A multiscale approach for modelling wave propagation in an arterial segment

A mathematical model of blood flow through an arterial vessel is presented and the wave propagation in it is studied numerically. Based on the assumption of long wavelength and small amplitude of the pressure waves, a quasi-one-dimensional (1D) differential model is adopted. It describes the non-linear fluid-wall interaction and includes wall deformation in both radial and axial directions. The 1D model is coupled with a six compartment lumped parameter model, which accounts for the global circulatory features and provides boundary conditions. The differential equations are first linearized to investigate the nature of the propagation phenomena. The full non-linear equations are then approximated with a numerical finite difference method on a staggered grid. Some numerical simulations show the characteristics of the wave propagation. The dependence of the flow, of the wall deformation and of the wave velocity on the elasticity parameter has been highlighted. The importance of the axial deformation is evidenced by its variation in correspondence of the pressure peaks. The wave disturbances consequent to a local stiffening of the vessel and to a compliance jump due to prosthetic implantations are finally studied.     

Pulse wave propagation in a model human arterial network: Assessment of 1-D visco-elastic simulations against in vitro measurements

The accuracy of the nonlinear one-dimensional (1-D) equations of pressure and flow wave propagation in Voigt-type visco-elastic arteries was tested against measurements in a well-defined experimental 1:1 replica of the 37 largest conduit arteries in the human systemic circulation. The parameters required by the numerical algorithm were directly measured in the in vitro setup and no data fitting was involved. The inclusion of wall visco-elasticity in the numerical model reduced the underdamped high-frequency oscillations obtained using a purely elastic tube law, especially in peripheral vessels, which was previously reported in this paper [Matthys et al., 2007. Pulse wave propagation in a model human arterial network: Assessment of 1-D numerical simulations against in vitro measurements. J. Biomech. 40, 3476-3486]. In comparison to the purely elastic model, visco-elasticity significantly reduced the average relative root-mean-square errors between numerical and experimental waveforms over the 70 locations measured in the in vitro model: from 3.0% to 2.5% (p<0.012) for pressure and from 15.7% to 10.8% (p<0.002) for the flow rate. In the frequency domain, average relative errors between numerical and experimental amplitudes from the 5th to the 20th harmonic decreased from 0.7% to 0.5% (p<0.107) for pressure and from 7.0% to 3.3% (p<10(-6)) for the flow rate. These results provide additional support for the use of 1-D reduced modelling to accurately simulate clinically relevant problems at a reasonable computational cost.     

Charge transport in a DNA model with solvent interaction

The charge transport in the modified DNA model is studied by taking into account the factor of solvent and the effect of coupling motions of nucleotides. We report on the presence of the modulational instability (MI) of a plane wave for charge migration in DNA and the generation of soliton-like excitations in DNA nucleotides. By applying the continuum approximation, we show that the original differential-difference equation for the DNA dynamics can be reduced to a set of three coupled nonlinear equations. The linear stability analysis of wave solutions of the coupled systems is performed and the growth rate of instability is found numerically. We also investigate the impact of solvent interaction. The solvent factor introduces a new behavior to the wave patterns, modifying also the intrinsic properties of localized structures. In the numerical simulations, we show that the solitons exists when taking into account the effect of solvent and confirms an highest propagation of localized structures in the systems. The effect of solvent forces introduces a robustness behavior to the formed patterns, reinforcing the idea that the information in the DNA model is confined and concentrated to specific regions for efficiency. We also show that the localized structures can be disappeared with the highest value of solvent factor and thereafter the information within the molecule is not perceptible or not transmitted to another sites.     

Heterogeneous mechanics of the mouse pulmonary arterial network

Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure–radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more physiologically realistic pressure versus radius relationship.     

One-dimensional model for propagation of a pressure wave in a model of the human arterial network: comparison of theoretical and experimental results

Pulse wave evaluation is an effective method for arteriosclerosis screening. In a previous study, we verified that pulse waveforms change markedly due to arterial stiffness. However, a pulse wave consists of two components, the incident wave and multireflected waves. Clarification of the complicated propagation of these waves is necessary to gain an understanding of the nature of pulse waves in vivo. In this study, we built a one-dimensional theoretical model of a pressure wave propagating in a flexible tube. To evaluate the applicability of the model, we compared theoretical estimations with measured data obtained from basic tube models and a simple arterial model. We constructed different viscoelastic tube set-ups: two straight tubes; one tube connected to two tubes of different elasticity; a single bifurcation tube; and a simple arterial network with four bifurcations. Soft polyurethane tubes were used and the configuration was based on a realistic human arterial network. The tensile modulus of the material was similar to the elasticity of arteries. A pulsatile flow with ejection time 0.3 s was applied using a controlled pump. Inner pressure waves and flow velocity were then measured using a pressure sensor and an ultrasonic diagnostic system. We formulated a 1D model derived from the Navier-Stokes equations and a continuity equation to characterize pressure propagation in flexible tubes. The theoretical model includes nonlinearity and attenuation terms due to the tube wall, and flow viscosity derived from a steady Hagen-Poiseuille profile. Under the same configuration as for experiments, the governing equations were computed using the MacCormack scheme. The theoretical pressure waves for each case showed a good fit to the experimental waves. The square sum of residuals (difference between theoretical and experimental wave-forms) for each case was <10.0%. A possible explanation for the increase in the square sum of residuals is the approximation error for flow viscosity. However, the comparatively small values prove the validity of the approach and indicate the usefulness of the model for understanding pressure propagation in the human arterial network.     

Wave Propagation Mediated by GABAB Synapse and Rebound Excitation in an Inhibitory Network: A Reduced Model Approach

A reduction method is used to analyze a spatially structured network model of inhibitory neurons. This network model displays wave propagation of postinhibitory rebound activity, which depends on GABA_B synaptic interactions among the neurons. The reduced model allows explicit solutions for the wavefronts and their velocity as a function of various parameters, such as the synaptic coupling strength. These predictions are shown to agree well with the numerical simulations of the conductance-based biophysical model.     

Roles of subcellular Na+ channel distributions in the mechanism of cardiac conduction

The gap junction and voltage-gated Na⁺ channel play an important role in the action potential propagation. The purpose of this study was to elucidate the roles of subcellular Na⁺ channel distribution in action potential propagation. To achieve this, we constructed the myocardial strand model, which can calculate the current via intercellular cleft (electric-field mechanism) together with gap-junctional current (gap-junctional mechanism). We conducted simulations of action potential propagation in a myofiber model where cardiomyocytes were electrically coupled with gap junctions alone or with both the gap junctions and the electric field mechanism. Then we found that the action potential propagation was greatly affected by the subcellular distribution of Na⁺ channels in the presence of the electric field mechanism. The presence of Na⁺ channels in the lateral membrane was important to ensure the stability of propagation under conditions of reduced gap-junctional coupling. In the poorly coupled tissue with sufficient Na⁺ channels in the lateral membrane, the slowing of action potential propagation resulted from the periodic and intermittent dysfunction of the electric field mechanism. The changes in the subcellular Na⁺ channel distribution might be in part responsible for the homeostatic excitation propagation in the diseased heart.     

Fluid–structure interaction in a fully coupled three-dimensional mitral–atrium–pulmonary model

This paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid–structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.

     

Longitudinal displacements of base pairs in DNA and effects on the dynamics of nonlinear excitations

A model of the DNA is proposed and studied analytically and numerically. The model is an extension of a well known model and describes the double helix as two chains of pendula (each pendulum representing a base). Each base (or pendulum) can rotate and translate along the helix axis. In the continuum limit the system is described by the perturbed Sine–Gordon equation describing the twist of the bases and by a nonlinear partial differential equation (PDE) describing the longitudinal displacements of the bases. This coupled system of PDEs was studied analytically using different approaches and the corresponding results were tested through numerical simulations. It was found that if the coupling parameters satisfy a well defined relationship, then there exist bounded travelling wave solutions.     

Experimental validation of a time-domain-based wave propagation model of blood flow in viscoelastic vessels

Time-domain-based one-dimensional wave propagation models of the arterial system are preferable over one-dimensional wave propagation models in the frequency domain since the latter neglect the non-linear convection forces present in the physiological situation, especially when the vessel is tapered. Moreover, one-dimensional wave propagation models of the arterial system can be used to provide boundary conditions for fully three-dimensional fluid-structure interaction computations that are usually defined in the time domain. In this study, a time-domain-based one-dimensional wave propagation model in a cross-sectional area, flow and pressure (A,q,p)-formulation is developed. Using this formulation, a constitutive law that includes viscoelasticity based on the mechanical behaviour of a Kelvin body, is introduced. The resulting pressure and flow waves travelling through a straight and tapered vessel are compared to experimental data obtained from measurements in an in vitro setup. The model presented shows to be well suited to predict wave propagation through these straight and tapered vessels with viscoelastic wall properties and hereto can serve as a time-domain-based method to model wave propagation in the human arterial system.     

A data-driven model to study utero-ovarian blood flow physiology during pregnancy

In this paper, we describe a mathematical model of the cardiovascular system in human pregnancy. An automated, closed-loop 1D–0D modelling framework was developed, and we demonstrate its efficacy in (1) reproducing measured multi-variate cardiovascular variables (pulse pressure, total peripheral resistance and cardiac output) and (2) providing automated estimates of variables that have not been measured (uterine arterial and venous blood flow, pulse wave velocity, pulsatility index). This is the first model capable of estimating volumetric blood flow to the uterus via the utero-ovarian communicating arteries. It is also the first model capable of capturing wave propagation phenomena in the utero-ovarian circulation, which are important for the accurate estimation of arterial stiffness in contemporary obstetric practice. The model will provide a basis for future studies aiming to elucidate the physiological mechanisms underlying the dynamic properties (changing shapes) of vascular flow waveforms that are observed with advancing gestation. This in turn will facilitate the development of methods for the earlier detection of pathologies that have an influence on vascular structure and behaviour.

     

In-vitro investigation of a potential wave pumping effect in human aorta

An impedance pump – also known as Liebau pump – is a simple valveless pump that operates based on the principles of wave propagation and reflection. It has been shown in embryonic zebrafish that a similar mechanism is responsible for the pumping action in the embryonic heart during the early stages before valve formation. Recent studies suggest that the cardiovascular system is designed to take advantage of wave propagation and reflection phenomena in the arterial network. In this study we report the results of an in-vitro study that examines the hypothesis that the adult human aorta acts as a passive pump based on Liebau effect. A hydraulic model with different compliant models of an artificial aorta was used for a series of in-vitro experiments. Our result indicates that wave propagation and reflection can result in a pumping mechanism in a compliant aorta.     

Excitation wave propagation as a possible mechanism for signal transmission in pancreatic islets of Langerhans

In response to glucose application, beta-cells forming pancreatic islets of Langerhans start bursting oscillations of the membrane potential and intracellular calcium concentration, inducing insulin secretion by the cells. Until recently, it has been assumed that the bursting activity of beta-cells in a single islet of Langerhans is synchronized across the whole islet due to coupling between the cells. However, time delays of several seconds in the activity of distant cells are usually observed in the islets of Langerhans, indicating that electrical/calcium wave propagation through the islets can occur. This work presents both experimental and theoretical evidence for wave propagation in the islets of Langerhans. Experiments with Fura-2 fluorescence monitoring of spatiotemporal calcium dynamics in the islets have clearly shown such wave propagation. Furthermore, numerical simulations of the model describing a cluster of electrically coupled beta-cells have supported our view that the experimentally observed calcium waves are due to electric pulses propagating through the cluster. This point of view is also supported by independent experimental results. Based on the model equations, an approximate analytical expression for the wave velocity is introduced, indicating which parameters can alter the velocity. We point to the possible role of the observed waves as signals controlling the insulin secretion inside the islets of Langerhans, in particular, in the regions that cannot be reached by any external stimuli such as high glucose concentration outside the islets.     

On the potentialities of 3D–1D coupled models in hemodynamics simulations

This work comprises a step towards the quantitative and qualitative analysis of coupled local and global hemodynamics phenomena in the arterial system. The aim of this work is to present some numerical examples to put in evidence the importance of the use of 3D–1D coupled models in hemodynamics problems when carrying out simulations of rather complex situations. Accordingly, some cases for which classical modeling cannot be applied are identified and solved. The results obtained here allow us to assess some interrelations between local pointwise quantities (defined at the level of the 3D model) and global mean quantities (defined at the level of the 1D model).     

Wave propagation in a model of the arterial circulation

The propagation of the arterial pulse wave in the large systemic arteries has been calculated using a linearised method of characteristics analysis to follow the waves generated by the heart. The model includes anatomical and physiological data for the 55 largest arteries adjusted so that the bifurcating tree of arteries is well matched for forward travelling waves. The peripheral arteries in the model are terminated by resistance elements which are adjusted to produce a physiologically reasonable distribution of mean blood flow. In the model, the pressure and velocity wave generated by the contraction of the left ventricle propagates to the periphery where it is reflected. These reflected waves are re-reflected by each of the bifurcations that they encounter and a very complex pattern of waves is generated. The results of the calculations exhibit many of the features of the systemic arteries, including the increase of the pulse pressure with distance away from the heart as well as the initial decrease and then the large increase in the magnitude of back flow during late systole going from the ascending aorta to the abdominal aorta to the arteries of the leg. The model is then used to study the effects of the reflection or absorption of waves by the heart and the mechanisms leading to the incisura are investigated. Calculations are carried out with the total occlusion of different arterial segments in order to model experiments in which the effects of the occlusion of different arteries on pressure and flow in the ascending aorta were measured. Finally, the effects of changes in peripheral resistance on pressure and velocity waveforms are also studied. We conclude from these calculations that the complex pattern of wave propagation in the large arteries may be the most important determinant of arterial haemodynamics.     

Soft Tissue Modelling of Cardiac Fibres for Use in Coupled Mechano-Electric Simulations

The numerical solution of the coupled system of partial differential and ordinary differential equations that model the whole heart in three dimensions is a considerable computational challenge. As a consequence, it is not computationally practical—either in terms of memory or time—to repeat simulations on a finer computational mesh to ensure that convergence of the solution has been attained. In an attempt to avoid this problem while retaining mathematical rigour, we derive a one dimensional model of a cardiac fibre that takes account of elasticity properties in three structurally defined axes within the myocardial tissue. This model of a cardiac fibre is then coupled with an electrophysiological cell model and a model of cellular electromechanics to allow us to simulate the coupling of the electrical and mechanical activity of the heart. We demonstrate that currently used numerical methods for coupling electrical and mechanical activity do not work in this case, and identify appropriate numerical techniques that may be used when solving the governing equations. This allows us to perform a series of simulations that: (i) investigate the effect of some of the assumptions inherent in other models; and (ii) reproduce qualitatively some experimental observations.     

Validation of a 3D computational fluid-structure interaction model simulating flow through an elastic aperture

This work presents a validation of a fluid-structure interaction computational model simulating the flow conditions in an in vitro mock heart chamber modeling mitral valve regurgitation during the ejection phase during which the trans-valvular pressure drop and valve displacement are not as large. The mock heart chamber was developed to study the use of 2D and 3D color Doppler techniques in imaging the clinically relevant complex intra-cardiac flow events associated with mitral regurgitation. Computational models are expected to play an important role in supporting, refining, and reinforcing the emerging 3D echocardiographic applications. We have developed a 3D computational fluid-structure interaction algorithm based on a semi-implicit, monolithic method, combined with an arbitrary Lagrangian-Eulerian approach to capture the fluid domain motion. The mock regurgitant mitral valve corresponding to an elastic plate with a geometric orifice, was modeled using 3D elasticity, while the blood flow was modeled using the 3D Navier-Stokes equations for an incompressible, viscous fluid. The two are coupled via the kinematic and dynamic conditions describing the two-way coupling. The pressure, the flow rate, and orifice plate displacement were measured and compared with numerical simulation results. In-line flow meter was used to measure the flow, pressure transducers were used to measure the pressure, and a Doppler method developed by one of the authors was used to measure the axial displacement of the orifice plate. The maximum recorded difference between experiment and numerical simulation for the flow rate was 4%, the pressure 3.6%, and for the orifice displacement 15%, showing excellent agreement between the two.