Automatic MRI segmentation of the developing neonatal brain

Detailed morphometric analysis of the neonatal brain is required to characterise normal brain development and investigate the neuroanatomical correlates of cognitive impairments. The segmentation of the brain in Magnetic Resonance Imaging (MRI) is a prerequisite to obtain quantitative measurements of regional brain structures. These measurements obtained at term-equivalent or early preterm age may lead to improved understanding of brain growth and may help evaluate long-term neurodevelopmental performance at an early stage. This thesis focuses on the development of an accurate segmentation algorithm for the neonatal brain MR images and its application in large cohorts of subjects. Neonatal brain segmentation is challenging due to the large anatomical variability as a result of the rapid brain development in the neonatal period. The lack of training data in the neonatal period, encoded in brain atlases, further hinders the development of automatic segmentation tools. A novel algorithm for the tissue segmentation of the neonatal brain is proposed. The algorithm is extended for the regional brain segmentation. This is the first segmentation method for the parcellation of the developing neonatal brain into multiple structures. A novel method is further proposed for the group-wise segmentation of the data that utilizes unlabelled data to complement the labelling information of brain atlases. Previous studies in the literature tended to overestimate the extent of the cortical region. A method based on the morphology of the cortex is introduced to correct for this over-segmentation. The segmentation method is applied on an extensive database of neonatal MR images. Regional volumetric, surface and diffusion tensor imaging measurements are derived from the early preterm period to term-equivalent age. These measurements allow characterisation of the regional brain development and the investigation of correlations with clinical factors. Finally, a spatio-temporal structural atlas is constructed for multiple regions of the neonatal brain.Open Acces

Resting State fMRI in the moving fetus: A robust framework for motion, bias field and spin history correction

There is growing interest in exploring fetal functional brain development, particularly with Resting State fMRI. However, during a typical fMRI acquisition, the womb moves due to maternal respiration and the fetus may perform large-scale and unpredictable movements. Conventional fMRI processing pipelines, which assume that brain movements are infrequent or at least small, are not suitable. Previous published studies have tackled this problem by adopting conventional methods and discarding as much as 40% or more of the acquired data. In this work, we developed and tested a processing framework for fetal Resting State fMRI, capable of correcting gross motion. The method comprises bias field and spin history corrections in the scanner frame of reference, Combined with slice to volume registration and scattered data interpolation to place all data into a consistent anatomical space. The aim is to recover an ordered set of samples suitable for further analysis using standard tools such as Group Independent Component Analysis (Group ICA). We have tested the approach using simulations and in vivo data acquired at 1.5 T. After full motion correction, Group ICA performed on a population of 8 fetuses extracted 20 networks, 6 of which were identified as matching those previously observed in preterm babies

Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multi-modal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared to term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.Keywords: feature similarity gradients, neonatal brain, preterm birth, MRI, neonatal corte

Cortical morphology at birth reflects spatiotemporal patterns of gene expression in the fetal human brain.

Funder: Royal Children's Hospital Foundation; funder-id: http://dx.doi.org/10.13039/100014607Funder: FP7 Ideas: European Research Council (); Grant(s): 319456Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal magnetic resonance imaging (MRI) in n = 292 healthy newborn infants (mean age at birth = 39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n = 156 samples from 16 brains, aged 12 to 37 postconceptional weeks [pcw]). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n = 64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis (PCA) of 6 measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated with estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons, and engaged in stem cell differentiation, neuron migration, and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder

Automated processing pipeline for neonatal diffusion MRI in the developing Human Connectome Project

The developing Human Connectome Project is set to create and make available to the scientific community a 4-dimensional map of functional and structural cerebral connectivity from 20 to 44 weeks post-menstrual age, to allow exploration of the genetic and environmental influences on brain development, and the relation between connectivity and neurocognitive function. A large set of multi-modal MRI data from fetuses and newborn infants is currently being acquired, along with genetic, clinical and developmental information. In this overview, we describe the neonatal diffusion MRI (dMRI) image processing pipeline and the structural connectivity aspect of the project. Neonatal dMRI data poses specific challenges, and standard analysis techniques used for adult data are not directly applicable. We have developed a processing pipeline that deals directly with neonatal-specific issues, such as severe motion and motion-related artefacts, small brain sizes, high brain water content and reduced anisotropy. This pipeline allows automated analysis of in-vivo dMRI data, probes tissue microstructure, reconstructs a number of major white matter tracts, and includes an automated quality control framework that identifies processing issues or inconsistencies. We here describe the pipeline and present an exemplar analysis of data from 140 infants imaged at 38-44 weeks post-menstrual age

Regional growth and atlasing of the developing human brain

AbstractDetailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area