Advanced neuroimaging techniques to study the development of the cerebral cortex, subplate and thalamus in preterm infants at 3 Tesla

Abstract

Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioural disturbances. Recent studies of older preterm children with cognitive impairments implicate morphological and functional cortical abnormalities. However elucidation of the preterm cortical abnormalities has been challenging due to specific neonatal features. Using 3 Tesla neonatal MR images and Expectation Maximisation/Markov Random Field segmentation with incorporation of a novel knowledge based technique for removal of mislabelled partial volume voxels, neonatal 3D cortical extraction was possible from 25 to 48 weeks gestation. This enabled the study of the true cortical scaling exponent, cortical thickness, regional volumes and curvature measurements. It showed a relative excess of the cortical surface area for its volume which corresponded with a change in the intrinsic curvature and fissuration up to 36 weeks gestation, after which, the relative growth of the surface area and volume were proportional leading to dominant changes in the extrinsic curvature and cortical folding. Thus the curvature measurements showed an important mechanistic property of convolution. By term equivalent age, the cortex was thicker and there were changes in cortical curvature although there were no differences in the cortical surface area of preterm infants compared to term born controls. There were specific frontal and parietal deficits in the cortical volume. Diffusion MR showed that although the early cortical anisotropy diminished to noise levels by 35 weeks, the mean diffusivity reduced during the entire third trimester due to changes in the radial diffusivity. Regional variations in the mean diffusivity occurred during development with frontal abnormalities persisting at term equivalent age. Subplate and thalamic quantification showed important development features during the third trimester, however in the absence of overt lesions no associations with cortical measures were found. Thus this thesis provides interesting and novel insights into the macroscopic and microscopic development of the cortex.