Personalization of cardiac models involves the optimization of organ tissue properties that vary spatially over the non-Euclidean geometry model of the heart. To represent the high-dimensional (HD) unknown of tissue properties, most existing works rely on a low-dimensional (LD) partitioning of the geometrical model. While this exploits the geometry of the heart, it is of limited expressiveness to allow partitioning that is small enough for effective optimization. Recently, a variational auto-encoder (VAE) was utilized as a more expressive generative model to embed the HD optimization into the LD latent space. Its Euclidean nature, however, neglects the rich geometrical information in the heart. In this paper, we present a novel graph convolutional VAE to allow generative modeling of non-Euclidean data, and utilize it to embed Bayesian optimization of large graphs into a small latent space. This approach bridges the gap of previous works by introducing an expressive generative model that is able to incorporate the knowledge of spatial proximity and hierarchical compositionality of the underlying geometry. It further allows transferring of the learned features across different geometries, which was not possible with a regular VAE. We demonstrate these benefits of the presented method in synthetic and real data experiments of estimating tissue excitability in a cardiac electrophysiological model.

The estimation of patient-specific tissue properties in the form of model parameters is important for personalized physiological models. However, these tissue properties are spatially varying across the underlying anatomical model, presenting a significance challenge of high-dimensional (HD) optimization at the presence of limited measurement data. A common solution to reduce the dimension of the parameter space is to explicitly partition the anatomical mesh, either into a fixed small number of segments or a multi-scale hierarchy. This anatomy-based reduction of parameter space presents a fundamental bottleneck to parameter estimation, resulting in solutions that are either too low in resolution to reflect tissue heterogeneity, or too high in dimension to be reliably estimated within feasible computation. In this paper, we present a novel concept that embeds a generative variational auto-encoder (VAE) into the objective function of Bayesian optimization, providing an implicit low-dimensional (LD) search space that represents the generative code of the HD spatially-varying tissue properties. In addition, the VAE-encoded knowledge about the generative code is further used to guide the exploration of the search space. The presented method is applied to estimating tissue excitability in a cardiac electrophysiological model. Synthetic and real-data experiments demonstrate its ability to improve the accuracy of parameter estimation with more than 10x gain in efficiency.

To improve the ability of VAE to disentangle in the latent space, existing works mostly focus on enforcing independence among the learned latent factors. However, the ability of these models to disentangle often decreases as the complexity of the generative factors increases. In this paper, we investigate the little-explored effect of the modeling capacity of a posterior density on the disentangling ability of the VAE. We note that the independence within and the complexity of the latent density are two different properties we constrain when regularizing the posterior density: while the former promotes the disentangling ability of VAE, the latter -- if overly limited -- creates an unnecessary competition with the data reconstruction objective in VAE. Therefore, if we preserve the independence but allow richer modeling capacity in the posterior density, we will lift this competition and thereby allow improved independence and data reconstruction at the same time. We investigate this theoretical intuition with a VAE that utilizes a non-parametric latent factor model, the Indian Buffet Process (IBP), as a latent density that is able to grow with the complexity of the data. Across three widely-used benchmark data sets and two clinical data sets little explored for disentangled learning, we qualitatively and quantitatively demonstrated the improved disentangling performance of IBP-VAE over the state of the art. In the latter two clinical data sets riddled with complex factors of variations, we further demonstrated that unsupervised disentangling of nuisance factors via IBP-VAE -- when combined with a supervised objective -- can not only improve task accuracy in comparison to relevant supervised deep architectures but also facilitate knowledge discovery related to task decision-making. A shorter version of this work will appear in the ICDM 2019 conference proceedings.

The success of deep learning in medical imaging is mostly achieved at the cost of a large labeled data set. Semi-supervised learning (SSL) provides a promising solution by leveraging the structure of unlabeled data to improve learning from a small set of labeled data. Self-ensembling is a simple approach used in SSL to encourage consensus among ensemble predictions of unknown labels, improving generalization of the model by making it more insensitive to the latent space. Currently, such an ensemble is obtained by randomization such as dropout regularization and random data augmentation. In this work, we hypothesize -- from the generalization perspective -- that self-ensembling can be improved by exploiting the stochasticity of a disentangled latent space. To this end, we present a stacked SSL model that utilizes unsupervised disentangled representation learning as the stochastic embedding for self-ensembling. We evaluate the presented model for multi-label classification using chest X-ray images, demonstrating its improved performance over related SSL models as well as the interpretability of its disentangled representations.

Noninvasive reconstruction of cardiac transmembrane potential (TMP) from surface electrocardiograms (ECG) involves an ill-posed inverse problem. Model-constrained regularization is powerful for incorporating rich physiological knowledge about spatiotemporal TMP dynamics. These models are controlled by high-dimensional physical parameters which, if fixed, can introduce model errors and reduce the accuracy of TMP reconstruction. Simultaneous adaptation of these parameters during TMP reconstruction, however, is difficult due to their high dimensionality. We introduce a novel model-constrained inference framework that replaces conventional physiological models with a deep generative model trained to generate TMP sequences from low-dimensional generative factors. Using a variational auto-encoder (VAE) with long short-term memory (LSTM) networks, we train the VAE decoder to learn the conditional likelihood of TMP, while the encoder learns the prior distribution of generative factors. These two components allow us to develop an efficient algorithm to simultaneously infer the generative factors and TMP signals from ECG data. Synthetic and real-data experiments demonstrate that the presented method significantly improve the accuracy of TMP reconstruction compared with methods constrained by conventional physiological models or without physiological constraints.

Deep learning networks have shown state-of-the-art performance in many image reconstruction problems. However, it is not well understood what properties of representation and learning may improve the generalization ability of the network. In this paper, we propose that the generalization ability of an encoder-decoder network for inverse reconstruction can be improved in two means. First, drawing from analytical learning theory, we theoretically show that a stochastic latent space will improve the ability of a network to generalize to test data outside the training distribution. Second, following the information bottleneck principle, we show that a latent representation minimally informative of the input data will help a network generalize to unseen input variations that are irrelevant to the output reconstruction. Therefore, we present a sequence image reconstruction network optimized by a variational approximation of the information bottleneck principle with stochastic latent space. In the application setting of reconstructing the sequence of cardiac transmembrane potential from bodysurface potential, we assess the two types of generalization abilities of the presented network against its deterministic counterpart. The results demonstrate that the generalization ability of an inverse reconstruction network can be improved by stochasticity as well as the information bottleneck.

While deep representation learning has become increasingly capable of separating task-relevant representations from other confounding factors in the data, two significant challenges remain. First, there is often an unknown and potentially infinite number of confounding factors coinciding in the data. Second, not all of these factors are readily observable. In this paper, we present a deep conditional generative model that learns to disentangle a task-relevant representation from an unknown number of confounding factors that may grow infinitely. This is achieved by marrying the representational power of deep generative models with Bayesian non-parametric factor models, where a supervised deterministic encoder learns task-related representation and a probabilistic encoder with an Indian Buffet Process (IBP) learns the unknown number of unobservable confounding factors. We tested the presented model in two datasets: a handwritten digit dataset (MNIST) augmented with colored digits and a clinical ECG dataset with significant inter-subject variations and augmented with signal artifacts. These diverse data sets highlighted the ability of the presented model to grow with the complexity of the data and identify the absence or presence of unobserved confounding factors.

Deep learning models have shown state-of-the-art performance in many inverse reconstruction problems. However, it is not well understood what properties of the latent representation may improve the generalization ability of the network. Furthermore, limited models have been presented for inverse reconstructions over time sequences. In this paper, we study the generalization ability of a sequence encoder decoder model for solving inverse reconstructions on time sequences. Our central hypothesis is that the generalization ability of the network can be improved by 1) constrained stochasticity and 2) global aggregation of temporal information in the latent space. First, drawing from analytical learning theory, we theoretically show that a stochastic latent space will lead to an improved generalization ability. Second, we consider an LSTM encoder-decoder architecture that compresses a global latent vector from all last-layer units in the LSTM encoder. This model is compared with alternative LSTM encoder-decoder architectures, each in deterministic and stochastic versions. The results demonstrate that the generalization ability of an inverse reconstruction network can be improved by constrained stochasticity combined with global aggregation of temporal information in the latent space.

The increasing availability of electrocardiogram (ECG) data has motivated the use of data-driven models for automating various clinical tasks based on ECG data. The development of subject-specific models are limited by the cost and difficulty of obtaining sufficient training data for each individual. The alternative of population model, however, faces challenges caused by the significant inter-subject variations within the ECG data. We address this challenge by investigating for the first time the problem of learning representations for clinically-informative variables while disentangling other factors of variations within the ECG data. In this work, we present a conditional variational autoencoder (VAE) to extract the subject-specific adjustment to the ECG data, conditioned on task-specific representations learned from a deterministic encoder. To encourage the representation for inter-subject variations to be independent from the task-specific representation, maximum mean discrepancy is used to match all the moments between the distributions learned by the VAE conditioning on the code from the deterministic encoder. The learning of the task-specific representation is regularized by a weak supervision in the form of contrastive regularization. We apply the proposed method to a novel yet important clinical task of classifying the origin of ventricular tachycardia (VT) into pre-defined segments, demonstrating the efficacy of the proposed method against the standard VAE.

The increasing availability of electrocardiogram (ECG) data has motivated the use of data-driven models for automating various clinical tasks based on ECG data. The development of subject-specific models are limited by the cost and difficulty of obtaining sufficient training data for each individual. The alternative of population model, however, faces challenges caused by the significant inter-subject variations within the ECG data. We address this challenge by investigating for the first time the problem of learning representations for clinically-informative variables while disentangling other factors of variations within the ECG data. In this work, we present a conditional variational autoencoder (VAE) to extract the subject-specific adjustment to the ECG data, conditioned on task-specific representations learned from a deterministic encoder. To encourage the representation for inter-subject variations to be independent from the task-specific representation, maximum mean discrepancy is used to match all the moments between the distributions learned by the VAE conditioning on the code from the deterministic encoder. The learning of the task-specific representation is regularized by a weak supervision in the form of contrastive regularization. We apply the proposed method to a novel yet important clinical task of classifying the origin of ventricular tachycardia (VT) into pre-defined segments, demonstrating the efficacy of the proposed method against the standard VAE.