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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. [ABSTRACT FROM AUTHOR]

Computational hemodynamics has become increasingly important within the context of precision medicine, providing major insight in cardiovascular pathologies. However, finding appropriate compromise between speed and accuracy remains challenging in computational hemodynamics for an extensive use in decision making. For example, in the ascending thoracic aorta, interactions between the blood and the aortic wall must be taken into account for the sake of accuracy, but these fluid structure interactions (FSI) induce significant computational costs, especially when the tissue exhibits a hyperelastic and anisotropic response. The objective of the current study is to use the Small On Large (SOL) theory to linearize the anisotropic hyperelastic behavior in order to propose a reduced-order model for FSI simulations of the aorta. The SOL method is tested for fully-coupled FSI simulations in a patient-specific aortic geometry presenting an Ascending Thoracic Aortic Aneurysm (aTAA). The same model is also simulated with a fully-coupled FSI with non-linear material behavior, without SOL linearization. Eventually, the results and computational times with and without the SOL are compared. The SOL approach is demonstrated to provide a significant reduction of computational costs for FSI analysis in the aTAA, and the results in terms of stress state distribution are comparable. The method is implemented in ANSYS and will be further evaluated for clinical applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In its permanent quest of mechanobiological homeostasis, our vasculature significantly adapts across multiple length and timescales in various physiological and pathological conditions. Computational modeling of vascular growth and remodeling (G&R) has significantly improved our insights into the mechanobiological 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. 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 bilayer 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 in 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although hundreds of samples obtained from ascending thoracic aortic aneurysms (ATAA) of patients undergoing elective surgical repair have already been characterized biomechanically, their rupture properties were always derived from uniaxial tensile tests. Due to their bulge shape, ATAAs are stretched biaxially in vivo. In order to understand the biaxial rupture of ATAAs, our group developed a novel methodology based on bulge inflation and full-field optical measurements. The objective of the current paper is threefold. Firstly, we will review the failure properties (maximum stress, maximum stretch) obtained by bulge inflation testing on a cohort of 31 patients and compare them with failure properties obtained by uniaxial tension in a previously published study. Secondly, we will investigate the relationship between the failure properties and the age of patients, showing that patients below 55 years of age display significantly higher strength. Thirdly, we will define a rupture risk based on the extensibility of the tissue and we will show that this rupture risk is strongly correlated with the physiological elastic modulus of the tissue independently of the age, ATAA diameter or the aortic valve phenotype of the patient. Statement of Significance Despite their medical importance, rupture properties of ascending thoracic aortic aneurysms (ATAA) subjected to biaxial tension were inexistent in the literature. In order to address this lack, our group developed a novel methodology based on bulge inflation and full-field optical measurements. Here we report rupture properties obtained with this methodology on 31 patients. It is shown for the first time that rupture occurs when the stretch applied to ATAAs reaches the maximum extensibility of the tissue and that this maximum extensibility correlates strongly with the elastic properties. The outcome is a better detection of at-risk individuals for elective surgical repair. [ABSTRACT FROM AUTHOR]

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. Statement of Significance 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. [ABSTRACT FROM AUTHOR]

Ascending thoracic aortic aneurysms (ATAAs) are focal, asymmetric dilatations of the aortic wall which are prone to rupture. To identify potential rupture locations in advance, it is necessary to consider the inhomogeneity of the ATAA at the millimeter scale. Towards this end, we have developed a combined experimental and computational approach using bulge inflation tests, digital image correlation (DIC), and an inverse membrane approach to characterize the pointwise stress, strain, and hyperelastic properties of the ATAA. Using this approach, the pointwise hyperelastic material properties were identified on 10 human ATAA samples collected from patients undergoing elective surgery to replace their ATAAs with a graft. Our method was able to capture the varying levels of heterogeneity in the ATAA from regional to local. It was shown for the first time that the material properties in the ATAA are unmistakably heterogeneous at length scales between 1 mm and 1 cm, which are length scales where vascular tissue is typically treated as homogeneous. The distributions of the material properties for each patient were also examined to study the inter- and intra-patient variability. Large inter-subject variability was observed in the elastic properties. [ABSTRACT FROM AUTHOR]

In this manuscript, we present a combined experimental and computational technique that can identify the heterogeneous elastic properties of planar soft tissues. By combining inverse membrane analysis, digital image correlation, and bulge inflation tests, we are able to identify a tissue's mechanical properties locally. To show how the proposed method could be implemented, we quantified the heterogeneous material properties of a human ascending thoracic aortic aneurysm (ATAA). The ATAA was inflated at a constant rate using a bulge inflation device until it ruptured. Every 3 kPa images were taken using a stereo digital image correlation system. From the images, the three-dimensional displacement of the sample surface was determined. A deforming NURBS mesh was derived from the displacement data, and the local strains were computed. The wall stresses at each pressure increment were determined using inverse membrane analysis. The local material properties of the ATAA were then identified using the pointwise stress and strain data. To show that it is necessary to consider the heterogeneous distribution of the mechanical properties in the ATAA, three different forward finite element simulations using pointwise, elementwise, and homogeneous material properties were compared. The forward finite element predictions revealed that heterogeneous nature of the ATAA must be accounted for to accurately reproduce the stress-strain response. [ABSTRACT FROM AUTHOR]

Keywords: Ascending thoracic aortic aneurysm; CFD; 4D MRI; risk of rupture; rupture stretch; TAWSS EN Ascending thoracic aortic aneurysm CFD 4D MRI risk of rupture rupture stretch TAWSS S58 S59 2 01/29/21 20191002 NES 191002 1. Ascending thoracic aortic aneurysm, CFD, 4D MRI, risk of rupture, rupture stretch, TAWSS. [Extracted from the article]

• Spatiotemporal hemodynamic heterogeneity was quantified in ATAA and healthy aortas. • Intravascular flow spatiotemporal heterogeneity influences the WSS topological skeleton. • Peculiar WSS topological skeleton features are linked to local ATAA wall stiffness. • The topological shear variation index is an indicator of local aortic wall degradation. • WSS topological skeleton and complex networks deeper explain the hemodynamics disruption in ATAA. 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. [ABSTRACT FROM AUTHOR]

Abstract 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 (h 2), the circumferential time averaged wall shear stress (TAWSS circumferential), 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 TAWSS circumferential 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, Flow eccentricity and PWV were found higher in Stage II due to the diameter reduction (Flow eccentricity = 0.60 in Stage I and Flow eccentricity = 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. [ABSTRACT FROM AUTHOR]

Highlights • In this manuscript we establish the first computational framework coupling patient-specific hemodynamics simulations in ascending thoracic aortic aneurysms with a computational mechanobiological model and simulate aneurysm progression for 4 subjects. • We determine computationally the conditions for aneurysm progression. The model shows that the rate of collagen production or cell mechano-sensitivity play the most critical roles. • Our patient-specific computational modeling coupling hemodynamics with mechanobiology is a promising approach to explore ATAA initiation and progression. Background and Objective. The prevention of ascending thoracic aortic aneurysms (ATAAs), which affect thousands of persons every year worldwide, remains a major issue. ATAAs may be caused by anything that weakens the aortic wall. Altered hemodynamics, which concerns a majority of patients with bicuspid aortic valves, has been shown to be related to such weakening and to contribute to ATAA development and progression. However the underlying mechanisms remain unclear and computational modeling in this field could help significantly to elucidate how hemodynamics and mechanobiology interact in ATAAs. Methods. Accordingly, we propose a numerical framework combining computational fluid dynamics and 4D flow magnetic resonance imaging (MRI) coupled with finite element (FE) analyses to simulate growth and remodeling (G&R) occurring in patient-specific aortas in relation with altered hemodynamics. The geometries and the blood velocities obtained from 4D flow MRI are used as boundary conditions for CFD simulations. CFD simulations provide an estimation of the wall shear stress (WSS) and relative residence time (RRT) distribution across the luminal surface of the wall. An initial insult is then applied to the FE model of the aortic wall, assuming that the magnitude of the insult correlates spatially with the normalized RRT distribution obtained from CFD simulations. G&R simulations are then performed. The material behavior of each Gauss point in these FE models is evolved continuously to compensate for the deviation of the actual wall stress distribution from the homeostatic state after the initial insult. The whole approach is illustrated on two healthy and two diseased subjects. The G&R parameters are calibrated against previously established statistical models of ATAA growth rates. Results. Among the variety of results provided by G&R simulations, the analysis focused especially on the evolution of the wall stiffness, which was shown to be a major risk factor for ATAAs. It was shown that the G&R parameters, such as for instance the rate of collagen production or cell mechanosensitivity, play a critical role in ATAA progression and remodeling. Conclusions. These preliminary findings show that patient-specific computational modeling coupling hemodynamics with mechanobiology is a promising approach to explore aneurysm progression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]