Learning Disentangled Representations in the Imaging Domain

Disentangled representation learning has been proposed as an approach to learning general representations even in the absence of, or with limited, supervision. A good general representation can be fine-tuned for new target tasks using modest amounts of data, or used directly in unseen domains achieving remarkable performance in the corresponding task. This alleviation of the data and annotation requirements offers tantalising prospects for applications in computer vision and healthcare. In this tutorial paper, we motivate the need for disentangled representations, present key theory, and detail practical building blocks and criteria for learning such representations. We discuss applications in medical imaging and computer vision emphasising choices made in exemplar key works. We conclude by presenting remaining challenges and opportunities.Comment: Submitted. This paper follows a tutorial style but also surveys a considerable (more than 200 citations) number of work

Semi-supervised Pathology Segmentation with Disentangled Representations.

Automated pathology segmentation remains a valuable diagnostic tool in clinical practice. However, collecting training data is challenging. Semi-supervised approaches by combining labelled and unlabelled data can offer a solution to data scarcity. An approach to semi-supervised learning relies on reconstruction objectives (as self-supervision objectives) that learns in a joint fashion suitable representations for the task. Here, we propose Anatomy-Pathology Disentanglement Network (APD-Net), a pathology segmentation model that attempts to learn jointly for the first time: disentanglement of anatomy, modality, and pathology. The model is trained in a semi-supervised fashion with new reconstruction losses directly aiming to improve pathology segmentation with limited annotations. In addition, a joint optimization strategy is proposed to fully take advantage of the available annotations. We evaluate our methods with two private cardiac infarction segmentation datasets with LGE-MRI scans. APD-Net can perform pathology segmentation with few annotations, maintain performance with different amounts of supervision, and outperform related deep learning methods

Deep learning for unsupervised domain adaptation in medical imaging: Recent advancements and future perspectives

Deep learning has demonstrated remarkable performance across various tasks in medical imaging. However, these approaches primarily focus on supervised learning, assuming that the training and testing data are drawn from the same distribution. Unfortunately, this assumption may not always hold true in practice. To address these issues, unsupervised domain adaptation (UDA) techniques have been developed to transfer knowledge from a labeled domain to a related but unlabeled domain. In recent years, significant advancements have been made in UDA, resulting in a wide range of methodologies, including feature alignment, image translation, self-supervision, and disentangled representation methods, among others. In this paper, we provide a comprehensive literature review of recent deep UDA approaches in medical imaging from a technical perspective. Specifically, we categorize current UDA research in medical imaging into six groups and further divide them into finer subcategories based on the different tasks they perform. We also discuss the respective datasets used in the studies to assess the divergence between the different domains. Finally, we discuss emerging areas and provide insights and discussions on future research directions to conclude this survey.Comment: Under Revie

Interpretable Diabetic Retinopathy Diagnosis based on Biomarker Activation Map

Deep learning classifiers provide the most accurate means of automatically diagnosing diabetic retinopathy (DR) based on optical coherence tomography (OCT) and its angiography (OCTA). The power of these models is attributable in part to the inclusion of hidden layers that provide the complexity required to achieve a desired task. However, hidden layers also render algorithm outputs difficult to interpret. Here we introduce a novel biomarker activation map (BAM) framework based on generative adversarial learning that allows clinicians to verify and understand classifiers decision-making. A data set including 456 macular scans were graded as non-referable or referable DR based on current clinical standards. A DR classifier that was used to evaluate our BAM was first trained based on this data set. The BAM generation framework was designed by combing two U-shaped generators to provide meaningful interpretability to this classifier. The main generator was trained to take referable scans as input and produce an output that would be classified by the classifier as non-referable. The BAM is then constructed as the difference image between the output and input of the main generator. To ensure that the BAM only highlights classifier-utilized biomarkers an assistant generator was trained to do the opposite, producing scans that would be classified as referable by the classifier from non-referable scans. The generated BAMs highlighted known pathologic features including nonperfusion area and retinal fluid. A fully interpretable classifier based on these highlights could help clinicians better utilize and verify automated DR diagnosis.Comment: 12 pages, 8 figure

Multimodal and disentangled representation learning for medical image analysis

Automated medical image analysis is a growing research field with various applications in modern healthcare. Furthermore, a multitude of imaging techniques (or modalities) have been developed, such as Magnetic Resonance (MR) and Computed Tomography (CT), to attenuate different organ characteristics. Research on image analysis is predominately driven by deep learning methods due to their demonstrated performance. In this thesis, we argue that their success and generalisation relies on learning good latent representations. We propose methods for learning spatial representations that are suitable for medical image data, and can combine information coming from different modalities. Specifically, we aim to improve cardiac MR segmentation, a challenging task due to varied images and limited expert annotations, by considering complementary information present in (potentially unaligned) images of other modalities. In order to evaluate the benefit of multimodal learning, we initially consider a synthesis task on spatially aligned multimodal brain MR images. We propose a deep network of multiple encoders and decoders, which we demonstrate outperforms existing approaches. The encoders (one per input modality) map the multimodal images into modality invariant spatial feature maps. Common and unique information is combined into a fused representation, that is robust to missing modalities, and can be decoded into synthetic images of the target modalities. Different experimental settings demonstrate the benefit of multimodal over unimodal synthesis, although input and output image pairs are required for training. The need for paired images can be overcome with the cycle consistency principle, which we use in conjunction with adversarial training to transform images from one modality (e.g. MR) to images in another (e.g. CT). This is useful especially in cardiac datasets, where different spatial and temporal resolutions make image pairing difficult, if not impossible. Segmentation can also be considered as a form of image synthesis, if one modality consists of semantic maps. We consider the task of extracting segmentation masks for cardiac MR images, and aim to overcome the challenge of limited annotations, by taking into account unannanotated images which are commonly ignored. We achieve this by defining suitable latent spaces, which represent the underlying anatomies (spatial latent variable), as well as the imaging characteristics (non-spatial latent variable). Anatomical information is required for tasks such as segmentation and regression, whereas imaging information can capture variability in intensity characteristics for example due to different scanners. We propose two models that disentangle cardiac images at different levels: the first extracts the myocardium from the surrounding information, whereas the second fully separates the anatomical from the imaging characteristics. Experimental analysis confirms the utility of disentangled representations in semi-supervised segmentation, and in regression of cardiac indices, while maintaining robustness to intensity variations such as the ones induced by different modalities. Finally, our prior research is aggregated into one framework that encodes multimodal images into disentangled anatomical and imaging factors. Several challenges of multimodal cardiac imaging, such as input misalignments and the lack of expert annotations, are successfully handled in the shared anatomy space. Furthermore, we demonstrate that this approach can be used to combine complementary anatomical information for the purpose of multimodal segmentation. This can be achieved even when no annotations are provided for one of the modalities. This thesis creates new avenues for further research in the area of multimodal and disentangled learning with spatial representations, which we believe are key to more generalised deep learning solutions in healthcare

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

Towards generalizable machine learning models for computer-aided diagnosis in medicine

Hidden stratification represents a phenomenon in which a training dataset contains unlabeled (hidden) subsets of cases that may affect machine learning model performance. Machine learning models that ignore the hidden stratification phenomenon--despite promising overall performance measured as accuracy and sensitivity--often fail at predicting the low prevalence cases, but those cases remain important. In the medical domain, patients with diseases are often less common than healthy patients, and a misdiagnosis of a patient with a disease can have significant clinical impacts. Therefore, to build a robust and trustworthy CAD system and a reliable treatment effect prediction model, we cannot only pursue machine learning models with high overall accuracy, but we also need to discover any hidden stratification in the data and evaluate the proposing machine learning models with respect to both overall performance and the performance on certain subsets (groups) of the data, such as the ‘worst group’. In this study, I investigated three approaches for data stratification: a novel algorithmic deep learning (DL) approach that learns similarities among cases and two schema completion approaches that utilize domain expert knowledge. I further proposed an innovative way to integrate the discovered latent groups into the loss functions of DL models to allow for better model generalizability under the domain shift scenario caused by the data heterogeneity. My results on lung nodule Computed Tomography (CT) images and breast cancer histopathology images demonstrate that learning homogeneous groups within heterogeneous data significantly improves the performance of the computer-aided diagnosis (CAD) system, particularly for low-prevalence or worst-performing cases. This study emphasizes the importance of discovering and learning the latent stratification within the data, as it is a critical step towards building ML models that are generalizable and reliable. Ultimately, this discovery can have a profound impact on clinical decision-making, particularly for low-prevalence cases