Characterising population variability in brain structure through models of whole-brain structural connectivity

Models of whole-brain connectivity are valuable for understanding neurological function. This thesis seeks to develop an optimal framework for extracting models of whole-brain connectivity from clinically acquired diffusion data. We propose new approaches for studying these models. The aim is to develop techniques which can take models of brain connectivity and use them to identify biomarkers or phenotypes of disease. The models of connectivity are extracted using a standard probabilistic tractography algorithm, modified to assess the structural integrity of tracts, through estimates of white matter anisotropy. Connections are traced between 77 regions of interest, automatically extracted by label propagation from multiple brain atlases followed by classifier fusion. The estimates of tissue integrity for each tract are input as indices in 77x77 ”connectivity” matrices, extracted for large populations of clinical data. These are compared in subsequent studies. To date, most whole-brain connectivity studies have characterised population differences using graph theory techniques. However these can be limited in their ability to pinpoint the locations of differences in the underlying neural anatomy. Therefore, this thesis proposes new techniques. These include a spectral clustering approach for comparing population differences in the clustering properties of weighted brain networks. In addition, machine learning approaches are suggested for the first time. These are particularly advantageous as they allow classification of subjects and extraction of features which best represent the differences between groups. One limitation of the proposed approach is that errors propagate from segmentation and registration steps prior to tractography. This can cumulate in the assignment of false positive connections, where the contribution of these factors may vary across populations, causing the appearance of population differences where there are none. The final contribution of this thesis is therefore to develop a common co-ordinate space approach. This combines probabilistic models of voxel-wise diffusion for each subject into a single probabilistic model of diffusion for the population. This allows tractography to be performed only once, ensuring that there is one model of connectivity. Cross-subject differences can then be identified by mapping individual subjects’ anisotropy data to this model. The approach is used to compare populations separated by age and gender

Affine Registration of label maps in Label Space

Two key aspects of coupled multi-object shape\ud analysis and atlas generation are the choice of representation\ud and subsequent registration methods used to align the sample\ud set. For example, a typical brain image can be labeled into\ud three structures: grey matter, white matter and cerebrospinal\ud fluid. Many manipulations such as interpolation, transformation,\ud smoothing, or registration need to be performed on these images\ud before they can be used in further analysis. Current techniques\ud for such analysis tend to trade off performance between the two\ud tasks, performing well for one task but developing problems when\ud used for the other.\ud This article proposes to use a representation that is both\ud flexible and well suited for both tasks. We propose to map object\ud labels to vertices of a regular simplex, e.g. the unit interval for\ud two labels, a triangle for three labels, a tetrahedron for four\ud labels, etc. This representation, which is routinely used in fuzzy\ud classification, is ideally suited for representing and registering\ud multiple shapes. On closer examination, this representation\ud reveals several desirable properties: algebraic operations may\ud be done directly, label uncertainty is expressed as a weighted\ud mixture of labels (probabilistic interpretation), interpolation is\ud unbiased toward any label or the background, and registration\ud may be performed directly.\ud We demonstrate these properties by using label space in a gradient\ud descent based registration scheme to obtain a probabilistic\ud atlas. While straightforward, this iterative method is very slow,\ud could get stuck in local minima, and depends heavily on the initial\ud conditions. To address these issues, two fast methods are proposed\ud which serve as coarse registration schemes following which the\ud iterative descent method can be used to refine the results. Further,\ud we derive an analytical formulation for direct computation of the\ud "group mean" from the parameters of pairwise registration of all\ud the images in the sample set. We show results on richly labeled\ud 2D and 3D data sets

From Error Probability to Information Theoretic (Multi-Modal) Signal Processing

We propose an information theoretic model that unifies a wide range of existing information theoretic signal processing algorithms in a compact mathematical framework. It is mainly based on stochastic processes, Markov chains and error probabilities. The proposed framework will allow us to discuss revealing analogies and differences between several well known algorithms and to propose interesting extensions resulting directly from our formalism. We will then describe how the theory can be applied to the rapidly emerging field of multi-modal signal processing: we will show how our framework can be efficiently used for multi-modal medical image processing and for joint analysis of multi-media sequences (audio and video)

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

Generative Models for Preprocessing of Hospital Brain Scans

I will in this thesis present novel computational methods for processing routine clinical brain scans. Such scans were originally acquired for qualitative assessment by trained radiologists, and present a number of difficulties for computational models, such as those within common neuroimaging analysis software. The overarching objective of this work is to enable efficient and fully automated analysis of large neuroimaging datasets, of the type currently present in many hospitals worldwide. The methods presented are based on probabilistic, generative models of the observed imaging data, and therefore rely on informative priors and realistic forward models. The first part of the thesis will present a model for image quality improvement, whose key component is a novel prior for multimodal datasets. I will demonstrate its effectiveness for super-resolving thick-sliced clinical MR scans and for denoising CT images and MR-based, multi-parametric mapping acquisitions. I will then show how the same prior can be used for within-subject, intermodal image registration, for more robustly registering large numbers of clinical scans. The second part of the thesis focusses on improved, automatic segmentation and spatial normalisation of routine clinical brain scans. I propose two extensions to a widely used segmentation technique. First, a method for this model to handle missing data, which allows me to predict entirely missing modalities from one, or a few, MR contrasts. Second, a principled way of combining the strengths of probabilistic, generative models with the unprecedented discriminative capability of deep learning. By introducing a convolutional neural network as a Markov random field prior, I can model nonlinear class interactions and learn these using backpropagation. I show that this model is robust to sequence and scanner variability. Finally, I show examples of fitting a population-level, generative model to various neuroimaging data, which can model, e.g., CT scans with haemorrhagic lesions

Landmark Localization, Feature Matching and Biomarker Discovery from Magnetic Resonance Images

The work presented in this thesis proposes several methods that can be roughly divided into three different categories: I) landmark localization in medical images, II) feature matching for image registration, and III) biomarker discovery in neuroimaging. The first part deals with the identification of anatomical landmarks. The motivation stems from the fact that the manual identification and labeling of these landmarks is very time consuming and prone to observer errors, especially when large datasets must be analyzed. In this thesis we present three methods to tackle this challenge: A landmark descriptor based on local self-similarities (SS), a subspace building framework based on manifold learning and a sparse coding landmark descriptor based on data-specific learned dictionary basis. The second part of this thesis deals with finding matching features between a pair of images. These matches can be used to perform a registration between them. Registration is a powerful tool that allows mapping images in a common space in order to aid in their analysis. Accurate registration can be challenging to achieve using intensity based registration algorithms. Here, a framework is proposed for learning correspondences in pairs of images by matching SS features and random sample and consensus (RANSAC) is employed as a robust model estimator to learn a deformation model based on feature matches. Finally, the third part of the thesis deals with biomarker discovery using machine learning. In this section a framework for feature extraction from learned low-dimensional subspaces that represent inter-subject variability is proposed. The manifold subspace is built using data-driven regions of interest (ROI). These regions are learned via sparse regression, with stability selection. Also, probabilistic distribution models for different stages in the disease trajectory are estimated for different class populations in the low-dimensional manifold and used to construct a probabilistic scoring function.Open Acces