Abdominal Aortic Aneurysm Intraluminal Thrombus Research Articles

Prediction of wall stress and oxygen flow in patient-specific abdominal aortic aneurysms: the role of intraluminal thrombus.

In this study, the biomechanical role of intraluminal thrombus (ILT) in an abdominal aortic aneurysm (AAA) is investigated. The implications of ILT in AAA are controversial in literature. Previous studies have demonstrated that ILT provides a biomechanical advantage by decreasing wall stress, whereas other studies have associated ILT with inhibiting oxygen transport and inducing aortic wall weakening. Therefore, we sought to explore the connection between ILT, mechanical stresses, and oxygen flow in different geometries of patient-specific aneurysms with varying ILT morphologies. The objective is to investigate the extent to which ILT influences the prediction of aneurysmal wall stresses that are associated with rupture, as well as oxygen concentrations to measure tissue oxygen deprivation. Three patient-specific AAA geometries are considered, and two models, one with ILT and one without ILT, are created for each patient to assess the effect of ILT presence. A fluid-structure interaction approach is used to couple the blood flow, wall deformation, and oxygen mass transport. Results are presented for hemodynamics patterns, wall stress measures, and oxygen metrics within the arterial wall. While ILT is found to reduce wall stress, simulations confirm that ILT decreases oxygen transport within the tissue significantly, leading to wall hypoxia.

The Effects of Geometric Features of Intraluminal Thrombus on the Vessel Wall Oxygen Deprivation.

The objective of this paper is to analyze the association of intraluminal thrombus (ILT) presence and morphology with oxygen transport in abdominal aortic aneurysms (AAA) and local hypoxia. The biomechanical role of the ILT layer in the evolution of the aneurysm is still not fully understood. ILT has been shown to create an inflammatory environment by reducing oxygen flux to the arterial wall and therefore decreasing its strength. It has been also hypothesized that the geometry of the ILT may further affect AAA rupture. However, no previous research has attempted to explore the effect of morphological features of ILT on oxygen distributions within the AAA, in a systematic manner. In this study, we perform a comprehensive analysis to investigate how physiologically meaningful variations in ILT geometric characteristics affect oxygen transport within an AAA. We simulate twenty-seven AAA models with variable ILT dimensions and investigate the extent to which ILT attenuates oxygen concentration in the arterial wall. Geometric variations studied include ILT thickness and ILT length, as well as the bulge diameter of the aneurysm which is related to ILT curvature. Computer simulations of coupled fluid flow-mass transport between arterial wall, ILT, and blood are solved and spatial variations of oxygen concentrations within the ILT and wall are obtained. The comparison of the results for all twenty-seven simulations supports the hypothesis that the presence of ILT in AAA correlates to significantly impaired oxygen transport to the aneurysmal wall. Mainly, we observed that ILT thickness and length are the parameters that influence decreased oxygen flow and concentration values the most, and thick thrombi exacerbate hypoxic conditions in the arterial wall, which may contribute to increased tissue degradation. Conversely, we observed that the arterial wall oxygen concentration is nearly independent of the AAA bulge diameter. This confirms that consideration of ILT size and anatomy is crucial in the analysis of AAA development.

Deep Learning to Automatically Segment and Analyze Abdominal Aortic Aneurysm from Computed Tomography Angiography.

Although segmentation of Abdominal Aortic Aneurysms (AAA) thrombus is a crucial step for both the planning of endovascular treatment and the monitoring of the intervention's outcome, it is still performed manually implying time consuming operations as well as operator dependency. The present paper proposes a fully automatic pipeline to segment the intraluminal thrombus in AAA from contrast-enhanced Computed Tomography Angiography (CTA) images and to subsequently analyze AAA geometry. A deep-learning-based pipeline is developed to localize and segment the thrombus from the CTA scans. The thrombus is first identified in the whole sub-sampled CTA, then multi-view U-Nets are combined together to segment the thrombus from the identified region of interest. Polygonal models are generated for the thrombus and the lumen. The lumen centerline is automatically extracted from the lumen mesh and used to compute the aneurysm and lumen diameters. The proposed multi-view integration approach returns an improvement in thrombus segmentation with respect to the single-view prediction. The thrombus segmentation model is trained over a training set of 63 CTA and a validation set of 8 CTA scans. By comparing the thrombus segmentation predicted by the model with the ground truth data, a Dice Similarity Coefficient (DSC) of 0.89 ± 0.04 is achieved. The AAA geometry analysis provided an Intraclass Correlation Coefficient (ICC) of 0.92 and a mean-absolute difference of 3.2 ± 2.4mm, for the measurements of the total diameter of the aneurysm. Validation of both thrombus segmentation and aneurysm geometry analysis is performed over a test set of 14 CTA scans. The developed deep learning models can effectively segment the thrombus from patients affected by AAA. Moreover, the diameters automatically extracted from the AAA show high correlation with those manually measured by experts.

IgG Anti-High Density Lipoprotein Antibodies Are Elevated in Abdominal Aortic Aneurysm and Associated with Lipid Profile and Clinical Features.

High-density lipoproteins cholesterol (HDLc) levels are decreased in abdominal aortic aneurysm (AAA), which is hallmarked by autoimmunity and lipid aortic deposits. To investigate whether IgG anti-HDL antibodies were present in AAA and their potential association with clinical features, IgG anti-HDL and total IgG along with HDLc plasma levels were measured in 488 AAA patients and 184 controls from the Viborg Vascular (VIVA) study, and in tissue-conditioned media from AAA intraluminal thrombus and media layer samples compared to control aortas. Higher IgG anti-HDL levels were found in AAA compared to controls, even after correcting for total IgG, and after adjusting for potential confounders. IgG anti-HDL levels were correlated with aortic diameter in univariate and adjusted multivariate analyses. IgG anti-HDL antibodies were negatively associated with HDLc levels before and after correcting for potential confounders. Increased anti-HDL antibodies were identified in tissue-conditioned media from AAA samples compared to healthy aortas, with higher levels being observed in the media layer. In conclusion, increased IgG anti-HDL levels (both in plasma and in tissue) are linked to AAA, associated with aortic diameter and HDLc levels. These data suggest a potential immune response against HDL in AAA and support an emerging role of anti-HDL antibodies in AAA.

The biaxial mechanical behaviour of abdominal aortic aneurysm intraluminal thrombus: Classification of morphology and the determination of layer and region specific properties

Intraluminal thrombus (ILT) is present in 75% of clinically-relevant abdominal aortic aneurysms (AAAs) yet, despite much research effort, its role in AAA biomechanics remains unclear. The aim of this work is to further evaluate the biomechanics of ILT and determine if different ILT morphologies have varying mechanical properties.Biaxial mechanical tests were performed on ILT samples harvested from 19 patients undergoing open surgical repair. ILT were separated into luminal, medial and medial/abluminal layers. A total of 356 tests were performed and the Cauchy stress (σ) and tangential modulus (TM) at a stretch ratio (λ) of 1.14 were recorded for each test in both the circumferential (θ) and longitudinal (L) directions.Our data revealed three distinct types of ILT morphologies, each with a unique set of mechanical properties. All ILT layers were found to be isotropic and inhomogeneous. Type 1 (n=10) was a multi-layered ILT (thick medial/abluminal layer) whose strength and stiffness decreased gradually from the luminal to the medial/abluminal layer. Type 2 (n=6) was a multi-layered ILT (thin/highly degraded medial/abluminal layer) whose strength and stiffness decreased abruptly between the luminal and medial/abluminal layer and Type 3 (n=3) is a single layered ILT with a lower strength and stiffness than Types 1 and 2. In a sub-study, we found the luminal layer to be stronger and stiffer in the posterior than the anterior region.This work provides further insights to the biomechanical behaviour of ILT and the use of our ILT classification may be useful in future studies.

Comparison of methods used to measure the thickness of soft tissues and their influence on the evaluation of tensile stress

Measuring the physical dimensions of soft tissue is difficult due to its deformable nature. Such measurements are used to evaluate the tissue's mechanical properties. Imprecise measurements of the tissue's thickness can alter the assessment of tensile stress which may have significant clinical relevance when used as a diagnostic tool. The performance of routinely used measurement methods including a (i) vernier calipers, (ii) micrometer, (iii) thickness gauge, (iv) glass slide technique coupled with (i) and (ii) and a (v) laser displacement sensor were assessed by comparing them to a photogrammetric technique which was considered to be the measurement standard. All measurements were performed on two tissue types: porcine aorta and human intraluminal thrombus from an abdominal aortic aneurysm (AAA) and results were compared against predetermined criteria whose limits represented a 10% change in experimentally derived tensile stress. The inter-rater and retest reliability of the vernier calipers, micrometer and thickness gauge were also investigated. The thickness gauge was shown to be the most reliable and could accurately measure the thickness of aortic tissue. The conditions of the criteria were not met by any instrument used to measure the thickness of the AAA intraluminal thrombus, however, the micrometer, which proved highly reliable, was considered the most suitable (effects on tensile stress: +14.7%). For both tissues the glass slide and laser techniques significantly over estimated the thickness measurement altering the tensile stress by up to −29.6%. This study highlights the effects of inaccurate measurements on the assessment of tensile stress and recommends a thickness gauge be used to measure structured tissue (aorta) and a micrometer for unstructured tissue (AAA intraluminal thrombus).

Increased levels of thioredoxin in patients with abdominal aortic aneurysms (AAAs). A potential link of oxidative stress with AAA evolution

ObjectiveOxidative stress is a main mechanism involved in vascular pathologies. Increased thioredoxin (TRX) levels have been observed in several oxidative stress-associated cardiovascular diseases. We aim to test the potential role of TRX as a biomarker of oxidative stress in abdominal aortic aneurysm (AAA). MethodsTRX levels were analysed in both AAA intraluminal thrombus (ILT) tissue and in tissue-conditioned media by immunohistochemistry, Western blot and ELISA. Moreover, serum TRX levels were assessed in AAA Caucasian patients by ELISA. ResultsTRX was mainly localized in the luminal part of ILT in AAA. Compared with the abluminal layer, TRX release was increased in the luminal layer of the ILT of AAA (31±9ng/ml vs. 9±3ng/ml, p<0.05). The interest of this approach is that we can identify proteins potentially released into the blood compartment, which could serve as biomarkers of the pathology. In a training population, serum TRX levels were significantly increased in patients with AAA relative to healthy subjects (50±6ng/ml vs. 26±3ng/ml, p<0.05). These results were validated in a second independent group of patients. Moreover, a positive correlation between TRX and AAA size (rho=0.5, p<0.001) was observed. Finally, in AAA samples with follow-up, TRX was positively associated to aneurismal growth rate (rho=0.25, p=0.027). ConclusionsTRX release is increased in the luminal part of AAA and TRX serum levels are increased in AAA patients compared with healthy subjects. TRX levels correlates with AAA size and expansion, suggesting its potential role as a biomarker of AAA evolution.

Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening

Purpose: Our previous computer models suggested that intraluminal thrombus (ILT) within an abdominal aortic aneurysm (AAA) attenuates oxygen diffusion to the AAA wall, possibly causing localized hypoxia and contributing to wall weakening. The purpose of this work was to investigate this possibility. Methods: In one arm of this study, patients with AAA were placed in one of two groups: (1) those with an ILT of 4-mm or greater thickness on the anterior surface or (2) those with little (< 4 mm) or no ILT at this site. During surgical resection but before aortic cross-clamping, a needle-type polarographic partial pressure of oxygen (Po2) electrode was inserted into the wall of the exposed AAA, and the Po2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. Mural and mid-ILT Po2 measurements were normalized by the intraluminal Po2 measurement to account for patient variability. In the second arm of this study, two AAA wall specimens were obtained from two different sites of the same aneurysm at the time of surgical resection: group I specimens had thick adherent ILT, and group II specimens had thinner or no adherent ILT. Nonaneurysmal tissue was also obtained from the infrarenal aorta of organ donors. Specimens were subjected to histologic, immunohistochemical, and tensile strength analyses to provide data on degree of inflammation (% area inflammatory cells), neovascularization (number of capillaries per high-power field), and tensile strength (peak attainable load). Additional specimens were subjected to Western blotting and immunohistochemistry for qualitative evaluation of expression of the cellular hypoxia marker oxygen-regulated protein. Results: The Po2 measured within the AAA wall in group I (n = 4) and group II (n = 7) patients was 18% ± 9% luminal value versus 60% ± 6% (mean ± SEM; P <.01). The normalized Po2 within the ILT of group I patients was 39% ± 10% (P =.08 with respect to the group I wall value). Group I tissue specimens showed greater inflammation (P <.05) compared with both group II specimens and nonaneurysmal tissue: 2.9% ± 0.6% area (n = 7) versus 1.7% ± 0.3% area (n = 7) versus 0.2% ± 0.1% area (n = 3), respectively. We found similar differences for neovascularization (number of vessels/high-power field), but only group I versus control was significantly different (P <.05): 16.9 ± 1.6 (n = 7) vs 13.0 ± 2.3 (n = 7) vs 8.7 ± 2.0 (n = 3), respectively. Both Western blotting and immunohistochemistry results suggest that oxygen-regulated protein is more abundantly expressed in group I versus group II specimens. Tensile strength of group I specimens was significantly less (P <.05) than that for group II specimens: 138 ± 19 N/cm2 (n = 7) versus 216 ± 34 N/cm2 (n = 7), respectively. Conclusion: Our results suggest that localized hypoxia occurs in regions of thicker ILT in AAA. This may lead to increased, localized mural neovascularization and inflammation, as well as regional wall weakening. We conclude that ILT may play an important role in the pathology and natural history of AAA. (J Vasc Surg 2001;34:291-9.)