Abdominal Aortic Aneurysm Thrombus Research Articles

Glycoprotein VI Platelet Receptor Blockade Attenuates Progression of Established Abdominal Aortic Aneurysms in Murine Models

Objective: Abdominal aortic aneurysms (AAA) frequently feature the formation of a nonocclusive intraluminal thrombus (ILT) along the site of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation via the glycoprotein VI receptor pathway impacts the pathogenesis of AAA. Methods and Results: RNA sequencing was performed on age-matched control human aortic tissue, AAA aortic tissue, and AAA ILT. Platelet transcripts comprised 25% of significantly enriched genes in the comparison of AAA thrombus to AAA tissue and control aortic wall, with GPVI increased by 9.1 Log2-FC (P = 3.21E−08). Circulating GPVI was significantly elevated in platelets isolated from AAA patients versus age-matched controls. Soluble GPVI (sGPVI—indicator of platelet activation), was significantly increased in the plasma of patients with fast-growing AAAs compared to slow-growing AAAs and healthy control subjects. To determine if GPVI blockade was protective from AAA progression, mice underwent either the angiotensin II (AngII) infusion or the topical elastase models of aneurysm formation. Following model initiation, aortic diameter was monitored by weekly ultrasounds. After two weeks, mice which developed an aneurysm (defined as an aortic diameter of >1.2mm) were randomized into control (IgG—50μg) or treatment (JAQ1—50μg, monoclonal GPVI antibody) groups. As expected, platelets isolated from JAQ1 treated mice did not activate in response to the GPVI specific agonist convulxin. Furthermore, JAQ1 treatment attenuated aneurysm progression, increased type I collagen deposition, attenuated macrophage accumulation, and increased survival in both murine AAA models versus IgG control treated mice. Conclusions: Platelets play a critical role in AAA pathophysiology and specific blockade of the GPVI-mediated activation pathway attenuates progression of established aneurysms in two independent murine models. Thus, our work demonstrates that specific targeting of GPVI to blunt platelet activation in AAA could be a potential therapeutic for a pathology with no current pharmacological treatments. R01HL147171-04 and R01HL158801-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 18814: Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms

Objective: Abdominal aortic aneurysms (AAA) frequently feature the formation of a nonocclusive intraluminal thrombus (ILT) along the site of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understand. Thus, we sought to investigate how platelet activation via the glycoprotein VI (GPVI) platelet receptor impacts the pathogenesis of AAA. Methods and Results: RNA sequencing of age-matched control human aortic tissue, AAA aortic tissue, and AAA ILT demonstrates that platelet transcripts comprised 25% of significantly enriched genes AAA thrombus compared to AAA tissue and control aortic wall, with GPVI increased by 9.1 Log2-FC (P = 3.21E -08 ). Examination of soluble GPVI (sGPVI), a specific marker of platelet activity, in 2 independent AAA patient cohorts is predictive of AAA case status, associates strongly with aneurysm growth rate, and better predicts the presence of a fast-growing AAA when compared to D-dimer. To determine if GPVI blockade ameliorates AAA progression, mice were subjected to either the angiotensin II (AngII) infusion or the topical elastase models of aneurysm formation. Following model initiation, aortic diameter was monitored by weekly ultrasounds. After two weeks, mice which developed an aneurysm (defined as an aortic diameter of >1.2mm) were randomized into control (IgG-50μg) or treatment (JAQ1-50μg, monoclonal GPVI antibody) groups. Treatment with JAQ1 blunted GPVI mediated platelet activation, attenuated aneurysm progression, and increased survival in both murine AAA models versus control. Conclusions: The highly specific platelet activation biomarker soluble glycoprotein VI strongly predicts both AAA case status and growth rate with potential use in identifying high risk patients. Specific blockade of GPVI-mediated platelet activation attenuates progression of established aneurysms in two independent murine models. Thus, our work demonstrates that specific targeting of GPVI to blunt platelet activation in AAA could be a potential therapeutic for a pathology with no current pharmacological treatments.

Abstract 155: Platelet-derived Transforming Growth Factor-β1 Ameliorates AAA in a Murine Model

Background: Platelets are rapidly recruited to the forming intraluminal thrombus in abdominal aortic aneurysm (AAA), stabilizing the aortic wall and preventing rupture. Adhesion and activation of platelets releases a mix of inflammatory mediators such as transforming growth factor β (TGFβ), which mediates cellular proliferation, inflammatory signaling, and fibrosis. Importantly, while TGFβ neutralization results in increased rupture and disease progression in mouse models of AAA, the source of protective TGFβ signaling remains controversial. We hypothesized that platelet-derived TGFβ1 attenuates aortic growth in the elastase AAA model. Methods and Results: Ldlr -/- mice with platelet-specific deletion of Tgfβ1 were produced by breeding hemizygous male mice expressing Cre under the control of the Pf4 promoter to female Tgfβ1 floxed mice (Jackson Labs). Mice were subjected to laparotomy and topical elastase application to the abdominal aorta (10 mg/mL porcine pancreatic elastase for 5 minutes) and sacrificed at day 28 to determine AAA progression via aortic diameter. Male TGFβ1-Pf4 Cre+ mice (n=8) had significantly increased abdominal aortic diameters compared to Male TGFβ1-Pf4 Cre- mice (n=7) ( Cre- : 1.70 ± 0.12 mm; Cre+ : 2.66 ± 0.25 mm; P < 0.004). Additionally, 25% of male TGFβ1-Pf4 Cre+ mice died of AAA rupture compared to 0% in the TGFβ1-Pf4 Cre- cohort. To determine if these actions were occurring via TGFβ1 activation of the TGFβ receptor 2 (βr 2 ), Ldlr -/- /βr2 Flox /PF4 Cre+ and Cre- mice were created, similarly to the previously described Tgfβ1 mice. Male βr2-Pf4 Cre+ (n=7) had increased aortic diameter compared to βr2-Pf4 Cre- (n=6) ( Cre- : 1.70± 0.20 mm; Cre+ : 2.45 ± 0.38 mm; P < 0.138). Additionally, female βr2-Pf4 Cre+ (n=9) also had significantly larger aortic diameters compared to βr2-Pf4 Cre- (n = 5) ( Cre- : 1.27± 0.04 mm; Cre+ : 1.90 ± 0.23 mm; P < 0.01). Conclusions: Our results further support TGFβ signaling playing a protective role in AAA. More specifically, platelet-derived TGFβ1 ligand and signaling via platelet TGFβr2 mitigates aortic diameter expansion. Further research into the pertinent TGFβ isoforms and the mechanism of TGFβr2 activation will ideally yield insights into therapeutic targets for an, as yet, intractable disease.

A poor outcome in non-occlusive thrombo-embolic limb ischaemia related to the dislocation of mural thrombus from an abdominal aortic aneurysm

BackgroundAcute thrombosis of an abdominal aortic aneurysm with acute limb ischaemia is an unusual complication and is associated with high mortality. Dislocation of the intrasaccular mural thrombus could be one of the mechanisms. For the most part, acute limb ischaemia presents with absent pulses, compatible with the clinical findings, which include pain, paraesthesia, and paralysis. Herein, we report a rare condition with detectable distal pulses in advanced limb ischaemia due to poor perfusion caused by the dislocation of mural thrombus from an abdominal aortic aneurysm.Case presentationA 74-year-old male patient with underlying hypertension and chronic renal disease presented at the emergency room with bilateral lower limb paralysis after falling on his back in the bathroom an hour prior. He reported numbness and weakness of his lower limbs, which was gradually worsening, over the past week. Physical examination showed cyanotic mottling of the lower limbs with paralysis. However, the dorsalis pedis pulse was intact. Computed tomography angiography showed a 7.3 cm abdominal aortic aneurysm containing highly irregular mural thrombus in the early phase, with slow perfusion of the contrast medium in the arteries below the bifurcation during the delayed phase. After traumatic spinal injury was excluded, an emergent endovascular aneurysm repair was performed. Although vital signs were initially stable post-surgery, both lower limbs were still paralysed and did not improve. He then experienced reperfusion injury with metabolic acidosis. There was no urine output despite intravenous hydration. Laboratory data included potassium 7.7 mEq/L, lactate 110 mg/dL, white blood cells 23,700/uL, and myoglobin 46,590 ng/mL. Even under critical medical care and continuous venovenous hemofiltration, his hemodynamic status worsened. He developed hypotension and needed endotracheal intubation because of loss of consciousness and respiratory failure. The patient finally died due to ventricular tachycardia even after several rounds of cardiopulmonary resuscitation with cardioversion.ConclusionThe unusual clinical presentation of detectable lower limb pulses in advanced limb ischaemia showed that poor blood perfusion related to dislocation of mural thrombus in abdominal aortic aneurysm might mislead clinicians and delay accurate diagnosis and treatment.

Extent of mural thrombus is not associated with increased 5-year mortality following elective AAA repair.

Mural thrombus in abdominal aortic aneurysm (AAA) has been associated with increased rates of aneurysm growth as well as adverse cardiovascular events. The extent of mural thrombus in thoracoabdominal aortic aneurysms has recently been linked to 1-year mortality following endovascular repair and has been hypothesized as a marker for reduced cardiac reserve. This study investigates whether the extent of mural thrombus in infra-renal AAA is associated with 5-year mortality following elective repair. Retrospective review of all patients undergoing elective infra-renal AAA repair at a single academic medical center between 2007 and 2016 was performed. The following variables at the time of surgery were investigated for association with 5-year mortality: age, sex, ethnicity, insurance status and co-morbidities, repair type, renal insufficiency, end-stage renal disease on dialysis, history of smoking, coronary artery disease, congestive heart failure, diabetes mellitus, hypertension, stroke, chronic obstructive pulmonary disease, body mass index category, AAA diameter, and ratio of aortic thrombus to total aneurysm diameter. Amongst 427 patients undergoing infra-renal AAA repair during the study period, 232 met extensive inclusion criteria. Univariate analysis found mean age (76 vs 72, p < 0.01), age cohort over 72 years (OR = 1.9, p = 0.04), renal insufficiency (OR = 3.1, p < 0.01), ESRD (OR = 6.5, p < 0.01), AAA diameter 6cm or greater (OR = 2.3, p < 0.01), and mean AAA diameter (61.36vs 56.99mm, p < 0.01) all predictive of 5-year mortality. Multivariate analysis revealed renal insufficiency (p < 0.01) and AAA diameter 6cm or greater (p = 0.03) to be significantly associated with 5-year mortality. The extent of mural thrombus was identical between 5-year survivors and non-survivors. The mean inner to outer AAA diameter was 0.65 in the survivor cohort and 0.64 in the mortality cohort. Inner to outer ratio of < 0.5 was identified in 23% of 5-year survivors and 27% of the mortality group. In our experience, the extent of mural thrombus in AAA does not influence long-term survival after elective repair. AAA repair may provide protection against circulating components of mural thrombus which have the potential to promote atherosclerotic-related adverse events. Patients with renal insufficiency and larger AAA have increased risk of mortality 5 years after elective repair.

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.

Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans.

Discovery of novel biomarkers for AAA growth prediction. Novel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction. Patients were prospectively recruited. Plasma samples were collected at baseline (n = 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n = 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10-12 weeks after surgery (n = 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n = 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers. We discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively. We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.

Further evidence on the relationship between abdominal aortic aneurysm and periodontitis: A cross-sectional study.

Periodontitis is a chronic inflammatory disease characterized by Gram-negative bacteria responsible for the degradation of tissues surrounding tooth. Moreover, periopathogens can invade the bloodstream, disseminate and promote cardiovascular disease, such as the link between Porphyromonas gingivalis and atherosclerosis. The aim of this study was to explore the relationship between the severity of periodontitis and of abdominal aortic aneurysm (AAA). This cross-sectional study compared patients with stable AAA (n = 30) and patients with unstable AAA (n = 31) based on aortic diameter, growth rate, and eligibility for surgical intervention. Periodontal clinical parameters were recorded as well as the Periodontal Inflamed Surface Area and the Periodontal Index for Risk of Infectiousness (PIRI). Microbiological analyses were performed on saliva and supragingival and subgingival plaque. Quantification of Tannerella forsythia (Tf), Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Fusobacterium nucleatum (Fn), and Prevotella intermedia (Pi) was done by quantitative polymerase chain reaction. The two AAA groups were homogeneous for age, sex, and most risk factors except hypertension and chronic obstructive pulmonary disease. Periodontal parameters were comparable but the proportion of patients with high PIRI scores was greater in those with unstable AAA (51.6% versus 23.3%). The probing depth (PD) and the proportion of PD >6 mm were positively correlated with AAA size and thrombus volume. Several associations were found between periopathogens such as Pg and AAA diameters and volumes, but no difference could be evidenced between stable and unstable AAA groups. Periodontitis was highly prevalent in both stable and unstable AAA patients. Severe and progressive periodontitis (stage IV and grade C) tended to be more frequent in the group of patients with unstable AAA. Moreover, Pg was observed in all the samples (saliva, supragingival, and subgingival plaque) and was correlated with AAA diameters and volumes. The study evidenced potential relationships between periodontitis severity and size of AAA.

Detection of Macrophage Localization in the Abdominal Aortic Aneurysm Wall Using Ex Vivo Superparamagnetic Iron Oxide–Enhanced Magnetic Resonance Imaging

Macrophages in the aneurysmal wall play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Superparamagnetic iron oxide (SPIO) is a macrophage-specific contrast agent that results in negative enhancement on magnetic resonance imaging (MRI). SPIO-enhanced MRI targeting the intraluminal thrombus of AAAs has been previously reported. However, macrophages in the media and adventitia of AAA wall have not been investigated in detail. This study aimed to evaluate macrophage localization using SPIO-enhanced MRI in the media and adventitia of AAA wall, as macrophages play a crucial role in AAA pathogenesis. Here, we included study and control patients planning to undergo open surgery for AAA. The study patients received SPIO injection 2days preoperatively (the SPIO group, n=7), whereas the control patients did not receive this injection (the control group). Exvivo MRI was performed on the harvested AAA wall in the SPIO group during the surgery. The concordance between the number of macrophages and berlin blue (BB)-stained areas was histologically evaluated in both groups. Moreover, the concordance between regions of interest in MR images and BB-stained areas was evaluated. The proportion of BB-stained macrophages was higher in the SPIO group (0.93; interquartile range [IQR], 0.83-0.95) than in the control group (0.03; IQR, 0.026-0.11) (P<0.05), indicating uptake of SPIO by macrophages in the AAA wall. A significant positive correlation was found between the number of BB-stained macrophages and BB-stained areas using Kendall rank correlation coefficient in the SPIO group (τ=0.58; P<0.05). Significant correlations were found in the distributions of the region of interest of SPIO-enhanced MRI and BB-stained areas in the media and adventitia in 5 of 7 patients. Macrophages present in the media and adventitia of the AAA wall showed an uptake of the SPIO contrast agent injected 2days prior, which were then detected by exvivo MRI. This suggests that SPIO-enhanced MR images help detect the localization of macrophages on the AAA wall, indicating its potential to serve as a novel index for AAA pathogenesis.

Feasibility of shear wave sonoelastography to detect endoleak and evaluate thrombus organization after endovascular repair of abdominal aortic aneurysm

To investigate the feasibility of shear wave sonoelastography (SWS) for endoleak detection and thrombus characterization of abdominal aortic aneurysm (AAA) after endovascular repair (EVAR). Participants who underwent EVAR were prospectively recruited between November 2014 and March 2016 and followed until March 2019. Elasticity maps of AAA were computed using SWS and compared to computed tomography angiography (CTA) and color Doppler ultrasound (CDUS). Two readers, blinded to the CTA and CDUS results, reviewed elasticity maps and B-mode images to detect endoleaks. Three or more CTAs per participant were analyzed: pre-EVAR, baseline post-EVAR, and follow-ups. The primary endpoint was endoleak detection. Secondary endpoints included correlation between total thrombus elasticity, proportion of fresh thrombus, and aneurysm growth between baseline and reference CTAs. A 3-year follow-up was made to detect missed endoleaks, EVAR complication, and mortality. Data analyses included Cohen's kappa; sensitivity, specificity, and positive predictive value (PPV); Pearson coefficient; and Student's t tests. Seven endoleaks in 28 participants were detected by the two SWS readers (k = 0.858). Sensitivity of endoleak detection with SWS was 100%; specificity and PPV averaged 67% and 50%, respectively. CDUS sensitivity was estimated at 43%. Aneurysm growth was significantly greater in the endoleak group compared to sealed AAAs. No correlation between growth and thrombus elasticity or proportion of fresh thrombus in AAAs was found. No new endoleaks were observed in participants with SWS negative studies. SWS has the potential to detect endoleaks in AAA after EVAR with comparable sensitivity to CTA and superior sensitivity to CDUS. • Dynamic elastography with shear wave sonoelastography (SWS) detected 100% of endoleaks in abdominal aortic aneurysm (AAA) follow-up that were identified by a combination of CT angiography (CTA) and color Doppler ultrasound (CDUS). • Based on elasticity maps, SWS differentiated endoleaks from thrombi within the aneurysm sac (p < 0.001). • After 3-year follow-up, no new endoleaks were observed in SWS negative examinations.

Magnetic resonance imaging assessment of proteolytic enzyme concentrations and biologic properties of intraluminal thrombus in abdominal aortic aneurysms

ObjectiveThe aim of the study was to determine whether magnetic resonance imaging (MRI) can be used in assessment of biologic activity of intraluminal thrombus (ILT) and proteolytic processes of the abdominal aortic aneurysm wall. MethodsUsing MRI, 50 patients with asymptomatic infrarenal abdominal aortic aneurysm were analyzed at the maximum aneurysm diameter on T1-weighted images in the arterial phase after administration of contrast material. Relative ILT signal intensity (SI) was determined as the ratio between ILT SI and psoas muscle SI. During surgery, the full thickness of the ILT and the adjacent part of the aneurysm wall were harvested at the maximal diameter for biochemical analysis. The concentrations of matrix metalloproteinase 9 and neutrophil elastase (NE/ELA) were analyzed in harvested thrombi, and the concentrations of collagen type III, elastin, and proteoglycans were analyzed in harvested aneurysm walls. ResultsA significant positive correlation was found between the NE/ELA concentration of the ILT and the relative SI (ρ = 0.309; P = .029). Furthermore, a negative correlation was observed between the elastin content of the aneurysm wall and the relative SI (ρ = −0.300; P = .034). No correlations were found between relative SI and concentration of matrix metalloproteinase 9, NE/ELA, collagen type III, or proteoglycan 4 in the aneurysm wall. ConclusionsThese findings indicate a potential novel use of MRI in prediction of thrombus proteolytic enzyme concentrations and the extracellular matrix content of the aneurysm wall, thus providing additional information for the risk of potential aneurysm rupture.

Anthropomorphic and biomechanical mockup for abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is an asymptomatic condition due to the dilation of abdominal aorta along with progressive wall degeneration, where rupture of AAA is life-threatening. Failures of AAA endovascular repair (EVAR) reflect our inadequate knowledge about the complex interaction between the aortic wall and medical devices. In this regard, we are presenting a hydrogel-based anthropomorphic mockup (AMM) to better understand the biomechanical constraints during EVAR. By adjusting the cryogenic treatments, we tailored the hydrogel to mimic the mechanical behavior of human AAA wall, thrombus and abdominal fat. A specific molding sequence and a pressurizing system were designed to reproduce the geometrical and diseased characteristics of AAA. A mechanically, anatomically and pathologically realistic AMM for AAA was developed for the first time, EVAR experiments were then performed with and without the surrounding fat. Substantial displacements of the aortic centerlines and vessel expansion were observed in the case without surrounding fat, revealing an essential framework created by the surrounding fat to account for the interactions with medical devices. In conclusion, the importance to consider surrounding tissue for the global deformation of AAA during EVAR was highlighted. Furthermore, potential use of this AMM for medical training was also suggested.

Evaluation of the distribution and progression of intraluminal thrombus in abdominal aortic aneurysms using high-resolution MRI.

Intraluminal thrombus (ILT) signal intensity on MRI has been studied as a potential marker of abdominal aortic aneurysm (AAA) progression. 1) To characterize the relationship between ILT signal intensity and AAA diameter; 2) to evaluate ILT change over time; and 3) to assess the relationship between ILT features and AAA growth. Prospective. Eighty AAA patients were imaged, and a subset (n = 41) were followed with repeated MRI for 16 ± 9 months. 3D black-blood fast-spin-echo sequence at 3 T. ILT was designated as "bright" if the signal was greater than 1.2 times that of adjacent psoas muscle. AAAs were divided into three groups based on ILT: Type 1: bright ILT; Type 2: isointense ILT; Type 3: no ILT. During follow-up, an active ILT change was defined as new ILT formation or an increase in ILT signal intensity to bright; stable ILT was defined as no change in ILT type or ILT became isointense from bright previously. Shapiro-Wilk test; Mann-Whitney U-test; Fisher's exact test; Kruskal-Wallis test; Spearman's r; intraclass correlation coefficient (ICC), Cohen's kappa. AAAs with Type 1 ILT were larger than those with Types 2 and 3 ILT (5.1 ± 1.1 cm, 4.4 ± 0.9 cm, 4.2 ± 0.8 cm, P = 0.008). The growth rate of AAAs with Type 1 ILT was significantly greater than that of AAAs with Types 2 and 3 ILT (2.6 ± 2.5, 0.6 ± 1.3, 1.5 ± 0.6 mm/year, P = 0.01). During follow-up, AAAs with active ILT changes had a 3-fold increased growth rate compared with AAAs with stable ILT (3.6 ± 3.0 mm/year vs. 1.2 ± 1.5 mm/year, P = 0.008). AAAs with bright ILT are larger in diameter and grow faster. Active ILT change is associated with faster AAA growth. Black-blood MRI can characterize ILT features and monitor their change over time, which may provide new insights into AAA risk assessment. 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:994-1001.

Magnetic resonance imaging of the intraluminal thrombus in abdominal aortic aneurysms: a quantitative and qualitative evaluation and correlation with growth rate.

The role of the intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) growth remains incompletely understood. MRI is superior to other methods in depicting the morphology of the ILT. This study brings preliminary, but novel information on the presence and morphological characteristics of the ILT and AAA growth rates in a screening cohort. Cohort study with 46 patients from the Viborg Vascular Trial. All underwent one non-contrast-enhanced magnetic resonance imaging (MRI) at the end of follow-up. ILT presence was noted and, if present, it was allocated to one of four morphological categories based on visual appearance and signal intensity on T2 weighted images. The mean growth rate was 1.95 mm/year ±0.87 (SD). The observation time was 5.59±0.63 (SD) years. ILT was present in AAA size groups as follows: 30-34.9 mm 20.00%, 35-39.9 mm 88.89%, 40-44.9 mm 81.25%, 45-49.9 mm 100% and 50-54.9 mm 100%. Out of 46, 8 had no ILT at the time of MRI. The presence of any sort of ILT yielded a significantly increased unadjusted and an adjusted growth rate of 1.09 mm/year (95% CI: 0.48; 1.70) and 1.24 mm/year (95% CI: 0.64; 1.83), respectively. All four thrombus types were retrospectively associated with an increased recorded growth rate compared with "no thrombus". Presence of a thin circumferential thrombus was retrospectively associated with the highest increase in growth rate, viz. 2.09 mm/year (95% CI: 1.23; 2.95). We observed faster growth rate in those AAA that had developed an ILT. Even faster growth was observed amongst those AAA containing a thin ILT located along the inner circumference.

BioPARR: A software system for estimating the rupture potential index for abdominal aortic aneurysms

An abdominal aortic aneurysm (AAA) is a permanent and irreversible dilation of the lower region of the aorta. It is a symptomless condition that, if left untreated, can expand until rupture. Despite ongoing efforts, an efficient tool for accurate estimation of AAA rupture risk is still not available. Furthermore, a lack of standardisation across current approaches and specific obstacles within computational workflows limit the translation of existing methods to the clinic. This paper presents BioPARR (Biomechanics based Prediction of Aneurysm Rupture Risk), a software system to facilitate the analysis of AAA using a finite element analysis based approach. Except semi-automatic segmentation of the AAA and intraluminal thrombus (ILT) from medical images, the entire analysis is performed automatically. The system is modular and easily expandable, allows the extraction of information from images of different modalities (e.g. CT and MRI) and the simulation of different modelling scenarios (e.g. with/without thrombus). The software uses contemporary methods that eliminate the need for patient-specific material properties, overcoming perhaps the key limitation to all previous patient-specific analysis methods. The software system is robust, free, and will allow researchers to perform comparative evaluation of AAA using a standardised approach. We report preliminary data from 48 cases.

Fluid displacement from intraluminal thrombus of abdominal aortic aneurysm as a result of uniform compression.

Objectives The results after aneurysm repair with an endovascular aneurysm sealing (EVAS) system are dependent on the stability of the aneurysm sac and particularly the intraluminal abdominal aortic thrombus (ILT). The postprocedural ILT volume is decreased compared with preprocedural ILT volume in aortic aneurysm patients treated with EVAS. We hypothesize that ILT is not stable in all patients and pressurization of the ILT may result in displacement of fluids from the ILT, no differently than serum is displaced from whole blood when it settles. To date, the mechanism and quantification of fluid displacement from ILT are unknown. Methods The study included 21 patients who underwent elective open abdominal aortic aneurysm repair. The ILT was harvested as a routine procedure during the operation. After excision of a histologic sample of the ILT specimen in four patients, ILT volume was measured and the ILT was compressed in a dedicated compression setup designed to apply uniform compression of 200 mmHg for 5 min. After compression, the volumes of the remaining thrombus and the displaced fluid were measured. Results The median (interquartile-range) of ILT volume before compression was 60 (66) mL, and a median of 5.7 (8.4) mL of fluid was displaced from the ILT after compression, resulting in a median thrombus volume decrease of 11% (10%). Fluid components can be up to 31% of the entire ILT volume. Histologic examination of four ILT specimens showed a reduction of the medial layer of the ILT after compression, which was the result of compression of fluid-containing canaliculi. Conclusions Applying pressure of 200 mmHg to abdominal aortic aneurysm ILT resulted in the displacement of fluid, with a large variation among patients. Fluid displacement may result in decrease of ILT volume during and after EVAS, which might have implications on pre-EVAS volume planning and on stability of the endobags during follow-up which may lead to migration, endoleak or both.

Hemodynamics-driven deposition of intraluminal thrombus in abdominal aortic aneurysms.

Accumulating evidence suggests that intraluminal thrombus plays many roles in the natural history of abdominal aortic aneurysms. There is, therefore, a pressing need for computational models that can describe and predict the initiation and progression of thrombus in aneurysms. In this paper, we introduce a phenomenological metric for thrombus deposition potential and use hemodynamic simulations based on medical images from 6 patients to identify best-fit values of the 2 key model parameters. We then introduce a shape optimization method to predict the associated radial growth of the thrombus into the lumen based on the expectation that thrombus initiation will create a thrombogenic surface, which in turn will promote growth until increasing hemodynamically induced frictional forces prevent any further cell or protein deposition. Comparisons between predicted and actual intraluminal thrombus in the 6 patient-specific aneurysms suggest that this phenomenological description provides a good first estimate of thrombus deposition. We submit further that, because the biologically active region of the thrombus appears to be confined to a thin luminal layer, predictions of morphology alone may be sufficient to inform fluid-solid-growth models of aneurysmal growth and remodeling.

Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results.

It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

Von Willebrand Factor and Prekallikrein in Plasma Are Associated With Thrombus Volume in Abdominal Aortic Aneurysms.

Disruption of the endothelial lining may be one of the events linking intraluminal thrombus and abdominal aortic aneurysm growth. In the present study, we examined whether von Willebrand factor activity in plasma, contact proteins of blood coagulation, and inflammatory biomarkers may be associated with intraluminal thrombus volume in search of a biochemical marker of endothelial damage and thrombus size. Prospective study, correlating potential endothelial biomarkers and intraluminal thrombus volume acquired by computed tomography angiography. Plasma was consecutively obtained from 38 patients with asymptomatic infrarenal abdominal aortic aneurysm. von Willebrand factor activity, thrombin generation time, factor XII, and prekallikrein concentration were measured in plasma on automated and in-house platforms. In total, 8 patients were excluded due to ongoing anticoagulant therapy, renal impairment, or nonappearance, thus leaving 30 patients for further analysis. All patients had computed tomography angiography, and intraluminal volume was quantified off-line by OsiriX 6.5. Median intraluminal thrombus volume was 42.7 mL. Spearman correlation analysis revealed a positive correlation between thrombus volume, von Willebrand factor activity (ρ = 0.56, P = .0013), and prekallikrein concentration in plasma (ρ = 0.54, P = .002). von Willebrand factor activity and concentration of prekallikrein may both be of importance regarding the evolution of thrombus in abdominal aortic aneurysm and possible biomarkers for aneurysm growth.

Von Willebrand Factor Activity in Plasma Associated with Thrombus Volume in Abdominal Aortic Aneurysms

Objectives: Disruption of the endothelial lining may be one of the events linking intraluminal thrombus (ILT) and abdominal aortic aneurysm (AAA) growth. Von Willebrand factor (vWf) is produced mainly in the endothelium and plays a key role in thrombus formation. In this study, we examined whether vWf activity in plasma and ILT-volume may be associated with endothelial damage and thrombus size. Design: A prospective study, correlating potential endothelial biomarkers and ILT volume acquired by computed tomography angiography (CTA). Materials & methods: Plasma was consecutively obtained from 38 patients with asymptomatic infrarenal AAA. Von Willebrand factor activity, thrombin generation, factor XII (F.XII) and prekallikrein (PK) were measured in plasma on automated and in house platforms. In total, eight patients were excluded due to ongoing anticoagulant therapy or decreased renal function (serum creatinine >105umol/l), thus leaving thirty patients for further analysis. All patients had a computed tomography angiography (CTA), and the intraluminal thrombus (ILT) volume was quantified offline by OsiriX 6.5. Results: The mean ILT volume was 61.8 ml [95%-CI: 47.3e76.4]. Pearson’s correlation analysis revealed a positive correlation between ILT-volume and vWf activity in plasma (r 1⁄4 0.63, P 1⁄4 0.002). In contrast, no correlations were observed between the ILT-volume and the other haemostatic measures. Conclusions: Von Willebrand factor activity in plasma correlates to AAA thrombus size. Our study suggests that vWf measurement in plasmamaybeabiochemicalmeasure formonitoringAAAprogression. Urgent Aggressive Best Medical Therapy Prior to Carotid Surgery Dramatically Reduces Recurrent Stroke Prior to Surgery Without Significantly Increasing Peri-operative Bleeding Complications R.K. Ramachandran , A. Owen-Falkenberg , B. Gottschalksen , K. Ellemann , S. Shahidi a,b,c a Department of Vascular Surgery, Regional Hospital Slagelse, Faelledvej 1, 4200 Slagelse, Denmark b Department of Anaesthesia, Regional Hospital Slagelse, Faelledvej 1, 4200 Slagelse, Denmark c Department of Neurology, University Hospital Roskilde, Koegevej 7-13, 4000