Quantification of cortical folding using MR image data

The cerebral cortex is a thin layer of tissue lining the brain where neural circuits perform important high level functions including sensory perception, motor control and language processing. In the third trimester the fetal cortex folds rapidly from a smooth sheet into a highly convoluted arrangement of gyri and sulci. Premature birth is a high risk factor for poor neurodevelopmental outcome and has been associated with abnormal cortical development, however the nature of the disruption to developmental processes is not fully understood. Recent developments in magnetic resonance imaging have allowed the acquisition of high quality brain images of preterms and also fetuses in-utero. The aim of this thesis is to develop techniques which quantify folding from these images in order to better understand cortical development in these two populations. A framework is presented that quantifies global and regional folding using curvature-based measures. This methodology was applied to fetuses over a wide gestational age range (21.7 to 38.9 weeks) for a large number of subjects (N = 80) extending our understanding of how the cortex folds through this critical developmental period. The changing relationship between the folding measures and gestational age was modelled with a Gompertz function which allowed an accurate prediction of physiological age. A spectral-based method is outlined for constructing a spatio-temporal surface atlas (a sequence of mean cortical surface meshes for weekly intervals). A key advantage of this method is the ability to do group-wise atlasing without bias to the anatomy of an initial reference subject. Mean surface templates were constructed for both fetuses and preterms allowing a preliminary comparison of mean cortical shape over the postmenstrual age range 28-36 weeks. Displacement patterns were revealed which intensified with increasing prematurity, however more work is needed to evaluate the reliability of these findings.Open Acces

The Developing Human Connectome Project: a minimal processing pipeline for neonatal cortical surface reconstruction

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity

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

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.Imperial Users onl

Deformability and Microcirculatory Flow of Red Blood Cells in Newborn Infants

Deformability of red blood cells is defined as their ability to deform (ie; to assume new shapes) in response to forces applied on the cell. This is essential for effective blood flow, particularly in the microcirculation, where red blood cells of about 8 um diameter flow through 3 to 4 um diameter vessels. Thus deformability of red blood cells is an important determinant of flow through microcirculation, of oxygen transport and release to the tissues and also of whole blood viscosity and red cell life span