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

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.

Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants

“…For example, from a multiple echo spin echo sequence, a quantitative T2-map as well as a T2-weighted image could be extracted. One can assume the myelination status of each functional pathway by transforming the T2-map to atlas space (Pannek et al, 2013), and by overlaying the probabilistic maps for quantification of T2 values (Oishi et al, 2011a). This approach is especially useful when DTI is not available.…”

Structural connectivity relates to perinatal factors and functional impairment at 7 years in children born very preterm

“…However, the same group demonstrated reduced thalamocortical connectivity in preterm compared with FT infants (Ball et al, 2013). Pannek et al also performed a connectome study in a small group of infants using NBS, revealing a specific fronto-temporal cortical network that differed between groups (Pannek et al, 2013). Differences between these infant findings and the current findings in 7 year-olds may be due to compensatory mechanisms during early childhood, or population and methodological differences between studies, as both previous infant studies used anisotropy to weight edges rather than normalized probabilistic streamline count.…”

The predictive validity of neonatal MRI for neurodevelopmental outcome in very preterm children

“…60 Widespread white matter regions have been shown to be vulnerable in preterm infants using region of interest, 60-62 TBSS, 63,64 tractography, 42,65 and structural connectivity 66,67 approaches, in particular, the posterior limb of the internal capsule, centrum semiovale, corpus callosum, corona radiata, and central and frontal white matter. Collectively, this body of research indicates alterations in major white matter tracts of VP infants in the neonatal period, potentially providing some insight into the impairments displayed in later childhood.…”