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Register a new userLearning Interpretable Anatomical Features Through Deep Generative Models: Application to Cardiac Remodeling
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Added by
Carlo Biffi
Publication date
2018
fields
Informatics Engineering
and research's language is
English
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Alterations in the geometry and function of the heart define well-established causes of cardiovascular disease. However, current approaches to the diagnosis of cardiovascular diseases often rely on subjective human assessment as well as manual analysis of medical images. Both factors limit the sensitivity in quantifying complex structural and functional phenotypes. Deep learning approaches have recently achieved success for tasks such as classification or segmentation of medical images, but lack interpretability in the feature extraction and decision processes, limiting their value in clinical diagnosis. In this work, we propose a 3D convolutional generative model for automatic classification of images from patients with cardiac diseases associated with structural remodeling. The model leverages interpretable task-specific anatomic patterns learned from 3D segmentations. It further allows to visualise and quantify the learned pathology-specific remodeling patterns in the original input space of the images. This approach yields high accuracy in the categorization of healthy and hypertrophic cardiomyopathy subjects when tested on unseen MR images from our own multi-centre dataset (100%) as well on the ACDC MICCAI 2017 dataset (90%). We believe that the proposed deep learning approach is a promising step towards the development of interpretable classifiers for the medical imaging domain, which may help clinicians to improve diagnostic accuracy and enhance patient risk-stratification.
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Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimers disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging.
Advances in deep learning (DL) have resulted in impressive accuracy in some medical image classification tasks, but often deep models lack interpretability. The ability of these models to explain their decisions is important for fostering clinical trust and facilitating clinical translation. Furthermore, for many problems in medicine there is a wealth of existing clinical knowledge to draw upon, which may be useful in generating explanations, but it is not obvious how this knowledge can be encoded into DL models - most models are learnt either from scratch or using transfer learning from a different domain. In this paper we address both of these issues. We propose a novel DL framework for image-based classification based on a variational autoencoder (VAE). The framework allows prediction of the output of interest from the latent space of the autoencoder, as well as visualisation (in the image domain) of the effects of crossing the decision boundary, thus enhancing the interpretability of the classifier. Our key contribution is that the VAE disentangles the latent space based on `explanations drawn from existing clinical knowledge. The framework can predict outputs as well as explanations for these outputs, and also raises the possibility of discovering new biomarkers that are separate (or disentangled) from the existing knowledge. We demonstrate our framework on the problem of predicting response of patients with cardiomyopathy to cardiac resynchronization therapy (CRT) from cine cardiac magnetic resonance images. The sensitivity and specificity of the proposed model on the task of CRT response prediction are 88.43% and 84.39% respectively, and we showcase the potential of our model in enhancing understanding of the factors contributing to CRT response.
In real-world applications, it is often expensive and time-consuming to obtain labeled examples. In such cases, knowledge transfer from related domains, where labels are abundant, could greatly reduce the need for extensive labeling efforts. In this scenario, transfer learning comes in hand. In this paper, we propose Deep Variational Transfer (DVT), a variational autoencoder that transfers knowledge across domains using a shared latent Gaussian mixture model. Thanks to the combination of a semi-supervised ELBO and parameters sharing across domains, we are able to simultaneously: (i) align all supervised examples of the same class into the same latent Gaussian Mixture component, independently from their domain; (ii) predict the class of unsupervised examples from different domains and use them to better model the occurring shifts. We perform tests on MNIST and USPS digits datasets, showing DVTs ability to perform transfer learning across heterogeneous datasets. Additionally, we present DVTs top classification performances on the MNIST semi-supervised learning challenge. We further validate DVT on a astronomical datasets. DVT achieves states-of-the-art classification performances, transferring knowledge across real stars surveys datasets, EROS, MACHO and HiTS, . In the worst performance, we double the achieved F1-score for rare classes. These experiments show DVTs ability to tackle all major challenges posed by transfer learning: different covariate distributions, different and highly imbalanced class distributions and different feature spaces.
Neural networks are proven to be remarkably successful for classification and diagnosis in medical applications. However, the ambiguity in the decision-making process and the interpretability of the learned features is a matter of concern. In this work, we propose a method for improving the feature interpretability of neural network classifiers. Initially, we propose a baseline convolutional neural network with state of the art performance in terms of accuracy and weakly supervised localization. Subsequently, the loss is modified to integrate robustness to adversarial examples into the training process. In this work, feature interpretability is quantified via evaluating the weakly supervised localization using the ground truth bounding boxes. Interpretability is also visually assessed using class activation maps and saliency maps. The method is applied to NIH ChestX-ray14, the largest publicly available chest x-rays dataset. We demonstrate that the adversarially robust optimization paradigm improves feature interpretability both quantitatively and visually.
Quantum physics experiments produce interesting phenomena such as interference or entanglement, which is a core property of numerous future quantum technologies. The complex relationship between a quantum experiments structure and its entanglement properties is essential to fundamental research in quantum optics but is difficult to intuitively understand. We present the first deep generative model of quantum optics experiments where a variational autoencoder (QOVAE) is trained on a dataset of experimental setups. In a series of computational experiments, we investigate the learned representation of the QOVAE and its internal understanding of the quantum optics world. We demonstrate that the QOVAE learns an intrepretable representation of quantum optics experiments and the relationship between experiment structure and entanglement. We show the QOVAE is able to generate novel experiments for highly entangled quantum states with specific distributions that match its training data. Importantly, we are able to fully interpret how the QOVAE structures its latent space, finding curious patterns that we can entirely explain in terms of quantum physics. The results demonstrate how we can successfully use and understand the internal representations of deep generative models in a complex scientific domain. The QOVAE and the insights from our investigations can be immediately applied to other physical systems throughout fundamental scientific research.
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