Challenging Current Semi-Supervised Anomaly Segmentation Methods for Brain MRI

In this work, we tackle the problem of Semi-Supervised Anomaly Segmentation (SAS) in Magnetic Resonance Images (MRI) of the brain, which is the task of automatically identifying pathologies in brain images. Our work challenges the effectiveness of current Machine Learning (ML) approaches in this application domain by showing that thresholding Fluid-attenuated inversion recovery (FLAIR) MR scans provides better anomaly segmentation maps than several different ML-based anomaly detection models. Specifically, our method achieves better Dice similarity coefficients and Precision-Recall curves than the competitors on various popular evaluation data sets for the segmentation of tumors and multiple sclerosis lesions.Comment: 10 pages, 4 figures, accepted to the MICCAI 2021 BrainLes Worksho

The role of noise in denoising models for anomaly detection in medical images

Pathological brain lesions exhibit diverse appearance in brain images, in terms of intensity, texture, shape, size, and location. Comprehensive sets of data and annotations are difficult to acquire. Therefore, unsupervised anomaly detection approaches have been proposed using only normal data for training, with the aim of detecting outlier anomalous voxels at test time. Denoising methods, for instance classical denoising autoencoders (DAEs) and more recently emerging diffusion models, are a promising approach, however naive application of pixelwise noise leads to poor anomaly detection performance. We show that optimization of the spatial resolution and magnitude of the noise improves the performance of different model training regimes, with similar noise parameter adjustments giving good performance for both DAEs and diffusion models. Visual inspection of the reconstructions suggests that the training noise influences the trade-off between the extent of the detail that is reconstructed and the extent of erasure of anomalies, both of which contribute to better anomaly detection performance. We validate our findings on two real-world datasets (tumor detection in brain MRI and hemorrhage/ischemia/tumor detection in brain CT), showing good detection on diverse anomaly appearances. Overall, we find that a DAE trained with coarse noise is a fast and simple method that gives state-of-the-art accuracy. Diffusion models applied to anomaly detection are as yet in their infancy and provide a promising avenue for further research.Comment: Submitted to Medical Image Analysis special issue for MIDL 202

Anomaly detection in brain imaging

Modern healthcare systems employ a variety of medical imaging technologies, such as X-ray, MRI and CT, to improve patient outcomes, time and cost efficiency, and enable further research. Artificial intelligence and machine learning have shown promise in enhancing medical image analysis systems, leading to a proliferation of research in the field. However, many proposed approaches, such as image classification or segmentation, require large amounts of professional annotations, which are costly and time-consuming to acquire. Anomaly detection is an approach that requires less manual effort and thus can benefit from scaling to datasets of ever-increasing size. In this thesis, we focus on anomaly localisation for pathology detection with models trained on healthy data without dense annotations. We identify two key weaknesses of current image reconstruction-based anomaly detection methods: poor image reconstruction and overdependency on pixel/voxel intensity for identification of anomalies. To address these weaknesses, we develop two novel methods: denoising autoencoder and context-tolocal feature matching, respectively. Finally, we apply both methods to in-hospital data in collaboration with NHS Greater Glasgow and Clyde. We discuss the issues of data collection, filtering, processing, and evaluation arising in applying anomaly detection methods beyond curated datasets. We design and run a clinical evaluation contrasting our proposed methods and revealing difficulties in gauging performance of anomaly detection systems. Our findings suggest that further research is needed to fully realise the potential of anomaly detection for practical medical imaging applications. Specifically, we suggest investigating anomaly detection methods that are able to take advantage of more types of supervision (e.g. weak-labels), more context (e.g. prior scans) and make structured end-to-end predictions (e.g. bounding boxes)

Exploring variability in medical imaging

Although recent successes of deep learning and novel machine learning techniques improved the perfor- mance of classification and (anomaly) detection in computer vision problems, the application of these methods in medical imaging pipeline remains a very challenging task. One of the main reasons for this is the amount of variability that is encountered and encapsulated in human anatomy and subsequently reflected in medical images. This fundamental factor impacts most stages in modern medical imaging processing pipelines. Variability of human anatomy makes it virtually impossible to build large datasets for each disease with labels and annotation for fully supervised machine learning. An efficient way to cope with this is to try and learn only from normal samples. Such data is much easier to collect. A case study of such an automatic anomaly detection system based on normative learning is presented in this work. We present a framework for detecting fetal cardiac anomalies during ultrasound screening using generative models, which are trained only utilising normal/healthy subjects. However, despite the significant improvement in automatic abnormality detection systems, clinical routine continues to rely exclusively on the contribution of overburdened medical experts to diagnosis and localise abnormalities. Integrating human expert knowledge into the medical imaging processing pipeline entails uncertainty which is mainly correlated with inter-observer variability. From the per- spective of building an automated medical imaging system, it is still an open issue, to what extent this kind of variability and the resulting uncertainty are introduced during the training of a model and how it affects the final performance of the task. Consequently, it is very important to explore the effect of inter-observer variability both, on the reliable estimation of model’s uncertainty, as well as on the model’s performance in a specific machine learning task. A thorough investigation of this issue is presented in this work by leveraging automated estimates for machine learning model uncertainty, inter-observer variability and segmentation task performance in lung CT scan images. Finally, a presentation of an overview of the existing anomaly detection methods in medical imaging was attempted. This state-of-the-art survey includes both conventional pattern recognition methods and deep learning based methods. It is one of the first literature surveys attempted in the specific research area.Open Acces

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

Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries

This two-volume set LNCS 12962 and 12963 constitutes the thoroughly refereed proceedings of the 7th International MICCAI Brainlesion Workshop, BrainLes 2021, as well as the RSNA-ASNR-MICCAI Brain Tumor Segmentation (BraTS) Challenge, the Federated Tumor Segmentation (FeTS) Challenge, the Cross-Modality Domain Adaptation (CrossMoDA) Challenge, and the challenge on Quantification of Uncertainties in Biomedical Image Quantification (QUBIQ). These were held jointly at the 23rd Medical Image Computing for Computer Assisted Intervention Conference, MICCAI 2020, in September 2021. The 91 revised papers presented in these volumes were selected form 151 submissions. Due to COVID-19 pandemic the conference was held virtually. This is an open access book

Learning Distributions of Functions on a Continuous Time Domain

This work presents several contributions on the topic of learning representations of function spaces, as well as on learning the dynamics of glioma growth as a particular instance thereof. We begin with two preparatory efforts, showing how expert knowledge can be leveraged efficiently in an interactive segmentation context, and presenting a proof of concept for inferring non-deterministic glioma growth patterns purely from data. The remainder of our work builds upon the framework of Neural Processes. We show how these models represent function spaces and discover that they can implicitly decompose the space into different frequency components, not unlike a Fourier transform. In this context we derive an upper bound on the maximum signal frequency Neural Processes can represent and show how to control the learned representations to only contain certain frequencies. We continue with an improvement of a more recent addition to the Neural Process family called ConvCNP, which we combine with a Gaussian Process to make it non-deterministic and to improve generalization. Finally, we show how to perform segmentation in the Neural Process framework by extending a typical segmentation architecture with spatio-temporal attention. The resulting model can interpolate complex spatial variations of segmentations over time and, applied to glioma growth, it is able to represent multiple temporally consistent growth trajectories, exhibiting realistic and diverse spatial growth patterns

Advanced machine learning methods for oncological image analysis

Cancer is a major public health problem, accounting for an estimated 10 million deaths worldwide in 2020 alone. Rapid advances in the field of image acquisition and hardware development over the past three decades have resulted in the development of modern medical imaging modalities that can capture high-resolution anatomical, physiological, functional, and metabolic quantitative information from cancerous organs. Therefore, the applications of medical imaging have become increasingly crucial in the clinical routines of oncology, providing screening, diagnosis, treatment monitoring, and non/minimally- invasive evaluation of disease prognosis. The essential need for medical images, however, has resulted in the acquisition of a tremendous number of imaging scans. Considering the growing role of medical imaging data on one side and the challenges of manually examining such an abundance of data on the other side, the development of computerized tools to automatically or semi-automatically examine the image data has attracted considerable interest. Hence, a variety of machine learning tools have been developed for oncological image analysis, aiming to assist clinicians with repetitive tasks in their workflow. This thesis aims to contribute to the field of oncological image analysis by proposing new ways of quantifying tumor characteristics from medical image data. Specifically, this thesis consists of six studies, the first two of which focus on introducing novel methods for tumor segmentation. The last four studies aim to develop quantitative imaging biomarkers for cancer diagnosis and prognosis. The main objective of Study I is to develop a deep learning pipeline capable of capturing the appearance of lung pathologies, including lung tumors, and integrating this pipeline into the segmentation networks to leverage the segmentation accuracy. The proposed pipeline was tested on several comprehensive datasets, and the numerical quantifications show the superiority of the proposed prior-aware DL framework compared to the state of the art. Study II aims to address a crucial challenge faced by supervised segmentation models: dependency on the large-scale labeled dataset. In this study, an unsupervised segmentation approach is proposed based on the concept of image inpainting to segment lung and head- neck tumors in images from single and multiple modalities. The proposed autoinpainting pipeline shows great potential in synthesizing high-quality tumor-free images and outperforms a family of well-established unsupervised models in terms of segmentation accuracy. Studies III and IV aim to automatically discriminate the benign from the malignant pulmonary nodules by analyzing the low-dose computed tomography (LDCT) scans. In Study III, a dual-pathway deep classification framework is proposed to simultaneously take into account the local intra-nodule heterogeneities and the global contextual information. Study IV seeks to compare the discriminative power of a series of carefully selected conventional radiomics methods, end-to-end Deep Learning (DL) models, and deep features-based radiomics analysis on the same dataset. The numerical analyses show the potential of fusing the learned deep features into radiomic features for boosting the classification power. Study V focuses on the early assessment of lung tumor response to the applied treatments by proposing a novel feature set that can be interpreted physiologically. This feature set was employed to quantify the changes in the tumor characteristics from longitudinal PET-CT scans in order to predict the overall survival status of the patients two years after the last session of treatments. The discriminative power of the introduced imaging biomarkers was compared against the conventional radiomics, and the quantitative evaluations verified the superiority of the proposed feature set. Whereas Study V focuses on a binary survival prediction task, Study VI addresses the prediction of survival rate in patients diagnosed with lung and head-neck cancer by investigating the potential of spherical convolutional neural networks and comparing their performance against other types of features, including radiomics. While comparable results were achieved in intra- dataset analyses, the proposed spherical-based features show more predictive power in inter-dataset analyses. In summary, the six studies incorporate different imaging modalities and a wide range of image processing and machine-learning techniques in the methods developed for the quantitative assessment of tumor characteristics and contribute to the essential procedures of cancer diagnosis and prognosis