When the machine does not know measuring uncertainty in deep learning models of medical images

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonRecently, Deep learning (DL), which involves powerful black box predictors, has outperformed human experts in several medical diagnostic problems. However, these methods focus exclusively on improving the accuracy of point predictions without assessing their outputs’ quality and ignore the asymmetric cost involved in different types of misclassification errors. Neural networks also do not deliver confidence in predictions and suffer from over and under confidence, i.e. are not well calibrated. Knowing how much confidence there is in a prediction is essential for gaining clinicians’ trust in the technology. Calibrated uncertainty quantification is a challenging problem as no ground truth is available. To address this, we make two observations: (i) cost-sensitive deep neural networks with Dropweights models better quantify calibrated predictive uncertainty, and (ii) estimated uncertainty with point predictions in Deep Ensembles Bayesian Neural Networks with DropWeights can lead to a more informed decision and improve prediction quality. This dissertation focuses on quantifying uncertainty using concepts from cost-sensitive neural networks, calibration of confidence, and Dropweights ensemble method. First, we show how to improve predictive uncertainty by deep ensembles of neural networks with Dropweights learning an approximate distribution over its weights in medical image segmentation and its application in active learning. Second, we use the Jackknife resampling technique to correct bias in quantified uncertainty in image classification and propose metrics to measure uncertainty performance. The third part of the thesis is motivated by the discrepancy between the model predictive error and the objective in quantified uncertainty when costs for misclassification errors or unbalanced datasets are asymmetric. We develop cost-sensitive modifications of the neural networks in disease detection and propose metrics to measure the quality of quantified uncertainty. Finally, we leverage an adaptive binning strategy to measure uncertainty calibration error that directly corresponds to estimated uncertainty performance and address problematic evaluation methods. We evaluate the effectiveness of the tools on nuclei images segmentation, multi-class Brain MRI image classification, multi-level cell type-specific protein expression prediction in ImmunoHistoChemistry (IHC) images and cost-sensitive classification for Covid-19 detection from X-Rays and CT image dataset. Our approach is thoroughly validated by measuring the quality of uncertainty. It produces an equally good or better result and paves the way for the future that addresses the practical problems at the intersection of deep learning and Bayesian decision theory. In conclusion, our study highlights the opportunities and challenges of the application of estimated uncertainty in deep learning models of medical images, representing the confidence of the model’s prediction, and the uncertainty quality metrics show a significant improvement when using Deep Ensembles Bayesian Neural Networks with DropWeights

Trustworthy clinical AI solutions: a unified review of uncertainty quantification in deep learning models for medical image analysis

The full acceptance of Deep Learning (DL) models in the clinical field is rather low with respect to the quantity of high-performing solutions reported in the literature. Particularly, end users are reluctant to rely on the rough predictions of DL models. Uncertainty quantification methods have been proposed in the literature as a potential response to reduce the rough decision provided by the DL black box and thus increase the interpretability and the acceptability of the result by the final user. In this review, we propose an overview of the existing methods to quantify uncertainty associated to DL predictions. We focus on applications to medical image analysis, which present specific challenges due to the high dimensionality of images and their quality variability, as well as constraints associated to real-life clinical routine. We then discuss the evaluation protocols to validate the relevance of uncertainty estimates. Finally, we highlight the open challenges of uncertainty quantification in the medical field

Efficient Bayesian Uncertainty Estimation for nnU-Net

The self-configuring nnU-Net has achieved leading performance in a large range of medical image segmentation challenges. It is widely considered as the model of choice and a strong baseline for medical image segmentation. However, despite its extraordinary performance, nnU-Net does not supply a measure of uncertainty to indicate its possible failure. This can be problematic for large-scale image segmentation applications, where data are heterogeneous and nnU-Net may fail without notice. In this work, we introduce a novel method to estimate nnU-Net uncertainty for medical image segmentation. We propose a highly effective scheme for posterior sampling of weight space for Bayesian uncertainty estimation. Different from previous baseline methods such as Monte Carlo Dropout and mean-field Bayesian Neural Networks, our proposed method does not require a variational architecture and keeps the original nnU-Net architecture intact, thereby preserving its excellent performance and ease of use. Additionally, we boost the segmentation performance over the original nnU-Net via marginalizing multi-modal posterior models. We applied our method on the public ACDC and M&M datasets of cardiac MRI and demonstrated improved uncertainty estimation over a range of baseline methods. The proposed method further strengthens nnU-Net for medical image segmentation in terms of both segmentation accuracy and quality control

Uncertainty Aware Training to Improve Deep Learning Model Calibration for Classification of Cardiac MR Images

Quantifying uncertainty of predictions has been identified as one way to develop more trustworthy artificial intelligence (AI) models beyond conventional reporting of performance metrics. When considering their role in a clinical decision support setting, AI classification models should ideally avoid confident wrong predictions and maximise the confidence of correct predictions. Models that do this are said to be well-calibrated with regard to confidence. However, relatively little attention has been paid to how to improve calibration when training these models, i.e., to make the training strategy uncertainty-aware. In this work we evaluate three novel uncertainty-aware training strategies comparing against two state-of-the-art approaches. We analyse performance on two different clinical applications: cardiac resynchronisation therapy (CRT) response prediction and coronary artery disease (CAD) diagnosis from cardiac magnetic resonance (CMR) images. The best-performing model in terms of both classification accuracy and the most common calibration measure, expected calibration error (ECE) was the Confidence Weight method, a novel approach that weights the loss of samples to explicitly penalise confident incorrect predictions. The method reduced the ECE by 17% for CRT response prediction and by 22% for CAD diagnosis when compared to a baseline classifier in which no uncertainty-aware strategy was included. In both applications, as well as reducing the ECE there was a slight increase in accuracy from 69% to 70% and 70% to 72% for CRT response prediction and CAD diagnosis respectively. However, our analysis showed a lack of consistency in terms of optimal models when using different calibration measures. This indicates the need for careful consideration of performance metrics when training and selecting models for complex high-risk applications in healthcare

TriadNet: Sampling-free predictive intervals for lesional volume in 3D brain MR images

The volume of a brain lesion (e.g. infarct or tumor) is a powerful indicator of patient prognosis and can be used to guide the therapeutic strategy. Lesional volume estimation is usually performed by segmentation with deep convolutional neural networks (CNN), currently the state-of-the-art approach. However, to date, few work has been done to equip volume segmentation tools with adequate quantitative predictive intervals, which can hinder their usefulness and acceptation in clinical practice. In this work, we propose TriadNet, a segmentation approach relying on a multi-head CNN architecture, which provides both the lesion volumes and the associated predictive intervals simultaneously, in less than a second. We demonstrate its superiority over other solutions on BraTS 2021, a large-scale MRI glioblastoma image database.Comment: Accepted for presentation at the Workshop on Uncertainty for Safe Utilization of Machine Learning in Medical Imaging (UNSURE) at MICCAI 202