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

Handling Label Uncertainty on the Example of Automatic Detection of Shepherd's Crook RCA in Coronary CT Angiography

Coronary artery disease (CAD) is often treated minimally invasively with a catheter being inserted into the diseased coronary vessel. If a patient exhibits a Shepherd's Crook (SC) Right Coronary Artery (RCA) - an anatomical norm variant of the coronary vasculature - the complexity of this procedure is increased. Automated reporting of this variant from coronary CT angiography screening would ease prior risk assessment. We propose a 1D convolutional neural network which leverages a sequence of residual dilated convolutions to automatically determine this norm variant from a prior extracted vessel centerline. As the SC RCA is not clearly defined with respect to concrete measurements, labeling also includes qualitative aspects. Therefore, 4.23% samples in our dataset of 519 RCA centerlines were labeled as unsure SC RCAs, with 5.97% being labeled as sure SC RCAs. We explore measures to handle this label uncertainty, namely global/model-wise random assignment, exclusion, and soft label assignment. Furthermore, we evaluate how this uncertainty can be leveraged for the determination of a rejection class. With our best configuration, we reach an area under the receiver operating characteristic curve (AUC) of 0.938 on confident labels. Moreover, we observe an increase of up to 0.020 AUC when rejecting 10% of the data and leveraging the labeling uncertainty information in the exclusion process.Comment: Accepted at ISBI 202

Improving Image Classification of Knee Radiographs: An Automated Image Labeling Approach

Large numbers of radiographic images are available in knee radiology practices which could be used for training of deep learning models for diagnosis of knee abnormalities. However, those images do not typically contain readily available labels due to limitations of human annotations. The purpose of our study was to develop an automated labeling approach that improves the image classification model to distinguish normal knee images from those with abnormalities or prior arthroplasty. The automated labeler was trained on a small set of labeled data to automatically label a much larger set of unlabeled data, further improving the image classification performance for knee radiographic diagnosis. We developed our approach using 7,382 patients and validated it on a separate set of 637 patients. The final image classification model, trained using both manually labeled and pseudo-labeled data, had the higher weighted average AUC (WAUC: 0.903) value and higher AUC-ROC values among all classes (normal AUC-ROC: 0.894; abnormal AUC-ROC: 0.896, arthroplasty AUC-ROC: 0.990) compared to the baseline model (WAUC=0.857; normal AUC-ROC: 0.842; abnormal AUC-ROC: 0.848, arthroplasty AUC-ROC: 0.987), trained using only manually labeled data. DeLong tests show that the improvement is significant on normal (p-value<0.002) and abnormal (p-value<0.001) images. Our findings demonstrated that the proposed automated labeling approach significantly improves the performance of image classification for radiographic knee diagnosis, allowing for facilitating patient care and curation of large knee datasets.Comment: This is the preprint versio

Interpretable Medical Imagery Diagnosis with Self-Attentive Transformers: A Review of Explainable AI for Health Care

Recent advancements in artificial intelligence (AI) have facilitated its widespread adoption in primary medical services, addressing the demand-supply imbalance in healthcare. Vision Transformers (ViT) have emerged as state-of-the-art computer vision models, benefiting from self-attention modules. However, compared to traditional machine-learning approaches, deep-learning models are complex and are often treated as a "black box" that can cause uncertainty regarding how they operate. Explainable Artificial Intelligence (XAI) refers to methods that explain and interpret machine learning models' inner workings and how they come to decisions, which is especially important in the medical domain to guide the healthcare decision-making process. This review summarises recent ViT advancements and interpretative approaches to understanding the decision-making process of ViT, enabling transparency in medical diagnosis applications

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