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.     

A thick walled viscoelastic model for the mechanics of arteries

A knowledge of the mechanics of arteries is of importance in the determination of vessel rheological properties and in the studies of blood flow and certain arterial diseases. Most existing arterial models treat only wave motions; however, other types of motion, in particular those associated with flow development and other end effects, occur in the vascular system. Thus, a model is needed which can be applied to a variety of possible types of motion.

An arterial model is described which includes the effects of thick walls, linear viscoelasticity, and wall tethering. The forms of the displacements and stresses are found independently of the exact form of the applied fluid stresses; thus, the results are applicable to a range of possible dynamical conditions. Displacements and stress states can then be found from experimental or theoretical knowledge of the blood pressure and flow. The results are applied to flow development and wave propagation regions in the arteries.     

Theoretical analysis of pressure pulse propagation in arterial vessels.

An original mathematical model of viscous fluid motion in a tapered and distensible tube is presented. The model equations are deduced by assuming a two-dimensional flow and taking into account the nonlinear terms in the fluid motion equations, as well as the nonlinear deformation of the tube wall. One distinctive feature of the model is the formal integration with respect to the radial coordinate of the Navier-Stokes equations by power series expansion. The consequent computational frame allows an easy, accurate evaluation of the effects produced by changing the values of all physical and geometrical tube parameters. The model is employed to study the propagation along an arterial vessel of a pressure pulse produced by a single flow pulse applied at the proximal vessel extremity. In particular, the effects of the natural taper angle of the arterial wall on pulse propagation are investigated. The simulation results show that tapering considerably influences wave attenuation but not wave velocity. The substantially different behavior of pulse propagation, depending upon whether it travels towards the distal extremity or in the opposite direction, is observed: natural tapering causes a continuous increase in the pulse amplitude as it moves towards the distal extremity; on the contrary, the reflected pulse, running in the opposite direction, is greatly damped. For a vessel with physical and geometrical properties similar to those of a canine femoral artery and 0.1 degree taper angle, the forward amplification is about 0.9 m-1 and the backward attenuation is 1.4 m-1, so that the overall tapering effect gives a remarkably damped pressure response. For a natural taper angle of 0.14 degrees the perturbation is almost extinct when the pulse wave returns to the proximal extremity.     

On the propagation of a wave front in viscoelastic arteries

In formulating a mathematical model of the arterial system, the one-dimensional flow approximation yields realistic pressure and flow pulses in the proximal as well as in the distal regions of a simulated arterial conduit, provided that the viscoelastic damping induced by the vessel wall is properly taken into account. Models which are based on a purely elastic formulation of the arterial wall properties are known to produce shocklike transitions in the propagating pulses which are not observed in man under physiological conditions. The viscoelastic damping characteristics are such that they are expected to reduce the tendency of shock formation in the model. In order to analyze this phenomenon, the propagation of first and second-order pressure waves is calculated with the aid of a wave front expansion, and criteria for the formation of shocks are derived. The application of the results to the human arterial system show that shock waves are not to be expected under normal conditions, while in case of a pathologically increased pressure rise at the root of the aorta, shocklike transitions may develop in the periphery. In particular, it is shown that second-order waves never lead to shock formation in finite time for the class of initial conditions and mechanical wave guides which are of interest in the mammalian circulation.     

Validation of a patient-specific one-dimensional model of the systemic arterial tree

The aim of this study is to develop and validate a patient-specific distributed model of the systemic arterial tree. This model is built using geometric and hemodynamic data measured on a specific person and validated with noninvasive measurements of flow and pressure on the same person, providing thus a patient-specific model and validation. The systemic arterial tree geometry was obtained from MR angiographic measurements. A nonlinear viscoelastic constitutive law for the arterial wall is considered. Arterial wall distensibility is based on literature data and adapted to match the wave propagation velocity of the main arteries of the specific subject, which were estimated by pressure waves traveling time. The intimal shear stress is modeled using the Witzig-Womersley theory. Blood pressure is measured using applanation tonometry and flow rate using transcranial ultrasound and phase-contrast-MRI. The model predicts pressure and flow waveforms in good qualitative and quantitative agreement with the in vivo measurements, in terms of wave shape and specific wave features. Comparison with a generic one-dimensional model shows that the patient-specific model better predicts pressure and flow at specific arterial sites. These results obtained let us conclude that a patient-specific one-dimensional model of the arterial tree is able to predict well pressure and flow waveforms in the main systemic circulation, whereas this is not always the case for a generic one-dimensional model.     

Comparison of pressure losses in steady non-Newtonian flow through experimental tapered and cylindrical arterial prostheses

The use of an arterial prosthesis with a tapered lumen has several important advantages; for example, improved stability of flow, increased wall shear and better matching of its size with that of the host vessel. Tapering may, however, lead to increased energy losses, particularly if the angle of taper is large and the flow is high. This study is concerned with the determination of pressure drop for steady and laminar converging flow through rigid wall models of tapered arterial grafts. The angles of taper examined ranged from 0.5° to 1.0°. Aqueous solutions of polyacrylamide, with non-Newtonian viscous properties similar to those of blood, were used. The pressure drops across the tapered tubes were measured and the data were measured and the data were related to the pressure loss in cylindrical tubes of equivalent dimensions. Expressions for the ratio of the pressure drop in a tapered tube to that in a cylindrical tube for steady flow of a power law fluid were derived; there was good agreement between the predicted and the measured pressure drop ratios over a wide range of flows. The results of this study may be applied to the design of tapered arterial grafts. The pressure losses to be expected in tapered bypass grafts having various dimensions can easily be computed.     

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.     

A novel porous media-based approach to outflow boundary resistances of 1D arterial blood flow models

In this paper we introduce a novel method for prescribing terminal boundary conditions in one-dimensional arterial flow networks. This is carried out by coupling the terminal arterial vessel with a poro-elastic tube, representing the flow resistance offered by microcirculation. The performance of the proposed porous media-based model has been investigated through several different numerical examples. First, we investigate model parameters that have a profound influence on the flow and pressure distributions of the system. The simulation results have been compared against the waveforms generated by three elements (RCR) Windkessel model. The proposed model is also integrated into a realistic arterial tree, and the results obtained have been compared against experimental data at different locations of the network. The accuracy and simplicity of the proposed model demonstrates that it can be an excellent alternative for the existing models.

     

Comparative study of viscoelastic arterial wall models in nonlinear one-dimensional finite element simulations of blood flow

It is well known that blood vessels exhibit viscoelastic properties, which are modeled in the literature with different mathematical forms and experimental bases. The wide range of existing viscoelastic wall models may produce significantly different blood flow, pressure, and vessel deformation solutions in cardiovascular simulations. In this paper, we present a novel comparative study of two different viscoelastic wall models in nonlinear one-dimensional (1D) simulations of blood flow. The viscoelastic models are from papers by Holenstein et al. in 1980 (model V1) and Valdez-Jasso et al. in 2009 (model V2). The static elastic or zero-frequency responses of both models are chosen to be identical. The nonlinear 1D blood flow equations incorporating wall viscoelasticity are solved using a space-time finite element method and the implementation is verified with the Method of Manufactured Solutions. Simulation results using models V1, V2 and the common static elastic model are compared in three application examples: (i) wave propagation study in an idealized vessel with reflection-free outflow boundary condition; (ii) carotid artery model with nonperiodic boundary conditions; and (iii) subject-specific abdominal aorta model under rest and simulated lower limb exercise conditions. In the wave propagation study the damping and wave speed were largest for model V2 and lowest for the elastic model. In the carotid and abdominal aorta studies the most significant differences between wall models were observed in the hysteresis (pressure-area) loops, which were larger for V2 than V1, indicating that V2 is a more dissipative model. The cross-sectional area oscillations over the cardiac cycle were smaller for the viscoelastic models compared to the elastic model. In the abdominal aorta study, differences between constitutive models were more pronounced under exercise conditions than at rest. Inlet pressure pulse for model V1 was larger than the pulse for V2 and the elastic model in the exercise case. In this paper, we have successfully implemented and verified two viscoelastic wall models in a nonlinear 1D finite element blood flow solver and analyzed differences between these models in various idealized and physiological simulations, including exercise. The computational model of blood flow presented here can be utilized in further studies of the cardiovascular system incorporating viscoelastic wall properties.     

Computer simulation of arterial flow with applications to arterial and aortic stenoses

A computer model for simulating pressure and flow propagation in the human arterial system is developed. The model is based on the one-dimensional flow equations and includes nonlinearities arising from geometry and material properties. Fifty-five arterial segments, representing the various major arteries, are combined to form the model of the arterial system. Particular attention is paid to the development of peripheral pressure and flow pulses under normal flow conditions and under conditions of arterial and aortic stenoses. Results show that the presence of severe arterial stenoses significantly affects the nature of the distal pressure and flow pulses. Aortic stenoses also have a profound effect on central and peripheral pressure pulse formation. Comparison with the published experimental data suggests that the model is capable of simulating arterial flow under normal flow conditions as well as conditions of stenotic obstructions in a satisfactory manner.     

Flow measurements in an atherosclerotic curved, tapered femoral artery model of man

Flow visualization and pressure measurements were made for physiological conditions in a model derived from a femoral angiogram of a patient with lesion localization on the inner curvature wall and with vessel taper. Effects of curvature and taper were evaluated separately in other curved, tapered, smooth and straight, tapered, smooth models. Double helical secondary flow patterns were modified by plaque on the inner wall, and flow separations were observed between plaques at higher flow rates and Reynolds numbers. Pressure drop data for the plaque simulation model were similar in trend with Reynolds number as for the smooth model, but flow resistances were 25 to 40 percent higher. Significant pressure drops were measured due to the mild taper which could be estimated from momentum considerations, and smaller increased pressure drops were found due to curvature effects at the higher Dean numbers. Flow resistances for in vivo pulsatile flow simulation were about 10 percent higher than for steady flow for the plaque model, whereas no differences were observed for the smooth model.     

Mechanics of blood flow

The historical development of the mechanics of blood flow can be traced from ancient times, to Leonardo da Vinci and Leonhard Euler and up to the present times with increasing biological knowledge and mathematical analysis. In the last two decades, quantitative and numerical methods have steadily given more complete and precise understanding. In the arterial system wave propagation computations based on nonlinear one-dimensional modeling have given the best representation of pulse wave propagation. In the veins, the theory of unsteady flow in collapsible tubes has recently been extensively developed. In the last decade, progress has been made in describing the blood flow at junctions, through stenoses, in bends and in capillary blood vessels. The rheological behavior of individual red blood cells has been explored. A working model consists of an elastic membrane filled with viscous fluid. This model forms a basis for understanding the viscous and viscoelastic behavior of blood.     

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.

     

Effects of arterial wall models and measurement uncertainties on cardiovascular model predictions

We developed a methodology to assess and compare the prediction quality of cardiovascular models for patient-specific simulations calibrated with uncertainty-hampered measurements. The methodology was applied in a one-dimensional blood flow model to estimate the impact of measurement uncertainty in wall model parameters on the predictions of pressure and flow in an arterial network. We assessed the prediction quality of three wall models that have been widely used in one-dimensional blood flow simulations. A 37-artery network, previously used in one experimental and several simulation studies, was adapted to patient-specific conditions with a set of three clinically measurable inputs: carotid–femoral wave speed, mean arterial pressure and area in the brachial artery. We quantified the uncertainty of the predicted pressure and flow waves in eight locations in the network and assessed the sensitivity of the model prediction with respect to the measurements of wave speed, pressure and cross-sectional area. Furthermore, we developed novel time-averaged sensitivity indices to assess the contribution of model parameters to the uncertainty of time-varying quantities (e.g., pressure and flow). The results from our patient-specific network model demonstrated that our novel indices allowed for a more accurate sensitivity analysis of time-varying quantities compared to conventional Sobol sensitivity indices.     

Pulse wave propagation in a model human arterial network: assessment of 1-D numerical simulations against in vitro measurements

A numerical model based on the nonlinear, one-dimensional (1-D) equations of pressure and flow wave propagation in conduit arteries is tested against a well-defined experimental 1:1 replica of the human arterial tree. The tree consists of 37 silicone branches representing the largest central systemic arteries in the human, including the aorta, carotid arteries and arteries that perfuse the upper and lower limbs and the main abdominal organs. The set-up is mounted horizontally and connected to a pulsatile pump delivering a periodic output similar to the aortic flow. Terminal branches end in simple resistance models, consisting of stiff capillary tubes leading to an overflow reservoir that reflects a constant venous pressure. The parameters required by the numerical algorithm are directly measured in the in vitro set-up and no data fitting is involved. Comparison of experimental and numerical pressure and flow waveforms shows the ability of the 1-D time-domain formulation to capture the main features of pulse wave propagation measured throughout the system test. As a consequence of the simple resistive boundary conditions used to reduce the uncertainty of the parameters involved in the simulation, the experimental set-up generates waveforms at terminal branches with additional non-physiological oscillations. The frequencies of these oscillations are well captured by the 1-D model, even though amplitudes are overestimated. Adding energy losses in bifurcations and including fluid inertia and compliance to the purely resistive terminal models does not reduce the underdamped effect, suggesting that wall visco-elasticity might play an important role in the experimental results. Nevertheless, average relative root-mean-square errors between simulations and experimental waveforms are smaller than 4% for pressure and 19% for the flow at all 70 locations studied.     

A circle of Willis simulation using distensible vessels and pulsatile flow

The development of a one-dimensional numerical (finite-difference) model of the arterial network surrounding the circle of Willis is described based on the full Navier-Stokes and conservation of mass equations generalized for distensible vessels. The present model assumes an elastic wall defined by a logarithmic pressure-area relation obtained from the literature. The viscous term in the momentum equation is evaluated using the slope of a Karman-Pohlhausen velocity profile at the vessel boundary. The afferent vessels (two carotids and two vertebrals) are forced with a canine physiologic pressure signature corresponding to an aortic site. The network associated with each main efferent artery of the circle is represented by a single vessel containing an appropriate amount of resistance so that the mean flow through the system is distributed in accordance with the weight of brain irrigated by each vessel as determined from a steady flow model of the same network. This resistance is placed a quarter wave-length downstream from the heart to insure proper reflection from the terminations, where the quarter wavelength is determined using the frequency corresponding to the first minimum on an input impedance-frequency diagram obtained at the heart. Computer results are given as time histories of pressure and flow at any model nodal point starting from initial conditions of null flow and constant pressure throughout the model. Variations in these pressure and flow distributions caused by the introduction of pathologic situations into the model illustrate the efficacy of the simulation and of the circle in equalizing and redistributing flows in abnormal situations.     

Fast blood-flow simulation for large arterial trees containing thousands of vessels

Blood flow modelling has previously been successfully carried out in arterial trees to study pulse wave propagation using nonlinear or linear flow solvers. However, the number of vessels used in the simulations seldom grows over a few hundred. The aim of this work is to present a computationally efficient solver coupled with highly detailed arterial trees containing thousands of vessels. The core of the solver is based on a modified transmission line method, which exploits the analogy between electrical current in finite-length conductors and blood flow in vessels. The viscoelastic behaviour of the arterial-wall is taken into account using a complex elastic modulus. The flow is solved vessel by vessel in the frequency domain and the calculated output pressure is then used as an input boundary condition for daughter vessels. The computational results yield pulsatile blood pressure and flow rate for every segment in the tree. This solver is coupled with large arterial trees generated from a three-dimensional constrained constructive optimisation algorithm. The tree contains thousands of blood vessels with radii spanning ~1 mm in the root artery to ~30 μm in leaf vessels. The computation takes seconds to complete for a vasculature of 2048 vessels and less than 2 min for a vasculature of 4096 vessels on a desktop computer.