Search Results (13)

Intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) is associated with disease progression and complications. This study investigates the relationship between nitric oxide (NO) concentration and ILT in AAA patients using patient-specific computational fluid dynamics (CFD) models. Four AAA patients with ILT were enrolled. Patient-specific models of the aorta and branch arteries were constructed followed by CFD simulations. NO concentration was modeled based on endothelial shear stress response and its transport within the arterial lumen and wall. Hemodynamic parameters, including wall shear stress (WSS) and its derivatives, were analyzed alongside NO distribution. ILT accumulation was primarily located in the infrarenal abdominal aorta. Regions of decreased NO concentration correlated with ILT accumulated areas, whereas regions with decreased TAWSS and increased OSI were less consistent with ILT accumulation. A negative correlation was observed between the thrombus area and NO concentration, with p values of less than 0.001 for four patients. The time-average area NO concentration values of lumen area with ILT were lower than those of non-ILT sections. Spatially, NO was unevenly distributed, with thicker thrombus in regions of lower NO concentration. NO distribution could serve as a better potential personalized marker for thrombosis prediction in AAA compared to WSS-derived parameters. Full article

Background: An intraluminal, non-occlusive thrombus (ILT) is a common feature in an abdominal aortic aneurysm (AAA). This study investigated the relative progression of ILT vs. AAA volume using a novel parameter, the so-called thrombus burden ratio (TBR), in non-treated AAAs. Parameters potentially associated with TBR progression were analyzed and TBR progression in large vs. small and fast- vs. slow-growing AAAs was assessed. Methods: This retrospective, single-center study analyzed sequential contrast-enhanced computed tomography angiography (CTA) scans between 2009 and 2018 from patients with an AAA before surgical treatment. Patients’ medical data and CTA scans were analyzed at two given time points. The TBR was calculated as a ratio of ILT and AAA volume, and relative TBR progression was calculated by normalization for time between sequential CTA scans. Spearman’s correlation was applied to identify morphologic parameters correlating with TBR progression, and multivariate linear regression analysis was used to evaluate the association of clinical and morphological parameters with TBR progression. Results: A total of 35 patients were included. The mean time between CT scans was 16 ± 15.9 months. AAA volume progression was 12 ± 3% and ILT volume progression was 36 ± 13%, resulting in a TBR progression of 11 ± 4%, suggesting overproportioned ILT growth. TBR progression was 0.8 ± 0.8% per month. Spearman’s correlation verified ILT growth as the most relevant parameter contributing to TBR progression (R = 0.51). Relative TBR progression did not differ significantly in large vs. small and fast- vs. slow-growing AAAs. In the multivariate regression analysis, none of the studied factors were associated with TBR progression. Conclusion: TBR increases during AAA development, indicating an overproportioned ILT vs. AAA volume growth. The TBR may serve as a useful parameter, as it incorporates the ILT volume growth relative to the AAA volume, therefore combining two important parameters that are usually reported separately. Yet, the clinical relevance in helping to identify potential corresponding risk factors and the evaluation of patients at risk needs to be further validated in a larger study cohort. Full article

An intraluminal thrombus (ILT) is present in the majority of abdominal aortic aneurysms, playing a crucial role in their growth and rupture. Although most computational studies do not include the ILT, in the present study, this is taken into account, laying out the whole simulation procedure, namely, from computed tomography scans to medical image segmentation, geometry reconstruction, mesh generation, biomaterial modeling, finite element analysis, and post-processing, all carried out in open software. By processing the tomography scans of a patient’s aneurysm before and after rupture, digital twins are reconstructed assuming a uniform aortic wall thickness. The ILT and the aortic wall are assigned different biomaterial models; namely, the first is modeled as an isotropic linear elastic material, and the second is modeled as the Mooney–Rivlin hyperelastic material as well as the transversely isotropic hyperelastic Holzapfel–Gasser–Ogden nonlinear material. The implementation of the latter requires the designation of local Cartesian coordinate systems in the aortic wall, suitably oriented in space, for the proper orientation of the collagen fibers. The composite aneurysm geometries (ILT and aortic wall structures) are loaded with normal and hypertensive static intraluminal pressure. Based on the calculated stress and strain distributions, ILT seems to be protecting the aneurysm from a structural point of view, as the highest stresses appear in the thrombus-free areas of the aneurysmal wall. Full article

Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAAs); however, the molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines, and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples. PGG was predicted to bind with high affinity to most vascular proteins, the active sites of MMPs, and several cytokines known to be present in AAAs. Finally, despite potential binding to fibrin, PGG was shown to diffuse readily through thrombus at physiologic pressures. In conclusion, PGG can bind to all the normal and aneurysmal aorta protein components with high affinity, potentially protecting the tissue from degradation and exerting anti-inflammatory activities. Diffusion studies showed that thrombus presence in AAAs is not a barrier to endovascular treatment. Together, these results provide a deeper understanding of the clinical potential of PGG as a non-surgical treatment of AAAs. Full article

Abdominal aortic aneurysm (AAA) is a critical health disorder, where the abdominal aorta dilates more than 50% of its normal diameter. Enlargement in abdominal aorta alters the hemodynamics and flow-induced forces on the AAA wall. Depending on the flow conditions, the hemodynamic forces on the wall may result in excessive mechanical stresses that lead to AAA rupture. The risk of rupture can be predicted using advanced computational techniques such as computational fluid dynamics (CFD) and fluid–structure interaction (FSI). For a reliable rupture risk assessment, formation of intraluminal thrombus (ILT) and uncertainty in arterial material properties should be taken into account, mainly due to the patient-specific differences and unknowns in AAAs. In this study, AAA models are computationally investigated by performing CFD simulations combined with FSI analysis. Various levels of ILT burdens are artificially generated in a realistic AAA geometry, and the peak effective stresses are evaluated to elucidate the effect of material models and ILT formation. The results indicate that increasing the ILT burden leads to lowered effective stresses on the AAA wall. The material properties of the artery and ILT are also effective on the stresses; however, these effects are limited compared to the effect of ILT volume in the AAA sac. Full article

Abdominal aortic aneurysms (AAA) continue to pose a high mortality risk despite advances in medical imaging and surgery. Intraluminal thrombus (ILT) is detected in most AAAs and may critically impact their development. Therefore, understanding ILT deposition and growth is of practical importance. To assist in managing these patients, the scientific community has been researching the relationship between intraluminal thrombus (ILT) and hemodynamic parameters wall shear stress (WSS) derivatives. This study analyzed three patient-specific AAA models reconstructed from CT scans using computational fluid dynamics (CFD) simulations and a pulsatile non-Newtonian blood flow model. The co-localization and relationship between WSS-based hemodynamic parameters and ILT deposition were examined. The results show that ILT tends to occur in regions of low velocity and time-averaged WSS (TAWSS) and high oscillation shear index (OSI), endothelial cell activation potential (ECAP), and relative residence time (RRT) values. ILT deposition areas were found in regions of low TAWSS and high OSI independently of the nature of flow near the wall characterized by transversal WSS (TransWSS). A new approach is suggested which is based on the estimation of CFD-based WSS indices specifically in the thinnest and thickest ILT areas of AAA patients; this approach is promising and supports the effectiveness of CFD as a decision-making tool for clinicians. Further research with a larger patient cohort and follow-up data are needed to confirm these findings. Full article

Red blood cells are found within the abdominal aortic aneurysm (AAA), in the intraluminal thrombus (ILT), and in neovessels. Hemolysis promotes aortic degeneration, e.g., by heme-induced reactive oxygen species formation. To reduce its toxicity, hemoglobin is endocytosed by the CD163 receptor and heme is degraded by heme oxygenase-1 (HO-1). A soluble form (sCD163) is discussed as an inflammatory biomarker representing the activation of monocytes and macrophages. HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO1) are antioxidant genes that are induced by the Nrf2 transcription factor, but their regulation in AAA is only poorly understood. The aim of the present study was to analyze linkages between CD163, Nrf2, HO-1, and NQO1 and to clarify if plasma sCD163 has diagnostic and risk stratification potential. Soluble CD163 was 1.3-fold (p = 0.015) higher in AAA compared to patients without arterial disease. The difference remained significant after adjusting for age and sex. sCD163 correlated with the thickness of the ILT (r_s = 0.26; p = 0.02) but not with the AAA diameter or volume. A high aneurysmal CD163 mRNA was connected to increases in NQO1, HMOX1, and Nrf2 mRNA. Further studies are needed to analyze the modulation of the CD163/HO-1/NQO1 pathway with the overall goal of minimizing the detrimental effects of hemolysis. Full article

Pharmacotherapy for abdominal aortic aneurysm (AAA) can be useful for prevention, especially in people at higher risk, for slowing down AAA progression, as well as for post-surgery adjuvant treatment. Our review focuses on novel pharmacotherapy approaches targeted towards slowing down progression of AAA, known also as secondary prevention therapy. Guidelines for AAA are not specific to slow down the expansion rate of an abdominal aortic aneurysm, and therefore no medical therapy is recommended. New ideas are urgently needed to develop a novel medical therapy. We are hopeful that in the future, pharmacologic treatment will play a key role in the prevention and treatment of AAA. Full article

Determination of abdominal aortic aneurysm (AAA) rupture risk involves the accurate prediction of mechanical stresses acting on the arterial tissue, as well as the wall strength which has a correlation with oxygen supply within the aneurysmal wall. Our laboratory has previously reported the significance of an intraluminal thrombus (ILT) presence and morphology on localized oxygen deprivation by assuming a uniform consistency of ILT. The aim of this work is to investigate the effects of ILT structural composition on oxygen flow by adopting a multilayered porous framework and comparing a two-layer ILT model with one-layer models. Three-dimensional idealized and patient-specific AAA geometries are generated. Numerical simulations of coupled fluid flow and oxygen transport between blood, arterial wall, and ILT are performed, and spatial variations of oxygen concentrations within the AAA are obtained. A parametric study is conducted, and ILT permeability and oxygen diffusivity parameters are individually varied within a physiological range. A gradient of permeability is also defined to represent the heterogenous structure of ILT. Results for oxygen measures as well as filtration velocities are obtained, and it is found that the presence of any ILT reduces and redistributes the concentrations in the aortic wall markedly. Moreover, it is found that the integration of a porous ILT significantly affects the oxygen transport in AAA and the concentrations are linked to ILT’s permeability values. Regardless of the ILT stratification, maximum variation in wall oxygen concentrations is higher in models with lower permeability, while the concentrations are not sensitive to the value of the diffusion coefficient. Based on the observations, we infer that average one-layer parameters for ILT material characteristics can be used to reasonably estimate the wall oxygen concentrations in aneurysm models. Full article

Abdominal aortic aneurysm (AAA) is a common cardiovascular disease resulting in morbidity and mortality in older adults due to rupture. Currently, AAA treatment relies entirely on invasive surgical treatments, including open repair and endovascular, which carry risks for small aneurysms (diameter < 55 mm). There is an increasing need for the development of pharmacological intervention for early AAA. Over the last decade, it has been increasingly recognized that intraluminal thrombus (ILT) is involved in the growth, remodeling, and rupture of AAA. ILT has been described as having both biomechanically protective and biochemically destructive properties. Platelets are the second most abundant cells in blood circulation and play an integral role in the formation, expansion, and proteolytic activity of ILT. However, the role of platelets in the ILT-potentiated AAA progression/rupture remains unclear. Researchers are seeking pharmaceutical treatment strategies (e.g., anti-thrombotic/anti-platelet therapies) to prevent ILT formation or expansion in early AAA. In this review, we mainly focus on the following: (a) the formation/deposition of ILT in the progression of AAA; (b) the dual role of ILT in the progression of AAA (protective or detrimental); (c) the function of platelet activity in ILT formation; (d) the application of anti-platelet drugs in AAA. Herein, we present challenges and future work, which may motivate researchers to better explain the potential role of ILT in the pathogenesis of AAA and develop anti-platelet drugs for early AAA. Full article

The current stratification model of aneurysm rupture seems to be insufficient in some clinical cases. In our study, we determined the differences in wall structure between ruptured and unruptured aneurysms. We obtained computed tomography angiograms and categorized them into the following three groups, consisting of 49 patients each: the group with ruptured abdominal aortic aneurysms (rAAA), symptomatic (sAAA), and asymptomatic (aAAA). The three-dimensional AAA anatomy was digitally reconstructed for each patient through semi-automatically obtained segmentation, and each aneurysm was distinguished by the following three parameters: AFL (aneurysm flow lumen), ILT (intraluminal thrombus), and calcifications. The AFL volume was greater in rAAA compared with aAAA (p = 0.004), the ILT volume was greater in aAAA than in rAAA (p = 0.013), and the AFL/ILT surface ratio was bigger in rAAA than in aAAA (p < 0.001), sAAA than in aAAA (p = 0.033), and rAAA than in sAAA (p = 0.016). AFL/ILT surface*100 was defined as an independent predictive factor of rAAA to aAAA (OR 1.187; 95% CI 1.099–1.281), to sAAA (OR 1.045; 95% CI 1.004–1.087), and in sAAA vs. aAAA (OR 1.067; 95% CI 1.017–1.119). Consequently, the wall of rAAA differs significantly from unruptured aneurysms. The AFL/ILT surface ratio might indicate an increased risk of aneurysm rupture and the occurrence of symptoms in AAA. Full article

An intraluminal thrombus (ILT), which accumulates large numbers of neutrophils, plays a key role in abdominal aortic aneurysm (AAA) pathogenesis. This study aimed to compare levels of selected neutrophil inflammatory mediators in thick and thin ILT, plus adjacent AAA walls, to determine whether levels depend on ILT thickness. Neutrophil mediator levels were analysed by enzyme-linked immunosorbent assays in thick and thin segments of ILT, plus adjacent aneurysm wall sections, taken from one aneurysm sac each from 36 AAA patients. In aneurysmal walls covered by thick ILT, neutrophil elastase and TNF-a levels were significantly higher, as were concentrations of IL-6, in thick ILT compared to thin layers. Positive correlations of NGAL, MPO, and neutrophil elastase were observed between thick ILT and the adjacent wall and thin ILT and the adjacent wall, suggesting that these mediators probably infiltrate thick AAA compartments as well as thin. These observations might support the idea that neutrophil mediators and inflammatory cytokines differentially accumulate in AAA tissues according to ILT thickness. The increased levels of neutrophil mediators within thicker AAA segments might suggest the existence of an intensified proinflammatory state that in turn presumably might preferentially weaken the AAA wall at that region. Full article

The role of intraluminal thrombus (ILT) in the rupture of abdominal aortic aneurysms (AAA) is controversial, and it is unclear whether it increases or decreases the risk of rupture. This research aims to find a clear answer to this question. Previous computer modelling suggests that an ILT lowers oxygen dissemination to the AAA wall, contributing to wall thinning. The methodology used in this study determines the amount of oxygen reaching the aneurysm wall after passing through the ILT by using the porous nature of the ILT to recreate the condition as closely as feasible. Using computed tomographic images, patient-specific three-dimensional (3D) AAA geometries were recreated. Modelling blood and oxygen flow in AAA was obtained using a computational fluid dynamics (CFD) approach. Our findings indicated that the oxygen volume percentage had completely reached the aneurysm wall. Only at the inlet and outflow did the greatest wall shear stress (WSS) occur, with a significant drop in the central region of the aneurysm wall. CFD was used to calculate the velocity, pressure, and WSS of aortic blood flow. ILT had no effect on oxygen flow to the aneurysm wall, disproving the theory that it produces local hypoxia. Full article