Differential cortical microstructural maturation in the preterm human brain with diffusion kurtosis and tensor imaging

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.

Diffusion-MRI-based regional cortical microstructure at birth for predicting neurodevelopmental outcomes of 2-year-olds

“…During emergence of brain circuits, increasing dendritic arborization (Bystron et al, 2008;Sidman and Rakic, 1973), synapses formation (Huttenlocher and Dabholkar, 1997), and myelination of intracortical axons (Yakovlev and Lecours, 1967) disrupt the highly organized radial glia in the immature cortex and result in cortical FA decreases. Such reproducible cortical FA change patterns were documented in many studies of perinatal human brain development (Ball et al, 2013;Huang et al, 2006;Huang et al, 2009;Huang et al, 2013;Kroenke et al, 2007;McKinstry et al, 2002;Neil et al, 1998;Ouyang et al, 2019a;Ouyang et al, 2019b;Yu et al, 2016), suggesting sensitivity of cortical FA measures to maturational processes of cortical microstructure. Diffusion-MRI-based regional cortical microstructure at birth, encoding rich "footage" of regional cellular and molecular processes, may provide novel information regarding typical cortical development and biomarkers for neuropsychiatric disorders.…”

“…2) is probably due to sensitivity of cortical microstructural changes to maturational processes involving synaptic formation, dendritic arborization and axonal growth. Distinctive maturation processes manifested by differentiated cortical FA changes across cortical regions in fetal and infant brains were reproducibly reported development (Ball et al, 2013;Huang et al, 2006;Huang et al, 2009;Huang et al, 2013;Kroenke et al, 2007;McKinstry et al, 2002;Neil et al, 1998;Ouyang et al, 2019a;Ouyang et al, 2019b;Yu et al, 2016). Although cortical thickness, volume or surface area from structural MRI scans (i.e.…”

“…Cortical microstructure at birth, encoding rich "footage" of regional cellular and molecular processes in early human brain development, was evaluated as the baseline measurements for prediction. Our previous studies (Huang et al, 2009;Ouyang et al, 2019b;Yu et al, 2016) found that individual neonate cortical microstructure profile characterized by different levels of dendritic arborization could be reliably quantified with dMRI-based cortical FA that reveals cortical maturation signature.…”

“…Cortical microstructure quantified by FA is more directly associated with specific cortical regions and thus certain cortical functions, compared to association of structural networks to the cortical regions through end point connectivity. Our previous study (Ouyang et al, 2019b) demonstrated that cortical FA predicted neonate age with high accuracy. Regionally distinctive cortical microstructure around birth encodes the information that may predict distinctive functions manifested by future behavior and potentially identify the most sensitive regions as imaging markers to detect early behavioral abnormality.…”

“…Out of 107 recruited neonates, high-resolution (0.656x0.656x1.6 mm 3 ) dMRI data were acquired from 87 neonates, of which 46 underwent a follow-up study at their two years of age for neurobehavioral assessments of cognitive, language and motor abilities. Cortical microstructural architectures at birth were quantified by cortical FA on the cortical skeleton to alleviate partial volume effects (Ouyang et al, 2019b;Yu et al, 2016). Regional cortical FA measures were then used to form feature vectors to predict neurodevelopmental outcomes at 2 years of age.…”