Evolving Mural Defects, Dilatation, and Biomechanical Dysfunction in Angiotensin II-Induced Thoracic Aortopathies.

BACKGROUND: Thoracic aortopathy associates with extracellular matrix remodeling and altered biomechanical properties. We sought to quantify the natural history of thoracic aortopathy in a common mouse model and to correlate measures of wall remodeling such as aortic dilatation or localized mural defects with evolving microstructural composition and biomechanical properties of the wall. METHODS: We combined a high-resolution multimodality imaging approach (panoramic digital image correlation and optical coherence tomography) with histopathologic examinations and biaxial mechanical testing to correlate spatially, for the first time, macroscopic mural defects and medial degeneration within the ascending aorta with local changes in aortic wall composition and mechanical properties. RESULTS: Findings revealed strong correlations between local decreases in elastic energy storage and increases in circumferential material stiffness with increasing proximal aortic diameter and especially mural defect size. Mural defects tended to exhibit a pronounced biomechanical dysfunction that is driven by an altered organization of collagen and elastic fibers. CONCLUSIONS: While aneurysmal dilatation is often observed within particular segments of the aorta, dissection and rupture initiate as highly localized mechanical failures. We show that wall composition and material properties are compromised in regions of local mural defects, which further increases the dilatation and overall structural vulnerability of the wall. Identification of therapies focused on promoting robust collagen accumulation may protect the wall from these vulnerabilities and limit the incidence of dissection and rupture.

Stress Analysis in AAA does not Predict Rupture Location Correctly in Patients with Intraluminal Thrombus.

BACKGROUND: A biomechanical approach to the rupture risk of an abdominal aortic aneurysm could be a solution to ensure a personalized estimate of this risk. It is still difficult to know in what conditions, the assumptions made by biomechanics, are valid. The objective of this work was to determine the individual biomechanical rupture threshold and to assess the correlation between their rupture sites and the locations of their maximum stress comparing two computed tomography scan (CT) before and at time of rupture. METHODS: We included 5 patients who had undergone two CT; one within the last 6 months period before rupture and a second CT scan just before the surgical procedure for the rupture. All DICOM data, both pre- and rupture, were processed following the same following steps: generation of a 3D geometry of the abdominal aortic aneurysm, meshing and computational stress analysis using the finite element method. We used two different modelling scenarios to study the distribution of the stresses, a "wall" model without intraluminal thrombus (ILT) and a "thrombus" model with ILT. RESULTS: The average time between the pre-rupture and rupture CT scans was 44 days (22-97). The median of the maximum stresses applied to the wall between the pre-rupture and rupture states were 0.817 MPa (0.555-1.295) and 1.160 MPa (0.633-1.625) for the "wall" model; and 0.365 MPa (0.291-0.753) and 0.390 MPa (0.343-0.819) for the "thrombus" model. There was an agreement between the site of rupture and the location of maximum stress for only 1 patient, who was the only patient without ILT. CONCLUSIONS: We observed a large variability of stress values at rupture sites between patients. The rupture threshold strongly varied between individuals depending on the intraluminal thrombus. The site of rupture did not correlate with the maximum stress except for 1 patient.

Atomic Force Microscopy Stiffness Mapping in Human Aortic Smooth Muscle Cells.

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.

Material Identification on Thin Shells Using the Virtual Fields Method, Demonstrated on the Human Eardrum.

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.

Design, Development, and Temporal Evaluation of a Magnetic Resonance Imaging-Compatible In Vitro Circulation Model Using a Compliant Abdominal Aortic Aneurysm Phantom.

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.

Patient Specific Computer Modelling for Automated Sizing of Fenestrated Stent Grafts.

OBJECTIVE: The aim was to validate a computational patient specific model of Zenith® fenestrated device deployment in abdominal aortic aneurysms to predict fenestration positions. METHODS: This was a retrospective analysis of the accuracy of numerical simulation for fenestrated stent graft sizing. Finite element computational simulation was performed in 51 consecutive patients that underwent successful endovascular repair with Zenith® fenestrated stent grafts in two vascular surgery units with a high volume of aortic procedures. Longitudinal and rotational clock positions of fenestrations were measured on the simulated models. These measurements were compared with those obtained by (i) an independent observer on the post-operative computed tomography (CT) scan and (ii) by the stent graft manufacturer planning team on the pre-operative CT scan. (iii) Pre- and post-operative positions were also compared. Longitudinal distance and clock face discrepancies >3 mm and 15°, respectively, were considered significant. Reproducibility was assessed using Bland-Altman and linear regression analysis. RESULTS: A total of 195 target arteries were analysed. Both Bland-Altman and linear regression showed good reproducibility between the three measurement techniques performed. The median absolute difference between the simulation and post-operative CT scan was 1.0 ± 1.1 mm for longitudinal distance measurements and 6.9 ± 6.1° for clock positions. The median absolute difference between the planning centre and post-operative CT scan was 0.8 ± 0.8 mm for longitudinal distance measurements and 5.1 ± 5.0° for clock positions. Finally, the median absolute difference between the simulation and the planning centre was 0.96 ± 0.97 mm for longitudinal distance measurements and 4.8 ± 3.6° for clock positions. CONCLUSION: The numerical model of deployed fenestrated stent grafts is accurate for planning position of fenestrations. It has been validated in 51 patients, for whom fenestration locations were similar to the sizing performed by physicians and the planning centre.

Structural intensity assessment on shells via a finite element approximation.

Structural intensity on plates or shells can provide insights on how the vibrational energy is transmitted throughout a sample. Its assessment via experimental deflections are widely documented in the case of plates, which just requires the computation of spatial derivatives of out-of-plane displacements or velocities and a knowledge of the sample's material properties. However, if the structural intensity is to be assessed on arbitrary shells, a more elaborate data processing is required. The in-plane displacements become relevant terms and the spatial derivatives along a predefined local coordinate system need to be computed. Here, a method from which experimental data is interpolated on a finite element mesh is proposed. First, the global displacements and shape of a sample's outer-surface are measured. These data are then projected on a quadratic mesh, where the Kirchhoff plate theory is invoked for the individual elements. The data differentiation is computed via quadratic shape functions, from which the strains and structural intensity are estimated. Through the obtained vibrational energy results on the basis of measured displacement and shape data and by validating the method via a numerical simulation, the proposed work has shown to be a reliable tool to assess energy transmission on irregular shells.

Novel Methodology for Characterizing Regional Variations in the Material Properties of Murine Aortas.

Many vascular disorders, including aortic aneurysms and dissections, are characterized by localized changes in wall composition and structure. Notwithstanding the importance of histopathologic changes that occur at the microstructural level, macroscopic manifestations ultimately dictate the mechanical functionality and structural integrity of the aortic wall. Understanding structure-function relationships locally is thus critical for gaining increased insight into conditions that render a vessel susceptible to disease or failure. Given the scarcity of human data, mouse models are increasingly useful in this regard. In this paper, we present a novel inverse characterization of regional, nonlinear, anisotropic properties of the murine aorta. Full-field biaxial data are collected using a panoramic-digital image correlation (p-DIC) system. An inverse method, based on the principle of virtual power (PVP), is used to estimate values of material parameters regionally for a microstructurally motivated constitutive relation. We validate our experimental-computational approach by comparing results to those from standard biaxial testing. The results for the nondiseased suprarenal abdominal aorta from apolipoprotein-E null mice reveal material heterogeneities, with significant differences between dorsal and ventral as well as between proximal and distal locations, which may arise in part due to differential perivascular support and localized branches. Overall results were validated for both a membrane and a thick-wall model that delineated medial and adventitial properties. Whereas full-field characterization can be useful in the study of normal arteries, we submit that it will be particularly useful for studying complex lesions such as aneurysms, which can now be pursued with confidence given the present validation.

Integration of cross-links, discrete fiber distributions and of a non-local theory in the Homogenized Constrained Mixture Model to Simulate Patient-Specific Thoracic Aortic Aneurysm Progression.

Thoracic aortic aneurysms (TAA) represent a critical health issue for which computational models can significantly contribute to better understand the physiopathology. Among different computational frameworks, the Homogenized Constrained Mixture Theory has shown to be a computationally efficient option, allowing the inclusion of several mechanically significant constituents into a layer-specific mixture. Different patient-specific Growth and Remodeling (G&R) models correctly predicted TAA progression, although simplifications such as the inclusion of a limited number of collagen fibers and imposed boundary conditions might limit extensive analyses. The current study aims to enhance existing models by incorporating several discrete collagen fibers and to remove restrictive boundary conditions of the previous models. The implementation of discretized fiber dispersion presents a more realistic description of the vessel, while the removal of boundary conditions was addressed by including cross-links in the model to provide a supplemental stiffness against through-thickness shearing, a feature that was previously absent, and by the development of a non-local framework that ensures the stable deposition and degradation of collagen fibers. With these improvements, the current model represents a step forward towards more robust and comprehensive simulations of TAA growth.

3D growth and remodeling theory supports the hypothesis of staphyloma formation from local scleral weakening under normal intraocular pressure.

The purpose of this study was to assess whether growth and remodeling (G&R) theory could explain staphyloma formation from a local scleral weakening-as could occur from age-related elastin degradation, myopia progression, or other factors. A finite element model of a healthy eye was reconstructed, including the lamina cribrosa, the peripapillary sclera, and the peripheral sclera. The homogenized constrained mixture model was employed to simulate the adaptation of the sclera to alterations in its biomechanical environment over a duration of 13.7 years. G&R processes were triggered by reducing the shear stiffness of the ground matrix in the peripapillary sclera and lamina cribrosa by 85%. Three distinct G&R scenarios were investigated: (1) low mass turnover rate in combination with transmural volumetric growth; (2) high mass turnover rate in combination with transmural volumetric growth; and (3) high mass turnover rate in combination with mass density growth. In scenario 1, we observed a significant outpouching of the posterior pole, closely resembling the shape of a Type-III staphyloma. Additionally, we found a notable change in scleral curvature and a thinning of the peripapillary sclera by 84%. In contrast, scenario 2 and 3 exhibited less drastic deformations, with stable posterior staphylomas after approximately 7 years. Our proposed framework suggests that local scleral weakening is sufficient to trigger staphyloma formation under a normal level of intraocular pressure. Our model also reproduced characteristics of Type-III staphylomas. With patient-specific scleral geometries (as could be obtained with wide-field optical coherence tomography), our framework could be clinically translated to help us identify those at risks of developing posterior staphylomas.

A data-driven computational methodology towards a pre-hospital Acute Ischaemic Stroke screening tool using haemodynamics waveforms.

BACKGROUND AND OBJECTIVE: Acute Ischaemic Stroke (AIS), a significant global health concern, results from occlusions in cerebral arteries, causing irreversible brain damage. Different type of treatments exist depending on the size and location of the occlusion. Challenges persist in achieving faster diagnosis and treatment, which needs to happen in the first hours after the onset of symptoms to maximize the chances of patient recovery. The current diagnostic pipeline, i.e. "drip and ship", involves diagnostic via advanced imaging tools, only available in large clinical facilities, which poses important delays. This study investigates the feasibility of developing a machine learning model to diagnose and locate occluding blood clots from velocity waveforms, which can be easily be obtained with portable devices such as Doppler Ultrasound. The goal is to explore this approach as a cost-effective and time-efficient alternative to advanced imaging techniques typically available only in large hospitals. METHODS: Simulated haemodynamic data is used to conduct blood flow simulations representing healthy and different AIS scenarios using a population-based database. A Machine Learning classification model is trained to solve the inverse problem, this is, detect and locate a potentially occluding thrombus from measured waveforms. The classification process involves two steps. First, the region where the thrombus is located is classified into nine groups, including healthy, left or right large vessel occlusion, left or right anterior cerebral artery, and left or right posterior cerebral artery. In a second step, the bifurcation generation of the thrombus location is classified as small, medium, or large vessel occlusion. RESULTS: The proposed methodology is evaluated for data without noise, achieving a true prediction rate exceeding 95% for both classification steps mentioned above. The inclusion of up to 20% noise reduces the true prediction rate to 80% for region detection and 70% for bifurcation generation detection. CONCLUSIONS: This study demonstrates the potential effectiveness and efficiency of using haemodynamic data and machine learning to detect and locate occluding thrombi in AIS patients. Although the geometric and topological data used in this study are idealized, the results suggest that this approach could be applicable in real-world situations with appropriate adjustments. Source code is available in https://github.com/ahmetsenemse/Acute-Ischaemic-Stroke-screening-tool-.

Experimental validation of auxetic stent designs: three-point bending of 3D printed Titanium prototypes.

Introduction: Numerical simulations have demonstrated the superior bending flexibility of auxetic stents compared to conventional stent designs for endovascular procedures. However, conventional stent manufacturing techniques struggle to produce complex auxetic stent designs, fueling the adoption of additive manufacturing techniques. Methods: In this study, we employed DMLS additive manufacturing to create Titanium Ti64 alloy stent prototypes based on auxetic stent designs investigated in a previous study. These prototypes were then subjected to experimental three-point bending tests. Result: The experimental results were replicated using a finite element model, which showed remarkable accuracy in predicting the bending flexibility of four auxetic stents and two conventional stents. Discussion: Although this validation study demonstrates the promising potential of DMLS and other additive manufacturing methods for fabricating auxetic stents, further optimization of current stent design limitations and the incorporation of post-processing techniques are essential to enhance the reliability of these additive manufacturing processes.

Computational Comparison of the Mechanical Behavior of Aortic Stent-Grafts Derived from Auxetic Unit Cells.

PURPOSE: Inappropriate stent-graft (SG) flexibility has been frequently associated with endovascular aortic repair (EVAR) complications such as endoleaks, kinks, and SG migration, especially in tortuous arteries. Stents derived from auxetic unit cells have shown some potential to address these issues as they offer an optimum trade-off between radial stiffness and bending flexibility. METHODS: In this study, we utilized an established finite element (FE)-based approach to replicate the mechanical response of a SG iliac limb derived from auxetic unit cells in a virtual tortuous iliac aneurysm using a combination of a 180° U-bend and intraluminal pressurization. This study aimed to compare the mechanical performance (flexibility and durability) of SG limbs derived from auxetic unit cells and two commercial SG limbs (Z-stented SG and circular-stented SG models) in a virtual tortuous iliac aneurysm. Maximal graft strain and maximum stress in stents were employed as criteria to estimate the durability of SGs, whereas the maximal luminal reduction rate and the bending stiffness were used to assess the flexibility of the SGs. RESULTS: SG limbs derived from auxetic unit cells demonstrated low luminal reduction (range 4-12%) with no kink, in contrast to Z-stented SG, which had a kink in its central area alongside a high luminal reduction (44%). CONCLUSIONS: SG limbs derived from auxetic unit cells show great promise for EVAR applications even at high angulations such as 180°, with acceptable levels of durability and flexibility.

Ultrasound Probe Pressure Affects Aortic Wall Stiffness: A Patient-Specific Computational Study in Abdominal Aortic Aneurysms.

PURPOSE: Ultrasound imaging is key in the management of patients with an abdominal aortic aneurysm (AAA). It was recently shown that the cyclic diameter variations between diastole and systole, which can be quantified with US imaging, increase significantly with the strength of the applied probe pressure on the patient's abdomen. The goal of this study is to investigate this effect more thoroughly. METHODS: With finite-element modeling, pulsatile blood pressure and probe pressure are simulated in three patient-specific geometries. Two distinct models for the aortic wall were simulated: a nonlinear hyperelastic and a linear elastic model. In addition, varying stiffness was considered for the surrounding tissues. The effect of light, moderate, and firm probe pressure was quantified on the stresses and strains in the aortic wall, and on two in vivo stiffness measures. In addition, the Elasticity Loss Index was proposed to quantify the change in stiffness due to probe pressure. RESULTS: Firm probe pressure decreased the measured aortic stiffness, and material stiffness was affected only when the wall was modeled as nonlinear, suggesting a shift in the stress-strain curve. In addition, stiffer surrounding tissues and a more elongated aneurysm sac decreased the responsiveness to the probe pressure. CONCLUSION: The effect of probe pressure on the AAA wall stiffness was clarified. In particular, the AAA wall nonlinear behavior was found to be of primary importance in determining the probe pressure response. Thus, further work will intend to make use of this novel finding in a clinical context.

Experimental Protocols to Test Aortic Soft Tissues: A Systematic Review.

Experimental protocols are fundamental for quantifying the mechanical behaviour of soft tissue. These data are crucial for advancing the understanding of soft tissue mechanics, developing and calibrating constitutive models, and informing the development of more accurate and predictive computational simulations and artificial intelligence tools. This paper offers a comprehensive review of experimental tests conducted on soft aortic tissues, employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, based on the Scopus, Web of Science, IEEE, Google Scholar and PubMed databases. This study includes a detailed overview of the test method protocols, providing insights into practical methodologies, specimen preparation and full-field measurements. The review also briefly discusses the post-processing methods applied to extract material parameters from experimental data. In particular, the results are analysed and discussed providing representative domains of stress-strain curves for both uniaxial and biaxial tests on human aortic tissue.

Finite element analysis of the mechanical performances of 8 marketed aortic stent-grafts.

PURPOSE: To assess numerically the flexibility and mechanical stresses undergone by stents and fabric of currently manufactured stent-grafts. METHODS: Eight marketed stent-graft limbs (Aorfix, Anaconda, Endurant, Excluder, Talent, Zenith Flex, Zenith LP, and Zenith Spiral-Z) were modeled using finite element analysis. A numerical benchmark combining bending up to 180° and pressurization at 150 mmHg of the stent-grafts was performed. Stent-graft flexibility, assessed by the calculation of the luminal reduction rate, maximal stresses in stents, and maximal strains in fabric were assessed. RESULTS: The luminal reduction rate at 90° was <20% except for the Talent stent-graft. The rate at 180° was higher for Z-stented models (Talent, Endurant, Zenith, and Zenith LP; range 39%-78%) than spiral (Aorfix, Excluder, and Zenith Spiral-Z) or circular-stented (Anaconda) devices (range 14%-26%). At 180°, maximal stress was higher for Z-stented stent-grafts (range 370-622 MPa) than spiral or circular-stented endografts (range 177-368 MPa). At 90° and 180°, strains in fabric were low and did not differ significantly among the polyester stent-grafts (range 0.5%-7%), while the expanded polytetrafluoroethylene fabric of the Excluder stent-graft underwent higher strains (range 11%-18%). CONCLUSION: Stent design strongly influences mechanical performances of aortic stent-grafts. Spiral and circular stents provide greater flexibility, as well as lower stress values than Z-stents, and thus better durability.

Biomechanics of porcine renal arteries and role of axial stretch.

It is known that arteries experience significant axial stretches in vivo. Several authors have shown that the axial force needed to maintain an artery at its in vivo axial stretch does not change with transient cyclical pressurization over normal ranges. However, the axial force phenomenon of arteries has never been explained with microstructural considerations. In this paper we propose a simple biomechanical model to relate the specific axial force phenomenon of arteries to the predicted load-dependent average collagen fiber orientation. It is shown that (a) the model correctly predicts the authors' experimentally measured biaxial behavior of pig renal arteries and (b) the model predictions are in agreement with additional experimental results reported in the literature. Finally, we discuss the implications of the model for collagen fiber orientation and deposition in arteries.

Patient-Specific Numerical Simulations of Endovascular Procedures in Complex Aortic Pathologies: Review and Clinical Perspectives.

The endovascular technique is used in the first line treatment in many complex aortic pathologies. Its clinical outcome is mostly determined by the appropriate selection of a stent-graft for a specific patient and the operator's experience. New tools are still needed to assist practitioners with decision making before and during procedures. For this purpose, numerical simulation enables the digital reproduction of an endovascular intervention with various degrees of accuracy. In this review, we introduce the basic principles and discuss the current literature regarding the use of numerical simulation for endovascular management of complex aortic diseases. Further, we give the future direction of everyday clinical applications, showing that numerical simulation is about to revolutionize how we plan and carry out endovascular interventions.

A Hybrid Mock Circulatory Loop for Fluid Dynamic Characterization of 3D Anatomical Phantoms.

GOAL: 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. METHODS: 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: 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. SIGNIFICANCE: 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.