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BACKGROUND: Early embryonic aortic arches (AA) are a dynamic vascular structures that are in the process of shaping into the great arteries of cardiovascular system. Previously, a time-lapsed mechanosensitive gene expression map was established for AA subject to altered mechanical loads in the avian embryo. To validate this map, we investigated effects on vascular microstructure and material properties following the perturbation of key genes using an in-house microvascular gene knockdown system. RESULTS: All siRNA vectors show a decrease in the expression intensity of desired genes with no significant differences between vectors. In TGFß3 knockdowns, we found a reduction in expression intensities of TGFß3 (≤76%) and its downstream targets such as ELN (≤99.6%), Fbn1 (≤60%), COL1 (≤52%) and COL3 (≤86%) and an increase of diameter in the left AA (23%). MMP2 knockdown also reduced expression levels in MMP2 (≤30%) and a 6-fold increase in its downstream target COL3 with a decrease in stiffness of the AA wall and an increase in the diameter of the AA (55%). These in vivo measurements were confirmed using immunohistochemistry, western blotting and a computational growth model of the vascular extracellular matrix (ECM). CONCLUSIONS: Localized spatial genetic modification of the aortic arch region governs the vascular phenotype and ECM composition of the embryo and can be integrated with mechanically-induced congenital heart disease models.
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BACKGROUND: The Food and Drug Administration (FDA) blood pump is an open-source benchmark cardiovascular device introduced for validating computational and experimental performance analysis tools. The time-resolved velocity field for the whole impeller has not been established, as is undertaken in this particle image velocimetry (PIV) study. The level of instantaneous velocity fluctuations is important, to assess the flow-induced rotor vibrations which may contribute to the total blood damage. METHODS: To document these factors, time-resolved two-dimensional PIV experiments were performed that were precisely phase-locked with the impeller rotation angle. The velocity fields in the impeller and in the volute conformed with the previous single blade passage experiments of literature. RESULTS: Depending on the impeller orientation, present experiments showed that volute outlet nozzle flow can fluctuate up to 34% during impeller rotation, with a maximum standard experimental uncertainty of 2.2%. Likewise, the flow fields in each impeller passage also altered in average 33.5%. Considerably different vortex patterns were observed for different blade passages, with the largest vortical structures reaching an average core radii of 7 mm. The constant volute area employed in the FDA pump design contributes to the observed velocity imbalance, as illustrated in our velocity measurements. CONCLUSIONS: By introducing the impeller orientation parameter for the nozzle flow, this study considers the possible uncertainties influencing pump flow. Expanding the available literature data, analysis of inter-blade relative velocity fields is provided here for the first-time to the best of our knowledge. Consequently, our research fills a critical knowledge gap in the understanding of the flow dynamics of an important benchmark cardiovascular device. This study prompts the need for improved hydrodynamic designs and optimized devices to be used as benchmark test devices, to build more confidence and safety in future ventricular assist device performance assessment studies.
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BACKGROUND: Pulmonary valve replacement is recommended in patients with repaired tetralogy of Fallot based on cardiac magnetic resonance imaging (MRI) criteria. This procedure is performed by surgical or transcatheter approaches. OBJECTIVE: We aimed to investigate the differences in preprocedural MRI characteristics (volume, function, strain) and morphology of the right ventricular outflow tract and branch pulmonary arteries in patients for whom surgical or transcatheter pulmonary valve replacement was planned. MATERIALS AND METHODS: Cardiac MRI of 166 patients with tetralogy of Fallot were analyzed. Of these, 36 patients for whom pulmonary valve replacement was planned were included. Magnetic resonance imaging characteristics, right ventricular outflow tract morphology, branch pulmonary artery flow distribution and diameter were compared between surgical and transcatheter groups. Spearman correlation and Kruskal-Wallis tests were performed. RESULTS: Circumferential and radial MRI strain for the right ventricle were lower in the surgical group (P=0.045 and P=0.046, respectively). The diameter of the left pulmonary artery was significantly lower (P=0.021) and branch pulmonary artery flow and diameter ratio were higher (P=0.044 and P = 0.002, respectively) in the transcatheter group. There was a significant correlation between right ventricular outflow tract morphology and right ventricular end-diastolic volume index and global circumferential and radial MRI strain (P=0.046, P=0.046 and P= 0.049, respectively). CONCLUSION: Preprocedural MRI strain, right-to-left pulmonary artery flow, diameter ratio and morphological features of the right ventricular outflow tract were significantly different between the two groups. A transcatheter approach may be recommended for patients with branch pulmonary artery stenosis, since both pulmonary valve replacement and branch pulmonary artery stenting can be performed in the same session.
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Insuficiência da Valva Pulmonar , Valva Pulmonar , Tetralogia de Fallot , Humanos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/cirurgia , Imageamento por Ressonância Magnética , Resultado do Tratamento , Estudos RetrospectivosRESUMO
In the embryonic heart, blood flow is distributed through a bilaterally paired artery system composed of the aortic arches (AAs). The purpose of this study is to establish an understanding of the governing mechanism of microstructural maturation of the AA matrix and its reversibility, toward the desired macroscopic vessel lumen diameter and thickness for healthy, abnormal, and in ovo repaired abnormal mechanical loading. While matrix-remodeling mechanisms were significantly different for normal versus conotruncal banding (CTB), both led to an increase in vessel lumen. Correlated with right-sided flow increase at Hamburger & Hamilton stages 21, intermittent load switching between collagen I and III with elastin and collagen-IV defines the normal process. However, decreases in collagen I, elastin, vascular endothelial growth factor-A, and fibrillin-1 in CTB were recovered almost fully following the CTB-release model, primarily because of the pressure load changes. The complex temporal changes in matrix proteins are illustrated through a predictive finite-element model based on elastin and collagen load-sharing mechanism to achieve lumen area increase and thickness increase resulting from wall shear stress and tissue strain, respectively. The effect of embryonic timing in cardiac interventions on AA microstructure was established where abnormal mechanical loading was selectively restored at the key stage of development. Recovery of the normal mechanical loading via early fetal intervention resulted in delayed microstructural maturation. Temporal elastin increase, correlated with wall shear stress, is required for continuous lumen area growth.NEW & NOTEWORTHY The present study undertakes comparative analyses of the mechanistic differences of the arterial matrix microstructure and dynamics in the three fundamental processes of control, conotruncal banded, and released conotruncal band in avian embryo. Among other findings, this study provides specific evidence on the restorative role of elastin during the early lumen growth process. During vascular development, a novel intermittent load-switching mechanism between elastin and collagen, triggered by a step increase in wall shear stress, governs the chronic vessel lumen cross-sectional area increase. Mimicking the fetal cardiovascular interventions currently performed in humans, the early release of the abnormal mechanical load rescues the arterial microstructure with time lag.
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Aorta Torácica/embriologia , Hemodinâmica , Estresse Mecânico , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , Aorta Torácica/ultraestrutura , Embrião de Galinha , Colágeno/metabolismo , Circulação Coronária , Elastina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Clinical success of extracorporeal membrane oxygenation (ECMO) depends on the proper venous cannulation. Venovenous (VV) ECMO is the preferred clinical intervention as it provides a single-site access by utilizing a VV double lumen cannula (VVDLC) with a higher level of mobilization and physical rehabilitation. Concurrent venous blood drainage and oxygenated blood infusion in the right atrium at the presence of the cannula makes the flow dynamics complex where potential mixing of venous and oxygenated blood can drastically decrease the overall performance of ECMO. There are no studies focusing on the neonatal and pediatric populations, in which the flow related effects are critical due to the small atrium size. In this study, fluid dynamics of infusion outflow jet for two commercially available neonatal VVDLC is analyzed using particle image velocimetry (PIV). Moreover, six new designs are proposed for the infusion channel geometry and compared. Important flow parameters such as flow turning angle (FTA), velocity decay, potential core, and turbulent intensity are investigated for the proposed models. The experiments showed that the outflow parameters of commercial cannulae such as FTA are strongly dependent on the operating Re number. This may result in a drastic efficiency reduction for cannula operating at off-design flow conditions. Moreover, the infusion outlet tip structure and jet internal guiding pathway (JIGP) was observed to greatly affect the outflow flow features. This is of paramount importance since the anatomical positioning of the cannula and the infusion outlet is strongly dependent on the outflow properties such as FTA.
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Oxigenação por Membrana Extracorpórea , Cânula , Criança , Humanos , Recém-Nascido , VeiasRESUMO
OBJECTIVE: Malposition of dual lumen cannula is a frequent and challenging complication in neonates and plays a significant role in shaping the in vitro device hemodynamics. This study aims to analyze the effect of the dual lumen cannula malposition on right-atrial hemodynamics in neonatal patients using an experimentally validated computational fluid dynamics model. METHODS: A computer model was developed for clinically approved dual lumen cannula (13Fr Origen Biomedical, Austin, Texas, USA) oriented inside the atrium of a 3-kg neonate with normal venous return. Atrial hemodynamics and dual lumen cannula malposition were systematically simulated for two rotations (antero-atrial and atrio-septal) and four translations (two intravascular movements along inferior vena cava and two dislodged configurations in the atrium). A multi-domain compartmentalized mesh was prepared to allow the site-specific evaluation of important hemodynamic parameters. Transport of each blood stream, blood damage levels, and recirculation times are quantified and compared to dual lumen cannula in proper position. RESULTS: High recirculation levels (39 ± 4%) in malpositioned cases resulted in poor oxygen saturation where maximum recirculation of up to 42% was observed. Apparently, Origen dual lumen cannula showed poor inferior vena cava blood-capturing efficiency (48 ± 8%) but high superior vena cava blood-capturing efficiency (86 ± 10%). Dual lumen cannula malposition resulted in corresponding changes in residence time (1.7 ± 0.5 seconds through the tricuspid). No significant differences in blood damage were observed among the simulated cases compared to normal orientation. Compared to the correct dual lumen cannula position, both rotational and translational displacements of the dual lumen cannula resulted in significant hemodynamic differences. CONCLUSION: Rotational or translational movement of dual lumen cannula is the determining factor for atrial hemodynamics, venous capturing efficiency, blood residence time, and oxygenated blood delivery. Results obtained through computational fluid dynamics methodology can provide valuable foresight in assessing the performance of the dual lumen cannula in patient-specific configurations.
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Cânula/normas , Cateterismo/métodos , Oxigenação por Membrana Extracorpórea/métodos , Hemodinâmica , Humanos , Recém-NascidoRESUMO
In a typical open-heart surgery, the blood flow through the aortic cannula is a critical element of the cardiopulmonary bypass (CPB) procedure. Especially for the neonatal and pediatric CPB flow conditions, the need for small hydraulic diameter and large blood flow results confined turbulent jet flow regimes that exacerbate blood damage and platelet activation. Simultaneously, the confined jet wake leads to complex stagnation and recirculating flows that cause considerable thrombosis, blood, and endothelial cell damage through the aorta. Thus, an ideal neonatal CPB cannula should be able to generate optimal jet expansion so that sufficient cerebral perfusion is achieved through the head-neck vessels to avoid postoperative neurological complications and developmental defects in children. To address these challenges, a formal bio-inspired design framework is conducted to reach the desired cannula function through novel analogous biological components, first-time in literature. Among the biological jet flow regimes studied, the ventricle filling-jet generated through the atrio-ventricle (AV) valves are found to be the most promising. Inspired from human AV valve shapes, 8 different novel cannula designs, considering the size constrains of neonatal and pediatric patients are built via high-accurate micro stereo-lithography. Using 2-dimensional time-resolved particle image velocimetry the turbulent jet wake characteristics are measured and compared. The proposed designs have exhibited a significant improvement as compared to standard circular cannula by around 30% reduction in maximum outflow velocity and more than 80% reduction in potential core length and spatial energy dissipation which results in a lower risk of cardiovascular and blood damage.
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Valva Aórtica , Ponte Cardiopulmonar/instrumentação , Cateterismo/instrumentação , Valva Aórtica/anatomia & histologia , Biomimética , Velocidade do Fluxo Sanguíneo , Cânula , Desenho de Equipamento , Humanos , Recém-Nascido , Modelos Cardiovasculares , Reologia , Dispositivos de Acesso VascularRESUMO
Clinical success of pediatric veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is associated with the double lumen cannula cardiovascular device design as well as its anatomic orientation in the atrium. The positions of cannula ports with respect to the vena cavae and the tricuspid valve are believed to play a significant role on device hemodynamics. Despite various improvements in ECMO catheters, especially for the neonatal and congenital heart patients, it is still challenging to select a catalogue size that would fit to most patients optimally. In effect, the local unfavorable blood flow characteristics of the cannula would translate to an overall loss of efficiency of the ECMO circuit. In this study, the complex flow regime of a neonatal double lumen cannula, positioned in a patient-specific right atrium, is presented for the first time in literature. A pulsatile computational fluid dynamics (CFD) solver that is validated for cardiovascular device flow regimes was used to perform the detailed flow, oxygenated blood transport, and site-specific blood damage analysis using an integrated cannula and right atrium model. A standard 13Fr double lumen cannula was scanned using micro-CT, reconstructed and simulated under physiologic flow conditions. User defined scalar transport equations allowed the quantification of the mixing and convection of oxygenated and deoxygenated blood as well as blood residence times and hemolysis build-up. Site-specific CFD analysis provided key insight into the hemodynamic challenges encountered in cannula design and the associated intra-atrial flow patterns. Due to neonatal flow conditions, an ultra high velocity infusion jet emanated from the infusion port and created a zone of major recirculation in the atrium. This flow regime influenced the delivery of the oxygenated blood to the tricuspid valve. Elevated velocities and complex gradients resulted in higher wall shear stresses (WSS) particularly at the infusion port having the highest value followed by the aspiration hole closest to the drainage port. Our results show that, in a cannula that is perfectly oriented in the atrium, almost 38% of the oxygenated blood is lost to the atrial circulation while only half of the blood from inferior vena cava (IVC) can reach to the tricuspid valve. As such, approximately 6% of venous blood from superior vena cava (SVC) can be delivered to tricuspid. High values of hemolysis index were observed with blood damage encountered around infusion hole (0.025%). These results warrant further improvements in the cannula design to achieve optimal performance of ECMO and better patient outcomes.
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Cânula/efeitos adversos , Oxigenação por Membrana Extracorpórea/instrumentação , Átrios do Coração/fisiopatologia , Hemodinâmica/fisiologia , Modelos Cardiovasculares , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Lactente , Fluxo Sanguíneo Regional , Insuficiência Respiratória/terapia , Valva Tricúspide/fisiopatologia , Veias CavasRESUMO
Cardiopulmonary bypass (CPB) procedure is employed to repair most congenital heart defects (CHD). Cannulation is a critical component of this procedure where the location and diameter of cannula controls the hemodynamic performance. State-of-the-art computational studies of neonatal CPB employed an isolated aortic arch region by truncating the three-dimensional (3D) patient-specific cerebral system. The present work expanded these studies where the 3D patient-specific MRI reconstruction of the cerebral system, including the Circle of Willis (CoW), is integrated with a hypoplastic neonatal aortic arch. The inlet of the arterial cannula is assigned a steady velocity boundary condition of the CPB pump, while all outlets are modeled as resistance boundary conditions, thus allowing acute comparisons between different cannula configurations. Three-dimensional (3D) flow simulations in the aortic arch model are performed at a Reynolds number of 2150 using an experimentally validated commercial solver. Results demonstrate that the inclusion of 3D CoW is essential to predict the accurate head-neck blood perfusion and therefore critical in deciding the neonatal aortic cannulation strategy preoperatively. Using this integrated model two CPB configurations are studied, where the cannulas were placed at innominate artery (IA) (IA-cannula configuration) and ductus arteriosus (DA) (DA-cannula configuration). Configuration change produced significant differences in flow splits and local hemodynamics of blood flow throughout the whole aortic arch, neck and cerebral arteries. Percent flow rate differences between the IA- and DA-cannula configurations are computed to be: 19%, for descending aorta, 198% for ascending aorta (perfusing coronary arteries), 91% for right anterior cerebral artery, and 68% for left anterior cerebral artery. Another important finding is the retrograde flow at vertebral arteries for IA-cannula configuration, but not for DA-cannula. These results may help to translate better neonatal arterial cannulae design for minimizing cerebral complications during CPB procedures.
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Ponte Cardiopulmonar , Círculo Arterial do Cérebro/anatomia & histologia , Simulação por Computador , Hemodinâmica/fisiologia , Aorta Torácica/anatomia & histologia , Aorta Torácica/fisiologia , Aorta Torácica/cirurgia , Cateterismo Cardíaco/métodos , Ponte Cardiopulmonar/métodos , Artérias Cerebrais/anatomia & histologia , Artérias Cerebrais/fisiologia , Círculo Arterial do Cérebro/fisiologia , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Humanos , Imageamento Tridimensional , Recém-NascidoRESUMO
Vascular growth and remodeling during embryonic development are associated with blood flow and pressure induced stress distribution, in which residual strains and stresses play a central role. Residual strains are typically measured by performing in vitro tests on the excised vascular tissue. In this paper, we investigated the possibility of estimating residual strains and stresses using physiological pressure-radius data obtained through in vivo noninvasive measurement techniques, such as optical coherence tomography or ultrasound modalities. This analytical approach first tested with in vitro results using experimental data sets for three different arteries such as rabbit carotid artery, rabbit thoracic artery, and human carotid artery based on Fung's pseudostrain energy function and Delfino's exponential strain energy function (SEF). We also examined residual strains and stresses in the human swine iliac artery using the in vivo experimental ultrasound data sets corresponding to the systolic-to-diastolic region only. This allowed computation of the in vivo residual stress information for loading and unloading states separately. Residual strain parameters as well as the material parameters were successfully computed with high accuracy, where the relative errors are introduced in the range of 0-7.5%. Corresponding residual stress distributions demonstrated global errors all in acceptable ranges. A slight discrepancy was observed in the computed reduced axial force. Results of computations performed based on in vivo experimental data obtained from loading and unloading states of the artery exhibited alterations in material properties and residual strain parameters as well. Emerging noninvasive measurement techniques combined with the present analytical approach can be used to estimate residual strains and stresses in vascular tissues as a precursor for growth estimates. This approach is also validated with a finite element model of a general two-layered artery, where the material remodeling states and residual strain generation are investigated.
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Artérias/fisiologia , Pressão Sanguínea/fisiologia , Diagnóstico por Imagem/métodos , Modelos Cardiovasculares , Rigidez Vascular/fisiologia , Animais , Artérias/anatomia & histologia , Artérias/diagnóstico por imagem , Simulação por Computador , Módulo de Elasticidade/fisiologia , Humanos , Coelhos , Resistência ao Cisalhamento/fisiologia , Estresse Mecânico , Resistência à Tração/fisiologia , UltrassonografiaRESUMO
With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial/temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneurysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Participants were free to choose boundary conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (PIV) were carried out in a silicone model of one of the provided aneurysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peak-systolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that while a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.
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Aneurisma Roto/fisiopatologia , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Circulação Cerebrovascular , Aneurisma Intracraniano/fisiopatologia , Modelos Cardiovasculares , Simulação por Computador , Humanos , Resistência ao CisalhamentoRESUMO
BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a major human congenital heart defect that results in single ventricle physiology and high mortality. Clinical data indicate that intracardiac blood flow patterns during cardiac morphogenesis are a significant etiology. We used the left atrial ligation (LAL) model in the chick embryo to test the hypothesis that LAL immediately alters intracardiac flow streams and the biomechanical environment, preceding morphologic and structural defects observed in HLHS. RESULTS: Using fluorescent dye injections, we found that intracardiac flow patterns from the right common cardinal vein, right vitelline vein, and left vitelline vein were altered immediately following LAL. Furthermore, we quantified a significant ventral shift of the right common cardinal and right vitelline vein flow streams. We developed an in silico model of LAL, which revealed that wall shear stress was reduced at the left atrioventricular canal and left side of the common ventricle. CONCLUSIONS: Our results demonstrate that intracardiac flow patterns change immediately following LAL, supporting the role of hemodynamics in the progression of HLHS. Sites of reduced WSS revealed by computational modeling are commonly affected in HLHS, suggesting that changes in the biomechanical environment may lead to abnormal growth and remodeling of left heart structures.
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Simulação por Computador , Circulação Coronária , Síndrome do Coração Esquerdo Hipoplásico/embriologia , Modelos Cardiovasculares , Animais , Velocidade do Fluxo Sanguíneo , Embrião de Galinha , Modelos Animais de Doenças , Átrios do Coração/embriologia , Átrios do Coração/patologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/patologiaRESUMO
Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFß family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.
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Receptores de Ativinas Tipo I/metabolismo , Malformações Arteriovenosas/metabolismo , Velocidade do Fluxo Sanguíneo/fisiologia , Receptores de Ativinas Tipo I/genética , Animais , Malformações Arteriovenosas/etiologia , Embrião não Mamífero , Hibridização in Situ Fluorescente , Telangiectasia Hemorrágica Hereditária/etiologia , Telangiectasia Hemorrágica Hereditária/metabolismo , Peixe-ZebraRESUMO
The pathology of the human abdominal aortic aneurysm (AAA) and its relationship to the later complication of intraluminal thrombus (ILT) formation remains unclear. The hemodynamics in the diseased abdominal aorta are hypothesized to be a key contributor to the formation and growth of ILT. The objective of this investigation is to establish a reliable 3D flow visualization method with corresponding validation tests with high confidence in order to provide insight into the basic hemodynamic features for a better understanding of hemodynamics in AAA pathology and seek potential treatment for AAA diseases. A stereoscopic particle image velocity (PIV) experiment was conducted using transparent patient-specific experimental AAA models (with and without ILT) at three axial planes. Results show that before ILT formation, a 3D vortex was generated in the AAA phantom. This geometry-related vortex was not observed after the formation of ILT, indicating its possible role in the subsequent appearance of ILT in this patient. It may indicate that a longer residence time of recirculated blood flow in the aortic lumen due to this vortex caused sufficient shear-induced platelet activation to develop ILT and maintain uniform flow conditions. Additionally, two computational fluid dynamics (CFD) modeling codes (Fluent and an in-house cardiovascular CFD code) were compared with the two-dimensional, three-component velocity stereoscopic PIV data. Results showed that correlation coefficients of the out-of-plane velocity data between PIV and both CFD methods are greater than 0.85, demonstrating good quantitative agreement. The stereoscopic PIV study can be utilized as test case templates for ongoing efforts in cardiovascular CFD solver development. Likewise, it is envisaged that the patient-specific data may provide a benchmark for further studying hemodynamics of actual AAA, ILT, and their convolution effects under physiological conditions for clinical applications.
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Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/fisiopatologia , Imageamento Tridimensional/métodos , Modelos Cardiovasculares , Reologia/métodos , Trombose/fisiopatologia , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/patologia , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Simulação por Computador , Humanos , Trombose/etiologia , Trombose/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Advanced material models and material characterization of soft biological tissues play an essential role in pre-surgical planning for vascular surgeries and transcatheter interventions. Recent advances in heart valve engineering, medical device and patch design are built upon these models. Furthermore, understanding vascular growth and remodeling in native and tissue-engineered vascular biomaterials, as well as designing and testing drugs on soft tissue, are crucial aspects of predictive regenerative medicine. Traditional nonlinear optimization methods and finite element (FE) simulations have served as biomaterial characterization tools combined with soft tissue mechanics and tensile testing for decades. However, results obtained through nonlinear optimization methods are reliable only to a certain extent due to mathematical limitations, and FE simulations may require substantial computing time and resources, which might not be justified for patient-specific simulations. To a significant extent, machine learning (ML) techniques have gained increasing prominence in the field of soft tissue mechanics in recent years, offering notable advantages over conventional methods. This review article presents an in-depth examination of emerging ML algorithms utilized for estimating the mechanical characteristics of soft biological tissues and biomaterials. These algorithms are employed to analyze crucial properties such as stress-strain curves and pressure-volume loops. The focus of the review is on applications in cardiovascular engineering, and the fundamental mathematical basis of each approach is also discussed. METHODS: The review effort employed two strategies. First, the recent studies of major research groups actively engaged in cardiovascular soft tissue mechanics are compiled, and research papers utilizing ML and deep learning (DL) techniques were included in our review. The second strategy involved a standard keyword search across major databases. This approach provided 11 relevant ML articles, meticulously selected from reputable sources including ScienceDirect, Springer, PubMed, and Google Scholar. The selection process involved using specific keywords such as "machine learning" or "deep learning" in conjunction with "soft biological tissues", "cardiovascular", "patient-specific," "strain energy", "vascular" or "biomaterials". Initially, a total of 25 articles were selected. However, 14 of these articles were excluded as they did not align with the criteria of focusing on biomaterials specifically employed for soft tissue repair and regeneration. As a result, the remaining 11 articles were categorized based on the ML techniques employed and the training data utilized. RESULTS: ML techniques utilized for assessing the mechanical characteristics of soft biological tissues and biomaterials are broadly classified into two categories: standard ML algorithms and physics-informed ML algorithms. The standard ML models are then organized based on their tasks, being grouped into Regression and Classification subcategories. Within these categories, studies employ various supervised learning models, including support vector machines (SVMs), bagged decision trees (BDTs), artificial neural networks (ANNs) or deep neural networks (DNNs), and convolutional neural networks (CNNs). Additionally, the utilization of unsupervised learning approaches, such as autoencoders incorporating principal component analysis (PCA) and/or low-rank approximation (LRA), is based on the specific characteristics of the training data. The training data predominantly consists of three types: experimental mechanical data, including uniaxial or biaxial stress-strain data; synthetic mechanical data generated through non-linear fitting and/or FE simulations; and image data such as 3D second harmonic generation (SHG) images or computed tomography (CT) images. The evaluation of performance for physics-informed ML models primarily relies on the coefficient of determination R 2 . In contrast, various metrics and error measures are utilized to assess the performance of standard ML models. Furthermore, our review includes an extensive examination of prevalent biomaterial models that can serve as physical laws for physics-informed ML models. CONCLUSION: ML models offer an accurate, fast, and reliable approach for evaluating the mechanical characteristics of diseased soft tissue segments and selecting optimal biomaterials for time-critical soft tissue surgeries. Among the various ML models examined in this review, physics-informed neural network models exhibit the capability to forecast the mechanical response of soft biological tissues accurately, even with limited training samples. These models achieve high R 2 values ranging from 0.90 to 1.00. This is particularly significant considering the challenges associated with obtaining a large number of living tissue samples for experimental purposes, which can be time-consuming and impractical. Additionally, the review not only discusses the advantages identified in the current literature but also sheds light on the limitations and offers insights into future perspectives.
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Vascular smooth muscle cells (VSMCs) are subject to interstitial flow-induced shear stress, which is a critical parameter in cardiovascular disease progression. Transmural pressure loading and residual stresses alter the hydraulic conductivity of the arterial layers and modulate the interstitial fluid flux through the arterial wall. In this paper, a biphasic multilayer model of a common carotid artery (CCA) with anisotropic fiber-reinforced soft tissue and strain-dependent permeability is developed in FEBio software. After the verification of the numerical predictions, age-related arterial thickening and stiffening effects on arterial deformation and interstitial flow are computed under physiological geometry and physical parameters. We found that circumferential residual stress shifts outward in each layer and its gradient increases up to 6 times with aging. Internally pressurized CCA displays nonlinear deformation. In the aged artery, the circumferential stress becomes greater on the media layer (82-158 kPa) and lower on the intima and adventitia (19-23 kPa and 25-28 kPa, respectively). The radial compression of the intima reduces the total hydraulic conductivity by 48% in the young and 16% in the aged arterial walls. Consequently, the average radial interstitial flux increases with pressure by 14% in the young and 91% in the aged arteries. Accordingly, the flow shear stress experienced by the VSMCs becomes more significant for aged arteries, which may accelerate cardiovascular disease progression compared to young arteries.
Assuntos
Doenças Cardiovasculares , Humanos , Idoso , Fenômenos Biomecânicos , Artéria Carótida Primitiva/fisiologia , Túnica Média/fisiologia , Estresse MecânicoRESUMO
Fontan Failure (FF) is a common problem for single-ventricle patients as they reach adulthood. Although several mechanisms may cause FF, an optimized blood flow stream through the surgical conduits is essential to avoid excessive energy loss (EL). Recent clinical studies showed EL is related to the quality of life, exercise capacity, and hepatic function since the single-ventricle feeds pulmonary and systemic circulation serially. 4D flow MRI effectively estimates EL in Fontan circulation and allows clinicians to compare the effectiveness of the treatment strategy concerning pre-intervention. Here, we present 26-year-old women with FF who had normal cardiac catheterization findings and were treated according to high EL definitions that are measured through 4D flow MRI.
RESUMO
In complex cardiovascular surgical reconstructions, conduit materials that avoid possible large-scale structural deformations should be considered. A fundamental mode of mechanical complication is torsional buckling which occurs at the anastomosis site due to the mechanical instability, leading surgical conduit/patch surface deformation. The objective of this study is to investigate the torsional buckling behavior of commonly used materials and to develop a practical method for estimating the critical buckling rotation angle under physiological intramural vessel pressures. For this task, mechanical tests of four clinically approved materials, expanded polytetrafluoroethylene (ePTFE), Dacron, porcine and bovine pericardia, commonly used in pediatric cardiovascular surgeries, are conducted (n = 6). Torsional buckling initiation tests with n = 4 for the baseline case (L = 7.5 cm) and n = 3 for the validation of ePTFE (L = 15 cm) and Dacron (L = 15 cm and L = 25 cm) for each are also conducted at low venous pressures. A practical predictive formulation for the buckling potential is proposed using experimental observations and available theory. The relationship between the critical buckling rotation angle and the lumen pressure is determined by balancing the circumferential component of the compressive principal stress with the shear stress generated by the modified critical buckling torque, where the modified critical buckling torque depends linearly on the lumen pressure. While the proposed technique successfully predicted the critical rotation angle values lying within two standard deviations of the mean in the baseline case for all four materials at all lumen pressures, it could reliably predict the critical buckling rotation angles for ePTFE and Dacron samples of length 15 cm with maximum relative errors of 31% and 38%, respectively, in the validation phase. However, the validation of the performance of the technique demonstrated lower accuracy for Dacron samples of length 25 cm at higher pressure levels of 12 mmHg and 15 mmHg. Applicable to all surgical materials, this formulation enables surgeons to assess the torsional buckling potential of vascular conduits noninvasively. Bovine pericardium has been found to exhibit the highest stability, while Dacron (the lowest) and porcine pericardium have been identified as the least stable with the (unitless) torsional buckling resistance constants, 43,800, 12,300 and 14,000, respectively. There was no significant difference between ePTFE and Dacron, and between porcine and bovine pericardia. However, both porcine and bovine pericardia were found to be statistically different from ePTFE and Dacron individually (p < 0.0001). ePTFE exhibited highly nonlinear behavior across the entire strain range [0, 0.1] (or 10% elongation). The significant differences among the surgical materials reported here require special care in conduit construction and anastomosis design.
Assuntos
Teste de Materiais , Animais , Bovinos , Estresse Mecânico , Politetrafluoretileno/química , Suínos , Pressão , Criança , Humanos , Fenômenos Biomecânicos , Prótese Vascular , Torque , Pericárdio/fisiologiaRESUMO
OBJECTIVE: To assess the biomechanical implications of excessive stent protrusion into the aortic arch in relation to thoracic aortic stent graft (TASG) collapse by simulating the structural load and quantifying the fluid dynamics on the TASG wall protrusion extended into a model arch. METHODS: One-way coupled fluid-solid interaction analyses were performed to investigate the flow-induced hemodynamic and structural loads exerted on the proximal protrusion of the TASG and aortic wall reconstructed from a patient who underwent traumatic thoracic aortic injury repair. Mechanical properties of a Gore TAG thoracic endoprosthesis (W. L. Gore and Assoc, Flagstaff, Ariz) were assessed via experimental radial compression testing and incorporated into the computational modeling. The TASG wall protrusion geometry was characterized by the protrusion extension (PE) and by the angle (θ) between the TASG and the lesser curvature of the aorta. The effect of θ was explored with the following four models with PE fixed at 1.1 cm: θ = 10 degrees, 20 degrees, 30 degrees, and 40 degrees. The effect of PE was evaluated with the following four models with θ fixed at 10 degrees: PE = 1.1 cm, 1.4 cm, 1.7 cm and 2.0 cm. RESULTS: The presence of TASG wall protrusion into the aortic arch resulted in the formation of swirling, complex flow regions in the proximal luminal surface of the endograft. High PE values (PE = 2.0 cm) led to a markedly reduced left subclavian flow rate (0.27 L/min), low systolic perfusion pressure (98 mm Hg), and peak systolic TASG diameter reduction (2 mm). The transmural pressure load across the TASG was maximum for the model with the highest PE and θ, 15.2 mm Hg for the model with PE = 2.0 cm and θ = 10 degrees, and 11.6 mm Hg for PE = 1.1 cm and θ = 40 degrees. CONCLUSIONS: The findings of this study suggest that increased PE imparts an apparent risk of distal end-organ malperfusion and proximal hypertension and that both increased PE and θ lead to a markedly increased transmural pressure across the TASG wall, a load that would portend TASG collapse. Patient-specific computational modeling may allow for identification of patients with high risk of TASG collapse and guide preventive intervention. CLINICAL RELEVANCE: A potentially devastating complication that may occur after endovascular repair of traumatic thoracicaortic injuries is stent graft collapse. Although usually asymptomatic, stent graft collapse may be accompanied by adverse hemodynamic consequences. Numerous anatomic and device-related factors contribute to the development of collapse, but predictive factors have not yet been clearly defined. In the present study, we assessed the relevant hemodynamics and solid mechanics underlying stent graft collapse using a computational fluid-structure interaction framework of stent graft malapposition. Our findings suggest that both increased stent graft angle and extension into the aortic arch lead to a markedly increased transmural pressure across the stent graft wall, portending collapse. Patient-specific computational modeling may allow for identification of patients at high risk for collapse and aid in planning for an additional, prophylactic intervention to avert its occurrence.
Assuntos
Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Simulação por Computador , Procedimentos Endovasculares/instrumentação , Modelos Cardiovasculares , Falha de Prótese , Stents , Algoritmos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aortografia/métodos , Fenômenos Biomecânicos , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Análise de Falha de Equipamento , Hemodinâmica , Humanos , Imageamento Tridimensional , Masculino , Teste de Materiais , Desenho de Prótese , Interpretação de Imagem Radiográfica Assistida por Computador , Fluxo Sanguíneo Regional , Estresse Mecânico , Tomografia Computadorizada por Raios XRESUMO
Apicocaval juxtaposition (ACJ) is a rare congenital heart defect associated with single ventricle physiology where optimal positioning of the Fontan conduit for completion of total cavopulmonary connection (TCPC) is still controversial. In ACJ, the cardiac apex is ipsilateral with the inferior vena cava (IVC), risking kinking and collapse of the Fontan conduit at the apex of the heart. The purpose of this study is to evaluate two viable routes for Fontan conduit connection in patients with ACJ, using computational fluid dynamics. Internal energy loss evaluations were used to determine contribution of conduit curvature to the energy efficiency of each cavopulmonary anastomosis configuration. This percentage of energy loss contribution was found to be greater in the case of a curved extracardiac conduit connection (44%, 4.1 mW) traveling behind the ventricular apex, connecting the IVC to the left pulmonary artery, than the straighter lateral tunnel conduit (6%, 1.4 mW) installed through the ventricular apex. In contrast, net energy loss across the anastomosis was significantly lower with extracardiac TCPC (9.3 mW) in comparison with lateral tunnel TCPC (23.2 mW), highlighting that a curved Fontan conduit is favorable provided that it is traded off for a superior cavopulmonary connection efficiency. Therefore, a relatively longer and curved Fontan conduit has been demonstrated to be a suitable connection option independent of anatomical situations.