The normal healthy aortic valve (AoV) has three leaflets, two of which have outflows to the coronary arteries. Blood flow through the coronary ostia will have an impact on AoV dynamics and the surrounding haemodynamics, leading to differential shear stress distributions at the aortic side of the three leaflets. In addition, aortic root haemodynamics may also be influenced by the non-Newtonian behaviour of blood which is known as a shear-thinning fluid due to the aggregation of red blood cells at low shear rate. However, the combined effect of coronary and non-Newtonian flow on AoV haemodynamics has not been studied in an anatomically realistic setting. In this study, strongly coupled fluid–structure interaction (FSI) analyses were performed on a natural, healthy AoV, with and without accounting for coronary outflows and non-Newtonian properties of blood. Our results showed that the influence of coronary outflow is more pronounced than employing a non-Newtonian model, and their combined effect is non-negligible, particularly on wall shear stress. Incorporating coronary outflow and non-Newtonian properties increased time-averaged wall shear stress (TAWSS) in the aortic sinus by up to 108.45%; it also increased TAWSS on the aortic side of valve leaflets by 41.04%, 44.76%, and 54.91% on the left, right and non-coronary leaflet, respectively. These results highlight the importance of incorporating coronary outflow and non-Newtonian properties when accurate predictions of wall shear stress and its related parameters are critical.

Big mechanically-active culture systems (BigMACS) are promising to stimulate, control, and pattern cell and tissue behaviours with less soluble factor requirements. However, it remains challenging to predict if and how distributed mechanical forces impact single-cell behaviours to pattern tissue. In this study, we introduce a tissue-scale finite element analysis framework able to correlate sub-cellular quantitative histology with centimetre-scale biomechanics. Our framework is relevant to diverse BigMACS, including media perfusion, tensile-stress, magnetic, and pneumatic tissue culture platforms. We apply our framework to understand how the design and operation of a multi-axial soft robotic bioreactor can spatially control mesenchymal stem cell (MSC) proliferation, orientation, differentiation to smooth muscle, and extracellular vascular matrix deposition. We find MSC proliferation and matrix deposition to positively correlate with mechanical stimulation but cannot be locally patterned by soft robot mechanical stimulation within a centimetre scale tissue. In contrast, local stress distribution was able to locally pattern MSC orientation and differentiation to smooth muscle phenotypes, where MSCs aligned perpendicular to principal stress direction and expressed increased α-SMA with increasing 3D Von Mises Stresses from 0 to 15 kPa. Altogether, our new biomechanical-histological simulation framework is a promising technique to derive the future mechanical design equations to control cell behaviours and engineer patterned tissue.

This study aimed to characterize the altered hemodynamics and wall mechanics in ascending thoracic aortic aneurysms (ATAA) by employing fully coupled two-way fluid–structure interaction (FSI) analyses. Our FSI models incorporated hyperelastic wall mechanical properties, prestress, and patient-specific inlet velocity profiles (IVP) extracted from 4D flow magnetic resonance imaging (MRI). By performing FSI analyses on 7 patient-specific ATAA models and 6 healthy aortas, the primary objective of the study was to compare hemodynamic and biomechanical features in ATAA versus healthy controls. A secondary objective was to examine the need for 4D flow MRI-derived IVP in FSI simulations by comparing results with those using two commonly adopted idealized IVPs: Flat-IVP and Para-IVP for selected cases. Our results show that, compared to the healthy aortas, the ATAA models exhibited highly disturbed blood flow in the ascending aorta. Consequently, maximum turbulent kinetic energy (TKE) at peak systole (155.0 ± 188.4 Pa) and maximum time-averaged wall shear stress (TAWSS) (8.6 ± 6.5 Pa) were significantly higher in the ATAA cohort, compared to 0.6 ± 0.5 Pa and 2.8 ± 0.7 Pa in the healthy aortas. Peak wall stress was also nearly doubled in the ATAA group (414 ± 108 kPa vs. 215 ± 31 kPa). Additionally, comparisons of simulation results across models with different IVPs underscore the importance of prescribing 3D-IVP at the inlet, especially for ATAA cases. Using idealized IVPs in two selected ATAA models (P1 and P7) substantially reduced the maximum TKE from 571 Pa to 0.01 Pa (Flat-IVP) and 0.02 Pa (Para-IVP) in P1 and from 73 Pa to 0.01 Pa (Flat-IVP) and 0.08 Pa (Para-IVP) in P7, while the maximum TAWSS in the ascending aorta decreased from 9.6 Pa to 0.7 Pa (Flat-IVP) and 0.9 Pa (Para-IVP) in P1, and from 3.6 Pa to 1.2 Pa and 0.9 Pa, respectively, in P7. Moreover, idealized IVPs also caused the peak wall stress to reduce by up to 11.5% in P1 with severe aortic valve stenosis, and by up to 2% in P7 with mild aortic regurgitation. These results highlight the importance of FSI simulations combined with 4D flow MRI in capturing realistic hemodynamic and biomechanical changes in aneurysmal aortas.

Background: Intracranial artery calcification detected on CT imaging is a recognized risk factor for ischemic cerebrovascular diseases, but the underlying etiology of this association remains unclear. Differences in objective morphometric characteristics of these calcifications may partially explain this association, yet these measurements are largely absent in the literature. We investigated intracranial artery calcification morphometry in patients with recent anterior ischemic stroke or TIA, assessing potential differences between calcifications in both intracranial carotid arteries (ICAs) located ipsilateral and contralateral to the cerebral ischemia. Methods: Among 100 patients (mean age 69.6 (SD 8.8) years) presenting to academic neurology departments, 3D reconstructions of both ICAs were based on clinical CT-angiography images. On these reconstructions, a luminal centerline and cross-sections perpendicular to this centerline were created, facilitating the assessment of calcification morphometry, spatial orientation and stenosis severity. Differences in calcification characteristics between ICAs were assessed using two-sided Wilcoxon signed-rank and χ² tests. Results: Among 200 arteries, a median of four (IQR 2–6) individual calcifications were counted, with a mean area of 1.8 (IQR 1.2–2.7) mm², a mean arc width of 43.5 (IQR 32.3–53.2) degrees, and median longitudinal extent of 15.4 (IQR 5.9–27.0) mm. Calcifications were most often present in the anatomical C4 section (56.0%), with predominantly posterosuperior orientation (38.5%) and 42.0% had a local stenosis severity > 70%. None of these aspects significantly differed between ICAs, and this remained after restricting analyses to patients with undetermined etiology. Conclusions: We found no differences in morphometrical or spatial aspects of calcifications between ICAs ipsilateral and contralateral to the cerebral ischemia.

Background: Bioprosthetic aortic valves (BPAV) have been increasingly used for surgical aortic valve replacement (SAVR), but long-term complications associated with structural valve deterioration remain a concern. The structural behaviour of the valve and its surrounding haemodynamics play a key role in the long-term outcome of SAVR, and these can be quantitively analysed by means of fluid-structure interaction (FSI) simulation. The aim of this study was to develop a fully coupled FSI model for patient-specific analysis of BPAV haemodynamics. Methods: Using the Edwards Magna Ease valve as an example, the workflow included reconstruction of the aortic root from CT images and the creation of valve geometric model based on available measurements made on the device. Two-way fully coupled FSI simulations were performed under patient-specific flow conditions derived from 4D flow magnetic resonance imaging (MRI), the latter also provided data for model validation. Results: The simulation results were in good agreement with haemodynamic features extracted from 4D flow MRI and relevant data in the literature. Furthermore, the FSI model provided additional information that cannot be measured in vivo, including wall shear stress and its derivatives on the valve leaflets and in the aortic root. Conclusion: The FSI workflow presented in this study offers a promising tool for patient-specific assessment of aortic valve haemodynamics, and the results may help elucidate the role of haemodynamics in structural valve deterioration.

The opening and closing dynamics of the aortic valve (AV) has a strong influence on haemodynamics in the aortic root, and both play a pivotal role in maintaining normal physiological functions of the valve. The aim of this study was to establish a subject-specific fluid–structure interaction (FSI) workflow capable of simulating the motion of a tricuspid healthy valve and the surrounding haemodynamics under physiologically realistic conditions. A subject-specific aortic root was reconstructed from magnetic resonance (MR) images acquired from a healthy volunteer, whilst the valve leaflets were built using a parametric model fitted to the subject-specific aortic root geometry. The material behaviour of the leaflets was described using the isotropic hyperelastic Ogden model, and subject-specific boundary conditions were derived from 4D-flow MR imaging (4D-MRI). Strongly coupled FSI simulations were performed using a finite volume-based boundary conforming method implemented in FlowVision. Our FSI model was able to simulate the opening and closing of the AV throughout the entire cardiac cycle. Comparisons of simulation results with 4D-MRI showed a good agreement in key haemodynamic parameters, with stroke volume differing by 7.5% and the maximum jet velocity differing by less than 1%. Detailed analysis of wall shear stress (WSS) on the leaflets revealed much higher WSS on the ventricular side than the aortic side and different spatial patterns amongst the three leaflets.

Aortic valve disease is often treated with bioprosthetic valves. An alternative treatment is aortic valve neocuspidization which is a relatively new reparative procedure whereby the three aortic cusps are replaced with patient pericardium or bovine tissues. Recent research indicates that aortic blood flow is disturbed, and turbulence effects have yet to be evaluated in either bioprosthetic or aortic valve neocuspidization valve types in patient-specific settings. The aim of this study is to better understand turbulence production in the aorta and evaluate its effects on laminar and turbulent wall shear stress. Four patients with aortic valve disease were treated with either bioprosthetic valves (n=2) or aortic valve neocuspidization valvular repair (n=2). Aortic geometries were segmented from magnetic resonance images (MRI), and 4D flow MRI was used to derive physiological inlet and outlet boundary conditions. Pulsatile large-eddy simulations were performed to capture the full range of laminar, transitional and turbulence characteristics in the aorta. Turbulence was produced in all aortas with highest levels occurring during systolic deceleration. In the ascending aorta, turbulence production is attributed to a combination of valvular skew, valvular eccentricity, and ascending aortic dilation. In the proximal descending thoracic aorta, turbulence production is dependent on the type of arch-descending aorta connection (e.g., a narrowing or sharp bend) which induces flow separation. Laminar and turbulent wall shear stresses are of similar magnitude throughout late systolic deceleration and diastole, although turbulent wall shear stress magnitudes exceed laminar wall shear stresses between 27.3% and 61.1% of the cardiac cycle. This emphasises the significance of including turbulent wall shear stress to improve our comprehension of progressive arterial wall diseases. The findings of this study recommend that aortic valve treatments should prioritise minimising valvular eccentricity and skew in order to mitigate turbulence generation.

Purpose: Finite element analysis (FEA) has been used to predict wall stress in ascending thoracic aortic aneurysm (ATAA) in order to evaluate risk of dissection or rupture. Patient-specific FEA requires detailed information on ATAA geometry, loading conditions, material properties, and wall thickness. Unfortunately, measuring aortic wall thickness and mechanical properties non-invasively poses a significant challenge, necessitating the use of non-patient-specific data in most FE simulations. This study aimed to assess the impact of employing non-patient-specific material properties and wall thickness on ATAA wall stress predictions. Methods: FE simulations were performed on 13 ATAA geometries reconstructed from computed tomography angiography (CTA) images. Patient-specific material properties and wall thicknesses were made available from a previous study where uniaxial tensile testing was performed on tissue samples obtained from the same patients. The ATAA wall models were discretised with hexahedral elements and prestressed. For each ATAA model, FE simulations were conducted using patient-specific material properties and wall thicknesses, and group-mean values derived from all tissue samples included in the same experimental study. Literature-based material property and wall thickness were also obtained from the literature and applied to 4 representative cases. Additional FE simulations were performed on these 4 cases by employing group-mean and literature-based wall thicknesses. Results: FE simulations using the group-mean material property produced peak wall stresses comparable to those obtained using patient-specific material properties, with a mean deviation of 7.8%. Peak wall stresses differed by 20.8% and 18.7% in patients with exceptionally stiff or compliant walls, respectively. Comparison to results using literature-based material properties revealed larger discrepancies, ranging from 5.4% to 28.0% (mean 20.1%). Bland-Altman analysis showed significant discrepancies in areas of high wall stress, where wall stress obtained using patient-specific and literature-based properties differed by up to 674 kPa, compared to 227 kPa between patient-specific and group-mean properties. Regarding wall thickness, using the literature-based value resulted in even larger discrepancies in predicted peak stress, ranging from 24.2% to 30.0% (mean 27.3%). Again, using the group-mean wall thickness offered better predictions with a difference less than 5% in three out of four cases. While peak wall stresses were most affected by the choice of mechanical properties or wall thickness, the overall distribution of wall stress hardly changed. Conclusions: Our study demonstrated the importance of incorporating patient-specific material properties and wall thickness in FEA for risk prediction of aortic dissection or rupture. Our future efforts will focus on developing inverse methods for non-invasive determination of patient-specific wall material parameters and wall thickness.

OBJECTIVES: Aortic valve neocuspidalization aims to replace the 3 aortic cusps with autologous pericardium pre-treated with glutaraldehyde, and it is a surgical alternative to the classical aortic valve replacement (AVR). Image-based patient-specific computational fluid dynamics allows the derivation of shear stress on the aortic wall [wall shear stress (WSS)]. Previous studies support a potential link between increased WSS and histological alterations of the aortic wall. The aim of this study is to compare the WSS of the ascending aorta in patients undergoing aortic valve neocuspidalization versus AVR with biological prostheses. METHODS: This is a prospective nonrandomized clinical trial. Each patient underwent a 4D-flow cardiac magnetic resonance scan after surgery, which informed patient-specific computational fluid dynamics models to evaluate WSS at the ascending aortic wall. The adjusted variables were calculated by summing the residuals obtained from a multivariate linear model (with ejection fraction and left ventricle outflow tract-aorta angle as covariates) to the mean of the variables. RESULTS: Ten patients treated with aortic valve neocuspidalization were enrolled and compared with 10 AVR patients. The aortic valve neocuspidalization group showed a significantly lower WSS in the outer curvature segments of the proximal and distal ascending aorta as compared to AVR patients (P = 0.0179 and 0.0412, respectively). WSS levels remained significantly lower along the outer curvature of the proximal aorta in the aortic valve neocuspidalization population, even after adjusting the WSS for the ejection fraction and the left ventricle outflow tract-aorta angle [2.44 Pa (2.17-3.01) vs 1.94 Pa (1.72-2.01), P = 0.02]. CONCLUSIONS: Aortic valve neocuspidalization hemodynamical features are potentially associated with a lower WSS in the ascending aorta as compared to commercially available bioprosthetic valves.

Introduction: Thoracic endovascular aortic repair (TEVAR) of the arch is challenging given its complex geometry and the involvement of supra-aortic arteries. Different branched endografts have been designed for use in this region, but their haemodynamic performance and the risk for post-intervention complications are not yet clear. This study aims to examine aortic haemodynamics and biomechanical conditions following TVAR treatment of an aortic arch aneurysm with a two-component single-branched endograft. Methods: Computational fluid dynamics and finite element analysis were applied to a patient-specific case at different stages: pre-intervention, post-intervention and follow-up. Physiologically accurate boundary conditions were used based on available clinical information. Results: Computational results obtained from the post-intervention model confirmed technical success of the procedure in restoring normal flow to the arch. Simulations of the follow-up model, where boundary conditions were modified to reflect change in supra-aortic vessel perfusion observed on the follow-up scan, predicted normal flow patterns but high levels of wall stress (up to 1.3M MPa) and increased displacement forces in regions at risk of compromising device stability. This might have contributed to the suspected endoleaks or device migration identified at the final follow up. Discussion: Our study demonstrated that detailed haemodynamic and biomechanical analysis can help identify possible causes for post-TEVAR complications in a patient-specific setting. Further refinement and validation of the computational workflow will allow personalised assessment to aid in surgical planning and clinical decision making.

Background and Objective: Numerical simulations of blood flow are a valuable tool to investigate the pathophysiology of ascending thoratic aortic aneurysms (ATAA). To accurately reproduce in vivo hemodynamics, computational fluid dynamics (CFD) models must employ realistic inflow boundary conditions (BCs). However, the limited availability of in vivo velocity measurements, still makes researchers resort to idealized BCs. The aim of this study was to generate and thoroughly characterize a large dataset of synthetic 4D aortic velocity profiles sampled on a 2D cross-section along the ascending aorta with features similar to clinical cohorts of patients with ATAA. Methods: Time-resolved 3D phase contrast magnetic resonance (4D flow MRI) scans of 30 subjects with ATAA were processed through in-house code to extract anatomically consistent cross-sectional planes along the ascending aorta, ensuring spatial alignment among all planes and interpolating all velocity fields to a reference configuration. Velocity profiles of the clinical cohort were extensively characterized by computing flow morphology descriptors of both spatial and temporal features. By exploiting principal component analysis (PCA), a statistical shape model (SSM) of 4D aortic velocity profiles was built and a dataset of 437 synthetic cases with realistic properties was generated. Results: Comparison between clinical and synthetic datasets showed that the synthetic data presented similar characteristics as the clinical population in terms of key morphological parameters. The average velocity profile qualitatively resembled a parabolic-shaped profile, but was quantitatively characterized by more complex flow patterns which an idealized profile would not replicate. Statistically significant correlations were found between PCA principal modes of variation and flow descriptors. Conclusions: We built a data-driven generative model of 4D aortic inlet velocity profiles, suitable to be used in computational studies of blood flow. The proposed software system also allows to map any of the generated velocity profiles to the inlet plane of any virtual subject given its coordinate set.

Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction results as a numerical model and physical prototype. This numerical one-way and two-way fluid-structure interaction study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms via direct pressurisation and ring tensile testing. Phantoms within a compliance range of 1.4–68.0%/100 mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with moderately statistically significant differences in measured compliance ranging between 10 and 20% for the two methods. One-way fluid-structure interaction coupling underestimated arterial wall compliance by up to 14.7% compared with two-way coupled models. Overall, Solaris™ (Smooth-On) matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.