3D geometric reconstruction of thoracic aortic aneurysms

Background

Ruptured abdominal aortic aneurysms (AAAs) are the 13^th leading cause of death in the United States. While AAA rupture may occur without significant warning, its risk assessment is generally based on critical values of the maximum AAA diameter (>5 cm) and AAA-growth rate (>0.5 cm/year). These criteria may be insufficient for reliable AAA-rupture risk assessment especially when predicting possible rupture of smaller AAAs.

Methods

Based on clinical evidence, eight biomechanical factors with associated weighting coefficients were determined and summed up in terms of a dimensionless, time-dependent severity parameter, SP(t). The most important factor is the maximum wall stress for which a semi-empirical correlation has been developed.

Results

The patient-specific SP(t) indicates the risk level of AAA rupture and provides a threshold value when surgical intervention becomes necessary. The severity parameter was validated with four clinical cases and its application is demonstrated for two AAA cases.

Conclusion

As part of computational AAA-risk assessment and medical management, a patient-specific severity parameter 0 < SP(t) < 1.0 has been developed. The time-dependent, normalized SP(t) depends on eight biomechanical factors, to be obtained via a patient's pressure and AAA-geometry measurements. The resulting program is an easy-to-use tool which allows medical practitioners to make scientific diagnoses, which may save lives and should lead to an improved quality of life.     

3D geometric reconstruction of thoracic aortic aneurysms

Background  

The thoracic aortic aneurysm (TAA) is a pathology that involves an expansion of the aortic diameter in the thoracic aorta, leading to risk of rupture. Recent studies have suggested that internal wall stress, which is affected by TAA geometry and the presence or absence of thrombus, is a more reliable predictor of rupture than the maximum diameter, the current clinical criterion. Accurate reconstruction of TAA geometry is a crucial step in patient-specific stress calculations.     

Inverse identification of local stiffness across ascending thoracic aortic aneurysms

Biomechanics and Modeling in Mechanobiology - 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...     

Computer modelling of maximal displacement forces in endoluminal thoracic aortic stent graft

The objective of this study was to determine the orientation and magnitude of maximal displacement forces (DFs) in the thoracic aortic aneurysm endograft (TAA endograft) in three-dimensional (3D) space. Theoretical computer model representing the anatomically worst-case scenario with respect to DF magnitude was used to calculate the magnitude and orientation of maximal DF. A patient-specific anatomical computer model of typically seen, average size anatomy was used to analyse the progression of DF throughout the cardiac cycle. Maximal DFs were 35.01 and 37.32 N in standing and supine position, respectively, in 46-mm diameter TAA graft with 90° bend. A patient-specific model shows that a maximal DF magnitude is achieved at the peak systolic flow. In both models, the orientation of the DF vector was perpendicular to the greater curvature of the aorta, with upward (cranial) and sideways components. The effect of shearing force on the total DF that acts on the TAA endograft was found negligible due to the several orders of magnitude stronger contribution of pressure forces to the total DF relative to the wall shear stress contribution, resulting in aortic diameters and angulation being the main drivers of DF. It was discovered that the TAA endografts can be subjected to much stronger DF than previously suspected. The magnitude of maximal DF in thoracic aorta in the worst-case scenario could be as high as 35.01 N (standing) and 37.32 N (supine). This new information should be used in the process of designing new generations of TAA endografts with better migration resistance properties.     

Biomechanical response of ascending thoracic aortic aneurysms: association with structural remodelling

Ascending thoracic aortic aneurysms (ATAA) were resected from patients during graft replacement and non-aneurysmal vessels during autopsy. Tissues were histomechanically tested according to region and orientation, and the experimental recordings reduced with a Fung-type strain--energy function, affording faithful biomechanical characterisation of the vessel response. The material and rupture properties disclosed that ATAA and non-aneurysmal aorta were stiffer and stronger circumferentially, accounted by preferential collagen reinforcement. The deviation of microstructure in the right lateral region, with a longitudinal extracellular matrix and smooth muscle element sub-intimally, reflects the regional differences in material properties identified. ATAA had no effect on strength, but caused stiffening and extensibility reduction, corroborating our histological observation of deficient elastin but not collagen content. Our findings may serve as input data for the implementation of finite element models, to be used as improved surgical intervention criteria, and may further our understanding of the pathophysiology of ATAA and aortic dissection.     

Keratocytes generate traction forces in two phases

Forces generated by goldfish keratocytes and Swiss 3T3 fibroblasts have been measured with nanonewton precision and submicrometer spatial resolution. Differential interference contrast microscopy was used to visualize deformations produced by traction forces in elastic substrata, and interference reflection microscopy revealed sites of cell-substratum adhesions. Force ranged from a few nanonewtons at submicrometer spots under the lamellipodium to several hundred nanonewtons under the cell body. As cells moved forward, centripetal forces were applied by lamellipodia at sites that remained stationary on the substratum. Force increased and abruptly became lateral at the boundary of the lamellipodium and the cell body. When the cell retracted at its posterior margin, cell-substratum contact area decreased more rapidly than force, so that stress (force divided by area) increased as the cell pulled away. An increase in lateral force was associated with widening of the cell body. These mechanical data suggest an integrated, two-phase mechanism of cell motility: (1) low forces in the lamellipodium are applied in the direction of cortical flow and cause the cell body to be pulled forward; and (2) a component of force at the flanks pulls the rear margins forward toward the advancing cell body, whereas a large lateral component contributes to detachment of adhesions without greatly perturbing forward movement.     

Hypergravity affects cell traction forces of fibroblasts

Cells sense and react on changes of the mechanical properties of their environment and, likewise, respond to external mechanical stress applied to them. However, whether the gravitational field as overall body force modulates cellular behavior is unclear. Different studies demonstrated that micro- and hypergravity influences the shape and elasticity of cells, initiate cytoskeleton reorganization, and influence cell motility. All these cellular properties are interconnected and contribute to forces that cells apply on their surrounding microenvironment. Yet, studies that investigated changes of cell traction forces under hypergravity conditions are scarce. Here, we performed hypergravity experiments on 3T3 fibroblast cells using the large-diameter centrifuge at the European Space Agency - European Space Research and Technology Centre. Cells were exposed to hypergravity of up to 19.5 g for 16 h in both the upright and the inverted orientation with respect to the g-force vector. We observed a decrease in cellular traction forces when the gravitational field was increased up to 5.4 g, followed by an increase of traction forces for higher gravity fields up to 19.5 g independent of the orientation of the gravity vector. We attribute the switch in cellular response to shear thinning at low g-forces, followed by significant rearrangement and enforcement of the cytoskeleton at high g-forces.     

Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states

Aneurysms of the thoracic aorta are a “silent killer” with no evident clinical signs until the fatal outcome. Molecular and genetic bases of thoracic aortic aneurysms mainly include transforming growth factor beta signaling, smooth muscle contractile units and metabolism genes, and extracellular matrix genes. In recent studies, a role of Notch signaling, among other pathways, has emerged in disease pathogenesis. Notch is a highly conserved signaling pathway that regulates the development and differentiation of many types of tissues and influences major cellular processes such as cell proliferation, differentiation and apoptosis. Mutations in several Notch signaling components have been associated with a number of heart defects, demonstrating an essential role of Notch signaling both in cardiovascular system development and its maintenance during postnatal life. This review discusses the role of Notch signaling in the pathogenesis of thoracic aortic aneurysms considering development and maintenance of the aortic root and how developmental regulations by Notch signaling may influence thoracic aortic aneurysms.     

细胞内铜/锌超氧化物歧化酶在人胸主动脉夹层的表达研究

目的:探讨细胞内铜/锌超氧化物岐化酶(copper zinc superoxide dismutase,Cu/Zn-SOD,SOD-1)在人胸主动脉夹层(humanthoracic aortic dissection,hTAD)中的表达情况及其在hTAD中的可能作用。方法:蛋白质印迹法(Western blot,WB)检测SOD-1在TAD和正常人胸主动脉(NA)中膜组织中的表达情况,免疫组织化学染色(immunohistochemistry,IHC)验证SOD-1在动脉壁中的表达和定位。结果:蛋白质印迹和免疫组化染色均显示SOD-1在TAD组表达量较NA组减低(P<0.05);免疫组化染色进一步显示,SOD-1主要位于主动脉壁中膜平滑肌细胞的胞质内,其在夹层主动脉壁中膜撕开处表达缺失。结论:SOD-1在TAD中表达量减少,可能由于参与氧化应激引起的脂质过氧化和炎症反应,以及细胞外基质(extracellular matrix,ECM)的降解等机制所致。     

Regulation of NaK-ATPase by platelet-derived growth factors in cultured rat thoracic aortic smooth muscle cells

Regulation of (Na⁺ + K⁺)-adenosine triphosphatase (NaK-ATPase) by platelet-derived growth factor (PDGF) in cultured rat thoracic aortic smooth muscle cells (SMC) was examined. PDGF-BB enhances SMC proliferation and NaK-ATPase activity. Ouabain, an inhibitor of NaK-ATPase activity, prevents PDGF-BB-induced SMC proliferation. As shown by Western blot and immunochemiluminescence analysis, PDGF-BB also enhances ₁, truncated ₁, and ₁ NaK-ATPase subunit levels. PDGF-AA and PDGF-AB show no effect on ₁ and truncated ₁ levels in slot blot analysis. Induction of NaK-ATPase subunit levels by PDGF-BB could be one of the initial events in vascular SMC proliferation.     

Regulation of fibronectin by platelet-derived growth factors in cultured rat thoracic aortic smooth muscle cells

Induction of Fibronectin (FN) gene expression by platelet-derived growth factor (PDGF) isoforms in rat thoracic aortic smooth muscle cells (SMC) was examined. PDGF-BB enhances FN levels in SMC cultures in a time- and concentration-response fashion. PDGF-AA and PDGF-AB show no effect on FN levels. The effects of insulin and insulin-like growth factor-I (IGF-I) on PDGF-BB-induced FN levels were examined. No additivity of FN levels is observed between PDGF-BB and insulin and/or IGF-I. Experiments also show that PDGF-BB enhances FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. Induction of FN and FN mRNA levels by PDGF-BB could be one of the initial events in vascular SMC proliferation and extracellular matrix expansion, leading to atherosclerosis and hypertension.     

Experimental characterization of rupture in human aortic aneurysms using a full-field measurement technique

The present study aims at investigating biomechanical failure behaviour of human aneurismal aortic tissues so as to diagnose the rupture risk of aneurysms more accurately. An inflation test is performed on aneurismal aortic tissues up to failure and full-field measurements are achieved using stereo digital image correlation. Then, an appropriate constitutive model derived from histological structure of arteries is adopted to retrieve the Cauchy stress. The virtual fields method is used as an inverse procedure to identify material parameters. Next, the Cauchy stress components are calculated from the identified parameters and the measured Lagrange strain fields. Finally, an important stress parameter which can quantify the strength of aneurismal tissues is derived from the failure stress of aneurismal tissues.     

Prostaglandin and thromboxane synthesis by tissue slices from human aortic aneurysms

Sliced portions of the walls of human aortic aneurysms were incubated with extracts of human plasma and serum to determine the profile of prostanoid production. 6-Oxo-prostaglandin (PG) F1 alpha, PGE2, PGF2 alpha, and thromboxane (TX) B2 were measured by gas chromatography/electron capture mass spectrometry. 6-Oxo-PGF1 alpha, the stable hydrolysis product of PGI2, was the major cyclooxygenase product but substantial amounts of TXB2 (the hydrolysis product of TXA2), with smaller amounts of PGE2 and PGF2 alpha were also synthesised. These prostanoids could contribute to the response of the vascular wall to injury, thereby influencing the disease process. Serum extracts stimulated PGI2 and TXA2 synthesis, probably as a result of their Ca2+ content.     

Nonlinear model of human descending thoracic aortic segments with residual stresses

The nonlinear static deformation of human descending thoracic aortic segments is investigated. The aorta segments are modeled as straight axisymmetric circular cylindrical shells with three hyperelastic anisotropic layers and residual stresses by using an advanced nonlinear shell theory with higher-order thickness deformation not available in commercial finite element codes. The residual stresses are evaluated in the closed configuration in an original way making use of the multiplicative decomposition. The model was initially validated through comparison with published numerical and experimental data for artery and aorta segments. Then, two different cases of healthy thoracic descending aorta segments were numerically simulated. Material data and residual stresses used in the models came from published layer-specific experiments for human aortas. The material model adopted in the study is the mechanically based Gasser–Ogden–Holzapfel, which takes into account collagen fiber dispersion. Numerical results present a difference between systolic and diastolic inner radii close to the data available in literature from in vivo measurements for the corresponding age groups. Constant length of the aortic segment between systolic and diastolic pressures was obtained for the material model that takes the dispersion of the fiber orientations into account.     

Flexible substrata for the detection of cellular traction forces

By modulating adhesion signaling and cytoskeletal organization, mechanical forces play an important role in various cellular functions, from propelling cell migration to mediating communication between cells. Recent developments have resulted in several new approaches for the detection, analysis and visualization of mechanical forces generated by cultured cells. Combining these methods with other approaches, such as green-fluorescent protein (GFP) imaging and gene manipulation, proves to be particularly powerful for analyzing the interplay between extracellular physical forces and intracellular chemical events.     

Regulation of fibronectin expression by PDGF-BB And IGF-I in cultured rat thoracic aortic adventitial fibroblasts.

Regulation of fibronectin (FN) by Platelet-derived Growth Factor-BB (PDGF-BB) and Insulin-like Growth Factor-I (IGF-I) in cultured rat thoracic aortic adventitial fibroblasts were examined. PDGF-BB enhances FN mRNA levels in a time and concentration-dependent fashion. The effect of IGF-I on PDGF-BB-induced FN levels was also examined. There was a larger increase in FN mRNA levels (4-fold) in the cells treated with both IGF-I and PDGF-BB than with either IGF-I (2-fold) or PDGF-BB (2-fold) alone. The effects of PDGF-BB and IGF-I on FN levels were examined. There was a larger increase in FN levels (135%) in the cells treated with both PDGF-BB and IGF-I than with either PDGF-BB (43%) or IGF-I (45%) alone. Regulation of adventitial fibroblast FN may lead to blood vessel diseases and/or angiogenesis.