25 research outputs found

    Examining the development of brain structure in utero with fetal MRI, acquired as part of the Developing Human Connectome Project

    Get PDF
    The human brain is an incredibly complex organ, and the study of it traverses many scales across space and time. The development of the brain is a protracted process that begins embryonically but continues into adulthood. Although neural circuits have the capacity to adapt and are modulated throughout life, the major structural foundations are laid in utero during the fetal period, through a series of rapid but precisely timed, dynamic processes. These include neuronal proliferation, migration, differentiation, axonal pathfinding, and myelination, to name a few. The fetal origins of disease hypothesis proposed that a variety of non-communicable diseases emerging in childhood and adulthood could be traced back to a series of risk factors effecting neurodevelopment in utero (Barker 1995). Since this publication, many studies have shown that the structural scaffolding of the brain is vulnerable to external environmental influences and the perinatal developmental window is a crucial determinant of neurological health later in life. However, there remain many fundamental gaps in our understanding of it. The study of human brain development is riddled with biophysical, ethical, and technical challenges. The Developing Human Connectome Project (dHCP) was designed to tackle these specific challenges and produce high quality open-access perinatal MRI data, to enable researchers to investigate normal and abnormal neurodevelopment (Edwards et al., 2022). This thesis will focus on investigating the diffusion-weighted and anatomical (T2) imaging data acquired in the fetal period, between the second to third trimester (22 – 37 gestational weeks). The limitations of fetal MR data are ill-defined due to a lack of literature and therefore this thesis aims to explore the data through a series of critical and strategic analysis approaches that are mindful of the biophysical challenges associated with fetal imaging. A variety of analysis approaches are optimised to quantify structural brain development in utero, exploring avenues to relate the changes in MR signal to possible neurobiological correlates. In doing so, the work in this thesis aims to improve mechanistic understanding about how the human brain develops in utero, providing the clinical and medical imaging community with a normative reference point. To this aim, this thesis investigates fetal neurodevelopment with advanced in utero MRI methods, with a particular emphasis on diffusion MRI. Initially, the first chapter outlines a descriptive, average trajectory of diffusion metrics in different white matter fiber bundles across the second to third trimester. This work identified unique polynomial trajectories in diffusion metrics that characterise white matter development (Wilson et al., 2021). Guided by previous literature on the sensitivity of DWI to cellular processes, I formulated a hypothesis about the biophysical correlates of diffusion signal components that might underpin this trend in transitioning microstructure. This hypothesis accounted for the high sensitivity of the diffusion signal to a multitude of simultaneously occurring processes, such as the dissipating radial glial scaffold, commencement of pre-myelination and arborization of dendritic trees. In the next chapter, the methods were adapted to address this hypothesis by introducing another dimension, and charting changes in diffusion properties along developing fiber pathways. With this approach it was possible to identify compartment-specific microstructural maturation, refining the spatial and temporal specificity (Wilson et al., 2023). The results reveal that the dynamic fluctuations in the components of the diffusion signal correlate with observations from previous histological work. Overall, this work allowed me to consolidate my interpretation of the changing diffusion signal from the first chapter. It also serves to improve understanding about how diffusion signal properties are affected by processes in transient compartments of the fetal brain. The third chapter of this thesis addresses the hypothesis that cortical gyrification is influenced by both underlying fiber connectivity and cytoarchitecture. Using the same fetal imaging dataset, I analyse the tissue microstructural change underlying the formation of cortical folds. I investigate correlations between macrostructural surface features (curvature, sulcal depth) and tissue microstructural measures (diffusion tensor metrics, and multi-shell multi-tissue decomposition) in the subplate and cortical plate across gestational age, exploring this relationship both at the population level and within subjects. This study provides empirical evidence to support the hypotheses that microstructural properties in the subplate and cortical plate are altered with the development of sulci. The final chapter explores the data without anatomical priors, using a data-driven method to extract components that represent coordinated structural maturation. This analysis aims to examine if brain regions with coherent patterns of growth over the fetal period converge on neonatal functional networks. I extract spatially independent features from the anatomical imaging data and quantify the spatial overlap with pre-defined neonatal resting state networks. I hypothesised that coherent spatial patterns of anatomical development over the fetal period would map onto the functional networks observed in the neonatal period. Overall, this thesis provides new insight about the developmental contrast over the second to third trimester of human development, and the biophysical correlates affecting T2 and diffusion MR signal. The results highlight the utility of fetal MRI to research critical mechanisms of structural brain maturation in utero, including white matter development and cortical gyrification, bridging scales from neurobiological processes to whole brain macrostructure. their gendered constructions relating to women

    Extraction of Structural Metrics from Crossing Fiber Models

    Get PDF
    Diffusion MRI (dMRI) measurements allow us to infer the microstructural properties of white matter and to reconstruct fiber pathways in-vivo. High angular diffusion imaging (HARDI) allows for the creation of more and more complex local models connecting the microstructure to the measured signal. One of the challenges is the derivation of meaningful metrics describing the underlying structure from the local models. The aim hereby is to increase the specificity of the widely used metric fractional anisotropy (FA) by using the additional information contained within the HARDI data. A local model which is connected directly to the underlying microstructure through the model of a single fiber population is spherical deconvolution. It produces a fiber orientation density function (fODF), which can often be interpreted as superposition of multiple peaks, each associated to one relatively coherent fiber population (bundle). Parameterizing these peaks one is able to disentangle and characterize these bundles. In this work, the fODF peaks are approximated by Bingham distributions, capturing first and second order statistics of the fiber orientations, from which metrics for the parametric quantification of fiber bundles are derived. Meaningful relationships between these measures and the underlying microstructural properties are proposed. The focus lies on metrics derived directly from properties of the Bingham distribution, such as peak length, peak direction, peak spread, integral over the peak, as well as a metric derived from the comparison of the largest peaks, which probes the complexity of the underlying microstructure. These metrics are compared to the conventionally used fractional anisotropy (FA) and it is shown how they may help to increase the specificity of the characterization of microstructural properties. Visualization of the micro-structural arrangement is another application of dMRI. This is done by using tractography to propagate the fiber layout, extracted from the local model, in each voxel. In practice most tractography algorithms use little of the additional information gained from HARDI based local models aside from the reconstructed fiber bundle directions. In this work an approach to tractography based on the Bingham parameterization of the fODF is introduced. For each of the fiber populations present in a voxel the diffusion signal and tensor are computed. Then tensor deflection tractography is performed. This allows incorporating the complete bundle information, performing local interpolation as well as using multiple directions per voxel for generating tracts. Another aspect of this work is the investigation of the spherical harmonic representation which is used most commonly for the fODF by means of the parameters derived from the Bingham distribution fit. Here a strong connection between the approximation errors in the spherical representation of the Dirac delta function and the distribution of crossing angles recovered from the fODF was discovered. The final aspect of this work is the application of the metrics derived from the Bingham fit to a number of fetal datasets for quantifying the brain’s development. This is done by introducing the Gini-coefficient as a metric describing the brain’s age

    CHARACTERIZATION OF BRAIN TISSUE MICROSTRUCTURES WITH DIFFUSION MRI

    Get PDF
    Diffusion MRI is a useful medical imaging tool for noninvasive mapping of the neuroanatomy and brain connectivity. In this dissertation, we worked on developing diffusion MRI techniques to probe brain tissue microstructures from various perspectives. Spatial resolution of the diffusion MRI is the key to obtain accurate microstructural information. In Chapter 2 and 3, we focused on developing high-resolution in vivo diffusion MRI techniques, such as 3D fast imaging sequence and a localized imaging approach using selective excitation RF pulses. We demonstrated the power of the superior resolution in delineating complex microstructures in the live mouse brain. With the high resolution diffusion MRI data, we were able to map the intra-hippocampal connectivity in the mouse brain, which showed remarkable similarity with tracer studies (Chapter 4). Using the localized fast imaging technique, we were the first to achieve in utero diffusion MRI of embryonic mouse brain, which revealed the microstructures in the developing brains and the changes after inflammatory injury (Chapter 5). The second half of the dissertation explores the restricted water diffusion at varying diffusion times and microstructure scales, using the oscillating gradient spin-echo (OGSE) diffusion MRI. We showed in the live normal mouse brains that unique tissue contrasts can be obtained at different oscillating frequency. We demonstrated in a neonatal mouse model of hypoxia-ischemia, that in the edema brain tissues, diffusion MRI signal changed much faster with oscillating frequency compared to the normal tissue, indicating significant changes in cell size associated with cytotoxic edema (Chapter 6). In the mild injury mice, OGSE showed exquisite sensitivity in detecting subtle injury in the hippocampus, which may relate to microstructural changes in smaller scales, such as the subcellular organelles (Chapter 7). Finally, we addressed the technical issues of OGSE diffusion MRI, and proposed a new hybrid OGSE sequence with orthogonally placed pulsed and oscillating gradients to suppress the perfusion related pseudo-diffusion (Chapter 8). In conclusion, we developed in vivo high-resolution diffusion techniques, and time-dependent diffusion measurements to characterize brain tissue microstructures in the normal and diseased mouse brains. The knowledge gained from this dissertation study may advance our understanding on microstructural basis of diffusion MRI

    Anisotropy Across Fields and Scales

    Get PDF
    This open access book focuses on processing, modeling, and visualization of anisotropy information, which are often addressed by employing sophisticated mathematical constructs such as tensors and other higher-order descriptors. It also discusses adaptations of such constructs to problems encountered in seemingly dissimilar areas of medical imaging, physical sciences, and engineering. Featuring original research contributions as well as insightful reviews for scientists interested in handling anisotropy information, it covers topics such as pertinent geometric and algebraic properties of tensors and tensor fields, challenges faced in processing and visualizing different types of data, statistical techniques for data processing, and specific applications like mapping white-matter fiber tracts in the brain. The book helps readers grasp the current challenges in the field and provides information on the techniques devised to address them. Further, it facilitates the transfer of knowledge between different disciplines in order to advance the research frontiers in these areas. This multidisciplinary book presents, in part, the outcomes of the seventh in a series of Dagstuhl seminars devoted to visualization and processing of tensor fields and higher-order descriptors, which was held in Dagstuhl, Germany, on October 28–November 2, 2018

    Anisotropy Across Fields and Scales

    Get PDF
    This open access book focuses on processing, modeling, and visualization of anisotropy information, which are often addressed by employing sophisticated mathematical constructs such as tensors and other higher-order descriptors. It also discusses adaptations of such constructs to problems encountered in seemingly dissimilar areas of medical imaging, physical sciences, and engineering. Featuring original research contributions as well as insightful reviews for scientists interested in handling anisotropy information, it covers topics such as pertinent geometric and algebraic properties of tensors and tensor fields, challenges faced in processing and visualizing different types of data, statistical techniques for data processing, and specific applications like mapping white-matter fiber tracts in the brain. The book helps readers grasp the current challenges in the field and provides information on the techniques devised to address them. Further, it facilitates the transfer of knowledge between different disciplines in order to advance the research frontiers in these areas. This multidisciplinary book presents, in part, the outcomes of the seventh in a series of Dagstuhl seminars devoted to visualization and processing of tensor fields and higher-order descriptors, which was held in Dagstuhl, Germany, on October 28–November 2, 2018

    Longitudinal analysis of extreme prematurity: a neuroimage investigation of early brain development

    Get PDF
    Brain development is a complex process, and disruptions from its normal course may affect the later neurological outcome of an individual. Preterm infants are at higher risk of disability, since a substantial part of brain development happens outside the mother’s womb, making it vulnerable to a range of insults. Understanding the early brain development during the preterm period is of critical importance and magnetic resonance imaging (MRI) allows us to investigate this. Methodologically, this is a challenging task, as classical approaches of studying longitudinal development over this period do not cope with the large changes taking place. This thesis focuses on the development of tools to study the changes in cortical folding, shape of different brain structures and microstructural changes over the preterm period from longitudinal data of extremely preterm-born infants. It describes a tissue segmentation pipeline, optimised on a postmortem fetal dataset, and then focuses on finding longitudinal correspondences between the preterm and termequivalent brain regions and structures in extremely preterm-born infants using MRI. Three novel registration techniques are proposed for longitudinal registration of this challenging data. These are based on matching the spectral components associated with either the cortical surfaces, diffusion tensor images, or both. These allow us to quantify longitudinal changes in different brain regions and structures. We investigated changes in cortical folding of different lobes, microstructural changes and tracts in the white matter, cortical thickness and changes in cortical fractional anisotropy and mean diffusivity. We used cortical surface registration to look at shape differences between controls and extremely preterm-born young adults to gain an insight into the long-term impact of prematurity. This research may contribute to the development of early biomarkers for predicting the neurological outcome of preterm infants and illuminate our understanding of brain development during this crucial period

    Functional and structural connectivity of reading networks in the adult brain

    Get PDF
    Language processing draws upon many distributed regions in the brain. Reading in particular is a skill that emerges from the interaction between brain regions involved in phonological and orthographical processing. This project examined the reading network in adults (18-35 years old) with and without developmental dyslexia. Each participant was assessed on a comprehensive battery of standardised neuropsychological tests, which assessed IQ, reading accuracy and comprehension, spelling, phonological processing, working memory, grammatical understanding, motor coordination, and expressive and receptive language skills. In addition, each participant underwent a non-invasive MRI scan, during which structural and functional images were acquired. More specifically, T1-weighted and diffusion-weighted images were acquired to assess structural networks in the brain, whereas a simple reading task and resting-state fMRI were acquired to assess the functional networks involved in reading. Individuals with dyslexia were found to show reduced activation and reduced connectivity in regions typically associated with skilled reading. Moreover, results suggested that they rely on more effortful processing and attentional mechanisms instead to compensate for their reading difficulties. All in all, results indicated that individuals with developmental dyslexia had abnormal functional and structural brain networks related to reading performance, as well as other functions, such as working memory. These findings suggest that for successful reading remediation, it is important to focus on the integration of phonology with orthography, as well as with working memory. Literacy problems such as developmental dyslexia are thus better characterised as a complex disorder with multiple deficits rather than by a single phonological deficit

    Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

    Get PDF
    The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus
    corecore