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Relationship Between Ascending Thoracic Aortic Aneurysms Hemodynamics and Biomechanical Properties
Abstract and Figures
Goal: Ascending thoracic aortic aneurysm (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 (CFD) analyses were performed and validated on 10 patients using patient-specific data derived from CT scan and 4D MRI. Systolic wall shear stress (WSS), 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 10 aTAA samples resected during surgical repair. The biomechanical and rupture properties of these samples were derived: the burst pressure, the physiological tangent elastic modulus (E_physio), the Cauchy stress at rupture (
$\sigma_{\rm rupt}$
), the rupture stretch (
$\lambda_{\rm rupt}$
) and the rupture stretch criterion (
$\gamma_{\rm stretch}$
). Statistical analysis was performed to determine correlation between all variables. Results: Statistically highly significant (p<0.01) positive correlation between
$\lambda_{\rm rupt}$
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.
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... It is a versatile imaging technique that has developed tremendously over the last few years. 2 This led to the introduction of several potential biomarkers for aneurysm progression and rupture based on various disease mechanisms. [16][17][18] Magnetic resonance biomarkers can be categorized as hemodynamic, molecular, and wall biomarkers. Hemodynamic biomarkers include those that quantify the dynamics of flowing blood and parameters that arise from that such as shear stress. ...
... Several quantitative MRI-based biomarkers have been described in the included articles. Eight articles involved a hemodynamic biomarker 8,18,[27][28][29][30][31][32] (Table 1), 5 articles involved a wall biomarker 9,33 -36 (Table 2), and 8 articles involved a molecular biomarker 16,21,[37][38][39][40][41][42] (Table 3). Only 1 study was conducted on an MR scanner with a nonclinical field strength of 9.4T. ...
... 9,33 Fifteen studies (71%) included patients. Of those, 2 studies included patients with Marfan syndrome (MFS), 28,32 3 studies included TAA patients, 18,27,32 and 10 studies included AAA patients. 8,29,31,[33][34][35][36][39][40][41] Two studies 8,32 used the term dilated aorta because not all included patients sufficed the definition of aneurysm. ...
Purpose:
In current practice, the diameter of an aortic aneurysm is utilized to estimate the rupture risk and decide upon timing of elective repair, although it is known to be imprecise and not patient-specific. Quantitative magnetic resonance imaging (MRI) enables the visualization of several biomarkers that provide information about processes within the aneurysm and may therefore facilitate patient-specific risk stratification. We performed a scoping review of the literature on quantitative MRI techniques to assess aortic aneurysm progression and rupture risk, summarized these findings, and identified knowledge gaps.
Methods:
Literature concerning primary research was of interest and the medical databases PubMed, Scopus, Embase, and Cochrane were systematically searched. This study used the PRISMA protocol extension for scoping reviews. Articles published between January 2010 and February 2023 involving animals and/or humans were included. Data were extracted by 2 authors using a predefined charting method.
Results:
A total of 1641 articles were identified, of which 21 were included in the scoping review. Quantitative MRI-derived biomarkers were categorized into hemodynamic (8 studies), wall (5 studies) and molecular biomarkers (8 studies). Fifteen studies included patients and/or healthy human subjects. Animal models were investigated in the other 6 studies. A cross-sectional study design was the most common, whereas 5 animal studies had a longitudinal component and 2 studies including patients had a prospective design. A promising hemodynamic biomarker is wall shear stress (WSS), which is estimated based on 4D-flow MRI. Molecular biomarkers enable the assessment of inflammatory and wall deterioration processes. The ADAMTS4-specific molecular magnetic resonance (MR) probe showed potential to predict abdominal aortic aneurysm (AAA) formation and rupture in a murine model. Wall biomarkers assessed using dynamic contrast-enhanced (DCE) MRI showed great potential for assessing AAA progression independent of the maximum diameter.
Conclusion:
This scoping review provides an overview of quantitative MRI techniques studied and the biomarkers derived from them to assess aortic aneurysm progression and rupture risk. Longitudinal studies are needed to validate the causal relationships between the identified biomarkers and aneurysm growth, rupture, or repair. In the future, quantitative MRI could play an important role in the personalized risk assessment of aortic aneurysm rupture.
Clinical impact:
The currently used maximum aneurysm diameter fails to accurately assess the multifactorial pathology of an aortic aneurysm and precisely predicts rupture in a patient-specific manner. Quantitative magnetic resonance imaging (MRI) enables the detection of various quantitative parameters involved in aneurysm progression and subsequent rupture. This scoping review provides an overview of the studied quantitative MRI techniques, the biomarkers derived from them, and recommendations for future research needed for the implementation of these biomarkers. Ultimately, quantitative MRI could facilitate personalized risk assessment for patients with aortic aneurysms, thereby reducing untimely repairs and improving rupture prevention.
... Суммарно основными ранними признаками аортопатии, возникающими даже при нормальном диаметре аорты и определяющими риск расслоения аорты, помимо высоких пиковых скоростей являются: более высокая спираль, наличие и усиление силы вихрей, низкое пиковое систолическое напряжение сдвига, повышенная эксцентричность с неоднородным распределением WSS [6,10]. ...
... Сохранение естественной кривизны и физиологических условий кровотока является целью реконструктивной хирургии грудной аорты у пациентов с расслоением. 4D МР-потока может предоставить полезную информацию о количественных параметрах кровотока, определяющих развитие поздних осложнений, и способствовать лучшему пониманию взаимосвязи между гидродинамикой и механическими нагрузками, действующими на стенку аорты и сосудистых протезов [10]. ...
The study of blood flow is becoming a new trend in cardiology and cardiovascular surgery. Based on the literature and our own data, a review is presented on the use of 4D flow in diseases of the heart and blood vessels. The main state of the question about the features of the application of the technique in various pathologies of the cardiovascular system is described in detail, the priorities, limitations and promising directions of the technique application are considered taking into account the goals of practical medicine. The review consists of two parts. The first is devoted to general issues, limitations of the technique, and issues of 4D flow mapping in patients with lesions of the great vessels. In the second part, the emphasis is on the use of 4D flow magnetic resonance imaging in the study of intraventricular blood flow and the application of the technique in congenital heart and vascular diseases.
... Методы вычислительной гемодинамики, такие как фазово-контрастная магнитно-резонансная томография (2D МРТ), помимо размеров позволяет выявить биомеханические критерии, отражающие ремоделирование сосудистой стенки на ранних этапах, с возможностью динамического контроля гемодинамических изменений [11][12][13]. Таким образом, внедрение персонифицированного превентивного подхода в клиническую практику позволит выйти на новый уровень диагностики и хирургического лечения заболеваний аорты [14][15][16]. ...
Background . Vascular stiffness is an important predictor of cardiovascular disease. The vascular wall biomechanical parameters change not only in patients with genetic disorders of the connective tissue. This means that, regardless of etiology, the early detection of a progressive loss of aortic elasticity is of great clinical importance in preventing the development of severe complications. Assessment of aortic biomechanical parameters using magnetic resonance imaging (MRI) is a new level of visualization for aortic diseases allowing to improve surgical tactics and prevent complications. A number of biomechanical parameters determined by aortic MRI demonstrates the process of its wall remodeling, so their analysis will allow to develope an algorithm for the early diagnosis of aneurysms and the threat of acute aortic syndrome.
Objective : using aortic MRI data, to evaluate the aortic biomechanical parameters and hemodynamics at pre- and postoperative stages and their impact on the occurrence of complications and relapses in the long-term period.
Material and methods . Between 2020 and 2023, in Petrovsky Russian Scientific Center of Surgery, aortic MRI was performed prospectively before and after surgery in 107 patients with diagnoses of ascending aortic aneurysm (55 patients: 48 (87%) males and 7 (13%) females, mean age 79.4±14.91 years) and DeBakey type I and III aortic dissection, chronic stage (52 patients: 44 (85%) males and 8 (15%) females, mean age 54.32±10.41 years).
Results . The quantitative data analysis in the postoperative period showed a decrease in the aortic wall elastic properties in the form of extensibility (0.4 [0.34; 0.54] %/mm Hg in the aneurysm group; 0.5 [0.25; 0.55] %/mmHg in the dissection group) and an increase in stiffness in the form of Young’s modulus (0.6 [0.38; 0.68] MPa in the aneurysm group; 0.5 [0.39; 0.83] MPa in the dissection group). Hemodynamic changes in the dissection group after surgery demonstrated a significant increase in values of maximum velocity in the descending aorta (78.6 [66.24; 130.78] cm/sec) and pressure gradient at the celiac trunk level (2.10 [1.76; 6.84] mm Hg). When assessing the pulse wave velocity parameter in both groups, high values were noted with a tendency to increase after surgery (in the aneurysm group, 7.7 [5.7; 20.3] cm/s before surgery versus 8.7 [6.5; 10.65] cm/s after surgery; in the dissection group, 9.7 [6.8; 12.9] versus 12.7 [7.7; 15.7] cm/s, respectively).
Conclusion . Monitoring general hemodynamics and blood flow patterns together with an assessment of the aortic wall elasticity will make it possible to identify patients with borderline aortic dilatation. At the same time, studies of the aortic prosthetic segment are of particular interest. The obtained data on hemodynamic changes occuring at the border of the prosthetic and native segments of the operated aorta can confirm and justify the development of a complication in the form of distal stent graft-induced new entry (dSINE).
... Аорта также является сложной биомеханической системой, и в ряде ситуаций при исходно имеющихся нарушениях ее функционирования на микроскопическом уровне могут присутствовать определенные отличительные особенности (строения, эластических свойств и т. д.) -патологические паттерны. Такие паттерны могут быть выявлены, что, соответственно, делает возможным предсказание морфологически определенных и ассоциированных с высоким риском осложнений серьезных патологических изменений аорты [11][12][13]. В большинстве случаев машинного обучения проблема поиска паттернов, в наибольшей степени ассоциированных с заболеваниями грудной аорты, решается в процессе классификации. Исходная информация хранится в «обучающих образцах» -крупных наборах данных, которые используются в обучении алгоритма (машины). ...
Despite their relatively low prevalence compared to cardiac valve lesions and coronary heart disease, thoracic aortic aneurysm and dissection are potentially fatal and represent serious public health problems. The indications for surgical treatment in most thoracic aortic diseases are predominantly based on the maximum aortic diameter in a particular area. Congenital connective tissue disorder, thoracic aortic anomalies (e.g., coarctation), family history of aneurysms, aortic dissections, and sudden deaths are considered as additional risk factors of aortic-related complications influencing the “stricter” indications and lowering the “threshold” aortic diameter. At the same time, a certain proportion of patients with aortic diseases develop aortic dissection and rupture in normal or near-normal thoracic aortic diameter in certain section. Many factors influence the development of aortic diseases and complications, and assessing the contribution to the aetiology and pathogenesis of each factor is difficult. Machine learning and mathematical modeling using artificial intelligence is an actively developing area of computer science, which also finds application in medicine, in particular in the study, diagnosis, and treatment of thoracic aortic aneurysms and dissections. This article discusses modern methods of data analysis, prediction of thoracic aortic aneurysms and dissections, treatment planning in thoracic aortic diseases, and prediction of complications using machine learning and artificial intelligence.
Background
Maximum diameter measurements are used to assess the rupture risk of abdominal aortic aneurysms (AAAs); however, these are not precise enough to predict all ruptures. Four‐dimensional (4D) flow MRI‐derived parameters provide additional information by visualizing hemodynamics in AAAs but merit further investigation before they are clinically applicable.
Purpose
To assess the reproducibility of 4D flow MRI‐derived hemodynamics, to investigate possible correlations with lumen and maximum diameter, and to explore potential relationships with vorticity and aneurysm growth.
Study Type
Prospective single‐arm study.
Population
A total of 22 (71.5 ± 6.1 years, 20 male) asymptomatic AAA patients with a maximum diameter of at least 30 mm.
Field Strength/Sequence
A 3.0 T/Free‐breathing 4D flow MRI phase‐contrast acquisition with retrospective ECG‐gating.
Assessment
Patients underwent two consecutive 4D flow MRI scans 1‐week apart. Aortic volumes were segmented from time‐averaged phase contrast magnetic resonance angiographies. Reproducibility was assessed by voxelwise analysis after registration. Mean flow velocity, mean wall shear stress (WSS), mean lumen diameter, and qualitative vorticity scores were assessed. In addition, Dixon MRI and retrospective surveillance data were used to study maximum diameter (including thrombus), intraluminal thrombus volume (ILT), and growth rate.
Statistical Tests
For reproducibility assessment, Bland–Altman analyses, Pearson correlation, Spearman's correlation, and orthogonal regression were conducted. Potential correlations between hemodynamics and vorticity scores were assessed using linear regression. P < 0.05 was considered statistically significant.
Results
Test–retest median Pearson correlation coefficients for flow velocity and WSS were 0.85 (IQR = 0.08) m/sec and 0.82 (IQR = 0.10) Pa, respectively. Mean WSS significantly correlated with mean flow velocity ( R = 0.75) and inversely correlated with mean lumen diameter ( R = −0.73). No significant associations were found between 4D flow MRI‐derived hemodynamic parameters and maximum diameter (flow velocity: P = 0.98, WSS: P = 0.22).
Data Conclusion
A 4D flow MRI is robust for assessing the hemodynamics within AAAs. No correlations were found between hemodynamic parameters and maximum diameter, ILT volume and growth rate.
Level of Evidence
2
Technical Efficacy
Stage 2
Objective
The objective of this review was to identify quantitative biomechanical measurements of human tissues, the methods for obtaining these measurements, and the primary motivations for conducting biomechanical research.
Introduction
Medical skills trainers are a safe and useful tool for clinicians to use when learning or practicing medical procedures. The haptic fidelity of these devices is often poor, which may be because the synthetic materials chosen for these devices do not have the same mechanical properties as human tissues. This review investigates a heterogenous body of literature to identify which biomechanical properties are available for human tissues, the methods for obtaining these values, and the primary motivations behind conducting biomechanical tests.
Inclusion criteria
Studies containing quantitative measurements of the biomechanical properties of human tissues were included. Studies that primarily focused on dynamic and fluid mechanical properties were excluded. Additionally, studies only containing animal, in silico , or synthetic materials were excluded from this review.
Methods
This scoping review followed the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). Sources of evidence were extracted from CINAHL (EBSCO), IEEE Xplore, MEDLINE (PubMed), Scopus, and engineering conference proceedings. The search was limited to the English language. Two independent reviewers screened titles and abstracts as well as full-text reviews. Any conflicts that arose during screening and full-text review were mediated by a third reviewer. Data extraction was conducted by 2 independent reviewers and discrepancies were mediated through discussion. The results are presented in tabular, figure, and narrative formats.
Results
Data were extracted from a total of 186 full-text publications. All of the studies, except for 1, were experimental. Included studies came from 33 different countries, with the majority of the studies coming from the United States. Human tissues samples were ex vivo , and the most commonly studied tissue type was musculoskeletal. In this study, nearly 200 unique biomechanical values were reported, and the most commonly reported value was Young’s (elastic) modulus. The most common type of mechanical test performed was tensile testing, and the most common reason for testing human tissues was to characterize biomechanical properties. Although the number of published studies on biomechanical properties of human tissues has increased over the past 20 years, there are many gaps in the literature. Of the 186 included studies, only 7 used human tissues for the design or validation of medical skills training devices. Furthermore, in studies where biomechanical values for human tissues have been obtained, a lack of standardization in engineering assumptions, methodologies, and tissue preparation may implicate the usefulness of these values.
Conclusions
This review is the first of its kind to give a broad overview of the biomechanics of human tissues in the published literature. With respect to high-fidelity haptics, there is a large gap in the published literature. Even in instances where biomechanical values are available, comparing or using these values is difficult. This is likely due to the lack of standardization in engineering assumptions, testing methodology, and reporting of the results. It is recommended that journals and/or experts in engineering fields conduct further research to investigate the feasibility of implementing reporting standards.
Review Registration
Open Science Framework osf.io/fgb34
Background:
Marfan syndrome (MFS) is a genetic disorder caused by mutations in fibrillin-1 and is characterized by thoracic aortic aneurysms and other complications. Previous studies revealed sexual dimorphisms in aortic aneurysm formation in patients with MFS. The present study aimed to investigate the combined role of a high-fat diet (HFD) and biological sex in aortic disease using the mgR/mgR MFS mouse model.
Methods:
Male and female mgR/mgR mice as well as wild-type (WT) littermate mice were fed a control diet (CD, 10% fat) or HFD (60% fat) from 4 to 12 weeks of age. Key aortic disease parameters analyzed included the diameter of the aortic wall; elastic fiber fragmentation; proteoglycan content; mRNA levels of Mmp12, Col1a1, Col3a1, and Fbn1; and fibrillin-1 deposition in the aortic wall.
Results:
HFD-fed female mgR/mgR mice had significantly reduced aortic diameters (35%), elastic fiber fragmentation (56%), pathologically enhanced proteoglycans (45%), and expression of Mmp12 (64%), Col1a1 (41%), and Col3a1 (43%) compared to male mgR/mgR mice on HFD. Fibrillin-1 deposition and Fbn1 mRNA levels were unaffected. The data reveal a protective effect of HFD in female mice. In contrast, CD did not exert any protective effects.
Conclusion:
This study demonstrates a specific sexual dimorphism in MFS mice, with HFD exerting an explicit protective effect on aortic disease severity in female mice. These preclinical data may be useful for developing nutritional recommendations for individuals with MFS in the longer term.
Hypertension is a major predisposing factor to initiate thoracic aortopathy. The objective of this study is to investigate effect of hypertension on delamination and tensile strength of ascending thoracic aortic aneurysms (ATAAs). A total of 35 fresh ATAA samples were harvested from 19 hypertensive and 16 non-hypertensive patients during elective aortic surgery. Peeling tests with two extension rates were performed to determine delamination strength, while uniaxial tensile (UT) tests were employed to measure failure stresses. The delamination strength and failure stresses of the ATAAs were further correlated with patient ages for hypertensive and non-hypertensive groups. The delamination strength to peel apart the ATAA tissue along the longitudinal direction was statistically significantly lower for the hypertensive patients than that of the non-hypertensive patients (35 ± 11 vs. 49 ± 9 mN/mm, p = 0.02). A higher delamination strength was measured if peeling was performed with a higher extension rate. The circumferential failure stresses were significantly lower for the hypertensive ATAAs than those of the non-hypertensive ATAAs (1.03 ± 0.27 vs. 1.43 ± 0.38 MPa, p = 0.02). Histology showed that laminar structures of elastic fibers were mainly disrupted in the hypertensive ATAAs. The longitudinal delamination strength of the ATAAs was significantly decreased and strongly correlated with ages for the hypertensive patients. Strong inverse correlations were also identified between the circumferential and longitudinal failure stresses of the ATAAs and ages for the hypertensive patients. Results suggest that the ATAAs of the elderly hypertensive patients may have a higher propensity for dissection or rupture. The dissection properties of the ATAA tissue are rate dependent.
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.
Aortic dissection is the most common catastrophe of the thoracic aorta, with a very high rate of mortality. Type A dissection is often associated with an ascending thoracic aortic aneurysm (ATAA). However, it is widely acknowledged that the risk of type A dissection cannot be reliably predicted simply by measuring the ATAA diameter and there is a pressing need for more reliable risk predictors. It was previously shown that there is a significant correlation between a rupture criterion based on the ultimate stretch of the ATAA and the local extensional stiffness of the aorta. Therefore, reconstructing regional variations of the extensional stiffness across the aorta appears highly important. In this paper, we present a novel noninvasive inverse method to identify the patient-specific local extensional stiffness of aortic walls based on preoperative gated CT scans. Using these scans, a structural mesh is defined across the aorta with a set of nodes attached to the same material points at different time steps throughout the cardiac cycle. For each node, time variations of the position are analyzed using Fourier series, permitting the reconstruction of the local strain distribution (fundamental term). Relating these strains to tensions with the extensional stiffness, and writing the local equilibrium satisfied by the tensions, the local extensional stiffness is finally derived at every position. The methodology is applied onto the ascending and descending aorta of three patients. Interestingly, the regional distribution of identified stiffness properties appears heterogeneous across the ATAA. Averagely, the identified stiffness is also compared with values obtained using other nonlocal methodologies. The results support the possible noninvasive prediction of stretch-based rupture criteria in clinical practice using local stiffness reconstruction.
Ascending thoracic aortic aneurysms (ATAA) are a life-threatening pathology provoking an irreversible dilation with a high associated risk of aortic rupture or dissection and death of the patient. Rupture or dissection of ATAAs remains unpredictable and has been documented to occur at diameters less than 4.5 cm for nearly 60% of patients. Other factors than the aneurysm diameter may highly affect the predisposition to rupture. In order to have a better insight in rupture risk prediction, a bulge inflation bench was developed to test ATAAs samples collected on patients during surgical interventions. Preoperative dynamic CT scans on a cohort of 13 patients were analyzed to estimate volumetric and cross-sectional distensibility. A failure criteria based on in vitro ultimate stretch showed a significant correlation with the aortic membrane stiffness deduced from in vivo distensibility. These results reinforce the significance of stretch-based rupture criteria and their possible non-invasive prediction in clinical practice.
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 (10¹⁰ 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.
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 (EL') 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 EL' (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.
Vascular Smooth Muscle Cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissections share numerous characteristics, including aetiologies and histopathological alterations: vSMC disappearance, medial areas of mucoid degeneration, and ExtraCellular Matrix (ECM) breakdown. Three aetiologies predominate in TAAD in humans: i) genetic causes in heritable familial forms, ii) an association with bicuspid aortic valves and iii) a sporadic degenerative form linked to the aortic aging process. Genetic forms include mutations in vSMC genes encoding for molecules of the ECM or the TGF-β pathways, or participating in vSMC tone. On the other hand, aneurysms and dissections, whatever their aetiologies, are characterized by an increase in wall permeability leading to transmural advection of plasma proteins which could interact with vSMCs and ECM components. In this context, blood-borne plasminogen appears to play an important role, because its outward convection through the wall is increased in TAAD, and it could be converted to active plasmin at the vSMC membrane. Active plasmin can induce vSMC disappearance, proteolysis of adhesive proteins, activation of MMPs and release of TGF-β from its ECM storage sites. Conversely, vSMCs could respond to aneurysmal biomechanical and proteolytic injury by an epigenetic phenotypic switch, including constitutional overexpression and nuclear translocation of Smad2 and an increase in antiprotease and ECM protein synthesis. In contrast, such an epigenetic phenomenon is not observed in dissections. In this context, dysfunction of proteins involved in vSMC tone are interesting to study, particularly in interaction with plasma protein transport through the wall and TGF-β activation, to establish the relationship between these dysfunctions and ECM proteolysis.
The vitality of the cardiovascular system, which consists of the heart, vas culature, and blood, depends on its response to a host of complex stimuli, including biological, chemical, electrical, mechanical, and thermal. The focus of this book, however, is on the response of the heart and arteries to mechanical loads from the perspective of nonlinear solid mechanics. Through my own research in this field, I have come to realize that study ing the complex responses of cardiovascular cells, tissues, and organs nec essarily requires a combined theoretical, experimental, and computational approach. Theory is needed to guide the performance and interpretation of experiments as well as to synthesize the results; experiment is needed to study the responses of the system to well-controlled loads and to test can didate hypotheses and theories; and due to the geometric and material non linearities inherent to cardiovascular mechanics, computation is needed to analyze data as well as to solve boundary and initial value problems that correspond to either experimental or in vivo conditions. One of the primary goals of this book is to introduce together basic analytical, experimental, and computational methods and to illustrate how these methods can and must be integrated to gain a more complete understanding of the bio mechanics of the heart and vasculature. Despite the focus on cardiovascu lar mechanics, the fundamental methods, indeed many of the specific results, are generally applicable to many different soft tissues.
We present a comprehensive and original framework for the biomechanical analysis of patients affected by ascending thoracic aorta aneurysm and aortic insufficiency. Our aim is to obtain crucial indications about the role played by deranged hemodynamics on the ATAAs risk of rupture. Computational fluid dynamics analysis was performed using patient-specific geometries and boundary conditions derived from 4D MRI. Blood flow helicity and wall shear stress descriptors were assessed. A bulge inflation test was carried out in vitro on the 4 ATAAs after surgical repair. The healthy volunteers showed no eccentric blood flow, a mean TAWSS of 1.5 ± 0.3 Pa and mean OSI of 0.325 ± 0.025. In 3 aneurismal patients, jet flow impingement on the aortic wall resulted in large TAWSS values and low OSI which were amplified by the AI degree. However, the tissue strength did not appear to be significantly reduced. The fourth patient, which showed the lowest TAWSS due to the absence of jet flow, had the smallest strength in vitro. Interestingly this patient presented a bovine arch abnormality. Jet flow impingement with high WSS values is frequent in ATAAs and our methodology seems to be appropriate for determining whether it may increase the risk of rupture or not.