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A computational modeling framework for pre-clinical evaluation of cardiac mapping systems

There are a variety of difficulties in evaluating clinical cardiac mapping systems, most notably the inability to record the transmembrane potential throughout the entire heart during patient procedures which prevents the comparison to a relevant “gold standard”. Cardiac mapping systems are comprised of hardware and software elements including sophisticated mathematical algorithms, both of which continue to undergo rapid innovation. The purpose of this study is to develop a computational modeling framework to evaluate the performance of cardiac mapping systems. The framework enables rigorous evaluation of a mapping system’s ability to localize and characterize (i.e., focal or reentrant) arrhythmogenic sources in the heart. The main component of our tool is a library of computer simulations of various dynamic patterns throughout the entire heart in which the type and location of the arrhythmogenic sources are known. Our framework allows for performance evaluation for various electrode configurations, heart geometries, arrhythmias, and electrogram noise levels and involves blind comparison of mapping systems against a “silver standard” comprised of computer simulations in which the precise transmembrane potential patterns throughout the heart are known. A feasibility study was performed using simulations of patterns in the human left atria and three hypothetical virtual catheter electrode arrays. Activation times (AcT) and patterns (AcP) were computed for three virtual electrode arrays: two basket arrays with good and poor contact and one high-resolution grid with uniform spacing. The average root mean squared difference of AcTs of electrograms and those of the nearest endocardial action potential was less than 1 ms and therefore appears to be a poor performance metric. In an effort to standardize performance evaluation of mapping systems a novel performance metric is introduced based on the number of AcPs identified correctly and those considered spurious as well as misclassifications of arrhythmia type; spatial and temporal localization accuracy of correctly identified patterns was also quantified. This approach provides a rigorous quantitative analysis of cardiac mapping system performance. Proof of concept of this computational evaluation framework suggests that it could help safeguard that mapping systems perform as expected as well as provide estimates of system accuracy.

59 BASIC BIOLOGICAL SCIENCES↗

Machine learning based reconstruction of intracardiac electrical behavior based on electrocardiograms

A computer-based system and process are disclosed for reconstructing the internal electrical behavior of a patient's heart based partly or wholly on the patient's electrocardiogram (ECG). The output of the process may include, for example, a cardiac activation map, and/or a representation of transmembrane potentials over time. The process advantageously does not require any medical imaging of the patient, and does not require any special medical equipment. For example, the patient's activation map and transmembrane potentials may be reconstructed based solely on a preexisting or newly-obtained 12-lead cardiac ECG of the patient. The process makes use of a machine learning model, such as a neural network based model, trained with actual and/or simulated ECGs and intracardiac electrical data (typically transmembrane potentials) of many thousands of patients. Because an insufficient quantity of such data exists for actual patients, model training may be performed using ECGs and intracardiac electrical data obtained through computer simulations.

Blake, Robert↗

Intrinsically stretchable electrode array enabled in vivo electrophysiological mapping of atrial fibrillation at cellular resolution

Electrophysiological mapping of chronic atrial fibrillation (AF) at high throughput and high resolution is critical for understanding its underlying mechanism and guiding definitive treatment such as cardiac ablation, but current electrophysiological tools are limited by either low spatial resolution or electromechanical uncoupling of the beating heart. To overcome this limitation, here we introduce a scalable method for fabricating a tissue-like, high-density, fully elastic electrode (elastrode) array capable of achieving real-time, stable, cellular level-resolution electrophysiological mapping in vivo. Testing with acute rabbit and porcine models, the device is proven to have robust and intimate tissue coupling while maintaining its chemical, mechanical, and electrical properties during the cardiac cycle. The elastrode array records epicardial atrial signals with comparable efficacy to currently available endocardial-mapping techniques but with 2 times higher atrial-to-ventricular signal ratio and >100 times higher spatial resolution and can reliably identify electrical local heterogeneity within an area of simultaneously identified rotor-like electrical patterns in a porcine model of chronic AF.

60 APPLIED LIFE SCIENCES↗

Graphene Electric Field Sensor Enables Single Shot Label-Free Imaging of Bioelectric Potentials

The measurement of electrical activity across systems of excitable cells underlies current progress in neuroscience, cardiac pharmacology, and neurotechnology. However, bioelectricity spans orders of magnitude in intensity, space, and time, posing substantial technological challenges. The development of methods permitting network-scale recordings with high spatial resolution remains key to studies of electrogenic cells, emergent networks, and bioelectric computation. Here, for this work, we demonstrate single-shot and label-free imaging of extracellular potentials with high resolution across a wide field-of-view. The critically coupled waveguide-amplified graphene electric field (CAGE) sensor leverages the field-sensitive optical transitions in graphene to convert electric potentials into the optical regime. As a proof-of-concept, we use the CAGE sensor to detect native electrical activity from cardiac action potentials with tens-of-microns resolution, simultaneously map the propagation of these potentials at tissue-scale, and monitor their modification by pharmacological agents. This platform is robust, scalable, and compatible with existing microscopy techniques for multimodal correlative imaging.

47 OTHER INSTRUMENTATION↗

Intracardiac Electrical Imaging using the 12-lead ECG: A Machine Learning Approach using Synthetic Data

Current state-of-the-art techniques for non-invasive imaging of cardiac electrical phenomena require voltage recordings from dozens of different torso locations and anatomical models built from expensive medical diagnostic imaging procedures. Here this study aimed to assess if recent machine learning advances could alternatively reconstruct electroanatomical maps at clinically relevant resolutions using only the standard 12-lead electrocardiogram (ECG) as input. To that end, a computational study was conducted to generate a dataset of over 16000 detailed cardiac simulations, which was then used to train neural network (NN) architectures designed to exploit both spatial and temporal correlations in the ECG signal. Analysis over a validation set showed average errors in activation map reconstruction below 1.7 msec over 75 intracardiac locations. Furthermore, phenotypical patterns of activation and the morphology of the activation potential were correctly reconstructed. The approach offers opportunities to stratify patients non-invasively, both retrospectively and prospectively, using metrics otherwise only available through invasive clinical procedures.

59 BASIC BIOLOGICAL SCIENCES↗

Machine Learning for Cardiac Electrical Imaging

PyTorch code for cardiac electrical imaging using the 12-lead ECG. This code is associated with the paper from CINC 2022. If you use this code, please cite: Paper : https://cinc.org/2022/Program/accepted/26_Preprint.pdf Dataset : https://library.ucsd.edu/dc/object/bb29449106 The code support two tasks: Task 1: Activation Map Reconstruction from ECG Task 2: Transmembrane potential Reconstruction from ECG

Larma, MikelLandajuela↗

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial

Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantitative cross-species translators of cardiac myocyte electrophysiology: Model training, experimental validation, and applications

Animal experimentation is key in the evaluation of cardiac efficacy and safety of novel therapeutic compounds. However, interspecies differences in the mechanisms regulating excitation-contraction coupling can limit the translation of experimental findings from animal models to human physiology and undermine the assessment of drugs’ efficacy and safety. Here, we built a suite of translators for quantitatively mapping electrophysiological responses in ventricular myocytes across species. We trained these statistical operators using a broad dataset obtained by simulating populations of our biophysically detailed computational models of action potential and Ca 2+ transient in mouse, rabbit, and human. We then tested our translators against experimental data describing the response to stimuli, such as ion channel block, change in beating rate, and β-adrenergic challenge. We demonstrate that this approach is well suited to predicting the effects of perturbations across different species or experimental conditions and suggest its integration into mechanistic studies and drug development pipelines.

60 APPLIED LIFE SCIENCES↗

Comparison of Machine Learning and Deep Learning for View Identification from Cardiac Magnetic Resonance Images

Background: Artificial intelligence is increasingly utilized to aid in the interpretation of cardiac magnetic resonance (CMR) studies. One of the first steps is the identification of the imaging plane depicted, which can be achieved by both deep learning (DL) and classical machine learning (ML) techniques without user input. We aimed to compare the accuracy of ML and DL for CMR view classification and to identify potential pitfalls during training and testing of the algorithms. Methods: To train our DL and ML algorithms, we first established datasets by retrospectively selecting 200 CMR cases. The models were trained using two different cohorts (passively and actively curated) and applied data augmentation to enhance training. Once trained, the models were validated on an external dataset, consisting of 20 cases acquired at another center. We then compared accuracy metrics and applied class activation mapping (CAM) to visualize DL model performance. Results: The DL and ML models trained with the passively-curated CMR cohort were 99.1% and 99.3% accurate on the validation set, respectively. However, when tested on the CMR cases with complex anatomy, both models performed poorly. After training and testing our models again on all 200 cases (active cohort), validation on the external dataset resulted in 95% and 90% accuracy, respectively. The CAM analysis depicted heat maps that demonstrated the importance of carefully curating the datasets to be used for training. Conclusions: Both DL and ML models can accurately classify CMR images, but DL outperformed ML when classifying images with complex heart anatomy.

artificial intelligence↗