Developmental trajectory of thalamus topography during the late preterm and perinatal period in normal development, after premature birth and in congenital heart defects

Abstract

The thalamus plays a critical role in neural circuit maturation and brain connectivity. It is well known to show a characteristic topographical organization of local and long-range connectivity, yet developmental changes in this topography remains incompletely understood. Our study aims to first validate the use of diffusion MRI for the topographic delineation of thalamic subdivisions (nuclei), to characterize thalamic topography during development and assess the impact of congenital heart defects (CHD) on thalamus development.We used local fiber orientation distribution functions, derived from diffusion MRI (dMRI) data, to subdivide the thalamus into seven clusters. We first evaluated the within-subject reproducibility of a dMRI based clustering method across 30 adults scan-rescan datasets (n = 30) using K-means clustering, achieving reproducible segmentation of the thalamus into seven parts. This was applied to a large developmental cohort comprising normally developing infants from the term-born dHCP cohort (n = 68, gestational age [GW] at MRI scan ranging from 37.4 to 44.8 weeks, mean ± SD: 41.4 ± 2.1 weeks) and the Zurich cohort (n = 42, GW at MRI ranging from 39.0 to 48.7 weeks, mean ± SD: 42.55 ± 1.96 weeks). The cohort also included preterm-born dHCP cohort (n = 48, GW at MRI scan ranging from 29.3 to 37.4 corrected gestational weeks, mean ± SD: 34.4 ± 2.02 weeks) and one case of a postmortem fetal specimen (n = 1, GW at MRI = 21 weeks). Cluster volumes were analyzed as a function of age using multivariate linear regression. Differences in cluster volumes between control subjects (n = 42, GW at MRI ranging from 39.0 to 48.7 weeks, mean ± SD: 42.55 ± 1.96 weeks) and newborns with congenital heart disease (CHD) (n = 49, GW at MRI ranging from 37.6 to 42.9 weeks, mean ± SD: 40.23 ± 1.30 weeks) were analyzed using variance analysis, controlling for sex and age at MRI scan.The clustering on average had a within-subject overlap of 0.811 (Dice overlap metric). While absolute thalamus volumes increased with age, their relative volumes remained stable in the studied developmental period. CHD infants shown reduced absolute volumes in six of the seven thalamic nuclei, with significant increasing in the relative volume of the cluster overlapping with the mediodorsal nucleus.While the perinatal period comprises rapid developmental events including the maturation of white matter, the topography of thalamic circuitry remains stable. Our study highlights alterations in thalamic topology and potential impacts on brain connectivity in CHD infants. By leveraging local diffusion properties from diffusion MRI, our validated segmentation technique offers a robust, data-centric approach to thalamic delineation.