The Cerebral Structural Abnormalities in Very Preterm Children: A Surface-based Study

Survival rates for infants born prematurely (\u3c 37 weeks gestation) have improved dramatically in the last few decades. In contrast, the neurobehavioral outcomes have not improved to a great extent and remain to be a major concern. To date, a limited number of structural MRI studies have shown many regional cortical abnormalities in Very Preterm (VPT) infants and children that are associated with these neurobehavioral impairments. The majority of these studies have been focused on the neonatal period. The underlying neural mechanisms for these alterations in cerebral development remain unclear. In addition, no studies have been published showing longitudinal neuroimaging data in VPT infants through childhood and examining the trajectory of these alterations in brain development. We have followed a unique cohort of 24 low-risk VPT infants and 24 Term Control (TC) infants from birth through early childhood who underwent magnetic resonance imaging at term equivalent postmenstrual age and neurobehavioral evaluation through seven years of age. This thesis is focused on magnetic resonance imaging data that were obtained at 7 years of age. Cortical surface reconstructions were generated from structural magnetic resonance imaging data using FreeSurfer 4.4.0 with manual editing to ensure the surface quality. In the first aim, the alterations in cortical development were analyzed by volumetric and surface based approaches. Reductions in total cortical grey matter, white matter, cortical surface area and gyrification index were found in VPT-born children compared to TC children. Regional cortical shape abnormalities in VPT-born children were identified as well, with a shallower anterior superior temporal sulcus, smaller relative surface area in the inferior sensori-motor cortex, posterior superior temporal cortex, and a larger relative surface area in medial frontoparietal cortex. In the second aim, the regional surface area expansion between infancy and 7 years of age was examined for 12 TC infants compared to 24 TC 7 year olds, and 14 VPT infants compared to 24 VPT 7 year olds. Cerebral surface area expanded as much as 5-fold in the inferior sensori-motor cortex and the parietal-temporal cortex in both VPT and TC populations, while the surface area in medial temporal cortex and insular region only expanded 2.5 fold. In addition, the surface area of prefrontal cortex showed greater relative expansion in VPT individuals than that in TC individuals. In the third and final aim, sex differences in TC and VPT children were explored using the global volume and folding measurements. The extent of regional cortical shape abnormalities in 24 VPT subjects was also evaluated in relation to the sex of the child. In TC and VPT children, a trend toward larger volumes and cortical surface area was observed for males. However, comparing male VPT to male TC children revealed a greater loss of white matter volume and a greater reduction in surface area. In addition, male VPT children had significantly more regional cortical folding alterations than female VPT children, including a shallower superior temporal sulcus and sylvian fissure in the right hemisphere, smaller relative surface area in inferior sensori-motor cortex and angular gyri in both hemispheres, and larger relative surface area in medial frontoparietal cortex in the right hemisphere, when compared to the corresponding TC children. In summary, this body of scientific work has extended our knowledge of the cerebral alterations in VPT-born children at 7 years of age by defining the nature of regional alterations and suggesting differential patterns in cerebral expansion during childhood. Finally, it appears that greater disturbance in cerebral structure occurs in male VPT-born children. These findings have been undertaken in a small cohort of VPT children and will benefit from replication in a larger cohort and exploration of the neuropsychological correlates