John L. Sapp

Xiajun Jiang, Zhiyuan Li, Ryan Missel et al.

Clinical adoption of personalized virtual heart simulations faces challenges in model personalization and expensive computation. While an ideal solution is an efficient neural surrogate that at the same time is personalized to an individual subject, the state-of-the-art is either concerned with personalizing an expensive simulation model, or learning an efficient yet generic surrogate. This paper presents a completely new concept to achieve personalized neural surrogates in a single coherent framework of meta-learning (metaPNS). Instead of learning a single neural surrogate, we pursue the process of learning a personalized neural surrogate using a small amount of context data from a subject, in a novel formulation of few-shot generative modeling underpinned by: 1) a set-conditioned neural surrogate for cardiac simulation that, conditioned on subject-specific context data, learns to generate query simulations not included in the context set, and 2) a meta-model of amortized variational inference that learns to condition the neural surrogate via simple feed-forward embedding of context data. As test time, metaPNS delivers a personalized neural surrogate by fast feed-forward embedding of a small and flexible number of data available from an individual, achieving -- for the first time -- personalization and surrogate construction for expensive simulations in one end-to-end learning framework. Synthetic and real-data experiments demonstrated that metaPNS was able to improve personalization and predictive accuracy in comparison to conventionally-optimized cardiac simulation models, at a fraction of computation.

Md Shakil Zaman, Jwala Dhamala, Pradeep Bajracharya et al.

Probabilistic estimation of cardiac electrophysiological model parameters serves an important step towards model personalization and uncertain quantification. The expensive computation associated with these model simulations, however, makes direct Markov Chain Monte Carlo (MCMC) sampling of the posterior probability density function (pdf) of model parameters computationally intensive. Approximated posterior pdfs resulting from replacing the simulation model with a computationally efficient surrogate, on the other hand, have seen limited accuracy. In this paper, we present a Bayesian active learning method to directly approximate the posterior pdf function of cardiac model parameters, in which we intelligently select training points to query the simulation model in order to learn the posterior pdf using a small number of samples. We integrate a generative model into Bayesian active learning to allow approximating posterior pdf of high-dimensional model parameters at the resolution of the cardiac mesh. We further introduce new acquisition functions to focus the selection of training points on better approximating the shape rather than the modes of the posterior pdf of interest. We evaluated the presented method in estimating tissue excitability in a 3D cardiac electrophysiological model in a range of synthetic and real-data experiments. We demonstrated its improved accuracy in approximating the posterior pdf compared to Bayesian active learning using regular acquisition functions, and substantially reduced computational cost in comparison to existing standard or accelerated MCMC sampling.

Jwala Dhamala, John L. Sapp, B. Milan Horácek et al.

Estimation of patient-specific model parameters is important for personalized modeling, although sparse and noisy clinical data can introduce significant uncertainty in the estimated parameter values. This importance source of uncertainty, if left unquantified, will lead to unknown variability in model outputs that hinder their reliable adoptions. Probabilistic estimation model parameters, however, remains an unresolved challenge because standard Markov Chain Monte Carlo sampling requires repeated model simulations that are computationally infeasible. A common solution is to replace the simulation model with a computationally-efficient surrogate for a faster sampling. However, by sampling from an approximation of the exact posterior probability density function (pdf) of the parameters, the efficiency is gained at the expense of sampling accuracy. In this paper, we address this issue by integrating surrogate modeling into Metropolis Hasting (MH) sampling of the exact posterior pdfs to improve its acceptance rate. It is done by first quickly constructing a Gaussian process (GP) surrogate of the exact posterior pdfs using deterministic optimization. This efficient surrogate is then used to modify commonly-used proposal distributions in MH sampling such that only proposals accepted by the surrogate will be tested by the exact posterior pdf for acceptance/rejection, reducing unnecessary model simulations at unlikely candidates. Synthetic and real-data experiments using the presented method show a significant gain in computational efficiency without compromising the accuracy. In addition, insights into the non-identifiability and heterogeneity of tissue properties can be gained from the obtained posterior distributions.

Prashnna Kumar Gyawali, Zhiyuan Li, Cameron Knight et al.

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.

Sandesh Ghimire, Jwala Dhamala, Prashnna Kumar Gyawali et al.

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.

Sandesh Ghimire, Prashnna Kumar Gyawali, Jwala Dhamala et al.

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.

Prashnna K Gyawali, Cameron Knight, Sandesh Ghimire et al.

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.

Sandesh Ghimire, Prashnna Kumar Gyawali, John L Sapp et al.

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.

Prashnna K Gyawali, B. Milan Horacek, John L. Sapp et al.

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.