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It remains difficult to predict when which patients with abdominal aortic aneurysm (AAA) will require surgery. The aim was to study the accuracy of geometric and biomechanical analysis of small AAAs to predict reaching the threshold for surgery, diameter growth rate and rupture or symptomatic aneurysm. 189 patients with AAAs of diameters 40–50 mm were included, 161 had undergone two CTAs. Geometric and biomechanical variables were used in prediction modelling. Classifications were evaluated with area under receiver operating characteristic curve (AUC) and regressions with correlation between observed and predicted growth rates. Compared with the baseline clinical diameter, geometric-biomechanical analysis improved prediction of reaching surgical threshold within four years (AUC 0.80 vs 0.85, p = 0.031) and prediction of diameter growth rate (r = 0.17 vs r = 0.38, p = 0.0031), mainly due to the addition of semiautomatic diameter measurements. There was a trend towards increased precision of volume growth rate prediction (r = 0.37 vs r = 0.45, p = 0.081). Lumen diameter and biomechanical indices were the only variables that could predict future rupture or symptomatic AAA (AUCs 0.65–0.67). Enhanced precision of diameter measurements improves the prediction of reaching the surgical threshold and diameter growth rate, while lumen diameter and biomechanical analysis predicts rupture or symptomatic AAA.

Rupture of unstable atherosclerotic plaques with a large lipid-rich necrotic core and a thin fibrous cap cause myocardial infarction and stroke. Yet it has not been possible to assess this for individual patients. Clinical guidelines still rely on use of luminal narrowing, a poor indicator but one that persists for lack of effective means to do better. We present a case study demonstrating the assessment of biomechanical indices pertaining to plaque rupture risk non-invasively for individual patients enabled by histologically validated tissue characterization.Routinely acquired clinical images of plaques were analyzed to characterize vascular wall tissues using software validated by histology (ElucidVivo, Elucid Bioimaging Inc.). Based on the tissue distribution, wall stress and strain were then calculated at spatial locations with varied fibrous cap thicknesses at diastolic, mean and systolic blood pressures.The von Mises stress of 152 [131, 172] kPa and the equivalent strain of 0.10 [0.08, 0.12] were calculated where the fibrous cap thickness was smallest (560 μm) (95% CI in brackets). The stress at this location was at a level predictive of plaque failure. Stress and strain at locations with larger cap thicknesses were calculated to be lower, demonstrating a clinically relevant range of risk levels.Patient specific tissue characterization can identify distributions of stress and strain in a clinically relevant range. This capability may be used to identify high-risk lesions and personalize treatment decisions for individual patients with cardiovascular disease and improve prevention of myocardial infarction and stroke.

Hip fractures are a major health problem with high socio-economic costs. Subject-specific finite element (FE) models have been suggested to improve the fracture risk assessment, as compared to clinical tools based on areal bone mineral density, by adding an estimate of bone strength. Typically, such FE models are limited to estimate bone strength and possibly the fracture onset, but do not model the fracture process itself. The aim of this study was to use a discrete damage approach to simulate the full fracture process in subject-specific femur models under stance loading conditions. A framework based on the partition of unity finite element method (PUFEM), also known as XFEM, was used. An existing PUFEM framework previously used on a homogeneous generic femur model was extended to include a heterogeneous material description together with a strain-based criterion for crack initiation. The model was tested on two femurs, previously mechanically tested in vitro. Our results illustrate the importance of implementing a subject-specific material distribution to capture the experimental fracture pattern under stance loading. Our models accurately predicted the fracture pattern and bone strength (1% and 5% error) in both investigated femurs. This is the first study to simulate complete fracture paths in subject-specific FE femur models and it demonstrated how discrete damage models can provide a more complete picture of fracture risk by considering both bone strength and fracture toughness in a subject-specific fashion.

External (mechanical) stimuli influence cell function at the level of gene expression and thereby contribute to the overall control of Soft Biological Tissues' (SBT) structure and function. SBT seem to adapt towards stable homeostatic mechanical conditions, and failure of reaching homeostasis may result in pathologies. SBT adaptation has to obey basic physical principles, and even within these constraints, a large number of SBT adaptation models have been proposed. Recent SBT models integrated the tissue's microstructure and directly addressed length scales of individual tissue constituents, which in turn allowed linking biomechanical and biochemical adaptation aspects. Despite adaptation models being based on very different hypotheses, many of them lead to physically reasonable results. Most interestingly, the recently developed homogenized Constrained Mixture Model reported very similar predictions than the original Constrained Mixture Model. This key observation indicates that the simpler kinematics-based approach is indeed able to capture the overall consequences of the continuous production and degradation of SBT constituents. However, mainly due to the scarcity of relevant experiment data, not a single model has been thoroughly validated against clearly specified modeling objectives. Consequently, much more interdisciplinary experimental work is required to guide SBT modeling activities. Nevertheless, predictive biomechanical SBT adaption models would not only be of considerable scientific interest, but would also have a large number of practical applications.

Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2–5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p

A biomechanical stress analysis could help to identify carotid plaques that are vulnerable to rupture, and hence reduce the risk of thrombotic strokes. Mechanical stress predictions critically depend on the plaque's constitutive properties, and the present study introduces a concept to derive viscoelastic parameters through an experimental-numerical approach. Carotid plaques were harvested from two patients during carotid endarterectomy (CEA), and, in total, nine test specimens were investigated. A novel in-vitro mechanical testing protocol, which allows for dynamic testing, keeping the carotid plaque components together, was introduced. Macroscopic pictures overlaid by histological stains allowed for the segmentation of plaque tissues, in order to develop high-fidelity and low-fidelity Finite Element Method (FEM) models of the test specimens. The FEM models together with load-displacement data from the mechanical testing were used to extract constitutive parameters through inverse parameter estimation. The applied inverse parameter estimation runs in stages, first addressing the hyperelastic parameters then the viscoelastic ones. Load-displacement curves from the mechanical testing showed strain stiffening and viscoelasticity, as is expected for both normal and diseased carotid tissue. The estimated constitutive properties of plaque tissue were comparable to previously reported studies. Due to the highly non-linear elasticity of vascular tissue, the applied parameter estimation approach is, as with many similar approaches, sensitive to the initial guess of the parameters.

Arterial physiology relies on a delicate three-dimensional (3D) organization of cells and extracellular matrix, which is remarkably altered by vascular diseases like abdominal aortic aneurysms (AAA). The ability to explore the micro-histology of the aorta wall is important in the study of vascular pathologies and in the development of vascular constitutive models, i.e., mathematical descriptions of biomechanical properties of the wall. The present study reports and validates a fast image processing sequence capable of quantifying collagen fiber organization from histological stains. Powering and re-normalizing the histogram of the classical fast Fourier transformation (FFT) is a key step in the proposed analysis sequence. This modification introduces a powering parameterw, which was calibrated to best fit the reference data obtained using classical FFT and polarized light microscopy (PLM) of stained histological slices of AAA wall samples. The values ofw= 3 and 7 give the best correlation (Pearson's correlation coefficient larger than 0.7,R2about 0.7) with the classical FFT approach and PLM measurements. A fast and operator independent method to identify collagen organization in the arterial wall was developed and validated. This overcomes severe limitations of currently applied methods like PLM to identify collagen organization in the arterial wall.

Wall stress analysis of abdominal aortic aneurysm (AAA) is a promising method of identifying AAAs at high risk of rupture. However, neglecting residual strains (RS) in the load-free configuration of patient-specific finite element analysis models is a sever limitation that strongly affects the computed wall stresses. Although several methods for including RS have been proposed, they cannot be directly applied to patient-specific AAA simulations. RS in the AAA wall are predicted through volumetric tissue growth that aims at satisfying the homogeneous stress hypothesis at mean arterial pressure load. Tissue growth is interpolated linearly across the wall thickness and aneurysm tissues are described by isotropic constitutive formulations. The total deformation is multiplicatively split into elastic and growth contributions, and a staggered schema is used to solve the field variables. The algorithm is validated qualitatively at a cylindrical artery model and then applied to patient-specific AAAs (n = 5). The induced RS state is fully three-dimensional and in qualitative agreement with experimental observations, i.e., wall strips that were excised from the load-free wall showed stress-releasing-deformations that are typically seen in laboratory experiments. Compared to RS-free simulations, the proposed algorithm reduced the von Mises stress gradient across the wall by a tenfold. Accounting for RS leads to homogenized wall stresses, which apart from reducing the peak wall stress (PWS) also shifted its location in some cases. The present study demonstrated that the homogeneous stress hypothesis can be effectively used to predict RS in the load-free configuration of the vascular wall. The proposed algorithm leads to a fast and robust prediction of RS, which is fully capable for a patient-specific AAA rupture risk assessment. Neglecting RS leads to non-realistic wall stress values that severely overestimate the PWS.

Background: Results of biomechanical simulation of the abdominal aortic aneurysm (AAA) depend on the constitutive description of the wall. Based on in vitro and in vivo experimental data several constitutive models for the AAA wall have been proposed in the literature. Those models differ strongly from each other and their impact on the computed stress in biomechanical simulation is not clearly understood. Methods: Finite element (FE) models of AAAs from 7 patients who underwent elective surgical repair were used to compute wall stresses. AAA geometry was reconstructed from CT angiography (CT-A) data and patient-specific (PS) constitutive descriptions of the wall were derived from planar biaxial testing of anterior wall tissue samples. In total 28 FE models were used, where the wall was described by either patient-specific or previously reported study-average properties. This data was derived from either uniaxial or biaxial in vitro testing. Computed wall stress fields were compared on node-by-node basis. Results: Different constitutive models for the AAA wall cause significantly different predictions of wall stress. While study-average data from biaxial testing gives globally the same stress field as the patient-specific wall properties, the material model based on uniaxial test data overestimates the wall stress on average by 30. kPa or about 67% of the mean stress. A quasi-linear description based on the in vivo measured distensibility of the AAA wall leads to a completely altered stress field and overestimates the wall stress by about 75. kPa or about 167% of the mean stress. Conclusion: The present study demonstrated that the constitutive description of the wall is crucial for AAA wall stress prediction. Consequently, results obtained using different models should not be mutually compared unless different stress gradients across the wall are not taken into account. Highly nonlinear material models should be preferred when the response of AAA to increased blood pressure is investigated, while the quasi-linear model with high initial stiffness produces negligible stress gradients across the wall and thus, it is more appropriate when response to mean blood pressure is calculated. QC 20130819

Assessing the risk for abdominal aortic aneurysm (AAA) rupture is critical in the management of aneurysm patients and an individual assessment is possible with the biomechanical rupture risk assessment. Such an assessment could potentially be improved by a constitutive AAA wall model that accounts for irreversible damage-related deformations. Because of that the present study estimated the elastic and inelastic properties of the AAA wall through a mixed experimental-numerical approach. Specifically, finite element (FE) models of bone-shaped tensile specimens were used to merge data from failure testing of the AAA wall with their measured collagen orientation distribution. A histo-mechanical constitutive model for collagen fibers was employed, where plastic fibril sliding determined not only remaining deformations but also weakening of the fiber. The developed FE models were able to replicate the experimentally recorded load-displacement property of all 16 AAA wall specimens that were investigated in the study. Tensile testing in longitudinal direction of the AAA defined a Cauchy strength of 569(SD 411) kPa that was reached at a stretch of 1.436(SD 0.118). The stiffness and strength of specimens decreased with the wall thickness and were elevated (p = 0.018; p = 0.030) in patients with chronic obstructive pulmonary disease (COPD). Smoking affected the tissue parameters that were related to the irreversible deformation response, and no correlation with gender and age was found. The observed effects on the biomechanical properties of the AAA wall could have long-term consequences for the management of aneurysm patients, i.e., specifically they might influence future AAA rupture risk assessments. However, in order to design appropriate clinical validation studies our findings should firstly be verified in a larger patient cohort. QC 20130719

Quantification of the mechanical properties of atherosclerotic plaque has shown to be important in assessing carotid artery plaque vulnerability. For such, shear wave elastography (SWE) has been applied on both in-vitro and in-vivo setups. The aim of this study was to build an ex-vivo setup for combined evaluation of plaque characteristics using SWE and micro-computed tomography (μCT). As a proof-of-concept of the constructed experimental setup, a single human carotid plaque specimen was extracted during carotid endarterectomy. The plaque was imaged in the μCT system, and subsequently imaged using SWE. For the SWE measurement, group and phase velocity was extracted from the obtained in-phase/quadrature data, with its spatial distribution being compared to anatomical features visible in the μCT images. The results indicated wave velocity changes at boundaries identified in the μCT, with group velocity data slightly increasing when entering a calcified nodule. Additionally, μCT images seemed to provide good contrast between several plaque constituens using the defined imaging settings. Overall, the study represents a proof-of-concept for detailed ex-vivo plaque analysis using combined SWE and μCT, with obtained wave speed and shear modulus values falling within observed values for atherosclerotic plaque tissue. With an experimental setup defined, future studies on carotid plaque behaviour both in SWE and μCT is enabled, where a large-scale plaque study could be performed to investigate the ability of SWE to differentiate between different plaque types.

A fundamental understanding of the mechanical properties of the extracellular matrix (ECM) is critically important to quantify the amount of macroscopic stress and/or strain transmitted to the cellular level of vascular tissue. Structural constitutive models integrate histological and mechanical information, and hence, allocate stress and strain to the different microstructural components of the vascular wall. The present work proposes a novel multi-scale structural constitutive model of passive vascular tissue, where collagen fibers are assembled by proteoglycan (PG) cross-linked collagen fibrils and reinforce an otherwise isotropic matrix material. Multiplicative kinematics account for the straightening and stretching of collagen fibrils, and an orientation density function captures the spatial organization of collagen fibers in the tissue. Mechanical and structural assumptions at the collagen fibril level define a piece-wise analytical stress-stretch response of collagen fibers, which in turn is integrated over the unit sphere to constitute the tissue's macroscopic mechanical properties. The proposed model displays the salient macroscopic features of vascular tissue, and employs the material and structural parameters of clear physical meaning. Likewise, the constitutive concept renders a highly efficient multi-scale structural approach that allows for the numerical analysis at the organ level. Model parameters were estimated from isotropic mean-population data of the normal and aneurysmatic aortic wall and used to predict in-vivo stress states of patient-specific vascular geometries, thought to demonstrate the robustness of the particular Finite Element (FE) implementation. The collagen fibril level of the multi-scale constitutive formulation provided an interface to integrate vascular wall biology and to account for collagen turnover.

Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear–stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ 2 -method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau–Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

The elastic strain energy potential for nonlinear fibre-reinforced materials is customarily obtained by superposition of the potentials of the matrix and of each family of fibres. Composites with statistically oriented fibres, such as biological tissues, can be seen as being reinforced by a continuous infinity of fibre families, the orientation of which can be represented by means of a probability density function defined on the unit sphere (i.e. the solid angle). In this case, the superposition procedure gives rise to an integral form of the elastic potential such that the deformation features in the integral, which therefore cannot be calculated a priori . As a consequence, an analytical use of this potential is impossible. In this paper, we implemented this integral form of the elastic potential into a numerical procedure that evaluates the potential, the stress and the elasticity tensor at each deformation step. The numerical integration over the unit sphere is performed by means of the method of spherical designs, in which the result of the integral is approximated by a suitable sum over a discrete subset of the unit sphere. As an example of application, we modelled the collagen fibre distribution in articular cartilage, and used it in simulating displacement-controlled tests: the unconfined compression of a cylindrical sample and the contact problem in the hip joint.

The reliable assessment of Abdominal Aortic Aneurysm rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. Intra-luminal thrombus (ILT) has multiple biomechanical and biochemical impacts on the underlying aneurysm wall and thrombus failure might be linked to aneurysm rupture. Histological slices from 7 ILTs were analyzed using a sequence of automatic image processing and feature analyzing steps. Derived microstructural data was used to define Representative Volume Elements (RVE), which in turn allowed the estimation of microscopic material properties using the non-linear Finite Element Method. ILT tissue exhibited complex microstructural arrangement with larger pores in the abluminal layer than in the luminal layer. The microstructure was isotropic in the abluminal layer, whereas pores started to orient along the circumferential direction towards the luminal site. ILT's macroscopic (reversible) deformability was supported by large pores in the microstructure and the inhomogeneous structure explains in part the radially changing macroscopic constitutive properties of ILT. Its microscopic properties decreased just slightly from the luminal to the abluminal layer. The present study provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture. Data provided in this study allow an integration of structural information from medical imaging for example, to estimate ILT's macroscopic mechanical properties.

Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data. Fil: Comellas, Ester. Universidad Politécnica de Catalunya; España Fil: Gasser, T. Christian. KTH Royal Institute of Technology; Suecia Fil: Bellomo, Facundo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; Argentina Fil: Oller Martinez, Sergio Horacio. Universidad Politécnica de Catalunya; España

A methodology is proposed that identifies optimal stent devices for specific clinical criteria. It enables to predict the effect of stent designs on the mechanical environment of stenotic arteries. In particular, we present a numerical study which is based on the interaction of a vascular stent with a patient-specific, atherosclerotic human iliac lesion of type V. The stress evolution in four different tissue components during and after stenting is investigated. The geometric model of the artery is obtained through MRI, while anisotropic material models are applied to describe the behavior of tissues at finite strains. In order to model the observed fissuring and dissection of the plaque under dilation, the undeformed configuration of the arterial wall incorporates two initial tears. The 3D balloon-stent-artery interaction problem is modeled by means of a contact algorithm, which is based on a C(2)-continuous surface parametrization, hence avoiding numerical instabilities of standard facet-based techniques. In the simulations three different stent designs are studied. The performance of each stent is characterized by scalar quantities relating to stress changes in the artery, contact forces, and changes in lumen area after stenting. The study concludes by suggesting two optimal stent designs for two different clinically relevant parameters.

Balloon angioplasty intervention is traumatic to arterial tissue. Fracture mechanisms such as plaque fissuring and/or dissection occur and constitute major contributions to the lumen enlargement. However, these types of mechanically-based traumatization of arterial tissue are also contributing factors to both acute procedural complications and chronic restenosis of the treatment site. We propose physical and finite element models, which are generally useable to trace fissuring and/or dissection in atherosclerotic plaques during balloon angioplasty interventions. The arterial wall is described as an anisotropic, heterogeneous, highly deformable, nearly incompressible body, whereas tissue failure is captured by a strong discontinuity kinematics and a novel cohesive zone model. The numerical implementation is based on the partition of unity finite element method and the interface element method. The later is used to link together meshes of the different tissue components. The balloon angioplasty-based failure mechanisms are numerically studied in 3D by means of an atherosclerotic-prone human external iliac artery, with a type V lesion. Image-based 3D geometry is generated and tissue-specific material properties are considered. Numerical results show that in a primary phase the plaque fissures at both shoulders of the fibrous cap and stops at the lamina elastica interna. In a secondary phase, local dissections between the intima and the media develop at the fibrous cap location with the smallest thickness. The predicted results indicate that plaque fissuring and dissection cause localized mechanical trauma, but prevent the main portion of the stenosis from high stress, and hence from continuous tissue damage.

The paper deals with the modeling of balloon angioplasty by considering the balloon-induced overstretch of remnant non-diseased tissues in atherosclerotic arteries. A stenotic artery is modeled as a heterogenous structure composed of adventitia, media and a model plaque, and residual stresses are considered. The constitutive models are able to capture the anisotropic elastic tissue response in addition to the inelastic phenomena associated with tissue stretches beyond the physiological domain. The inelastic model describes the experimentally-observed changes of the wall during balloon inflation, i.e. non-recoverable deformation, and tissue weakening. The contact of the artery with a balloon catheter is simulated by a point-to-surface strategy. The states of deformations and stresses within the artery before, during and after balloon inflation are computed, compared and discussed. The 3D stress states at physiological loading conditions before and after balloon inflation differ significantly, and even compressive normal stresses may occur in the media after dilation.

Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon characterizing blood flow in the small vessels (micrometre to millimetre size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (millimetre to centimetre size), the extent of this migration and its interaction with secondary flows has not been fully elucidated. RBC migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface, which could influence vessel wall disease processes in and adjacent to the intima. Phillips' shear-induced particle migration model, coupled to the Quemada viscosity model, was employed to simulate the macroscopic behaviour of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and on the lateral-external side of the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, along the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall haematocrit are correlated with the near-wall shear layer and with the secondary flows induced by the vessel curvature. In particular, secondary flows accentuate the initial lowering in RBC near-wall concentration by convecting RBCs from the inner curvature side to the outer curvature side. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus induced by the presence of secondary flows. The lowering of wall haematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial pressure, to local hypoxia.

AAA disease is a serious condition and a multidisciplinary approach including biomechanics is needed to better understand and more effectively treat this disease. A rupture risk assessment is central to the management of AAA patients, and biomechanical simulation is a powerful tool to assist clinical decisions. Central to such a simulation approach is a need for robust and physiologically relevant models. Vascular tissue senses and responds actively to changes in its mechanical environment, a crucial tissue property that might also improve the biomechanical AAA rupture risk assessment. Specifically, constitutive modeling should not only focus on the (passive) interaction of structural components within the vascular wall, but also how cells dynamically maintain such a structure. In this article, after specifying the objectives of an AAA rupture risk assessment, the histology and mechanical properties of AAA tissue, with emphasis on the wall, are reviewed. Then a histomechanical constitutive description of the AAA wall is introduced that specifically accounts for collagen turnover. A test case simulation clearly emphasizes the need for constitutive descriptions that remodels with respect to the mechanical loading state. Finally, remarks regarding modeling of realistic clinical problems and possible future trends conclude the article. QC 20131127

A better understanding of the inherent properties of vascular tissue to adapt to its mechanical environment is crucial to improve the predictability of biomechanical simulations. Fibrillar collagen in the vascular wall plays a central role in tissue adaptation owing to its relatively short lifetime. Pathological alterations of collagen turnover may fail to result in homeostasis and could be responsible for abdominal aortic aneurysm (AAA) growth at later stages of the disease. For this reason our previously reported multiscale constitutive framework (Martufi, G. & Gasser, T. C. 2011 J. Biomech . 44 , 2544–2550 ( doi:10.1016/j.jbiomech.2011.07.015 )) has been enriched by a collagen turnover model. Specifically, the framework's collagen fibril level allowed a sound integration of vascular wall biology, and the impact of collagen turnover on the macroscopic properties of AAAs was studied. To this end, model parameters were taken from the literature and/or estimated from clinical follow-up data of AAAs (on average 50.7 mm-large). Likewise, the in vivo stretch of the AAA wall was set, such that 10 per cent of collagen fibres were engaged. Results showed that the stretch spectrum, at which collagen fibrils are deposed, is the most influential parameter, i.e. it determines whether the vascular geometry grows, shrinks or remains stable over time. Most importantly, collagen turnover also had a remarkable impact on the macroscopic stress field. It avoided high stress gradients across the vessel wall, thus predicted a physiologically reasonable stress field. Although the constitutive model could be successfully calibrated to match the growth of small AAAs, a rigorous validation against experimental data is crucial to further explore the model's descriptive and predictive capabilities.

Background The predictions of stress fields in Abdominal Aortic Aneurysm (AAA) depend on constitutive descriptions of the aneurysm wall and the Intra-luminal Thrombus (ILT). ILT is a porous diluted structure (biphasic solid–fluid material) and its impact on AAA biomechanics is controversially discussed in the literature. Specifically, pressure measurements showed that the ILT cannot protect the wall from the arterial pressure, while other (numerical and experimental) studies showed that at the same time it reduces the stress in the wall. Method To explore this phenomenon further a poroelastic description of the ILT was integrated in Finite Element (FE) Models of the AAA. The AAA model was loaded by a pressure step and a cyclic pressure wave and their transition into wall tension was investigated. To this end ILT’s permeability was varied within a microstructurally motivated range. Results The two-phase model verified that the ILT transmits the entire mean arterial pressure to the wall while, at the same time, it significantly reduces the stress in the wall. The predicted mean stress in the AAA wall was insensitive to the permeability of the ILT and coincided with the results of AAA models using a single-phase ILT description. Conclusion At steady state, the biphasic ILT behaves like a single-phase material in an AAA model. Consequently, computational efficient FE single-phase models, as they have been exclusively used in the past, accurately predict the wall stress in AAA models.

Biomechanical studies on abdominal aortic aneurysms (AAA) seek to provide for better decision criteria to undergo surgical intervention for AAA repair. More accurate results can be obtained by using appropriate material models for the tissues along with accurate geometric models and more realistic boundary conditions for the lesion. However, patient-specific AAA models are generated from gated medical images in which the artery is under pressure. Therefore, identification of the AAA zero pressure geometry would allow for a more realistic estimate of the aneurysmal wall mechanics. This study proposes a novel iterative algorithm to find the zero pressure geometry of patient-specific AAA models. The methodology allows considering the anisotropic hyperelastic behavior of the aortic wall, its thickness and accounts for the presence of the intraluminal thrombus. Results on 12 patient-specific AAA geometric models indicate that the procedure is computational tractable and efficient, and preserves the global volume of the model. In addition, a comparison of the peak wall stress computed with the zero pressure and CT-based geometries during systole indicates that computations using CT-based geometric models underestimate the peak wall stress by 59 ± 64 and 47 ± 64 kPa for the isotropic and anisotropic material models of the arterial wall, respectively.

We made an error in the numerical example simulating the unconfined compression of a cylindrical cartilage sample, given in §5.2. In articular cartilage, the collagen fibres are close to lying on the transverse plane in the superficial zone and close to aligned with the axial direction in the deep zone. These two opposite situations correspond to model (A) and model (B), respectively, as described in §3.4 and figure 1. In both cases, the limit for the concentration parameter b approaching zero yields isotropy, which is attained in the middle zone. In our example, we imposed b to vary linearly with the coordinate running from the bone – cartilage interface to the articular surface: from 5 to 0 (model (B)) in the deep zone, and from 0 to 5 (model (A)) in the superficial zone. Also, in order to reproduce the experiment of Park et al. [1], we ‘cut’ a 0.5 mm layer of the deep zone, so that the concentration parameter b was varying from 2.85 to 0 in the deep zone. Because of an error in a sign in our code, the fibre distribution in the cylindrical sample of §5.2 is upside-down, i.e. model (A) was used in place of model (B), and vice versa. As a result of this error, things went such that a 0.5 mm layer of superficial (rather than deep) zone was ‘cut’. This implies that the contour plot shown in figure 4 is only roughly but not exactly upside-down, and the force response in figure 3 is not accurate because the zonal subdivision (deep-middle-superficial) is not as desired. Furthermore, the comparison of the radial displacement of the lateral boundary in figure 4 with the experiments of Fortin et al. [2] was not appropriate, as the radial displacements in their tests were relative to a cartilage sample attached to a layer of subchondral bone, which constrains radial displacement at the bone – cartilage interface. While these errors do not affect the validity of the model nor the robustness of the numerical implementation, we felt it was important to correct them.

Collagen is a structural protein responsible for the mechanical strength, stiffness and toughness of biological tissues like skin, tendon, bone, cornea, lung and vasculature. In the present study we considered the enlargement of the aneurysm as a consequence of a pathological degradation and synthesis of collagen, i.e. malfunction of collagen turn-over. Consequently, the vascular wall is modeled by an (inert) matrix material representing the elastin, which is reinforced by a dynamic structure of bundles of collagen. Specifically, collagen is formed by a continuous stress-mediated process: deposited in the current configuration and removed by a constant degradation rate. Finally the micro-plane concept is used for the Finite Element implementation of the constitutive law. The model proposed within this study has a strong biological motivation and is able to capture both non-linear mechanics of aortic tissue and saline feature of AAA growth. Besides that, the micro-plane approach allows a straight forward FE implementation and preliminary results indicate its numerical robustness.Copyright © 2011 by ASME

A Pacemaker electrode can penetrate the heart wall, and to design a penetration-resistent lead tip sound knowledge regarding failure of ventricular tissue is required. Numerical simulations can be particular helpful in that respect, but depend on a reliable constitutive description for ventricular tissue. In this study an anisotropic hyperelastic model for the myocardium has been implemented and compared to predictions from an isotropic description. Specifically, the response due to pushing a rigid punch into the myocardium was studied. Results between anisotropic and isotropic descriptions of the myocardium differed significantly, which justified the implementation of an anisotropic model for the myocardium.Copyright © 2011 by ASME

Understanding the failure and damage mechanisms of soft biological tissue is critical to a sensitive and specific characterization of tissue injury tolerance and its relation to biological responses. Despite increasing experimental and analytical efforts, failure-related irreversible effects of soft biological tissue are still poorly understood. There is still no clear definition of what "damage" of a soft biological material is, and conventional macroscopic indicators, as known from damage of engineering materials for example, may not identify the tissue's tolerance to injury appropriately. To account for the complex three-dimensional arrangement of collagen, a microfiber model approach is applied, where constitutive relations for collagen fibers are integrated over the unit sphere, which in turn defines the tissue's macroscopic properties. A collagen fiber is represented by a bundle of proteoglycan cross-linked collagen fibrils that undergoes irreversible deformations when exceeding its elastic tensile limit. The proposed constitutive model is able to predict strain stiffening at physiological strain levels and does not exhibit a clear macroscopic elastic limit, two typical features known from soft biological tissue testing. An elastic-predictor/plastic-corrector implementation of the model is followed and constitutive parameters are estimated from in vitro test data from a particular abdominal aortic aneurysm (AAA). Damage-based structural instabilities of the AAA under different inflation conditions are investigated, where the collagen orientation density has been estimated from its in vivo stress state.

Lead perforation is a rare but serious clinical complication of pacemaker implantation, and towards understanding this malfunction, the present study investigated myocardial failure due to deep penetration by an advancing rigid punch. To this end, a non-linear Finite Element model was developed that integrates constitutive data published in the literature with information from in vitro tensile testing in cross-fibre direction of porcine myocardial tissue. The Finite Element model considered non-linear, isotropic and visco-elastic properties of the myocardium, and tissue failure was phenomenologically described by a Traction Separation Law. In vitro penetration testing of porcine myocardium was used to validate the Finite Element model, and a particular objective of the study was to investigate the impact of different constitutive parameters on the simulated results. Specifically, results demonstrated that visco-elastic properties of the tissue strongly determine the failure process, whereas dissipative effects directly related to failure had a minor impact on the simulation results. In addition, non-linearity of the bulk material did not change the predicted peak penetration force and the simulations did not reveal elastic crack-tip blunting. The performed study provided novel insights into ventricular failure due to deep penetration, and provided useful information with which to develop numerical failure models.

Lead perforation is a rare but serious complication of pacemaker implantations, and in the present study the associated tissue failure was investigated by means of in-vitro penetration of porcine and bovine ventricular tissue. Rectangular patches from the right ventricular free wall and the interventricular septum were separated, bi-axially stretched and immersed in physiological salt solution at 37 ∘ C before load displacement curves of in total 891 penetrations were recorded. To this end flat-bottomed cylindrical punches of different diameters were used, and following mechanical testing the penetration sites were histological analyzed using light and electron microscopes. Penetration pressure, i.e. penetration force divided by punch cross-sectional area decreased slightly from 2.27(SD 0.66) to 1.76 ( SD 0.46 ) N / mm 2 for punches of 1.32 to 2.30 mm in diameter, respectively. Deep penetration formed cleavages aligned with the local fiber orientation of the tissue, and hence, a mode-I crack developed, where the crack faces were wedged open by the advancing punch. The performed study derived novel failure data from ventricular tissue due to deep penetration and uncovered associated failure mechanisms. This provides information to derive mechanical failure models, which are essential to enrich our current understanding of failure of soft biological tissues and to guide medical device development.

Aortic dissection occurs frequently and is clinically challenging; the underlying mechanics remain unclear. The present study investigates the dissection properties of the media of 15 human abdominal aortas (AAs) by means of direct tension tests (n=8) and peeling tests (n=12). The direct tension test demonstrates the strength of the media in the radial direction, while the peeling test allows a steady-state investigation of the dissection propagation. To explore the development of irreversible microscopic changes during medial dissection, histological images (n=8) from four AAs at different peeling stages are prepared and analyzed. Direct tension tests of coin-shaped medial specimens result in a radial failure stress of 140.1+/-15.9 kPa (mean+/-SD, n=8). Peeling tests of rectangular-shaped medial strips along the circumferential and axial directions provide peeling force/width ratios of 22.9+/-2.9 mN/mm (n=5) and 34.8+/-15.5 mN/mm (n=7); the related dissection energies per reference area are 5.1+/-0.6 mJ/cm(2) and 7.6+/-2.7 mJ/cm(2), respectively. Although student's t-tests indicate that force/width values of both experimental tests are not significantly different (alpha=0.05, p=0.125), the strikingly higher resisting force/width obtained for the axial peeling tests is perhaps indicative of anisotropic dissection properties of the human aortic media. Peeling in the axial direction of the aorta generates a remarkably "rougher" dissection surface with respect to the surface generated by peeling in the circumferential direction. Histological analysis of the stressed specimens reveals that tissue damage spreads over approximately six to seven elastic laminae, which is about 15-18% of the thickness of the abdominal aortic media, which forms a pronounced cohesive zone at the dissection front.

A rupture risk assessment is critical to the clinical treatment of abdominal aortic aneurysm (AAA) patients. The biomechanical AAA rupture risk assessment quantitatively integrates many known AAA rupture risk factors but the variability of risk predictions due to model input uncertainties remains a challenging limitation. This study derives a probabilistic rupture risk index (PRRI). Specifically, the uncertainties in AAA wall thickness and wall strength were considered, and wall stress was predicted with a state-of-the-art deterministic biomechanical model. The discriminative power of PRRI was tested in a diameter-matched cohort of ruptured ( n = 7) and intact ( n = 7) AAAs and compared to alternative risk assessment methods. Computed PRRI at 1.5 mean arterial pressure was significantly ( p = 0.041) higher in ruptured AAAs (20.21(s.d. 14.15%)) than in intact AAAs (3.71(s.d. 5.77)%). PRRI showed a high sensitivity and specificity (discriminative power of 0.837) to discriminate between ruptured and intact AAA cases. The underlying statistical representation of stochastic data of wall thickness, wall strength and peak wall stress had only negligible effects on PRRI computations. Uncertainties in AAA wall stress predictions, the wide range of reported wall strength and the stochastic nature of failure motivate a probabilistic rupture risk assessment. Advanced AAA biomechanical modelling paired with a probabilistic rupture index definition as known from engineering risk assessment seems to be superior to a purely deterministic approach.

Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau-Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.

Collagen is the most abundant protein in mammals and provides the abdominal aortic aneurysm (AAA) wall with mechanical strength, stiffness and toughness. Specifically, the spatial orientation of collagen fibers in the wall has a major impact on its mechanical properties. Apart from valuable microhistological information, this data can be integrated by histomechanical constitutive models thought to improve biomechanical simulations, i.e. to improve the biomechanical rupture risk assessment of AAAs. Tissue samples (n = 24) from the AAA wall were harvested during elective AAA repair, fixated, embedded, sectioned and investigated by polarized light microscopy. The birefringent properties of collagen were reinforced by picrosirius red staining and the three-dimensional collagen fiber orientations were identified with a universal rotary stage. Two constitutive models for collagen fibers were used to integrate the identified structural information in a macroscopic AAA wall model. The collagen fiber orientation in the AAA wall was widely dispersed and could be captured by a Bingham distribution function (κ1=11.6,κ2=9.7)(κ1=11.6,κ2=9.7). The dispersion was much larger in the tangential plane than in the cross-sectional plane, and no significant difference between the medial and adventitial layers could be identified. The layered directional organization of collagen in normal aortas was not evident in the AAA. The collagen organization identified, combined with constitutive descriptions of collagen fibers that depend on its orientation, explain the anisotropic (orthotropic) mechanical properties of the AAA wall. The mechanical properties of collagen fibers depend largely on their undulation, which is an important structural parameter that requires further experimental investigation.