Automatic Spatial Estimation of White Matter Hyperintensities Evolution in Brain MRI using Disease Evolution Predictor Deep Neural Networks

Funds from the Indonesia Endowment Fund for Education (LPDP), Ministry of Finance, Republic of Indonesia (MFR); Row Fogo Charitable Trust (Grant No. BRO-D.FID3668413)(MCVH); Wellcome Trust (patient recruitment, scanning, primary study Ref No. WT088134/Z/09/A); Fondation Leducq (Perivascular Spaces Transatlantic Network of Excellence); EU Horizon 2020 (SVDs@Target); and the MRC UK Dementia Research Institute at the University of Edinburgh (Wardlaw programme) are gratefully acknowledged. The Titan Xp used for this research was donated by the NVIDIA Corporation.Peer reviewedPublisher PD

Development of machine learning schemes for segmentation, characterisation, and evolution prediction of white matter hyperintensities in structural brain MRI

White matter hyperintensities (WMH) are neuroradiological features seen in T2 Fluid-Attenuated Inversion Recovery (T2-FLAIR) brain magnetic resonance imaging (MRI) and have been commonly associated with stroke, ageing, dementia, and Alzheimer’s disease (AD) progression. As a marker of neuro-degenerative disease, WMH may change over time and follow the clinical condition of the patient. In contrast to the early longitudinal studies of WMH, recent studies have suggested that the progression of WMH may be a dynamic, non-linear process where different clusters of WMH may shrink, stay unchanged, or grow. In this thesis, these changes are referred to as the “evolution of WMH”. The main objective of this thesis is to develop machine learning methods for prediction of WMH evolution in structural brain MRI from one-time (baseline) assessment. Predicting the evolution of WMH is challenging because the rate and direction of WMH evolution varies greatly across previous studies. Furthermore, the evolution of WMH is a non-deterministic problem because some clinical factors that possibly influence it are still not known. In this thesis, different learning schemes of deep learning algorithm and data modalities are proposed to produce the best estimation of WMH evolution. Furthermore, a scheme to simulate the non-deterministic nature of WMH evolution, named auxiliary input, was also proposed. In addition to the development of prediction model for WMH evolution, machine learning methods for segmentation of early WMH, characterisation of WMH, and simulation of WMH progression and regression are also developed as parts of this thesis

Deep generative models for medical image synthesis and strategies to utilise them

Medical imaging has revolutionised the diagnosis and treatments of diseases since the first medical image was taken using X-rays in 1895. As medical imaging became an essential tool in a modern healthcare system, more medical imaging techniques have been invented, such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT), Ultrasound, etc. With the advance of medical imaging techniques, the demand for processing and analysing these complex medical images is increasing rapidly. Efforts have been put on developing approaches that can automatically analyse medical images. With the recent success of deep learning (DL) in computer vision, researchers have applied and proposed many DL-based methods in the field of medical image analysis. However, one problem with data-driven DL-based methods is the lack of data. Unlike natural images, medical images are more expensive to acquire and label. One way to alleviate the lack of medical data is medical image synthesis. In this thesis, I first start with pseudo healthy synthesis, which is to create a ‘healthy’ looking medical image from a pathological one. The synthesised pseudo healthy images can be used for the detection of pathology, segmentation, etc. Several challenges exist with this task. The first challenge is the lack of ground-truth data, as a subject cannot be healthy and diseased at the same time. The second challenge is how to evaluate the generated images. In this thesis, I propose a deep learning method to learn to generate pseudo healthy images with adversarial and cycle consistency losses to overcome the lack of ground-truth data. I also propose several metrics to evaluate the quality of synthetic ‘healthy’ images. Pseudo healthy synthesis can be viewed as transforming images between discrete domains, e.g. from pathological domain to healthy domain. However, there are some changes in medical data that are continuous, e.g. brain ageing progression. Brain changes as age increases. With the ageing global population, research on brain ageing has attracted increasing attention. In this thesis, I propose a deep learning method that can simulate such brain ageing progression. Specifically, longitudinal brain data are not easy to acquire; if some exist, they only cover several years. Thus, the proposed method focuses on learning subject-specific brain ageing progression without training on longitudinal data. As there are other factors, such as neurodegenerative diseases, that can affect brain ageing, the proposed model also considers health status, i.e. the existence of Alzheimer’s Disease (AD). Furthermore, to evaluate the quality of synthetic aged images, I define several metrics and conducted a series of experiments. Suppose we have a pre-trained deep generative model and a downstream tasks model, say a classifier. One question is how to make the best of the generative model to improve the performance of the classifier. In this thesis, I propose a simple procedure that can discover the ‘weakness’ of the classifier and guide the generator to synthesise counterfactuals (synthetic data) that are hard for the classifier. The proposed procedure constructs an adversarial game between generative factors of the generator and the classifier. We demonstrate the effectiveness of this proposed procedure through a series of experiments. Furthermore, we consider the application of generative models in a continual learning context and investigate the usefulness of them to alleviate spurious correlation. This thesis creates new avenues for further research in the area of medical image synthesis and how to utilise the medical generative models, which we believe could be important for future studies in medical image analysis with deep learning