Mechano-biology in the thoracic aortic aneurysm: a review and case study

An aortic aneurysm is a permanent and localized dilatation of the aorta resulting from an irreversible loss of structural integrity of the aortic wall. The infrarenal segment of the abdominal aorta is the most common site of aneurysms; however, they are also common in the ascending and descending thoracic aorta. Many cases remain undetected because thoracic aortic aneurysms (TAAs) are usually asymptomatic until complications such as aortic dissection or rupture occurs. Clinical estimates of rupture potential and dissection risk, and thus interventional planning for TAAs, are currently based primarily on the maximum diameter and growth rate. The growth rate is calculated from maximum diameter measurements at two subsequent time points; however, this measure cannot reflect the complex changes of vessel wall morphology and local areas of weakening that underline the strong regional heterogeneity of TAA. Due to the high risks associated with both open and endovascular repair, an intervention is only justified if the risk for aortic rupture or dissection exceeds the interventional risks. Consequently, TAAs clinical management remains a challenge, and new methods are needed to better identify patients for elective repair. We reviewed the pathophysiology of TAAs and the role of mechanical stresses and mathematical growth models in TAA management; as a proof of concept, we applied a multiscale biomechanical analysis to a case study of TAA.     

Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.     

Mechanical instability of normal and aneurysmal arteries

Tortuous arteries associated with aneurysms have been observed in aged patients with atherosclerosis and hypertension. However, the underlying mechanism is poorly understood. The objective of this study was to determine the effect of aneurysms on arterial buckling instability and the effect of buckling on aneurysm wall stress. We investigated the mechanical buckling and post-buckling behavior of normal and aneurysmal carotid arteries and aorta’s using computational simulations and experimental measurements to elucidate the interrelationship between artery buckling and aneurysms. Buckling tests were done in porcine carotid arteries with small aneurysms created using elastase treatment. Parametric studies were done for model aneurysms with orthotropic nonlinear elastic walls using finite element simulations. Our results demonstrated that arteries buckled at a critical buckling pressure and the post-buckling deflection increased nonlinearly with increasing pressure. The presence of an aneurysm can reduce the critical buckling pressure of arteries, although the effect depends on the aneurysm’s dimensions. Buckled aneurysms demonstrated a higher peak wall stress compared to unbuckled aneurysms under the same lumen pressure. We conclude that aneurysmal arteries are vulnerable to mechanical buckling and mechanical buckling could lead to high stresses in the aneurysm wall. Buckling could be a possible mechanism for the development of tortuous aneurysmal arteries such as in the Loeys–Dietz syndrome.     

Mechanics, mechanobiology, and modeling of human abdominal aorta and aneurysms

Biomechanical factors play fundamental roles in the natural history of abdominal aortic aneurysms (AAAs) and their responses to treatment. Advances during the past two decades have increased our understanding of the mechanics and biology of the human abdominal aorta and AAAs, yet there remains a pressing need for considerable new data and resulting patient-specific computational models that can better describe the current status of a lesion and better predict the evolution of lesion geometry, composition, and material properties and thereby improve interventional planning. In this paper, we briefly review data on the structure and function of the human abdominal aorta and aneurysmal wall, past models of the mechanics, and recent growth and remodeling models. We conclude by identifying open problems that we hope will motivate studies to improve our computational modeling and thus general understanding of AAAs.     

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms.Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions.The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat''s descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta.We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat.     

Fluid-structure interaction of a patient-specific abdominal aortic aneurysm treated with an endovascular stent-graft

Background  

Abdominal aortic aneurysms (AAA) are local dilatations of the infrarenal aorta. If left untreated they may rupture and lead to death. One form of treatment is the minimally invasive insertion of a stent-graft into the aneurysm. Despite this effective treatment aneurysms may occasionally continue to expand and this may eventually result in post-operative rupture of the aneurysm. Fluid-structure interaction (FSI) is a particularly useful tool for investigating aneurysm biomechanics as both the wall stresses and fluid forces can be examined.     

Including surrounding tissue improves ultrasound-based 3D mechanical characterization of abdominal aortic aneurysms

ObjectivesIn this study the influence of surrounding tissues including the presence of the spine on wall stress analysis and mechanical characterization of abdominal aortic aneurysms using ultrasound imaging has been investigated.MethodsGeometries of 7 AAA patients and 11 healthy volunteers were acquired using 3-D ultrasound and converted to finite element based models. Model complexity of externally unsupported (aorta-only) models was complemented with inclusion of both soft tissue around the aorta and a spine support dorsal to the aorta. Computed 3-D motion of the aortic wall was verified by means of ultrasound speckle tracking. Resulting stress, strain, and estimated shear moduli were analyzed to quantify the effect of adding surrounding material supports.ResultsAn improved agreement was shown between the ultrasound measurements and the finite element tissue and spine models compared to the aorta-only models. Peak and 99-percentile Von Mises stress showed an overall decrease of 23–30%, while estimated shear modulus decreased with 12–20% after addition of the soft tissue. Shear strains in the aortic wall were higher in areas close to the spine compared to the anterior region.ConclusionsImproving model complexity with surrounding tissue and spine showed a homogenization of wall stresses, reduction in homogeneity of shear strain at the posterior side of the AAA, and a decrease in estimated aortic wall shear modulus. Future research will focus on the importance of a patient-specific spine geometry and location.     

Pulsatile flow in fusiform models of abdoiminal aortic aneurysms: flow fields, velocity patterns and flow-induced wall stresses

As one important step in the investigation of the mechanical factors that lead to rupture of abdominal aortic aneurysms, flow fields and flow-induced wall stress distributions have been investigated in model aneurysms under pulsatile flow conditions simulating the in vivo aorta at rest. Vortex pattern emergence and evolution were evaluated, and conditions for flow stability were delineated. Systolic flow was found to be forward-directed throughout the bulge in all the models, regardless of size. Vortices appeared in the bulge initially during deceleration from systole, then expanded during the retrograde flow phase. The complexity of the vortex field depended strongly on bulge diameter In every model, the maximum shear stress occurred at peak systole at the distal bulge end, with the greatest shear stress developing in a model corresponding to a 4.3 cm AAA in vivo. Although the smallest models exhibited stable flow throughout the cycle, flow in the larger models became increasingly unstable as bulge size increased, with strong amplification of instability in the distal half of the bulge. These data suggest that larger aneurysms in vivo may be subject to more frequent and intense turbulence than smaller aneurysms. Concomitantly, increased turbulence may contribute significantly to wall stress magnitude and thereby to risk of rupture.     

Ruptured mycotic aortic aneurysm in a sooty mangabey (Cercocebus atys)

Mycotic aortic aneurysm is a local, irreversible dilatation of the aorta associated with destruction of the vessel wall by infection and is a grave clinical condition associated with high morbidity and mortality in humans. Rupture of aortic aneurysms can be spontaneous, idiopathic, or due to severe trauma, and the condition has been associated with bacterial and, rarely, fungal infections in humans and animals. Here, we describe a case of ruptured spontaneous aortic aneurysm associated with zygomycetic infection in a 21-y-old female sooty mangabey. The animal did not present with any significant clinical signs before being found dead. At necropsy, she was in good body condition, and the thoracic cavity had a large amount of clotted blood filling the left pleural space and surrounding the lung lobes. Near the aortic arch, the descending thoracic aorta was focally perforated (diameter, approximately 0.15 cm), and clotted blood adhered to the tunica adventitia. The aortic intima had multiple, firm, pale-yellow nodules (diameter, 0.25 to 0.5 cm). Histopathologically, these nodules consisted of severe multifocal pyogranulomatous inflammation intermixed with necrosis, fibrin, and broad, infrequently septate, thin-walled fungal hyphae. Immunohistochemistry revealed fungal hyphae characteristic of Mucormycetes (formerly Zygomycetes), and PCR analysis identified the organism as Basidiobolus spp. Dissemination of the fungus beyond the aorta was not noted. Spontaneous aortic aneurysms have been described in nonhuman primates, but this is the first reported case of a ruptured spontaneous aortic aneurysm associated with entomophthoromycetic infection in a sooty mangabey.     

3D reconstruction and manufacture of real abdominal aortic aneurysms: from CT scan to silicone model

Abdominal aortic aneurysm (AAA) can be defined as a permanent and irreversible dilation of the infrarenal aorta. AAAs are often considered to be an aorta with a diameter 1.5 times the normal infrarenal aorta diameter. This paper describes a technique to manufacture realistic silicone AAA models for use with experimental studies. This paper is concerned with the reconstruction and manufacturing process of patient-specific AAAs. 3D reconstruction from computed tomography scan data allows the AAA to be created. Mould sets are then designed for these AAA models utilizing computer aided designcomputer aided manufacture techniques and combined with the injection-moulding method. Silicone rubber forms the basis of the resulting AAA model. Assessment of wall thickness and overall percentage difference from the final silicone model to that of the computer-generated model was performed. In these realistic AAA models, wall thickness was found to vary by an average of 9.21%. The percentage difference in wall thickness recorded can be attributed to the contraction of the casting wax and the expansion of the silicone during model manufacture. This method may be used in conjunction with wall stress studies using the photoelastic method or in fluid dynamic studies using a laser-Doppler anemometry. In conclusion, these patient-specific rubber AAA models can be used in experimental investigations, but should be assessed for wall thickness variability once manufactured.     

Biomechanical characterization of tissue types in murine dissecting aneurysms based on histology and 4D ultrasound-derived strain

Abdominal aortic aneurysm disease is the local enlargement of the aorta, typically in the infrarenal section, causing up to 200,000 deaths/year. In vivo information to characterize the individual elastic properties of the aneurysm wall in terms of rupture risk is lacking. We used a method that combines 4D ultrasound and direct deformation estimation to compute in vivo 3D Green-Lagrange strain in murine angiotensin II-induced dissecting aortic aneurysms, a commonly used mouse model. After euthanasia, histological staining of cross-sectional sections along the aorta was performed in areas where in vivo strains had previously been measured. The histological sections were segmented into intact and fragmented elastin, thrombus with and without red blood cells, and outer vessel wall including the adventitia. Meshes were then created from the individual contours based on the histological segmentations. The isolated contours of the outer wall and lumen from both imaging modalities were registered individually using a coherent point drift algorithm. 2D finite element models were generated from the meshes, and the displacements from the registration were used as displacement boundaries of the lumen and wall contours. Based on the resulting deformed contours, the strains recorded were grouped according to segmented tissue regions. Strains were highest in areas containing intact elastin without thrombus attachment. Strains in areas with intact elastin and thrombus attachment, as well as areas with disrupted elastin, were significantly lower. Strains in thrombus regions with red blood cells were significantly higher compared to thrombus regions without. We then compared this analysis to statistical distribution indices and found that the results of each aligned, elucidating the relationship between vessel strain and structural changes. This work demonstrates the possibility of advancing in vivo assessments to a microstructural level ultimately improving patient outcomes.

     

Pulsatile flow visualization in the abdominal aorta under differing physiologic conditions: implications for increased susceptibility to atherosclerosis.

The infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta.     

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.     

Computed tomography in the diagnosis of complicated abdominal aortic aneurysms

The paper analyzes the results of computed tomography (CT) conducted in 54 patients with complicated abdominal aortic aneurysms (AAA). Of them, 37 cases were diagnosed as having a complete rupture. There was dissection of the wall of the aneurysmally altered aorta and its slight tear in 11 and 6 cases, respectively. CT has been shown to allow one to diagnose complications due to AAA, their pattern, and site, to identify the factors that increase a risk for rupture, such as a slight tear of the inner layers of the wall of the aneurysmal abdominal aorta and its wall dissection. This all assists in solving a variety of the problems associated with treatment policy and may substantially reduce postoperative morbidity in this group of patients.     

Numerical simulation of fluid–structure interaction in bypassed DeBakey III aortic dissection

It was found that bypass graft alone could achieve great effects in treating aortic dissection. In order to investigate the mechanical mechanism and the haemodynamic validity of the bypassing treatment for DeBakey III aortic dissection, patient-specific models of DeBakey III aortic dissection treated with different bypassing strategies were constructed. One of the bypassing strategies is bypassing between ascending aorta and abdominal aorta, and the other is bypassing between left subclavian artery and abdominal aorta. Numerical simulations under physiological flow conditions based on fluid–structure interaction were performed using finite element method. The results show that blood flow velocity, pressure and vessel wall displacement of false lumen are all reduced after bypassing. This phenomenon indicates that bypassing is an effective surgery for the treatment of DeBakey III aortic dissection. The effectiveness to cure through lumen is better when bypassing between left subclavian artery and abdominal aorta, while the effectiveness to cure blind lumen is better when bypassing between ascending aorta and abdominal aorta.     

Intraluminal thrombus thickness is not related to lower concentrations of trace elements in the wall of infrarenal abdominal aortic aneurysms

BackgroundIntraluminal thrombus (ILT) formation plays a significant role in the progression of infrarenal abdominal aortic aneurysms (AAA). Potentially, as ILT thickness increases the availability of trace elements in the aneurysm wall could decrease thereby leading to oxidative stress and intensifying pro-inflammatory cytokine generation.AimTo determine if thrombus thickness is related to the concentration of trace elements in the wall of infrarenal AAA.Patients and methodsThe concentrations of trace elements in the wall of the aneurysm sack and ILT obtained from 19 consecutive patients during surgery for infrarenal AAA were determined using emission spectrometry.ResultsThe concentrations of magnesium, zinc, manganese, and lead in the wall of AAA were significantly greater than in the ILT. Only the concentration of copper was lower in the AAA wall compared with the thrombus. The concentration of calcium, phosphorus, zinc, lead, copper, and magnesium increased with ILT thickness. The concentrations of no other trace elements in the wall of AAA were found to be related to the ILT thickness.ConclusionsIntraluminal thrombus thickness is not associated with a lower concentration of trace elements in the wall of the infrarenal AAA. Thus, the intraluminal thrombus participates in the progression of AAA by mechanisms independent of trace element supply to the wall of the aneurysm sack.     

Towards an understanding of the mechanics underlying aortic dissection

Acute aortic dissection and associated aortic catastrophes are among the most devastating forms of cardiovascular disease, with a remarkably high morbidity and mortality despite current medical and surgical treatment. The mechanics underlying aortic dissection are incompletely understood, and a further understanding of the relevant fluid and solid mechanics may yield not only a better appreciation of its pathogenesis, but also the development of improved diagnostic and therapeutic strategies. After illustrating some of the inadequacies with respect to the extant work on the mechanics of aortic dissection, we alternatively postulate that the clinical hemodynamic disturbances that render the aorta susceptible to the initiation of dissection are principally elevated maximum systolic and mean aortic blood pressure, whereas the hemodynamic disturbances that facilitate propagation of dissection are principally elevated pulse pressure and heart rate. Furthermore, abnormal aortic mechanical properties and/or geometry are requisite for dissection to occur. Specifically, we propose that the degree of anisotropy will directly influence the probability of future aortic dissection. Imaging of the aorta may provide information regarding aortic anisotropy and geometry, and in combination with a hemodynamic risk assessment, has the potential to be able to prospectively identify patients at high risk for future aortic dissection thereby facilitating prophylactic intervention. The aim of the paper is to identify the main mechanical issues that have a bearing on aortic dissection, and to suggest an appropriate mathematical model for describing the problem.     

Establishment of a New Murine Elastase-Induced Aneurysm Model Combined with Transplantation

Introduction

The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.

Methods

Adult male mice (n = 6–9 per group) underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.

Results

Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11±0.10 mm vs. 0.75±0.03 mm; p≤0,001). Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.

Conclusions

We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals.     

The detection of<Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> in aneurysm of abdominal aorta and in normal aortic wall of organ donors

Sixty patients underwent surgery due to abdominal aortic aneurysms; the group included 30 patients with asymptomatic aneurysm and 30 with ruptured aneurysm. A control group comprised 30 organ donors. Surgical specimens derived from aneurysm or aorta fragments were investigated for Chlamydia pneumoniae DNA using PCR. In asymptomatic aneurysms, DNA was found in 9 cases (29%), and in ruptured aneurysms in 14 cases (49%). In the control group, C. pneumoniae DNA was not detected in an aortic wall. These results suggest that healthy aortic wall is not susceptible to chlamydial infection. A large number of aneurysm infections implies C. pneumoniae role in proteolysis and degradation of the aneurysm wall. The biological effect of this process may cause an enlargement of the aneurysm.