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

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.

Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography

“…While the changes in the later part of gestation (>30 weeks) conform to expected postnatal trajectories depicting an increase in FA and a decrease in MD, these trends are unapparent or appear reversed in several major white matter tracts earlier in gestation (22–29 weeks). These age‐related changes in diffusion properties are consistent with the observations reported by Wilson et al ( 2021 ).This divergence indicates that at earlier developmental stages different biologic processes drive diffusivity and anisotropy in the parenchyma and consequently along the traversing white matter tracts. In addition, our segment‐based analysis of selected commissural, projection, and association tracts demonstrates considerable within‐tract heterogeneity in maturation, with distinct local developmental trajectories.…”

Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment following Early Erythropoietin among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial

“…It is possible that the white matter effects would not have been visible by the time of the 36 weeks PMA MRI. Similarly, FA values continue to increase as infants approach full term, so perhaps an MRI performed at a later age would be better able to detect differences between treatment groups [97].…”

Deciphering the developmental order and microstructural patterns of early white matter pathways in a diffusion MRI based fetal brain atlas

“…25,55 However, they did not observe the initial decrease of FA in WM bundles as reported in this and other recent studies, maybe due to the limited number of subjects involved. 26,27 The theory ignored the change in volume and total amount of axons in WM bundles; and also, the third order polynomial function the authors adopted is not optimal for characterizing growth curves, or for dividing developmental stages. In the view of the multi-modal dMRI-based developmental pattern uncovered in the current study, we hypothesize four phases corresponding to distinct microstructural events, considering both volumetric and microstructural changes of the axonal bundles (Figure 5a).…”