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Three-dimensional vortex flow past a tilting disc valve using a segregated finite element scheme

Laminar vortical flow around a fully opened Bjo¨rk–Shiley valve in an aorta is obtained by solving the three-dimensional incompressible Navier–Stokes equations. Used is a noniterative implicit finite-element Navier–Stokes code developed by the authors, which makes use of the well-known finite difference algorithm PISO. The code utilizes segregated formulation and efficient iterative matrix solvers such as PCGS and ICCG. Computational results show that the three-dimensional vortical flow is recirculating with large shear in the sinus region of the valve chamber. Passing through the valve, the flow is split into major upper and lower jet flows. The spiral vortices generated by the disk are advected in the wake and attenuated rapidly downstream by diffusion. It is shown also that the shear stress becomes maximum near the leading edge of the disk valve.

Numerical Analysis of Three-Dimensional Bjo¨ rk–Shiley Valvular Flow in an Aorta

The work presented in this paper is part of an ongoing effort to use mathematical models to investigate the effects of microgravity on the cardiovascular system. In particular a thirteen compartment lumped parameter representation of the cardiovascular system is used to simulate some of the current hypotheses concerning the mechanism of post-flight orthostatic intolerance. Simulations are compared to astronaut stand test data pre- and post-flight in an effort to quantitatively evaluate alternative hypotheses.

Computational models of cardiovascular function for analysis of post-flight orthostatic intolerance

Orthostatic intolerance following spaceflight remains a critical problem in the current life-science space program. The study presented in this paper is part of an ongoing effort to use mathematical models to investigate the effects of gravitational stresses on the cardiovascular system of normals and microgravity adapted individuals. The authors employ a 12 compartment lumped parameter representation of the hemodynamic system coupled to set-point models of the arterial baroreflex and the cardiopulmonary reflex to investigate the transient response of heart rate to orthostatic stress. They simulate current hypotheses concerning the mechanisms underlying post-spaceflight orthostatic intolerance over a range of physiologically reasonable values and compare the simulations to astronaut stand-test data pre- and post-flight. Furthermore, the authors explore the effects of a potential countermeasure.

Computational model of cardiovascular function during orthostatic stress

New methods are currently being developed that provide a direct connection between the left ventricle and the distal portion of an obstructed coronary artery. Optimal design of such a device can be aided by the use of numerical analysis. Here, computational results are presented showing the hemodynamic flows through a bypass shunt providing flow to a stenosed coronary artery. A PISO type finite element method is used to solve the three-dimensional incompressible Navier-Stokes equations for flow passing through a bypass shunt into the occluded coronary artery. Time-varying inlet flow from the left ventricle is obtained from a simulation of the entire coronary and systemic circulations. The main objective of this study is to delineate the influence of shunt angle on detailed flow patterns. Three different shunt angles are examined. Computational results show a recirculating region generated near the junction of the …

Finite element analysis of blood flow via a shunt from the left ventricle to the distal segment of a stenosed coronary artery

In this study, a computational method is presented to simulate the hemodynamics of patients after the Fontan procedure. The short-term feedback control models are implemented to assess the hemodynamic responses of the patients exposed to stresses such as gravity or hemorrhage. To construct the base line state of the Fontan model, we assume an increase in venous tone, an increase in heart rate, and an increase in systemic resistance all of which are based on clinical observations. For the verification of the present method we simulate a lower body negative pressure (LBNP) test and hemorrhage (20% blood volume loss). Both simulation results are compared to experimental data from the literature. Furthermore, it is shown that cardiac output decreases when the shunt resistance increases.

Computational modeling of the cardiovascular system after Fontan procedure

The objective of this study is to develop a model of the cardiovascular system capable of simulating the short-term (≤5 min) transient and steady-state hemodynamic responses to head-up tilt and lower body negative pressure. The model consists of a closed-loop lumped-parameter representation of the circulation connected to set-point models of the arterial and cardiopulmonary baroreflexes. Model parameters are largely based on literature values. Model verification was performed by comparing the simulation output under baseline conditions and at different levels of orthostatic stress to sets of population-averaged hemodynamic data reported in the literature. On the basis of experimental evidence, we adjusted some model parameters to simulate experimental data. Orthostatic stress simulations are not statistically different from experimental data (two-sided test of significance with Bonferroni adjustment for …

Computational modeling of cardiovascular response to orthostatic stress

A moving actuator type pump has been developed as a multifunctional Korean artificial heart (AnyHeart™). The pump consists of a moving actuator as an energy converter, right and left sacs, polymer (or mechanical) valves, and a rigid polyurethane housing. The actuator containing a brushless DC motor moves back and forth on an epicyclical gear train to produce a pendular motion, which compresses both sacs alternately. Of its versatile functions of ventricular assist device and total artificial heart use, we have evaluated the system performance as a single or biventricular assist device through in vitro and in vivo experiments. Pump performance and anatomical feasibility were tested using various animals of different sizes. In the case of single ventricular assist device (VAD) use, one of the sacs remained empty and a mini-compliance chamber was attached to either an outflow or inflow port of the unused sac. The …

Application of the Moving-Actuator Type Pump as a Ventricular Assist Device: In vitro and in Vivo Studies

Flow through compliant tubes with linear taper in wall thickness is numerically simulated by finite element analysis. Two models are examined: a compliant channel and an axisymmetric tube. For verification of the numerical method, flow through a compliant stenotic vessel is simulated and compared to existing experimental data. Steady two-dimensional flow in a collapsible channel with initial tension is also simulated and the results are compared with numerical solutions from the literature. Computational results for an axisymmetric tube show that as cross-sectional area falls with a reduction in downstream pressure, flow rate increases and reaches a maximum when the speed index (mean velocity divided by wave speed) is near unity at the point of minimum cross-sectional area, indicative of wave-speed flow limitation or “choking” (flow speed equals wave speed) in previous one-dimensional studies. For further …

Numerical simulation of steady flow in a compliant tube or channel with tapered wall thickness

Flow in the blood sac of the Korean artificial heart is numerically simulated by finite element method. Fluid‐structure interaction algorithm is employed to compute the three‐dimensional blood flow interacting with the sac material. For verification of the numerical method of fluid‐structure interaction, two‐dimensional flow in a collapsible channel with initial tension is simulated and the results are compared with numerical solutions from the literature. Incompressible viscous flow and linear elastic solid are assumed for the blood and the sac material in the device, respectively. The motion of the actuator is simplified by a time‐varying pressure boundary condition imposed on the outer surface of the sac. Numerical solutions on the unsteady three‐dimensional blood flow in the sac are provided for the cactus‐type model in this study. During systole, the inlet is closed and the blood sac is squeezed by the action of the …

Numerical analysis of the three‐dimensional blood flow in the Korean artificial heart

Recent advances in computer performance and affordability have accelerated their application to understanding biological phenomena. Computational models are now an integral part of biological and biomedical research. This paper presents a range of examples that illustrate the important role that computational simulation plays in research in the biological and biomedical sciences.

Role of simulation in understanding biological systems

A bypass conduit and related methods include implanting a bypass in the heart between a heart chamber and an at least partially occluded artery to directly flow blood from the chamber to the artery. The bypass conduit is configured to have a higher resistance to blood flow in a first direction than in a second direction without any active flow control mechanism. The bypass conduit may have a first end defining a first opening and a second end defining a second opening and a wall extending between the two ends that defines a lumen extending between the two openings. The ends and the wall of the conduit are configured to have a higher resistance to blood flow in a first direction than in a second direction. A method of bypassing an at least partially occluded artery includes determining a resistance to blood flow of the artery at a location of an at least partial occlusion and selecting a conduit having a configuration …

Conduit designs and related methods for optimal flow control

Quality of Service (QoS)-constrained policy has an advantage to guarantee QoS requirements requested by users. Quorum systems can ensure the consistency and availability of replicated data despite the benign failure of data repositories. We propose a Quorum based resource management scheme, which includes a system resource and network resource, both of which can satisfy the requirements of application QoS. We also propose the resource reconfiguration algorithm based on temporal execution time estimation method. Resource reconfiguration performs the reshuffling of the current available resource set for maintaining the quality level of the resources. We evaluate the effectiveness of resource reconfiguration mechanism in a Heart Hemodynamics analysis. Our approach increases the stability of execution environment as well as decreases the completion time compared to the method that does …

Resource reconfiguration scheme based on temporal quorum status estimation in computational grids

Left Ventricular conduits and related methods are disclosed for achieving bypass of a partially or completely occluded coronary artery. More broadly, conduits for allowing com munication of bodily fluids from one portion of a patient's body to another and related methods are disclosed, including conduits for forming a blood flow path from a chamber of the heart to a vessel or from one vessel to another. In other embodiments, the conduits achieve a coronary artery bypass by allowing blood communication between the left ventricle and the coronary artery or between a proximal portion of the coronary artery and a distal portion of the coronary artery. The conduits may be placed completely through the heart wall or extend only partially therein. Conduits may take on a variety of configurations for allowing the control of blood flow therethrough, including curved or tapered shapes. The conduits may also follow a variety of …

Left ventricular conduits to coronary arteries and methods for coronary bypass

Blood flow in the twin-pulse life-support system (T-PLS) pulsatile blood pump was simulated using a three-dimensional rigid body–fluid–solid interaction model. This model can delineate the blood flow in the T-PLS resulting from operation of a moving actuator. The numerical method used in this study was a commercial finite element package called ADINA. We used a contact and fluid–solid interaction model to compute the blood hemodynamics in the sac. Blood flow is generated by the motion of the actuator, which strongly interacts with the solid material surrounding the blood. To obtain basic bioengineering data on the optimum operation of the T-PLS, we simulated four models in which the actuator moved at different speeds and investigated both the flow pattern and the distribution of shear stress. During the contraction phase, a strong axial flow is observed around the outlet, whereas there is stagnant …

Computational analysis of the three-dimensional hemodynamics of the blood sac in the twin-pulse life-support system

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, ie, tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion …

Computational analysis of tumor angiogenesis patterns using a two-dimensional model

(63) Continuation of application No. 09/534,038, filed on Mar. R EleFlat, Iy assiI Rise

Quality of Service (QoS)-constrained policy has an advantage in that it satisfies QoS requirements requested by users. We propose a Quorum based resource management scheme in Grid and resource reconfiguration algorithm based on temporal execution time estimation for satisfying QoS. We compare and evaluate the processing time and deviation of the resource reconfiguration algorithm using a Heart Hemodynamics analysis.

Resource reconfiguration scheme based on temporal quorum status estimation for grid management

We aim at introducing a Cl− homeostasis to the cardiac ventricular cell model (Kyoto model), which includes the sarcomere shortening and the mitochondria oxidative phosphorylation. First, we examined mechanisms underlying the cell volume regulation in a simple model consisting of Na+/K+ pump, Na+–K+–2Cl− cotransporter 1 (NKCC1), cystic fibrosis transmembrane conductance regulator, volume-regulated Cl− channel and background Na+, K+ and Cl− currents. The high intracellular Cl− concentration of approximately 30 mM was achieved by the balance between the secondary active transport via NKCC1 and passive currents. Simulating responses to Na+/K+ pump inhibition revealed the essential role of Na+/K+ pump in maintaining the cellular osmolarity through creating the negative membrane potential, which extrudes Cl− from a cell, confirming the previous model study in the skeletal muscle. In …

Modelling Cl− homeostasis and volume regulation of the cardiac cell

We developed a comprehensive cell model that simulates the sequential cellular events from membrane excitation to contraction in the human ventricle. By combining this ventricular cell model with a lumped circulation model, we examined how blood pressure dynamics in the ventricle and aorta are related to the cellular processes. To convert cell contraction into ventricular pressure using Laplace's law, we introduced a simple geometric model of a ventricle: one shaped like a thin-walled hemisphere. The force of contraction of a single cell induces tension in the hemispheric ventricular wall, which generates the ventricular and aortic pressures in the lumped circulation model. The time courses of the hemodynamic properties, as well as the volume–pressure trajectory of the left ventricle, were well reproduced. Our multi-scale cardiovascular model, which covers from cardiac cells to the circulatory system, simulates …

A new multi-scale simulation model of the circulation: from cells to system

Vascular endothelial cell (VEC) responds to wall shear stress that has not only spatial variation, but also temporal gradient. To simplify the problem, we first studied how the calcium dynamics of VEC responded to the steady wall shear stress of varying magnitude in a stenosed artery. We then studied how the VEC responded to the periodic shear stress that had temporal variation, as in the pulsatile blood flow. To investigate the multiphysics model of VEC in vitro, we used a mathematical model for intracellular calcium dynamics and a computational fluid dynamics (CFD) method for arterial wall shear stress, either steady or periodic. The CFD results showed that for the steady stenotic flow, the wall shear stress in the recirculating flow was lower than the threshold value, 4 dyne/cm2, at two particular points: flow separation and flow reattachment. For these subthreshold shear stresses, the peak value of the transient calcium response did not hit the normal saturated level, but reached a reduced magnitude. We investigated the effect of severity of stenosis (SOS) of the stenosed artery. For the pulsatile flow, the so-called shear stress slew rate or the temporal gradient of the first upsurge of the periodic flow was an important factor for the VEC calcium dynamics. The calcium response had a finite range of parameter for SOS and shear stress slew rate in which the calcium response was more sensitive than elsewhere, showing a sigmoid pattern.

A new multiphysics model for the physiological responses of vascular endothelial cells to fluid shear stress

We present a computational study of re-entry wave propagation which were does using an electrophysiological model of a human ventricular cell and the associated magnetic field map in three-dimensional (3D) cardiac tissue. A re-entry wave caused by cardiac disease can induce ventricular fibrillation, the major cause of sudden cardiac death. Magnetocardiographs (MCG) can detect early heart muscle ischemia. However, the clinical parameters for using MCGs to identify heart ischemia are poorly understood. Therefore, we examined the details of the magnetic field variation and related physiological parameters for a re-entry wave in 3D cardiac tissue. We used a new human cardiac cell model to simulate action potential (AP) propagation in a 3D rectangular parallelepiped block of tissue, and a finite element method and Galerkin approximation to discretize the 3D domain spatially. The re-entry wave was …

Magnetocardiographic pattern analysis of re-entry wave propagation in three-dimensional ventricular tissue by using a human cardiac cell model

Employing a novel two-dimensional computational model we have simulated the feedback between angiogenesis and tumor growth dynamics. Analyzing vessel formation and elongation towards the concentration gradient of the tumor-derived angiogenetic basic fibroblast growth factor, bFGF, we assumed that prior to the blood vessels reaching the tumor surface, the resulting pattern of tumor growth is symmetric, circular with a common center point. However, after the vessels reach the tumor surface, we assumed that the growth rate of that particular cancer region is accelerated compared to the tumor surface section that lacks neo-vascularization. Therefore, the resulting asymmetric tumor growth pattern is biased towards the site of the nourishing vessels. The simulation results show over time an increase in vessel density, a decrease in vessel branching length, and an increase in fracticality of the vascular branching architecture. Interestingly, over time the fractal dimension displayed a sigmoidal pattern with a reduced rate increase at earlier and later tumor growth stages due to distinct characteristics in vessel length and density. The finding that, at later stages, higher vascular fracticality resulted in a marked increase of tumor slice volume provides further in silico evidence for a functional impact of vascular patterns on cancer growth.

Analyzing the dynamic relationship between tumor growth and angiogenesis in a two dimensional finite element model

We introduce a novel beamforming method named separative surface potential activity beamformer (sSPAB) for MCG source localization. By using this method, we can visualize an activity map of the action potential (AMAP) on the myocardial surface corresponding to a time-specific waveform of measured magnetic fields with an MCG. The method is especially feasible for localization of a rhythmic activity and we used this method for studies of atrial fibrillation (AF). Included in the study were four patients with chronic AF. The obtained f-waves show periodic oscillatory behaviors. By using the sSPAB, we separate the f-wave from the other activations and localize the position of a reentry circuit corresponding to the f-wave. By separating the f-wave time-by-time and visualizing the AMAP for each time-separated waveform, we were able to infer the propagation trace of the AF. After the MCG map-guided minimal AF …

Separative surface potential activation beamformer for localizing reentrant excitation of atrial fibrillation

Recently, many studies reported various advanced e-Health service systems in patient care monitoring utilizing sensor networks and questionnaire systems. We propose an informant driven e-Health service system for the identification of heart rate related mental stress factors with a simple operation of informant-client model. Through performance analysis, we show that the proposed system is a cost-effective stress identification system applicable to mobile wireless networks.

Informant Driven e-Health Service for Identification of Heart Rate Changes from Mental Stress

Atrial fibrillation is the most prevalent arrhythmia, but the mechanisms by which it develops are not clear. Recently, over 90% of paroxysmal atrial fibrillation was found to be located inside the main pulmonary veins (PVs). We found that single cardiac myocytes isolated from the main PVs of rabbits generate spontaneous action potentials (SAP). We therefore assayed the electrical characteristics of these cardiomyocytes. Among the diverse ionic currents identified were INa, ICa,L, IK1, IKr, IKs, Ito, IKsus, Incx, Ipump, IKH and ICl,Ca. In contrast, IK1 was minimal, IKs could be detected only in the presence of 10μM forskolin, and we were unable to detect If and ICa,T, the most important currents for pacemaking activity in sinoatrial node cells. To identify the main cause of SAP, we developed a model that can explain the electrical properties of these cardiomyocytes. After reconstructing the ionic currents based on …

Simulation of spontaneous action potentials of cardiomyocytes in pulmonary veins of rabbits

We developed a numerical model that predicts cardiovascular system response to hemodialysis, focusing on the effect of sodium profile during treatment.

Numerical simulation of the effect of sodium profile on cardiovascular response to hemodialysis

System and method provide an on-line high-performance diagnosis service for cardiovascular disorders. A client requests a high-performance diagnosis by transmitting real electrocardiographic treatment data and magnetocardio graphic treatment data of a human body being a treatment object and virtual heart simulation parameters to a medical service server. The medical service server, in response to the diagnosis request, analyzes the real electrocardiographic treatment data to generate an electrocardiographic analysis result, and performs a virtual heart simulation using the simu lation parameters to generate a pseudo electrocardiogram and magnetocardiogram. Further, the medical service server determines a disease state of the human body on the basis of the electrocardiographic analysis result, the magnetocardio graphic treatment data and the pseudo electrocardiogram and magnetocardiogram, and …

System and method for providing cardiovascular disorder diagnosis services

It has been suggested that Tae-Eum peoples are prone to obesity. Although extensive clinical observations have shown this tendency in Sasang Constitutional Medicine (SCM), no scientific hypothesis has been proposed to delineate its mechanism. According to SCM theory, Tae-Eum peoples have a hypoactive lung system and a hyperactive liver system. In this paper we propose a new hypothesis explaining the tendency of obesity in Tae-Eum people in the viewpoint of cell physiology. The hypoactive lung system might imply an attenuated'respiration'at the cell/subcell level, namely mitochondrial oxygen consumption. Because a functional weakness in mitochondria energy metabolism indicates intrinsic hypo-activity in the consumption (or production) of metabolic energy, we deduced that the tendency can easily induce body weight gain via an increase in anabolism. This relation is also introduced in the graph of cellular metabolic power against body weight. To test this hypothesis, we analyzed the clinical data with 863 subjects. Statistical analysis of the data showed that Tae-Eum peoples had relatively a lower cellular metabolic power, and that the percentage of peoples with BMI> 25 was significantly higher than that of the other constitutional types.

Mitochondria hypothesis on the obesity-prone tendency in Tae-Eum people

Forskolin, a potent activator of adenylyl cyclases, has been implicated in modulating angiogenesis, but the underlying mechanism has not been clearly elucidated. We investigated the signal mechanism by which forskolin regulates angiogenesis. Forskolin stimulated angiogenesis of human endothelial cells and in vivo neovascularization, which was accompanied by phosphorylation of CREB, ERK, Akt, and endothelial nitric oxide synthase (eNOS) as well as NO production and VEGF expression. Forskolin-induced CREB phosphorylation, VEGF promoter activity, and VEGF expression were blocked by the PKA inhibitor PKI. Moreover, phosphorylation of ERK by forskolin was inhibited by the MEK inhibitor PD98059, but not PKI. The forskolin-induced Akt/eNOS/NO pathway was completely inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, but not significantly suppressed by PKI. These inhibitors …

Forskolin increases angiogenesis through the coordinated cross-talk of PKA-dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling

As science technology grows, medical application is becoming more complex to solve the physiological problems within expected time. Workflow management systems (WMS) in Grid computing are promising solution to solve the sophisticated problem such as genomic analysis, drug discovery, disease identification, etc. Although existing WMS can provide basic management functionality in Grid environment, consideration of user requirements such as performance, reliability and interaction with user is missing. In this paper, we propose hybrid workflow management system for heart disease identification and discuss how to guarantee different user requirements according to user SLA. The proposed system is applied to Physio-Grid e-health platform to identify human heart disease with ECG analysis and Virtual Heart Simulation (VHS) workflow applications.

Policy-based hybrid workflow management system for heart disease identification

Workflow management systems (WMS) in Grid computing are becoming more important to solve the sophisticated problem such as genomic analysis, drug discovery, disease identification, etc. In this paper, we discuss how to guarantee different user requirements according to user SLA in Grid workflow management system. An adaptive workflow management system for Quality of Service (QoS) constrained medical Grid application is designed and implemented to provide QoS awareness WMS and is applied to Physio-Grid e-health platform to identify human heart disease. The experimental result shows that the proposed system can flexibly enhance the Physio-Grid platform in terms of SLA guarantee of different user.

Adaptive workflow-policy based management scheme for advanced heart disease identification

This study investigated the spiral wave dynamics in cardiac tissue according to the severity of fibrosis in the hypertrophic humanventricle by simulating propagation of the electric wave. We used amodel of the human ventricular cell to describe the cellularelectrophysiology and a two-dimensional monodomain method to compute the electric wave propagation in ventricular tissue using finiteelement approximation. To delineate the effect of fibrosis on thewave dynamics, a model of hypertrophic cardiac tissue with randomlydistributed fibroblasts was simulated. The electrical conductivityof the fibroblasts was estimated from the experimental data. In thefibrotic cardiac tissue, we generated a reentrant wave and predictedits dynamic variation according to the severity of fibrosis. Compared to the reentrant wave in normal tissue, a conduction delaywas observed in the fibrotic tissue. Furthermore, one spiral wavebroke into …

Simulation of Reentrant Wave Dynamics in Cardiac Tissue According to the Severity of Fibrosis

Blood is composed of blood cells suspended in plasma. The viscosity of blood varies with clinical conditions that influence blood cell aggregation and the hematocrit, and involves hemodynamic changes in vessels directly [1–3]. Generally, in arteries with diameters larger than 3 mm, the viscosity of blood is essentially constant when the shear rate exceeds 100 s−1 [4]. By contrast, in capillaries with diameters smaller than 400 μm, the decrease in the vessel diameter reduces the viscosity of blood by redistributing blood cells at the center of the vessel [5]. Therefore, we should consider non-Newtonian blood flow behavior according to the flow conditions in blood vessels. This section briefly describes the basics of fluid mechanics that might be useful for understanding cerebral hemodynamics.

Hemodynamics

Bilateral intimal thickening of the distal internal carotid arteries (ICAs) and the development of many collateral vessels in the base of the brain characterize moyamoya disease (MMD). Although the etiology of and the reason why MMD is limited to the major intracranial vessels remain unclear, flow dynamics, such as shear stress, may be related to its smooth-muscle cell migration. Therefore, this study was performed to determine the local hemodynamic factor, which concerns the predominance of specific anatomical sites, such as the distal ICA in the early stage and the proximal posterior cerebral artery (PCA) in the advanced stage of MMD.

Computational analysis of hemodynamics using a two-dimensional model in moyamoya disease

Background/Aim: We previously developed the cold dialysate regeneration system (CDRS) for use in daily home hemodialysis (HD). This study evaluates the long-term efficacy of the CDRS using a mathematical method. Method: HD with the CDRS was simulated using a method that integrates the mass-transfer model and the dialyzer solute kinetics model with a newly proposed model of CDRS function. Results: We mathematically assessed the long-term efficacy of HD with the CDRS. The weekly treatment time required for HD with the CDRS was reduced significantly using the daily dialysis method; it required only an 11% longer treatment time to obtain the corrected equivalent renal clearance and a 14% shorter time for the standard Kt/V, compared with thrice weekly treatment with conventional HD. Conclusion: By developing a mathematical model to test the long-term efficacy of the new CDRS, we …

Mathematical analysis of the long-term efficacy of daily home hemodialysis therapy with a cold dialysate regeneration system

In this letter, we discuss a sensor-integrated system model for metabolic syndrome prediction with workflow system. This model measures not only a cell temperature variation using invasive method but also controlling simulation for metabolic syndrome prediction. To identify the system realization, we discuss the schemes for predicting metabolic syndrome from measurement of mitochondrial activity by using high precision sensors and integrated simulation model of human energetic under high performance workflow computing environment. To predict metabolic syndrome, we built a sensor-integrated chamber that had network interface to deliver analysis results of human cells, annotation data from public hospital, and metabolic data. Using the proposed system, we showed the possibility to evaluate the functionality of human mitochondria and analyze energy metabolism.

A cooperative metabolic syndrome estimation with high precision sensing unit

For blood purification systems using a semipermeable membrane, the convective mass transfer by ultrafiltration plays an important role in toxin removal. The increase in the ultrafiltration rate can improve the toxin removal efficiency of the device, ultimately reducing treatment time and cost. In this study, we assessed the effects of pulsatile flow on the efficiency of the convective toxin removal in blood purification systems using theoretical methods.

Computational assessment of the effects of a pulsatile pump on toxin removal in blood purification

This paper will introduce basic information on mitochondrial medicine and the direction of research. This paper will first introduce basic information on mitochondrial medicine and the direction of research. Then, it will delineate recent research on biomedical engineering methods and applications of mitochondrial medicine and discuss prospects of this research.

Mitochondrial medicine and biomedical engineering

Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by the marked presence of inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated in the pathogenesis of nasal polyposis. The study was designed to investigate whether interferon-gamma (IFN-γ) can induce the augmentation of galectin-9 expression and induce the expression of galectin-9 in nasal polyps. We examined the correlation between galectin-9 expression and eosinophil infiltration in nasal polyps. In addition, we identified the signaling pathways involved in the elevation of galectin-9 expression in response to IFN-γ. Our data demonstrate that the involvement of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal …

Expression of galectin-9 by IFN-γ stimulated human nasal polyp fibroblasts through MAPK, PI3K, and JAK/STAT signaling pathways

In this study, we determined the optimal position and direction of a one-channel bipolar electrocardiogram (ECG), used ubiquitously in healthcare. To do this, we developed a three-dimensional (3D) electrophysiological model of the heart coupled with a torso model that can generate a virtual body surface potential map (BSPM). Finite element models of the atria and ventricles incorporated the electrophysiological dynamics of atrial and ventricular myocytes, respectively. The torso model, in which the electric wave pattern on the cardiac tissue is reflected onto the body surface, was implemented using a boundary element method. Using the model, we derived the optimal positions of two electrodes, 5 cm apart, of the bipolar ubiquitous ECG (U-ECG) for detecting the P, R, and T waves. This model can be used as a simulation tool to design U-ECG device for use for various arrhythmia and normal patients.

Predicting the optimal position and direction of a ubiquitous ECG using a multi-scale model of cardiac electrophysiology

Based on the similarity between a reentrant wave in cardiac tissue and a vortex in fluid dynamics, the authors hypothesised that a new non-dimensional index, like the Reynolds number in fluid dynamics, may play a critical role in categorising reentrant wave dynamics. Therefore the goal of the present study is to devise a new index to characterise electric wave conduction in cardiac tissue and examined whether this index can be used as a biomarker for categorising the reentrant wave pattern in cardiac tissue. Similar to the procedure used to derive the Reynolds number in fluid dynamics, the authors used a non-dimensionalisation technique to obtain the new index. Its usefulness was verified using a two-dimensional simulation model of electrical wave propagation in cardiac tissue. The simulation results showed that electrical waves in cardiac tissue move into an unstable region when the index exceeds a threshold …

New index for categorising cardiac reentrant wave: in silico evaluation

Left ventricular assist device (LVAD) support under cannulation connected from the left atrium to the aorta (LA-AA) is used as a bridge to recovery in heart failure patients because it is non-invasive to ventricular muscle. However, it has serious problems, such as valve stenosis and blood thrombosis due to the low ejection fraction of the ventricle. We theoretically estimated the effect of the in-series cannulation, connected from ascending aorta to descending aorta (AA-DA), on ventricular unloading as an alternative to the LA-AA method. We developed a theoretical model of a LVAD-implanted cardiovascular system that included coronary circulation. Using this model, we compared hemodynamic responses according to various cannulation methods such as LA-AA, AA-DA, and a cannulation connected from the left ventricle to ascending aorta (LV-AA), under continuous and pulsatile LVAD supports. The AA-DA method provided 14% and 18% less left ventricular peak pressure than the LA-AA method under continuous and pulsatile LVAD conditions, respectively. The LA-AA method demonstrated higher coronary flow than AA-DA method. Therefore, the LA-AA method is more advantageous in increasing ventricular unloading whereas the AA-DA method is a better choice to increase coronary perfusion.

Theoretical estimation of cannulation methods for left ventricular assist device support as a bridge to recovery

The human body requires a complex circulatory system to supply nutrients to, and to remove metabolic waste products from, its tissues. Given this primary purpose, circulatory function is closely related to the hemodynamic characteristics of blood vessels. This includes not only macroscale fluid dynamics, but also mass transfer in the microvasculature. Many experimental and clinical studies have examined these characteristics of vascular function. Over the past 50 years, mathematical modeling has become a powerful adjunct to such studies, as modeling provides a rational framework within which to analyze the cardiovascular system.

Computational Analysis of Cardiovascular Hemodynamics

Facing the increasing demands and challenges in the area of chronic disease care, various studies on the healthcare system which can, whenever and wherever, extract and process patient data have been conducted. Chronic diseases are the long-term diseases and require the processes of the real-time monitoring, multidimensional quantitative analysis, and the classification of patients' diagnostic information. A healthcare system for chronic diseases is characterized as an at-hospital and at-home service according to a targeted environment. Both services basically aim to provide patients with accurate diagnoses of disease by monitoring a variety of physical states with a number of monitoring methods, but there are differences between home and hospital environments, and the different characteristics should be considered in order to provide more accurate diagnoses for patients, especially, patients having …

An integrated healthcare system for personalized chronic disease care in home–hospital environments

A bipolar mini-ECG for ubiquitous healthcare (U-ECG) has been introduced, and various studies using the U-ECG device are in progress. Because it uses two electrodes within a small torso surface area, the design of the U-ECG must be suitable for detecting ECG signals. Using a 3-D model of cardiac electrophysiology, we have developed a simulation method for identifying the optimal placement of U-ECG electrodes on the torso surface. We simulated the heart-torso model to obtain a body surface potential map and ECG waveforms, which were compared with the empirical data. Using this model, we determined the optimal placement of the two U-ECG electrodes, spaced 5 cm apart, for detecting the P, R, and T waves. The ECG data, obtained using the optimal U-ECG placement for a specific wave, showed a clear shape for the target wave, but equivocal shapes for the other waves. The present study provides an …

Patient-specific identification of optimal ubiquitous electrocardiogram (U-ECG) placement using a three-dimensional model of cardiac electrophysiology

•  L‐type Ca2+ channels are inactivated by an increase in intracellular [Ca2+], known as Ca2+‐dependent inactivation (CDI), and are inhibited by Ca2+ released from the sarcoplasmic reticulum (SR), known as release‐dependent inhibition (RDI).
•  RDI was greatly enhanced by the removal of Na+–Ca2+ exchange (Incx), and attenuated by blocking Ca2+ release from the sarcoplasmic reticulum (SR), and abolished by Ca2+ chelator.
•  We analysed the role of ICaL, SR and Incx and found Incx prevented CDI by controlling [Ca2+] in the junctional subsarcolemmal space ([Ca2+]JSS).
•  With previously developed model and the addition of Ca2+ binding kinetics of L‐type Ca2+ channels (ICaLs), we successfully reproduced CDI and RDI.
•  From this simulation, we found Incx actively participated in controlling CDI by the regulation of [Ca2+]JSS and by controlling SR Ca2+ refilling.

Analysis of factors affecting Ca2+‐dependent inactivation dynamics of L‐type Ca2+ current of cardiac myocytes in pulmonary vein of rabbit

(57) abstract A method of determining optimal parameters for measuring biological signals of a real body by using a virtual body model modeling a virtual body simulating the real body includes generating a plurality of virtual biological signals of the Vir tual body using the virtual body model by changing param eters that determine characteristics of the virtual biological signals; selecting at least one of the virtual biological signals based on a characteristic of one of the biological signals of the real body; and outputting at least one parameter used togen erate the selected at least one virtual biological signal as at least one optimal parameter for measuring the one biological signal of the real body.

Method of and apparatus for determining optimal parameters for measuring biological signals based on virtual body model

This work reviews the main aspects of human bioenergetics and the dynamics of the cardiovascular system, with emphasis on modelling their physiological characteristics. The methods used to study human bioenergetics and circulation dynamics, including the use of mathematical models, are summarised. The main characteristics of human bioenergetics, including mitochondrial metabolism and global energy balance, are first described, and the systemic aspects of blood circulation and related physiological issues are introduced. The authors also discuss the present status of studies of human bioenergetics and blood circulation. Then, the limitations of the existing studies are described in an effort to identify directions for future research towards integrated and comprehensive modelling. This review emphasises that a multi-scale and multi-physical approach to bioenergetics and blood circulation that considers …

Systemic modelling of human bioenergetics and blood circulation

Sasang constitutional medicine (SCM) is a traditional form of medicine that is widely used in Korea to clinically diagnose and treat disease. The main characteristic of SCM is its classification of people according to physical constitution. The theory asserts that four different types of physical constitution exist: Taeyang, Soyang, Taeeum, and Soeum. One noticeable clinical observation in SCM is that Taeeum-type people are prone to obesity. Although extensive clinical investigations have shown this tendency in SCM, no scientific hypothesis has been proposed to delineate its mechanism. According to SCM theory, Taeeum-type people have a hypoactive lung system and a hyperactive liver system. In this paper, we propose a new hypothesis explaining this finding from a physiological viewpoint. A functional weakness in the lung system indicates intrinsic hypoactivity in the consumption of metabolic energy, therefore we …

Taeeum-type people in Sasang constitutional medicine have a reduced mitochondrial metabolism

To quantify the reduction in workload during intra-aortic balloon pump (IABP) therapy, indirect parameters are used, such as the mean arterial pressure during diastole, product of heart rate and peak systolic pressure, and pressure-volume area. Therefore, we investigated the cardiac energy consumption during IABP therapy using a cardiac electromechanics model. We incorporated an IABP function into a previously developed electromechanical model of the ventricle with a lumped model of the circulatory system and investigated the cardiac energy consumption at different IABP inflation volumes. When the IABP was used at inflation level 5, the cardiac output and stroke volume increased 11%, the ejection fraction increased 21%, the stroke work decreased 1%, the mean arterial pressure increased 10%, and the ATP consumption decreased 12%. These results show that although the ATP consumption is decreased significantly, stroke work is decreased only slightly, which indicates that the IABP helps the failed ventricle to pump blood efficiently.

Computational quantification of the cardiac energy consumption during intra-aortic balloon pumping using a cardiac electromechanics model

The purpose of this study was to propose a patient-specific model of atrial fibrillation (AF) and apply it to virtual radiofrequency ablation (RFA). We obtained patient-specific geometries of the left atrium (LA) from CT data and constructed three-dimensional (3D) simulation models. A bidomain Courtemanche model was used to simulate the 3D electric waves on the LA surface, and an S1-S2 protocol was applied to induce AF in the model. To identify scar areas in the models, we converted clinically measured voltage data on the LA surface to the scar maps of the simulation model. Then, after initiation of AF, we applied the virtual ablation scheme to the model and investigated whether the AF was terminated by the scheme. The computed results of AF and ablation were similar to those of clinical observation, providing a clinically important simulation method for preclinical virtual trials of AF treatment.

A patient-specific model of virtual ablation for atrial fibrillation

The current study proposes a model of the cardiovascular system that couples heart cell mechanics with arterial hemodynamics to examine the physiological role of arterial blood pressure (BP) in left ventricular hypertrophy (LVH). We developed a comprehensive multiphysics and multiscale cardiovascular model of the cardiovascular system that simulates physiological events, from membrane excitation and the contraction of a cardiac cell to heart mechanics and arterial blood hemodynamics. Using this model, we delineated the relationship between arterial BP or pulse wave velocity and LVH. Computed results were compared with existing clinical and experimental observations. To investigate the relationship between arterial hemodynamics and LVH, we performed a parametric study based on arterial wall stiffness, which was obtained in the model. Peak cellular stress of the left ventricle and systolic blood pressure (SBP) in the brachial and central arteries also increased; however, further increases were limited for higher arterial stiffness values. Interestingly, when we doubled the value of arterial stiffness from the baseline value, the percentage increase of SBP in the central artery was about 6.7% whereas that of the brachial artery was about 3.4%. It is suggested that SBP in the central artery is more critical for predicting LVH as compared with other blood pressure measurements.

An integrative model of the cardiovascular system coupling heart cellular mechanics with arterial network hemodynamics

A variety of biological theories and facts have been integrated into computer software and databases. This has made it possible for computer scientists, mathematicians, and physicists to collaborate with biologists to build a well-known tool of system biology called the virtual cell (VCell)(1). Data on cellular biochemistry and cell structure have been merged into this system to explain how cells produce complex physiological and metabolic processes. Because a cell behaves like a highly complex factory that organizes thousands of different molecules to produce a specialized function, the VCell must implement cellular biological functions with proper parameters and models. In this sense, the VCell is a computational framework with tools for describing, predicting, and understanding intricate cellular biological systems through modeling and simulations. This tool is also very useful for guiding experimental design …

Introduction to Virtual Cell and its Possible Application to Toxicity

Although complex fractionated electrogram (CFE) is known to be a target for catheter ablation of fibrillation, its physiological meaning in fibrillation wave-dynamics remains to be clarified. We evaluated the spatiotemporal relationships among the parameters of fibrillation wave-dynamics by simulation modeling. We generated maps of CFE-cycle length (CFE-CL), local dominant frequency (LDF), wave break (WB), and phase singularity (PS) of fibrillation in 2-dimensional homogeneous bidomain cardiac modeling (1,000× 1,000 cells ten Tusscher model). We compared spatiotemporal correlations by dichotomizing each maps into 10× 10 lattice zones. In spatial distribution, WB and PS showed excellent correlation (R= 0.963, P< 0.001). CFE-CL had weak correlations with WB (R= 0.288, P< 0.001), PS (R= 0.313, P< 0.001), and LDF (R=-0.411, P< 0.001). However, LDF did not show correlation with PS or WB. PSs were mostly distributed at the periphery of low CFE-CL area. Virtual ablation (5% of critical mass) of CFE-CL< 100 ms terminated fibrillation at 14.3 sec, and high LDF ablation (5% of critical mass) changed fibrillation to organized tachycardia, respectively. In homogeneous 2D fibrillation modeling, CFE-CL was weakly correlated with WB, PS, and LDF, spatiotemporally. PSs are mostly positioned at the periphery of low CFE-CL areas, and virtual ablation targeting low CFE-CL regions terminated fibrillation successfully.

The relationship among complex fractionated electrograms, wavebreak, phase singularity, and local dominant frequency in fibrillation wave-dynamics: a modeling comparison study

By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text References Special issue on Toward physiome based therapeutics

Special issue on" Toward physiome based therapeutics".


            The fractional flow reserve (FFR) is a widely used clinical index to evaluate the functional severity of coronary stenosis. 
            A computer simulation method based on patients’ computed tomography (CT) data is a plausible non-invasive approach for computing the FFR. 
            This method can provide a detailed solution for the stenosed coronary hemodynamics by coupling computational fluid dynamics (CFD) with the lumped parameter model (LPM) of the cardiovascular system. 
            In this work, we have implemented a simple computational method to compute the FFR. As this method uses only coronary arteries for the CFD model and includes only the LPM of the coronary vascular system, 
            it provides simpler boundary conditions for the coronary geometry and is computationally more efficient than existing approaches.
        

A novel patient-specific model to compute coronary fractional flow reserve

The heart characteristic length, the inverse of conduction velocity (CV), and the inverse of the refractory period are known to determine vulnerability to cardiac fibrillation (fibrillation number, FibN) in in silico or ex vivo models. The purpose of this study was to validate the accuracy of FibN through in silico atrial modeling and to evaluate its clinical application in patients with atrial fibrillation (AF) who had undergone radiofrequency catheter ablation. We compared the maintenance duration of AF at various FibNAF values using in silico bidomain atrial modeling. Among 60 patients (72% male, 54 ± 13 years old, 82% with paroxysmal AF) who underwent circumferential pulmonary vein isolation (CPVI) for AF rhythm control, we examined the relationship between FibNAF and postprocedural AF inducibility or induction pacing cycle length (iPCL). Clinical FibNAF was calculated using left atrium (LA) dimension …

Fibrillation number based on wavelength and critical mass in patients who underwent radiofrequency catheter ablation for atrial fibrillation

When using a pulsatile left ventricular assist device (LVAD), it is important to reduce the cardiac load variations of the native heart because severe cardiac load variations can induce ventricular arrhythmia. In this study, we investigated the effect of counter-pulsation control of the LVAD on the reduction of cardiac load variation.

Effect of counter-pulsation control of a pulsatile left ventricular assist device on working load variations of the native heart

Using a three-dimensional electromechanical model of the canine ventricles with dyssynchronous heart failure, we investigated the relationship between severity of valve regurgitation and ventricular mechanical responses. The results demonstrated that end-systolic tension in the septum and left ventricular free wall was significantly lower under the condition of mitral regurgitation (MR) than under aortic regurgitation (AR). Stroke work in AR was higher than that in MR. On the other hand, the difference in stroke volume between the two conditions was not significant, indicating that AR may cause worse pumping efficiency than MR in terms of consumed energy and performed work.

Computational analysis of the effect of valvular regurgitation on ventricular mechanics using a 3D electromechanics model

Plant lectins have attracted much attention for biomedical applications including targeted drug delivery system and therapy against tumors and microbial infections. The main problem of using lectins as a biomedical tool is a batch-to-batch variation in isoforms content. The production of lectins using recombination tools has the advantage of obtaining high amounts of proteins with more precise properties, but there are only a handful of functional recombinant lectins presently available. A fetuin/asialo-fetuin specific lectin, Rhodobindin, has unique tandem repeats structure which makes it useful in exploiting for recombinant lectin. We developed three functional recombinant lectins using E. coli expression system: one from full cDNA sequence and two from fragmentary sequences of Rhodobindin. Hemagglutinating activity and solubility of the recombinant lectins were highest at OD 0.7 cell concentration at 20 °C. The optimized process developed in this study was suitable for the quality-controlled production of high amounts of soluble recombinant lectins.

Functional recombinants designed from a fetuin/asialofetuin-specific marine algal lectin, rhodobindin

In view of the above problems, the goal of our invention is to provide an arrhythmia-diagnosing device that is capable of predicting and diagnosing electrical wave tornados, one cause of arrhythmia, by using a non-dimensional parameter, to identify patients at risk of death or brain death from arrhythmias and significantly reduce the mortality of these patients.

Arrhythmia diagnosis method and device

Vagal nerve activity has been known to play a crucial role in the induction and maintenance of atrial fibrillation (AF). However, it is unclear how the distribution and concentration of local acetylcholine (ACh) promotes AF. In this study, we investigated the effect of the spatial distribution and concentration of ACh on fibrillation patterns in an in silico human atrial model. A human atrial action potential model with an ACh-dependent K+ current (IKAch) was used to examine the effect of vagal activation. A simulation of cardiac wave dynamics was performed in a realistic 3D model of the atrium. A model of the ganglionated plexus (GP) and nerve was developed based on the “octopus hypothesis”. The pattern of cardiac wave dynamics was examined by applying vagal activation to the GP areas or randomly. AF inducibility in the octopus hypothesis-based GP and nerve model was tested. The effect of the ACh concentration level was also examined. In the single cell simulation, an increase in the ACh concentration shortened APD90 and increased the maximal slope of the restitution curve. In the 3D simulation, a random distribution of vagal activation promoted wavebreaks while ACh secretion limited to the GP areas did not induce a noticeable change in wave dynamics. The octopus hypothesis-based model of the GP and nerve exhibited AF inducibility at higher ACh concentrations. In conclusion, a 3D in silico model of the GP and parasympathetic nerve based on the octopus model exhibited higher AF inducibility with higher ACh concentrations.

Inducibility of human atrial fibrillation in an in silico model reflecting local acetylcholine distribution and concentration

Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation.

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity

A left ventricular assist device (LVAD) is normally contraindicated in significant aortic regurgitation (AR) and requires intraoperative valve repair or exclusion. Nevertheless, AR can coexist with an LVAD, so a valid question when asked might still be of clinical significance. The purpose of this study is to analyze the effects of valve regurgitation on the pumping efficacy of continuous and pulsatile LVADs with a computational method.

Mathematical analysis of the effects of valvular regurgitation on the pumping efficacy of continuous and pulsatile left ventricular assist devices


            Flow resistances exerted in the coronary arteries are key parameters for the image-based computer simulation of coronary hemodynamics. 
            A simple and reliable estimation of resistances is crucial for computing the fractional flow reserve (FFR) of stenosed coronary arteries. 
            In this study, we propose a novel method to estimate flow resistances using vessel length, which can be used across various image modalities. 
            We validated this method by comparing it with the traditional muscle volume-based method and clinical data.
        

Estimation of the flow resistances exerted in coronary arteries using a vessel length-based method

Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their ρ0 cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration.

Minimal systems analysis of mitochondria-dependent apoptosis induced by cisplatin

Flow resistances exerted in the coronary arteries are the key parameters for the image-based computer simulation of coronary hemodynamics. The resistances depend on the anatomical characteristics of the coronary system. A simple and reliable estimation of the resistances is a compulsory procedure to compute the fractional flow reserve (FFR) of stenosed coronary arteries, an important clinical index of coronary artery disease. The cardiac muscle volume reconstructed from computed tomography (CT) images has been used to assess the resistance of the feeding coronary artery (muscle volume-based method). In this study, we estimate the flow resistances exerted in coronary arteries by using a novel method. Based on a physiological observation that longer coronary arteries have more daughter branches feeding a larger mass of cardiac muscle, the method measures the vessel lengths from coronary …


            This study investigates the relationship between fractional flow reserve (FFR) and wall shear stress (WSS) using a virtual stenosis model of coronary arteries. 
            The research explores how FFR decreases and WSS increases as stenotic severity progresses. Simulations based on patient-specific models of coronary arteries were used to validate the model. 
            The findings may aid clinicians in understanding the relationship between FFR and WSS, helping to improve patient-specific treatment strategies.
        

A patient-specific virtual stenotic model of the coronary artery to analyze the relationship between fractional flow reserve and wall shear stress

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in-silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL< 120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p< 0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r= 0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p< 0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p< 0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was …

Spatial reproducibility of complex fractionated atrial electrogram depending on the direction and configuration of bipolar electrodes: an in-silico modeling study

As the stenotic severity of a patient increases, fractional flow reserve (FFR) decreases, whereas the maximum wall shear stress (WSSmax) increases. However, the way in which these values can change according to stenotic severity has not previously been investigated. The aim of this study is to devise a virtual stenosis model to investigate variations in the coronary hemodynamic parameters of patients according to stenotic severity.

The role of the autonomic nervous system (ANS) on atrial fibrillation (AF) is difficult to demonstrate in the intact human left atrium (LA) due to technical limitations of the current electrophysiological mapping technique. We examined the effects of the ANS on the initiation and maintenance of AF by employing a realistic in silico human left atrium (LA) model integrated with a model of ganglionated plexi (GPs).

Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study

Swirl flow is often found in proximal coronary arteries, because the aortic valves can induce swirl flows in the coronary artery due to vortex formation. In addition, the curvature and tortuosity of arterial configurations can also produce swirl flows. The present study was performed to investigate fractional flow reserve alterations in a post-stenotic distal part due to the presence of pre-stenotic swirl flow by computational fluid dynamics analysis for virtual stenotic models by quantifying fractional flow reserve(FFR). Simplified stenotic coronary models were divided into those with and without pre-stenotic swirl flow. Various degrees of virtual stenosis were grouped into three grades: mild, moderate, and severe, with degree of stenosis of 0 ~ 40%, 50 ~ 60%, and 70 ~ 90%, respectively. In this study, three-dimensional computational hemodynamic simulations were performed under hyperemic conditions in virtual stenotic …

The influences of swirl flow on fractional flow reserve in mild/moderate/severe stenotic coronary arterial models


            This study validates a novel vessel-length based computational fluid dynamics (CFD) method for calculating fractional flow reserve (FFR) from coronary computed tomography angiography (CT-FFR). 
            The study involved 117 patients and demonstrated that CT-FFR provides better diagnostic accuracy than CCTA alone in identifying functionally significant coronary artery disease. 
            CT-FFR was computed using a personal computer with improved efficiency, making it more applicable in clinical practice.
        

Diagnostic Performance of a Novel Method for Fractional Flow Reserve Computed from Noninvasive Computed Tomography Angiography (NOVEL-FLOW Study)

La angina vasospástica (AVS) puede causar daño endotelial y formación de trombo. El objetivo de este estudio es evaluar mediante tomografía de coherencia óptica (OCT) la incidencia de trombo y las características de la placa en segmentos con espasmo coronario comparados con segmentos sin espasmo en pacientes con sospecha de AVS.

Presencia de trombo y erosión de placa en pacientes con angina vasospástica mediante tomografía de coherencia óptica

Coronary computed tomography angiography (CCTA)-derived fractional flow reserve from computed tomography (CT-FFR) may provide better diagnostic performance over CCTA alone, but the complexity of its method limits the use in clinical environment. The aim of the present study is to validate a newly developed vessel-length based computational fluid dynamics scheme for the computation of FFR based on CCTA data, compare them with invasively measured FFR, and evaluate its diagnostic performance with that of CCTA. One hundred seventeen patients from 4 medical institutions who had clinically indicated invasive coronary angiography for suspected coronary artery disease (CAD) were enrolled. Invasive FFR measurement was performed in 218 vessels and these measurements were regarded as the reference standard. The accuracy, sensitivity, specificity, positive predictive value, and negative …

Diagnostic performance of a novel method for fractional flow reserve computed from noninvasive computed tomography angiography (NOVEL-FLOW Study)

Those classified as Tae-Eum (TE)-type people in Sasang constitutional medicine (SCM) are prone to obesity. Although extensive clinical observations have confirmed this tendency, the underlying physiological mechanisms are unknown. Here, we propose a novel hypothesis using integrative physiology to explain this phenomenon.

Lower cellular metabolic power can be an explanation for obesity trend in Tae-Eum type: hypothesis and clinical observation

Hemodynamic simulation for quantifying fractional flow reserve (FFR) is often performed in a patient-specific geometry of coronary arteries reconstructed from the images from various imaging modalities. Because optical coherence tomography (OCT) images can provide more precise vascular lumen geometry, regardless of stenotic severity, hemodynamic simulation based on OCT images may be effective. The aim of this study is to perform OCT–FFR simulations by coupling a 3D CFD model from geometrically correct OCT images with a LPM based on vessel lengths extracted from CAG data with clinical validations for the present method.

A vessel length-based method to compute coronary fractional flow reserve from optical coherence tomography images

We previously reported that stable rotors are observed in in-silico human atrial fibrillation (AF) models, and are well represented by a dominant frequency (DF). In the current study, we hypothesized that the outcome of DF ablation is affected by conduction velocity (CV) conditions and examined this hypothesis using in-silico 3D-AF modeling.

Effectiveness of atrial fibrillation rotor ablation is dependent on conduction velocity: An in-silico 3-dimensional modeling study

The biomechanics of the cerebral venous system plays an important role in determining blood flow to the brain. Computational approaches to help elucidate the role of the cerebral venous system in health and disease have largely focused on lumped-parameter models and one-dimensional computational fluid dynamics simulations. To expand upon the prior work, and to investigate the possible role of cerebral venous collapse in normal physiology and pathological conditions, we developed a fluid-structure interaction (FSI) model of the cerebral venous transverse sinus (TS), coupled to a lumpedparameter representation of the upstream cerebral circulation to provide boundary conditions for the FSI simulation. We simulated the effects of local venous hemodynamics on the TS distention and investigated TS vascular collapse under increased intracranial pressure, as has been hypothesized in the pathogenesis of idiopathic intracranial hypertension. Our baseline simulations reproduced pressures and flows in the cerebral venous system that compared favorably with what has been reported in the literature. The FSI simulations under increased intracranial pressure showed a decreased venous flow through and progressive collapse of the TS veins. Our simulations captured the dynamic behavior of the vascular collapse and may help shed light on the interactions between the cerebrovascular and cerebrospinal fluid spaces in health and disease.

Fluid-structure interaction in the cerebral venous sinus

Individuals with Mibyeong are difficult to identify. Although extensive research has attempted to introduce an easy and clear method for Mibyeong diagnosis, the indices used to categorize Mibyeong severity are unclear. We hypothesized that individuals with severe Mibyeong have reduced physiological function

Physiological indices for the categorization of Mibyeong severity (vol 6, pg 88, 2017)

Valvular insufficiency affects cardiac responses and the pumping efficacy of left ventricular assist devices (LVADs) when patients undergo LVAD therapy. Knowledge of the effect of valvular regurgitation on the function of LVADs is important when treating heart failure patients. The goal of this study was to examine the effect of valvular regurgitation on the ventricular mechanics of a heart under LVAD treatment and the pumping efficacy of an LVAD using a computational model of the cardiovascular system. For this purpose, a 3D electromechanical model of failing ventricles in a human heart was coupled with a lumped-parameter model of valvular regurgitation and an LVAD-implanted vascular system. We used the computational model to predict cardiac responses with respect to the severity of valvular regurgitation in the presence of LVAD treatment. An LVAD could reduce left ventricle (LV) pressure (up to 34 …

Computational analysis of the effect of mitral and aortic regurgitation on the function of ventricular assist devices using 3D cardiac electromechanical model

The biomechanics of the cerebral venous system plays an important role in determining blood flow to the brain. Computational approaches to help elucidate the role of the cerebral venous system in health and disease have largely focused on lumped-parameter models and one-dimensional computational fluid dynamics simulations. To expand upon the prior work, and to investigate the possible role of cerebral venous collapse in normal physiology and pathological conditions, we developed a fluid-structure interaction (FSI) model of the cerebral venous transverse sinus (TS), coupled to a lumped-parameter representation of the upstream cerebral circulation to provide boundary conditions for the FSI simulation. We simulated the effects of local venous hemodynamics on the TS distention and investigated TS vascular collapse under increased intracranial pressure, as has been hypothesized in the pathogenesis of …

Fluid-structure interaction in the cerebral venous transverse sinus

Background: The arrhythmogenic role of complex atrial morphology has not yet been clearly elucidated. We hypothesized that bumpy tissue geometry can induce action potential duration (APD) dispersion and wavebreak in atrial fibrillation (AF).

Pro-arrhythmogenic effects of heterogeneous tissue curvature―A suggestion for role of left atrial appendage in atrial fibrillation―

We aimed to propose a novel computational approach to predict the electromechanical performance of pre- and post-mitral valve cerclage annuloplasty (MVCA). Furthermore, we tested a virtual estimation method to optimize the left ventricular basement tightening scheme using a pre-MVCA computer model. The present model combines the three-dimensional (3D) electromechanics of the ventricles with the vascular hemodynamics implemented in a lumped parameter model. 3D models of pre- and post-MVCA were reconstructed from the computed tomography (CT) images of two patients and simulated by solving the electromechanical-governing equations with the finite element method. Computed results indicate that reduction of the dilated heart chambers volume (reverse remodeling) appears to be dependent on ventricular stress distribution. Reduced ventricular stresses in the basement after MVCA treatment were observed in the patients who showed reverse remodeling of heart during follow up over 6 months. In the case who failed to show reverse remodeling after MVCA, more virtual tightening of the ventricular basement diameter than the actual model can induce stress unloading, aiding in heart recovery. The simulation result that virtual tightening of the ventricular basement resulted in a marked increase of myocardial stress unloading provides in silico evidence for a functional impact of MVCA treatment on cardiac mechanics and post-operative heart recovery. This technique contributes to establishing a pre-operative virtual rehearsal procedure before MVCA treatment by using patient-specific cardiac electromechanical modeling of pre …

Computational analysis of the electromechanical performance of mitral valve cerclage annuloplasty using a patient-specific ventricular model

Background: Catheter ablation of persistent atrial fibrillation (AF) is still challenging and is characterized by a significant AF recurrence rate; however, no optimal extra-pulmonary vein lesion set is known. We previously reported the clinical feasibility of in silico simulation-guided AF catheter ablation.

Clinical Usefulness of Simulation-Guided Catheter Ablation of Atrial Fibrillation: Updated Outcome of a Multicenter Prospective Randomized Study

Although bipolar electrograms (Bi-egms) are commonly used for catheter mapping and ablation of cardiac arrhythmias, the accuracy and reproducibility of Bi-egms have not been evaluated. We aimed to clarify the influence of the catheter orientation (CO), catheter contact angle (CA), local conduction velocity (CV), scar size, and catheter type on the Bi-egm morphology using an in silico 3-dimensional realistic model of atrial fibrillation. We constructed a 3-dimensional, realistic, in silico left atrial model with activation wave propagation including bipolar catheter models. Bi-egms were obtained by computing the extracellular potentials from the distal and proximal electrodes. The amplitude and width were measured on virtual Bi-egms obtained under different conditions created by changing the CO according to the wave direction, catheter-atrial wall CA, local CV, size of the non-conductive area, and catheter type. Bipolar voltages were also compared between virtual and clinically acquired Bi-egms. Bi-egm amplitudes were lower for a perpendicular than parallel CO relative to the wave direction (p<0.001), lower for a 90° than 0° CA (p<0.001), and lower for a CV of 0.13m/s than 0.48m/s (p<0.001). Larger sized non-conductive areas were associated with a decreased bipolar amplitude (p<0.001) and increased bipolar width (p<0.001). Among three commercially available catheters (Orion, Pentaray, and Thermocool), those with more narrowly spaced and smaller electrodes produced higher voltages on the virtual Bi-egms (p<0.001). Multiple factors including the CO, CA, CV, and catheter design significantly influence the Bi-egm morphology. Universal …

Multiple factors influence the morphology of the bipolar electrogram: An in silico modeling study

Predicting the sites in coronary arteries that are susceptible to plaque deposition is essential for the development of clinical treatment strategies and prevention. However, to date, no physiological biomarkers for this purpose have been developed. We hypothesized that the possibility of plaque deposition at a specific site in the coronary artery is associated with wall shear stress (WSS) and fractional flow reserve (FFR).

Prediction of plaque progression in coronary arteries based on a novel hemodynamic index calculated from virtual stenosis method

The physiomic approach is now widely used in the diagnosis of cardiovascular diseases. There are two possible methods for cardiovascular physiome: the traditional mathematical model and the machine learning (ML) algorithm. ML is used in almost every area of society for various tasks formerly performed by humans. Specifically, various ML techniques in cardiovascular medicine are being developed and improved at unprecedented speed. The benefits of using ML for various tasks is that the inner working mechanism of the system does not need to be known, which can prove convenient in situations where determining the inner workings of the system can be difficult. The computation speed is also often higher than that of the traditional mathematical models. The limitations with ML are that it inherently leads to an approximation, and special care must be taken in cases where a high accuracy is required. Traditional mathematical models are, however, constructed based on underlying laws either proven or assumed. The results from the mathematical models are accurate as long as the model is. Combining the advantages of both the mathematical models and ML would increase both the accuracy and efficiency of the simulation for many problems. In this review, examples of cardiovascular physiome where approaches of mathematical modeling and ML can be combined are introduced.

Toward a grey box approach for cardiovascular physiome

The proarrhythmic risk is a major concern in drug development. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative has proposed the JTpeak interval on electrocardiograms (ECGs) and qNet, an in silico metric, as new biomarkers that may overcome the limitations of the hERG assay and QT interval. In this study, we simulated body-surface ECGs from patch-clamp data using realistic models of the ventricles and torso to explore their suitability as new in silico biomarkers for cardiac safety. We tested seven drugs in this study: dofetilide (high proarrhythmic risk), ranolazine, verapamil (QT increasing, but safe), bepridil, cisapride, mexiletine, and diltiazem. Human ventricular geometry was reconstructed from computed tomography (CT) images, and a Purkinje fiber network was mapped onto the endocardial surface. The electrical wave propagation in the ventricles was obtained by solving a reaction-diffusion equation using finite-element methods. The body-surface ECG data were calculated using a torso model that included the ventricles. The effects of the drugs were incorporated in the model by partly blocking the appropriate ion channels. The effects of the drugs on single-cell action potential (AP) were examined first, and three-dimensional (3D) body-surface ECG simulations were performed at free Cmax values of 1×, 5×, and 10×. In the single-cell and ECG simulations at 5× Cmax, dofetilide, but not verapamil or ranolazine, caused arrhythmia. However, the non-increasing JTpeak caused by verapamil and ranolazine that has been observed in humans was not reproduced in our simulation. Our results demonstrate the potential of 3D …

Three-Dimensional Heart Model-Based Screening of Proarrhythmic Potential by in silico Simulation of Action Potential and Electrocardiograms

Early prediction of the occurrence of ventricular tachyarrhythmia (VTA) has a potential to save patients’ lives. VTA includes ventricular tachycardia (VT) and ventricular fibrillation (VF). Several studies have achieved promising performances in predicting VT and VF using traditional heart rate variability (HRV) features. However, as VTA is a life-threatening heart condition, its prediction performance requires further improvement. To improve the performance of predicting VF, we used the QRS complex shape features, and traditional HRV features were also used for comparison. We extracted features from 120-s-long HRV and electrocardiogram (ECG) signals (QRS complex signed area and R-peak amplitude) to predict the VF onset 30 s before its occurrence. Two artificial neural network (ANN) classifiers were trained and tested with two feature sets derived from HRV and the QRS complex shape based on a 10-fold cross-validation. The prediction accuracy estimated using 11 HRV features was 72%, while that estimated using four QRS complex shape features yielded a high prediction accuracy of 98.6%. The QRS complex shape could play a significant role in performance improvement of predicting the occurrence of VF. Thus, the results of our study can be considered by the researchers who are developing an application for an implantable cardiac defibrillator (ICD) when to begin ventricular defibrillation.

Machine learning approach to predict ventricular fibrillation based on QRS complex shape

Catheter ablation of persistent atrial fibrillation (AF) is still challenging, no optimal extra-pulmonary vein lesion set is known. We previously reported the clinical feasibility of computational modeling-guided AF catheter ablation.

Clinical usefulness of computational modeling-guided persistent atrial fibrillation ablation: updated outcome of multicenter randomized study

The instantaneous wave-free ratio (iFR) is a recently introduced vasodilator-free index to assess the functional severity of coronary stenosis in the resting state, while fractional flow reserve (FFR) is the gold standard index in hyperemia. The computed instantaneous wave-free ratio (CT-iFR) is a noninvasive method to estimate iFR using computer simulations. Here, we developed a vessel-length-based CT-iFR method in patient-specific models of coronary arteries. This method was implemented by coupling a three-dimensional computational fluid dynamics model with a lumped parameter model (LPM) of coronary circulation in a non-hyperemic resting state. A time-varying resistance in the LPM was used for the iFR simulation. In total, 50 coronary vessels of 32 patients were computed, and their CT-iFR values were compared with clinically measured iFRs to evaluate the diagnostic performance of the present CT-iFR …

Diagnostic performance of a vessel-length-based method to compute the instantaneous wave-free ratio in coronary arteries

Safety evaluation of drugs requires examination of the risk of generating Torsade de Pointes (TdP) because it can lead to sudden cardiac death. Until recently, the QT interval in the electrocardiogram (ECG) has been used in the evaluation of TdP risk because the QT interval is known to be associated with the development of TdP. Although TdP risk evaluation based on QT interval has been successful in removing drugs with TdP risk from the market, some safe drugs may have also been affected due to the low specificity of QT interval-based evaluation. For more accurate evaluation of drug safety, the comprehensive in vitro proarrhythmia assay (CiPA) has been proposed by regulatory agencies, industry, and academia. Although the CiPA initiative includes in silico evaluation of cellular action potential as a component, attempts to utilize in silico simulation in drug safety evaluation are expanding, even to simulating …

In silico models for evaluating proarrhythmic risk of drugs

Clinical applications of physiome models Page 1 CLINICAL APPLICATIONS OF PHYSIOME MODELS EDITED BY: Eun Bo Shim, Thomas Heldt and Chae Hun Leem PUBLISHED IN: Frontiers in Physiology Page 2 About Frontiers Frontiers is more than just an open-access publisher of scholarly articles: it is a pioneering approach to the world of academia

Clinical applications of physiome models

The interatrial conduction, including Bachmann's bundle, the posterior septal conduction, the anterior septal conduction, and the cavo‐tricuspid isthmus, contributes to the maintenance mechanisms of atrial fibrillation in a 3D biatrial model.
The interatrial conduction ablation including a cavo‐tricuspid isthmus ablation significantly affects the wave dynamics of atrial fibrillation (AF) and facilitates the AF termination or atrial tachycardia conversion of the AF after the circumferential pulmonary vein isolation.
Additional cavo‐tricuspid isthmus ablation after the circumferential pulmonary vein isolation improves long‐term rhythm outcome after clinical AF catheter ablation.

Electrophysiological significance of the interatrial conduction including cavo‐tricuspid isthmus during atrial fibrillation


            This study evaluates a noninvasive, vessel-length-based method for computing the instantaneous wave-free ratio (iFR) in coronary arteries using a combination of three-dimensional computational fluid dynamics (CFD) and a lumped parameter model (LPM).
            The study involved 32 patients and compared computed iFR (CT-iFR) with clinically measured iFR. The results showed good diagnostic accuracy, suggesting that CT-iFR could serve as a noninvasive alternative for guiding percutaneous coronary intervention (PCI) strategies.
        

In this paper, we present a computationally efficient cellular mathematical model that accounts for the boundary collective behavior of a cell group by hepatocyte growth factor. The large cell group is modeled using continuum-based finite elements with incompressible hyperelastic materials for the nonlinear elastic behaviors. The total Lagrangian formulation is used enabling for large deformations, and the explicit time integration scheme without the Newton-Raphson iterative solution required for a time step is adopted to model the dynamics of the collective cell migration. With the explicit time integration and low order finite elements under the total Lagrangian framework, the proposed model is much computationally efficient for modeling the dynamic mechanical behavior of a cell colony. Detailed comparison to the experimental data shows that the proposed mathematical model provides a quantitatively accurate …

Continuum-based modeling of collective cell migration

Automatic three-dimensional (3-D) reconstruction of the coronary arteries (CA) from medical imaging modalities is still a challenging task. In this study, we present a deep learning-based method of automatic identification of the two ends of the vessel from X-ray coronary angiography (XCA). We also present a method of using template models of CA in matching the two-dimensional segmented vessels from two different angles of XCA. For the deep learning network, we used a U-net consisting of an encoder (Resnet) and a decoder. The two ends of the vessel were manually labeled to generate training images. The network was trained with 2,342, 1,907, and 1,523 labeled images for the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), respectively. For template models of CA, ten reconstructed 3-D models were averaged for each artery. The accuracy of correspondence using template models was compared with that of manual matching. The deep learning network pointed the proximal region (20% of the total length) in 97.7, 97.5, and 96.4% of 315, 201, and 167 test images for LAD, LCX, and RCA, respectively. The success rates in pointing the distal region were 94.9, 89.8, and 94.6%, respectively. The average distances between the projected points from the reconstructed 3-D model to the detector and the points on the segmented vessels were not statistically different between the template and manual matchings. The computed FFR was not significantly different between the two matchings either. Deep learning methodology is feasible in identifying the two ends of the vessel in XCA, and the accuracy of using …

A simple method for automatic 3D reconstruction of coronary arteries from X-ray angiography

Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation.

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