Assessment of Structural Connectivity in the Preterm Brain at Term Equivalent Age Using Diffusion MRI and T2 Relaxometry: A Network-Based Analysis

Kerstin Pannek,Paul B Colditz,Stephen Rose,Xanthy Hatzigeorgiou,Gaolang Gong

doi:10.1371/journal.pone.0068593

Abstract

Preterm birth is associated with a high prevalence of adverse neurodevelopmental outcome. Non-invasive techniques which can probe the neural correlates underpinning these deficits are required. This can be achieved by measuring the structural network of connections within the preterm infant's brain using diffusion MRI and tractography. We used diffusion MRI and T2 relaxometry to identify connections with altered white matter properties in preterm infants compared to term infants. Diffusion and T2 data were obtained from 9 term neonates and 18 preterm-born infants (born <32 weeks gestational age) at term equivalent age. Probabilistic tractography incorporating multiple fibre orientations was used in combination with the Johns Hopkins neonatal brain atlas to calculate the structural network of connections. Connections of altered diffusivity or T2, as well as their relationship with gestational age at birth and postmenstrual age at the time of MRI, were identified using the network based statistic framework. A total of 433 connections were assessed. FA was significantly reduced in 17, and T2 significantly increased in 18 connections in preterm infants, following correction for multiple comparisons. Cortical networks associated with affected connections mainly involved left frontal and temporal cortical areas: regions which are associated with working memory, verbal comprehension and higher cognitive function – deficits which are often observed later in children and adults born preterm. Gestational age at birth correlated with T2, but not diffusion in several connections. We found no association between diffusion or T2 and postmenstrual age at the time of MRI in preterm infants. This study demonstrates that alterations in the structural network of connections can be identified in preterm infants at term equivalent age, and that incorporation of non-diffusion measures such as T2 in the connectome framework provides complementary information for the assessment of brain development.

Highlights

Preterm birth constitutes a significant health burden, with long term sequelea including cerebral palsy, mild motor impairments, cognitive deficits and educational difficulties [1,2]
Diffusion Magnetic Resonance Imaging (MRI) is suited to studying brain development because of its ability to probe the random motion of water molecules, with resultant diffusivity measures shown to be influenced by on-going maturation in early life, including typically increased fractional anisotropy (FA) and decreased mean diffusivity (MD) with increasing age [7]
Information regarding gestational age at birth (GA) at birth and birth weight were unavailable for 2 term born infants, and these infants were subsequently excluded from group analysis that used postmenstrual age at the time of MRI as a confounding variable

Summary

Introduction

Preterm birth constitutes a significant health burden, with long term sequelea including cerebral palsy, mild motor impairments, cognitive deficits and educational difficulties [1,2]. Several MRI-derived indices, including fractional anisotropy (FA) and the transverse relaxation time T2, have been shown to be affected by the on-going organisation of white matter (WM), premyelination and myelination seen in preterm and term infants in the first years of life Diffusion MRI is suited to studying brain development because of its ability to probe the random motion of water molecules, with resultant diffusivity measures shown to be influenced by on-going maturation in early life, including typically increased fractional anisotropy (FA) and decreased mean diffusivity (MD) with increasing age [7]. Ball et al [24] recently demonstrated microstructural differences in the thalamocortical connectome between preterm and term infants scanned at term age; no study has, assessed the cortico-cortical network of connections in preterm infants

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