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Development of human white matter pathways in utero over the second and third trimester

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article numbere2023598118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number20
DOIs
Published18 May 2021

Bibliographical note

Funding Information: We thank the patients who agreed to participate in this work and the staff of St. Thomas? Hospital London. This work was supported by the European Research Council under the European Union Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 319456. We acknowledge infrastructure support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust, King?s College London, and the NIHR-BRC at Guy?s and St Thomas? NHS Foundation Trust. We also acknowledge grant support in part from the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at King?s College London (WT 203148/Z/16/Z) and the Medical Research Council (UK) (MR/K006355/1 and MR/L011530/1). J.O. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 206675/Z/17/Z). J.O. and A.D.E. received support from the Medical Research Council Centre for Neurodevelopmental Disorders, King?s College London (Grant MR/N026063/1). T.A. was supported by an MRC Clinician Scientist Fellowship (MR/P008712/1). Support for this work was also provided by the NIHR-BRC at Kings College London, Guy?s and St Thomas? NHS Foundation Trust in partnership with King?s College London, and King?s College Hospital NHS Foundation Trust. Funding Information: ACKNOWLEDGMENTS. We thank the patients who agreed to participate in this work and the staff of St. Thomas’ Hospital London. This work was supported by the European Research Council under the European Union Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 319456. We acknowledge infrastructure support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust, King’s College London, and the NIHR-BRC at Guy’s and St Thomas’ NHS Foundation Trust. We also acknowledge grant support in part from the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z) and the Medical Research Council (UK) (MR/K006355/1 and MR/L011530/1). J.O. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 206675/Z/17/Z). J.O. and A.D.E. received support from the Medical Research Council Centre for Neurodevelopmental Disorders, King’s College London (Grant MR/N026063/1). T.A. was supported by an MRC Clinician Scientist Fellowship (MR/P008712/1). Support for this work was also provided by the NIHR-BRC at Kings College London, Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London, and King’s College Hospital NHS Foundation Trust. Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth.

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