Intense changes in cortical microstructure occur during early infancy. Here, we aimed to study cortical maturation over this largely unexplored developmental period using quantitative MRI in 17 infants from 1 to 5 post-natal months. By taking benefit of robust intra- and inter-individual registrations of anatomical images and parametric maps, we measured T1, T2 relaxation times, and DTI longitudinal diffusivity over cortical surfaces and regions of interest. Results showed that each parameter relevantly but differently reflects the progressive maturation. This suggests that multi-parametric approaches might provide interpretable measures of the developing microstructure by accounting for the parameters complementarity.
The study was conducted in 17 healthy term-born infants (age at MRI: 3-21 weeks), under a protocol approved by the Institutional Ethical. Acquisitions were performed on a 3T Trio Siemens system. Echo-planar imaging (EPI) sequences were used to estimate T1, T2 and DTI maps in less than 11min (1.8mm isotropic spatial resolution)3,6. T2-weighted images (1x1x1.1mm3) were acquired with a turbo-spin echo sequence5, and processed semi-automatically to reconstruct inner cortical surfaces and extract cortical sulci7,8. Parametric maps were registered to T2-weighted images using elastic deformations4 providing an accurate overlay of cortical ribbons across modalities. T1, T2 and λ// values were then projected on cortical surfaces (Figure 1).
To align cortical surfaces across infants, we used a 2-step registration strategy. The DISCO approach9 aimed to align selected cortical sulci (easily recognizable in infants and covering the whole brain (see Figure 2) , while the DARTEL algorithm10 aimed to register cortical strips over the group.
Based on this DISCO+DARTEL registration, we computed average T1, T2 and λ// maps over the group, and we analyzed these parameters over cortical regions using an infant parcellation manually delineated from one of the studied subject5 and deformed by the DISCO+DARTEL deformations. We here selected some regions of interest to highlight differences in maturation and assess the parameters significance and complementarity.
Compared with 1-step strategies, the DISCO+DARTEL approach improved the registration of anatomical images, cortical surfaces, sulci and strips over the group (Figure 2).
Across infants, we observed that T1, T2 and λ// decreased with age, and were higher in frontal, lateral occipital and temporal regions than in primary cortices (Figure 1). Nevertheless, these maturational differences were not always obvious at the individual level, depending on the infant and parametric map.
This asynchrony was better revealed on average maps over the group (Figure 3), with lower T1, T2 and λ// in primary than associative regions. Nevertheless, these parameters showed differences in terms of value distributions over the whole brain, and of maturational ordering across the selected cortical regions (especially for Heschl and inferior temporal gyri).
In this study, we reliably evaluated the maturation of cortical microstructure in infants, over a period that has been little studied so far. In comparison with previous studies of the developing brain2,11,12, the use of quantitative MRI parameters stemming from relaxometry and diffusometry enabled us to compare regions and subjects without requiring additional processing (e.g. spatial bias correction, signal normalization). Nevertheless, with our approach, the differential maturation across cortical regions was much more visible over the group than at the individual level.
Generally, we observed a more advanced maturation in primary regions than in adjacent unimodal and higher-order associative regions, in agreement with benchmark post mortem studies of cortical synaptogenesis1 and sub-cortical white matter myelination13. Contrarily to recent descriptions in infants from one year of age14, we did not observe relationships between cortical maturation, surface curvature or folding patterns (except around the central sulcus and calcarine fissure that house primary sensori-motor and visual cortices).
Finally, it seems that T1, T2 and λ// parameters provide distinct information on the maturation and microstructure of the infant cortical regions. A multi-parametric approach may thus take benefit from this complementarity as proposed for white matter bundles3.
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