Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Multicentre performance evaluation of the E170 Module for MODULAR ANALYTICS

The E170 module was evaluated at 13 sites in an international multicentre study. The objective of the study was to assess the analytical performance of 49 analytes, and to collect feedback on the system's reliability and practicability. The typical, within-run coefficients of variation (CVs) for most of the quantitative assays ranged between 1 and 2% while a range of 2-4% was achieved with the infectious disease methods. Total precision CVs were found to be within the manufacturer's expected performance ranges, demonstrating good concordance of the system's measuring channels and a high reproducibility during the 2-4-week trial period. The functional sensitivity of 11 selected assays met the clinical requirements (e.g., thyreotroponin (TSH) 0.008 mU/l, troponin T 0.02 µg/l, total prostate-specific antigen (PSA) 0.03 µg/l). The E170 showed no drift during an 8-hour period and no relevant reagent carryover. Accuracy was confirmed by ring trial experiments and method comparisons vs. Elecsys® 2010. The reliability and practicability of the system's hardware and software met with, or even exceeded, the evaluator's requirements. Workflow studies showed that E170 can cover the combined workload of various routine analysers in a variety of laboratory environment. Throughput and sample processing time requirements were achieved while personnel ‘hands-on-time' could be reduce

MRI-guided non-invasive epicardial mapping in patients with implanted pacing devices

Developing patient-specific 3D heart models to non-invasively localize arrhythmic foci. My research focussed on the application of MRI and complex electrocardiography in patients with MRI conditional pacemaker systems

XML Markup for maintenance management of critical care medical devices

Preventive maintenance of biomedical devices is of particular concern to avoid failures and breakdowns, especially for critical care and life supporting devices. Signs of potential failures are not always visible and so, they should be inspected and tested periodically using the appropriate technology. Patient simulators have become one of the essential tools for any biomedical department on every health institution, but its cost is still high to be afforded by everyone. The Labview interactive virtual instrument SIMPAC, a simple PC-based patient simulator, showed to be a low cost powerful tool for simulation of healthy and pathological conditions using signals repositories of different biomedical devices such as EEG, ECG, etc., and also to record the output signals of devices like pacemakers, defibrillators, etc. Here we present an enhancement of the tool which consists of adding a secure reporting feature using XML for presenting tests results, applying digital signature for granting report integrity, assuring this way that reports can not be altered by intentional or accidental manipulation of the data contained on it, according to the terms of the medical technology law. In addition, SIMPAC brings a low cost solution for teaching and practical purposes.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Design and clinical validation of novel imaging strategies for analysis of arrhythmogenic substrate

_CURRENT CHALLENGES IN ELECTROPHYSIOLOGY_ Technical advances in cardiovascular electrophysiology have resulted in an increasing number of catheter ablation procedures reaching 200 000 in Europe for the year 2013. These advanced interventions are often complex and time consuming and may cause significant radiation exposure. Furthermore, a substantial number of ablation procedures remain associated with poor (initial) outcomes and frequently require ≥1 redo procedures. Innovations in modalities for substrate imaging could facilitate our understanding of the arrhythmogenic substrate, improve the design of patient-specific ablation strategies and improve the results of ablation procedures. _NOVEL SUBSTRATE IMAGING MODALITIES_ __Cardiac magnetic resonance__ Cardiac magnetic resonance imaging (CMR) can be considered the most comprehensive and suitable modality for the complete electrophysiology and catheter ablation workup (including patient selection, procedural guidance, and [procedural] follow-up). Utilizing inversion recovery CMR, fibrotic myocardium can be visualized and quantified 10–15 min after intravenous administration of Gadolinium contrast. This imaging technique is known as late Gadolinium enhancement (LGE) imaging. Experimental models have shown excellent agreement between size and shape in LGE CMR and areas of myocardial infarction by histopathology. Recent studies have also demonstrated how scar size, shape and location from pre-procedural LGE can be useful in guiding ventricular tachycardia’s (VT) ablation or atrial fibrillation (AF) ablation. These procedures are often time-consuming due to the preceding electrophysiological mapping study required to identify slow conduction zones involved in re-entry circuits. Post-processed LGE images provide scar maps, which could be integrated with electroanatomic mapping systems to facilitate these procedures. __Inverse potential mapping__ Through the years, various noninvasive electrocardiographic imaging techniques have emerged that estimate epicardial potentials or myocardial activation times from potentials recorded on the thorax. Utilizing an inverse procedure, the potentials on the heart surface or activation times of the myocardium are estimated with the recorded body surface potentials as source data. Although this procedure only estimates the time course of unipolar epicardial electrograms, several studies have demonstrated that the epicardial potentials and electrograms provide substantial information about intramyocardial activity and have great potential to facilitate risk-stratification and generate personalized ablation strategies. __Objectives of this thesis__ 1. To evaluate the utility of cardiac magnetic resonance derived geometrical and tissue characteristic information for patient stratification and guidance of AF ablation. 2. To design and evaluate the performance of a finite element model based inverse potential mapping in predicting the arrhythmogenic focus in idiopathic ventricular tachycardia using invasive electro-anatomical activation mapping as a reference standard

Numerical methods for the detection of phase defect structures in excitable media

Electrical waves that rotate in the heart organize dangerous cardiac arrhythmias. Finding the region around which such rotation occurs is one of the most important practical questions for arrhythmia management. For many years, the main method for finding such regions was so-called phase mapping, in which a continuous phase was assigned to points in the heart based on their excitation status and defining the rotation region as a point of phase singularity. Recent analysis, however, showed that in many rotation regimes there exist phase discontinuities and the region of rotation must be defined not as a point of phase singularity, but as a phase defect line. In this paper, we use this novel methodology and perform a comparative study of three different phase definitions applied to in silico data and to experimental data obtained from optical voltage mapping experiments on monolayers of human atrial myocytes. We introduce new phase defect detection algorithms and compare them with those that appeared in literature already. We find that the phase definition is more important than the algorithm to identify sudden spatial phase variations. Sharp phase defect lines can be obtained from a phase derived from local activation times observed during one cycle of arrhythmia. Alternatively, similar quality can be obtained from a reparameterization of the classical phase obtained from observation of a single timeframe of transmembrane potential. We found that the phase defect line length was (35.9 ± 6.2)mm in the Fenton-Karma model and (4.01 ± 0.55)mm in cardiac human atrial myocyte monolayers. As local activation times are obtained during standard clinical cardiac mapping, the methods are also suitable to be applied to clinical datasets. All studied methods are publicly available and can be downloaded from an institutional web-server. © 2022 Kabus et al. access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Fonds Wetenschappelijk Onderzoek, FWO: 1177022N, G025820N; Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-926; KU Leuven: GPUL/20/012DK is supported by KU Leuven grant GPUL/20/012. LA was funded by a KU Leuven FLOF grant and a FWO-Flanders fellowship, grant 1177022N; LL was funded by KU Leuven and FWO-Flanders, grant G025820N. Research at Sechenov University was financed by The Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers "Digital biodesign and personalized healthcare" 075-15-2020-926. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to Sven O. Dekker, Niels Harlaar, Daniël A. Pijnappels and Antoine A.F. de Vries for providing optical voltage mapping data of cardiomyogenically differentiated hiAM monolayers. Moreover, we thank Tim De Coster for helpful comments on the analogy between a PDL and the spiral wave tip trajectory

CMOS MULTI-MODAL INTEGRATED SYSTEMS FOR FUTURE BIOELECTRONICS AND BIOSENSORS

Cells are the basic structural biological units of all known living organisms. They are highly sophisticated system with thousands of molecules operating in hundreds of pathways to maintain their proper functions, phenotypes, and physiological behaviors. With this scale of complexity, cells often exhibit multi-physiological properties as their cellular fingerprints from external stimulations. In order to further advance the frontiers in bioscience and biotechnologies such as stem cell manufacturing, synthetic biology, and regenerative medicine, it is required to comprehend complex cell physiology of living cells. Therefore, a comprehensive set of technologies is needed to harvest quantitative biological data from given cell samples. Such demands have stimulated extensive research on new bioelectronics and biosensors to characterize their functional information by converting their biological activities to electrical signals. As a result, various bioelectronics and biosensors are reported and employed in many in vivo and in vitro applications. Since sensing electrodes of the devices are physically in touch with biological/chemical samples and record their signals, long-term biocompatibility and chemical/mechanical stability is of paramount importance in numerous biological applications. Furthermore, the devices should achieve high sensitivity/resolution/linearity, large field-of-view (FoV), multi-modal sensing, and real-time monitoring, while maintaining small feature size of devices to use small volume of biological/chemical samples and reduce cost. As a result, My Ph.D research aims to study interfacial electrochemical impedance spectroscopy (EIS) of electrodes with different combination of materials/sizes and to design novel multi-modal sensing/actuation array architectures with CMOS compatible in-house post-processing to address the design challenges of the bioelectronics and biosensors.Ph.D

together with details of a mailing list and links to documentation and tutorials

Abstract Chaste -Cancer, Heart And Soft Tissue Environment -is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cellbased simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to 're-invent the wheel' with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular testdriven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence a

Studies of Polycyclic Aromatic Hydrocarbons in Dungeness Crabs: Biomonitoring, Physiologically Based Toxicokinetic Model, and Human Health Risk Assessment

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous pollutants released into the environment from the incomplete combustion of organic material and petrochemical sources. PAH are persistent molecules that partition into sediments and biota in the aquatic environment. PAH such as benzo[a]pyrene, are of concern because they are metabolised into potentially carcinogenic chemicals that can cause tumours in fish and mammals. The purpose of this research was three-fold, (1) to explore the use of the dungeness crab for monitoring PAH in the aquatic environment, (2) to adapt a physiologically based toxicokinetic (PBTK) model to describe the disposition of benzo[a]pyrene in the dungeness crab, and (3) to examine the lifetime cancer risk to humans associated with the consumption of PAH contaminated crabs. Kitimat Arm is an aquatic ecosystem in British Columbia, contaminated with PAH by industrial processes. Dungeness crabs were collected at several sites within this fjord, and concentrations of PAH were determined in the crabs by GCIMS. A synchronous fluorescence spectroscopy assay was adapted to screen crab haemolymph samples for pyrene and it\u27s metabolites. PAH could be readily determined in the tissues of crabs and tissue concentrations decreased with distance from the source of the PAH contamination. Therefore, crabs were an effective tool for monitoring PAH contamination in the fjord. A PBTK model was adapted to describe the disposition of benzo[a]pyrene in the dungeness crab. The model was composed of seven compartments representing the major tissues of the crab. The flux of benzo[a]pyrene in each compartment was described by algebraic and mass-balance differential equations, coded into Visual Basic and solved numerically by an Excel spreadsheet. The model was implemented with parameters, calibrated, and validated using data obtained empirically. The model successfully predicted benzo[a]pyrene concentrations in the tissue compartments after simulated exposures to benzo[a]pyrene by intravascular, oral and water exposure routes. A human health risk assessment was conducted to evaluate the lifetime cancer risk associated with consumption of PAH contaminated crabs from Kitimat Arm. Deterministic and stochastic risk assessment models were implemented. There was an excess cancer risk associated with consumption of crabs from Hospital Beach, an area near the source of PAH contamination