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We present a novel multimodal deep learning framework for cardiac resynchronisation therapy (CRT) response prediction from 2D echocardiography and cardiac magnetic resonance (CMR) data. The proposed method first uses the `nnU-Net segmentation model to extract segmentations of the heart over the full cardiac cycle from the two modalities. Next, a multimodal deep learning classifier is used for CRT response prediction, which combines the latent spaces of the segmentation models of the two modalities. At inference time, this framework can be used with 2D echocardiography data only, whilst taking advantage of the implicit relationship between CMR and echocardiography features learnt from the model. We evaluate our pipeline on a cohort of 50 CRT patients for whom paired echocardiography/CMR data were available, and results show that the proposed multimodal classifier results in a statistically significant improvement in accuracy compared to the baseline approach that uses only 2D echocardiography data. The combination of multimodal data enables CRT response to be predicted with 77.38% accuracy (83.33% sensitivity and 71.43% specificity), which is comparable with the current state-of-the-art in machine learning-based CRT response prediction. Our work represents the first multimodal deep learning approach for CRT response prediction.
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.
Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimising the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimised for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients the predictive accuracy (quantified by Harrells C-index) was significantly higher (p < .0001) for our model C=0.73 (95$%$ CI: 0.68 - 0.78) than the human benchmark of C=0.59 (95$%$ CI: 0.53 - 0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival.
In recent years, convolutional neural networks have demonstrated promising performance in a variety of medical image segmentation tasks. However, when a trained segmentation model is deployed into the real clinical world, the model may not perform optimally. A major challenge is the potential poor-quality segmentations generated due to degraded image quality or domain shift issues. There is a timely need to develop an automated quality control method that can detect poor segmentations and feedback to clinicians. Here we propose a novel deep generative model-based framework for quality control of cardiac MRI segmentation. It first learns a manifold of good-quality image-segmentation pairs using a generative model. The quality of a given test segmentation is then assessed by evaluating the difference from its projection onto the good-quality manifold. In particular, the projection is refined through iterative search in the latent space. The proposed method achieves high prediction accuracy on two publicly available cardiac MRI datasets. Moreover, it shows better generalisation ability than traditional regression-based methods. Our approach provides a real-time and model-agnostic quality control for cardiac MRI segmentation, which has the potential to be integrated into clinical image analysis workflows.
Predicting clinical outcome is remarkably important but challenging. Research efforts have been paid on seeking significant biomarkers associated with the therapy response or/and patient survival. However, these biomarkers are generally costly and invasive, and possibly dissatifactory for novel therapy. On the other hand, multi-modal, heterogeneous, unaligned temporal data is continuously generated in clinical practice. This paper aims at a unified deep learning approach to predict patient prognosis and therapy response, with easily accessible data, e.g., radiographics, laboratory and clinical information. Prior arts focus on modeling single data modality, or ignore the temporal changes. Importantly, the clinical time series is asynchronous in practice, i.e., recorded with irregular intervals. In this study, we formalize the prognosis modeling as a multi-modal asynchronous time series classification task, and propose a MIA-Prognosis framework with Measurement, Intervention and Assessment (MIA) information to predict therapy response, where a Simple Temporal Attention (SimTA) module is developed to process the asynchronous time series. Experiments on synthetic dataset validate the superiory of SimTA over standard RNN-based approaches. Furthermore, we experiment the proposed method on an in-house, retrospective dataset of real-world non-small cell lung cancer patients under anti-PD-1 immunotherapy. The proposed method achieves promising performance on predicting the immunotherapy response. Notably, our predictive model could further stratify low-risk and high-risk patients in terms of long-term survival.
Retrospectively gated cine (retro-cine) MRI is the clinical standard for cardiac functional analysis. Deep learning (DL) based methods have been proposed for the reconstruction of highly undersampled MRI data and show superior image quality and magnitude faster reconstruction time than CS-based methods. Nevertheless, it remains unclear whether DL reconstruction is suitable for cardiac function analysis. To address this question, in this study we evaluate and compare the cardiac functional values (EDV, ESV and EF for LV and RV, respectively) obtained from highly accelerated MRI acquisition using DL based reconstruction algorithm (DL-cine) with values from CS-cine and conventional retro-cine. To the best of our knowledge, this is the first work to evaluate the cine MRI with deep learning reconstruction for cardiac function analysis and compare it with other conventional methods. The cardiac functional values obtained from cine MRI with deep learning reconstruction are consistent with values from clinical standard retro-cine MRI.