lifex-fiber: an open tool for myofibers generation in cardiac computational models

Background: Modeling the whole cardiac function involves the solution of several complex multi-physics and multi-scale models that are highly computationally demanding, which call for simpler yet accurate, high-performance computational tools. Despite the efforts made by several research groups, no software for whole-heart fully coupled cardiac simulations in the scientific community has reached full maturity yet.Results: In this work we present life(x)-fiber, an innovative tool for the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, which are the essential building blocks for modeling the electrophysiological, mechanical and electromechanical cardiac function, from single-chamber to whole-heart simulations. life(x)-fiber is the first publicly released module for cardiac simulations based on life(x), an open-source, high-performance Finite Element solver for multi-physics, multi-scale and multi-domain problems developed in the framework of the iHEART project, which aims at making in silico experiments easily reproducible and accessible to a wide community of users, including those with a background in medicine or bio-engineering.Conclusions: The tool presented in this document is intended to provide the scientific community with a computational tool that incorporates general state of the art models and solvers for simulating the cardiac function within a high-performance framework that exposes a user-and developer-friendly interface. This report comes with an extensive technical and mathematical documentation to welcome new users to the core structure of life(x)-fiber and to provide them with a possible approach to include the generated cardiac fibers into more sophisticated computational pipelines. In the near future, more modules will be successively published either as pre-compiled binaries for x86-64 Linux systems or as open source software

Comprehensive Sun-to-Earth analysis of the Geoeffective Solar event of June 21, 2015: Effects on the Magnetosphere - Plasmasphere - Ionosphere system

A full-halo coronal mass ejection left the sun on June 21, 2015 from the active region NOAA 12371 encountering Earth on June 22, 2015, generating a G3 strong geomagnetic storm. The CME was associated with an M2 class flare observed at 01:42 UT, located near the center disk (N12E16). Using satellite data from solar, heliospheric, magnetospheric missions and ground-based instruments, we performed a comprehensive Sun-to-Earth analysis. In particular, we analyzed the active region evolution using ground-based and satellite instruments (BBSO, IRIS, HINODE, SDO/AIA, RHESSI -- Halpha, EUV, UV, X), the AR magnetograms, using data from SDO HMI, the relative particle data, using PAMELA instruments and the effects of interplanetary perturbation on cosmic ray intensity. We also evaluated the 1-8 $\AA$ soft X-ray and low-frequenct ($\sim$ 1 MHz) Type III radio burst time-integrated intensity (or fluence) of the flare in order to make a prediction of the associated Solar Energetic Particle (SEP) event by using the model developed by \cite{Laurenza09}. Inaddition, using ground based observations from lower to higher latitudes (INTERMAGNET - EMMA, etc.), we reconstructed the ionospheric current system associated to the geomagnetic Sudden Commencement. Furthermore, SuperDARN measurements are used to image the global ionospheric polar convection during the SSC and during the principal phases of the geomagnetic storm. Moreover, we investigated the dynamics of the plasmasphere during the different phases of the geomagnetic storm by examining the time evolution of the radial profiles of the equatorial plasma mass density derived from field line resonances detected at the EMMA network (1.5 $<$ L $<$ 6.5). Finally, we presented the general features of the geomagnetic response to the CME, by applying innovative data analysis tools that allow to investigate the time variation of ground-based observations of the Earth's magnetic field during the associated geomagnetic storm

An electromechanics-driven fluid dynamics model for the simulation of the whole human heart

We introduce a multiphysics and geometric multiscale computational model, suitable to describe the hemodynamics of the whole human heart, driven by a four-chamber electromechanical model. We first present a study on the calibration of the biophysically detailed RDQ20 active contraction model (Regazzoni et al., 2020) that is able to reproduce the physiological range of hemodynamic biomarkers. Then, we demonstrate that the ability of the force generation model to reproduce certain microscale mechanisms, such as the dependence of force on fiber shortening velocity, is crucial to capture the overall physiological mechanical and fluid dynamics macroscale behavior. This motivates the need for using multiscale models with high biophysical fidelity, even when the outputs of interest are relative to the macroscale. We show that the use of a high-fidelity electromechanical model, combined with a detailed calibration process, allows us to achieve a remarkable biophysical fidelity in terms of both mechanical and hemodynamic quantities. Indeed, our electromechanical-driven CFD simulations – carried out on an anatomically accurate geometry of the whole heart – provide results that match the cardiac physiology both qualitatively (in terms of flow patterns) and quantitatively (when comparing in silico results with biomarkers acquired in vivo). Moreover, we consider the pathological case of left bundle branch block, and we investigate the consequences that an electrical abnormality has on cardiac hemodynamics thanks to our multiphysics integrated model. The computational model that we propose can faithfully predict a delay and an increasing wall shear stress in the left ventricle in the pathological condition. The interaction of different physical processes in an integrated framework allows us to faithfully describe and model this pathology, by capturing and reproducing the intrinsic multiphysics nature of the human heart

Modeling cardiac muscle fibers in ventricular and atrial electrophysiology simulations

Since myocardial fibers drive the electric signal propagation throughout the myocardium, accurately modeling their arrangement is essential for simulating heart electrophysiology (EP). Rule-Based-Methods (RBMs) represent a commonly used strategy to include cardiac fibers in computational models. A particular class of such methods is known as Laplace-Dirichlet-Rule-Based-Methods (LDRBMs) since they rely on the solution of Laplace problems. In this work we provide a unified framework, based on LDRBMs, for generating full heart muscle fibers. First, we review existing ventricular LDRBMs providing a communal mathematical description and introducing also some modeling improvements with respect to the existing literature. We then carry out a systematic comparison of LDRBMs based on meaningful biomarkers produced by numerical EP simulations. Next we propose, for the first time, a LDRBM to be used for generating atrial fibers. The new method, tested both on idealized and realistic atrial models, can be applied to any arbitrary geometries. Finally, we present numerical results obtained in a realistic whole heart where fibers are included for all the four chambers using the discussed LDRBMs

lifex-ep: a robust and efficient software for cardiac electrophysiology simulations

Background: Simulating the cardiac function requires the numerical solution of multi-physics and multi-scale mathematical models. This underscores the need for streamlined, accurate, and high-performance computational tools. Despite the dedicated endeavors of various research teams, comprehensive and user-friendly software programs for cardiac simulations, capable of accurately replicating both normal and pathological conditions, are still in the process of achieving full maturity within the scientific community. Results: This work introduces lifex-ep, a publicly available software for numerical simulations of the electrophysiology activity of the cardiac muscle, under both normal and pathological conditions. lifex-ep employs the monodomain equation to model the heart's electrical activity. It incorporates both phenomenological and second-generation ionic models. These models are discretized using the Finite Element method on tetrahedral or hexahedral meshes. Additionally, lifex-ep integrates the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, previously released in Africa et al., 2023, within lifex-fiber. As an alternative, users can also choose to import myofibers from a file. This paper provides a concise overview of the mathematical models and numerical methods underlying lifex-ep, along with comprehensive implementation details and instructions for users. lifex-ep features exceptional parallel speedup, scaling efficiently when using up to thousands of cores, and its implementation has been verified against an established benchmark problem for computational electrophysiology. We showcase the key features of lifex-ep through various idealized and realistic simulations conducted in both normal and pathological scenarios. Furthermore, the software offers a user-friendly and flexible interface, simplifying the setup of simulations using self-documenting parameter files. Conclusions: lifex-ep provides easy access to cardiac electrophysiology simulations for a wide user community. It offers a computational tool that integrates models and accurate methods for simulating cardiac electrophysiology within a high-performance framework, while maintaining a user-friendly interface. lifex-ep represents a valuable tool for conducting in silico patient-specific simulations

A comprehensive and biophysically detailed computational model of the whole human heart electromechanics

While ventricular electromechanics is extensively studied, four-chamber heart models have only been addressed recently; most of these works however neglect atrial contraction. Indeed, as atria are characterized by a complex physiology influenced by the ventricular function, developing computational models able to capture the physiological atrial function and atrioventricular interaction is very challenging. In this paper, we propose a biophysically detailed electromechanical model of the whole human heart that considers both atrial and ventricular contraction. Our model includes: i) an anatomically accurate whole-heart geometry; ii) a comprehensive myocardial fiber architecture; iii) a biophysically detailed microscale model for the active force generation; iv) a 0D closed-loop model of the circulatory system; v) the fundamental interactions among the different core models; vi) specific constitutive laws and model parameters for each cardiac region. Concerning the numerical discretization, we propose an efficient segregated-intergrid-staggered scheme and we employ recently developed stabilization techniques that are crucial to obtain a stable formulation in a four-chamber scenario. We are able to reproduce the healthy cardiac function for all the heart chambers, in terms of pressure-volume loops, time evolution of pressures, volumes and fluxes, and three-dimensional cardiac deformation, with unprecedented matching (to the best of our knowledge) with the expected physiology. We also show the importance of considering atrial contraction, fibers-stretch-rate feedback and suitable stabilization techniques, by comparing the results obtained with and without these features in the model. The proposed model represents the state-of-the-art electromechanical model of the iHEART ERC project and is a fundamental step toward the building of physics-based digital twins of the human heart

RF Design of the X-band Linac for the EuPRAXIA@SPARC_LAB Project

We illustrate the RF design of the X-band linac for the upgrade of the SPARC_LAB facility at INFN-LNF (EuPRAXIA@SPARC_LAB). The structures are travelling wave (TW) cavities, working on the 2π/3 mode, fed by klystrons with pulse compressor systems. The tapering of the cells along the structure and the cell profiles have been optimized to maximize the effective shunt impedance keeping under control the maximum value of the modified Poynting vector, while the couplers have been designed to have a symmetric feeding and a reduced pulsed heating. In the paper we also present the RF power distribution layout of the accelerating module and a preliminary mechanical design

Marine phycotoxin levels in shellfish-14 years of data gathered along the Italian coast

Along the Italian coasts, toxins of algal origin in wild and cultivated shellfish have been reported since the 1970s. In this study, we used data gathered by the Veterinary Public Health Institutes (IZS) and the Italian Environmental Health Protection Agencies (ARPA) from 2006 to 2019 to investigate toxicity events along the Italian coasts and relate them to the distribution of potentially toxic species. Among the detected toxins (OA and analogs, YTXs, PTXs, STXs, DAs, AZAs), OA and YTX were those most frequently reported. Levels exceeding regulatory limits in the case of OA (≤2,448 μg equivalent kg-1) were associated with high abundances of Dinophysis spp., and in the case of YTXs (≤22 mg equivalent kg-1) with blooms of Gonyaulax spinifera, Lingulodinium polyedra, and Protoceratium reticulatum. Seasonal blooms of Pseudo-nitzschia spp. occur all along the Italian coast, but DA has only occasionally been detected in shellfish at concentrations always below the regulatory limit (≤18 mg kg-1). Alexandrium spp. were recorded in several areas, although STXs (≤13,782 μg equivalent kg-1) rarely and only in few sites exceeded the regulatory limit in shellfish. Azadinium spp. have been sporadically recorded, and AZAs have been sometimes detected but always in low concentrations (≤7 μg equivalent kg-1). Among the emerging toxins, PLTX-like toxins (≤971 μg kg-1 OVTX-a) have often been detected mainly in wild mussels and sea urchins from rocky shores due to the presence of Ostreopsis cf. ovata. Overall, Italian coastal waters harbour a high number of potentially toxic species, with a few HAB hotspots mainly related to DSP toxins. Nevertheless, rare cases of intoxications have occurred so far, reflecting the whole Mediterranean Sea conditions

Gamma-Ray Burst observations by the high-energy charged particle detector on board the CSES-01 satellite between 2019 and 2021

In this paper we report the detection of five strong Gamma-Ray Bursts (GRBs) by the High-Energy Particle Detector (HEPD-01) mounted on board the China Seismo-Electromagnetic Satellite (CSES-01), operational since 2018 on a Sun-synchronous polar orbit at a $\sim$ 507 km altitude and 97$^\circ$ inclination. HEPD-01 was designed to detect high-energy electrons in the energy range 3 - 100 MeV, protons in the range 30 - 300 MeV, and light nuclei in the range 30 - 300 MeV/n. Nonetheless, Monte Carlo simulations have shown HEPD-01 is sensitive to gamma-ray photons in the energy range 300 keV - 50 MeV, even if with a moderate effective area above $\sim$ 5 MeV. A dedicated time correlation analysis between GRBs reported in literature and signals from a set of HEPD-01 trigger configuration masks has confirmed the anticipated detector sensitivity to high-energy photons. A comparison between the simultaneous time profiles of HEPD-01 electron fluxes and photons from GRB190114C, GRB190305A, GRB190928A, GRB200826B and GRB211211A has shown a remarkable similarity, in spite of the different energy ranges. The high-energy response, with peak sensitivity at about 2 MeV, and moderate effective area of the detector in the actual flight configuration explain why these five GRBs, characterised by a fluence above $\sim$ 3 $\times$ 10$^{-5}$ erg cm$^{-2}$ in the energy interval 300 keV - 50 MeV, have been detected.Comment: Accepted for publication in The Astrophysical Journal (ApJ