Inflation of an artery leading to aneurysm formation and rupture

Formation and rupture of aneurysms due to the inflation of an artery with collagen fibers distributed in two preferred directions, subjected to internal pressure and axial stretch are examined within the framework of nonlinear elasticity. A two layer tube model with a fiber-reinforced composite based incompressible anisotropic hyperelastic constitutive material is employed to model the stress-strain behavior of the artery wall with distributed collagen fibers. The artery wall takes up a uniform inflation deformation, and there are no aneurysms in the artery under the normal condition. But an aneurysm may be formed in arteries when the stiffness of the fibers is decreased to a certain value or the direction of the fibers is changed to a certain degree towards the circumferential direction. The aneurysm may expand to much large extent and become complex in shape. One portion of the aneurysm becomes highly distended as a bubble while the rest remains lightly inflated. The rupture of the aneurysm is discussed along with the distribution of stresses. Critical pressures and the rupture pressures are given for different collagen fiber orientations or stiffness. Furthermore, the stability of the solutions is discussed to explain the formation of aneurysm.     

Haemodynamics and wall remodelling of a growing cerebral aneurysm: a computational model

We have developed a computational simulation model for investigating an often postulated hypothesis connected with aneurysm growth. This hypothesis involves a combination of two parallel and interconnected mechanisms: according to the first mechanism, an endothelium-originating and wall shear stress-driven apoptotic behavior of smooth muscle cells, leading to loss of vascular tone is believed to be important to the aneurysm behavior. Vascular tone refers to the degree of constriction experienced by a blood vessel relative to its maximally dilated state. All resistance and capacitance vessels under basal conditions exhibit some degree of smooth muscle contraction that determines the diameter, and hence tone, of the vessel. The second mechanism is connected to the arterial wall remodeling. Remodeling of the arterial wall under constant tension is a biomechanical process of rupture, degradation and reconstruction of the medial elastin and collagen fibers. In order to investigate these two mechanisms within a computationally tractable framework, we devise mechanical analogues that involve three-dimensional haemodynamics, yielding estimates of the wall shear stress and pressure fields and a quasi-steady approach for the apoptosis and remodeling of the wall. These analogues are guided by experimental information for the connection of stimuli to responses at a cellular level, properly averaged over volumes or surfaces. The model predicts aneurysm growth and can attribute specific roles to the two mechanisms involved: the smooth muscle cell-related loss of tone is important to the initiation of aneurysm growth, but cannot account alone for the formation of fully grown sacks; the fiber-related remodeling is pivotal for the latter.     

An inelastic multi-mechanism constitutive equation for cerebral arterial tissue

Intracranial aneurysms (ICA) are abnormal saccular dilations of cerebral arteries, commonly found at apices of arterial bifurcations and outer walls of curved arterial segments. Histological evidence suggests the stages in ICA development include the deformation of a segment of arterial wall into a “bleb” with no identifiable neck region followed by the development of an aneurysm with a clear neck. Afterwards, the aneurysm may undergo further enlargement, possibly with significant biological response including calcification and thrombosis. Past studies of the biomechanics of cerebral aneurysm tissue have been directed at modeling elastic deformations of pre-existing aneurysms. Taking this approach, the aneurysm wall is treated as a different entity than the arterial tissue from which it developed. In the current work, a nonlinear, inelastic, dual-mechanism constitutive equation for cerebral arterial tissue is developed. It is the first to model the recruitment of collagen fibers and degradation of the internal elastic lamina, two important characteristics of early stage aneurysm formation.     

Evaluating patient-specific abdominal aortic aneurysm wall stress based on flow-induced loading

In this paper, we develop a physiologic wall stress analysis procedure by incorporating experimentally measured, non-uniform pressure loading in a patient-based finite element simulation. First, the distribution of wall pressure is measured in a patient-based lumen cast at a series of physiologically relevant steady flow rates. Then, using published equi-biaxial stress-deformation data from aneurysmal tissue samples, a nonlinear hyperelastic constitutive equation is used to describe the mechanical behavior of the aneurysm wall. The model accounts of the characteristic exponential stiffening due to the rapid engagement of nearly inextensible collagen fibers and assumes, as a first approximation, an isotropic behavior of the arterial wall. The results show a complex wall stress distribution with a localized maximum principal stress value of 660 kPa on the inner surface of the posterior surface of the aneurysm bulge, a considerably larger value than has generally been reported in calculations of wall stress under the assumption of uniform loading. This is potentially significant since the posterior wall has been suggested as a common site of rupture, and the aneurysmal tensile strength reported by other authors is of the same order of magnitude as the maximum stress value found here.     

Do cardiac aneurysms blow out?

The possibility is suggested that cardiac aneurysms are formed when an infarcted region of the ventricular wall becomes elastically unstable and "blows out". The consequence of such a blowout could be a large saccular aneurysm or even cardiac rupture. We use a nonlinear stress-strain relation capable of describing both the passive and active myocardial wall to examine this possibility in terms of large-deformation membrane theory. Ventricular infarcts made of a material having physical properties like rubber would be expected to blow out, but those made of passive myocardium would not.     

Modeling rupture of growing aneurysms

Growth and rupture of aneurysms are driven by micro-structural alterations of the arterial wall yet precise mechanisms underlying the process remain to be uncovered. In the present work we examine a scenario when the aneurysm evolution is dominated by turnover of collagen fibers. In the latter case it is natural to hypothesize that rupture of individual fibers (or their bonds) causes the overall aneurysm rupture. We examine this hypothesis in computer simulations of growing aneurysms in which constitutive equations describe both collagen evolution and failure. Failure is enforced in constitutive equations by limiting strain energy that can be accumulated in a fiber. Within the proposed theoretical framework we find a range of parameters that lead to the aneurysm rupture. We conclude in a qualitative agreement with clinical observations that some aneurysms will rupture while others will not.     

A computational model for understanding the micro-mechanics of collagen fiber network in the tunica adventitia

Abdominal aortic aneurysm is a prevalent cardiovascular disease with high mortality rates. The mechanical response of the arterial wall relies on the organizational and structural behavior of its microstructural components, and thus, a detailed understanding of the microscopic mechanical response of the arterial wall layers at loads ranging up to rupture is necessary to improve diagnostic techniques and possibly treatments. Following the common notion that adventitia is the ultimate barrier at loads close to rupture, in the present study, a finite element model of adventitial collagen network was developed to study the mechanical state at the fiber level under uniaxial loading. Image stacks of the rabbit carotid adventitial tissue at rest and under uniaxial tension obtained using multi-photon microscopy were used in this study, as well as the force–displacement curves obtained from previously published experiments. Morphological parameters like fiber orientation distribution, waviness, and volume fraction were extracted for one sample from the confocal image stacks. An inverse random sampling approach combined with a random walk algorithm was employed to reconstruct the collagen network for numerical simulation. The model was then verified using experimental stress–stretch curves. The model shows the remarkable capacity of collagen fibers to uncrimp and reorient in the loading direction. These results further show that at high stretches, collagen network behaves in a highly non-affine manner, which was quantified for each sample. A comprehensive parameter study to understand the relationship between structural parameters and their influence on mechanical behavior is presented. Through this study, the model was used to conclude important structure–function relationships that control the mechanical response. Our results also show that at loads close to rupture, the probability of failure occurring at the fiber level is up to 2%. Uncertainties in usually employed rupture risk indicators and the stochastic nature of the event of rupture combined with limited knowledge on the microscopic determinants motivate the development of such an analysis. Moreover, this study will advance the study of coupling microscopic mechanisms to rupture of the artery as a whole.

     

Fluid-structure interaction in abdominal aortic aneurysms: effects of asymmetry and wall thickness

Background  

Abdominal aortic aneurysm (AAA) is a prevalent disease which is of significant concern because of the morbidity associated with the continuing expansion of the abdominal aorta and its ultimate rupture. The transient interaction between blood flow and the wall contributes to wall stress which, if it exceeds the failure strength of the dilated arterial wall, will lead to aneurysm rupture. Utilizing a computational approach, the biomechanical environment of virtual AAAs can be evaluated to study the affects of asymmetry and wall thickness on this stress, two parameters that contribute to increased risk of aneurysm rupture.     

Fluid-structure interaction effects on sac-blood pressure and wall stress in a stented aneurysm

An aneurysm is a local artery ballooning greater than 50% of its nominal diameter with a risk of sudden rupture. Minimally invasive repair can be achieved by inserting surgically a stent-graft, called an endovascular graft (EVG), which is either straight tubular curved tubular or bifurcating. However post-procedural complications may arise because of elevated stagnant blood pressure in the cavity, i.e., the sac formed by the EVG and the weakened aneurysm wall In order to investigate the underlying mechanisms leading to elevated sac-pressures and hence to potentially dangerous wall stress levels and aneurysm rupture, a transient 3-D stented abdominal aortic aneurysm model and a coupled fluid-structure interaction solver were employed. Simulation results indicate that, even without the presence of endoleaks (blood flowing into the cavity), elevated sac pressure can occur due to complex fluid-structure interactions between the luminal blood flow, EVG wall, intra-sac stagnant blood, including an intra-luminal thrombus, and the aneurysm wall. Nevertheless, the impact of sac-blood volume changes due to leakage on the sac pressure and aneurysm wall stress was analyzed as well. While blood flow conditions, EVG and aneurysm geometries as well as wall mechanical properties play important roles in both sac pressure and wall stress generation, it is always the maximum wall stress that is one of the most critical parameters in aneurysm rupture prediction. All simulation results are in agreement with experimental data and clinical observations.     

Improving the Efficiency of Abdominal Aortic Aneurysm Wall Stress Computations

An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses.     

Blood flow dynamics in saccular aneurysm models of the basilar artery

Blood flow dynamics under physiologically realistic pulsatile conditions plays an important role in the growth, rupture, and surgical treatment of intracranial aneurysms. The temporal and spatial variations of wall pressure and wall shear stress in the aneurysm are hypothesized to be correlated with its continuous expansion and eventual rupture. In addition, the assessment of the velocity field in the aneurysm dome and neck is important for the correct placement of endovascular coils. This paper describes the flow dynamics in two representative models of a terminal aneurysm of the basilar artery under Newtonian and non-Newtonian fluid assumptions, and compares their hemodynamics with that of a healthy basilar artery. Virtual aneurysm models are investigated numerically, with geometric features defined by beta = 0 deg and beta = 23.2 deg, where beta is the tilt angle of the aneurysm dome with respect to the basilar artery. The intra-aneurysmal pulsatile flow shows complex ring vortex structures for beta = 0 deg and single recirculation regions for beta = 23.2 deg during both systole and diastole. The pressure and shear stress on the aneurysm wall exhibit large temporal and spatial variations for both models. When compared to a non-Newtonian fluid, the symmetric aneurysm model (beta = 0 deg) exhibits a more unstable Newtonian flow dynamics, although with a lower peak wall shear stress than the asymmetric model (beta = 23.2 deg). The non-Newtonian fluid assumption yields more stable flows than a Newtonian fluid, for the same inlet flow rate. Both fluid modeling assumptions, however, lead to asymmetric oscillatory flows inside the aneurysm dome.     

Elastic and collagenous networks in vascular diseases

Supravalvular aortic stenosis (SVAS), Marfan syndrome (MFS) and Ehlers-Danlos syndrome type IV (EDS IV) are three clinical entities characterized by vascular abnormalities that result from mutations of structural components of the extracellular matrix (ECM). Analyses of naturally occurring human mutations and of artificially generated deficiencies in the mouse have provided insights into the pathogenesis of these heritable disorders of the connective tissue. SVAS is associated with haploinsufficiency of elastin, one of the two major components of the elastic fibers. SVAS is characterized by narrowing of the arterial lumen due to the failure of regulation of cellular proliferation and matrix deposition. Mutations in fibrillin 1 are the cause of dissecting aneurysm leading to rupture of the ascending aorta. Fibrillin-1 is the building block of the microfibrils that span the entire thickness of the aortic wall and are a major component of the elastic fibers that reside in the medial layer. The vascular hallmark of EDS IV is rupture of large vessels. The phenotype is caused by mutations in type III collagen. The mutations ultimately affect the overall architecture of the collagenous network and the biomechanical properties of the adventitial layer of the vessel wall. Altogether, these genotype-phenotype correlations document the diversified contributions of distinct extracellular macroaggregates to the assembly and function of the vascular matrix.     

Mechanical stresses in abdominal aortic aneurysms: influence of diameter, asymmetry, and material anisotropy

Biomechanical studies suggest that one determinant of abdominal aortic aneurysm (AAA) rupture is related to the stress in the wall. In this regard, a reliable and accurate stress analysis of an in vivo AAA requires a suitable 3D constitutive model. To date, stress analysis conducted on AAA is mainly driven by isotropic tissue models. However, recent biaxial tensile tests performed on AAA tissue samples demonstrate the anisotropic nature of this tissue. The purpose of this work is to study the influence of geometry and material anisotropy on the magnitude and distribution of the peak wall stress in AAAs. Three-dimensional computer models of symmetric and asymmetric AAAs were generated in which the maximum diameter and length of the aneurysm were individually controlled. A five parameter exponential type structural strain-energy function was used to model the anisotropic behavior of the AAA tissue. The anisotropy is determined by the orientation of the collagen fibers (one parameter of the model). The results suggest that shorter aneurysms are more critical when asymmetries are present. They show a strong influence of the material anisotropy on the magnitude and distribution of the peak stress. Results confirm that the relative aneurysm length and the degree of aneurysmal asymmetry should be considered in a rupture risk decision criterion for AAAs.     

Mechanical instability of normal and aneurysmal arteries

Tortuous arteries associated with aneurysms have been observed in aged patients with atherosclerosis and hypertension. However, the underlying mechanism is poorly understood. The objective of this study was to determine the effect of aneurysms on arterial buckling instability and the effect of buckling on aneurysm wall stress. We investigated the mechanical buckling and post-buckling behavior of normal and aneurysmal carotid arteries and aorta’s using computational simulations and experimental measurements to elucidate the interrelationship between artery buckling and aneurysms. Buckling tests were done in porcine carotid arteries with small aneurysms created using elastase treatment. Parametric studies were done for model aneurysms with orthotropic nonlinear elastic walls using finite element simulations. Our results demonstrated that arteries buckled at a critical buckling pressure and the post-buckling deflection increased nonlinearly with increasing pressure. The presence of an aneurysm can reduce the critical buckling pressure of arteries, although the effect depends on the aneurysm’s dimensions. Buckled aneurysms demonstrated a higher peak wall stress compared to unbuckled aneurysms under the same lumen pressure. We conclude that aneurysmal arteries are vulnerable to mechanical buckling and mechanical buckling could lead to high stresses in the aneurysm wall. Buckling could be a possible mechanism for the development of tortuous aneurysmal arteries such as in the Loeys–Dietz syndrome.     

Wall stress and flow dynamics in abdominal aortic aneurysms: finite element analysis vs. fluid–structure interaction

Abdominal aortic aneurysm (AAA) rupture is the clinical manifestation of an induced force exceeding the resistance provided by the strength of the arterial wall. This force is most frequently assumed to be the product of a uniform luminal pressure acting along the diseased wall. However fluid dynamics is a known contributor to the pathogenesis of AAAs, and the dynamic interaction of blood flow and the arterial wall represents the in vivo environment at the macro-scale. The primary objective of this investigation is to assess the significance of assuming an arbitrary estimated peak fluid pressure inside the aneurysm sac for the evaluation of AAA wall mechanics, as compared with the non-uniform pressure resulting from a coupled fluid–structure interaction (FSI) analysis. In addition, a finite element approach is utilised to estimate the effects of asymmetry and wall thickness on the wall stress and fluid dynamics of ten idealised AAA models and one non-aneurysmal control. Five degrees of asymmetry with uniform and variable wall thickness are used. Each was modelled under a static pressure-deformation analysis, as well as a transient FSI. The results show that the inclusion of fluid flow yields a maximum AAA wall stress up to 20% higher compared to that obtained with a static wall stress analysis with an assumed peak luminal pressure of 117 mmHg. The variable wall models have a maximum wall stress nearly four times that of a uniform wall thickness, and also increasing with asymmetry in both instances. The inclusion of an axial stretch and external pressure to the computational domain decreases the wall stress by 17%.     

Wall stress and flow dynamics in abdominal aortic aneurysms: finite element analysis vs. fluid-structure interaction

Abdominal aortic aneurysm (AAA) rupture is the clinical manifestation of an induced force exceeding the resistance provided by the strength of the arterial wall. This force is most frequently assumed to be the product of a uniform luminal pressure acting along the diseased wall. However fluid dynamics is a known contributor to the pathogenesis of AAAs, and the dynamic interaction of blood flow and the arterial wall represents the in vivo environment at the macro-scale. The primary objective of this investigation is to assess the significance of assuming an arbitrary estimated peak fluid pressure inside the aneurysm sac for the evaluation of AAA wall mechanics, as compared with the non-uniform pressure resulting from a coupled fluid-structure interaction (FSI) analysis. In addition, a finite element approach is utilised to estimate the effects of asymmetry and wall thickness on the wall stress and fluid dynamics of ten idealised AAA models and one non-aneurysmal control. Five degrees of asymmetry with uniform and variable wall thickness are used. Each was modelled under a static pressure-deformation analysis, as well as a transient FSI. The results show that the inclusion of fluid flow yields a maximum AAA wall stress up to 20% higher compared to that obtained with a static wall stress analysis with an assumed peak luminal pressure of 117 mmHg. The variable wall models have a maximum wall stress nearly four times that of a uniform wall thickness, and also increasing with asymmetry in both instances. The inclusion of an axial stretch and external pressure to the computational domain decreases the wall stress by 17%.     

A fluid–structure interaction-based numerical investigation on the evolution of stress,strength and rupture potential of an abdominal aortic aneurysm

An abdominal aortic aneurysm (AAA) is an irreversible dilation of the abdominal artery. Once an aneurysm is detected by doctors, clinical intervention is usually recommended. The interventions involve traditional open surgery repair and endovascular aneurysm repair with a stent graft. Both types of prophylactic procedures are expensive and not without any risk to the patient. It is very difficult to balance the risk of aneurysm repair and the chance of rupture. The reason lies in that the changing trend of characteristic physical quantities with the evolution of AAA and the mechanisms that give rise to it are still not completely clear. In this study, computational 3D patient-specific model for investigating AAA development was established based on computed tomography (CT) images. Results showed that as the aneurysm evolved, peak wall stress and time-averaged wall shear stress distribution patterns changed. The expansion of AAA wall resulted in the increment of peak stress. The AAA wall compliance not only showed different magnitudes at different cross-sections of the aneurismal body, but also changed with the development of the aneurysm. Furthermore, minimum wall strength and rupture potential index during the three stages of AAA evolution were also investigated in detail. This study might provide valuable information on how to further explore the mechanical basis and the rupture potential during AAA evolution, and that it may assist clinical diagnostic procedures and avoid the potential risk of unnecessary surgical intervention.     

Fluid-structure interaction modeling of aneurysmal arteries under steady-state and pulsatile blood flow: a stability analysis

Tortuous aneurysmal arteries are often associated with a higher risk of rupture but the mechanism remains unclear. The goal of this study was to analyze the buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow. To accomplish this goal, we analyzed the buckling behavior of model carotid and abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI) method with realistic waveforms boundary conditions. FSI simulations were done under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure and axial tension on stability. Our results indicated that aneurysmal artery buckled at the critical buckling pressure and its deflection nonlinearly increased with increasing lumen pressure. Buckling elevates the peak stress (up to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher than under static pressure at the peak lumen pressure of 130 mmHg. Buckling results show an increase in lumen shear stress at the inner side of the maximum deflection. Vortex flow was dramatically enlarged with increasing lumen pressure and artery diameter. Aneurysmal arteries are more susceptible than normal arteries to mechanical instability which causes high stresses in the aneurysm wall that could lead to aneurysm rupture.     

Role of elastin anisotropy in structural strain energy functions of arterial tissue

The vascular wall exhibits nonlinear anisotropic mechanical properties. The identification of a strain energy function (SEF) is the preferred method to describe its complex nonlinear elastic properties. Earlier constituent-based SEF models, where elastin is modeled as an isotropic material, failed in describing accurately the tissue response to inflation–extension loading. We hypothesized that these shortcomings are partly due to unaccounted anisotropic properties of elastin. We performed inflation–extension tests on common carotid of rabbits before and after enzymatic degradation of elastin and applied constituent-based SEFs, with both an isotropic and an anisotropic elastin part, on the experimental data. We used transmission electron microscopy (TEM) and serial block-face scanning electron microscopy (SBFSEM) to provide direct structural evidence of the assumed anisotropy. In intact arteries, the SEF including anisotropic elastin with one family of fibers in the circumferential direction fitted better the inflation–extension data than the isotropic SEF. This was supported by TEM and SBFSEM imaging, which showed interlamellar elastin fibers in the circumferential direction. In elastin-degraded arteries, both SEFs succeeded equally well in predicting anisotropic wall behavior. In elastase-treated arteries fitted with the anisotropic SEF for elastin, collagen engaged later than in intact arteries. We conclude that constituent-based models with an anisotropic elastin part characterize more accurately the mechanical properties of the arterial wall when compared to models with simply an isotropic elastin. Microstructural imaging based on electron microscopy techniques provided evidence for elastin anisotropy. Finally, the model suggests a later and less abrupt collagen engagement after elastase treatment.     

The association of wall mechanics and morphology: a case study of abdominal aortic aneurysm growth

The purpose of this study is to evaluate the potential correlation between peak wall stress (PWS) and abdominal aortic aneurysm (AAA) morphology and how it relates to aneurysm rupture potential. Using in-house segmentation and meshing software, six 3-dimensional (3D) AAA models from a single patient followed for 28 months were generated for finite element analysis. For the AAA wall, both isotropic and anisotropic materials were used, while an isotropic material was used for the intraluminal thrombus (ILT). These models were also used to calculate 36 geometric indices characteristic of the aneurysm morphology. Using least squares regression, seven significant geometric features (p?相似文献