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This work presents the development of a Hybrid Mock Circulatory Loop (HMCL) to simulate hemodynamics at patient-specific level in terms of both 3D geometry and inlet/outlet boundary conditions.Clinical data have been processed to define the morphological and functional patient-specific settings. A piston pump is used to impose a parametric flow rate profile at the inlet of the hemodynamic circuit. In order to guarantee the physiological pressure and flow conditions, a specific hybrid chamber system including a real-time control has been designed and implemented. The developed system was validated firstly in a single outlet branch model and, secondly, on a 3D printed patient-specific multi-branch phantom. Finally, for the 3D phantom, the outlet flow profiles were compared with the corresponding in-vivo flow data.Results showed that the root mean squared error between the prescribed setpoint and the measured pressures was always below 3 mmHg (about 2.5%) for all cases. The obtained flow profiles for the patient-specific model were in agreement with the related functional in-vivo data.The capability to reproduce physiological hemodynamics condition, with high-fidelity, plays a significant role in the cardiovascular research. The developed platform can be used to assess the performances of cardiovascular devices, to validate numerical simulations, and to test imaging systems.

Aortic smooth muscle cells (SMCs) play a vital role in maintaining mechanical homeostasis in the aorta. We recently found that SMCs of aneurysmal aortas apply larger traction forces than SMCs of healthy aortas. This result was explained by the significant increase of hypertrophic SMCs abundance in aneurysms. In this study, we investigate whether the cytoskeleton stiffness of SMCs may also be altered in aneurysmal aortas. For that, we use atomic force microscopy (AFM) nano-indentation with a specific mode that allows subcellular-resolution mapping of the local stiffness across a specified region of interest of the cell. Aortic SMCs from a commercial human lineage (AoSMCs, Lonza) and primary aneurysmal SMCs (AnevSMCs) are cultured in conditions promoting the development of their contractile apparatus, and seeded on hydrogels with stiffness properties of 12 kPa and 25 kPa. Results show that all SMCs exhibit globally a lognormal stiffness distribution, with medians in the range 10–30 kPa. The mean of stiffness distributions is 16 kPa in aneurysmal SMCs and 12 kPa in healthy cells, but the differences are not statistically significant due to the large dispersion of AFM nano-indentation stiffness. We conclude that the possible alterations previously found in aneurysmal SMCs do not affect significantly the AFM nano-indentation stiffness of their cytoskeleton.

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.

It is widely accepted that the nonlinear macroscopic mechanical behavior of soft tissue is governed by fiber straightening and re-orientation. Here, we provide a quantitative assessment of this phenomenon, by means of a continuum micromechanics approach. Given the negligibly small bending stiffness of crimped fibers, the latter are represented through a number of hypoelastic straight fiber phases with different orientations, being embedded into a hypoelastic matrix phase. The corresponding representative volume element (RVE) hosting these phases is subjected to ``macroscopic'' strain rates, which are downscaled to fiber and matrix strain rates on the one hand, and to fiber spins on the other hand. This gives quantitative access to the fiber decrimping (or straightening) phenomenon under non-affine conditions, i.e. in the case where the fiber orientations cannot be simply linked to the macroscopic strain state. In the case of tendinous tissue, such an RVE relates to the fascicle material with 50 micrometers characteristic length, made up of crimped collagen bundles and a gel-type matrix in-between. The fascicles themselves act as parallel fibers in a similar matrix at the scale of a tissue-related RVE with 500 micrometers characteristic length. As evidenced by a sensitivity analysis and confirmed by various mechanical tests, it is the initial crimping angle which drives both the degree of straightening and the shape of the macroscopic stress-strain curve, while the final linear portion of this curve depends almost exclusively on the collagen bundle elasticity. Our model also reveals the mechanical cooperation of the tissue's key microstructural components: while the fibers carry tensile forces, the matrices undergo hydrostatic pressure.

Growth and remodelling (G&R) of biological tissues are mechanisms which respectively involve a change in mass and material properties. In particular, arterial media calcification (AMC) is a patholo...

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

BACKGROUND: Digital image correlation (DIC) methods are increasingly used for non-contact optical assessment of geometry and deformation in soft tissue biomechanics, thus providing the full-field strain estimates needed for robust inverse material characterization. Despite the well-known flexibility and ease of use of DIC, issues related to spatial resolution and depth-of-field remain challenging in studies of quasi-cylindrical biological samples such as arteries. OBJECTIVE: After demonstrating that standard surrounding multi-view DIC systems are inappropriate for such usage, we submit that both the optical setup and the data analysis need to be specifically designed with respect to the size of the arterial sample of interest. Accordingly, we propose novel and optimized DIC systems for two distinct ranges of arterial diameters: less than 2.5 mm (murine arteries) and greater than 10 mm (human arteries). METHODS: We designed, set up, and validated a four-camera panoramic-DIC system for testing murine arteries and a multi-biprism DIC system for testing human arteries. Both systems enable dynamic 360-deg measurements with refraction correction over the entire surface of submerged samples in their native geometries. RESULTS: Illustrative results for 3D shape and full-surface deformation fields were obtained for a mouse infrarenal aorta and a latex cylinder of size similar to the human infrarenal aorta. CONCLUSION: Results demonstrated the feasibility and accuracy of both proposed methods in providing quantitative information on the regional behavior of arterial samples tested in vitro under physiologically relevant loading.

International audience; In this paper we introduce a new method simulating stent graft deployment for assisting endovascular repair of abdominal aortic aneurysms. The method relies on intraoperative images coupled with mechanical models. A multi-step algorithm has been developed to increase the reliability of simulations. The first step predicts the position of the stent graft within the aorta. The second step is an axisymmetric geometric reconstruction of each individual stent. The third step minimizes the rotation of each stent around its main axis. Finally, the last step virtually deploys each stent within a deployment box extracted from the preoperative CT scan. A proof of concept is performed on a patient. The accuracy is compatible with the clinical threshold of 3 mm: the average distance between target and simulated stents is 1.73 ± 0.37 mm. Fenestrations of the stent-graft are reconstructed with a maximum error of less than 2.5 mm, which is enables a secure catheterization of secondary arteries. In summary, the method is able to assist EVAR practitioners by providing all necessary information for a fast and accurate stent graft positioning, combining intraoperative data and a mechanical model in a very low cost framework.

Vascular clamping often causes injury to arterial tissue, leading to a cascade of cellular and extracellular events. A reliable in silico prediction of these processes following vascular injury could help us to increase our understanding thereof, and eventually optimize surgical techniques or drug delivery to minimize the amount of long-term damage. However, the complexity and interdependency of these events make translation into constitutive laws and their numerical implementation particularly challenging. We introduce a finite element simulation of arterial clamping taking into account acute endothelial denudation, damage to extracellular matrix, and smooth muscle cell loss. The model captures how this causes tissue inflammation and deviation from mechanical homeostasis, both triggering vascular remodeling. A number of cellular processes are modeled, aiming at restoring this homeostasis, i.e., smooth muscle cell phenotype switching, proliferation, migration, and the production of extracellular matrix. We calibrated these damage and remodeling laws by comparing our numerical results to in vivo experimental data of clamping and healing experiments. In these same experiments, the functional integrity of the tissue was assessed through myograph tests, which were also reproduced in the present study through a novel model for vasodilator and -constrictor dependent smooth muscle contraction. The simulation results show a good agreement with the in vivo experiments. The computational model was then also used to simulate healing beyond the duration of the experiments in order to exploit the benefits of computational model predictions. These results showed a significant sensitivity to model parameters related to smooth muscle cell phenotypes, highlighting the pressing need to further elucidate the biological processes of smooth muscle cell phenotypic switching in the future. ispartof: Frontiers In Bioengineering And Biotechnology vol:8 ispartof: location:Switzerland status: published

Characterization of material parameters from experimental data remains challenging, especially on biological structures. One of such techniques allowing for the inverse determination of material parameters from measurement data is the virtual fields method (VFM). However, application of the VFM on general structures of complicated shape has not yet been extensively investigated. In this paper, we extend the framework of the VFM method to thin curved solids in three-dimensional, commonly denoted shells. Our method is then used to estimate the Young's modulus and hysteretic damping of the human eardrum. By utilizing Kirchhoff plate theory, we assume that the behavior of the shell varies linearly through the thickness. The total strain of the shell can then be separated in a bending and membrane strain. This in turn allowed for an application of the VFM based only on data of the outer surface of the shell. We validated our method on simulated and experimental data of a human eardrum made to vibrate at certain frequencies. It was shown that the identified material properties were accurately determined based only on data from the outer surface and are in agreement with literature. Additionally, we observed that neither the bending nor the membrane strain in an human eardrum can be neglected and both contribute significantly to the total strain found experimentally.

International audience; Computational modeling can provide insight into understanding the damage mechanisms of soft biological tissues. Our gradient‐enhanced damage model presented in a previous publication has shown advantages in considering the internal length scales and in satisfying mesh independence for simulating damage, growth and remodeling processes. Performing sensitivity analyses for this model is an essential step towards applications involving uncertain patient‐specific data. In this paper, a numerical analysis approach is developed. For that we integrate two existing methods, that is, the gradient‐enhanced damage model and the surrogate model‐based probability analysis. To increase the computational efficiency of the Monte Carlo method in uncertainty propagation for the nonlinear hyperelastic damage analysis, the surrogate model based on Legendre polynomial series is employed to replace the direct FEM solutions, and the sparse grid collocation method (SGCM) is adopted for setting the collocation points to further reduce the computational cost in training the surrogate model. The effectiveness of the proposed approach is illustrated by two numerical examples, including an application of artery dilatation mimicking to the clinical problem of balloon angioplasty.

International audience; Textile-based implant (mesh) treatment is considered as a standard of care for abdominal wall hernia repair. Computational models and simulations have appeared as one of the most promising approach to investigate biomechanics related to hernia repair and to improve clinical outcomes. This paper presents a novel anisotropic hypo-elastoplastic constitutive model specifically established for surgical knitted textile implants. The major mechanical characteristics of these materials such as anisotropy and permanent set have been reproduced. For the first time ever, we report an extensive mechanical characterization of one of these meshes, including cyclic uniaxial tension, planar equibiaxial tension and plunger type testing. These tests highlight the complex mechanical behavior with strong nonlinearity, anisotropy and permanent set. The novel anisotropic hypo-elasto-plastic constitutive model has been identified based on the tensile experiments and validated successfully against the data of the plunger experiment. In the future, implementation of this characterization and modeling approach to additional surgical knitted textiles should be the direction to follow in order to develop clinical decision support software for abdominal wall repair.

Endovascular aortic repair (EVAR) has become the preferred intervention option for aortic aneurysms and dissections. This is because EVAR is much less invasive than the alternative open surgery repair. While in-hospital mortality rates are smaller for EVAR than open repair (1%-2% vs. 3%-5%), the early benefits of EVAR are lost after 3 years due to larger rates of complications in the EVAR group. Clinicians follow instructions for use (IFU) when possible, but are left with personal experience on how to best proceed and what choices to make with respect to stent-graft (SG) model choice, sizing, procedural options, and their implications on long-term outcomes. Computational modeling of SG deployment in EVAR and tissue remodeling after intervention offers an alternative way of testing SG designs in silico, in a personalized way before intervention, to ultimately select the strategies leading to better outcomes. Further, computational modeling can be used in the optimal design of SGs in cases of complex geometries. In this review, we address some of the difficulties and successes associated with computational modeling of EVAR procedures. There is still work to be done in all areas of EVAR in silico modeling, including model validation, before models can be applied in the clinic, but much progress has already been made. Critical to clinical implementation are current efforts focusing on developing fast algorithms that can achieve (near) real-time solutions, as well as ways of dealing with inherent uncertainties related to patient aortic wall degradation on an individualized basis. We are optimistic that EVAR modeling in the clinic will soon become a reality to help clinicians optimize EVAR interventions and ultimately reduce EVAR-associated complications.

International audience; In this paper, we investigate the progression of Ascending Thoracic Aortic Aneurysms (ATAA) using a computational model of Growth and Remodeling (G&R) taking into account the composite (elastin, four collagen fiber families and Smooth Muscle Cells-SMCs) and multi-layered (media and adventitia) nature of the aorta. The G&R model, which is based on the homogenized Constrained Mixture theory, is implemented as a UMAT in the Abaqus finite-element package. Each component of the mixture is assigned a strain energy density function: nearly-incompressible neo-Hookean for elastin and Fung-type for collagen and SMCs. Active SMCs tension is additionally considered, through a length-tension relationship having a classic inverted parabola shape, in order to investigate its effects on the progression of ATAA in a patient-specific model. A sensitivity analysis is performed to evaluate the potential impact of variations in the parameters of the length-tension relationships. These variations reflect in variations of SMCs normal tone during ATAA progression, with active stress contributions ranging between 30% (best case scenario) and 0% (worst case scenario) of the total wall circumferential stress. Low SMCs active stress in the worst case scenarios, in fact, affect the rates of collagen deposition by which the elastin loss is gradually compensated by collagen deposition in the simulated ATAA progression, resulting eventually in larger aneurysm diameters. The types of length-tension relationships leading to a drop of SMCs active stress in our simulations reveal a critical condition which could also result in SMCs apoptosis.

In this paper, we evaluate computationally the influence of blood flow eccentricity and valve phenotype (bicuspid (BAV) and tricuspid (TAV) aortic valve) on hemodynamics in ascending thoracic aortic aneurysm (ATAA) patients. 5 TAV ATAA, 5 BAV ATAA (ascending aorta diameter > 35 mm) and 2 healthy subjects underwent 4D flow MRI. The 3D velocity profiles obtained from 4D flow MRI were given as input boundary conditions to a computational fluid dynamics analysis (CFD) model. After performing the CFD analyses, we verified that the obtained time-averaged velocity profiles and flow eccentricity were in good agreement with 4D flow MRI. Then we used the CFD analyses to evaluate the time-averaged wall shear stress (TAWSS) and the local normalized helicity (LNH). We found that the flow eccentricities at the aortic root were not significantly different (p > 0.05) between TAV and BAV phenotypes. TAWSS (R2 = 0.697, p = 0.025) and absolute LNH (R2 = 0.964, p 0.001) are in good correlation with flow eccentricity. We conclude that eccentricity at the aortic root is a major determinant of hemodynamics patterns in ATAA patients regardless of the aortic valve phenotype.

BackgroundAortic dissection (AD) is a common pathology and challenging clinical problem. A better understanding of the biomechanical effects preceding its initiation is essential for predicting adverse events on a patient-specific basis. Moreover, the predictability of patient-specific biomechanics-based computational models is hampered by uncertainty about boundary conditions and material properties.ObjectivePredisposition of thoracic aortic aneurysms (TAA) to ADs can be related to the degradation of biomechanically important constituents in the aortic wall of TAAs. The goal of the present study is to develop a new methodology to measure strain fields in aortic tissues subjected to radial tensile loading, combining optical coherence tomography (OCT) and digital image correlation (DIC).MethodsRadial tensile tests are performed on 5 samples collected from a healthy porcine descending thoracic aorta and 2 samples collected from a human ascending thoracic aortic aneurysm. At each step of the radial tensile test, the OCT technique is used to acquire images of the sample presenting a speckle pattern generated by the optical signature of the tissue. The speckle pattern is used to quantify displacement and strain fields using DIC. Stress-strain data are also measured throughout the analyzed range.ResultsResults show that strain commonly localizes very early during tensile tests, at the location where the crack onset occurs. Aneurysm samples even show a sharper localization than healthy porcine tissues.ConclusionThis suggests the importance of extending the analysis to a larger number of human samples using our new methodology to better identify the conditions predisposing aortas to dissection.

The degeneration of the arterial wall at the basis of the ascending thoracic aortic aneurysm (ATAA) is a complex multifactorial process, which may lead to clinical complications and, ultimately, death. Individual genetic, biological or hemodynamic factors are inadequate to explain the heterogeneity of ATAA development/progression mechanisms, thus stimulating the analysis of their complex interplay. Here the disruption of the hemodynamic environment in the ATAA is investigated integrating patient-specific computational hemodynamics, CT-based in vivo estimation of local aortic stiffness and advanced fluid mechanics methods of analysis. The final aims are (1) deciphering the ATAA spatiotemporal hemodynamic complexity and its link to near-wall topological features, and (2) identifying the existing links between arterial wall degeneration and hemodynamic insult. Technically, two methodologies are applied to computational hemodynamics data, the wall shear stress (WSS) topological skeleton analysis, and the Complex Networks theory. The same analysis was extended to the healthy aorta. As main findings of the study, we report that: (1) different spatiotemporal heterogeneity characterizes the ATAA and healthy hemodynamics, that markedly reflect on their WSS topological skeleton features; (2) a link (stronger than canonical WSS-based descriptors) emerges between the variation of contraction/expansion action exerted by WSS on the endothelium along the cardiac cycle, and ATAA wall stiffness. The findings of the study suggest the use of advanced methods for a deeper understanding of the hemodynamics disruption in ATAA, and candidate WSS topological skeleton features as promising indicators of local wall degeneration.

Biomechanical characterization of abdominal aortic aneurysms (AAAs) has become commonplace in rupture risk assessment studies. However, its translation to the clinic has been greatly limited due to the complexity associated with its tools and their implementation. The unattainability of patient-specific tissue properties leads to the use of generalized population-averaged material models in finite element analyses, which adds a degree of uncertainty to the wall mechanics quantification. In addition, computational fluid dynamics modeling of AAA typically lacks the patient-specific inflow and outflow boundary conditions that should be obtained by nonstandard of care clinical imaging. An alternative approach for analyzing AAA flow and sac volume changes is to conduct in vitro experiments in a controlled laboratory environment. In this study, we designed, built, and characterized quantitatively a benchtop flow loop using a deformable AAA silicone phantom representative of a patient-specific geometry. The impedance modules, which are essential components of the flow loop, were fine-tuned to ensure typical intraluminal pressure conditions within the AAA sac. The phantom was imaged with a magnetic resonance imaging (MRI) scanner to acquire time-resolved images of the moving wall and the velocity field inside the sac. Temporal AAA sac volume changes lead to a corresponding variation in compliance throughout the cardiac cycle. The primary outcome of this work was the design optimization of the impedance elements, the quantitative characterization of the resistive and capacitive attributes of a compliant AAA phantom, and the exemplary use of MRI for flow visualization and quantification of the deformed AAA geometry.

Chronic infusion of angiotensin-II in atheroprone (ApoE−/−) mice provides a reproducible model of dissection in the suprarenal abdominal aorta, often with a false lumen and intramural thrombus that thickens the wall. Such lesions exhibit complex morphologies, with different regions characterized by localized changes in wall composition, microstructure, and properties. We sought to quantify the multiaxial mechanical properties of murine dissecting aneurysm samples by combining in vitro extension-distension data with full-field multimodality measurements of wall strain and thickness to inform an inverse material characterization using the virtual fields method. A key advance is the use of a digital volume correlation approach that allows for characterization of properties not only along and around the lesion, but also across its wall. Specifically, deformations are measured at the adventitial surface by tracking motions of a speckle pattern using a custom panoramic digital image correlation technique while deformations throughout the wall and thrombus are inferred from optical coherence tomography. These measurements are registered and combined in 3D to reconstruct the reference geometry and compute the 3D finite strain fields in response to pressurization. Results reveal dramatic regional variations in material stiffness and strain energy, which reflect local changes in constituent area fractions obtained from histology but emphasize the complexity of lesion morphology and damage within the dissected wall. This is the first point-wise biomechanical characterization of such complex, heterogeneous arterial segments. Because matrix remodeling is critical to the formation and growth of these lesions, we submit that quantification of regional material properties will increase the understanding of pathological mechanical mechanisms underlying aortic dissection.

The aim of the present work is to propose a robust computational framework combining computational fluid dynamics (CFD) and 4D flow MRI to predict the progressive changes in hemodynamics and wall rupture index (RPI) induced by aortic morphological evolutions in patients harboring ascending thoracic aortic aneurysms (ATAAs). An analytical equation has been proposed to predict the aneurysm progression based on age, sex, and body surface area. Parameters such as helicity, wall shear stress (WSS), time-averaged WSS, oscillatory shear index, relative residence time, and viscosity were evaluated for two patients at different stages of aneurysm growth, and compared with age-sex-matched healthy subjects. The study shows that evolution of hemodynamics and RPI, despite being very slow in ATAAs, is strongly affected by morphological alterations and, in turn could impact biomechanical factors and aortic mechanobiology. An aspect of the current work is that the patient-specific 4D MRI data sets were obtained with a follow-up of 1 year and the measured time-averaged velocity maps and flow eccentricity were compared with the CFD simulation for validation. The computational framework presented here is capable of capturing the blood flow patterns and the hemodynamic descriptors during the various stages of aneurysm growth. Further investigations will be conducted in order to verify these results on a larger cohort of patients and with long follow-up times to finally elucidate the link between deranged hemodynamics, AA geometry, and wall mechanical properties in ATAAs.

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; In this paper, the objective is to assess the histomechanical effects of collagen proteolysis in arteries under loading conditions reproducing in vivo environment. Thirteen segments of common porcine carotid arteries (8 proximal and 5 distal) were immersed in a bath of bacterial collagenase and tested with a pulsatile tension/inflation machine. Diameter, pressure and axial load were monitored throughout the tests and used to derive the stress-stretch curves and to determine the secant circumferential stiffness. Results were analyzed separately for proximal and distal segments, before and after 1, 2 and 3 hours of enzymatic degradation. A histological analysis was performed to relate the arterial microstructure to its mechanical behavior under collagen proteolysis. Control (before enzymatic degradation) and treated populations (after 1, 2 or 3 hours of enzymatic degradation) were found statistically incomparable, and histology confirmed the alteration of the fibrous structure of collagen bundles induced by the collagenase treatment. A decrease of the secant circumferential stiffness of the arterial wall was noticed mostly at the beginning of the treatment, and was less pronounced after 1 hour. These results constitute an important set of enzymatically damaged arteries that can be used to validate biomechanical computational models correlating structure and properties of blood vessels.

We recently developed an approach to characterize local nonlinear, anisotropic mechanical properties of murine arteries by combining biaxial extension-distension testing, panoramic digital image correlation, and an inverse method based on the principle of virtual power. This experimental-computational approach was illustrated for the normal murine abdominal aorta assuming uniform wall thickness. Here, however, we extend our prior approach by adding an optical coherence tomography (OCT) imaging system that permits local reconstructions of wall thickness. This multimodality approach is then used to characterize spatial variations of material and structural properties in ascending thoracic aortic aneurysms (aTAA) from two genetically modified mouse models (fibrillin-1 and fibulin-4 deficient) and to compare them with those from angiotensin II-infused apolipoprotein E-deficient and wild-type control ascending aortas. Local values of stored elastic energy and biaxial material stiffness, computed from spatial distributions of the best fit material parameters, varied significantly with circumferential position (inner vs. outer curvature, ventral vs. dorsal sides) across genotypes and treatments. Importantly, these data reveal an inverse relationship between material stiffness and wall thickness that underlies a general linear relationship between stiffness and wall stress across aTAAs. OCT images also revealed sites of advanced medial degeneration, which were captured by the inverse material characterization. Quantification of histological data further provided high-resolution local correlations among multiple mechanical metrics and wall microstructure. This is the first time that such structural defects and local properties have been characterized mechanically, which can better inform computational models of aortopathy that seek to predict where dissection or rupture may initiate.

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.

The numerical simulation of Growth and Remodelling (G&R) of soft tissues has attracted increasing attention over the last few years, especially in the case of predicting the progression of mechanob...

Abdominal wall hernia (AWH) is a protrusion of the abdominal cavity contents through a defect in the abdominal wall. AWH repair is one of the most common surgeries worldwide and the use of mesh has...

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; In its permanent quest of mechanobiological homeostasis, our vascula-ture significantly adapts across multiple length and time scales in various physiological and pathological conditions. Computational modeling of vascular growth and remodeling (G&R) has significantly improved our insights of the mechanobio-logical processes of diseases such as hypertension or aneurysms. However, patient-specific computational modeling of ascending thoracic aortic aneurysm (ATAA) evolution, based on finite-element models (FEM), remains a challenging scientific problem with rare contributions, despite the major significance of this topic of research. Challenges are related to complex boundary conditions and geometries combined with layer-specific G&R responses. To address these challenges, in the current paper, we employed the constrained mixture model (CMM) to model the arterial wall as a mixture of different constituents such as elastin, collagen fiber families and smooth muscle cells (SMCs). Implemented in Abaqus as a UMAT, this first patient-specific CMM-based FEM of G&R in human ATAA was first validated for canonical problems such as single-layer thick-wall cylindrical and bi-layer thick-wall toric arterial geometries. Then it was used to predict ATAA evolution for a patient-specific aortic geometry, showing that the typical shape of an ATAA can be simply produced by elastin proteolysis localized in regions of deranged hemodymanics. The results indicate a transfer of stress to the adventitia by elastin loss and continuous adaptation of the stress distribution due to change of ATAA shape. Moreover, stress redistribution leads to collagen deposition where the maximum elastin mass is lost, which in turn leads to stiffening of the arterial wall. As future work, the predictions of this G&R framework will be validated on datasets of patient-specific ATAA geometries followed up over a significant number of years.

Fibrous collagen networks are well known to play a central role in the passive biomechanical response of soft connective tissues to applied loads. In the current chapter we focus on vascular tissues and share our extensive experience in coupling mechanical loading and multi-photon imaging to investigate, across arteries, species and testing conditions, how collagen fibers move in response to mechanical loading. More specifically, we assess the deformations of collagen networks in rabbit, porcine or human arteries under different loading scenarios: uniaxial tension on flat samples, tension-inflation on tubular samples, bulge inflation on flat samples. We always observe that collagen fibers exhibit a wavy or crimped shape in load-free conditions, and tend to uncrimp when loads are applied, engaging sequentially to become the main load-bearing component. This sequential engagement, which is responsible for the nonlinear mechanical behaviour, is essential for an artery to function normally and appears to be less pronounced for arteries in elderly and aneurysmal patients. Although uncrimping of collagen fibers is a universal mechanism, we also observe large fiber rotations specific to tensile loading, with significant realignment along the loading axis. A unified approach is proposed to compare observations and quantitative analyses as the type of image processing may affect significantly the estimation of collagen fiber deformations. In summary, this chapter makes an important review of the basic roles of arterial microstructure and its deformations on the global mechanical response. Eventually, directions for future studies combining mechanical loading and multi-photon imaging are suggested, with the aim of addressing open questions related to tissue adaptation and rupture.

International audience; Endovascular aneurysm repair (EVAR) is a current alternative treatment for thoracic and abdominal aortic aneurysms, but is still sometimes compromised by possible complications such as device migration or endoleaks. In order to assist clinicians in preventing these complications, finite element analysis (FEA) is a promising tool. However, the strong material and geometrical nonlinearities added to the complex multiple contacts result in costly finite-element models. To reduce this computational cost, we establish here an alternative and systematic methodology to simplify the computational simulations of stent-grafts (SG) based on FEA. The model reduction methodology relies on equivalent shell models with appropriate geometrical and mechanical parameters. It simplifies significantly the contact interactions but still shows very good agreement with a complete reference finite-element model. Finally, the computational time for EVAR simulations is reduced of a factor 6 to 10. An application is shown for the deployment of a SG during thoracic endovascular repair, showing that the developed methodology is both effective and accurate to determine the final position of the deployed SG inside the aneurysm.

Quantifying local aortic stiffness properties in vivo is acknowledged as essential to assess the severity of an ascending thoracic aortic aneurysm (ATAA). Recently, the LESI (local extensional stiffness identification) methodology has been established to quantify non-invasively local stiffness properties of ATAAs using electrocardiographic-gated computed tomography (ECG-gated CT) scans. The aim of the current study was to determine the most sensitive markers of local ATAA stiffness estimation with the hypothesis that direct measures of local ATAA stiffness could better detect the high-risk patients. A cohort of 30 patients (12 BAV and 18 TAV) referred for aortic size evaluation by ECG-gated CT were recruited. For each patient, the extensional stiffness Q was evaluated by the LESI methodology whilst computational flow analyses were also performed to derive hemodynamics markers such as the wall shear stress (WSS). A strong positive correlation was found between the extensional stiffness and the aortic pulse pressure (R = 0.644 and p < 0.001). Interestingly, a significant positive correlation was also found between the extensional stiffness and patients age for BAV ATAAs (R = 0.619 and p = 0.032), but not for TAV ATAAs (R = −0.117 and p = 0.645). No significant correlation was found between the extensional stiffness and WSS evaluated locally. There was no significant difference either in the extensional stiffness between BAV ATAAs and TAV ATAAs (Q = 3.6 ± 2.5 MPa.mm for BAV ATAAs vs Q = 5.3 ± 3.1 MPa.mm for TAV ATAAs, p = 0.094). Future work will focus on relating the extensional stiffness to the patient-specific rupture risk of ATAAs on larger cohorts to confirm the promising interest of the LESI methodology.

Knowledges of both local stress and strength are needed for a reliable evaluation of the rupture risk for ascending thoracic aortic aneurysm (ATAA). In this study, machine learning is applied to predict the local strength of ATAA tissues based on tension-strain data collected through in vitro inflation tests on tissue samples. Inputs to machine learning models are tension, strain, slope, and curvature values at two points on the low strain region of the tension-strain curve. The models are trained using data from locations where the tissue ruptured, and subsequently applied to data from intact sites to predict the local rupture strength. The predicted strengths are compared with the known strength at rupture sites as well as the highest tension the tissues experienced at the intact sites. A local rupture index, which is the ratio of the end tension to the predicted rupture strength, is computed. The 'hot spots' of the rupture index are found to match the rupture sites better than those of the peak tension. The study suggests that the strength of ATAA tissue could be reliably predicted from early phase response features defined in this work.

Goal: A non-invasive method is proposed to identify in vivo the passive mechanical properties of deep soft tissues in the human leg. How: Force-displacement curves in response to a localized compression of the calf are measured with a custom made experimental setup. The material parameters of a finite element model are then calibrated against the experimental curves using a genetic algorithm. A thorough investigation of the efficacy of this method to identify such mechanical properties is conducted through a design of experiments analysis and mixed numerical - experimental validations. Results: It is the first time that a thorough analysis is conducted to really separate the contribution of deep and superficial tissues in the response to compression tests and this permits to estimate the parameters of deep soft tissues on four subjects independently of the response of their other tissues. Two strain energy density functions are compared. It is shown that a 2nd order reduced polynomial better describes the passive mechanical behavior of the deep soft tissues of the leg than the neo-Hookean 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.

Objective: Ascending thoracic aortic aneu-rysm (aTAA) is a major cause of human deaths. Despite important recent progress to better understand its pathogenesis and development, the role played by deranged hemodynamics on aTAA risk of rupture is still partially unknown. Our aim was to develop and apply a novel methodology to assess the correlation between aTAA rupture risk and hemodynamic biomarkers combining for the first time in vivo , in vitro , and in silico analyses. Methods: Computational fluid dynamic analyses were performed and validated on ten patients using patient-specific data derived from CT scan and four-dimensional MRI. Systolic wall shear stress, time-averaged wall shear stress (TAWSS), flow eccentricity (Floweccentricity), and helicity intensity (h2) were assessed. A bulge inflation test was carried out in vitro on the ten aTAA samples resected during surgical repair. The biomechanical and rupture properties of these samples were derived: the burst pressure, the physiological tangent elastic modulus $({{{\bf{E}}_{{\bf{physio}}}}})$ , the Cauchy stress at rupture $({{{\bf{\sigma }}_{{\bf{rupt}}}}})$ , the rupture stretch $({{{\bf{\lambda }}_{{\bf{rupt}}}}})$ , and the rupture stretch criterion $({\Upsilon_{\boldsymbol{stretch}}})$ . Statistical analysis was performed to determine correlation between all variables. Results: Statistically highly significant (p ${{\bf{\lambda }}_{{\bf{rupt}}}}$ and the TAWSS (r = 0.867 and p = 0.001) was found. Conclusion: This study shows that relatively low TAWSS significantly correlates with reduced rupture properties in aTAAs. Significance: Understanding the pathogenesis of aTAA remains crucial to reduce morbidity and mortality. Our aim is to establish possible correlations between aTAA rupture risk and hemodynamic biomarkers by combining for the first time in vivo , in vitro , and in silico analyses.

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

International audience; The mechanical integrity of arteries is of prime importance, for a proper oxygen and nutrients delivery to all organs. To optimize their mechanical properties, healthy arteries exhibit a complex hierarchical microstructure which ensures a sufficient compliance at low stresses and which stiffens at higher stresses, preventing over-dilatation. In this article, we propose a vast literature survey on how the mechanical properties of arteries are related to structural features. We first review the characteristics of arterial microstructure and composition and then we review the mechanical behavior of arteries. This allows evidencing, for the first time, the strong correlation existing between elastin and collagen contents within the arterial wall. However, bringing together most of the available mechanical tests on arterial walls shows the important variability of the mechanical arterial response. The presentation is organized at three different scales: at the tissue (macroscopic) scale, at the (micrometer) scale of the fiber networks, and at the (submicrometer) fibrillar and cellular scale. Glossary: Autoclave: pressure chamber used to carry out processes requiring elevated temperature and pressure different from ambient air pressure. In the sequel, autoclaving is used to separate soluble proteins (such as collagen) from non-soluble proteins (such as elastin). Constitutive relation: in mechanics, material-specific relation between stress and strain that characterizes the response of the material to an applied mechanical loading. In vivo pre stretch and pre stress: The in vivo state of the arterial tissue is not free of mechanical loading; in particular, it is subjected to an axial elongation and residual stresses. Staining: auxiliary technique used in microscopy to highlight structures in materials. For biological tissues, it involves the use of structure-specific dyes. Nomenclature: not needed

International audience; Purpose. It has been reported clinically that rupture or dissections in thoracic aortic aneurysms (TAA) often occur due to hypertension which may be modelled with sudden increase of peripheral resistance, inducing acute changes of blood volumes in the aorta. There is clinical evidence that more compliant aneurysms are less prone to rupture as they can sustain such changes of volume. The aim of the current paper is to verify this paradigm by evaluating computationally the role played by the variation of peripheral resistance and the impact of aortic stiffness onto peak wall stress in ascending TAA. Methods. Fluid-Structure Interaction (FSI) analyses were performed using patient-specific geometries and boundary conditions derived from 4D MRI datasets acquired on a patient. Blood was assumed incompressible and was treated as a non-Newtonian fluid using the Carreau model while the wall mechanical properties were obtained from the bulge inflation tests carried out in vitro after surgical repair. The Navier Stokes equations were solved in ANSYS Fluent. The Arbitrary Lagrangian Eulerian formulation was used to account for the wall deformations. At the interface between the solid domain and the fluid domain, the fluid pressure was transferred to the wall and the displacement of the wall was transferred to the fluid. The two systems were connected by the System Coupling component which controls the solver execution of fluid and solid simulations in ANSYS. Fluid and solid domains were solved sequentially starting from the fluid simulations. Results. Distributions of blood flow, wall shear stress and wall stress were evaluated in the ascending thoracic aorta using the FSI analyses. We always observed a significant flow eccentricity in the simulations, in very good agreement with velocity profiles measured using 4D MRI. The results also showed significant increase of peak wall stress due to the increase of peripheral resistance and aortic stiffness. In the worst case scenario, the largest peripheral resistance (10 10 kg.s.m-4) and stiffness (10 MPa) resulted in a maximal principal stress equal to 702 kPa, whereas it was only 77 kPa in normal conditions. Conclusions. This is the first time that the risk of rupture of an aTAA is quantified in case of the combined effects of hypertension and aortic stiffness increase. Our findings suggest that a stiffer TAA may have the most altered distribution of wall stress and an acute change of peripheral vascular resistance could significantly increase the risk of rupture for a stiffer aneurysm.

The Ross procedure is a surgical procedure where a diseased aortic valve is replaced by the person's own pulmonary valve. The proximal segment of the pulmonary artery is thereby placed in aortic position and therefore suddenly exposed to a sevenfold increase in blood pressure. Excessive dilatation of this pulmonary autograft is a common complication and has excited interest about mechanobiological adaptation in such situations. Mathematical modelling of growth and remodelling is a relevant approach to improve insights into this phenomenon. We introduced an algorithm that models the continuous degradation and deposition of extracellular matrix in an artery according to the constrained mixture theory. To compute temporal variations of collagen and elastin mass and to deduce related mechanical properties of the remodelled artery, we discretized time and defined a finite number of cohorts for each collagen fiber family. The degradation and production rates of each cohort were mediated by the difference between ambient and homeostatic stress within each fiber cohort. We applied the algorithm to predict the adaptation of a pulmonary autograft over an extended period and compared the results to experimental data obtained in sheep. We were able to consistently reproduce the experimentally observed remodeling effects such as dilatation and delayed collagen fiber recruitment. Our simulations revealed how elastin takes up the excessive stress in overstretched regions of the tissue. In conclusion, the algorithm yields very promising results regarding autograft adaptation in overstretched conditions. Future work will focus on other situations of vascular adaptation where growth-related deformations will be considered. ispartof: ZAMM-Zeitschrift fur Angewandte Mathematik und Mechanik vol:98 issue:12 pages:2239-2257 status: published

Ascending thoracic aorta aneurysm (ATAA) is the 19th common cause of human deaths. Despite important recent progress to better understand the pathogenesis and the development of the disease, the ro...

International audience; Endovascular repair of abdominal aortic aneurysms faces some adverse outcomes, such as kinks or endoleaks related to incomplete stent apposition, which are difficult to predict and which restrain its use although it is less invasive than open surgery. Finite element simulations could help to predict and anticipate possible complications biomechanically induced, thus enhancing practitioners' stent-graft sizing and surgery planning, and giving indications on patient eligibility to endovascular repair. The purpose of this work is therefore to develop a new numerical methodology to predict stent-graft final deployed shapes after surgery. The simulation process was applied on three clinical cases, using preoperative scans to generate patient-specific vessel models. The marketed devices deployed during the surgery, consisting of a main body and one or more iliac limbs or extensions, were modeled and their deployment inside the corresponding patient aneurysm was simulated. The numerical results were compared to the actual deployed geometry of the stent-grafts after surgery that was extracted from postoperative scans. We observed relevant matching between simulated and actual deployed stent-graft geometries, especially for proximal and distal stents outside the aneurysm sac which are particularly important for practitioners. Stent locations along the vessel centerlines in the three simulations were always within a few millimeters to actual stents locations. This good agreement between numerical results and clinical cases makes finite element simulation very promising for preoperative planning of endovascular repair.

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; Biomechanics of the extracellular matrix in arteries determines their macroscopic mechanical behavior. In particular, the distribution of collagen fibers and bundles plays a significant role. Experimental data showed that in most arterial walls there are preferred fiber directions. However, the realignment of collagen fibers during tissue deformation is still controversial: whilst authors claim that fibers should undergo affine deformations, others showed the contrary. In order to have an insight about this important question of affine deformations at the microscopic scale, we measured the realignment of collagen fibers in the adven-titia layer of carotid arteries using multiphoton microscopy combined with an unprecedented Fourier based method. We compared the realignment for two types of macroscopic loading applied on arterial segments: axial tension under constant pressure (scenario 1) and inflation under constant axial length (scenario 2). Results showed that, although the tissue underwent macroscopic stretches beyond 1.5 in the circumferential direction, fiber directions remained unchanged during scenario 2 loading. Conversely, fibers strongly realigned along the axis direction for scenario 2 Witold Krasny 1,2,3,4 et al. 1 loading. In both cases, the motion of collagen fibers did not satisfy affine deformations , with a significant difference between both cases: affine predictions strongly underestimated fiber reorientations in uniaxial tension and overestimated fiber reorientations during inflation at constant length. Finally, we explained this specific kinematics of collagen fibers by the complex tension-compression interactions between very stiff collagen fibers and compliant surrounding proteins. A tenseg-rity representation of the extracellular matrix in the adventitia taking into account these interactions was proposed to model the motion of collagen fibers during tissue deformation.

Goal: Hexahedral automatic model generation is a recurrent problem in computer vision and computational biomechanics. It may even become a challenging problem when one wants to develop a patient-specific finite element (FE) model of the left ventricle (LV), particularly when only low resolution images are available. In the present study, a fast and efficient algorithm is presented and tested to address such a situation. Methods: A template FE hexahedral model was created for an LV geometry using a general electric ultrasound (US) system. A system of centerline was considered for this LV mesh. Then, the nodes located over the endocardial and epicardial surfaces are, respectively, projected from this centerline onto the actual endocardial and epicardial surfaces reconstructed from a patient's US data. Finally, the position of the internal nodes is derived by finding the deformations with minimal elastic energy. This approach was applied to eight patients suffering from congestive heart disease. An FE analysis was performed to derive the stress induced in the LV tissue by diastolic blood pressure on each of them. Results: Our model morphing algorithm was applied successfully and the obtained meshes showed only marginal mismatches when compared to the corresponding US geometries. The diastolic FE analyses were successfully performed in seven patients to derive the distribution of principal stresses. Conclusion: The original model morphing algorithm is fast and robust with low computational cost. Significance: This low-cost model morphing algorithm may be highly beneficial for future patient-specific reduced-order modeling of the LV with potential application to other crucial organs.