Segmentation of brain MRI during early childhood

The objective of this thesis is the development of automatic methods to measure the changes in volume and growth of brain structures in prematurely born infants. Automatic tools for accurate tissue quantification from magnetic resonance images can provide means for understanding how the neurodevelopmental effects of the premature birth, such as cognitive, neurological or behavioural impairment, are related to underlying changes in brain anatomy. Understanding these changes forms a basis for development of suitable treatments to improve the outcomes of premature birth. In this thesis we focus on the segmentation of brain structures from magnetic resonance images during early childhood. Most of the current brain segmentation techniques have been focused on the segmentation of adult or neonatal brains. As a result of rapid development, the brain anatomy during early childhood differs from anatomy of both adult and neonatal brains and therefore requires adaptations of available techniques to produce good results. To address the issue of anatomical differences of the brain during early childhood compared to other age-groups, population-specific deformable and probabilistic atlases are introduced. A method for generation of population-specific prior information in form of a probabilistic atlas is proposed and used to enhance existing segmentation algorithms. The evaluation of registration-based and intensity-based approaches shows the techniques to be complementary in the quality of automatic segmentation in different parts of the brain. We propose a novel robust segmentation method combining the advantages of both approaches. The method is based on multiple label propagation using B-spline non-rigid registration followed by EM segmentation. Intensity inhomogeneity is a shading artefact resulting from the acquisition process, which significantly affects modern high resolution MR data acquired at higher magnetic field strengths. A novel template based method focused on correcting the intensity inhomogeneity in data acquired at higher magnetic field strengths is therefore proposed. The proposed segmentation method combined with proposed intensity inhomogeneity correction method offers a robust tool for quantification of volumes and growth of brain structures during early childhood. The tool have been applied to 67 T1-weigted images of subject at one and two years of age

Symmetric diffeomorphic modeling of longtudinal structural MRI

This technology report describes the longitudinal registration approach that we intend to incorporate into SPM12. It essentially describes a group-wise intra-subject modeling framework, which combines diffeomorphic and rigid-body registration, incorporating a correction for the intensity inhomogeneity artifact usually seen in MRI data. Emphasis is placed on achieving internal consistency and accounting for many of the mathematical subtleties that most implementations overlook. The implementation was evaluated using examples from the OASIS Longitudinal MRI Data in Non-demented and Demented Older Adults

Statistical analysis for longitudinal MR imaging of dementia

Serial Magnetic Resonance (MR) Imaging can reveal structural atrophy in the brains of subjects with neurodegenerative diseases such as Alzheimer’s Disease (AD). Methods of computational neuroanatomy allow the detection of statistically significant patterns of brain change over time and/or over multiple subjects. The focus of this thesis is the development and application of statistical and supporting methodology for the analysis of three-dimensional brain imaging data. There is a particular emphasis on longitudinal data, though much of the statistical methodology is more general. New methods of voxel-based morphometry (VBM) are developed for serial MR data, employing combinations of tissue segmentation and longitudinal non-rigid registration. The methods are evaluated using novel quantitative metrics based on simulated data. Contributions to general aspects of VBM are also made, and include a publication concerning guidelines for reporting VBM studies, and another examining an issue in the selection of which voxels to include in the statistical analysis mask for VBM of atrophic conditions. Research is carried out into the statistical theory of permutation testing for application to multivariate general linear models, and is then used to build software for the analysis of multivariate deformation- and tensor-based morphometry data, efficiently correcting for the multiple comparison problem inherent in voxel-wise analysis of images. Monte Carlo simulation studies extend results available in the literature regarding the different strategies available for permutation testing in the presence of confounds. Theoretical aspects of longitudinal deformation- and tensor-based morphometry are explored, such as the options for combining within- and between-subject deformation fields. Practical investigation of several different methods and variants is performed for a longitudinal AD study

Analysis of the developing brain using image registration

Imperial Users onl

Combining global and local information for the segmentation of MR images of the brain

Magnetic resonance imaging can provide high resolution volumetric images of the brain with exceptional soft tissue contrast. These factors allow the complex structure of the brain to be clearly visualised. This has lead to the development of quantitative methods to analyse neuroanatomical structures. In turn, this has promoted the use of computational methods to automate and improve these techniques. This thesis investigates methods to accurately segment MRI images of the brain. The use of global and local image information is considered, where global information includes image intensity distributions, means and variances and local information is based on the relationship between spatially neighbouring voxels. Methods are explored that aim to improve the classification and segmentation of MR images of the brain by combining these elements. Some common artefacts exist in MR brain images that can be seriously detrimental to image analysis methods. Methods to correct for these artifacts are assessed by exploring their effect, first with some well established classification methods and then with methods that combine global information with local information in the form of a Markov random field model. Another characteristic of MR images is the partial volume effect that occurs where signals from different tissues become mixed over the finite volume of a voxel. This effect is demonstrated and quantified using a simulation. Analysis methods that address these issues are tested on simulated and real MR images. They are also applied to study the structure of the temporal lobes in a group of patients with temporal lobe epilepsy. The results emphasise the benefits and limitations of applying these methods to a problem of this nature. The work in this thesis demonstrates the advantages of using global and local information together in the segmentation of MR brain images and proposes a generalised framework that allows this information to be combined in a flexible way

Bayesian generative learning of brain and spinal cord templates from neuroimaging datasets

In the field of neuroimaging, Bayesian modelling techniques have been largely adopted and recognised as powerful tools for the purpose of extracting quantitative anatomical and functional information from medical scans. Nevertheless the potential of Bayesian inference has not yet been fully exploited, as many available tools rely on point estimation techniques, such as maximum likelihood estimation, rather than on full Bayesian inference. The aim of this thesis is to explore the value of approximate learning schemes, for instance variational Bayes, to perform inference from brain and spinal cord MRI data. The applications that will be explored in this work mainly concern image segmentation and atlas construction, with a particular emphasis on the problem of shape and intensity prior learning, from large training data sets of structural MR scans. The resulting computational tools are intended to enable integrated brain and spinal cord morphometric analyses, as opposed to the approach that is most commonly adopted in neuroimaging, which consists in optimising separate tools for brain and spine morphometrics

Spatio-temporal Modeling and Analysis of Brain Development

The incidence of preterm birth is increasing and has emerged as a leading cause of neurodevelopmental impairment in childhood. In early development, defined here as the period before and around birth, the brain undergoes significant morphological, functional and appearance changes. The scope and rate of change is arguably greater than at any other time in life, but quantitative markers of this period of development are limited. Improved understanding of cerebral changes during this critical period is important for mapping normal growth, and for investigating mechanisms of injury associated with risk factors for maldevelopment such as premature birth. The objective of this thesis is the development of methods for spatio-temporal modeling and quantitative measures of brain development that can assist understanding the patterns of normal growth and can guide interventions designed to reduce the burden of preterm brain injury. An approach for constructing high-definition spatio-temporal atlases of the developing brain is introduced. A novelty in the proposed approach is the use of a time-varying kernel width, to overcome the variations in the distribution of subjects at different ages. This leads to an atlas that retains a consistent level of detail at every time-point. The resulting 4D fetal and neonatal average atlases have greater anatomic definition than currently available 4D atlases, an important factor in improving registrations between the atlas and individual subjects with clear anatomical structures and atlas-based automatic segmentation. The fetal atlas provides a natural benchmark for assessing preterm born neonates and gives some insight into differences between the groups. Also, a novel framework for longitudinal registration which can accommodate large intra-subject anatomical variations is introduced. The framework exploits previously developed spatio-temporal atlases, which can aid the longitudinal registration process as it provides prior information about the missing anatomical evolution between two scans taken over large time-interval. Finally, a voxel-wise analysis framework is proposed which complements the analysis of changes in brain morphology by the study of spatio-temporal signal intensity changes in multi-modal MRI, which can offer a useful marker of neurodevelopmental changes

Advanced Image Analysis for Modeling the Aging Brain

Both normal aging and neurodegenerative diseases such as Alzheimer’s disease (AD) cause morphological changes of the brain due to neurodegeneration. As neurodegeneration due to disease may be difficult to distinguish from that of normal aging, interpretation of magnetic resonance (MR) brain images in the context of diagnosis of neurodegenerative diseases is challenging, especially in the early stages of the disease. This thesis presented comprehensive models of the aging brain and novel computer-aided diagnosis methods, based on advanced, quantitative analysis of brain MR images, facilitating the differentiation between normal and abnormal neurodegeneration. I aimed to evaluate and develop methods for clinical decision support using features derived from MR brain images: I evaluated a classification method to predict global cognitive decline in the general population, evaluated five brain segmentation methods and developed a spatio-temporal model of morphological differences in the brain due to normal aging. To create this model I developed two novel techniques that allow performing non-rigid groupwise image registration on large imaging datasets. The novel aging brain models and computer-aided diagnosis methods facilitate the differentiation between normal and abnormal neurodegeneration. This will help in establishing more accurate diagnoses of patients, and in identifying patients at risk of developing neurodegenerative disease before symptoms emerge. In the future, the method’s performance and efficacy should be evaluated in clinical practice

Improvements in the registration of multimodal medical imaging : application to intensity inhomogeneity and partial volume corrections

Alignment or registration of medical images has a relevant role on clinical diagnostic and treatment decisions as well as in research settings. With the advent of new technologies for multimodal imaging, robust registration of functional and anatomical information is still a challenge, particular in small-animal imaging given the lesser structural content of certain anatomical parts, such as the brain, than in humans. Besides, patient-dependent and acquisition artefacts affecting the images information content further complicate registration, as is the case of intensity inhomogeneities (IIH) showing in MRI and the partial volume effect (PVE) attached to PET imaging. Reference methods exist for accurate image registration but their performance is severely deteriorated in situations involving little images Overlap. While several approaches to IIH and PVE correction exist these methods still do not guarantee or rely on robust registration. This Thesis focuses on overcoming current limitations af registration to enable novel IIH and PVE correction methods.El registre d'imatges mèdiques té un paper rellevant en les decisions de diagnòstic i tractament clíniques així com en la recerca. Amb el desenvolupament de noves tecnologies d'imatge multimodal, el registre robust d'informació funcional i anatòmica és encara avui un repte, en particular, en imatge de petit animal amb un menor contingut estructural que en humans de certes parts anatòmiques com el cervell. A més, els artefactes induïts pel propi pacient i per la tècnica d'adquisició que afecten el contingut d'informació de les imatges complica encara més el procés de registre. És el cas de les inhomogeneïtats d'intensitat (IIH) que apareixen a les RM i de l'efecte de volum parcial (PVE) característic en PET. Tot i que existeixen mètodes de referència pel registre acurat d'imatges la seva eficàcia es veu greument minvada en casos de poc solapament entre les imatges. De la mateixa manera, també existeixen mètodes per la correcció d'IIH i de PVE però que no garanteixen o que requereixen un registre robust. Aquesta tesi es centra en superar aquestes limitacions sobre el registre per habilitar nous mètodes per la correcció d'IIH i de PVE