Abstract
Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural network configuration at 20 PMW and small-world network organization could exist as early as 20 PMW. These findings offer a preliminary record of the fetal brain structural connectome maturation from the middle fetal stage to birth and reveal the critical role of non-WM neural fibers in structural network configuration in the middle fetal stage.
Highlights
From the middle fetal stage until birth, complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern (e.g., Johnson et al, 2009; Miller et al, 2014) in the human fetal brain, yielding dramatic morphological and microstructural changes, and macroscale connectomic transitions
Stronger and More Efficient Structural Network from the Middle Fetal Stage to Birth We found that fetal brain structural configuration becomes stronger and more efficient from 20 to 40 postmenstrual weeks (PMW)
With high resolution dMRI of fetal brains at 20, 35, and 40 PMW, we quantified the structural network transitions and delineated the profile of whole brain neural fibers underlying the structural network architecture based on DTI tractography and graph theory analysis
Summary
From the middle fetal stage until birth, complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern (e.g., Johnson et al, 2009; Miller et al, 2014) in the human fetal brain, yielding dramatic morphological and microstructural changes, and macroscale connectomic transitions. The migration pathways formed by glial fibers usually take place across the cerebral wall, which is a prominent compartment of the human fetal brain and can be typically divided into multiple layers from near the ventricle to the outermost cortical plate (e.g., Kostovicet al., 2002; Huang et al, 2013; Yu et al, 2016) In parallel to those maturational processes, human fetal brain white matter (WM) axons appear (Bayer and Altman, 2004, 2005), and structural connections based on axons emerge during this period. Quantifying structural connectome development can, shed light on brain reconfiguration in this critical yet rarely studied developmental period, and reveal alterations of the connectome under neuropathological conditions Such wiring dynamics have not been quantitatively delineated from the middle fetal stage to birth
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