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

Rapid Segmentation Techniques for Cardiac and Neuroimage Analysis

Recent technological advances in medical imaging have allowed for the quick acquisition of highly resolved data to aid in diagnosis and characterization of diseases or to guide interventions. In order to to be integrated into a clinical work flow, accurate and robust methods of analysis must be developed which manage this increase in data. Recent improvements in in- expensive commercially available graphics hardware and General-Purpose Programming on Graphics Processing Units (GPGPU) have allowed for many large scale data analysis problems to be addressed in meaningful time and will continue to as parallel computing technology improves. In this thesis we propose methods to tackle two clinically relevant image segmentation problems: a user-guided segmentation of myocardial scar from Late-Enhancement Magnetic Resonance Images (LE-MRI) and a multi-atlas segmentation pipeline to automatically segment and partition brain tissue from multi-channel MRI. Both methods are based on recent advances in computer vision, in particular max-flow optimization that aims at solving the segmentation problem in continuous space. This allows for (approximately) globally optimal solvers to be employed in multi-region segmentation problems, without the particular drawbacks of their discrete counterparts, graph cuts, which typically present with metrication artefacts. Max-flow solvers are generally able to produce robust results, but are known for being computationally expensive, especially with large datasets, such as volume images. Additionally, we propose two new deformable registration methods based on Gauss-Newton optimization and smooth the resulting deformation fields via total-variation regularization to guarantee the problem is mathematically well-posed. We compare the performance of these two methods against four highly ranked and well-known deformable registration methods on four publicly available databases and are able to demonstrate a highly accurate performance with low run times. The best performing variant is subsequently used in a multi-atlas segmentation pipeline for the segmentation of brain tissue and facilitates fast run times for this computationally expensive approach. All proposed methods are implemented using GPGPU for a substantial increase in computational performance and so facilitate deployment into clinical work flows. We evaluate all proposed algorithms in terms of run times, accuracy, repeatability and errors arising from user interactions and we demonstrate that these methods are able to outperform established methods. The presented approaches demonstrate high performance in comparison with established methods in terms of accuracy and repeatability while largely reducing run times due to the employment of GPU hardware

Enhancing the spatial resolution of hyperpolarized carbon‐13 MRI of human brain metabolism using structure guidance

Funder: Mark Foundation Institute for Cancer ResearchFunder: Cambridge Experimental Cancer Medicine CentreFunder: Alan Turing Institute; Id: http://dx.doi.org/10.13039/100012338Funder: Cantab Capital Institute for the Mathematics of InformationPurpose: Dynamic nuclear polarization is an emerging imaging method that allows noninvasive investigation of tissue metabolism. However, the relatively low metabolic spatial resolution that can be achieved limits some applications, and improving this resolution could have important implications for the technique. Methods: We propose to enhance the 3D resolution of carbon‐13 magnetic resonance imaging (13C‐MRI) using the structural information provided by hydrogen‐1 MRI (1H‐MRI). The proposed approach relies on variational regularization in 3D with a directional total variation regularizer, resulting in a convex optimization problem which is robust with respect to the parameters and can efficiently be solved by many standard optimization algorithms. Validation was carried out using an in silico phantom, an in vitro phantom and in vivo data from four human volunteers. Results: The clinical data used in this study were upsampled by a factor of 4 in‐plane and by a factor of 15 out‐of‐plane, thereby revealing occult information. A key finding is that 3D super‐resolution shows superior performance compared to several 2D super‐resolution approaches: for example, for the in silico data, the mean‐squared‐error was reduced by around 40% and for all data produced increased anatomical definition of the metabolic imaging. Conclusion: The proposed approach generates images with enhanced anatomical resolution while largely preserving the quantitative measurements of metabolism. Although the work requires clinical validation against tissue measures of metabolism, it offers great potential in the field of 13C‐MRI and could significantly improve image quality in the future

Medical Image Modality Synthesis and Resolution Enhancement Based on Machine Learning Techniques

To achieve satisfactory performance from automatic medical image analysis algorithms such as registration or segmentation, medical imaging data with the desired modality/contrast and high isotropic resolution are preferred, yet they are not always available. We addressed this problem in this thesis using 1) image modality synthesis and 2) resolution enhancement. The first contribution of this thesis is computed tomography (CT)-tomagnetic resonance imaging (MRI) image synthesis method, which was developed to provide MRI when CT is the only modality that is acquired. The main challenges are that CT has poor contrast as well as high noise in soft tissues and that the CT-to-MR mapping is highly nonlinear. To overcome these challenges, we developed a convolutional neural network (CNN) which is a modified U-net. With this deep network for synthesis, we developed the first segmentation method that provides detailed grey matter anatomical labels on CT neuroimages using synthetic MRI. The second contribution is a method for resolution enhancement for a common type of acquisition in clinical and research practice, one in which there is high resolution (HR) in the in-plane directions and low resolution (LR) in the through-plane direction. The challenge of improving the through-plane resolution for such acquisitions is that the state-of-art convolutional neural network (CNN)-based super-resolution methods are sometimes not applicable due to lack of external LR/HR paired training data. To address this challenge, we developed a self super-resolution algorithm called SMORE and its iterative version called iSMORE, which are CNN-based yet do not require LR/HR paired training data other than the subject image itself. SMORE/iSMORE create training data from the HR in-plane slices of the subject image itself, then train and apply CNNs to through-plane slices to improve spatial resolution and remove aliasing. In this thesis, we perform SMORE/iSMORE on multiple simulated and real datasets to demonstrate their accuracy and generalizability. Also, SMORE as a preprocessing step is shown to improve segmentation accuracy. In summary, CT-to-MR synthesis, SMORE, and iSMORE were demonstrated in this thesis to be effective preprocessing algorithms for visual quality and other automatic medical image analysis such as registration or segmentation

Reasoning with Uncertainty in Deep Learning for Safer Medical Image Computing

Deep learning is now ubiquitous in the research field of medical image computing. As such technologies progress towards clinical translation, the question of safety becomes critical. Once deployed, machine learning systems unavoidably face situations where the correct decision or prediction is ambiguous. However, the current methods disproportionately rely on deterministic algorithms, lacking a mechanism to represent and manipulate uncertainty. In safety-critical applications such as medical imaging, reasoning under uncertainty is crucial for developing a reliable decision making system. Probabilistic machine learning provides a natural framework to quantify the degree of uncertainty over different variables of interest, be it the prediction, the model parameters and structures, or the underlying data (images and labels). Probability distributions are used to represent all the uncertain unobserved quantities in a model and how they relate to the data, and probability theory is used as a language to compute and manipulate these distributions. In this thesis, we explore probabilistic modelling as a framework to integrate uncertainty information into deep learning models, and demonstrate its utility in various high-dimensional medical imaging applications. In the process, we make several fundamental enhancements to current methods. We categorise our contributions into three groups according to the types of uncertainties being modelled: (i) predictive; (ii) structural and (iii) human uncertainty. Firstly, we discuss the importance of quantifying predictive uncertainty and understanding its sources for developing a risk-averse and transparent medical image enhancement application. We demonstrate how a measure of predictive uncertainty can be used as a proxy for the predictive accuracy in the absence of ground-truths. Furthermore, assuming the structure of the model is flexible enough for the task, we introduce a way to decompose the predictive uncertainty into its orthogonal sources i.e. aleatoric and parameter uncertainty. We show the potential utility of such decoupling in providing a quantitative “explanations” into the model performance. Secondly, we introduce our recent attempts at learning model structures directly from data. One work proposes a method based on variational inference to learn a posterior distribution over connectivity structures within a neural network architecture for multi-task learning, and share some preliminary results in the MR-only radiotherapy planning application. Another work explores how the training algorithm of decision trees could be extended to grow the architecture of a neural network to adapt to the given availability of data and the complexity of the task. Lastly, we develop methods to model the “measurement noise” (e.g., biases and skill levels) of human annotators, and integrate this information into the learning process of the neural network classifier. In particular, we show that explicitly modelling the uncertainty involved in the annotation process not only leads to an improvement in robustness to label noise, but also yields useful insights into the patterns of errors that characterise individual experts

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low-and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource

Is attention all you need in medical image analysis? A review

Medical imaging is a key component in clinical diagnosis, treatment planning and clinical trial design, accounting for almost 90% of all healthcare data. CNNs achieved performance gains in medical image analysis (MIA) over the last years. CNNs can efficiently model local pixel interactions and be trained on small-scale MI data. The main disadvantage of typical CNN models is that they ignore global pixel relationships within images, which limits their generalisation ability to understand out-of-distribution data with different 'global' information. The recent progress of Artificial Intelligence gave rise to Transformers, which can learn global relationships from data. However, full Transformer models need to be trained on large-scale data and involve tremendous computational complexity. Attention and Transformer compartments (Transf/Attention) which can well maintain properties for modelling global relationships, have been proposed as lighter alternatives of full Transformers. Recently, there is an increasing trend to co-pollinate complementary local-global properties from CNN and Transf/Attention architectures, which led to a new era of hybrid models. The past years have witnessed substantial growth in hybrid CNN-Transf/Attention models across diverse MIA problems. In this systematic review, we survey existing hybrid CNN-Transf/Attention models, review and unravel key architectural designs, analyse breakthroughs, and evaluate current and future opportunities as well as challenges. We also introduced a comprehensive analysis framework on generalisation opportunities of scientific and clinical impact, based on which new data-driven domain generalisation and adaptation methods can be stimulated

Applications of Deep Learning Techniques for Automated Multiple Sclerosis Detection Using Magnetic Resonance Imaging: A Review

Multiple Sclerosis (MS) is a type of brain disease which causes visual, sensory, and motor problems for people with a detrimental effect on the functioning of the nervous system. In order to diagnose MS, multiple screening methods have been proposed so far; among them, magnetic resonance imaging (MRI) has received considerable attention among physicians. MRI modalities provide physicians with fundamental information about the structure and function of the brain, which is crucial for the rapid diagnosis of MS lesions. Diagnosing MS using MRI is time-consuming, tedious, and prone to manual errors. Research on the implementation of computer aided diagnosis system (CADS) based on artificial intelligence (AI) to diagnose MS involves conventional machine learning and deep learning (DL) methods. In conventional machine learning, feature extraction, feature selection, and classification steps are carried out by using trial and error; on the contrary, these steps in DL are based on deep layers whose values are automatically learn. In this paper, a complete review of automated MS diagnosis methods performed using DL techniques with MRI neuroimaging modalities is provided. Initially, the steps involved in various CADS proposed using MRI modalities and DL techniques for MS diagnosis are investigated. The important preprocessing techniques employed in various works are analyzed. Most of the published papers on MS diagnosis using MRI modalities and DL are presented. The most significant challenges facing and future direction of automated diagnosis of MS using MRI modalities and DL techniques are also provided

U-Net and its variants for medical image segmentation: theory and applications

U-net is an image segmentation technique developed primarily for medical image analysis that can precisely segment images using a scarce amount of training data. These traits provide U-net with a very high utility within the medical imaging community and have resulted in extensive adoption of U-net as the primary tool for segmentation tasks in medical imaging. The success of U-net is evident in its widespread use in all major image modalities from CT scans and MRI to X-rays and microscopy. Furthermore, while U-net is largely a segmentation tool, there have been instances of the use of U-net in other applications. As the potential of U-net is still increasing, in this review we look at the various developments that have been made in the U-net architecture and provide observations on recent trends. We examine the various innovations that have been made in deep learning and discuss how these tools facilitate U-net. Furthermore, we look at image modalities and application areas where U-net has been applied.Comment: 42 pages, in IEEE Acces