Dynamical models and machine learning for supervised segmentation

This thesis is concerned with the problem of how to outline regions of interest in medical images, when the boundaries are weak or ambiguous and the region shapes are irregular. The focus on machine learning and interactivity leads to a common theme of the need to balance conflicting requirements. First, any machine learning method must strike a balance between how much it can learn and how well it generalises. Second, interactive methods must balance minimal user demand with maximal user control. To address the problem of weak boundaries,methods of supervised texture classification are investigated that do not use explicit texture features. These methods enable prior knowledge about the image to benefit any segmentation framework. A chosen dynamic contour model, based on probabilistic boundary tracking, combines these image priors with efficient modes of interaction. We show the benefits of the texture classifiers over intensity and gradient-based image models, in both classification and boundary extraction. To address the problem of irregular region shape, we devise a new type of statistical shape model (SSM) that does not use explicit boundary features or assume high-level similarity between region shapes. First, the models are used for shape discrimination, to constrain any segmentation framework by way of regularisation. Second, the SSMs are used for shape generation, allowing probabilistic segmentation frameworks to draw shapes from a prior distribution. The generative models also include novel methods to constrain shape generation according to information from both the image and user interactions. The shape models are first evaluated in terms of discrimination capability, and shown to out-perform other shape descriptors. Experiments also show that the shape models can benefit a standard type of segmentation algorithm by providing shape regularisers. We finally show how to exploit the shape models in supervised segmentation frameworks, and evaluate their benefits in user trials

Machine learning use for prognostic purposes in multiple sclerosis

The course of multiple sclerosis begins with a relapsing-remitting phase, which evolves into a secondarily progressive form over an extremely variable period, depending on many factors, each with a subtle influence. To date, no prognostic factors or risk score have been validated to predict disease course in single individuals. This is increasingly frustrating, since several treatments can prevent relapses and slow progression, even for a long time, although the possible adverse effects are relevant, in particular for the more effective drugs. An early prediction of disease course would allow differentiation of the treatment based on the expected aggressiveness of the disease, reserving high-impact therapies for patients at greater risk. To increase prognostic capacity, approaches based on machine learning (ML) algorithms are being attempted, given the failure of other approaches. Here we review recent studies that have used clinical data, alone or with other types of data, to derive prognostic models. Several algorithms that have been used and compared are described. Although no study has proposed a clinically usable model, knowledge is building up and in the future strong tools are likely to emerge

Advanced Computational Methods for Oncological Image Analysis

[Cancer is the second most common cause of death worldwide and encompasses highly variable clinical and biological scenarios. Some of the current clinical challenges are (i) early diagnosis of the disease and (ii) precision medicine, which allows for treatments targeted to specific clinical cases. The ultimate goal is to optimize the clinical workflow by combining accurate diagnosis with the most suitable therapies. Toward this, large-scale machine learning research can define associations among clinical, imaging, and multi-omics studies, making it possible to provide reliable diagnostic and prognostic biomarkers for precision oncology. Such reliable computer-assisted methods (i.e., artificial intelligence) together with clinicians’ unique knowledge can be used to properly handle typical issues in evaluation/quantification procedures (i.e., operator dependence and time-consuming tasks). These technical advances can significantly improve result repeatability in disease diagnosis and guide toward appropriate cancer care. Indeed, the need to apply machine learning and computational intelligence techniques has steadily increased to effectively perform image processing operations—such as segmentation, co-registration, classification, and dimensionality reduction—and multi-omics data integration.

A robust framework for medical image segmentation through adaptable class-specific representation

Medical image segmentation is an increasingly important component in virtual pathology, diagnostic imaging and computer-assisted surgery. Better hardware for image acquisition and a variety of advanced visualisation methods have paved the way for the development of computer based tools for medical image analysis and interpretation. The routine use of medical imaging scans of multiple modalities has been growing over the last decades and data sets such as the Visible Human Project have introduced a new modality in the form of colour cryo section data. These developments have given rise to an increasing need for better automatic and semiautomatic segmentation methods. The work presented in this thesis concerns the development of a new framework for robust semi-automatic segmentation of medical imaging data of multiple modalities. Following the specification of a set of conceptual and technical requirements, the framework known as ACSR (Adaptable Class-Specific Representation) is developed in the first case for 2D colour cryo section segmentation. This is achieved through the development of a novel algorithm for adaptable class-specific sampling of point neighbourhoods, known as the PGA (Path Growing Algorithm), combined with Learning Vector Quantization. The framework is extended to accommodate 3D volume segmentation of cryo section data and subsequently segmentation of single and multi-channel greyscale MRl data. For the latter the issues of inhomogeneity and noise are specifically addressed. Evaluation is based on comparison with previously published results on standard simulated and real data sets, using visual presentation, ground truth comparison and human observer experiments. ACSR provides the user with a simple and intuitive visual initialisation process followed by a fully automatic segmentation. Results on both cryo section and MRI data compare favourably to existing methods, demonstrating robustness both to common artefacts and multiple user initialisations. Further developments into specific clinical applications are discussed in the future work section

Machine Learning and its Application in Automatic Change Detection in Medical Images

Change detection is a fundamental problem in various fields, such as image surveillance, remote sensing, medical imaging, etc. The challenge of change detection in medical images is to detect disease-related changes while rejecting changes caused by noise, patient position change, and imaging acquisition artifacts such as field inhomogeneity. In this thesis, first, we overview the existing change detection methods, their underlying mathematical frameworks and limitations. Second, we present our contributions in solving the problem. We design optimal subspaces to approximate the background image in more efficient fashion. This is based on our structure principal component analysis, aiming to capture the structural similarity between scans in the context of change detection. We theoretically and numerically discuss the proper choices of norms used in the subspace approximation. The mathematical frameworks developed in this thesis consist of: (i) a new mathematical model to change detection by defining it as an optimization problem involving a cost function, input and output image sets, projection onto a subspace, and a similarity measure; (ii) development and implementation of numerical pipelines to compute the clinical changes by designing four mathematical algorithms; (iii) refining our algorithms by introducing the co-registration step utilizing the local dictionaries; and (iv) two new structure subspace learning models that are robust to outliers and noise, reduce the dimensionality of the dataset, and computationally efficient. We defined the co-registration step as a minimization problem involving a cost function, input and output image sets, a set of transform functions, projection onto a subspace, and a similarity measure. Based on the mathematical frameworks discussed above, numerical schemes are developed to automatically filter out clinically unrelated changes and identify true structure changes that may be of clinical importance. Our approaches are data-driven and utilize the knowledge of machine learning. We quantitatively analyze the performance of these algorithms using both synthetic and real human data. Our work has the potential to be used in computer aided diagnosis

Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Heterogeneous data fusion for brain psychology applications

This thesis aims to apply Empirical Mode Decomposition (EMD), Multiscale Entropy (MSE), and collaborative adaptive filters for the monitoring of different brain consciousness states. Both block based and online approaches are investigated, and a possible extension to the monitoring and identification of Electromyograph (EMG) states is provided. Firstly, EMD is employed as a multiscale time-frequency data driven tool to decompose a signal into a number of band-limited oscillatory components; its data driven nature makes EMD an ideal candidate for the analysis of nonlinear and non-stationary data. This methodology is further extended to process multichannel real world data, by making use of recent theoretical advances in complex and multivariate EMD. It is shown that this can be used to robustly measure higher order features in multichannel recordings to robustly indicate ‘QBD’. In the next stage, analysis is performed in an information theory setting on multiple scales in time, using MSE. This enables an insight into the complexity of real world recordings. The results of the MSE analysis and the corresponding statistical analysis show a clear difference in MSE between the patients in different brain consciousness states. Finally, an online method for the assessment of the underlying signal nature is studied. This method is based on a collaborative adaptive filtering approach, and is shown to be able to approximately quantify the degree of signal nonlinearity, sparsity, and non-circularity relative to the constituent subfilters. To further illustrate the usefulness of the proposed data driven multiscale signal processing methodology, the final case study considers a human-robot interface based on a multichannel EMG analysis. A preliminary analysis shows that the same methodology as that applied to the analysis of brain cognitive states gives robust and accurate results. The analysis, simulations, and the scope of applications presented suggest great potential of the proposed multiscale data processing framework for feature extraction in multichannel data analysis. Directions for future work include further development of real-time feature map approaches and their use across brain-computer and brain-machine interface applications