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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 20; pp. 1 - 7
• Main Authors: Wilson, Siân, Pietsch, Maximilian, Cordero-Grande, Lucilio, Price, Anthony N., Hutter, Jana, Xiao, Jiaxin, McCabe, Laura, Rutherford, Mary A., Hughes, Emer J., Counsell, Serena J., Tournier, Jacques-Donald, Arichi, Tomoki, Hajnal, Joseph V., Edwards, A. David, Christiaens, Daan, O’Muircheartaigh, Jonathan
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.05.2021
• Subjects: Abnormalities; Anisotropy; Biological Sciences; Cell migration; Cerebral Cortex - anatomy & histology; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - physiology; Connectome; Corpus callosum; Corpus Callosum - anatomy & histology; Corpus Callosum - diagnostic imaging; Corpus Callosum - physiology; Data acquisition; Diffusion Tensor Imaging; Female; Fetal Development - physiology; Fetus; Fetuses; Fibers; Gestation; Gestational Age; Human motion; Humans; Infant; Infant, Newborn; Magnetic resonance imaging; Maturation; Microstructure; Myelination; Neural networks; Neurodevelopment; Neurogenesis - physiology; Neurons - cytology; Neurons - physiology; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Premature birth; Substantia alba; Tensors; Thalamus; Thalamus - anatomy & histology; Thalamus - diagnostic imaging; Thalamus - physiology; Trends; Uterus - diagnostic imaging; Uterus - physiology; White Matter - anatomy & histology; White Matter - diagnostic imaging; White Matter - physiology; diffusion MRI; white matter; tractography; fetal
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2023598118

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.