Inverse method of stress analysis for cerebral aneurysms

We present a method for predicting the wall stress in a class of cerebral aneurysms. The method hinges on an inverse formulation of the elastostatic equilibrium problem; it takes as the input a deformed configuration and the corresponding pressure, and predicts the wall stress in the given deformed state. For a membrane structure, the inverse formulation possesses a remarkable feature, that is, it can practically determine the wall tension without accurate knowledge of the wall elastic properties. In this paper, we present a finite element formulation for the inverse membrane problem and perform material sensitivity studies on idealized lesions and an image-based cerebral aneurysm model.     

Prestressing in finite deformation abdominal aortic aneurysm simulation

In abdominal aortic aneurysm (AAA) simulation the patient-specific geometry of the object of interest is very often reconstructed from in vivo medical imaging such as CT scans. Such geometries represent a deformed configuration stressed by typical in vivo conditions. However, commonly, such structures are considered stress-free in simulation. In this contribution we sketch and compare two methods to introduce a physically meaningful stress/strain state to the obtained geometry for simulations in the finite strain regime and demonstrate the necessity of such prestressing techniques. One method is based on an inverse design analysis to calculate a stress-free reference configuration. The other method developed here is based on a modified updated Lagrangian formulation. Formulation of both methods is provided. Applicability and accurateness of both approaches are compared and evaluated utilizing fully three-dimensional patient-specific AAA structures in the finite strain regime.     

A forward incremental prestressing method with application to inverse parameter estimations and eye-specific simulations of posterior scleral shells

Numerical simulations or inverse numerical analyses of individual eyes or eye segments are often based on an eye-specific geometry obtained from in vivo medical images such as computed tomography (CT) scans or from in vitro 3D digitiser scans. These eye-specific geometries are usually measured while the eye is subjected to internal pressure. Due to the nonlinear stiffening of the collagen fibril network in the eye, numerical incorporation of the pre-existing stress/strain state may be essential for realistic eye-specific computational simulations. Existing prestressing methods either compute accurate predictions of the prestressed state or guarantee a unique solution. In this contribution, a forward incremental prestressing method is presented which unifies the advantages of the existing approaches by providing accurate and unique predictions of the pre-existing stress/strain state at the true measured geometry. The impact of prestressing is investigated on (i) the inverse constitutive parameter identification of a synthetic sclera inflation test and (ii) an eye-specific simulation that estimates the realistic mechanical response of a pre-loaded posterior monkey scleral shell. Evaluation of the pre-existing stress/strain state in the inverse analysis had a significant impact on the reproducibility of the constitutive parameters but may be estimated based on an approximative approach. The eye-specific simulation of one monkey eye shows that prestressing is required for accurate displacement and stress/strain predictions. The numerical results revealed an increasing error in displacement, strain and stress predictions with increasing pre-existing pressure load when the pre-stress/strain state is disregarded. Disregarding the prestress may lead to a significant underestimation of the strain/stress environment in the sclera and overestimation in the lamina cribrosa.     

Patient-specific initial wall stress in abdominal aortic aneurysms with a backward incremental method

Patient-specific wall stress simulations on abdominal aortic aneurysms may provide a better criterion for surgical intervention than the currently used maximum transverse diameter. In these simulations, it is common practice to compute the peak wall stress by applying the full systolic pressure directly on the aneurysm geometry as it appears in medical images. Since this approach does not account for the fact that the measured geometry is already experiencing a substantial load, it may lead to an incorrect systolic aneurysm shape. We have developed an approach to compute the wall stress on the true diastolic geometry at a given pressure with a backward incremental method. The method has been evaluated with a neo-Hookean material law for several simple test problems. The results show that the method can predict an unloaded configuration if the loaded geometry and the load applied are known. The effect of incorporating the initial diastolic stress has been assessed by using three patient-specific geometries acquired with cardiac triggered MR. The comparison shows that the commonly used approach leads to an unrealistically smooth systolic geometry and therefore provides an underestimation for the peak wall stress. Our backward incremental modelling approach overcomes these issues and provides a more plausible estimate for the systolic aneurysm volume and a significantly different estimate for the peak wall stress. When the approach is applied with a more complex material law which has been proposed specifically for abdominal aortic aneurysm similar effects are observed and the same conclusion can be drawn.     

Stress-free state of the red blood cell membrane and the deformation of its skeleton

The response of a red blood cell (RBC) to deformation depends on its membrane, a composite of a lipid bilayer and a skeleton, which is a closed, twodimensional network of spectrin tetramers as its bonds. The deformation of the skeleton and its lateral redistribution are studied in terms of the RBC resting state for a fixed geometry of the RBC, partially aspirated into a micropipette. The geometry of the RBC skeleton in its initial state is taken to be either two concentric circles, a references biconcave shape or a sphere. It is assumed that in its initial state the skeleton is distributed laterally in a homogeneous manner with its bonds either unstressed, presenting its stress-free state, or prestressed. The lateral distribution was calculated using a variational calculation. It was assumed that the spectrin tetramer bonds exhibit a linear elasticity. The results showed a significant effect of the initial skeleton geometry on its lateral distribution in the deformed state. The proposed model is used to analyze the measurements of skeleton extension ratios by the method of applying two modes of RBC micropipette aspiration.     

Rheology of fibrin clots: III. Shear creep and creep recovery of fine ligated and coarse unligated clots

Creep and creep recovery of human fibrin clots in small shearing deformations have been investigated over a time scale from 24 to 10⁴ s. Coarse, unligated dots and fine dots ligated by fibrinoligase in the presence of calcium ions were studied to suppllement previous data on coarse ligated and fine unligated clots. Stress was found to be proportional to strain up to at least a maximum shear strain (in torsion geometry) of 2.6%. The initial modulus (25 s after imposition of stress) is proportional to approximately the 1.5 power of concentration for fine ligated and coarse unligated clots. For fine unligated clots, there is comparatively little creep subsequent to the initial deformation; ligation (in this case involving mostly the γ chains) reduces the creep to nearly zero. For coarse unligated dots, there is substantially more creep under constant stress, and creep recovery is not complete. legation (in this casa involving both γ and α chains) largely suppresses the creep and causes the recovery to be complete. If the structure is fully formed before creep begins, tests of creep recovery by the Boltzmann superposition principle show adherence to linear viscoelastic behavior for all four clot types. Otherwise, the Boltzmann test fails and the recovery is much less than calculated. For fine ligated clots, the observed recovery agrees well with that calculated on the basis of a dual structure model in which an additional independent structure is built up in the deformed state, so that the state of ease after removal of stress is a balance between two structures deformed in opposite senses, it is postulated that the coherence and elastic modulus of the fine ligated dot are largely due to steric blocking of long protofibrils with a high flexural stiffness. In the coarse clot, it is proposed that the structure involves extensive branching of thick bundles of protofibrils, which become permanently secured by the ligation of the α chains of the fibrin.     

Model-based inverse estimation for active contraction stresses of tongue muscles using 3D surface shape in speech production

This paper presents a novel inverse estimation approach for the active contraction stresses of tongue muscles during speech. The proposed method is based on variational data assimilation using a mechanical tongue model and 3D tongue surface shapes for speech production. The mechanical tongue model considers nonlinear hyperelasticity, finite deformation, actual geometry from computed tomography (CT) images, and anisotropic active contraction by muscle fibers, the orientations of which are ideally determined using anatomical drawings. The tongue deformation is obtained by solving a stationary force-equilibrium equation using a finite element method. An inverse problem is established to find the combination of muscle contraction stresses that minimizes the Euclidean distance of the tongue surfaces between the mechanical analysis and CT results of speech production, where a signed-distance function represents the tongue surface. Our approach is validated through an ideal numerical example and extended to the real-world case of two Japanese vowels, /ʉ/ and /ɯ/. The results capture the target shape completely and provide an excellent estimation of the active contraction stresses in the ideal case, and exhibit similar tendencies as in previous observations and simulations for the actual vowel cases. The present approach can reveal the relative relationship among the muscle contraction stresses in similar utterances with different tongue shapes, and enables the investigation of the coordination of tongue muscles during speech using only the deformed tongue shape obtained from medical images. This will enhance our understanding of speech motor control.     

Joint stiffness of the ankle and the knee in running

The spring-mass model is a valid fundament to understand global dynamics of fast legged locomotion under gravity. The underlying concept of elasticity, implying leg stiffness as a crucial parameter, is also found on lower motor control levels, i.e. in muscle-reflex and muscle-tendon systems. Therefore, it seems reasonable that global leg stiffness emerges from local elasticity established by appropriate joint torques. A recently published model of an elastically operating, segmented leg predicts that proper adjustment of joint elasticities to the leg geometry and initial conditions of ground contact provides internal leg stability. Another recent study suggests that in turn the leg segmentation and the initial conditions may be a consequence of metabolic and bone stress constraints. In this study, the theoretical predictions were verified experimentally with respect to initial conditions and elastic joint characteristics in human running. Kinematics and kinetics were measured and the joint torques were estimated by inverse dynamics. Stiffnesses and elastic nonlinearities describing the resulting joint characteristics were extracted from parameter fits. Our results clearly support the theoretical predictions: the knee joint is always stiffer and more extended than the ankle joint. Moreover, the knee torque characteristic on the average shows the higher nonlinearity. According to literature, the leg geometry is a consequence of metabolic and material stress limitations. Adapted to this given geometry, the initial joint angle conditions in fast locomotion are a compromise between metabolic and control effort minimisation. Based on this adaptation, an appropriate joint stiffness ratio between ankle and knee passively safeguards the internal leg stability. The identified joint nonlinearities contribute to the linearisation of the leg spring.     

Identification of the material parameters of soft tissues in the compressed leg

Elastic compression is recommended in prophylaxis and the treatment of venous disorder of the human leg. However, the mechanisms of compression are not completely understood and the response of internal tissues to the external pressure is partially unknown. To address this later issue, a 3D FE model of a human leg is developed. The geometry is derived from 3D CT scans. The FE model is made up of soft tissues and rigid bones. An inverse method is applied to identify the properties of soft tissues which are modelled as hyperelastic, near-incompressible, homogeneous and isotropic materials. The principle is to calibrate the constitutive properties using CT scans carried out with and without the presence of a compression sock. The deformed geometry computed by the calibrated FE model is in agreement with the geometry deduced from the CT scans. The model also provides the internal pressure distribution, which may lead to medical exploitation in the future.     

Initial stress in biomechanical models of atherosclerotic plaques

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques.     

A modified Holzapfel-Ogden law for a residually stressed finite strain model of the human left ventricle in diastole

In this work, we introduce a modified Holzapfel-Ogden hyperelastic constitutive model for ventricular myocardium that accounts for residual stresses, and we investigate the effects of residual stresses in diastole using a magnetic resonance imaging–derived model of the human left ventricle (LV). We adopt an invariant-based constitutive modelling approach and treat the left ventricular myocardium as a non-homogeneous, fibre-reinforced, incompressible material. Because in vivo images provide the configuration of the LV in a loaded state even in diastole, an inverse analysis is used to determine the corresponding unloaded reference configuration. The residual stress in this unloaded state is estimated by two different methods. One is based on three-dimensional strain measurements in a local region of the canine LV, and the other uses the opening angle method for a cylindrical tube. We find that including residual stress in the model changes the stress distributions across the myocardium and that whereas both methods yield qualitatively similar changes, there are quantitative differences between the two approaches. Although the effects of residual stresses are relatively small in diastole, the model can be extended to explore the full impact of residual stress on LV mechanical behaviour for the whole cardiac cycle as more experimental data become available. In addition, although not considered here, residual stresses may also play a larger role in models that account for tissue growth and remodelling.     

Drug transport in artery walls: a sequential porohyperelastic-transport approach

A simulation framework for drug-eluting stents (DES) is presented that simulates the two distinct operational phases of a DES: stent deployment is simulated first, a mechanical porohyperelastic/elasto-plastic/contact analysis. This analysis calculates the interstitial fluid velocity as the result of interstitial fluid pressure gradients and mechanical deformations of the vessel wall. The deformed geometry, interstitial fluid velocity field and porosity field are extracted and used as input for the drug release simulation: a reaction-advection-diffusion (RAD) transport analysis calculating the spatial and temporal drug distribution. The advantage of this approach is that the deformed geometry and interstitial fluid velocity field are not assumed a priori, but are actually calculated using a stent deployment simulation. The framework is demonstrated simulating a DES in an idealised, 3D vessel. Varying mechanical and transport properties based on literature data are assigned to each of the three layers in the wall. The results of the drug release simulation for a period of one week show that the drug distributes longitudinally but will remain in the proximity of the stented area.     

Numerical simulation of the insertion process of an uncemented hip prosthesis in order to evaluate the influence of residual stress and contact distribution on the stem initial stability

The long-term success of a cementless total hip arthroplasty depends on the implant geometry and interface bonding characteristics (fit, coating and ingrowth) and on stem stiffness. This study evaluates the influence of stem geometry and fitting conditions on the evolution and distribution of the bone–stem contact, stress and strain during and after the hip stem insertion, by means of dynamic finite element techniques. Next, the influence of the mechanical state (bone–stem contact, stress and strain) resulted from the insertion process on the stem initial resistance to subsidence is investigated. In addition, a study on the influence of bone–stem interface conditions (friction) on the insertion process and on the initial stem stability under physiological loading is performed. The results indicate that for a stem with tapered shape the contact in the proximal part of the stem was improved, but contact in the calcar region was achieved only when extra press-fit conditions were considered. Changes in stem geometry towards a more tapered shape and extra press fit and variation in the bone–stem interface conditions (contact amount and high friction) led to a raise in the total insertion force. A direct positive relationship was found between the stem resistance to subsidence and stem geometry (tapering and press fit), bone–stem interface conditions (bone–stem contact and friction interface) and the mechanical status at the end of the insertion (residual stress and strain). Therefore, further studies on evaluating the initial performance of different stem types should consider the parameters describing the bone–stem interface conditions and the mechanical state resulted from the insertion process.     

Towards a biomechanics-based technique for assessing myocardial contractility: an inverse problem approach

This work presents the initial development and implementation of a novel 3D biomechanics-based approach to measure the mechanical activity of myocardial tissue, as a potential non-invasive tool to assess myocardial function. This technique quantifies the myocardial contraction forces developed within the ventricular myofibers in response to electro-physiological stimuli. We provide a 3D finite element formulation of a contraction force reconstruction algorithm, along with its implementation using magnetic resonance (MR) data. Our algorithm is based on an inverse problem solution governed by the fundamental continuum mechanics principle of conservation of linear momentum, under a first-order approximation of elastic and isotropic material conditions. We implemented our technique using a subject-specific ventricle model obtained by extracting the left ventricular anatomical features from a set of high-resolution cardiac MR images acquired throughout the cardiac cycle using prospective electrocardiographic gating. Cardiac motion information was extracted by non-rigid registration of the mid-diastole reference image to the remaining images of a 4D dataset. Using our technique, we reconstructed dynamic maps that show the contraction force distribution superimposed onto the deformed ventricle model at each acquired frame in the cardiac cycle. Our next objective will consist of validating this technique by showing the correlation between the presence of low contraction force patterns and poor myocardial functionality.     

Sensitivity of stress and strain calculations to passive material parameters in cardiac mechanical models using unloaded geometries

Cardiac stress (load) and strain (stretch) are widely studied indicators of cardiac function and outcome, but are difficult or impossible to directly measure in relation to the cardiac microstructure. An alternative approach is to estimate these states using computer methods and image-based measurements, but this still requires knowledge of the tissue material properties and the unloaded state, both of which are difficult to determine. In this work, we tested the sensitivity of these two interdependent unknowns (reference geometry and material parameters) on stress and strain calculations in cardiac tissue. Our study used a finite element model of the human ventricle, with a hyperelastic passive material model, and was driven by a cell model mediated active contraction. We evaluated 21 different published parameter sets for the five parameters of the passive material model, and for each set we optimised the corresponding unloaded geometry and contractility parameter to model a single pressure-volume loop. The resulting mechanics were compared, and calculated systolic stresses were largely insensitive to the chosen parameter set when an unloading algorithm was used. Meanwhile, material strain calculations varied substantially depending on the choice of material parameters. These results indicate that determining the correct material and unloaded configuration may be highly important to understand strain driven processes, but less so for calculating stress estimates.     

Initial stress and nonlinear material behavior in patient-specific AAA wall stress analysis

Rupture risk estimation of abdominal aortic aneurysms (AAA) is currently based on the maximum diameter of the AAA. A more critical approach is based on AAA wall stress analysis. For that, in most cases, the AAA geometry is obtained from CT-data and treated as a stress free geometry. However, during CT imaging, the AAA is subjected to a time-averaged blood pressure and is therefore not stress free. The aim of this study is to evaluate the effect of neglecting these initial stresses (IS) on the patient-specific AAA wall stress as computed by finite element analysis. Additionally, the contribution of the nonlinear material behavior of the AAA wall is evaluated.Thirty patients with maximum AAA diameters below the current surgery criterion were scanned with contrast-enhanced CT and the AAA's were segmented from the image data. The mean arterial blood pressure (MAP) was measured immediately after the CT-scan and used to compute the IS corresponding with the CT geometry and MAP. Comparisons were made between wall stress obtained with and without IS and with linear and nonlinear material properties.On average, AAA wall stresses as computed with IS were higher than without IS. This was also the case for the stresses computed with the nonlinear material model compared to the linear material model. However, omitting initial stress and material nonlinearity in AAA wall stress computations leads to different effects in the resulting wall stress for each AAA. Therefore, provided that other assumptions made are not predominant, IS cannot be discarded and a nonlinear material model should be used in future patient-specific AAA wall stress analyses.     

A novel approach to in vivo mitral valve stress analysis

Three-dimensional (3-D) echocardiography allows the generation of anatomically correct and time-resolved geometric mitral valve (MV) models. However, as imaged in vivo, the MV assumes its systolic geometric configuration only when loaded. Customarily, finite element analysis (FEA) is used to predict material stress and strain fields rendered by applying a load on an initially unloaded model. Therefore, this study endeavors to provide a framework for the application of in vivo MV geometry and FEA to MV physiology, pathophysiology, and surgical repair. We hypothesize that in vivo MV geometry can be reasonably used as a surrogate for the unloaded valve in computational (FEA) simulations, yielding reasonable and meaningful stress and strain magnitudes and distributions. Three experiments were undertaken to demonstrate that the MV leaflets are relatively nondeformed during systolic loading: 1) leaflet strain in vivo was measured using sonomicrometry in an ovine model, 2) hybrid models of normal human MVs as constructed using transesophageal real-time 3-D echocardiography (rt-3DE) were repeatedly loaded using FEA, and 3) serial rt-3DE images of normal human MVs were used to construct models at end diastole and end isovolumic contraction to detect any deformation during isovolumic contraction. The average linear strain associated with isovolumic contraction was 0.02 ± 0.01, measured in vivo with sonomicrometry. Repeated loading of the hybrid normal human MV demonstrated little change in stress or geometry: peak von Mises stress changed by <4% at all locations on the anterior and posterior leaflets. Finally, the in vivo human MV deformed minimally during isovolumic contraction, as measured by the mean absolute difference calculated over the surfaces of both leaflets between serial MV models: 0.53 ± 0.19 mm. FEA modeling of MV models derived from in vivo high-resolution truly 3-D imaging is reasonable and useful for stress prediction in MV pathologies and repairs.     

Microscopic investigation of erythrocyte deformation dynamics

The understanding of erythrocyte deformation under conditions of high shear stress and short exposure time is central to the study of hemorheology and hemolysis within prosthetic blood contacting devices. A combined computational and experimental microscopic study was conducted to investigate the erythrocyte deformation and its relation to transient stress fields. A microfluidic channel system with small channels fabricated using polydimethylsiloxane on the order of 100 mum was designed to generate transient stress fields through which the erythrocytes were forced to flow. The shear stress fields were analyzed by three-dimensional computational fluid dynamics. Microscopic images of deforming erythrocytes were experimentally recorded to obtain the changes in cell morphology over a wide range of fluid dynamic stresses. The erythrocyte elongation index (EI) increased from 0 to 0.54 with increasing shear stress up to 123 Pa. In this shear stress range, erythrocytes behaved like fluid droplets, and deformed and flowed following the surrounding fluid. Cells exposed to shear stress beyond 123 Pa (up to 5170 Pa) did not exhibit additional elongation beyond EI=0.54. Two-stage deformation of erythrocytes in response to shear stress was observed: an initial linear elongation with increasing shear stress and a plateau beyond a critical shear stress.