A Hybrid Similarity Measure Framework for Multimodal Medical Image Registration

Medical imaging is widely used today to facilitate both disease diagnosis and treatment planning practice, with a key prerequisite being the systematic process of medical image registration (MIR) to align either mono or multimodal images of different anatomical parts of the human body. MIR utilises a similarity measure (SM) to quantify the level of spatial alignment and is particularly demanding due to the presence of inherent modality characteristics like intensity non-uniformities (INU) in magnetic resonance images and large homogeneous non-vascular regions in retinal images. While various intensity and feature-based SMs exist for MIR, mutual information (MI) has become established because of its computational efficiency and ability to register multimodal images. It is however, very sensitive to interpolation artefacts in the presence of INU with noise and can be compromised when overlapping areas are small. Recently MI-based hybrid variants which combine regional features with intensity have emerged, though these incur high dimensionality and large computational overheads. To address these challenges and secure accurate, efficient and robust registration of images containing high INU, noise and large homogeneous regions, this thesis presents a new hybrid SM framework for 2D multimodal rigid MIR. The framework consistently provides superior quantitative and qualitative performance, while offering a uniquely flexible design trade-off between registration accuracy and computational time. It makes three significant technical contributions to the field: i) An expectation maximisation-based principal component analysis with mutual information (EMPCA-MI) framework incorporating neighbourhood feature information; ii) Two innovative enhancements to reduce information redundancy and improve MI computational efficiency; and iii) an adaptive algorithm to select the most significant principal components for feature selection. The thesis findings conclusively confirm the hybrid SM framework offers an accurate and robust 2D registration solution for challenging multimodal medical imaging datasets, while its inherent flexibility means it can also be extended to the 3D registration domain

Probabilistic prediction of Alzheimer’s disease from multimodal image data with Gaussian processes

Alzheimer’s disease, the most common form of dementia, is an extremely serious health problem, and one that will become even more so in the coming decades as the global population ages. This has led to a massive effort to develop both new treatments for the condition and new methods of diagnosis; in fact the two are intimately linked as future treatments will depend on earlier diagnosis, which in turn requires the development of biomarkers that can be used to identify and track the disease. This is made possible by studies such as the Alzheimer’s disease neuroimaging initiative which provides previously unimaginable quantities of imaging and other data freely to researchers. It is the task of early diagnosis that this thesis focuses on. We do so by borrowing modern machine learning techniques, and applying them to image data. In particular, we use Gaussian processes (GPs), a previously neglected tool, and show they can be used in place of the more widely used support vector machine (SVM). As combinations of complementary biomarkers have been shown to be more useful than the biomarkers are individually, we go on to show GPs can also be applied to integrate different types of image and non-image data, and thanks to their properties this improves results further than it does with SVMs. In the final two chapters, we also look at different ways to formulate both the prediction of conversion to Alzheimer’s disease as a machine learning problem and the way image data can be used to generate features for input as a machine learning algorithm. Both of these show how unconventional approaches may improve results. The result is an advance in the state-of-the-art for a very clinically important problem, which may prove useful in practice and show a direction of future research to further increase the usefulness of such method

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

Automating the multimodal analysis of musculoskeletal imaging in the presence of hip implants

In patients treated with hip arthroplasty, the muscular condition and presence of inflammatory reactions are assessed using magnetic resonance imaging (MRI). As MRI lacks contrast for bony structures, computed tomography (CT) is preferred for clinical evaluation of bone tissue and orthopaedic surgical planning. Combining the complementary information of MRI and CT could improve current clinical practice for diagnosis, monitoring and treatment planning. In particular, the different contrast of these modalities could help better quantify the presence of fatty infiltration to characterise muscular condition after hip replacement. In this thesis, I developed automated processing tools for the joint analysis of CT and MR images of patients with hip implants. In order to combine the multimodal information, a novel nonlinear registration algorithm was introduced, which imposes rigidity constraints on bony structures to ensure realistic deformation. I implemented and thoroughly validated a fully automated framework for the multimodal segmentation of healthy and pathological musculoskeletal structures, as well as implants. This framework combines the proposed registration algorithm with tailored image quality enhancement techniques and a multi-atlas-based segmentation approach, providing robustness against the large population anatomical variability and the presence of noise and artefacts in the images. The automation of muscle segmentation enabled the derivation of a measure of fatty infiltration, the Intramuscular Fat Fraction, useful to characterise the presence of muscle atrophy. The proposed imaging biomarker was shown to strongly correlate with the atrophy radiological score currently used in clinical practice. Finally, a preliminary work on multimodal metal artefact reduction, using an unsupervised deep learning strategy, showed promise for improving the postprocessing of CT and MR images heavily corrupted by metal artefact. This work represents a step forward towards the automation of image analysis in hip arthroplasty, supporting and quantitatively informing the decision-making process about patient’s management

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

Automated Morphometric Characterization of the Cerebral Cortex for the Developing and Ageing Brain

Morphometric characterisation of the cerebral cortex can provide information about patterns of brain development and ageing and may be relevant for diagnosis and estimation of the progression of diseases such as Alzheimer's, Huntington's, and schizophrenia. Therefore, understanding and describing the differences between populations in terms of structural volume, shape and thickness is of critical importance. Methodologically, due to data quality, presence of noise, PV effects, limited resolution and pathological variability, the automated, robust and time-consistent estimation of morphometric features is still an unsolved problem. This thesis focuses on the development of tools for robust cross-sectional and longitudinal morphometric characterisation of the human cerebral cortex. It describes techniques for tissue segmentation, structural and morphometric characterisation, cross-sectional and longitudinally cortical thickness estimation from serial MRI images in both adults and neonates. Two new probabilistic brain tissue segmentation techniques are introduced in order to accurately and robustly segment the brain of elderly and neonatal subjects, even in the presence of marked pathology. Two other algorithms based on the concept of multi-atlas segmentation propagation and fusion are also introduced in order to parcelate the brain into its multiple composing structures with the highest possible segmentation accuracy. Finally, we explore the use of the Khalimsky cubic complex framework for the extraction of topologically correct thickness measurements from probabilistic segmentations without explicit parametrisation of the edge. A longitudinal extension of this method is also proposed. The work presented in this thesis has been extensively validated on elderly and neonatal data from several scanners, sequences and protocols. The proposed algorithms have also been successfully applied to breast and heart MRI, neck and colon CT and also to small animal imaging. All the algorithms presented in this thesis are available as part of the open-source package NiftySeg

Gaussian mixture model classifiers for detection and tracking in UAV video streams.

Masters Degree. University of KwaZulu-Natal, Durban.Manual visual surveillance systems are subject to a high degree of human-error and operator fatigue. The automation of such systems often employs detectors, trackers and classifiers as fundamental building blocks. Detection, tracking and classification are especially useful and challenging in Unmanned Aerial Vehicle (UAV) based surveillance systems. Previous solutions have addressed challenges via complex classification methods. This dissertation proposes less complex Gaussian Mixture Model (GMM) based classifiers that can simplify the process; where data is represented as a reduced set of model parameters, and classification is performed in the low dimensionality parameter-space. The specification and adoption of GMM based classifiers on the UAV visual tracking feature space formed the principal contribution of the work. This methodology can be generalised to other feature spaces. This dissertation presents two main contributions in the form of submissions to ISI accredited journals. In the first paper, objectives are demonstrated with a vehicle detector incorporating a two stage GMM classifier, applied to a single feature space, namely Histogram of Oriented Gradients (HoG). While the second paper demonstrates objectives with a vehicle tracker using colour histograms (in RGB and HSV), with Gaussian Mixture Model (GMM) classifiers and a Kalman filter. The proposed works are comparable to related works with testing performed on benchmark datasets. In the tracking domain for such platforms, tracking alone is insufficient. Adaptive detection and classification can assist in search space reduction, building of knowledge priors and improved target representations. Results show that the proposed approach improves performance and robustness. Findings also indicate potential further enhancements such as a multi-mode tracker with global and local tracking based on a combination of both papers

Brain Lesion Segmentation through Image Synthesis and Outlier Detection

Cerebral small vessel disease (SVD) can manifest in a number of ways. Many of these result in hyperintense regions visible on T2-weighted magnetic resonance (MR) images. The automatic segmentation of these lesions has been the focus of many studies. However, previous methods tended to be limited to certain types of pathology, as a consequence of either restricting the search to the white matter, or by training on an individual pathology. Here we present an unsupervised abnormality detection method which is able to detect abnormally hyperintense regions on FLAIR regardless of the underlying pathology or location. The method uses a combination of image synthesis, Gaussian mixture models and one class support vector machines, and needs only be trained on healthy tissue. We evaluate our method by comparing segmentation results from 127 subjects with SVD with three established methods and report significantly superior performance across a number of metrics