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

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

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

VIOLA - A multi-purpose and web-based visualization tool for neuronal-network simulation output

Neuronal network models and corresponding computer simulations are invaluable tools to aid the interpretation of the relationship between neuron properties, connectivity and measured activity in cortical tissue. Spatiotemporal patterns of activity propagating across the cortical surface as observed experimentally can for example be described by neuronal network models with layered geometry and distance-dependent connectivity. The interpretation of the resulting stream of multi-modal and multi-dimensional simulation data calls for integrating interactive visualization steps into existing simulation-analysis workflows. Here, we present a set of interactive visualization concepts called views for the visual analysis of activity data in topological network models, and a corresponding reference implementation VIOLA (VIsualization Of Layer Activity). The software is a lightweight, open-source, web-based and platform-independent application combining and adapting modern interactive visualization paradigms, such as coordinated multiple views, for massively parallel neurophysiological data. For a use-case demonstration we consider spiking activity data of a two-population, layered point-neuron network model subject to a spatially confined excitation originating from an external population. With the multiple coordinated views, an explorative and qualitative assessment of the spatiotemporal features of neuronal activity can be performed upfront of a detailed quantitative data analysis of specific aspects of the data. Furthermore, ongoing efforts including the European Human Brain Project aim at providing online user portals for integrated model development, simulation, analysis and provenance tracking, wherein interactive visual analysis tools are one component. Browser-compatible, web-technology based solutions are therefore required. Within this scope, with VIOLA we provide a first prototype.Comment: 38 pages, 10 figures, 3 table

3D micro-computed tomography of trabecular and cortical bone architecture with application to a rat model of immobilisation osteoporosis

Bone mass and microarchitecture are the main determinants of bone strength. Three-dimensional micro-computed tomogrpahy has the potential to examine complete bones of small laboratory animals with very high resolution in a non-invasive way. In the presented work, the proximal part of the tibiae of hindlimb unloaded and control rats were measured with 3D MicroCT, and the secondary spongiosa of the scanned region was evaluated using direct evaluation techniques that do not require model assumptions. For determination of the complete bone status, the cortex of the tibiae was evaluated and characterised by its thickness. It is shown that with the proposed anatomically conforming volume of interest (VOI), up to an eight-fold volume increase can be evaluated compared to cubic or spherical VOIs. A pronounced trabecular bone loss of −50% is seen after 23 days of tail suspension. With the new evaluation techniques, it is shown that most of this bone loss is caused by the thinning of trabeculae, and to a lesser extent by a decrease in their number. What changes most radically is the structure type: the remaining bone is more rod-like than the control group's bone. Cortical bone decreases less than trabecular bone, with only −18% after 23 day

Segmentation of Infant Brain Using Nonnegative Matrix Factorization

This study develops an atlas-based automated framework for segmenting infants\u27 brains from magnetic resonance imaging (MRI). For the accurate segmentation of different structures of an infant\u27s brain at the isointense age (6-12 months), our framework integrates features of diffusion tensor imaging (DTI) (e.g., the fractional anisotropy (FA)). A brain diffusion tensor (DT) image and its region map are considered samples of a Markov-Gibbs random field (MGRF) that jointly models visual appearance, shape, and spatial homogeneity of a goal structure. The visual appearance is modeled with an empirical distribution of the probability of the DTI features, fused by their nonnegative matrix factorization (NMF) and allocation to data clusters. Projecting an initial high-dimensional feature space onto a low-dimensional space of the significant fused features with the NMF allows for better separation of the goal structure and its background. The cluster centers in the latter space are determined at the training stage by the K-means clustering. In order to adapt to large infant brain inhomogeneities and segment the brain images more accurately, appearance descriptors of both the first-order and second-order are taken into account in the fused NMF feature space. Additionally, a second-order MGRF model is used to describe the appearance based on the voxel intensities and their pairwise spatial dependencies. An adaptive shape prior that is spatially variant is constructed from a training set of co-aligned images, forming an atlas database. Moreover, the spatial homogeneity of the shape is described with a spatially uniform 3D MGRF of the second-order for region labels. In vivo experiments on nine infant datasets showed promising results in terms of the accuracy, which was computed using three metrics: the 95-percentile modified Hausdorff distance (MHD), the Dice similarity coefficient (DSC), and the absolute volume difference (AVD). Both the quantitative and visual assessments confirm that integrating the proposed NMF-fused DTI feature and intensity MGRF models of visual appearance, the adaptive shape prior, and the shape homogeneity MGRF model is promising in segmenting the infant brain DTI