No abstract

During the third trimester, the human brain undergoes rapid cellular and molecular processes that reshape the structural architecture of the cerebral cortex. Knowledge of cortical differentiation obtained predominantly from histological studies is limited in localized and small cortical regions. How cortical microstructure is differentiated across cortical regions in this critical period is unknown. In this study, the cortical microstructural architecture across the entire cortex was delineated with non-Gaussian diffusion kurtosis imaging as well as conventional diffusion tensor imaging of 89 preterm neonates aged 31–42 postmenstrual weeks. The temporal changes of cortical mean kurtosis (MK) or fractional anisotropy (FA) were heterogeneous across the cortical regions. Cortical MK decreases were observed throughout the studied age period, while cortical FA decrease reached its plateau around 37 weeks. More rapid decreases in MK were found in the primary visual region, while faster FA declines were observed in the prefrontal cortex. We found that distinctive cortical microstructural changes were coupled with microstructural maturation of associated white matter tracts. Both cortical MK and FA measurements predicted the postmenstrual age of preterm infants accurately. This study revealed a differential 4D spatiotemporal cytoarchitectural signature inferred by non-Gaussian diffusion barriers inside the cortical plate during the third trimester. The cytoarchitectural processes, including dendritic arborization and neuronal density decreases, were inferred by regional cortical FA and MK measurements. The presented findings suggest that cortical MK and FA measurements could be used as effective imaging markers for cortical microstructural changes in typical and potentially atypical brain development.

During the 3rd trimester, dramatic structural changes take place in the human brain, underlying the neural circuit formation. The survival rate of premature infants has increased significantly in recent years. The large morphological differences of the preterm brain at 33 or 36 postmenstrual weeks (PMW) from the brain at 40PMW (full term) make it necessary to establish age-specific atlases for preterm brains. In this study, with high quality (1.5 × 1.5 × 1.6 mm imaging resolution) diffusion tensor imaging (DTI) data obtained from 84 healthy preterm and term-born neonates, we established age-specific preterm and term-born brain templates and atlases at 33, 36 and 39PMW. Age-specific DTI templates include a single-subject template, a population-averaged template with linear transformation and a population-averaged template with nonlinear transformation. Each of the age-specific DTI atlases includes comprehensive labeling of 126 major gray matter (GM) and white matter (WM) structures, specifically 52 cerebral cortical structures, 40 cerebral WM structures, 22 brainstem and cerebellar structures and 12 subcortical GM structures. From 33 to 39 PMW, dramatic morphological changes of delineated individual neural structures such as ganglionic eminence and uncinate fasciculus were revealed. The evaluation based on measurements of Dice ratio and L1 error suggested reliable and reproducible automated labels from the age-matched atlases compared to labels from manual delineation. Applying these atlases to automatically and effectively delineate microstructural changes of major WM tracts during the 3rd trimester was demonstrated. The established age-specific DTI templates and atlases of 33, 36 and 39 PMW brains may be used for not only understanding normal functional and structural maturational processes but also detecting biomarkers of neural disorders in the preterm brains.

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.