An orthotropic viscoelastic model for the passive myocardium: continuum basis and numerical treatment

This study deals with the viscoelastic constitutive modeling and the respective computational analysis of the human passive myocardium. We start by recapitulating the locally orthotropic inner structure of the human myocardial tissue and model the mechanical response through invariants and structure tensors associated with three orthonormal basis vectors. In accordance with recent experimental findings the ventricular myocardial tissue is assumed to be incompressible, thick-walled, orthotropic and viscoelastic. In particular, one spring element coupled with Maxwell elements in parallel endows the model with viscoelastic features such that four dashpots describe the viscous response due to matrix, fiber, sheet and fiber-sheet fragments. In order to alleviate the numerical obstacles, the strictly incompressible model is altered by decomposing the free-energy function into volumetric-isochoric elastic and isochoric-viscoelastic parts along with the multiplicative split of the deformation gradient which enables the three-field mixed finite element method. The crucial aspect of the viscoelastic formulation is linked to the rate equations of the viscous overstresses resulting from a 3-D analogy of a generalized 1-D Maxwell model. We provide algorithmic updates for second Piola–Kirchhoff stress and elasticity tensors. In the sequel, we address some numerical aspects of the constitutive model by applying it to elastic, cyclic and relaxation test data obtained from biaxial extension and triaxial shear tests whereby we assess the fitting capacity of the model. With the tissue parameters identified, we conduct (elastic and viscoelastic) finite element simulations for an ellipsoidal geometry retrieved from a human specimen.     

Leukocyte deformability: finite element modeling of large viscoelastic deformation.

An axisymmetric deformation of a viscoelastic sphere bounded by a prestressed elastic thin shell in response to external pressure is studied by a finite element method. The research is motivated by the need for understanding the passive behavior of human leukocytes (white blood cells) and interpreting extensive experimental data in terms of the mechanical properties. The cell at rest is modeled as a sphere consisting of a cortical prestressed shell with incompressible Maxwell fluid interior. A large-strain deformation theory is developed based on the proposed model. General non-linear, large strain constitutive relations for the cortical shell are derived by neglecting the bending stiffness. A representation of the constitutive equations in the form of an integral of strain history for the incompressible Maxwell interior is used in the formulation of numerical scheme. A finite element program is developed, in which a sliding boundary condition is imposed on all contact surfaces. The mathematical model developed is applied to evaluate experimental data of pipette tests and observations of blood flow.     

A model for the nonlinear elastic response of large arteries

The nonlinear elastic response of large arteries subjected to finite deformations due to action of biaxial principal stresses, is described by simple constitutive equations. Generalized measures of strain and stress are introduced to account for material nonlinearity. This also ensures the existence of a strain energy density function. The orthotropic elastic response is described via quasi-linear relations between strains and stresses. One nonlinear parameter which defines the measures of strain and stress, and three elastic moduli are assumed to be constants. The lateral strain parameters (equivalent to Poisson's ratios in infinitesimal deformations) are deformation dependent. This dependence is defined by empirical relations developed via the incompressibility condition, and by the introduction of a fifth material parameter. The resulting constitutive model compares well with biaxial experimental data of canine carotid arteries.     

A visco-hyperelastic model for skeletal muscle tissue under high strain rates

In this paper, a visco-hyperelastic skeletal muscle model is developed. The constitutive relation is based on the definition of a Helmholtz free energy function. It is assumed that the Helmholtz energy can be decomposed into volumetric and isochoric parts; furthermore, the isochoric energy can be decoupled into hyperelastic and viscous parts. The model developed involves 14 material parameters and its performance is evaluated by comparing the finite element simulation results with the published experimental studies on the New Zealand white rabbit tibialis anterior muscle. Results show that this model is able to describe the visco-hyperelastic behaviour of both passive and active skeletal muscle tissues under high strain rates (10/s and 25/s).     

A 3D active-passive numerical skeletal muscle model incorporating initial tissue strains. Validation with experimental results on rat tibialis anterior muscle

This paper presents a three-dimensional finite element model of skeletal muscle and its validation incorporating inital tissue strains. A constitutive relation was determined by using a convex free strain energy function (SEF) where active and passive response contributions were obtained fitting experimental data from the rat tibialis anterior (TA) muscle. The passive and active finite strains response was modelled within the framework of continuum mechanics by a quasi-incompressible transversely isotropic material formulation. Magnetic resonance images (MRI) were obtained to reconstruct the external geometry of the TA. This geometry includes initial strains also taken into account in the numerical model. The numerical results show excellent agreement with the experimental results when comparing reaction force-extension curves both in passive and active tests. The proposed constitutive model for the muscle is implemented in a subroutine in the commercial finite element software package ABAQUS.     

Compression behavior of porcine spinal cord white matter

Spinal cord injury often results from a compressive load; however, the compression behavior of spinal cord white matter has not been clearly established. Quantifying the compression behavior is important for advancing our understanding of spinal cord injury mechanics and facilitating the use of finite element models to study injury. The objective of this study was to characterize the unconfined compression behavior of isolated white matter segments and determine the constitutive model which best captured the stress-strain behavior. Spinal cord white matter samples were harvested immediately following sacrifice from juvenile Yorkshire pigs (n=104). The samples were compressed to 40% strain at four strain rates (0.005, 0.05, 0.5, and 5.0/s) and allowed to relax for 60s. The effects of preload, peak strain, sample aspect ratio, and time post mortem on peak stress, and constitutive model parameters were also examined. Strain rate had a significant effect on peak stress (p<0.001). A first-order Ogden model best captured the loading response of spinal cord white matter (R(2)=0.99) and a viscoelastic material model combining a first-order Ogden model with a 3-term Prony series effectively captured the effect of strain rate and the relaxation response. This study showed spinal cord white matter to be less stiff than previously estimated by inverse finite element methods, which will have a significant effect on finite element model predictions of the magnitude and distribution of stresses and strains in the spinal cord. This study is the first to quantify the unconfined compression response of spinal cord white matter.     

Adjoint multi-start-based estimation of cardiac hyperelastic material parameters using shear data

Cardiac muscle tissue during relaxation is commonly modeled as a hyperelastic material with strongly nonlinear and anisotropic stress response. Adapting the behavior of such a model to experimental or patient data gives rise to a parameter estimation problem which involves a significant number of parameters. Gradient-based optimization algorithms provide a way to solve such nonlinear parameter estimation problems with relatively few iterations, but require the gradient of the objective functional with respect to the model parameters. This gradient has traditionally been obtained using finite differences, the calculation of which scales linearly with the number of model parameters, and introduces a differencing error. By using an automatically derived adjoint equation, we are able to calculate this gradient more efficiently, and with minimal implementation effort. We test this adjoint framework on a least squares fitting problem involving data from simple shear tests on cardiac tissue samples. A second challenge which arises in gradient-based optimization is the dependency of the algorithm on a suitable initial guess. We show how a multi-start procedure can alleviate this dependency. Finally, we provide estimates for the material parameters of the Holzapfel and Ogden strain energy law using finite element models together with experimental shear data.     

A finite element study of invariant-based orthotropic constitutive equations in the context of myocardial material parameter estimation

A previous study investigated a number of invariant-based orthotropic and transversely isotropic constitutive equations for their suitability to fit three-dimensional simple shear mechanics data of passive myocardial tissue. The study was based on the assumption of a homogeneous deformation. Here, we extend the previous study by performing an inverse finite element material parameter estimation. This ensures a more realistic deformation state and material parameter estimates. The constitutive relations were compared on the basis of (i) ‘goodness of fit’: how well they fit a set of six shear deformation tests and (ii) ‘variability’: how well determined the material parameters are over the range of experiments. These criteria were utilised to discuss the advantages and disadvantages of the constitutive relations. It was found that a specific form of the polyconvex type as well as the exponential Fung-type equations were most suitable for modelling the orthotropic behaviour of myocardium under simple shear.     

Epicardial suction: a new approach to mechanical testing of the passive ventricular wall

The lack of an appropriate three-dimensional constitutive relation for stress in passive ventricular myocardium currently limits the utility of existing mathematical models for experimental and clinical applications. Previous experiments used to estimate parameters in three-dimensional constitutive relations, such as biaxial testing of excised myocardial sheets or passive inflation of the isolated arrested heart, have not included significant transverse shear deformation or in-plane compression. Therefore, a new approach has been developed in which suction is applied locally to the ventricular epicardium to introduce a complex deformation in the region of interest, with transmural variations in the magnitude and sign of nearly all six strain components. The resulting deformation is measured throughout the region of interest using magnetic resonance tagging. A nonlinear, three-dimensional, finite element model is used to predict these measurements at several suction pressures. Parameters defining the material properties of this model are optimized by comparing the measured and predicted myocardial deformations. We used this technique to estimate material parameters of the intact passive canine left ventricular free wall using an exponential, transversely isotropic constitutive relation. We tested two possible models of the heart wall: first, that it was homogeneous myocardium, and second, that the myocardium was covered with a thin epicardium with different material properties. For both models, in agreement with previous studies, we found that myocardium was nonlinear and anisotropic with greater stiffness in the fiber direction. We obtained closer agreement to previously published strain data from passive filling when the ventricular wall was modeled as having a separate, isotropic epicardium. These results suggest that epicardium may play a significant role in passive ventricular mechanics.     

Effect of colchicine on viscoelastic properties of neutrophils

The effect of colchicine (15-60 micrograms/ml) on the viscoelastic properties of human neutrophils was studied by the micropipette technique. The small deformation of the neutrophil in response to a step aspiration pressure was analyzed by using a three-element model in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, mu. Colchicine treatment of neutrophils caused decreases in K2 and mu without affecting K1. The results indicate that the integrity of the microtubules plays a significant role in providing the viscoelastic resistance (as represented by the Maxwell element in the model) of neutrophils to deforming stress.     

A frame-invariant formulation of Fung elasticity

Fung elasticity refers to the hyperelasticity constitutive relation proposed by Fung and co-workers for describing the pseudo-elastic behavior of biological soft tissues undergoing finite deformation. A frame-invariant formulation of Fung elasticity is provided for material symmetries ranging from orthotropy to isotropy, which uses Lamé-like material constants. In the orthotropic case, three orthonormal vectors are used to define mutually orthogonal planes of symmetry and associated texture tensors. The strain energy density is then formulated as an isotropic function of the Lagrangian strain and texture tensors. The cases of isotropy and transverse isotropy are derived from the orthotropic case. Formulations are provided for both material and spatial frames. These formulations are suitable for implementation into finite element codes. It is also shown that the strain energy function can be naturally uncoupled into a dilatational and a distortional part, to facilitate the computational implementation of incompressibility.     

Development of an in vivo method for determining material properties of passive myocardium

Calculation of mechanical stresses and strains in the left ventricular (LV) myocardium by the finite element (FE) method relies on adequate knowledge of the material properties of myocardial tissue. In this paper, we present a model-based estimation procedure to characterize the stress-strain relationship in passive LV myocardium. A 3D FE model of the LV myocardium was used, which included morphological fiber and sheet structure and a nonlinear orthotropic constitutive law with different stiffness in the fiber, sheet, and sheet-normal directions. The estimation method was based on measured wall strains. We analyzed the method's ability to estimate the material parameters by generating a set of synthetic strain data by simulating the LV inflation phase with known material parameters. In this way we were able to verify the correctness of the solution and to analyze the effects of measurement and model error on the solution accuracy and stability. A sensitivity analysis was performed to investigate the observability of the material parameters and to determine which parameters to estimate. The results showed a high degree of coupling between the parameters governing the stiffness in each direction. Thus, only one parameter in each of the three directions was estimated. For the tested magnitudes of added noise and introduced model errors, the resulting estimated stress-strain characteristics in the fiber and sheet directions converged with good accuracy to the known relationship. The sheet-normal stress-strain relationship had a higher degree of uncertainty as more noise was added and model error was introduced.     

Material parameter identification of arterial wall layers from homogenised stress-strain data

Multilayer structure of the artery can have significant effects on the resulting mechanical behaviour of the artery wall. Separation of the artery into individual layers is sometimes performed to identify the layer-specific parameters of constitutive model proposed by Holzapfel, Gasser and Ogden (HGO model). Inspired by this single-layer model, a double-layer model was formulated and used for identification of material parameters from homogenised stress-strain data (of non-separated artery wall). The paper demonstrates that the layer-specific parameters of the double-layer constitutive model can be identified without the need of artery separation. The resulting double-layer model can credibly describe the homogenised stress-strain behaviour of the real artery wall including large-strain stiffening effects attributed to multilayer nature of the artery.     

A Bimodular Theory for Finite Deformations: Comparison of Orthotropic Second-order and Exponential Stress Constitutive Equations for Articular Cartilage

Cartilaginous tissues, such as articular cartilage and the annulus fibrosus, exhibit orthotropic behavior with highly asymmetric tensile–compressive responses. Due to this complex behavior, it is difficult to develop accurate stress constitutive equations that are valid for finite deformations. Therefore, we have developed a bimodular theory for finite deformations of elastic materials that allows the mechanical properties of the tissue to differ in tension and compression. In this paper, we derive an orthotropic stress constitutive equation that is second-order in terms of the Biot strain tensor as an alternative to traditional exponential type equations. Several reduced forms of the bimodular second-order equation, with six to nine parameters, and a bimodular exponential equation, with seven parameters, were fit to an experimental dataset that captures the highly asymmetric and orthotropic mechanical response of cartilage. The results suggest that the bimodular second-order models may be appealing for some applications with cartilaginous tissues.     

Mechanical properties of brain tissue in tension

This paper contains experimental results of in vitro, uniaxial tension of swine brain tissue in finite deformation as well as proposes a new hyper-viscoelastic constitutive model for the brain tissue. The experimental results obtained for two loading velocities, corresponding to strain rates of 0.64 and 0.64 x 10(-2)s(-1), are presented. We believe that these are the first ever experiments of this kind. The applied strain rates were similar to those applied in our previous study, focused on explaining brain tissue properties in compression. The stress-strain curves are convex downward for all extension rates. The tissue response stiffened as the loading speed increased, indicating a strong stress-strain rate dependence. Swine brain tissue was found to be considerably softer in extension than in compression. Previously proposed in the literature brain tissue constitutive models, developed based on experimental data collected in compression are shown to be inadequate to explain tissue behaviour in tension. A new, non-linear, viscoelastic model based on the generalisation of the Ogden strain energy hyper-elastic constitutive equation is proposed. The new model accounts well for brain tissue deformation behaviour in both tension and compression (natural strain in <-0.3,0.2>) for strain rates ranging over five orders of magnitude.     

Determination of material parameters of the two-dimensional Holzapfel–Weizsäcker type model based on uniaxial extension data of arterial walls

Soft tissues are anisotropic materials yet a majority of mechanical property tests have been uniaxial, which often failed to recapitulate the tensile response in other directions. This paper aims to study the feasibility of determining material parameters of anisotropic tissues by uniaxial extension with a minimal loss of anisotropic information. We assumed that by preselecting a certain constitutive model, we could give the constitutive parameters based on uniaxial extension data from orthogonal strip samples. In our study, the Holzapfel–Weizsäcker type strain energy density function (H–W model) was used to determine the material parameters of arterial walls from two fresh donation bodies. The key points we applied were the relationships between strain components in uniaxial tensile tests and the methods of stochastic optimisation. Further numerical experiments were taken. The estimate–effect ratio, defined by the number of data with the precision of estimation less than 0.5% over whole size of data, was calculated to demonstrate the feasibility of our method. The material parameters for Chinese aorta and pulmonary artery were given with the maximum root mean square (RMS) errors 0.042, and the minimal estimate–effect ratio in numerical experiments was 90.79%. Our results suggest that the constitutive parameters of arterial walls can be determined from uniaxial extension data, given the passive mechanical behaviour governed by H–W model. This method may apply to other tissues using different constitutive models.     

Myocardial material parameter estimation

The passive material properties of myocardium play a major role in diastolic performance of the heart. In particular, the shear behaviour is thought to play an important mechanical role due to the laminar architecture of myocardium. We have previously compared a number of myocardial constitutive relations with the aim to extract their suitability for inverse material parameter estimation. The previous study assumed a homogeneous deformation. In the present study we relaxed the homogeneous assumption by implementing these laws into a finite element environment in order to obtain more realistic measures for the suitability of these laws in both their ability to fit a given set of experimental data, as well as their stability in the finite element environment. In particular, we examined five constitutive laws and compare them on the basis of (i) "goodness of fit": how well they fit a set of six shear deformation tests, (ii) "determinability": how well determined the objective function is at the optimal parameter fit, and (iii) "variability": how well determined the material parameters are over the range of experiments. Furthermore, we compared the FE results with those from the previous study.It was found that the same material law as in the previous study, the orthotropic Fung-type "Costa-Law", was the most suitable for inverse material parameter estimation for myocardium in simple shear.     

Internal viscoelastic loading in cat papillary muscle.

The passive mechanical properties of myocardium were defined by measuring force responses to rapid length ramps applied to unstimulated cat papillary muscles. The immediate force changes following these ramps recovered partially to their initial value, suggesting a series combination of viscous element and spring. Because the stretched muscle can bear force at rest, the viscous element must be in parallel with an additional spring. The instantaneous extension-force curves measured at different lengths were nonlinear, and could be made to superimpose by a simple horizontal shift. This finding suggests that the same spring was being measured at each length, and that this spring was in series with both the viscous element and its parallel spring (Voigt configuration), so that the parallel spring is held nearly rigid by the viscous element during rapid steps. The series spring in the passive muscle could account for most of the series elastic recoil in the active muscle, suggesting that the same spring is in series with both the contractile elements and the viscous element. It is postulated that the viscous element might be coupled to the contractile elements by a compliance, so that the load imposed on the contractile elements by the passive structures is viscoelastic rather than purely viscous. Such a viscoelastic load would give the muscle a length-independent, early diastolic restoring force. The possibility is discussed that the length-independent restoring force would allow some of the energy liberated during active shortening to be stored and released during relaxation.     

A visco-hyperelastic-damage constitutive model for the analysis of the biomechanical response of the periodontal ligament

The periodontal ligament (PDL), as other soft biological tissues, shows a strongly non-linear and time-dependent mechanical response and can undergo large strains under physiological loads. Therefore, the characterization of the mechanical behavior of soft tissues entails the definition of constitutive models capable of accounting for geometric and material non-linearity. The microstructural arrangement determines specific anisotropic properties. A hyperelastic anisotropic formulation is adopted as the basis for the development of constitutive models for the PDL and properly arranged for investigating the viscous and damage phenomena as well to interpret significant aspects pertaining to ordinary and degenerative conditions. Visco-hyperelastic models are used to analyze the time-dependent mechanical response, while elasto-damage models account for the stiffness and strength decrease that can develop under significant loading or degenerative conditions. Experimental testing points out that damage response is affected by the strain rate associated with loading, showing a decrease in the damage limits as the strain rate increases. These phenomena can be investigated by means of a model capable of accounting for damage phenomena in relation to viscous effects. The visco-hyperelastic-damage model developed is defined on the basis of a Helmholtz free energy function depending on the strain-damage history. In particular, a specific damage criterion is formulated in order to evaluate the influence of the strain rate on damage. The model can be implemented in a general purpose finite element code. The accuracy of the formulation is evaluated by using results of experimental tests performed on animal model, accounting for different strain rates and for strain states capable of inducing damage phenomena. The comparison shows a good agreement between numerical results and experimental data.