Gernot Plank

Karli Gillette, Matthias A. F. Gsell, Claudia Nagel et al.

Mechanistic cardiac electrophysiology models allow for personalized simulations of the electrical activity in the heart and the ensuing electrocardiogram (ECG) on the body surface. As such, synthetic signals possess known ground truth labels of the underlying disease and can be employed for validation of machine learning ECG analysis tools in addition to clinical signals. Recently, synthetic ECGs were used to enrich sparse clinical data or even replace them completely during training leading to improved performance on real-world clinical test data. We thus generated a novel synthetic database comprising a total of 16,900 12 lead ECGs based on electrophysiological simulations equally distributed into healthy control and 7 pathology classes. The pathological case of myocardial infraction had 6 sub-classes. A comparison of extracted features between the virtual cohort and a publicly available clinical ECG database demonstrated that the synthetic signals represent clinical ECGs for healthy and pathological subpopulations with high fidelity. The ECG database is split into training, validation, and test folds for development and objective assessment of novel machine learning algorithms.

Franz Thaler, Darko Stern, Gernot Plank et al.

Myocardial infarction (MI) is one of the most prevalent cardiovascular diseases and consequently, a major cause for mortality and morbidity worldwide. Accurate assessment of myocardial tissue viability for post-MI patients is critical for diagnosis and treatment planning, e.g. allowing surgical revascularization, or to determine the risk of adverse cardiovascular events in the future. Fine-grained analysis of the myocardium and its surrounding anatomical structures can be performed by combining the information obtained from complementary medical imaging techniques. In this work, we use late gadolinium enhanced (LGE) magnetic resonance (MR), T2-weighted (T2) MR and balanced steady-state free precession (bSSFP) cine MR in order to semantically segment the left and right ventricle, healthy and scarred myocardial tissue, as well as edema. To this end, we propose the Multi-Sequence Cascading Refinement CNN (MS-CaRe-CNN), a 2-stage CNN cascade that receives multi-sequence data and generates predictions of the anatomical structures of interest without considering tissue viability at Stage 1. The prediction of Stage 1 is then further refined in Stage 2, where the model additionally distinguishes myocardial tissue based on viability, i.e. healthy, scarred and edema regions. Our proposed method is set up as a 5-fold ensemble and semantically segments scar tissue achieving 62.31% DSC and 82.65% precision, as well as 63.78% DSC and 87.69% precision for the combined scar and edema region. These promising results for such small and challenging structures confirm that MS-CaRe-CNN is well-suited to generate semantic segmentations to assess the viability of myocardial tissue, enabling downstream tasks like personalized therapy planning.

Franz Thaler, Martin Urschler, Mateusz Kozinski et al.

We tackle the challenging problem of single-source domain generalization (DG) for medical image segmentation. To this end, we aim for training a network on one domain (e.g., CT) and directly apply it to a different domain (e.g., MR) without adapting the model and without requiring images or annotations from the new domain during training. We propose a novel method for promoting DG when training deep segmentation networks, which we call SRCSM. During training, our method diversifies the source domain through semantic-aware random convolution, where different regions of a source image are augmented differently, based on their annotation labels. At test-time, we complement the randomization of the training domain via mapping the intensity of target domain images, making them similar to source domain data. We perform a comprehensive evaluation on a variety of cross-modality and cross-center generalization settings for abdominal, whole-heart and prostate segmentation, where we outperform previous DG techniques in a vast majority of experiments. Additionally, we also investigate our method when training on whole-heart CT or MR data and testing on the diastolic and systolic phase of cine MR data captured with different scanner hardware, where we make a step towards closing the domain gap in this even more challenging setting. Overall, our evaluation shows that SRCSM can be considered a new state-of-the-art in DG for medical image segmentation and, moreover, even achieves a segmentation performance that matches the performance of the in-domain baseline in several settings.

Alice Ragonesi, Stefania Fresca, Karli Gillette et al.

Wolff-Parkinson-White (WPW) syndrome is a cardiac electrophysiology (EP) disorder caused by the presence of an accessory pathway (AP) that bypasses the atrioventricular node, faster ventricular activation rate, and provides a substrate for atrio-ventricular reentrant tachycardia (AVRT). Accurate localization of the AP is critical for planning and guiding catheter ablation procedures. While traditional diagnostic tree (DT) methods and more recent machine learning (ML) approaches have been proposed to predict AP location from surface electrocardiogram (ECG), they are often constrained by limited anatomical localization resolution, poor interpretability, and the use of small clinical datasets. In this study, we present a Deep Learning (DL) model for the localization of single manifest APs across 24 cardiac regions, trained on a large, physiologically realistic database of synthetic ECGs generated using a personalized virtual heart model. We also integrate eXplainable Artificial Intelligence (XAI) methods, Guided Backpropagation, Grad-CAM, and Guided Grad-CAM, into the pipeline. This enables interpretation of DL decision-making and addresses one of the main barriers to clinical adoption: lack of transparency in ML predictions. Our model achieves localization accuracy above 95%, with a sensitivity of 94.32% and specificity of 99.78%. XAI outputs are physiologically validated against known depolarization patterns, and a novel index is introduced to identify the most informative ECG leads for AP localization. Results highlight lead V2 as the most critical, followed by aVF, V1, and aVL. This work demonstrates the potential of combining cardiac digital twins with explainable DL to enable accurate, transparent, and non-invasive AP localization.

Carlos Ruiz Herrera, Thomas Grandits, Gernot Plank et al.

We propose FiberNet, a method to estimate \emph{in-vivo} the cardiac fiber architecture of the human atria from multiple catheter recordings of the electrical activation. Cardiac fibers play a central role in the electro-mechanical function of the heart, yet they are difficult to determine in-vivo, and hence rarely truly patient-specific in existing cardiac models. FiberNet learns the fiber arrangement by solving an inverse problem with physics-informed neural networks. The inverse problem amounts to identifying the conduction velocity tensor of a cardiac propagation model from a set of sparse activation maps. The use of multiple maps enables the simultaneous identification of all the components of the conduction velocity tensor, including the local fiber angle. We extensively test FiberNet on synthetic 2-D and 3-D examples, diffusion tensor fibers, and a patient-specific case. We show that 3 maps are sufficient to accurately capture the fibers, also in the presence of noise. With fewer maps, the role of regularization becomes prominent. Moreover, we show that the fitted model can robustly reproduce unseen activation maps. We envision that FiberNet will help the creation of patient-specific models for personalized medicine. The full code is available at http://github.com/fsahli/FiberNet.

Federica Caforio, Francesco Regazzoni, Stefano Pagani et al.

The development of biophysical models for clinical applications is rapidly advancing in the research community, thanks to their predictive nature and their ability to assist the interpretation of clinical data. However, high-resolution and accurate multi-physics computational models are computationally expensive and their personalisation involves fine calibration of a large number of parameters, which may be space-dependent, challenging their clinical translation. In this work, we propose a new approach which relies on the combination of physics-informed neural networks (PINNs) with three-dimensional soft tissue nonlinear biomechanical models, capable of reconstructing displacement fields and estimating heterogeneous patient-specific biophysical properties. The proposed learning algorithm encodes information from a limited amount of displacement and, in some cases, strain data, that can be routinely acquired in the clinical setting, and combines it with the physics of the problem, represented by a mathematical model based on partial differential equations, to regularise the problem and improve its convergence properties. Several benchmarks are presented to show the accuracy and robustness of the proposed method and its great potential to enable the robust and effective identification of patient-specific, heterogeneous physical properties, s.a. tissue stiffness properties. In particular, we demonstrate the capability of the PINN to detect the presence, location and severity of scar tissue, which is beneficial to develop personalised simulation models for disease diagnosis, especially for cardiac applications.

Franz Thaler, Matthias A. F. Gsell, Gernot Plank et al.

Late gadolinium enhanced (LGE) magnetic resonance (MR) imaging is widely established to assess the viability of myocardial tissue of patients after acute myocardial infarction (MI). We propose the Cascading Refinement CNN (CaRe-CNN), which is a fully 3D, end-to-end trained, 3-stage CNN cascade that exploits the hierarchical structure of such labeled cardiac data. Throughout the three stages of the cascade, the label definition changes and CaRe-CNN learns to gradually refine its intermediate predictions accordingly. Furthermore, to obtain more consistent qualitative predictions, we propose a series of post-processing steps that take anatomical constraints into account. Our CaRe-CNN was submitted to the FIMH 2023 MYOSAIQ challenge, where it ranked second out of 18 participating teams. CaRe-CNN showed great improvements most notably when segmenting the difficult but clinically most relevant myocardial infarct tissue (MIT) as well as microvascular obstructions (MVO). When computing the average scores over all labels, our method obtained the best score in eight out of ten metrics. Thus, accurate cardiac segmentation after acute MI via our CaRe-CNN allows generating patient-specific models of the heart serving as an important step towards personalized medicine.

Franz Thaler, Darko Stern, Gernot Plank et al.

Atrial fibrillation (AF) represents the most prevalent type of cardiac arrhythmia for which treatment may require patients to undergo ablation therapy. In this surgery cardiac tissues are locally scarred on purpose to prevent electrical signals from causing arrhythmia. Patient-specific cardiac digital twin models show great potential for personalized ablation therapy, however, they demand accurate semantic segmentation of healthy and scarred tissue typically obtained from late gadolinium enhanced (LGE) magnetic resonance (MR) scans. In this work we propose the Left Atrial Cascading Refinement CNN (LA-CaRe-CNN), which aims to accurately segment the left atrium as well as left atrial scar tissue from LGE MR scans. LA-CaRe-CNN is a 2-stage CNN cascade that is trained end-to-end in 3D, where Stage 1 generates a prediction for the left atrium, which is then refined in Stage 2 in conjunction with the original image information to obtain a prediction for the left atrial scar tissue. To account for domain shift towards domains unknown during training, we employ strong intensity and spatial augmentation to increase the diversity of the training dataset. Our proposed method based on a 5-fold ensemble achieves great segmentation results, namely, 89.21% DSC and 1.6969 mm ASSD for the left atrium, as well as 64.59% DSC and 91.80% G-DSC for the more challenging left atrial scar tissue. Thus, segmentations obtained through LA-CaRe-CNN show great potential for the generation of patient-specific cardiac digital twin models and downstream tasks like personalized targeted ablation therapy to treat AF.

Matthias Höfler, Francesco Regazzoni, Stefano Pagani et al.

Active stress models in cardiac biomechanics account for the mechanical deformation caused by muscle activity, thus providing a link between the electrophysiological and mechanical properties of the tissue. The accurate assessment of active stress parameters is fundamental for a precise understanding of myocardial function but remains difficult to achieve in a clinical setting, especially when only displacement and strain data from medical imaging modalities are available. This work investigates, through an in-silico study, the application of physics-informed neural networks (PINNs) for inferring active contractility parameters in time-dependent cardiac biomechanical models from these types of imaging data. In particular, by parametrising the sought state and parameter field with two neural networks, respectively, and formulating an energy minimisation problem to search for the optimal network parameters, we are able to reconstruct in various settings active stress fields in the presence of noise and with a high spatial resolution. To this end, we also advance the vanilla PINN learning algorithm with the use of adaptive weighting schemes, ad-hoc regularisation strategies, Fourier features, and suitable network architectures. In addition, we thoroughly analyse the influence of the loss weights in the reconstruction of active stress parameters. Finally, we apply the method to the characterisation of tissue inhomogeneities and detection of fibrotic scars in myocardial tissue. This approach opens a new pathway to significantly improve the diagnosis, treatment planning, and management of heart conditions associated with cardiac fibrosis.

Franz Thaler, Darko Stern, Gernot Plank et al.

As the leading cause of death worldwide, cardiovascular diseases motivate the development of more sophisticated methods to analyze the heart and its substructures from medical images like Computed Tomography (CT) and Magnetic Resonance (MR). Semantic segmentations of important cardiac structures that represent the whole heart are useful to assess patient-specific cardiac morphology and pathology. Furthermore, accurate semantic segmentations can be used to generate cardiac digital twin models which allows e.g. electrophysiological simulation and personalized therapy planning. Even though deep learning-based methods for medical image segmentation achieved great advancements over the last decade, retaining good performance under domain shift -- i.e. when training and test data are sampled from different data distributions -- remains challenging. In order to perform well on domains known at training-time, we employ a (1) balanced joint training approach that utilizes CT and MR data in equal amounts from different source domains. Further, aiming to alleviate domain shift towards domains only encountered at test-time, we rely on (2) strong intensity and spatial augmentation techniques to greatly diversify the available training data. Our proposed whole heart segmentation method, a 5-fold ensemble with our contributions, achieves the best performance for MR data overall and a performance similar to the best performance for CT data when compared to a model trained solely on CT. With 93.33% DSC and 0.8388 mm ASSD for CT and 89.30% DSC and 1.2411 mm ASSD for MR data, our method demonstrates great potential to efficiently obtain accurate semantic segmentations from which patient-specific cardiac twin models can be generated.

Thomas Grandits, Simone Pezzuto, Gernot Plank

The field of cardiac electrophysiology tries to abstract, describe and finally model the electrical characteristics of a heartbeat. With recent advances in cardiac electrophysiology, models have become more powerful and descriptive as ever. However, to advance to the field of inverse electrophysiological modeling, i.e. creating models from electrical measurements such as the ECG, the less investigated field of smoothness of the simulated ECGs w.r.t. model parameters need to be further explored. The present paper discusses smoothness in terms of the whole pipeline which describes how from physiological parameters, we arrive at the simulated ECG. Employing such a pipeline, we create a test-bench of a simplified idealized left ventricle model and demonstrate the most important factors for efficient inverse modeling through smooth cost functionals. Such knowledge will be important for designing and creating inverse models in future optimization and machine learning methods.

Thomas Grandits, Simone Pezzuto, Francisco Sahli Costabal et al.

Electroanatomical maps are a key tool in the diagnosis and treatment of atrial fibrillation. Current approaches focus on the activation times recorded. However, more information can be extracted from the available data. The fibers in cardiac tissue conduct the electrical wave faster, and their direction could be inferred from activation times. In this work, we employ a recently developed approach, called physics informed neural networks, to learn the fiber orientations from electroanatomical maps, taking into account the physics of the electrical wave propagation. In particular, we train the neural network to weakly satisfy the anisotropic eikonal equation and to predict the measured activation times. We use a local basis for the anisotropic conductivity tensor, which encodes the fiber orientation. The methodology is tested both in a synthetic example and for patient data. Our approach shows good agreement in both cases, with an RMSE of 2.2ms on the in-silico data and outperforming a state of the art method on the patient data. The results show a first step towards learning the fiber orientations from electroanatomical maps with physics-informed neural networks.