Intraluminal Thrombus Thickness Research Articles

Computational Study of Abdominal Aortic Aneurysm Walls Accounting for Patient-Specific Non-Uniform Intraluminal Thrombus Thickness and Distinct Material Models: A Pre- and Post-Rupture Case.

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.

Automatic Segmentation and Mechanical Characterisation of the Intraluminal Thrombus and Arterial Wall of Abdominal Aortic Aneurysms Using Time Resolved 3D Ultrasound Images

This study proposes a method for semi-automatic segmentation of abdominal aortic aneurysms (AAAs) and their intraluminal thrombus (ILT), based on time resolved 3D ultrasound (US), and validates results with computed tomography (CT). Moreover, mechanical properties of both wall and ILT are determined, and possible correlations with ILT size and blood pressure are investigated. A semi-automatic segmentation algorithm was developed combining a star-Kalman approach with a 3D snake algorithm. The segmented geometries of both lumen and inner vessel wall were validated with both manual US based segmentations and CT based segmentations. Finally, the lumen and vessel wall distensibility and ILT compressibility were estimated, and correlated to ILT size and blood pressure. For the vessel wall and lumen, the median Similarity Index (SI) was 92% (IQR 90, 94%) and 83% (IQR 75, 87%), respectively. The distensibility of the vessel wall could be determined in 37 out of 40 cases, and had a median value of 0.28 10-5 Pa-1 (IQR 0.18, 0.51⋅10-5). The median systolic-diastolic volume change of the ILT was determined successfully in 21 out of 40 patients, and was -0.57% (IQR -1.1, 1.2%). The vessel and lumen distensibility showed a strong correlation with the systolic pressure (p < .010), rather than with the diastolic pressure. Besides, the lumen distensibility was strongly correlated with the ILT thickness (p = .023). The performance of the semi-automatic segmentation algorithm was shown to be as good as the manual segmentations and highly dependent on the visibility of the ILT (limited contrast in seven patients and clutter in nine patients). This study shows promising results for mechanical characterisation of the vessel, and ILT, including a correlation between distensibility, ILT size, and blood pressure. For future work, inclusion rate needs to be increased by improving the image contrast with novel US techniques.

Biomechanics and early sac regression after endovascular aneurysm repair of abdominal aortic aneurysm

BackgroundSac regression after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is regarded as a marker of successful response to treatment. Several factors influence sac behavior after EVAR, yet little is known about the value of preoperative biomechanics. The aim of this study was to investigate the difference in aortic biomechanics between patients with and without sac regression. MethodsPatients treated with standard EVAR for infrarenal AAA at the Karolinska University Hospital between 2009 and 2012 with one preoperative and a minimum of two postoperative computed tomography angiography (CTA) scans were considered for inclusion in this single-center retrospective cohort study. Biomechanical indices such as AAA wall stress and wall stress-strength ratio as well as intraluminal thrombus (ILT) thickness and stress were measured preoperatively in A4ClinicRE (VASCOPS GmbH). AAA diameter and volume were analyzed on preoperative, 30-day, and 1-year CTAs. Patients were dichotomized based on sac regression, defined as a ≥5 mm decrease in maximal AAA diameter between the first two postoperative CTA scans. Multivariable logistic regression was used for analysis of factors associated with early sac regression. ResultsOf the 101 patients treated during the inclusion period, 64 were included. Thirty-nine (61%) demonstrated sac regression and 25 (39%) had a stable sac or sac increase. The mean patients age (73 years vs 76 years), male sex (85% vs 96%), and median AAA diameter (58 mm vs 58.5 mm) did not differ between patients with and without sac regression. Although no difference in preoperative biomechanics was seen between the groups, multivariable logistic regression revealed that a larger AAA diameter (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.06-1.51; P = .009) and smoking (OR, 22.1; 95% CI, 2.78-174; P = .003) were positively associated with sac regression. In contrast, the lumen diameter (OR, 0.87; 95% CI, 0.77-0.98; P = .023), ILT thickness (OR, 0.85; 95% CI, 0.75-0.97; P = .013), aspirin or direct-acting oral anticoagulant use (OR, 0.11; 95% CI, 0.02-0.61; P = .012), and mean ILT stress (OR, 0.35; 95% CI, 0.14-0.87; P = .024) showed a negative association. Patients with sac regression had fewer reinterventions (log-rank P = .010) and lower mortality (log-rank P = .012) at the 5-year follow-up. ConclusionsThis study, characterizing preoperative biomechanics in patients with and without sac regression, demonstrated a negative association between mean ILT stress and ILT thickness with a change in sac diameter after EVAR. Given that the ILT is a highly dynamic entity, further studies focusing on the role of the thrombus are needed. Furthermore, patients presenting with early sac regression had improved outcomes after EVAR.

Anticoagulants and reduced thrombus load in abdominal aortic aneurysms assessed with three-dimensional contrast-enhanced ultrasound examination.

The relationship between intraluminal thrombus (ILT) and abdominal aortic aneurysm (AAA) growth and rupture risk remains ambiguous. Studies have shown a limited effect of antiplatelet therapy on ILT size, whereas the impact of anticoagulant therapy on ILT is unresolved. This study aims to evaluate an association between antithrombotic therapy and ILT size assessed with three-dimensional contrast-enhanced ultrasound (3D-CEUS) examination in a cohort of patients with AAA. In a cross-sectional study, 309 patients with small AAAs were examined with 3D-CEUS. Patients were divided into three groups based on prescribed antithrombotic therapy: anticoagulant (n= 36), antiplatelet (n= 222), and no antithrombotic therapy (n= 51). Patient ILT size was calculated in volume and thickness and compared between the three groups. Patients on anticoagulants had a significantly lower estimated marginal mean ILT volume of 16mL (standard error [SE],±3.2) compared with 28mL (SE,±2.7) in the no antithrombotic group and 30mL (SE,±1.3) in the antiplatelet group when adjusting for AAA volume (P< .001) and comorbidities (P< .001). In addition, patients on anticoagulant therapy had significantly lower estimated marginal mean ILT thickness of 10mm (SE,±1.1) compared with 13mm (SE,±0.9) in the no antithrombotic group of and 13mm (SE,±0.4) in the antiplatelet group when adjusting for AAA diameter (P= .03) and comorbidities (P= .035). A 3D-CEUS examination is applicable for ILT assessment and demonstrates that patients with AAA on anticoagulant therapy have lower ILT thickness and volume than patients with AAA on antiplatelet therapy and those without antithrombotic therapy. Causality between anticoagulants and ILT size, and extrapolation to AAA growth and rupture risk, is unknown and merits further investigations, to further nuance US-based AAA surveillance strategy.

AI-powered assessment of biomarkers for growth prediction of abdominal aortic aneurysms

ObjectiveThe purpose of this study was to employ biomechanics-based biomarkers to locally characterize abdominal aortic aneurysm (AAA) tissue and investigate their relation to local aortic growth by means of an artificial intelligence model. MethodsThe study focused on a population of 36 patients with AAAs undergoing serial monitoring with electrocardiogram-gated multiphase computed tomography angiography acquisitions. The geometries of the aortic lumen and wall were reconstructed from the baseline scans and used for the baseline assessment of regional aortic weakness with three functional biomarkers, time-averaged wall-shear stress, in vivo principal strain, and intra-luminal thrombus thickness. The biomarkers were encoded as regional averages on axial and circumferential sections perpendicularly to the aortic centerline. Local diametric growth was obtained as difference in diameter between baseline and follow-up at the level of each axial section. An artificial intelligence model was developed to predict accelerated aneurysmal growth with the Extra Trees algorithm used as a binary classifier where the positive class represented regions that grew more than 2.5 mm/year. Additional clinical biomarkers, such as maximum aortic diameter at baseline, were also investigated as predictors of growth. ResultsThe area under the curve for the constructed receiver operating characteristic curve for the Extra Trees classifier showed a very good performance in predicting relevant aortic growth (area under the curve = 0.92), with the three biomechanics-based functional biomarkers being objectively selected as the main predictors of growth. ConclusionsThe use of features based on the functional and local characterization of the aortic tissue resulted in a superior performance in terms of growth prediction when compared with models based on geometrical assessments. With rapid growth linked to increasing risk for patients with AAAs, the ability to access functional information related to tissue weakening and disease progression at baseline has the potential to support early clinical decisions and improve disease management.

Deep Learning on Multiphysical Features and Hemodynamic Modeling for Abdominal Aortic Aneurysm Growth Prediction.

Prediction of abdominal aortic aneurysm (AAA) growth is of essential importance for the early treatment and surgical intervention of AAA. Capturing key features of vascular growth, such as blood flow and intraluminal thrombus (ILT) accumulation play a crucial role in uncovering the intricated mechanism of vascular adaptation, which can ultimately enhance AAA growth prediction capabilities. However, local correlations between hemodynamic metrics, biological and morphological characteristics, and AAA growth rates present high inter-patient variability that results in that the temporal-spatial biochemical and mechanical processes are still not fully understood. Hence, this study aims to integrate the physics-based knowledge with deep learning with a patch-based convolutional neural network (CNN) approach by incorporating important multiphysical features relating to its pathogenesis for validating its impact on AAA growth prediction. For this task, we observe that the unstructured multiphysical features cannot be directly employed in the kernel-based CNN. To tackle this issue, we propose a parameterization of features to leverage the spatio-temporal relations between multiphysical features. The proposed architecture was tested on different combinations of four features including radius, intraluminal thrombus thickness, time-average wall shear stress, and growth rate from 54 patients with 5-fold cross-validation with two metrics, a root mean squared error (RMSE) and relative error (RE). We conduct extensive experiments on AAA patients, the results show the effect of leveraging multiphysical features and demonstrate the superiority of the presented architecture to previous state-of-the-art methods in AAA growth prediction.

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.

Association of Aneurysm Tissue Neutrophil Mediator Levels with Intraluminal Thrombus Thickness in Patients with Abdominal Aortic Aneurysm.

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.

Association of vortical structures and hemodynamic parameters for regional thrombus accumulation in abdominal aortic aneurysms.

The intraluminal thrombus (ILT) has been shown to negatively impact the progression of the abdominal aortic aneurysms (AAAs). The formation of this thrombus layer has been connected to the local flow environment within AAAs, but the specific mechanisms leading to thrombus formation are still not fully understood. Our study investigated the association between vortical structures, near-wall hemodynamic metrics (e.g., time averaged wall shear stress (TAWSS) and oscillatory shear index (OSI)), and ILT accumulation in a longitudinal cohort of 14 AAAs (53 scans total). Vortices and hemodynamic parameters were estimated using hemodynamic simulations performed to each scan of each patient and compared to local 3D changes of ILT thickness between two consecutive scans (ΔILT). Results showed that vortices formed and remained strong and close to the lumen surface in AAAs without an ILT, while in AAAs with ILTs these detached from the lumen surface and dissipated nearby wall region where an increase in ILT thickness was observed. Although low TAWSS was observed in regions with and without ILT accumulation, an inverse correlation between and TAWSS was observed within the regions that experienced a thrombus growth. Our results support the idea that vortical structures might be playing a role modulating ILT accumulation into specific wall regions. Also, it submits the idea that the low TAWSS will be modulating the growth of thrombus within these preferred ILT accumulated regions.

Assessment of the Global and Regional Circumferential Strain of Abdominal Aortic Aneurysm with Different Size by Speckle-Tracking Echocardiography.

We aimed to use speckle-tracking echocardiography (STE) to quantify circumferential aortic strain of abdominal aortic aneurysms (AAA) with different size. A total of 87 AAA patients were included. The morphological variables, including aortic maximum diameter (MD), end systolic area (ESA), end diastolic area (EDA), and thickness and area of intraluminal thrombus (ILT), were measured by ultrasound. STE was applied to calculate circumferential strain (CS) at 6 equally divided segments of the aorta at MD. We evaluated the mean value of peak strain along the 6 segments as global circumferential strain (GCS). Large AAA (≥5.5 cm) patients had higher MD, ESA, EDA, AAA length, ILT thickness, and area, but lower fractional area change, GCS, and segmental CSs than small AAA (<5.5 cm) subjects (all P< .05). Compared with AAA <4.5 cm group, AAA patients ≥4.5 cm possessed increased MD, ESA, EDA, AAA length, ILT thickness, and area, which results were also reflected in the comparison between AAA <6.5 and ≥6.5 cm group. In small AAA patients, GCS and regional strains in CS1, CS3, and CS5 segments were lower in AAA subjects ≥4.5 cm than those <4.5 cm (all P<.05). However, no significant differences in the GCS and regional CS between ≥6.5 and <6.5 cm group were found. Correlation analysis revealed a significant negative association of GCS with MD, ESA, and EDA, even after adjusting the potential confounding factors (all P< .05). Our findings may yield insight into the structural strain characteristics of AAA wall with different size, which adds the benefit of using simple echocardiography-derived biomechanics to stratify AAA patients.

Morphologic Features of Symptomatic and Ruptured Abdominal Aortic Aneurysm in Asian Patients

To evaluate morphologic features of symptomatic and ruptured abdominal aortic aneurysms in Asian patients. Two hundred sixty four continuous candidates with an abdominal aortic aneurysm (AAA) were retrospectively identified from a tertiary hospital database between January 2017 and May 2019. The patients meeting inclusion criteria were divided into symptomatic or ruptured AAA (srAAA) and asymptomatic AAA (asAAA) groups. Their computed tomography angiographies were reconstructed using centerline technique and the geometric features of AAAs between the 2 groups were compared. One hundred two patients fulfilled selection criteria (mean age 71years, 80 men), comprising 35 srAAAs and 67 asAAAs. There was no essential association between gender, smoking or hypertension, and AAA-associated symptoms or rupture. The maximum diameter (5.8±1.4cm vs. 5.0±0.9cm; P=0.001), length (8.8±0.6cm vs. 7.0±0.3cm; P=0.002), and intraluminal thrombus (ILT) thickness (1.7±0.2cm vs. 1.3±0.1cm; P=0.039) of AAAs were independent risk factors for AAA-associated symptoms or rupture (binary logistic regression, P<0.05), but AAA length and ILT were strongly correlated with the AAA diameter (Pearson correlation coefficient value of 0.591 and 0.444) whereas other factors such as aneurysmal tortuosity, aneurysmal neck anatomy, or common iliac artery geometry were nonsignificant. AAA diameter, length, and intraluminal thrombus thickness were identified as risk factors for AAA-associated symptoms in Asian patients. While the diameter is regarded as the most important predictor for symptoms and rupture, AAA length and ILT thickness should also be taken into consideration when contemplating intervention, particularly for borderline and smaller aneurysms.

Influence of preoperative statins and aspirin administration on biological and magnetic resonance imaging properties in patients with abdominal aortic aneurysm.

Background: Main objective of this study was to evaluate the influence of statins and/or acetylsalicylic acid on biochemical characteristics of abdominal aortic aneurysm (AAA) wall and intraluminal thrombus (ILT). Patients and methods: Fifty patients with asymptomatic infrarenal AAA were analyzed using magnetic resonance imaging on T1w sequence. Relative ILT signal intensity (SI) was determined as a ratio between ILT and psoas muscle SI. Samples containing the full ILT thickness and aneurysm wall were harvested from the anterior surface at the level of the maximal diameter. The concentration of enzymes such as matrix metalloproteinase (MMP) 9, MMP2 and neutrophil elastase (NE/ELA) were analyzed in ILT and AAA wall; while collagen type III, elastin and proteoglycan 4 were analyzed in harvested AAA wall. Oxidative stress in the AAA wall was assessed by catalase and malondialdehyde activity in tissue samples. Results: Relative ILT signal intensity (1.09±0.41 vs 0.89±0.21, p=0.013) were higher in non-statin than in statin group. Patients who were taking aspirin had lower relative ILT area (0.89±0.19 vs 1.13.±0.44, p=0.016), and lower relative ILT signal intensity (0.85 [0.73-1.07] vs 1.01 [0.84-1.19], p=0.021) compared to non-aspirin group. There were higher concentrations of elastin in AAA wall among patients taking both of aspirin and statins (1.21 [0.77-3.02] vs 0.78 (0.49-1.05) ng/ml, p=0.044) than in patients who did not take both of these drugs. Conclusions: Relative ILT SI was lower in patients taking statin and aspirin. Combination of antiplatelet therapy and statins was associated with higher elastin concentrations in AAA wall.

Analysis of morphological and hemodynamical indexes in abdominal aortic aneurysms as preliminary indicators of intraluminal thrombus deposition.

In this paper, we study the correlation between the wall shear stress, a hemodynamical index derived from numerical simulations, and an new index MFA-ILT for the characterization of intraluminal thrombus (ILT) in the presence of abdominal aortic aneurysms. Based on the processing of medical images, we define our index MFA-ILT by projecting onto lumen surface a measure of the ILT thickness. From the physical point of view, hemodynamical indexes describe the mechanical stimuli at which the luminal surface of the vessel wall is subject to, due to blood flow. Specifically, we consider the time-averaged wall shear stress and the oscillatory shear index. The first index provides a measurement of the averaged magnitude of the shear stress; the second index measures the rate of change of shear stress. To reconstruct the hemodynamical indexes, we build in silico three-dimensional models. We use the same physical parameters and boundary conditions for all the aneurysms in the sample. The computer simulations do not require any additional invasive patient examination. We consider eleven cases of abdominal aortic aneurysms spanning a wide range of different morphological features. All the cases are characterized by a thin intraluminal thrombus. We can, therefore, assume that the lumen we currently observe does not significantly differ from the one before the thrombus deposition. Our results suggest that the value of wall shear stresses and intraluminal thrombus deposition are correlated. Moreover, we conclude that in six cases time-averaged wall shear stress provides a preliminary indication of the area at risk of thrombus deposition.

Intra-Luminal Thrombus Volume in Small Abdominal Aortic Aneurysms Assessed with Contrast Enhanced Three-Dimensional Ultrasound

Introduction - The intra-luminal thrombus (ILT) in abdominal aortic aneurysms (AAA) is suggested to weaken the aortic wall and contribute to aneurysm growth and eventually rupture (1–4). Thus, investigation of ILT has the potential to improve rupture risk prediction which today is predominantly based on diameter alone. Until recently, the ILT volume could only be determined by means of three-dimensional computed tomography angiography (3D-CTA) and ultrasound has not had a place in this context, although attractive due to its noninvasive nature. The primary aim of this study was to assess ILT volume using a novel ultrasound technology which combines three-dimensional ultrasound with contrast enhanced ultrasound (3D-CEUS) and compare these measures with 3D-CTA, using the latter as reference method. The second aim was to determine the reproducibility and repeatability of 3D-CEUS in ILT volume measurements. Methods - Between 1 January 2015 and 31 October 2016 (22 months), 143 patients with small asymptomatic AAA (US-diameter: 30-55 mm) were consecutively recruited. All patients underwent 3D-CEUS (Figure 1) and 3D-CTA the same day, in a mutually blinded setup. In total 15 patients were excluded due to CTA protocol deviation (n=2), inferior CEUS image quality (n=8) and AAA diameter > 55mm on US (n=5). Therefore, 128 patients (F/M; 22/106) with a mean AAA diameter of 45.1mm (SD ±6.2) were eligible for further analysis. Reproducibility assessment was performed on 30 patients who had an extra 3D-CEUS performed by a second physician. The ILT volume and maximum ILT thickness perpendicular to the AAA centerline was quantified off-line on a semi-automated quantification software (AAA-prototype v.2.0, Philips Research, Suresnes, France). Results - In 25 out of 128 patients, no ILT was found on 3D-CEUS, and confirmed on 3D-CTA analysis in all but one case. The mean ILT volume difference between 3D-CEUS and 3D-CT was 2.2ml (p=0.0001) equivalent to a 6% difference. The range of variability (ROV) was ±10.5ml. Likewise, the mean ILT thickness difference was 0.7mm (p= 0.002), with a ROV of ±4.5mm. The inter-observer variation of both ILT volume and ILT thickness measurement with 3D-CEUS was low, with reproducibility coefficients of 8.9ml and 3.0mm. A similar corresponding intra-observer variation of 7.5ml and 3.4mm, respectively, was found. Conclusion - Three-dimensional contrast enhanced ultrasound has demonstrated both good agreement and reproducibility in the assessment of ILT volume. It is expected that the method in the future can be implemented as a clinical tool in line with other advanced CEUS investigations. We foresee that ILT assessment with this novel ultrasound technique could be a valuable supplement in predicting rupture risk without radiation and nephrotoxic contrast agents.

Spatial Distribution of Abdominal Aortic Aneurysm Surface Expansion and Correlation With Maximum Diameter and Volume Growth

Abdominal aortic aneurysm (AAA) growth rate, measured as maximum diameter (Dmax) change over time, is used as a surrogate marker of rupture risk. However, AAA expansion presents significant spatial variability. We aim to record the spatial distribution of regional wall surface expansion. Thirty AAAs were retrospectively studied. Each AAA had one baseline and at least one follow-up computed tomography scan. Three-dimensional AAA models were reconstructed, and change in Dmax and total aneurysm volume was recorded to calculate annual growth rates. Regional surface growth was quantified using the VascForm algorithm, which is based on nonrigid point cloud registration and iterative closest point analysis. Maximum and average surface growths were calculated and correlated with the diameter/volume growth rates. Furthermore, to identify potential correlation between maximum thrombus (intraluminal thrombus) thickness and maximum surface growth, as well as between peak wall stress (PWS) and surface growth, their colocalization was examined. The median average annual surface growth was 6% (0%-28%), and the maximum surface growth 24% (11%-238%). There was strong evidence of a moderate correlation between Dmax and average as well as maximum surface growth. Regarding volumes, there was strong evidence of a very strong association with average surface growth rate and a moderate association with maximum surface growth rate (rho: 0.91, P<0.001; rho: 0.7, P<0.001, respectively). In 51.6% of the follow-ups, maximum surface growth occurred away from Dmax site. Sixteen cases presented maximum surface growth away and fifteen at the region of maximum initial intraluminal thrombus thickness. AAAs in the former group had significantly thinner initial intraluminal thrombus thickness (11.3 vs 19.5mm, P<0.001) than those in the latter. Apart from a single case, maximum surface growth did not occur at the PWS region. More than half of the lesions display maximum growth away from Dmax, suggesting that a more accurate method of analyzing AAA growth needs to be established in clinical practice that will take into account local surface growth.

Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.

The possibility that oxidative stress promotes degradation of the extracellular matrix and a relationship between intraluminal thrombus (ILT) thickness and proteolytic activity within the abdominal aortic aneurysm (AAA) wall has been suggested. In the present study, the hypothesis that thin ILT is correlated with an increase in oxidative stress-related enzymes and matrix metalloproteinase-9 (MMP-9) expression within the human AAA wall was investigated. We also studied the antioxidant activity of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase, and thioredoxin within the full-thickness AAA wall and through fluoroimmunohistochemical staining of catalase and MMP-9 expression within the inner and outer media, in relation to ILT thickness. Reactive oxygen species control the degradation and remodeling of the extracellular matrix by up-regulating proteolytic enzymes, such as MMPs. Results showed that oxidative stress and proteolytic enzyme expression were simultaneously, significantly higher within thin thrombus (≤10 mm)-covered aneurysm wall when compared with the wall covered by thick thrombus (≥25 mm). These findings provide the first demonstration, to our knowledge, of a causative link between oxidative stress instigating proteolytic enzyme expression at the tissue level and human AAA development. Presence of a thin circumferential thrombus should always be considered as a risk factor for the greatest increase in aneurysm growth rate and rupture, giving an indication for surgery timing.-Wiernicki, I., Parafiniuk, M., Kolasa-Wołosiuk, A., Gutowska, I., Kazimierczak, A., Clark, J., Baranowska-Bosiacka, I., Szumilowicz, P., Gutowski, P. Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.

Contrast Enhanced Three Dimensional Ultrasound for Intraluminal Thrombus Assessment in Abdominal Aortic Aneurysms

The impact of intraluminal thrombus (ILT) on abdominal aortic aneurysm (AAA) progression can be investigated non-invasively by three dimensional contrast enhanced ultrasound (3D-CEUS). The aim was to validate 3D-CEUS ILT volume and thickness measurements against computed tomography angiography (CTA), and to determine inter- and intra-operator reproducibility. The design was for a planned comparison of 3D-CEUS and CTA and of repeated 3D-CEUS measurements in a blinded set up. Consecutive patients with asymptomatic AAA (n=137, maximum diameter 30-55mm) from a single centre were consecutively assessed by CTA and 3D-CEUS in a blinded setup. After exclusion of failed CTA (n=2) and inconclusive 3D-CEUS (n=8), 127 3D-CEUS/CTA pairs were analysed by Bland-Altman plots. 3D-CEUS inter- and intra-operator reproducibility were determined in a subgroup (n=30) measured twice by two blinded investigators. In 24 of 127 (19%) patients, no ILT was found on 3D-CEUS. Intraluminal thrombus absence was confirmed by 3D-CTA analysis in all but two cases. Mean ILT volume difference between 3D-CEUS and CTA was 2.2mL (5% of mean volume) and range of variability (ROV) amounted to±10.2mL. Mean ILT thickness difference was 0.6mm with a ROV of ± 4.6mm 3D-CEUS inter-operator variations of ILT volume and thickness measurements were low (ROV±8.8mL and ±2.9mm, respectively). The corresponding intra-operator ROVs were ±7.5mL and ±3.3mm, respectively. 3D-CEUS demonstrated good reproducibility and a good agreement with CTA when estimating ILT volume and maximum thickness in AAA patients. It is a promising research tool to investigate potential interactions between ILT, AAA growth, and rupture.

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms

BackgroundThe hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. MethodsFactor levels were measured using enzyme-linked immunosorbent assay of protein extract. ResultsTissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α2-antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). ConclusionsThese results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall.

Intraluminal thrombus is associated with early rupture of abdominal aortic aneurysm

BackgroundThe implications of intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) are currently unclear. Previous studies have demonstrated that ILT provides a biomechanical advantage by decreasing wall stress, whereas other studies have associated ILT with aortic wall weakening. It is further unclear why some aneurysms rupture at much smaller diameters than others. In this study, we sought to explore the association between ILT and risk of AAA rupture, particularly in small aneurysms. MethodsPatients were retrospectively identified and categorized by maximum aneurysm diameter and rupture status: small (<60 mm) or large (≥60 mm) and ruptured (rAAA) or nonruptured (non-rAAA). Three-dimensional AAA anatomy was digitally reconstructed from computed tomography angiograms for each patient. Finite element analysis was then performed to calculate peak wall stress (PWS) and mean wall stress (MWS) using the patient's systolic blood pressure. AAA geometric properties, including normalized ILT thickness (mean ILT thickness/maximum diameter) and % volume (100 × ILT volume/total AAA volume), were also quantified. ResultsPatients with small rAAAs had PWS of 123 ± 51 kPa, which was significantly lower than that of patients with large rAAAs (242 ± 130 kPa; P = .04), small non-rAAAs (204 ± 60 kPa; P < .01), and large non-rAAAs (270 ± 106 kPa; P < .01). Patients with small rAAAs also had lower MWS (44 ± 14 kPa vs 82 ± 20 kPa; P < .02) compared with patients with large non-rAAAs. ILT % volume and normalized ILT thickness were greater in small rAAAs (68% ± 11%; 0.16 ± 0.04 mm) compared with small non-rAAAs (53% ± 16% [P = .02]; 0.11 ± 0.04 mm [P < .01]) and large non-rAAAs (57% ± 12% [P = .02]; 0.12 ± 0.03 mm [P < .01]). Increased ILT % volume was associated with both decreased MWS and decreased PWS. ConclusionsThis study found that although increased ILT is associated with lower MWS and PWS, it is also associated with aneurysm rupture at smaller diameters and lower stress. Therefore, the protective biomechanical advantage that ILT provides by lowering wall stress seems to be outweighed by weakening of the AAA wall, particularly in patients with small rAAAs. This study suggests that high ILT burden may be a surrogate marker of decreased aortic wall strength and a characteristic of high-risk small aneurysms.

Correlation of Intraluminal Thrombus Deposition, Biomechanics, and Hemodynamics with Surface Growth and Rupture in Abdominal Aortic Aneurysm—Application in a Clinical Paradigm

The natural history of abdominal aortic aneurysm (AAA) can be investigated through longitudinal evaluation of localized aneurysm characteristics exploiting clinical images. The major challenge is to identify corresponding regions between follow-ups. We have recently developed an algorithm (VascForm) based on nonrigid registration that can obtain surface correspondence and quantify surface growth distribution. A ruptured AAA with an initial computed tomography scan 2years ago was studied. Following 3-dimensional reconstruction of outer wall and luminal surfaces, the wall/thrombus thickness was obtained. Wall stress distribution was computed with finite element analysis, and computational fluid dynamics simulation was performed. VascForm was applied and allowed for the ruptured wall site to be traced back to the initial wall surface and be correlated with local initial intraluminal thrombus thickness, wall stress, and hemodynamic parameters. It also allowed for the quantification of wall surface growth based on surface element growth. Rupture occurred at the posterolateral side. Initial wall surface growth was in most regions 40%. However, a large section of the posterior wall presented 110% growth. Initial thrombus deposition was more prevalent anteriorly, and a posterior thrombus-free isle was present. Peak wall stress (initial and follow-up) occurred at AAA neck. Nonrigid registration revealed that rupture originated from the vicinity of the initial thrombus-free isle. Furthermore, rupture occurred at the wall region with the largest growth (110%). No clear correlation between hemodynamics and rupture site could be identified. High local surface growth correlates with rupture site and could therefore potentially become a marker of rupture risk. The ongoing application of this methodology to a large cohort of AAA patients will focus on identifying characteristic features of AAA regions that present high surface growth in follow-up evaluations, to assist in improved rupture risk estimation.