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Evolution of mechanical and structural properties in the Ascending Thoracic Aorta (ATA) is the results of complex mechanobiological processes. In this work, we address some numerical challenges in order to elaborate computational models of these processes. For that, we extend the state of the art of homogenized constrained mixture (hCM) models. In these models, prestretches are assigned to the mixed constituents in order to ensure local mechanical equilibrium macroscopically, and to maintain a homeostatic level of tension in collagen fibers microscopically. Although the initial prestretches were assumed as homogeneous in idealized straight tubes, more elaborate prestretch distributions need to be considered for curved geometrical models such as patient-specific ATA. Therefore, we introduce prestretches having a three-dimensional gradient across the ATA geometry in the homeostatic reference state. We test different schemes with the objective to ensure stable growth and remodeling (G&R) simulations on patient-specific curved vessels. In these simulations, aneurysm progression is triggered by tissue changes in the constituents such as mass degradation of intramural elastin. The results show that the initial prestretches are not only critical for the stability of numerical simulations, but they also affect the G&R response. Eventually, we submit that initial conditions required for G&R simulations need to be identified regionally for ensuring realistic patient-specific predictions of aneurysm progression.

This paper presents a method to derive the virtual fields for identifying constitutive model parameters using the Virtual Fields Method (VFM). The VFM is an approach to identify unknown constitutive parameters using deformation fields measured across a given volume of interest. The general principle for solving identification problems with the VFM is first to derive parametric stress field, where the stress components at any point depend on the unknown constitutive parameters, across the volume of interest from the measured deformation fields. Applying the principle of virtual work to the parametric stress fields, one can write scalar equations of the unknown parameters and solve the obtained system of equations to deduce the values of unknown parameters. However, no rules have been proposed to select the virtual fields in identification problems related to nonlinear elasticity and there are multiple strategies possible that can yield different results. In this work, we propose a systematic, robust and automatic approach to reconstruct the systems of scalar equations with the VFM. This approach is well suited to finite-element implementation and can be applied to any problem provided that full-field deformation data are available across a volume of interest. We also successfully demonstrate the feasibility of the novel approach by multiple numerical examples. Potential applications of the proposed approach are numerous in biomedical engineering where imaging techniques are commonly used to observe soft tissues and where alterations of material properties are markers of diseased states.List of symbols

The identification of nonhomogeneous elastic property distributions has been traditionally achieved with well acknowledged optimization based inverse approaches, but when full-field displacement measurements are available, the virtual fields method (VFM) can be computationally more efficient by converting the large-scale optimization problem into multiple small-scale optimization problems. A possible downside of the VFM so far was not to take into account prior knowledge, which is often available and needed when there is a very large number of unknowns and the inverse problem is ill-posed. In this work, different approaches are proposed for introducing regularization into the VFM, aiming to penalize the local variations of identified stiffness properties in order to reduce the effects of uncertainty in the inverse problem resolution. The feasibility and accuracy of the regularized VFM are tested through several numerical and experimental datasets. It is shown that the main advantage of the novel VFM approaches is the low computational cost, as large-scale inverse problems with 10,000 unknown parameters can be solved within several seconds using a standard personal computer. Although the regularized VFM can successfully detect a stiff inclusion in a soft solid with high accuracy, regularization also introduces unexpected spurious effects in the results, blurring the interface between soft and stiff regions. We also observed that the regularization did not improve the smoothness significantly due to local effects of the small-scale optimization problem introduced in the proposed VFM method. Therefore, traditional regularization, which penalizes local variations of identified stiffness properties, can be combined with the VFM to solve inverse problems with a high computational efficiency, but supplemental regularization conditions will need to be adapted in the future to better delineate soft-stiff interfaces with this methodology.

Previous studies have shown that the rupture properties of an ascending thoracic aortic aneurysm (ATAA) are strongly correlated with the pre-rupture response features. In this work, we present a two-step machine learning method to predict where the rupture is likely to occur in ATAA and what safety reserve the structure may have. The study was carried out using ATAA specimens from 15 patients who underwent surgical intervention. Through inflation test, full-field deformation data and post-rupture images were collected, from which the wall tension and surface strain distributions were computed. The tension-strain data in the pressure range of 9-18 kPa were fitted to a third-order polynomial to characterize the response properties. It is hypothesized that the region where rupture is prone to initiate is associated with a high level of tension buildup. A machine learning method is devised to predict the peak risk region. The predicted regions were found to match the actual rupture sites in 13 samples out of the total 15. In the second step, another machine learning model is utilized to predict the tissue's rupture strength in the peak risk region. Results suggest that the ATAA rupture risk can be reasonably predicted using tension-strain response in the physiological range. This may open a pathway for evaluating the ATAA rupture propensity using information of in vivo response.

Smooth muscle cells (SMCs) usually express a contractile phenotype in the healthy aorta. However, aortic SMCs have the ability to undergo profound changes in phenotype in response to changes in their extracellular environment, as occurs in ascending thoracic aortic aneurysms (ATAA). Accordingly, there is a pressing need to quantify the mechanobiological effects of these changes at single cell level. To address this need, we applied Traction Force Microscopy (TFM) on 759 cells coming from three primary healthy (AoPrim) human SMC lineages and three primary aneurysmal (AnevPrim) human SMC lineages, from age and gender matched donors. We measured the basal traction forces applied by each of these cells onto compliant hydrogels of different stiffness (4, 8, 12, 25 kPa). Although the range of force generation by SMCs suggested some heterogeneity, we observed that: 1. the traction forces were significantly larger on substrates of larger stiffness; 2. traction forces in AnevPrim were significantly higher than in AoPrim cells. We modelled computationally the dynamic force generation process in SMCs using the motor-clutch model and found that it accounts well for the stiffness-dependent traction forces. The existence of larger traction forces in the AnevPrim SMCs were related to the larger size of cells in these lineages. We conclude that phenotype changes occurring in ATAA, which were previously known to reduce the expression of elongated and contractile SMCs (rendering SMCs less responsive to vasoactive agents), tend also to induce stronger SMCs. Future work aims at understanding the causes of this alteration process in aortic aneurysms. Supplementary information The online version of this article (10.1007/s10237-020-01412-6) contains supplementary material, which is available to authorized users.

Ascending Thoracic Aortic Aneurysm (ATAA) is a permanent dilatation of the aorta which is usually related to tissue degeneration, hemodynamic conditions, lifestyle, environmental and genetic factors. As the mechanical conditions can become critical in a dilated aorta, a patient-specific computational model can be very useful to assist clinical decisions in the management of ATAAs. In this article, we model the biomechanical conditions of ATAA by performing Fluid–Structure Interaction (FSI) simulations in the SimVascular open-source software package. The patient-specific geometric model is reconstructed from Computed Tomography scan (CT). The numerical implementation takes into account patient-specific outlet conditions and a temporal flow variation at the model inlet. We performed a mesh convergence analysis on a new mesh reconstruction method in SimVascular and showed that it can significantly reduce the computational cost without impacting the accuracy.

With the rising popularity of endovascular aortic repair (EVAR) for aortic aneurysms and dissections, there is a crucial need for investigating the delayed appearance of post-EVAR complications such as stent-graft kinking, fracture and migration respectively. These complications have been noted to be influenced by the radial stiffness and bending flexibility attributes of stent-grafts. Auxetic designs with negative Poisson's ratio offer interesting advantages such as enhanced fracture toughness, superior indentation resistance and adaptive stiffness in response to intricate morphology for stenting applications over conventional stent designs. The objective of this study is to propose different auxetic stent candidates and to compare their mechanical performance with two conventional stent candidates for endovascular applications using numerical simulation through crimp/crushing tests for their radial stiffness and three-point bending/kinking tests for their flexibility, respectively. The results demonstrate that the novel hybrid auxetic designs (CRE and CSTAR) possess the best trade-off between radial stiffness and bending flexibility characteristics among all candidates for stent-graft applications.

Aneurysm shrinkage is clinically observed after successful endovascular aortic aneurysm repair (EVAR). However, global understanding of post-operative aneurysm evolutions remains weak. In this work, we propose to study these effects using numerical simulation. We set up a 3D finite-element model of post-EVAR vascular adaptation within an open-source finite-element code, which was initially developed for growth and remodeling (G&R). We modeled the endograft with a set of uniaxial prestrained springs that apply radial forces on the inner surface of the artery. Constitutive equations, momentum balance equations, and equations related to the mechanobiology of the artery were formulated based on the homogenized constrained mixture theory. We performed a sensitivity analysis by varying different selected parameters, namely oversizing and compliance of the stent-graft, gain parameters related to collagen G&R, and the residual pressure in the aneurysm sac. This permitted us to evaluate how each factor influences post-EVAR vascular adaptation. It was found that oversizing, compliance or gain parameters have a limited influence compared to that of the residual pressure in the aneurysm sac, which was found to play a critical role in the stability of aneurysm after stent-graft implantation. An excessive residual pressure larger than 50 mmHg can induce a continuous expansion of the aneurysm while a moderate residual pressure below this critical threshold yields continuous shrinkage of the aneurysm. Moreover, it was found that elderly patients, with relatively lower amounts of remnant elastin in the arterial wall, are more sensitive to the effect of residual pressure. Therefore, these results show that elderly patients may present a higher potential risk of aortic sac expansion due to intra-aneurysm sac pressure after EVAR than younger patients.

Magnetic resonance imaging (MRI) is the preferred modality to assess hemodynamics in healthy and diseased blood vessels. As an affordable and non-invasive alternative, Color-Doppler imaging is a good candidate. Nevertheless, Color-Doppler acquisitions provide only partial information on the blood velocity within the vessel. We present a framework to reconstruct 2D velocity fields in the aorta. We generated 2D Color-Doppler-like images from patient-specific Computational Fluid Dynamics (CFD) models of abdominal aortas and evaluated the framework's performance. The 2D velocity field reconstruction is based on the minimization of a cost function, in which the reconstructed velocities are constrained to satisfy fluid dynamics principles. The numerical evaluations show that the reconstructed vector flow fields agree with ground-truth velocities, with an average magnitude error of less than 4% and an average angular error of less than 2

It was recently submitted that the rupture risk of an ascending thoracic aortic aneurysm (ATAA) is strongly correlated with the aortic stiffness. To validate this assumption, we propose a non-invasive inverse method to identify the patient-specific local extensional stiffness of aortic walls based on gated CT scans. Using these images, the local strain distribution is reconstructed throughout the cardiac cycle. Subsequently, obtained strains are related to tensions, through local equilibrium equations, to estimate the local extensional stiffness at every position. We apply the approach on 11 patients who underwent a gated CT scan before surgical ATAA repair and whose ATAA tissue was tested after the surgical procedure to estimate the rupture risk criterion. We find a very good correlation between the rupture risk criterion and the local extensional stiffness. Finally it is shown that patients can be separated in two groups: a group of stiff and brittle ATAA with a rupture risk criterion above 0.9, and a group of relatively compliant ATAA with a rupture risk below 0.9. Although these results need to be repeated on larger cohorts to impact the clinical practice, they support the paradigm that local aortic stiffness is an important determinant of ATAA rupture risk.

International audience; There is growing experimental evidence for non-affine deformations occurring in different types of fibrous soft tissues; meaning that the fiber orientations do not follow the macroscopic deformation gradient. Suitable mathematical modeling of this phenomenon is an open challenge, which we here tackle in the framework of continuum micromechanics. From a rate-based analogon of Eshelby's inhomogeneity problem, we derive strain and spin concentration tensors relating macroscopic strain rate tensors applied to the boundaries of a Representative Volume Element (RVE), to strain rates and spins within the tissue microstructure, in particular those associated with fiber rotations due to external mechanical loading. After presenting suitable algorithms for integrating the resulting rate-type governing equations, a first relevance check of the novel modeling approach is undertaken, by comparison of model results to recent experiments performed on the adventitia layer of rabbit carotid tissue.

It is now a rather common approach to perform patient-specific stress analyses of arterial walls using finite-element models reconstructed from gated medical images. However, this requires to compute for every Gauss point the deformation gradient between the current configuration and a stress-free reference configuration. It is technically difficult to define such a reference configuration, and there is actually no guarantee that a stress-free configuration is physically attainable due to the presence of internal stresses in unloaded soft tissues. An alternative framework was proposed by Bellini et al. (Ann Biomed Eng 42(3):488-502, 2014). It consists of computing the deformation gradients between the current configuration and a prestressed reference configuration. We present here the first finite-element results based on this concept using the Abaqus software. The reference configuration is set arbitrarily to the in vivo average geometry of the artery, which is obtained from gated medical images and is assumed to be mechanobiologically homeostatic. For every Gauss point, the stress is split additively into the contributions of each individual load-bearing constituent of the tissue, namely elastin, collagen, smooth muscle cells. Each constituent is assigned an independent prestretch in the reference configuration, named the deposition stretch. The outstanding advantage of the present approach is that it simultaneously computes the in situ stresses existing in the reference configuration and predicts the residual stresses that occur after removing the different loadings applied onto the artery (pressure and axial load). As a proof of concept, we applied it on an ideal thick-wall cylinder and showed that the obtained results were consistent with corresponding experimental and analytical results of the well-known literature. In addition, we developed a patient-specific model of a human ascending thoracic aneurysmal aorta and demonstrated the utility in predicting the wall stress distribution in vivo under the effects of physiological pressure. Finally, we simulated the whole process preceding traditional in vitro uniaxial tensile testing of arteries, including excision from the body, radial cutting, flattening and subsequent tensile loading, showing how this process may impact the final mechanical properties derived from these in vitro tests.

Understanding stress-strain relationships in arteries is important for fundamental investigations in mechanobiology. Here we demonstrate the essential role of chemoelasticity in determining the mechanical properties of arterial tissues. Stepwise stress-relaxation uniaxial tensile tests were carried out on samples of porcine thoracic aortas immersed in a hyperosmotic solution. The tissue deformations were tracked using optical coherence tomography (OCT) during the tensile tests and digital volume correlation (DVC) was used to obtain measurements of depth-resolved strains across the whole thickness of the tested aortas. The hyperosmotic solution exacerbated chemoelastic effects, and we were able to measure different manifestations of these chemoelastic effects: swelling of the media inducing a modification of its optical properties, existence of a transverse tensile strain. For the first time ever to our best knowledge, 3D strains induced by chemoelastic effects in soft tissues were quantified thanks to the OCT-DVC method. Without doubt, chemoelasticity plays an essential role in arterial mechanobiology in vivo and future work should focus on characterizing chemoelastic effects in arterial walls under physiological and disease conditions. Statement of significance: Chemoelasticity, coupling osmotic phenomena and mechanical stresses, is essential in soft tissue mechanobiology. For the first time ever, we measure and analyze 3D strain fields induced by these chemoelastic effects thanks to the unique combination of OCT imaging and digital volume correlation., Comment: Acta Biomaterialia, Elsevier, 2019, in press

International audience; Finite element analyses using cohesive zone models (CZM) can be used to predict the fracture of atherosclerotic plaques but this requires setting appropriate values of the model parameters. In this study, material parameters of a CZM were identified for the first time on two groups of mice (ApoE-/- and ApoE-/- Col8-/-) using the measured force-displacement curves acquired during delamination tests. To this end, a 2D finite-element model of each plaque was solved using an explicit integration scheme. Each constituent of the plaque was modeled with a neo-Hookean strain energy density function and a CZM was used for the interface. The model parameters were calibrated by minimizing the quadratic deviation between the experimental force displacement curves and the model predictions. The elastic parameter of the plaque and the CZM interfacial parameter were successfully identified for a cohort of 11 mice. The results revealed that only the elastic parameter was significantly different between the two groups, ApoE-/- Col8-/- plaques being less stiff than ApoE-/- plaques. Finally, this study demonstrated that a simple 2D finite element model with cohesive elements can reproduce fairly well the plaque peeling global response. Future work will focus on understanding the main biological determinants of regional and inter-individual variations of the material parameters used in the model.

Ascending thoracic aortic aneurysms (ATAAs) are focal dilatations in the aorta that are prone to rupture or dissection. To accurately evaluate the rupture risk, one must know the local mechanical conditions at the rupture site and understand how rupture is triggered in a layered fibrous media. A challenge facing experimental studies of ATAA rupture is that the ATAA tissue is highly heterogeneous; experimental protocols that operate under the premise of tissue homogeneity will have difficulty delineating the location conditions. In this work, we employed a previously established pointwise identification method to characterize wall stress, strain, and property distributions to a sub-millimeter resolution. Based on the acquired field data, we obtained the local mechanical properties at the rupture site in nine ATAA tissue samples. The rupture stress, ultimate strain, energy density, and the toughness of the tested samples were also reported. Our results show that the direction of the rupture is aligned with the direction of maximum stiffness, indicating that higher stiffness is not always related to higher strength. It was also found that the rupture generally occurs at a location of highest stored energy. As a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the recruitment of collagen fibers in the deformation of the tissue is probably essential in ATAA rupture.A major challenge in the experimental study of aneurysm properties is that the tissues are heterogeneous. When the specimens are not reasonably homogeneous, traditional tests that work under the premise of tissue homogeneity cannot reliably delineate the local conditions at the rupture site. In this work, we investigated the local characteristics of rupture of human ascending aortic aneurysm tissue. We identified the stress, strain, and elastic properties to a submillimeter resolution. Based on the field values, we determined the local conditions - elastic properties, direction of maximum stiffness, stress, strain, energy consumption - at the rupture site. It was found that the tissues consistently cleave in the direction of the maximum stiffness, and generally occurs at the location of highest energy. Since a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the work suggests that the recruitment of collagen fibers in the deformation of the tissue is probably essential in aneurysm rupture.

The constrained mixture theory is an elegant way to incorporate the phenomenon of residual stresses in patient-specific finite element models of arteries. This theory assumes an in vivo reference geometry, obtained from medical imaging, and constituent-specific deposition stretches in the assumed reference state. It allows to model residual stresses and prestretches in arteries without the need for a stress-free reference configuration, most often unknown in patient-specific modeling. A finite element (FE) model requires material parameters, which are classically obtained by fitting the constitutive model to experimental data. The characterization of arterial tissue is often based on planar biaxial test data, to which nonlinear elastic fiber-reinforced material parameters are fitted. However, the introduction of the constrained mixture theory requires an adapted approach to parameter fitting. Therefore, we introduce an iterative fitting method, alternating between nonlinear least squares parameter optimization and an FE prestressing algorithm to obtain the correct constrained mixture material state during the mechanical test. We verify the method based on numerically constructed planar biaxial test data sets, containing ground truth sets of material parameters. The results show that the method converges to the correct parameter sets in just a few iterations. Next, the iterative fitting approach is applied to planar biaxial test data of ovine pulmonary artery tissue. The obtained results demonstrate a convergence towards constrained mixture compatible parameters, which differ significantly from classically obtained parameters. We show that this new modeling approach yields in vivo wall stresses similar to when using classically obtained parameters. However, due to the numerous advantages of constrained mixture modeling, our fitting method is relevant to obtain compatible material parameters, that may not be confused with parameters obtained in a classical way. ispartof: Journal of the Mechanical Behavior of Biomedical Materials vol:95 pages:124-135 ispartof: location:Netherlands status: published

A multiscale micromechanical model for soft tissue is presented. This model accounts for the progressive stiffening of the mechanical response due to load-induced microstructural rearrangements of the fibers within the microstructure. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

We report a patient-specific case of bicuspid aortic valve with fusion of right and left coronary leaflets (R-L type I BAV), moderate aortic valve deficiency and ascending thoracic aortic aneurysms (ATAA) who was treated by only ascending aorta replacement preserving the BAV. The flow eccentricity, the helicity intensity (h2), the circumferential time averaged wall shear stress (TAWSScircumferential), the cumulative viscous energy loss at the systolic peak ( E L ' ) and the pulse wave velocity (PWV) were calculated by combining 4D flow MRI and CFD analysis before (Stage I) and after (Stage II) the surgical procedure. CFD analyses assumed rigid walls, a non-Newtonian behavior for the blood and MRI measured patient-specific blood flow profiles as inlet boundary conditions. Stage II results showed suppression of recirculation in the ascending aorta, loss of jet flow impingement onto the aortic wall, maximum TAWSScircumferential decrease (from 6.69 Pa in Stage I to 6 Pa in Stage II), reduction of flow helicity (from 10.97 in Stage I to 8.47 in Stage II) and E L ' (from 15.8 mW in Stage I to 11.2 mW in Stage II). However, Floweccentricity and PWV were found higher in Stage II due to the diameter reduction (Floweccentricity = 0.60 in Stage I and Floweccentricity = 0.91 in Stage II; PWV = 3.80 m/s in Stage I and PWV = 9.37 m/s in Stage II). Our work has permitted to compute for the first time the hemodynamic alterations obtained after restoration of normal ascending aorta and sinotubular junction geometry even preserving an R-L type I BAV with still acceptable function.

International audience; The knee is the largest joint in the body and supports high loads, up to several times the body weight. It is vulnerable to injury during sport or professional activities, potentially leading to chronic knee instability. This instability is a functional issue to the patient and is characterized by a “wobbly” feeling. Different internal structures take part in joint stabilization by passive (ligaments, capsule) or active (neuro-muscular system and proprioception) action. The most common injury involves the anterior cruciate ligament (ACL) complete or partial rupture: it is involved in 24% of all knee injuries and 59% of ligamentous injuries [1]. In the United States,the annual incidence in the general population is approximately 1 in 3500 with 100,000 ACL reconstructions performed each year [2, 3]. These conditions are a huge burden on individualsand healthcare systems. Diagnosis of knee instability involves a discussion with the patient and a clinical examination, usually the Lachman test. It consists in a manual anterior translation of the tibia aiming at putting the ACL in tension. By practice, the examiner is able to grade the laxity by severity [4]. However, its sensitivity and specificity to detect complete ACL ruptures depends on the experience of the examiner, the patient’s body type and the delay between the accident and examination [5]. In order to reduce this variability, arthrometers were developed.These devices apply an increasing force to induce a postero-anterior drawer and measure the corresponding translation. Displacement-load curves of the healthy and injured knees are compared; ACL rupture is ascertained when differential laxity is higher than a certain threshold. Well-known arthrometer devices are the KT-1000 developed by [6] and the GNRB® [7]. The former is very popular and has been widely studied; its sensitivity to detect complete ACL ruptures is 77% and its specificity 90% (threshold: differential laxity of 3 mm at 130 N). Thelatter was developed recently; two studies [5, 7] highlighted the superiority of this device compared to similar apparatus. A differential threshold of 3 mm at 134 N is used to determine complete rupture: its sensitivity is 70% and specificity 99%. This arthrometer device is also used to diagnose partial ruptures (threshold of 1.5 mm at 134 N) with a sensitivity of 80% and a specificity of 87%.Knee braces or orthoses are usually part of the standard therapy for knee instability and are commonly prescribed by physicians and medical practitioners. Their claimed mechanical effects are to support/align the joint and increase proprioceptive input [8]. However, very few studies actually show significant actions, from biomechanical studies to therapeutic trials [9, 10]. Mechanical/ physiological effects have been emphasized, but the mechanisms of action have been poorly characterized [8, 9, 10, 11, 12, 13]. What is more, subjective evaluations of patients highlight a large demand for these products; therefore, their efficiency is still widely discussed among medical experts. In particular, therelative importance of the two principal stabilizing mechanisms is not known:- joint stiffening by adding supporting structures, e.g. hinged bars secured to the joint by straps and fabric (passive mechanism)- neuromuscular control enhancement by proprioceptive effect (active mechanism)As a consequence of these uncertainties, medical practitioners and manufacturers still lack a simple evaluation tool for knee orthoses. A French committee of experts highlighted this problem [14] and stated that orthoses must be evaluated by taking both the mechanisms of action and the desired therapeutic effects into account.Although the passive action of knee braces to prevent a drawer motion has already been characterized on surrogate limbs [15, 16, 17], only one attempt has been made to link these measures to corresponding expected in-vivo actions through numerical modelling [18, 19], highlighting a passive stiffening much lower than what is brought by intact ligaments. However, a real clinical study is still needed to validate the numerical results and investigate the influence of patient-specific factors such as morphology, injury severity, neuromuscular adaptation and instability feeling control.This study is aimed at objectively quantifying the joint stiffening action of various commercial braces in-vivo using a GNRB® arthrometer on a number of pathological patients.

The fluid mechanics community has been interested for many years in hemodynamics. More recently, significant endeavours of the solid mechanics community have permitted to establish constitutive equations and to achieve stress analyses in arterial lesions (atheromatous plaque in coronary or carotid arteries, aneurysms of the aorta). The mechanical properties of blood vessels have often been characterized ex vivo, but medical imaging, including MRI, now allows non-intrusive identifications in vivo. The spatial heterogeneity of these mechanical properties, even at the macroscopic scale, remains poorly explored despite its undeniable interest in understanding the mechanisms of remodeling and degeneration of the tissue. We are interested in the problem of identifying the fields of mechanical properties of aneurysms of the aorta. Scientific barriers are related to the complex geometry, the nonlinear and anisotropic behavior of tissues, the multiaxial loading conditions, and to the measurement of a local response in these tissues. Our identification approaches, based on digital image correlation field measurements and inverse methods, have demonstrated the link between the heterogeneity of mechanical properties and the existence of localized failure modes. A micromechanical approach has also made it possible to develop a mechanobiological model to reproduce the behavior of the aorta in surgical situations and a simulation software is being developed for assistance to personalized surgery in the cardiovascular field.

International audience; In this study, bulge inflation tests were used to characterize the failure response of 15 layers of human ascending thoracic aortic aneurysms (ATAA). Full field displacement data were collected during each of the mechanical tests using a digital image stereo-correlation (DIS-C) system. Using the collected displacement data, the local stress fields at burst were derived and the thickness evolution was estimated during the inflation tests. It was shown that rupture of the ATAA does not systematically occur at the location of maximum stress, but in a weakened zone of the tissue where the measured fields show strain localization and localized thinning of the wall. Our results are the first to show the existence of weakened zones in the aneurysmal tissue when rupture is imminent. An understanding these local rupture mechanics is necessary to improve clinical assessments of aneurysm rupture risk. Further studies must be performed to determine if these weakened zones can be detected in vivo using non-invasive techniques.

International audience; The mechanisms giving rise to vein tortuosity, which is often associated with varicosis, are poorly understood. Recent works suggest that significant biological changes in the wall of varicose veins may precede the mechanical aspects of the disease. To test the hypothesis of tortuosity being a consequence of these changes, a Finite Element model was developed based on previous experimental work on vein buckling. The model was then used to evaluate the effect of alterations of the mechanical behavior of the wall on tortuosity onset and severity. The results showed that increasing anisotropy toward the circumferential direction promotes tortuosity. An increase in wall stiffness tends to decrease the level of tortuosity but interestingly, if the vein segment is little or not pre-stretched such increase will not prevent, or it will even promote, the onset of tortuosity. These results provide additional arguments supporting the hypothesis of tortuosity being the consequence of biologically-induced changes in the varicose vein wall. Based on a 3D model of the leg and in vivo identification of the material properties of varicose veins, a clinical validation of these findings is being developed.

International audience; We present a comprehensive and original framework for the biomechanical analysis of patients affected by ascending thoracic aorta aneurysm and aortic insufficiency. Our aim is to obtain crucial indications about the role played by deranged hemody-namics on the ATAAs risk of rupture. Computational fluid dynamics analysis was performed using patient-specific geometries and boundary conditions derived from 4D MRI. Blood flow helicity and wall shear stress descriptors were assessed. A bulge inflation test was carried out in vitro on the 4 ATAAs after surgical repair. The healthy volunteers showed no eccentric blood flow, a mean TAWSS of 1.5±0.3 Pa and mean OSI of 0.325±0.025. In 3 aneurismal patients, jet flow impingement on the aortic wall resulted in large TAWSS values and low OSI which were amplified by the AI degree. However, the tissue strength did not appear to be significantly reduced. The fourth patient, which showed the lowest TAWSS due to the absence of jet flow, had the smallest strength in vitro. Interestingly this patient presented a bovine arch abnormality. Jet flow impingement with high WSS values is frequent in ATAAs and our methodology seems to be appropriate for determining whether it may increase the risk of rupture or not.

The load bearing properties of large blood vessels are principally conferred by collagen and elastin networks and their microstructural organization plays an important role in the outcomes of various arterial pathologies. In particular, these fibrous networks are able to rearrange and reorient spatially during mechanical deformations. In this study, we investigate for the first time whether these well-known morphological rearrangements are the same across the whole thickness of blood vessels, and subsequently if the underlying mechanisms that govern these rearrangements can be predicted using affine kinematics. To this aim, we submitted rabbit carotid samples to uniaxial load in three distinct deformation directions, while recording live images of the 3D microstructure using multiphoton microscopy. Our results show that the observed realignment of collagen and elastin in the media layer, along with elastin of the adventitia layer, remained limited to small angles that can be predicted by affine kinematics. We show also that collagen bundles of fibers in the adventitia layer behaved in significantly different fashion. They showed a remarkable capacity to realign in the direction of the load, whatever the loading direction. Measured reorientation angles of the fibers were significantly higher than affine predictions. This remarkable property of collagen bundles in the adventitia was never observed before, it shows that the medium surrounding collagen in the adventitia undergoes complex deformations challenging traditional hyperelastic models based on mixture theories. Statement of significance The biomechanical properties of arteries are conferred by the rearrangement under load of the collagen and elastin fibers making up the arterial microstructure. Their kinematics under deformation is not yet characterized for all fiber networks. In this respect we have submitted samples of arterial tissue to uniaxial tension, simultaneously to confocal imaging of their microstructure. Our method allowed identifying for the first time the remarkable ability of adventitial collagen fibers to reorient in the direction of the load, achieving reorientation rotations that exceeded those predicted by affine kinematics, while all other networks followed the affine kinematics. Our results highlight new properties of the microstructure, which might play a role in the outcomes of vascular pathologies like aneurysms.

Arterial tissue consists of multiple structurally important constituents that have individual material properties and associated stress-free configurations that evolve over time. This gives rise to residual stresses contributing to the homoeostatic state of stress in vivo as well as adaptations to perturbed loads, disease or injury. The existence of residual stresses in an intact but load-free excised arterial segment suggests compressive and tensile stresses, respectively, in the inner and outer walls. Accordingly, an artery ring springs open into a sector after a radial cut. The measurement of the opening angle is commonly used to deduce the residual stresses, which are the stresses required to close back the ring. The opening angle method provides an average estimate of circumferential residual stresses but it gives no information on local distributions through the thickness and along the axial direction. To address this lack, a new method is proposed in this article to derive maps of residual stresses using an approach based on the contour method. A piece of freshly excised tissue is carefully cut into the specimen, and the local distribution of residual strains and stresses is determined from whole-body digital image correlation measurements using an inverse approach based on a finite element model.

International audience; Secondary interventions after endovascular repair of abdominal aortic aneurysms are frequent because stent-graft (SG) related complications may occur (mainly endoleak and SG thrombosis). Complications have been related to insufficient SG flexibility, especially when devices are deployed in tortuous arteries. Little is known on the relationship between SG design and flexibility. Therefore, the aim of this study was to simulate numerically the bending of two manufactured SGs (Aorfix--Lombard Medical (A) and Zenith--Cook Medical Europe (Z)) using finite element analysis (FEA). Global SG behavior was studied by assessing stent spacing variation and cross-section deformation. Four criteria were defined to compare flexibility of SGs: maximal luminal reduction rate, torque required for bending, maximal membrane strains in graft and maximal Von Mises stress in stents. For angulation greater than 60°, values of these four criteria were lower with A-SG, compared to Z-SG. In conclusion, A-SG was more flexible than Z-SG according to FEA. A-SG may decrease the incidence of complications in the setting of tortuous aorto-iliac aneurysms. Our numerical model could be used to assess flexibility of further manufactured as well as newly designed SGs.

International audience; 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.

International audience; Objective Ascending thoracic aortic aneurysms (ATAA) are a life-threatening condition due to the risk of rupture or dissection. This risk is increased in the presence of a bicuspid aortic valve (BAV). The purpose of this study was to provide data on the elastic modulus of aortic wall of ATAA using uniaxial tensile testing in two different areas of the stress–strain relationship: physiological and maximum range of stresses. The influence of tissue location, tissue orientation and valve type on these parameters was investigated. Materials and methods Tissues freshly excised from ATAA with bicuspid or tricuspid aortic valve were obtained from greater and lesser curvature (GC and LC) and the specimens were tested uniaxially in circumferential (CIRC) and longitudinal (LONG) orientation. Maximum elastic modulus (MEM) was given by the maximum slope of the stress–strain curve before failure. Physiological modulus (PM) was derived from the Laplace law and from ranges of pressure of 80–120 mmHg. Means of each group of specimen were compared using Student's t-test to assess the influence of location, orientation and valve type on each mechanical parameter. Results PM was found to be significantly lower than the MEM (p < 0.001). The MEM and PM were significantly higher (p < 0.01) in the CIRC (n = 66) than in the LONG orientation (n = 42). The MEM was higher in the circumferential orientation in the BAV group (p < 0.001 in GC and p < 0.05 in LC). MEM and PM in GC specimens were higher in the longitudinal orientation than the LC specimens (p < 0.05). Conclusion This study demonstrates the anisotropy of the aortic wall in ATAA and provides data on the mechanical behaviour in the physiological range of pressure.

International audience; Transcatheter aortic valve implantation is a recent mini-invasive procedure to implant an aortic valve prosthesis. Prosthesis positioning in transcatheter aortic valve implantation appears as an important aspect for the success of the intervention. Accordingly, we developed a patient-specific finite element framework to predict the insertion of the stiff guidewire, used to position the aortic valve. We simulated the guidewire insertion for 2 patients based on their pre-operative CT scans. The model was designed to primarily predict the position and the angle of the guidewires in the aortic valve, and the results were successfully compared with intraoperative images. The present paper describes extensively the numerical model, which was solved by using the ANSYS software with an implicit resolution scheme, as well as the stabilization techniques which were used to overcome numerical instabilities. We performed sensitivity analysis on the properties of the guidewire (curvature angle, curvature radius, and stiffness) and the conditions of insertion (insertion force and orientation). We also explored the influence of the model parameters. The accuracy of the model was quantitatively evaluated as the distance and the angle difference between the simulated guidewires and the intraoperative ones. A good agreement was obtained between the model predictions and intraoperative views available for 2 patient cases. In conclusion, we showed that the shape of the guidewire in the aortic valve was mainly determined by the geometry of the patient's aorta and by the conditions of insertion (insertion force and orientation).

International audience; In this work, the application of the unnotched Iosipescu test for the evaluation of the radial variability of longitudinal–radial stiffness parameters of maritime pine wood was investigated. Rectangular specimens with grain at 45° were tested using the Iosipescu fixture. For this configuration both the transverse (Q22) and the shear (Q66) stiffness parameters can be simultaneously identified by the virtual fields method. Displacement fields were measured by the grid method. The strain fields were reconstructed from the raw displacement fields using a polynomial approximation scheme. For the tested wood material, it was found that both parameters decrease from the centre to about the middle radius of the stem and increase afterwards to the outermost positions. Moreover, a relatively good correlation was obtained between the patterns of radial variability of Q22 and Q66.