development in infants. Such studies are often based on quantitative analysis of anatomical segmentations of brain MR images. However, the large changes in brain shape and appearance associated with development, the lower signal to noise ratio and partial volume effects in the neonatal brain present challenges for automatic segmentation of neonatal MR imaging data. In this study, we propose a framework for accurate intensity-based segmentation of the developing neonatal brain, from the early preterm period to term-equivalent age, into 50 brain regions. We present a novel segmentation algorithm that models the intensities across the whole brain by introducing a structural hierarchy and anatomical constraints. The proposed method is compared to standard atlas-based techniques and improves label overlaps with respect to manual reference segmentations. We demonstrate that the proposed technique achieves highly accurate results and is very robust across a wide range of gestational ages, from 24 weeks gestational age to term-equivalent age.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                23 December 2019
                2020
                23 December 2019
                : 25
                : 102139
                Affiliations
                [a ]Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas's Hospital, London, SE1 7EH, United Kingdom
                [b ]Department of Forensic and Neurodevelopmental Science, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AB, United Kingdom
                Article
                S2213-1582(19)30485-1 102139
                10.1016/j.nicl.2019.102139
                6938981
                31887718
                683abf93-1803-43ac-b7e3-2e7fbed74d48
                © 2019 Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 27 June 2019
                : 15 December 2019
                : 21 December 2019
                Categories
                Regular Article

                brain,down syndrome,mri,fetal,neonatal
                brain, down syndrome, mri, fetal, neonatal

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