Deep generative modelling of the imaged human brain

Human-machine symbiosis is a very promising opportunity for the field of neurology given that the interpretation of the imaged human brain is a trivial feat for neither entity. However, before machine learning systems can be used in real world clinical situations, many issues with automated analysis must first be solved. In this thesis I aim to address what I consider the three biggest hurdles to the adoption of automated machine learning interpretative systems. For each issue, I will first elucidate the reader on its importance given the overarching narratives of both neurology and machine learning, and then showcase my proposed solutions to these issues through the use of deep generative models of the imaged human brain. First, I start by addressing what is an uncontroversial and universal sign of intelligence: the ability to extrapolate knowledge to unseen cases. Human neuroradiologists have studied the anatomy of the healthy brain and can therefore, with some success, identify most pathologies present on an imaged brain, even without having ever been previously exposed to them. Current discriminative machine learning systems require vast amounts of labelled data in order to accurately identify diseases. In this first part I provide a generative framework that permits machine learning models to more efficiently leverage unlabelled data for better diagnoses with either none or small amounts of labels. Secondly, I address a major ethical concern in medicine: equitable evaluation of all patients, regardless of demographics or other identifying characteristics. This is, unfortunately, something that even human practitioners fail at, making the matter ever more pressing: unaddressed biases in data will become biases in the models. To address this concern I suggest a framework through which a generative model synthesises demographically counterfactual brain imaging to successfully reduce the proliferation of demographic biases in discriminative models. Finally, I tackle the challenge of spatial anatomical inference, a task at the centre of the field of lesion-deficit mapping, which given brain lesions and associated cognitive deficits attempts to discover the true functional anatomy of the brain. I provide a new Bayesian generative framework and implementation that allows for greatly improved results on this challenge, hopefully, paving part of the road towards a greater and more complete understanding of the human brain

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

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Mathematical approaches for the clinical translation of hyperpolarised 13C imaging in oncology

Dissolution dynamic nuclear polarisation is an emerging clinical technique which enables the metabolism of hyperpolarised 13C-labelled molecules to be dynamically and non- invasively imaged in tissue. The first molecule to gain clinical approval is [1-13C]pyruvate, the conversion of which to [1-13C]lactate has been shown to detect early treatment re- sponse in cancers and correlate with tumour grade. As the technique has recently been translated into humans, accurate and reliable quantitative methods are required in order to detect, analyse and compare regions of altered metabolism in patients. Furthermore, there is a requirement to understand the biological processes which govern lactate pro- duction in tumours in order to draw reliable conclusions from this data. This work begins with a comprehensive analysis of the quantitative methods which have previously been applied to hyperpolarised 13C data and compares these to some novel approaches. The most appropriate kinetic model to apply to hyperpolarised data is determined and some simple, robust quantitative metrics are identified which are suitable for clinical use. A means of automatically segmenting 5D hyperpolarised imaging data using a fuzzy Markov random field approach is presented in order to reliably identify regions of abnormal metabolic activity. The utility of the algorithm is demonstrated on both in silico and animal data. To gain insight into the processes driving lactate metabolism, a mathematical model is developed which is capable of simulating tumour growth and treatment response under a range of metabolic and tissue conditions, focusing on the interaction between tumour and stroma. Finally, hyperpolarised 13C-pyruvate imaging data from the first human subjects to be imaged in Cambridge is analysed. The ability to detect and quantify lactate production in patients is demonstrated through application of the methods derived in earlier chapters. The mathematical approaches presented in this work have the potential to inform both the analysis and interpretation of clinical hyperpolarised 13C imaging data and to aid in the clinical translation of this technique.Joint funded by GlaxoSmithKline and the Cambridge Biomedical Research Centre

Two and three dimensional segmentation of multimodal imagery

The role of segmentation in the realms of image understanding/analysis, computer vision, pattern recognition, remote sensing and medical imaging in recent years has been significantly augmented due to accelerated scientific advances made in the acquisition of image data. This low-level analysis protocol is critical to numerous applications, with the primary goal of expediting and improving the effectiveness of subsequent high-level operations by providing a condensed and pertinent representation of image information. In this research, we propose a novel unsupervised segmentation framework for facilitating meaningful segregation of 2-D/3-D image data across multiple modalities (color, remote-sensing and biomedical imaging) into non-overlapping partitions using several spatial-spectral attributes. Initially, our framework exploits the information obtained from detecting edges inherent in the data. To this effect, by using a vector gradient detection technique, pixels without edges are grouped and individually labeled to partition some initial portion of the input image content. Pixels that contain higher gradient densities are included by the dynamic generation of segments as the algorithm progresses to generate an initial region map. Subsequently, texture modeling is performed and the obtained gradient, texture and intensity information along with the aforementioned initial partition map are used to perform a multivariate refinement procedure, to fuse groups with similar characteristics yielding the final output segmentation. Experimental results obtained in comparison to published/state-of the-art segmentation techniques for color as well as multi/hyperspectral imagery, demonstrate the advantages of the proposed method. Furthermore, for the purpose of achieving improved computational efficiency we propose an extension of the aforestated methodology in a multi-resolution framework, demonstrated on color images. Finally, this research also encompasses a 3-D extension of the aforementioned algorithm demonstrated on medical (Magnetic Resonance Imaging / Computed Tomography) volumes

Simplified inverse filter tracked affective acoustic signals classification incorporating deep convolutional neural networks

Facial expressions, verbal, behavioral, such as limb movements, and physiological features are vital ways for affective human interactions. Researchers have given machines the ability to recognize affective communication through the above modalities in the past decades. In addition to facial expressions, changes in the level of sound, strength, weakness, and turbulence will also convey affective. Extracting affective feature parameters from the acoustic signals have been widely applied in customer service, education, and the medical field. In this research, an improved AlexNet-based deep convolutional neural network (A-DCNN) is presented for acoustic signal recognition. Firstly, preprocessed on signals using simplified inverse filter tracking (SIFT) and short-time Fourier transform (STFT), Mel frequency Cepstrum (MFCC) and waveform-based segmentation were deployed to create the input for the deep neural network (DNN), which was applied widely in signals preprocess for most neural networks. Secondly, acoustic signals were acquired from the public Ryerson Audio-Visual Database of Affective Speech and Song (RAVDESS) affective speech audio system. Through the acoustic signal preprocessing tools, the basic features of the kind of sound signals were calculated and extracted. The proposed DNN based on improved AlexNet has a 95.88% accuracy on classifying eight affective of acoustic signals. By comparing with some linear classifications, such as decision table (DT) and Bayesian inference (BI) and other deep neural networks, such as AlexNet+SVM, recurrent convolutional neural network (R-CNN), etc., the proposed method achieves high effectiveness on the accuracy (A), sensitivity (S1), positive predictive (PP), and f1-score (F1). Acoustic signals affective recognition and classification can be potentially applied in industrial product design through measuring consumers’ affective responses to products; by collecting relevant affective sound data to understand the popularity of the product, and furthermore, to improve the product design and increase the market responsiveness

Large-scale inference in the focally damaged human brain

Clinical outcomes in focal brain injury reflect the interactions between two distinct anatomically distributed patterns: the functional organisation of the brain and the structural distribution of injury. The challenge of understanding the functional architecture of the brain is familiar; that of understanding the lesion architecture is barely acknowledged. Yet, models of the functional consequences of focal injury are critically dependent on our knowledge of both. The studies described in this thesis seek to show how machine learning-enabled high-dimensional multivariate analysis powered by large-scale data can enhance our ability to model the relation between focal brain injury and clinical outcomes across an array of modelling applications. All studies are conducted on internationally the largest available set of MR imaging data of focal brain injury in the context of acute stroke (N=1333) and employ kernel machines at the principal modelling architecture. First, I examine lesion-deficit prediction, quantifying the ceiling on achievable predictive fidelity for high-dimensional and low-dimensional models, demonstrating the former to be substantially higher than the latter. Second, I determine the marginal value of adding unlabelled imaging data to predictive models within a semi-supervised framework, quantifying the benefit of assembling unlabelled collections of clinical imaging. Third, I compare high- and low-dimensional approaches to modelling response to therapy in two contexts: quantifying the effect of treatment at the population level (therapeutic inference) and predicting the optimal treatment in an individual patient (prescriptive inference). I demonstrate the superiority of the high-dimensional approach in both settings

Applications of Artificial Intelligence in Medicine Practice

This book focuses on a variety of interdisciplinary perspectives concerning the theory and application of artificial intelligence (AI) in medicine, medically oriented human biology, and healthcare. The list of topics includes the application of AI in biomedicine and clinical medicine, machine learning-based decision support, robotic surgery, data analytics and mining, laboratory information systems, and usage of AI in medical education. Special attention is given to the practical aspect of a study. Hence, the inclusion of a clinical assessment of the usefulness and potential impact of the submitted work is strongly highlighted

Roadmap on signal processing for next generation measurement systems

Signal processing is a fundamental component of almost any sensor-enabled system, with a wide range of applications across different scientific disciplines. Time series data, images, and video sequences comprise representative forms of signals that can be enhanced and analysed for information extraction and quantification. The recent advances in artificial intelligence and machine learning are shifting the research attention towards intelligent, data-driven, signal processing. This roadmap presents a critical overview of the state-of-the-art methods and applications aiming to highlight future challenges and research opportunities towards next generation measurement systems. It covers a broad spectrum of topics ranging from basic to industrial research, organized in concise thematic sections that reflect the trends and the impacts of current and future developments per research field. Furthermore, it offers guidance to researchers and funding agencies in identifying new prospects.AerodynamicsMicrowave Sensing, Signals & System

New Directions for Contact Integrators

Contact integrators are a family of geometric numerical schemes which guarantee the conservation of the contact structure. In this work we review the construction of both the variational and Hamiltonian versions of these methods. We illustrate some of the advantages of geometric integration in the dissipative setting by focusing on models inspired by recent studies in celestial mechanics and cosmology.Comment: To appear as Chapter 24 in GSI 2021, Springer LNCS 1282