arXiv subjects

Blanca Rodriguez

Publications and source records attributed to Blanca Rodriguez.

13 recordsLinked to original sources

arXiv2025

Female anatomies disguise ECG abnormalities following myocardial infarction: an AI-enabled modelling and simulation study

The electrocardiogram (ECG) is modulated by torso-heart anatomy, and this challenges patients' diagnosis and risk stratification. This study aims to quantify how torso-heart anatomical factors affect sex-differences in ECG biomarkers in acute and chronic myocardial infarction (MI). We exploit the perfect control of AI-augmented multiscale modelling and simulation, based on clinical magnetic resonance imaging (MRI) data and ECGs for model construction and validation. A cohort of 1720 torso-ventricular anatomies (50% female) was constructed from MRIs of healthy and post-MI participants in the UK Biobank study. 8600 ECG simulations were performed considering anatomical variability and 3 electrophysiological stages (healthy, acutely ischemic, and infarcted). The effect of cardiac size, position, and orientation on each ECG biomarker was quantified. Female anatomies had larger distances between the infarct and ECG electrodes (relative to cardiac size), and larger angles between the infarct normal and ECG lead axes, both primarily caused by their more superior cardiac position. This reduced ST-elevation and caused low-amplitude late depolarisation and repolarisation tails to be missed, shortening QRS duration (QRSd) and T-peak-to-end interval (TpTe). The position and orientation of the heart impacted TpTe more severely than QRSd. AI-enabled mechanistic modelling and simulation identify smaller ventricles, superior cardiac position, and different ventricular orientation as key anatomical contributors of shorter QRS and T waves, and lower ST-elevation, in female versus male anatomies. This provides a blueprint for quantifying the impact of anatomical sex differences on functional markers and enables future work in tailoring clinical guidelines considering unique patient anatomy to reduce biased outcomes.

physics.med-ph↗

arXiv2025

An Automated Computational Pipeline for Generating Large-Scale Cohorts of Patient-Specific Ventricular Models in Electromechanical In Silico Trials

In recent years, human in silico trials have gained significant traction as a powerful approach to evaluate the effects of drugs, clinical interventions, and medical devices. In silico trials not only minimise patient risks but also reduce reliance on animal testing. However, the implementation of in silico trials presents several time-consuming challenges. It requires the creation of large cohorts of virtual patients. Each virtual patient is described by their anatomy with a volumetric mesh and electrophysiological and mechanical dynamics through mathematical equations and parameters. Furthermore, simulated conditions need definition including stimulation protocols and therapy evaluation. For large virtual cohorts, this requires automatic and efficient pipelines for generation of corresponding files. In this work, we present a computational pipeline to automatically create large virtual patient cohort files to conduct large-scale in silico trials through cardiac electromechanical simulations. The pipeline generates the files describing meshes, labels, and data required for the simulations directly from unprocessed surface meshes. We applied the pipeline to generate over 100 virtual patients from various datasets and performed simulations to demonstrate capacity to conduct in silico trials for virtual patients using verified and validated electrophysiology and electromechanics models for the context of use. The proposed pipeline is adaptable to accommodate different types of ventricular geometries and mesh processing tools, ensuring its versatility in handling diverse clinical datasets. By establishing an automated framework for large scale simulation studies as required for in silico trials and providing open-source code, our work aims to support scalable, personalised cardiac simulations in research and clinical applications.

cs.CE↗

arXiv2024

Solving the Inverse Problem of Electrocardiography for Cardiac Digital Twins: A Survey

Cardiac digital twins (CDTs) are personalized virtual representations used to understand complex cardiac mechanisms. A critical component of CDT development is solving the ECG inverse problem, which enables the reconstruction of cardiac sources and the estimation of patient-specific electrophysiology (EP) parameters from surface ECG data. Despite challenges from complex cardiac anatomy, noisy ECG data, and the ill-posed nature of the inverse problem, recent advances in computational methods have greatly improved the accuracy and efficiency of ECG inverse inference, strengthening the fidelity of CDTs. This paper aims to provide a comprehensive review of the methods of solving ECG inverse problem, the validation strategies, the clinical applications, and future perspectives. For the methodologies, we broadly classify state-of-the-art approaches into two categories: deterministic and probabilistic methods, including both conventional and deep learning-based techniques. Integrating physics laws with deep learning models holds promise, but challenges such as capturing dynamic electrophysiology accurately, accessing accurate domain knowledge, and quantifying prediction uncertainty persist. Integrating models into clinical workflows while ensuring interpretability and usability for healthcare professionals is essential. Overcoming these challenges will drive further research in CDTs.

cs.CV↗

arXiv2024

Personalized Topology-Informed Localization of Standard 12-Lead ECG Electrode Placement from Incomplete Cardiac MRIs for Efficient Cardiac Digital Twins

Cardiac digital twins (CDTs) offer personalized in-silico cardiac representations for the inference of multi-scale properties tied to cardiac mechanisms. The creation of CDTs requires precise information about the electrode position on the torso, especially for the personalized electrocardiogram (ECG) calibration. However, current studies commonly rely on additional acquisition of torso imaging and manual/semi-automatic methods for ECG electrode localization. In this study, we propose a novel and efficient topology-informed model to fully automatically extract personalized ECG standard electrode locations from 2D clinically standard cardiac MRIs. Specifically, we obtain the sparse torso contours from the cardiac MRIs and then localize the standard electrodes of 12-lead ECG from the contours. Cardiac MRIs aim at imaging of the heart instead of the torso, leading to incomplete torso geometry within the imaging. To tackle the missing topology, we incorporate the electrodes as a subset of the keypoints, which can be explicitly aligned with the 3D torso topology. The experimental results demonstrate that the proposed model outperforms the time-consuming conventional model projection-based method in terms of accuracy (Euclidean distance: $1.24 \pm 0.293$ cm vs. $1.48 \pm 0.362$ cm) and efficiency ($2$~s vs. $30$-$35$~min). We further demonstrate the effectiveness of using the detected electrodes for in-silico ECG simulation, highlighting their potential for creating accurate and efficient CDT models. The code is available at https://github.com/lileitech/12lead_ECG_electrode_localizer.

eess.IV↗

arXiv2024

Towards Enabling Cardiac Digital Twins of Myocardial Infarction Using Deep Computational Models for Inverse Inference

Cardiac digital twins (CDTs) have the potential to offer individualized evaluation of cardiac function in a non-invasive manner, making them a promising approach for personalized diagnosis and treatment planning of my-ocardial infarction (MI). The inference of accurate myocardial tissue properties is crucial in creating a reliable CDT of MI. In this work, we investigate the feasibility of inferring myocardial tissue properties from the electrocardiogram (ECG) within a CDT platform. The platform integrates multi-modal data, such as cardiac MRI and ECG, to enhance the accuracy and reliability of the inferred tissue properties. We perform a sensitivity analysis based on computer simulations, systematically exploring the effects of infarct location, size, degree of transmurality, and electrical ac-tivity alteration on the simulated QRS complex of ECG, to establish the limits of the approach. We subsequently present a novel deep computational model, comprising a dual-branch variational autoencoder and an inference model, to infer infarct location and distribution from the simulated QRS. The proposed model achieves mean Dice scores of 0.457 \pm 0.317 and 0.302 \pm 0.273 for the inference of left ventricle scars and border zone, respectively. The sensitivity analysis enhances our understanding of the complex relationship between infarct characteristics and electrophysiological features. The in silico experimental results show that the model can effectively capture the relationship for the inverse inference, with promising potential for clinical application in the future. The code will be released publicly once the manuscript is accepted for publication.

eess.SP↗

arXiv2024

Cardiac Digital Twin Pipeline for Virtual Therapy Evaluation

Cardiac digital twins are computational tools capturing key functional and anatomical characteristics of patient hearts for investigating disease phenotypes and predicting responses to therapy. When paired with large-scale computational resources and large clinical datasets, digital twin technology can enable virtual clinical trials on virtual cohorts to fast-track therapy development. Here, we present an automated pipeline for personalising ventricular anatomy and electrophysiological function based on routinely acquired cardiac magnetic resonance (CMR) imaging data and the standard 12-lead electrocardiogram (ECG). Using CMR-based anatomical models, a sequential Monte-Carlo approximate Bayesian computational inference method is extended to infer electrical activation and repolarisation characteristics from the ECG. Fast simulations are conducted with a reaction-Eikonal model, including the Purkinje network and biophysically-detailed subcellular ionic current dynamics for repolarisation. For each patient, parameter uncertainty is represented by inferring a population of ventricular models rather than a single one, which means that parameter uncertainty can be propagated to therapy evaluation. Furthermore, we have developed techniques for translating from reaction-Eikonal to monodomain simulations, which allows more realistic simulations of cardiac electrophysiology. The pipeline is demonstrated in a healthy female subject, where our inferred reaction-Eikonal models reproduced the patient's ECG with a Pearson's correlation coefficient of 0.93, and the translated monodomain simulations have a correlation coefficient of 0.89. We then apply the effect of Dofetilide to the monodomain population of models for this subject and show dose-dependent QT and T-peak to T-end prolongations that are in keeping with large population drug response data.

cs.CE↗

arXiv2023

Anatomical basis of sex differences in the electrocardiogram identified by three-dimensional torso-heart imaging reconstruction pipeline

The electrocardiogram (ECG) is used for diagnosis and risk stratification in myocardial infarction (MI). Women have a higher incidence of missed MI diagnosis and complications following infarction, and to address this we aim to provide quantitative information on sex-differences in ECG and torso-ventricular anatomical features and their interdependence. A novel computational automated pipeline is presented enabling the three-dimensional reconstruction of torso-ventricular anatomies for 425 post-MI subjects and 1051 healthy controls from UK Biobank clinical images. Regression models were created relating torso-ventricular and ECG parameters. We found that female hearts were positioned more posteriorly and superiorly than male, and in MI hearts were oriented more horizontally, especially for women. Post-MI women exhibited less QRS prolongation, requiring 27% more prolongation than men to exceed 120ms. Only half of the sex difference in QRS duration was associated with smaller female cavities. Lower STj amplitude in women was striking, associated with smaller ventricles, but also more superior and posterior cardiac position. Post-MI, T wave amplitude and R axis deviations were more strongly associated with posterior and horizontal cardiac positioning in women than in men. Our study highlights the need to quantify sex differences in anatomical features, their implications in ECG interpretation, and the application of clinical ECG thresholds in post-MI.

physics.med-ph↗

arXiv2023

Digital Twinning of the Human Ventricular Activation Sequence to Clinical 12-lead ECGs and Magnetic Resonance Imaging Using Realistic Purkinje Networks for in Silico Clinical Trials

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically-consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions.

physics.med-ph↗

arXiv2023

Influence of Myocardial Infarction on QRS Properties: A Simulation Study

The interplay between structural and electrical changes in the heart after myocardial infarction (MI) plays a key role in the initiation and maintenance of arrhythmia. The anatomical and electrophysiological properties of scar, border zone, and normal myocardium modify the electrocardiographic morphology, which is routinely analysed in clinical settings. However, the influence of various MI properties on the QRS is not intuitively predictable.In this work, we have systematically investigated the effects of 17 post-MI scenarios, varying the location, size, transmural extent, and conductive level of scarring and border zone area, on the forward-calculated QRS. Additionally, we have compared the contributions of different QRS score criteria for quantifying post-MI pathophysiology.The propagation of electrical activity in the ventricles is simulated via a Eikonal model on a unified coordinate system.The analysis has been performed on 49 subjects, and the results imply that the QRS is capable of identifying MI, suggesting the feasibility of inversely reconstructing infarct regions from QRS.There exist sensitivity variations of different QRS criteria for identifying 17 MI scenarios, which is informative for solving the inverse problem.

cs.CV↗

arXiv2022

Deep Computational Model for the Inference of Ventricular Activation Properties

Patient-specific cardiac computational models are essential for the efficient realization of precision medicine and in-silico clinical trials using digital twins. Cardiac digital twins can provide non-invasive characterizations of cardiac functions for individual patients, and therefore are promising for the patient-specific diagnosis and therapy stratification. However, current workflows for both the anatomical and functional twinning phases, referring to the inference of model anatomy and parameter from clinical data, are not sufficiently efficient, robust, and accurate. In this work, we propose a deep learning based patient-specific computational model, which can fuse both anatomical and electrophysiological information for the inference of ventricular activation properties, i.e., conduction velocities and root nodes. The activation properties can provide a quantitative assessment of cardiac electrophysiological function for the guidance of interventional procedures. We employ the Eikonal model to generate simulated electrocardiogram (ECG) with ground truth properties to train the inference model, where specific patient information has also been considered. For evaluation, we test the model on the simulated data and obtain generally promising results with fast computational time.

cs.CV↗

arXiv2020

Inference of ventricular activation properties from non-invasive electrocardiography

The realisation of precision cardiology requires novel techniques for the non-invasive characterisation of individual patients' cardiac function to inform therapeutic and diagnostic decision-making. The electrocardiogram (ECG) is the most widely used clinical tool for cardiac diagnosis. Its interpretation is, however, confounded by functional and anatomical variability in heart and torso. In this study, we develop new computational techniques to estimate key ventricular activation properties for individual subjects by exploiting the synergy between non-invasive electrocardiography and image-based torso-biventricular modelling and simulation. More precisely, we present an efficient sequential Monte Carlo approximate Bayesian computation-based inference method, integrated with Eikonal simulations and torso-biventricular models constructed based on clinical cardiac magnetic resonance (CMR) imaging. The method also includes a novel strategy to treat combined continuous (conduction speeds) and discrete (earliest activation sites) parameter spaces, and an efficient dynamic time warping-based ECG comparison algorithm. We demonstrate results from our inference method on a cohort of twenty virtual subjects with cardiac volumes ranging from 74 cm3 to 171 cm3 and considering low versus high resolution for the endocardial discretisation (which determines possible locations of the earliest activation sites). Results show that our method can successfully infer the ventricular activation properties from non-invasive data, with higher accuracy for earliest activation sites, endocardial speed, and sheet (transmural) speed in sinus rhythm, rather than the fibre or sheet-normal speeds.

q-bio.TO↗

arXiv2017

Variational Inference over Non-differentiable Cardiac Simulators using Bayesian Optimization

Performing inference over simulators is generally intractable as their runtime means we cannot compute a marginal likelihood. We develop a likelihood-free inference method to infer parameters for a cardiac simulator, which replicates electrical flow through the heart to the body surface. We improve the fit of a state-of-the-art simulator to an electrocardiogram (ECG) recorded from a real patient.

stat.ML↗

arXiv2017

Unlocking datasets by calibrating populations of models to data density: a study in atrial electrophysiology

The understanding of complex physical or biological systems nearly always requires a characterisation of the variability that underpins these processes. In addition, the data used to calibrate such models may also often exhibit considerable variability. A recent approach to deal with these issues has been to calibrate populations of models (POMs), that is multiple copies of a single mathematical model but with different parameter values. To date this calibration has been limited to selecting models that produce outputs that fall within the ranges of the dataset, ignoring any trends that might be present in the data. We present here a novel and general methodology for calibrating POMs to the distributions of a set of measured values in a dataset. We demonstrate the benefits of our technique using a dataset from a cardiac atrial electrophysiology study based on the differences in atrial action potential readings between patients exhibiting sinus rhythm (SR) or chronic atrial fibrillation (cAF) and the Courtemanche--Ramirez--Nattel model for human atrial action potentials. Our approach accurately captures the variability inherent in the experimental population, and allows us to identify the differences underlying stratified data as well as the effects of drug block.

q-bio.TO↗