Stereoscopically observed deformations of a compliant abdominal aortic aneurysm model

A new experimental setup has been implemented to precisely measure the deformations of an entire model abdominal aortic aneurysm (AAA). This setup addresses a gap between the computational and experimental models of AAA that have aimed at improving the limited understanding of aneurysm development and rupture. The experimental validation of the deformations from computational approaches has been limited by a lack of consideration of the large and varied deformations that AAAs undergo in response to physiologic flow and pressure. To address the issue of experimentally validating these calculated deformations, a stereoscopic imaging system utilizing two cameras was constructed to measure model aneurysm displacement in response to pressurization. The three model shapes, consisting of a healthy aorta, an AAA with bifurcation, and an AAA without bifurcation, were also evaluated with computational solid mechanical modeling using finite elements to assess the impact of differences between material properties and for comparison against the experimental inflations. The device demonstrated adequate accuracy (surface points were located to within 0.07?mm) for capturing local variation while allowing the full length of the aneurysm sac to be observed at once. The experimental model AAA demonstrated realistic aneurysm behavior by having cyclic strains consistent with reported clinical observations between pressures 80 and 120?mm Hg. These strains are 1-2%, and the local spatial variations in experimental strain were less than predicted by the computational models. The three different models demonstrated that the asymmetric bifurcation creates displacement differences but not cyclic strain differences within the aneurysm sac. The technique and device captured regional variations of strain that are unobservable with diameter measures alone. It also allowed the calculation of local strain and removed rigid body motion effects on the strain calculation. The results of the computations show that an asymmetric aortic bifurcation created displacement differences but not cyclic strain differences within the aneurysm sac.     

Unsteady flow of Casson fluids through the eccentric circular tube.

As a model of the flow through the false lumen of the dissecting aortic aneurysm, the starting and stopping flows of the Casson fluid through the eccentric circular tube are studied numerically. The calculations are performed by using the one-direction fully developed unsteady flow model. The calculation results show that the non-Newtonian property of the Casson fluid has the following two effects. One is the decrease in the flow rate through the false lumen, the other is the effect to strengthen the non-uniformity of the velocity distribution in the false lumen. Moreover, the calculations based on a triphasic waveform measured by McDonald are performed and the development of the dissecting aortic aneurysm is discussed on the basis of the calculated wall shear stress.     

Blood flow patterns and pressure loss in the ascending aorta: A comparative study on physiological and aneurysmal conditions

An aortic aneurysm is defined as a balloon-shaped bulging of all three histologic components of the aortic vessel walls (intima, media and adventitia). This dilation results from vessel weakening owing to remodeling, i.e. due to cystic degeneration of the Tunica media (Marfan), progression of atherosclerosis or presence of a bicuspid aortic valve. The growth rate of the aortic diameter varies from patient to patient and may progress until the aneurysm ultimately ruptures. The role of hemodynamics, i.e. blood flow patterns, and shear stresses that are supposed to intensify during aneurysm growth are not yet fully understood, but thought to play a key role in the enlargement process. The aim of this study is to characterize the aortic blood flow in a silicone model of a pathological aorta with ascending aneurysm, to analyze the differences in the blood flow pattern compared to a healthy aortic model, and to single out possible blood flow characteristics measurable using phase contrast magnetic resonance imaging (MRI) that could serve as indicators for aneurysm severity. MRI simulations were performed under physiological, pulsatile flow conditions using data obtained from optical three dimensional particle tracking measurements. In comparison to the healthy geometry, elevated turbulence intensity and pressure loss are measured in the diseased aorta, which we propose as a complimentary indicator for assessing the aneurysmal severity. Our results shed a light on the interplay between the blood flow dynamics and their contribution to the pathophysiology and possible role for future risk assessment of ascending aortic aneurysms.     

MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in experimental rats

Recent studies have suggested that inflammation actively participates in ascending aortic aneurysm formation. The aim of the present study was to evaluate the expression changes of adhesion molecules and MMPs in an experimental model of ascending aortic aneurysm induced by ascending aorta banding in Wistar rats. Twelve rats developed aortic dilation after ascending aorta banding treatment, while nine normal animals underwent surgery without banding were used as controls. Light microscope and scanning electron microscope showed that the wall of the ascending aorta became disorganized as well as infiltration by inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a significant increase in the immunostaining of MCP-1 was observed in the aneurysmal wall as compared to the normal aortic wall. Under similar experimental conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was markedly increased in the aneurysmal wall. In addition, gelatin zymographic analysis showed that the expression and activities of MMP-2 and MMP-9 were remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1 are involved in the pathogenesis of ascending aortic aneurysm and an increase in the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of ascending aortic aneurysm.     

基质金属蛋白酶3、9在升主动脉瘤中的表达

目的探讨基质金属蛋白酶3、9(MMP-3、MMP-9)在升主动脉瘤发病机制中的作用.方法将40只幼年Wistar大鼠随机分为对照组和实验组,制备升主动脉缩窄鼠模型.于术后3-5个月取升主动脉,采用HE染色和免疫组化技术,观察升主动脉形态学变化及MMP-3、MMP-9的蛋白表达.结果升主动脉瘤中MMP-3、MMP-9表达强阳性.结论 MMP-3、MMP-9在升主动脉瘤成因中有可能有重要作用.     

Hemodynamic analysis of a novel stent graft design with slit perforations in thoracic aortic aneurysm

Thoracic endovascular aortic repair (TEVAR) has been introduced as a less invasive approach to the treatment of thoracic aortic aneurysm (TAA). However, the effectiveness of TEVAR in the treatment of TAA is often limited due to the complex anatomy of aortic arch. Flow preservation at the three supra-aortic branches further increases the overall technical difficulty. This study proposes a novel stent graft design with slit perforations that can positively alter the hemodynamics at the aortic arch while maintaining blood flow to supra-aortic branches. We carried out a computational fluid dynamic (CFD) analysis to evaluate flow characteristics near stented aortic arch in simplified TAA models, followed by in-vitro experiments using particle image velocimetry (PIV) in a mock circulatory loop. The hemodynamics result was studied in terms of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and endothelial cell action potential (ECAP). The results showed that the stent graft with slit perforations can reduce the disturbed flow region considerably. Furthermore, the effect of the slits on flow preservation to the supra-aortic branches was simulated and compared with experimental results. The effectiveness of the stent graft with slit perforations in preserving flow to the branches was demonstrated by both simulated and experimental results. Low TAWSS and elevated ECAP were observed in the aortic arch aneurysm after the placement of the stent graft with slits, implying the potential of thrombus formation in the aneurysm. On the other hand, the effects of the stent grafts with full-slit design and half-slit design on the shear stress did not differ significantly. The present analysis indicated that not only could the stent graft with slit perforations shield the aneurysm from rupture, but also it resulted in a favorable environment for thrombus that can contribute to the shrinkage of the aneurysm.     

Improving the Efficiency of Abdominal Aortic Aneurysm Wall Stress Computations

An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses.     

Investigation of material modeling in fluid–structure interaction analysis of an idealized three-layered abdominal aorta: aneurysm initiation and fully developed aneurysms

Different material models for an idealized three-layered abdominal aorta are compared using computational techniques to study aneurysm initiation and fully developed aneurysms. The computational model includes fluid–structure interaction (FSI) between the blood vessel and the blood. In order to model aneurysm initiation, the medial region was degenerated to mimic the medial loss occurring in the inception of an aneurysm. Various cases are considered in order to understand their effects on the initiation of an abdominal aortic aneurysm. The layers of the blood vessel were modeled using either linear elastic materials or Mooney–Rivlin (otherwise known as hyperelastic) type materials. The degenerated medial region was also modeled in either linear elastic or hyperelastic-type materials and assumed to be in the shape of an arc with a thin width or a circular ring with different widths. The blood viscosity effect was also considered in the initiation mechanism. In addition, dynamic analysis of the blood vessel was performed without interaction with the blood flow by applying time-dependent pressure inside the lumen in a three-layered abdominal aorta. The stresses, strains, and displacements were compared for a healthy aorta, an initiated aneurysm and a fully developed aneurysm. The study shows that the material modeling of the vessel has a sizable effect on aneurysm initiation and fully developed aneurysms. Different material modeling of degeneration regions also affects the stress–strain response of aneurysm initiation. Additionally, the structural analysis without considering FSI (called noFSI) overestimates the peak von Mises stress by 52% at the interfaces of the layers.     

Measuring,reversing, and modeling the mechanical changes due to the absence of Fibulin-4 in mouse arteries

Mice with a smooth muscle cell (SMC)-specific deletion of Fibulin-4 (SMKO) show decreased expression of SMC contractile genes, decreased circumferential compliance, and develop aneurysms in the ascending aorta. Neonatal administration of drugs that inhibit the angiotensin II pathway encourages the expression of contractile genes and prevents aneurysm development, but does not increase compliance in SMKO aorta. We hypothesized that multidimensional mechanical changes in the aorta and/or other elastic arteries may contribute to aneurysm pathophysiology. We found that the SMKO ascending aorta and carotid artery showed mechanical changes in the axial direction. These changes were not reversed by angiotensin II inhibitors, hence reversing the axial changes is not required for aneurysm prevention. Mechanical changes in the circumferential direction were specific to the ascending aorta; therefore, mechanical changes in the carotid do not contribute to aortic aneurysm development. We also hypothesized that a published model of postnatal aortic growth and remodeling could be used to investigate mechanisms behind the changes in SMKO aorta and aneurysm development over time. Dimensions and mechanical behavior of adult SMKO aorta were reproduced by the model after modifying the initial component material constants and the aortic dilation with each postnatal time step. The model links biological observations to specific mechanical responses in aneurysm development and treatment.     

Induction of macrophage chemotaxis by aortic extracts from patients with Marfan syndrome is related to elastin binding protein

Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue with prominent skeletal, ocular, and cardiovascular manifestations. Aortic aneurysm and dissection are the major determinants of premature death in untreated patients. In previous work, we showed that extracts of aortic tissues from the mgR mouse model of Marfan syndrome showed increased chemotactic stimulatory activity related to the elastin-binding protein. Aortic samples were collected from 6 patients with Marfan syndrome and 8 with isolated aneurysms of the ascending aorta. Control samples were obtained from 11 organ donors without known vascular or connective tissue diseases. Soluble proteins extracted from the aortic samples of the two patient groups were compared against buffer controls and against the aortic samples from controls with respect to the ability to induce macrophage chemotaxis as measured using a modified Boyden chamber, as well as the reactivity to a monoclonal antibody BA4 against bioactive elastin peptides using ELISA. Samples from Marfan patients displayed a statistically significant increase in chemotactic inductive activity compared to control samples. Additionally, reactivity to BA4 was significantly increased. Similar statistically significant increases were identified for the samples from patients with idiopathic thoracic aortic aneurysm. There was a significant correlation between the chemotactic index and BA4 reactivity, and the increases in chemotactic activity of extracts from Marfan patients could be inhibited by pretreatment with lactose, VGVAPG peptides, or BA4, which indicates the involvement of EBP in mediating the effects. Our results demonstrate that aortic extracts of patients with Marfan syndrome can elicit macrophage chemotaxis, similar to our previous study on aortic extracts of the mgR mouse model of Marfan syndrome (Guo et al., Circulation 2006; 114:1855-62).     

Long Telomeres in Blood Leukocytes Are Associated with a High Risk of Ascending Aortic Aneurysm

Ascending aortic aneurysm is a connective tissue disorder. Even though multiple novel gene mutations have been identified, risk profiling and diagnosis before rupture still represent a challenge. There are studies demonstrating shorter telomere lengths in the blood leukocytes of abdominal aortic aneurysm patients. The aim of this study was to measure whether relative telomere lengths are changed in the blood leukocytes of ascending aortic aneurysm patients. We also studied the expression of telomerase in aortic tissue samples of ascending aortic aneurysms. Relative lengths of leukocyte telomeres were determined from blood samples of patients with ascending aortic aneurysms and compared with healthy controls. Telomerase expression, both at the level of mRNA and protein, was quantified from the aortic tissue samples. Mean relative telomere length was significantly longer in ascending aortic aneurysm blood samples compared with controls (T/S ratio 0.87 vs. 0.61, p<0.001). Expressions of telomerase mRNA and protein were elevated in the aortic aneurysm samples (p<0.05 and p<0.01). Our study reveals a significant difference in the mean length of blood leukocyte telomeres in ascending aortic aneurysm and controls. Furthermore, expression of telomerase, the main compensating factor for telomere loss, is elevated at both the mRNA and protein level in the samples of aneurysmal aorta. Further studies will be needed to confirm if this change in telomere length can serve as a tool for assessing the risk of ascending aortic aneurysm.     

Vascular wall flow-induced forces in a progressively enlarged aneurysm model

The current study is focused on the numerical investigation of the flow field induced by the unsteady flow in the vicinity of an abdominal aortic aneurysm model. The computational fluid dynamics code used is based on the finite volume method, and it has already been used in various bioflow studies. For modelling the rheological behaviour of blood, the Quemada non-Newtonian model is employed, which is suitable for simulating the two-phase character of blood namely a suspension of blood cells in plasma. For examining its non-Newtonian effects a comparison with a corresponding Newtonian flow is carried out. Furthermore, the investigation is focused on the distribution of the flow-induced forces on the interior wall of the aneurysm and in order to study the development of the distribution with the gradual enlargement of the aneurysm, three different degrees of aneurysm-growth have been assumed. Finally and for examining the effect of the distribution on the aneurysm growth, a comparison is made between the pressure and wall shear-stress distributions at the wall for each growth-degree.     

Vascular wall flow-induced forces in a progressively enlarged aneurysm model

The current study is focused on the numerical investigation of the flow field induced by the unsteady flow in the vicinity of an abdominal aortic aneurysm model. The computational fluid dynamics code used is based on the finite volume method, and it has already been used in various bioflow studies. For modelling the rheological behaviour of blood, the Quemada non-Newtonian model is employed, which is suitable for simulating the two-phase character of blood namely a suspension of blood cells in plasma. For examining its non-Newtonian effects a comparison with a corresponding Newtonian flow is carried out. Furthermore, the investigation is focused on the distribution of the flow-induced forces on the interior wall of the aneurysm and in order to study the development of the distribution with the gradual enlargement of the aneurysm, three different degrees of aneurysm-growth have been assumed. Finally and for examining the effect of the distribution on the aneurysm growth, a comparison is made between the pressure and wall shear-stress distributions at the wall for each growth-degree.     

On the inheritance of abdominal aortic aneurysm.

To determine the mode of inheritance of abdominal aortic aneurysm, data on first-degree relatives of 91 probands were collected. Results of segregation analysis performed on these data are reported. Many models, including nongenetic and genetic models, were compared using likelihood methods. The nongenetic model was rejected; statistically significant evidence in favor of a genetic model was found. Among the many genetic models compared, the most parsimonious genetic model was that susceptibility to abdominal aortic aneurysm is determined by a recessive gene at an autosomal diallelic major locus. A multifactorial component in addition to the major locus does not increase the likelihood of the data significantly.     

An Aortic Tampon for Emergency Control of Ruptured Abdominal Aneurysm

Ruptured abdominal aneurysm has now become a common surgical emergency, frequently amenable to successful resection and cure. The final result is often marred, however, by the effects of renal, coronary or cerebral ischemia resulting from dangerous hypotension during transportation of the patient to a vascular centre.An aortic catheter has been developed which is passed by way of a brachial artery cut-down so that it rests in the abdominal aorta. The balloon at its tip is then filled with sodium diatrizoate (Hypaque) so that it completely obstructs the aortic lumen just above the level of the aneurysm. Accurate positioning of the balloon to carefully preserve renal blood flow is facilitated by fluoroscopic control. The use of this procedure in three patients has been very satisfactory, with a dramatic return of consciousness and of normal blood pressure, without the need for further blood replacement. Subsequent surgery with dissection of the aneurysm was aided by the presence of the palpable inflated balloon.     

FHL1在胸主动脉瘤发病机制中的初步研究

目的:研究FHL1蛋白在胸主动脉瘤发病机制中的作用。方法:利用Western Blotting分析胸主动脉瘤患者与正常人主动脉组织中FHL1蛋白表达的情况,利用免疫组织化学检测FHL1蛋白在主动脉组织中的定位,并进一步分析该蛋白在两组中的表达情况,结合文献报道分析FHL1蛋白在胸主动脉瘤发病机制中的作用。结果:Western Blotting、免疫组织化学分析均表明FHL1蛋白在胸主动脉瘤患者主动脉组织表达水平较正常人明显降低,FHL1蛋白主要定位于主动脉血管平滑肌细胞的细胞质中。结论:FHL1蛋白在胸主动脉瘤患者主动脉组织中明显降低,这可能导致主动脉血管平滑肌细胞增殖能力下降,从而在胸主动脉瘤的发病中发挥重要的作用。     

A novel method for non-invasively detecting the severity and location of aortic aneurysms

The influence of an aortic aneurysm on blood flow waveforms is well established, but how to exploit this link for diagnostic purposes still remains challenging. This work uses a combination of experimental and computational modelling to study how aneurysms of various size affect the waveforms. Experimental studies are carried out on fusiform-type aneurysm models, and a comparison of results with those from a one-dimensional fluid–structure interaction model shows close agreement. Further mathematical analysis of these results allows the definition of several indicators that characterize the impact of an aneurysm on waveforms. These indicators are then further studied in a computational model of a systemic blood flow network. This demonstrates the methods’ ability to detect the location and severity of an aortic aneurysm through the analysis of flow waveforms in clinically accessible locations. Therefore, the proposed methodology shows a high potential for non-invasive aneurysm detectors/monitors.     

Pulsatile non-Newtonian haemodynamics in a 3D bifurcating abdominal aortic aneurysm model

Numerical prediction of non-Newtonian blood flow in a 3D abdominal aortic aneurysm bifurcating model is carried out. The non-Newtonian Carreau model is used to characterise the shear thinning behaviour of the human blood. A physical inlet velocity waveform incorporating a radial velocity distribution reasonably representative of a practical case configuration is employed. Case studies subject to both equal and unequal outlet pressures at iliac bifurcations are presented to display convincingly the downstream pressure influences on the flow behaviour within the aneurysm. Simulations indicate that the non-Newtonian aspects of the blood cannot at all be neglected or given a cursory treatment. The wall shear stress (WSS) is found to change significantly at both the proximal and distal ends of the aneurysm. At the peak systole, the WSS is peak around the bifurcation point, whereas the WSS becomes zero in the bifurcation point. Differential downstream pressure fields display significant effects regarding the flow evolution in the iliac arteries, whereas little or no effects are observed directly on the flow details in the aneurysm.     

Pulsatile non-Newtonian haemodynamics in a 3D bifurcating abdominal aortic aneurysm model

Numerical prediction of non-Newtonian blood flow in a 3D abdominal aortic aneurysm bifurcating model is carried out. The non-Newtonian Carreau model is used to characterise the shear thinning behaviour of the human blood. A physical inlet velocity waveform incorporating a radial velocity distribution reasonably representative of a practical case configuration is employed. Case studies subject to both equal and unequal outlet pressures at iliac bifurcations are presented to display convincingly the downstream pressure influences on the flow behaviour within the aneurysm. Simulations indicate that the non-Newtonian aspects of the blood cannot at all be neglected or given a cursory treatment. The wall shear stress (WSS) is found to change significantly at both the proximal and distal ends of the aneurysm. At the peak systole, the WSS is peak around the bifurcation point, whereas the WSS becomes zero in the bifurcation point. Differential downstream pressure fields display significant effects regarding the flow evolution in the iliac arteries, whereas little or no effects are observed directly on the flow details in the aneurysm.