REGISTRATION AND SEGMENTATION OF BRAIN MR IMAGES FROM ELDERLY INDIVIDUALS

Quantitative analysis of the MRI structural and functional images is a fundamental component in the assessment of brain anatomical abnormalities, in mapping functional activation onto human anatomy, in longitudinal evaluation of disease progression, and in computer-assisted neurosurgery or surgical planning. Image registration and segmentation is central in analyzing structural and functional MR brain images. However, due to increased variability in brain morphology and age-related atrophy, traditional methods for image registration and segmentation are not suitable for analyzing MR brain images from elderly individuals. The overall goal of this dissertation is to develop algorithms to improve the registration and segmentation accuracy in the geriatric population. The specific aims of this work includes 1) to implement a fully deformable registration pipeline to allow a higher degree of spatial deformation and produce more accurate deformation field, 2) to propose and validate an optimum template selection method for atlas-based segmentation, 3) to propose and validate a multi-template strategy for image normalization, which characterizes brain structural variations in the elderly, 4) to develop an automated segmentation and localization method to access white matter integrity (WMH) in the elderly population, and finally 5) to study the default-mode network (DMN) connectivity and white matter hyperintensity in late-life depression (LLD) with the developed registration and segmentation methods. Through a series of experiments, we have shown that the deformable registration pipeline and the template selection strategies lead to improved accuracy in the brain MR image registration and segmentation, and the automated WMH segmentation and localization method provides more specific and more accurate information about volume and spatial distribution of WMH than traditional visual grading methods. Using the developed methods, our clinical study provides evidence for altered DMN connectivity in LLD. The correlation between WMH volume and DMN connectivity emphasizes the role of vascular changes in LLD's etiopathogenesis

Diffeomorphic image registration with applications to deformation modelling between multiple data sets

Over last years, the diffeomorphic image registration algorithms have been successfully introduced into the field of the medical image analysis. At the same time, the particular usability of these techniques, in majority derived from the solid mathematical background, has been only quantitatively explored for the limited applications such as longitudinal studies on treatment quality, or diseases progression. The thesis considers the deformable image registration algorithms, seeking out those that maintain the medical correctness of the estimated dense deformation fields in terms of the preservation of the object and its neighbourhood topology, offer the reasonable computational complexity to satisfy time restrictions coming from the potential applications, and are able to cope with low quality data typically encountered in Adaptive Radiotherapy (ART). The research has led to the main emphasis being laid on the diffeomorphic image registration to achieve one-to-one mapping between images. This involves introduction of the log-domain parameterisation of the deformation field by its approximation via a stationary velocity field. A quantitative and qualitative examination of existing and newly proposed algorithms for pairwise deformable image registration presented in this thesis, shows that the log-Euclidean parameterisation can be successfully utilised in the biomedical applications. Although algorithms utilising the log-domain parameterisation have theoretical justification for maintaining diffeomorphism, in general, the deformation fields produced by them have similar properties as these estimated by classical methods. Having this in mind, the best compromise in terms of the quality of the deformation fields has been found for the consistent image registration framework. The experimental results suggest also that the image registration with the symmetrical warping of the input images outperforms the classical approaches, and simultaneously can be easily introduced to most known algorithms. Furthermore, the log-domain implicit group-wise image registration is proposed. By linking the various sets of images related to the different subjects, the proposed image registration approach establishes a common subject space and between-subject correspondences therein. Although the correspondences between groups of images can be found by performing the classic image registration, the reference image selection (not required in the proposed implementation), may lead to a biased mean image being estimated and the corresponding common subject space not adequate to represent the general properties of the data sets. The approaches to diffeomorphic image registration have been also utilised as the principal elements for estimating the movements of the organs in the pelvic area based on the dense deformation field prediction system driven by the partial information coming from the specific type of the measurements parameterised using the implicit surface representation, and recognising facial expressions where the stationary velocity fields are used as the facial expression descriptors. Both applications have been extensively evaluated based on the real representative data sets of three-dimensional volumes and two-dimensional images, and the obtained results indicate the practical usability of the proposed techniques

A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments

In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed locally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The generative model is first estimated on a control population, then, for each subject, the markers are computed for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolution. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are more located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quiet high. In this context, the model can be used to generate plausible morphological trajectories associated with the disease. Our method gives two interpretable scalar imaging biomarkers assessing the effects of aging and disease on brain morphology at the individual and population level. These markers confirm an acceleration of apparent aging for Alzheimer's subjects and can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales.Comment: NeuroImage, Elsevier, In pres

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

Variational Registration of Multiple Images with the SVD based SqN Distance Measure

Image registration, especially the quantification of image similarity, is an important task in image processing. Various approaches for the comparison of two images are discussed in the literature. However, although most of these approaches perform very well in a two image scenario, an extension to a multiple images scenario deserves attention. In this article, we discuss and compare registration methods for multiple images. Our key assumption is, that information about the singular values of a feature matrix of images can be used for alignment. We introduce, discuss and relate three recent approaches from the literature: the Schatten q-norm based SqN distance measure, a rank based approach, and a feature volume based approach. We also present results for typical applications such as dynamic image sequences or stacks of histological sections. Our results indicate that the SqN approach is in fact a suitable distance measure for image registration. Moreover, our examples also indicate that the results obtained by SqN are superior to those obtained by its competitors.Comment: 12 pages, 5 figures, accepted at the conference "Scale Space and Variational Methods" in Hofgeismar, Germany 201