White matter injury predicts disrupted functional connectivity and microstructure in very preterm born neonates

Abstract

ObjectiveTo determine whether the spatial extent and location of early-identified punctate white matter injury (WMI) is associated with regionally-specific disruptions in thalamocortical-connectivity in very-preterm born neonates.Methods37 very-preterm born neonates (median gestational age: 28.1 weeks; interquartile range [IQR]: 27–30) underwent early MRI (median age 32.9 weeks; IQR: 32–35), and WMI was identified in 13 (35%) neonates. Structural T1-weighted, resting-state functional Magnetic Resonance Imaging (rs-fMRI, n = 34) and Diffusion Tensor Imaging (DTI, n = 31) sequences were acquired using 3 T-MRI. A probabilistic map of WMI was developed for the 13 neonates demonstrating brain injury. A neonatal atlas was applied to the WMI maps, rs-fMRI and DTI analyses to extract volumetric, functional and microstructural data from regionally-specific brain areas. Associations of thalamocortical-network strength and alterations in fractional anisotropy (FA, a measure of white-matter microstructure) with WMI volume were assessed in general linear models, adjusting for age at scan and cerebral volumes.ResultsWMI volume in the superior (β = −0.007; p = .02) and posterior corona radiata (β = −0.01; p = .01), posterior thalamic radiations (β = −0.01; p = .005) and superior longitudinal fasciculus (β = −0.02; p = .001) was associated with reduced connectivity strength between thalamus and parietal resting-state networks. WMI volume in the left (β = −0.02; p = .02) and right superior corona radiata (β = −0.03; p = .008), left posterior corona radiata (β = −0.03; p = .01), corpus callosum (β = −0.11; p < .0001) and right superior longitudinal fasciculus (β = −0.02; p = .02) was associated with functional connectivity strength between thalamic and sensorimotor networks. Increased WMI volume was also associated with decreased FA values in the corpus callosum (β = −0.004, p = .015).ConclusionsRegionally-specific alterations in early functional and structural network complexity resulting from WMI may underlie impaired outcomes.

Infant Corpus Callosum Size After Surgery and Critical Care for Long-Gap Esophageal Atresia: Qualitative and Quantitative MRI

“…Given its pivotal role in facilitating cross-talk between cerebral hemispheres, aberrant CC development or injury may translate to altered motor and cognitive functional circuitry later in life [57][58][59][60] . Notably, former very premature neonates with white matter injury in the CC were shown to exhibit altered intrinsic functional connectivity between thalamic and sensorimotor networks 61 . Future studies of the CC should include complementary diffusion tensor imaging (DTI) analyses such as regional white matter measurements of fractional anisotropy and mean diffusivity as indicators of white matter microstructural integrity in the setting of perioperative critical care in infancy.…”

Current Evidence on Cell Death in Preterm Brain Injury in Human and Preclinical Models

“…As mentioned in the Introduction, EoP that covers the different injury patterns related to premature birth can affect either the WM or GM but, depending on the nature and the severity of the lesion, the extent of brain lesions could vary strongly between the individuals. With new emerging MRI techniques, better characterization of EoP now became possible and opens new understanding, such as functional connectivity, diffusion tensor imaging, fractional anisotropy measures and fiber tractography, and automated segmentation techniques for volume determination and growth (Ball et al, 2013;Gozdas et al, 2018;Schneider et al, 2018;Duerden et al, 2019;Jakab et al, 2019). The most prominent findings of EoP in VPT are (1) decreased global brain volume due to white (WM) and gray matter reduction [(GM); cortical GM as well as deep nuclear GM], (2) hydrocephalus ex vacuo (CSF), and (3) connectivity impairment (Dubois et al, 2008;Ball et al, 2013;Chau et al, 2013;Kidokoro et al, 2013;Friedrichs-Maeder et al, 2017;Gozdas et al, 2018;Duerden et al, 2019;Jakab et al, 2019).…”

Early Pain Exposure Influences Functional Brain Connectivity in Very Preterm Neonates

“…Despite the increasing evidence that repeated painful experiences during the first days of life in the neonatal intensive care environment may contribute to structural alterations of the preterm neonatal brain, little research has focused on the relationship between painful stressors and functional activity of the preterm brain at term corrected age (Smith et al, 2011). Recent studies demonstrated weaker functional connectivity in preterm neonates evaluated at term corrected age, with more severe alterations of network complexity in neonates with white matter injuries (Ball et al, 2016; Scheinost et al, 2016; Duerden et al, 2019). Nevertheless, little is known on the extent to which painful stressors may affect brain connectivity in these early phases, with potential consequences on future brain development, and plasticity.…”