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Clinical assessment of abdominal aortic aneurysm (AAA) intervention and rupture risk relies primarily on maximum diameter, but studies have shown that sole dependence on diameter has limitations. CTA-based radiomics, aneurysm and lumen area change rates (AACR, LACR) are measured to predict potential AAA events. Between January 2017 and November 2022, 260 AAA patients from four centers who underwent two preoperative CTA examinations were included in this retrospective study. The endpoint event is defined as AAA rupture or repair. Patients were categorized into event and no-event groups based on the occurrence of endpoint event during follow-up. AACR and LACR were assessed using baseline and follow-up CTA, with radiomics features extracted from the baseline images. C-statistics and the Kaplan–Meier analysis were used to evaluate the predictive performance. A total of 193 eligible infrarenal AAA patients were included, 176 (91.2%) were man and 17 (8.8%) were woman. The median follow-up was 33.4 (14.2, 57.4) months. Seven models were constructed, comprising the aneurysm-based Radscore model, lumen-based Radscore model, intraluminal thrombus (ILT)-based Radscore model, AACR model, LACR model, clinical model (including high-density lipoprotein, D -dimer, and baseline aneurysm diameter), and a merged model. On the external validation set, the C-index of seven models were 0.713 (0.574–0.853), 0.642 (0.499–0.786), 0.727 (0.600–0.854), 0.619 (0.484–0.753), 0.680 (0.530–0.830), 0.690 (0.557–0.824) and 0.760 (0.651–0.869), in that order. In the Kaplan–Meier analysis, the merged model was best-divided patients into high/low-risk groups with Log-rank p < 0.0001. The AARC and LARC between non-event and event groups have significant differences (AACR: 1.4 cm2/y vs. 2.3 cm2/y, p < 0.0001; LACR: 0.3 cm2/y vs. 1.1 cm2/y, p < 0.0001). CTA-based radiomics, AACR and LACR have good predictive value for outcome event in infrarenal AAA patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between chronic headache outcome and aneurysmal wall enhancement (AWE) on high-resolution vessel wall imaging (HR-VWI) in patients with unruptured intracranial aneurysms (UIAs) who underwent microsurgical clipping. Methods: Two hundred seventy-four UIA patients were retrospectively analyzed. Patients were grouped according to presence of AWE. AWE was subclassified as focal or uniform. Clinical and imaging data were recorded. Headache was evaluated using the 10-point numerical rating scale and Headache Impact Test-6 before and 6 months after surgery. Results: The proportions of patients reporting chronic headache in the no AWE, focal wall enhancement (FWE), and uniform wall enhancement (UWE) groups were 5.7%, 24.8%, and 41.8%, respectively. All patients in the UWE group who reported headache before surgery experienced headache improvement after surgery. Decrease in headache severity was greater in the UWE group than in the FWE group. Multivariate binary logistic regression showed that FWE (odds ratio (OR) 0.490; 95% confidence interval (CI), 0.262–0.917; p = 0.026) and small intraluminal thrombus (OR 0.336; 95% CI, 0.142–0.795; p = 0.013) were independent factors protective against preoperative headache. FWE (OR 0.377; 95% CI, 0.195–0.728; p = 0.004) and small intraluminal thrombus (OR 0.235; 95% CI, 0.088–0.630; p = 0.004) were independent predictors of no headache relief after surgery. Conclusions: AWE on HR-VWI is associated with relief of chronic headache after surgical clipping in patients with UIAs. Incidence of chronic headache was highest in patients exhibiting UWE. These patients also experienced the greatest improvement in headache after surgical clipping. Clinical relevance statement: This study revealed that high-resolution vessel wall imaging can demonstrate aneurysmal wall plaque and intraluminal thrombus, which may be prognostic imaging markers for chronic headache in patients with unruptured intracranial aneurysms. Key Points: • Aneurysmal wall enhancement may be associated with chronic headache. • Incidence of chronic headache was highest in patients with aneurysms exhibiting uniform wall enhancement. • Patients with aneurysms exhibiting uniform wall enhancement experienced the greatest improvement in headache after clipping. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Introduction: Abdominal aortic aneurysms (AAAs) with intraluminal thrombus (ILT) are suggested to be more prone to rupture than AAAs without. Prior studies indicate that the von Willebrand factor (vWf) plays a role in the formation of ILT since a positive correlation between ILT volume and vWf has been shown. vWf mediates the tethering of platelets at sites of endothelial injury, and the protease ADAMTS-13 cleaves larger forms of vWf, thus counteracting the thrombosis cascade and maintaining haemostatic balance. When investigating the largest quantifiable thrombus in the human body, it was hypothesised that circulating ADAMTS-13 activity may be associated with ILT size in patients with AAA and the aim was to explore this potential relationship using 3D contrast enhanced ultrasound (3D-CEUS) for ILT volume determination. Report: In this retrospective, exploratory study, 60 patients with AAA were evaluated, and the association between ILT volume and thickness and ADAMTS-13 was estimated using 3D-CEUS. ADAMTS-13 activity was measured in plasma samples obtained the same day. No association between ILT volume (r = −0.03, p = 0.84) or ILT thickness (r = 0.02, p = 0.87) and ADAMTS-13 activity was found. Likewise, when subdividing the group into lowest and highest 50% of ADAMTS-13 activity, the half with the lowest ADAMTS-13 activity (mean ILT volume ±standard deviation [SD]: 32 ± 34 mL) did not differ from the half with the highest ADAMTS-13 activity (43 ± 24 mL) when comparing ILT volume (p = 0.172, F = 2.95) and thickness (p = 0.070). Discussion: After evaluating the largest quantifiable intraluminal thrombus in the vasculature, it was concluded that, surprisingly, circulating ADAMTS-13 activity seems unrelated to ILT formation in AAA.

Thamer S Alhowaish,1,2 Moustafa S Alhamadh,2,3 Abdullah Alsulayhim,2,4 Najla Alotaibi,5 Azzam Abdulaziz Alrashid,2,3 Abdulrahman Yousef Alhabeeb,2,3 Muhannad Q Alqirnas,2,3 Eythar Alrushid,1,2 Mohammed S Alnafisah,1,2 Ajmal Ali Anversha1,2 1Division of Neurology, Department of Medicine, King Abdulaziz Medical City, Ministry of the National Guard Health Affairs (MNGHA), Riyadh, Kingdom of Saudi Arabia; 2King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh, 11481, Kingdom of Saudi Arabia; 3College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of the National Guard-Health Affairs, Riyadh, 14611, Kingdom of Saudi Arabia; 4Radiology Department, King Abdul Aziz Medical City, Riyadh, Kingdom of Saudi Arabia; 5College of Public Health, Oregon State University, Corvallis, OR, USACorrespondence: Ajmal Ali Anversha, Division of Neurology, King Abdulaziz Medical City, King Abdullah International Medical Research Center, Ministry of the National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia, Tel +966-11-8011111 Ext: 13460, Email drajmalali@yahoo.comBackground: Intraluminal thrombus (ILT) of the cervical arteries is an uncommon finding that can lead to acute or recurrent ischemic stroke. Currently, antithrombotic therapy in the form of antiplatelet and/or anticoagulation is considered the mainstay of treatment, but evidence of which one has a better outcome is lacking.Methods: A retrospective cohort study included 28 patients diagnosed with acute stroke or transient ischemic attack with ILT of the extracranial arteries from 2013 to 2022. The primary efficacy outcome was assessed as recurrent stroke, and the primary safety outcome was assessed as hemorrhagic complications. Secondary outcomes were assessed as the resolution of thrombi by CT angiography (CTA) and clinical improvement by the Modified Rankin Scale (mRS) and NIH Stroke Scale (NIHSS).Results: Out of 28 patients, more than half (57.1%; n = 16) were males with a mean age of 57.8 ± 9.5 years and an average BMI of 26.9 ± 4.5 kg/m2. As initial treatment, twenty-four patients received anticoagulation and four received antiplatelet agents. Recurrent strokes were found in four patients (14.29%), and all were initially treated with anticoagulation. One patient in the anticoagulation group had a significant retroperitoneal hemorrhage. None of the patients in the antiplatelets group had a recurrent stroke or bleeding event. Initial treatment with antiplatelet agents significantly improved the NIHSS on day 7 (P = 0.017). A significant improvement in NIHSS on day 90 was observed in the anticoagulant group (P = 0.011). In the follow-up CTA performed on 24 patients, 18 (75%) showed complete resolution (3 out of 3 (100%) in the antiplatelet group and 15 out of 21 (71.43%) in the anticoagulant group).Conclusion: Initial treatment with anticoagulants improves neurologic outcomes in patients with ILT-induced acute ischemic stroke but carries the risk of recurrent stroke and bleeding. However, initial treatment with dual antiplatelet agents appears to have comparable efficacy without sequelae, particularly in atherosclerosis-induced ILT.Keywords: stroke, free-floating thrombus, intraluminal thrombus, Intraluminal clot, doughnut sign, antithrombotic, anticoagulation, antiplatelet agents, stroke in Saudi Arabia

This study proposed a method for semi-automatic segmentation of abdominal aortic aneurysms (AAAs) and their intraluminal thrombus (ILT), based on time resolved 3D ultrasound (US), and validated results with computed tomography (CT). Mechanical properties of both wall and ILT were determined, and possible correlations with ILT size and blood pressure were 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 with 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 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 to diastolic volume change of the ILT was determined successfully in 21 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. Lumen distensibility was strongly correlated with 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 has shown promising results for mechanical characterisation of the vessel, and ILT, including a correlation between distensibility, ILT size, and blood pressure. For future work, the inclusion rate needs to be increased by improving the image contrast with novel US techniques. [ABSTRACT FROM AUTHOR]

In this study, numerical simulations and experiments were conducted on patient-specific normal abdominal aorta and abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) models, which were reconstructed from computed tomography angiography (CTA) images published online. A scale-adaptive simulation (SAS) of the abdominal aortic aneurysm with a posterior eccentric thrombus was performed and the reliability of the numerical simulation was verified by 2D particle image velocimetry (PIV) experimental results. The distribution of wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT) of the normal abdominal aorta and AAA were compared and discussed systematically according to the numerical simulation results under rest and exercise conditions. Numerical results indicated that ILT deposition positions were accompanied by low WSS, high OSI, and high RRT regions and were characterized by small vortex groups, which was due to the fragmentation of large vortex structures. The distribution law of the AAA wall parameters has an obvious correlation with the nearby vortex structure formation, development, fragmentation and dissipation. It was also found that high TAWSS, low OSI, and low RRT regions present in the middle and lower aneurysm walls under exercise condition reduce the risk of ILT formation and development.

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.

BACKGROUND:Intraluminal thrombus (ILT) signal intensity on MRI has been studied as a potential marker of abdominal aortic aneurysm (AAA) progression. PURPOSE: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. STUDY TYPE:Prospective. SUBJECTS:Eighty AAA patients were imaged, and a subset (n = 41) were followed with repeated MRI for 16 ± 9 months. FIELD STRENGTH/SEQUENCE:3D black-blood fast-spin-echo sequence at 3 T. ASSESSMENT: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. STATISTICAL TESTS:Shapiro-Wilk test; Mann-Whitney U-test; Fisher's exact test; Kruskal-Wallis test; Spearman's r; intraclass correlation coefficient (ICC), Cohen's kappa. RESULTS: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). DATA CONCLUSION: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. LEVEL OF EVIDENCE:2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:994-1001.

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 16 mL (standard error [SE], ±3.2) compared with 28 mL (SE, ±2.7) in the no antithrombotic group and 30 mL (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 10 mm (SE, ±1.1) compared with 13 mm (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. [ABSTRACT FROM AUTHOR]

In this study, numerical simulations and experiments were conducted on patient-specific normal abdominal aorta and abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) models, which were reconstructed from computed tomography angiography (CTA) images published online. A scale-adaptive simulation (SAS) of the abdominal aortic aneurysm with a posterior eccentric thrombus was performed and the reliability of the numerical simulation was verified by 2D particle image velocimetry (PIV) experimental results. The distribution of wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT) of the normal abdominal aorta and AAA were compared and discussed systematically according to the numerical simulation results under rest and exercise conditions. Numerical results indicated that ILT deposition positions were accompanied by low WSS, high OSI, and high RRT regions and were characterized by small vortex groups, which was due to the fragmentation of large vortex structures. The distribution law of the AAA wall parameters has an obvious correlation with the nearby vortex structure formation, development, fragmentation and dissipation. It was also found that high TAWSS, low OSI, and low RRT regions present in the middle and lower aneurysm walls under exercise condition reduce the risk of ILT formation and development. [ABSTRACT FROM AUTHOR]

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

The frozen elephant trunk is a standard treatment method for aortic arch pathologies extending into the descending aorta. We previously described the phenomenon of early postoperative intraluminal thrombosis within the frozen elephant trunk. We investigated the features and predictors of intraluminal thrombosis. A total of 281 patients (66% male, mean age 60 ± 12 years) underwent frozen elephant trunk implantation between May 2010 and November 2019. In 268 patients (95%), early postoperative computed tomography angiography was available to assess intraluminal thrombosis. The incidence of intraluminal thrombosis after frozen elephant trunk implantation was 8.2%. Intraluminal thrombosis was diagnosed early after the procedure (4.6 ± 2.9 days) and could be successfully treated with anticoagulation in 55% of patients. A total of 27% developed embolic complications. Mortality (27% vs 11%, P =.044) and morbidity were significantly higher in patients with intraluminal thrombosis. Our data showed a significant association of intraluminal thrombosis with prothrombotic medical conditions and anatomic slow flow features. The incidence of heparin-induced thrombopenia was higher in patients with intraluminal thrombosis (18% vs 3.3%, P =.011). Stent-graft diameter index, anticipated endoleak Ib, and degenerative aneurysm were significant independent predictors of intraluminal thrombosis. Therapeutic anticoagulation was a protective factor. Glomerular filtration rate, extracorporeal circulation time, postoperative rethoracotomy, and intraluminal thrombosis (odds ratio, 3.19, P =.047) were independent predictors of perioperative mortality. Intraluminal thrombosis is an underrecognized complication after frozen elephant trunk implantation. In patients with risk factors of intraluminal thrombosis indication for frozen elephant trunk should be carefully evaluated and postoperative anticoagulation considered. Early thoracic endovascular aortic repair extension should be considered in patients with intraluminal thrombosis to prevent embolic complications. Stent-graft designs should be improved to prevent intraluminal thrombosis after frozen elephant trunk implantation. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysms (AAAs) are a relatively common vascular pathology of the elderly with high morbidity potential. Irreversible degeneration of the aortic wall leads to lethal rupture if left untreated. Nearly all AAAs contain intraluminal thrombus (ILT) to a varying degree, yet the mechanisms explaining how thrombosis is disturbed in AAA are relatively unknown. This review examined the thrombotic complications associated with AAA, the impact of thrombosis on AAA surgical outcomes and AAA pathogenesis, and the use of antithrombotic therapy in the management of this disease. Methods: A literature search of the PubMed database was conducted using relevant keywords related to thrombosis and AAAs. Results: Thrombotic complications are relatively infrequent in AAA yet carry significant morbidity risks. The ILT can impact endovascular aneurysm repair by limiting anatomic suitability and influence the risk of endoleaks. Many of the pathologic mechanisms involved in AAA development, including hemodynamics, inflammation, oxidative stress, and aortic wall remodeling, contain pathways that interact with thrombosis. Conversely, the ILT can also be a source of biochemical stress and exacerbate these aneurysmal processes. In animal AAA models, antithrombotic therapies have shown favorable results in preventing and stabilizing AAA. Antiplatelet agents may be beneficial for reducing risks of major adverse cardiovascular events in AAA patients; however, neither antiplatelet nor anticoagulation is currently used solely for the management of AAA. Conclusions: Thrombosis and ILT may have detrimental effects on AAA growth, rupture risk, and patient outcomes, yet there is limited understanding of the pathologic thrombotic mechanisms in aneurysmal disease at the molecular level. Preventing ILT using platelet and coagulation inhibitors may be a reasonable theoretical target for aneurysm progression and stability; however, the practical benefits of current antithrombotic therapies in AAA are unclear. Further research is needed to demonstrate the extent to which thrombosis impacts AAA pathogenesis and to develop novel pharmacologic strategies for the medical management of this disease. : Clinical Relevance: Abdominal aortic aneurysm rupture is a leading cause of mortality in the United States. Currently, no pharmacologic or noninvasive interventions exist to prevent the development or halt the progression of this disease. The pathogenesis of abdominal aortic aneurysms is multifactorial and strongly influenced by thrombosis. The intraluminal thrombus has been gaining recent attention as an active mediator in aneurysm growth and rupture. In this review article, we will discuss the impact of thrombosis on patient outcomes, the use of antithrombotic therapy, and current understanding of the mechanisms behind pathologic thrombosis leading to the formation and maintenance of the intraluminal thrombus.

ObjectiveWe attempted to measure maximum transverse diameter (MTD) of and CT values of ILT by using multi-spiral computed tomography angiography (MSCTA) to investigate the predictive value of MTD with different CT values of thrombus on the risk of AAA rupture.MethodsForty-five intact abdominal aortic aneurysms (IAAA) and 17 ruptured abdominal aortic aneurysms (RAAA) were included in this study. MTD and CT values in their planes were measured from MSCTA images and aneurysm lumen and thrombus volumes were calculated for the range of different CT values.ResultsThe median of maximum CT value of thrombus at the plane of MTD was higher in RAAA (107.0 HU) than the median in IAAA (84.5 HU) (P < 0.001). Univariate logistic regression analysis showed that the maximum CT value was a risk factor for RAAA (P < 0.001). It was further found that the area under the ROC curve for thrombus maximum CT value in the MTD plane to predict RAAA was 0.848 (P < 0.001), with a cut-off value of 97.5 HU, a sensitivity of 82.35%, and a specificity of 84.44%. And the MTD of the abnormal lumen combined with the maximum CT value at its plane predicted RAAA with an area under the ROC curve of 0.901, a sensitivity of 76.47%, and a specificity of 97.78%. The further analysis of thrombus volume in the range of different CT value showed that median thrombus volume in RAAA in the range of 30 HU~150 HU was 124.2 cm3 which was higher than the median of 81.4 cm3 in IAAA (P = 0.005). To exclude confounding factors (aneurysm volume), we calculated the standardized thrombus (ILT volume/total aneurysm volume), and the thrombus volume in the range of 30 HU~150 HU in RAAA was positively correlated with the standardized thrombus volume (ρ = 0.885, P < 0.001), while the thrombus volume in the range of −100 HU~30 HU was not correlated with it (ρ = 0.309, P = 0.228).ConclusionsHigh-density ILT shown on MSCTA in AAAs is associated with aneurysm rupture, and its maximum transverse diameter combined with the maximum CT value in its plane is a better predictor of RAAA.

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

Objective: Extracranial vertebral artery dissection (EVAD) is one of the main causes of stroke in young and middle-aged patients. However, the diagnosis is challenging. This study aimed to identify the characteristics of EVAD on color duplex ultrasonography (CDU) and high-resolution magnetic resonance imaging (hrMRI), hoping to improve the accuracy and determine the relative contribution of vessel findings and clinical factors to acute ischemic events. Methods: Patients with unilateral EVAD were recruited and divided into ischemia and non-ischemia groups. Clinical features of patients and the lesion location; a variety of signs which indicate dissection, including the presence of an intimal flap, double lumen, intramural hematoma, dissecting aneurysm, intraluminal thrombus, and irregular lumen; and other quantitative parameters of each dissected segment on CDU and hrMRI were reviewed, respectively. Multiple logistic regression was performed to explore the association between clinical, imaging characteristics, and ischemic events in patients with unilateral EVAD. Results: Ninety-six patients with unilateral EVAD who met the inclusion criteria were enrolled during a six-year period. Overall, 41 cases (42.7%) were confirmed as ischemic stroke (n = 40) or transient ischemic attack (n = 1) during the 48 h after the onset of symptoms. Men, infections during the last week, and smoking were more common in the ischemia group. Intraluminal thrombus and occlusion on CDU weremore prevalent in patients with cerebral ischemia than in those without (36.6 vs. 5.5%; p < 0.001, and 39.0 vs. 9.1%; p = 0.001, respectively). On hrMRI, intraluminal thrombus and occlusion were also more frequent in the ischemia group than in the non-ischemia group (34.1 vs. 5.5%; p < 0.001, and 34.1 vs. 9.1%; p=0.003, respectively). In addition, lesion length on hrMRI was significantly longer for patients with ischemia (81.5 ± 41.7 vs. 64.7 ± 30.8mm; p = 0.025). In multivariable logistic regression analysis, male gender, infections during the last week, and the presence of intraluminal thrombus on CDU and hrMRI were independently associated with acute ischemic events. Conclusion: Male sex, infections during the last week, and the presence of intraluminal thrombus due to dissection are associated with an increased risk of ischemic events in patients with unilateral EVAD. [ABSTRACT FROM AUTHOR]

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

• IVES on 3D-T1W TSE and SIR on TOF-MRA were predictors of intraluminal thrombus. • Both SIR and the number of vessels with IVES had good diagnostic accuracy for intraluminal thrombus. • ICAS patients with intraluminal thrombus were more likely to experience cerebrovascular events. To investigate the association between the intravascular enhancement sign (IVES) and intraluminal thrombus (ILT) detected by high-resolution magnetic resonance vessel wall imaging (HR-VWI) in patients with middle cerebral artery (MCA) atherosclerosis. The data of patients who underwent HR-VWI between May 2021 and May 2023, including clinical information, the number of IVES vessels, stenosis degree, ILT, plaque features on 3D T1-weighted turbo spin echo sequences, and signal intensity ratio (SIR) on 3D time-of-flight magnetic resonance angiography, were retrospectively analyzed. Correlation and logistic regression analyses were performed. A total of 194 MCA plaques were identified in 132 patients (103 [53 %] on the left). Atherosclerosis with, relative to without, ILT was associated with a higher incidence of ischemic events, higher plaque enhancement and stenosis degrees, more vessels with IVES, and lower remodeling ratio, lumen area, wall area, total vessel area, and SIR. Multivariate logistic regression analysis showed significant and independent associations of the number of IVES vessels (OR = 1.089; 95 % CI [1.013–1.170]; P = 0.020) and SIR (OR = 0.007; 95 % CI [0.0004–0.124]; P < 0.001) with ILT. The number of vessels with the IVES (AUC = 0.81, 95 % CI [0.75–0.87]; P < 0.001) and SIR (AUC = 0.88, 95 % CI [0.82–0.94]; P < 0.001) sufficiently diagnosed ILT, and the AUC of the combination of the IVES and SIR was 0.89 (95 % CI [0.84–0.94]; P < 0.001). The number of IVES vessels and SIR are independent risk factors for ILT. They may provide new monitoring targets for stroke prevention in patients with atherosclerotic stenosis. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysms are a common condition of uncertain pathogenesis that can rupture if left untreated. Current recommended thresholds for planned repair are empirical and based entirely on diameter. It has been observed that some aneurysms rupture before reaching the threshold for repair whilst other larger aneurysms do not rupture. It is likely that geometry is not the only factor influencing rupture risk. Biomechanical indices aiming to improve and personalise rupture risk prediction require, amongst other things, knowledge of the material properties of the tissue and realistic constitutive models. These depend on the composition and organisation of the vessel wall which has been shown to undergo drastic changes with aneurysmal degeneration, with loss of elastin, smooth muscle cells, and an accumulation of isotropically arranged collagen. Most aneurysms are lined with intraluminal thrombus, which has an uncertain effect on the underlying vessel wall, with some authors demonstrating a reduction in wall stress and others a reduction in wall strength. The majority of studies investigating biomechanical properties of ex vivo abdominal aortic aneurysm tissues have used low-resolution techniques, such as tensile testing, able to measure the global material properties at the macroscale. High-resolution engineering techniques such as nanoindentation and atomic force microscopy have been modified for use in soft biological tissues and applied to vascular tissues with promising results. These techniques have the potential to advance the understanding and improve the management of abdominal aortic aneurysmal disease. [ABSTRACT FROM AUTHOR]

We introduce a poroelastic model for intraluminal thrombus (ILT) that captures both the flow within ILT and its deformation. The model for ILT is coupled with blood flow and arterial wall deformation and used to study the biomechanics in image-based abdominal aortic aneurysm (AAA) models. Three different patient-specific geometries were considered in this study. Using finite element analysis, numerical simulations were performed to investigate the role of ILT on the risk of AAA rupture as assessed by Peak Wall Stress (PWS). Our results indicate that the presence of ILT may reduce wall stress in AAA. However, our results indicate that ILT permeability has little effect on AAA PWS, and that similar values of PWS are obtained with both porous and nonporous ILT models. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. Up to now, there is still controversy on the choice of treatment method of AAA. Even so, the mechanisms of AAA progression are poorly defined, making targeting new therapies problematic. Current evidence favors an interaction of the hemodynamic microenvironment with local and systemic immune responses. In this review, we aim to provide an update of mechanisms in AAA progression, involving hemodynamics, perivascular adipose tissue, adventitial fibroblasts, vasa vasorum remodeling, intraluminal thrombus, and distribution of macrophage subtypes. [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysms (AAAs) represent a complex multifactorial hemodynamic, thrombotic, and inflammatory process that can ultimately result in aortic rupture and death. Despite improved screening and surgical management of AAAs, the mortality rates have remained high after rupture, and little progress has occurred in the development of nonoperative treatments. Intraluminal thrombus (ILT) is present in most AAAs and might be involved in AAA pathogenesis. The present review examined the latest clinical and experimental evidence for possible involvement of the ILT in AAA growth and rupture. Methods: A literature review was performed after a search of the PubMed database from 2012 to June 2020 using the terms “abdominal aortic aneurysm” and “intraluminal thrombus.” Results: The structure, composition, and hemodynamics of ILT formation and propagation were reviewed in relation to the hemostatic and proteolytic factors favoring ILT deposition. The potential effects of the ILT on AAA wall degeneration and rupture, including a review of the current controversies regarding the position, thickness, and composition of ILT, are presented. Although initially potentially protective against increased wall stress, increasing evidence has shown that an increased volume and greater age of the ILT have direct detrimental effects on aortic wall integrity, which might predispose to an increased rupture risk. Conclusions: ILT does not appear to be an innocent bystander in AAA pathophysiology. However, its exact role remains elusive and controversial. Despite computational evidence of a possible protective role of the ILT in reducing wall stress, increasing evidence has shown that the ILT promotes AAA wall degeneration in humans and in animal models. Further research, with large animal models and with more chronic ILT is crucial for a better understanding of the role of the ILT in AAAs and for the potential development of targeted therapies to slow or halt AAA progression.

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.

COVID-19 (Coronavirus disease 2019) caused by SARS-CoV-2 has a diverse constellation of neurological manifestations that include encephalopathy, stroke, Guillain–Barré syndrome, myelitis, and encephalitis. Intraluminal carotid thrombi (ILT) are infrequent lesions seen in only 1.6% of patients with acute ischemic stroke. Underlying atherosclerosis is the most common lesion associated with ILT formation. However, with COVID-19, we have encountered ILT in patients without significant atherosclerotic disease. The endothelial inflammation and hypercoagulable state associated with COVID-19 pose a risk of arterial and venous thromboembolism and could have contributed to this presentation although the exact pathophysiology and optimal treatment of ILT in COVID-19 remain elusive. Herein, we present a series of ischemic stroke patients with carotid ILT in the setting of a recent SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

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

Objective: We have previously demonstrated that human abdominal aortic aneurysm (AAA) rupture occurs in zones of low wall shear stress where flow recirculation and intraluminal thrombus (ILT) deposition are increased. Matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of AAA via its lytic effect on collagen and elastin. We hypothesize that flow-mediated ILT deposition promotes increased local inflammatory and MMP-9 activity that leads to AAA wall degeneration. The purpose of this study was to examine the correlation between predicted pulsatile flow dynamics and regional differences in MMP-9, elastin, collagen, and ILT deposition in human AAA. Methods: Full-thickness aortic tissue samples were collected from 24 patients undergoing open AAA repair. Control infrarenal aortic tissue was obtained from 6 patients undergoing aortobifemoral bypass. Full-thickness aortic tissue and ILT were assessed for MMP-9 levels using a cytokine array assay. Histologic and immunohistochemical assessment of inflammation, collagen and elastin content, and MMP-9 levels were also measured. Three-dimensional AAA geometry was generated from computed tomography angiogram (CTA) images using Mimics software and computational fluid dynamics was used to predict pulsatile aortic blood flow. Results: The majority of AAA showed eccentric ILT deposition which was correlated with predicted recirculation blood flow (R2 = –0.17; P < .05). The regions of high ILT were associated with significant increases in inflammation and loss of elastin and collagen compared with regions of low ILT, or with control tissue. MMP-9 was significantly higher in areas of high ILT deposition compared with areas devoid of ILT. Tissue MMP-9 was correlated with the thickness of ILT deposition (R2 = 0.46; P < .05), and was also present in high levels in thick compared with thin ILT. Conclusions: We have shown a correlation between flow-mediated ILT deposition with increased tissue levels of MMP-9 activity, increased inflammatory infiltrate, and decreased elastin and collagen content in stereotactically sampled human AAA, suggesting that ILT deposition is associated with local increases in proteolytic activity that may preferentially weaken and promote rupture at selected regions.

Introduction: Abdominal aortic aneurysms (AAAs) with intraluminal thrombus (ILT) are suggested to be more prone to rupture than AAAs without. Prior studies indicate that the von Willebrand factor (vWf) plays a role in the formation of ILT since a positive correlation between ILT volume and vWf has been shown. vWf mediates the tethering of platelets at sites of endothelial injury, and the protease ADAMTS-13 cleaves larger forms of vWf, thus counteracting the thrombosis cascade and maintaining haemostatic balance. When investigating the largest quantifiable thrombus in the human body, it was hypothesised that circulating ADAMTS-13 activity may be associated with ILT size in patients with AAA and the aim was to explore this potential relationship using 3D contrast enhanced ultrasound (3D-CEUS) for ILT volume determination., Report: In this retrospective, exploratory study, 60 patients with AAA were evaluated, and the association between ILT volume and thickness and ADAMTS-13 was estimated using 3D-CEUS. ADAMTS-13 activity was measured in plasma samples obtained the same day. No association between ILT volume ( r  = -0.03, p  = 0.84) or ILT thickness ( r  = 0.02, p  = 0.87) and ADAMTS-13 activity was found. Likewise, when subdividing the group into lowest and highest 50% of ADAMTS-13 activity, the half with the lowest ADAMTS-13 activity (mean ILT volume ±standard deviation [SD]: 32 ± 34 mL) did not differ from the half with the highest ADAMTS-13 activity (43 ± 24 mL) when comparing ILT volume ( p  = 0.172, F  = 2.95) and thickness ( p  = 0.070)., Discussion: After evaluating the largest quantifiable intraluminal thrombus in the vasculature, it was concluded that, surprisingly, circulating ADAMTS-13 activity seems unrelated to ILT formation in AAA., (© 2024 The Authors.)

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

Models that seek to improve our current understanding of biochemical processes and predict disease progression have been increasingly in use over the last decades. Recently, we proposed a finite element implementation of arterial wall growth and remodeling with application to abdominal aortic aneurysms (AAAs). The study focused on changes within the aortic wall and did not include the complex role of intraluminal thrombus (ILT) during the AAA evolution. Thus, in this work, we extend the model with a gradual deposition of ILT and its mechanical influence on AAA growth. Despite neglecting the increased biochemical activity due to the presence of a proteolytically active luminal layer of ILT, and thus underestimating rupture risk potential, we show that ILT helps to slow down the growth of the aneurysm in the axial direction by redirecting blood pressure loading from the axial-radial plane to predominately radial direction. This very likely lowers rupture potential. We also show that the ratio of ILT volume to volume sac is an important factor in AAA stabilization and that fully thrombosed aneurysms could stabilize quicker and at smaller maximum diameters compared to partially thrombosed ones. Furthermore, we show that ILT formation and the associated mural stress decrease negatively impact the wall constituent production and thickness. Although further studies that include increased biochemical degradation of the wall after the formation of ILT and ILT deposition based on hemodynamics are needed, the present findings highlight the dual role an ILT plays during AAA progression. [ABSTRACT FROM AUTHOR]

Computational fluid dynamics were used to assess hemodynamic changes in an actively rupturing abdominal aortic aneurysm (AAA) over a 9-day period. Active migration of contrast from the lumen into the thickest region of intraluminal thrombus (ILT) was demonstrated until it ultimately breached the adventitial layer. Four days after symptom onset, there was a discrete disruption of adventitial calcium with bleb formation at the site of future rupture. Rupture occurred in a region of low wall shear stress and was associated with a marked increase in AAA diameter from 6.6 to 8.4 cm. The cross-sectional area of the flow lumen increased across all time points from 6.28 to 12.08 cm2. The increase in luminal area preceded the increase in AAA diameter and was characterized by an overall deceleration in recirculation flow velocity with a coinciding increase in flow velocity penetrating the ILT. We show that there are significant hemodynamic and structural changes in the AAA flow lumen in advance of any appreciable increase in aortic diameter or rupture. The significant increase in AAA diameter with rupture suggests that AAA may actually rupture at smaller sizes than those measured on day of rupture. These findings have implications for algorithms the predict AAA rupture risk. [ABSTRACT FROM AUTHOR]

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

Purpose: Abdominal Aortic Aneurysms (AAA) have extreme medical prevalence as an asymptomatic cause of death in developed countries. The probability of AAA rupture is promoted by the localized oxygen loss in the AAA wall which occurs in part because many AAAs contain a layer called intraluminal thrombus (ILT). Considering this strong clinical association, the purpose of this study is to investigate the key features that constitute to the oxygen diffusion, and therefore hypoxia in AAA. Methods: A three-dimensional model of AAA containing ILT is created and numerical simulations are performed to simulate blood flow and oxygen distribution within the AAA. The model accounts for blood flow in the lumen and oxygen transport in the lumen, ILT, and arterial wall. The sub-model of the ILT is fully coupled with the wall sub-model as well as with the subdomain of the blood flow. The sensitivity of the oxygen flow with respect to the parameters of the problem is also analyzed. Results: Model simulations are used to investigate the relation between AAA physical properties, hemodynamics, and oxygen concentration in different geometries of AAA. The results demonstrate that the diameter of the AAA bulge has little effect on the oxygen flow, but that the thickness of the ILT layer has a profound effect. Moreover, a significant sensitivity to the oxygen supply from vasa vasorum and its notable impact on oxygen transport within AAA are observed. The variability of the arterial wall oxygen concentration to the oxygen reaction rate remains however very low. Conclusion: The presence of an ILT significantly impairs oxygen transport from the lumen to the wall. This study confirms that consideration of ILT size and anatomy may be important in considering the severity of a AAA, however, other parameters can also affect thrombus-mediated oxygen delivery within the aneurysmal wall. [ABSTRACT FROM AUTHOR]

This paper reports on modelling and simulation of the coupled mass and momentum transport through the arterial lumen and the porous arterial wall of an abdominal aortic aneurysm (AAA). The effect of porous structure and intramural flow, which is usually neglected, is essential to quantify the oxygen concentration in the aneurysmal wall and will be addressed in this work via a novel coupled fluid–porous structure–mass transport model for AAA. The computational solver provides a prediction of the filtration velocity and oxygen concentration in the artery and further simulations are used to investigate the relation between the wall oxygen concentration and permeability. The results demonstrate the essential coupling between blood and filtration flow and specifically how their interactions affect oxygen transport. [ABSTRACT FROM AUTHOR]

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.

Abdominal aortic aneurysm (AAA) is a vascular disorder caused by a dilatation of the aortic diameter that can be potentially lethal in case of rupture. Molecular mechanisms underlying the development of AAA are complex and not completely understood. However, inflammation plays a pivotal role in AAA development. Infiltration of inflammatory cells, especially macrophages, has been widely observed in lesion areas. Nevertheless, neutrophils have been gaining importance in the context of AAA. The release of neutrophil extracellular traps (NETs), extracellular structures formed by DNA, histones, granular and cytoplasmic proteins, is a recently discovered mechanism of neutrophil activation that can be triggered by endogenous inflammatory stimulus. The number of studies about the role of NETs in several vascular diseases like thrombosis and atherosclerosis has increased in last decade. However, its role in AAA has been scarcely analysed. The aim of this review is to deepen in the latest advances concerning the potential role neutrophils and especially NETs in AAA development. • Neutrophils play an active role in abdominal aortic aneurysm (AAA) development. • Inflammation and intraluminal thrombus formation are processes related to AAA. • Neutrophil extracellular traps (NETs) are involved in thrombotic and atherosclerotic diseases. • NETs could be formed during AAA formation contributing to its development. [ABSTRACT FROM AUTHOR]

The 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. Using 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. A 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. These 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs). Methods and results In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naïve patients with AAA and with a maximum aortic diameter 35–49 mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P  = 0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P  = 0.372). MRI diameter change was 2.5 mm vs. 1.8 mm (P  = 0.113), US diameter change 2.3 mm vs. 2.2 mm (P  = 0.778), and ILT volume change 12.9% vs. 10.4% (P  = 0.590). Conclusion In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor. Trial registration The TicAAA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02070653. [ABSTRACT FROM AUTHOR]

Purpose: To compare different anatomical characteristics between intact and ruptured large abdominal aortic aneurysms (rAAA >80 mm) with the goal of refining the process of estimating rupture risk. Materials and Methods: A retrospective study involving 62 male patients with large (>80 mm) aneurysms matched for age and smoking produced a 31-patient elective group with a mean maximum aneurysm diameter of 92±9.7 mm and a 31-patient rAAA group (mean maximum aneurysm diameter 95.7±12 mm). Preoperative computed tomography angiography scans were analyzed with a dedicated workstation, and anatomical characteristics of the aortic neck, iliac arteries, and aneurysm were compared in multivariable regression analyses; the outcomes are given as the odds ratio (OR) with 95% confidence interval (CI). The prognostic utility of several characteristics as predictors of rupture occurrence was examined with receiver operating characteristic (ROC) curves. Results: Anatomical characteristics differing significantly between elective and ruptured aneurysms were the infrarenal aortic neck diameters at 5 mm, 10 mm and 15 mm; the neck length and calcification; the common iliac artery (CIA) lengths; the iliac artery indexes; the left CIA and external iliac artery diameters; and the total and true lumen aneurysm volumes. Intraluminal thrombus (ILT) volume did not differ (p=0.76), although its distribution in elective vs ruptured cases did [absent: 0% vs 19%, respectively (p=0.025); circumferential: 61% vs 35%, respectively (p=0.04)]. Total aneurysm volume was higher in rAAA (442±140 mL) vs intact AAA (331±143 mL, p=0.014), while the ILT/total aneurysm volume rate was lower in rAAA (55%) vs intact AAA (70%, p=0.02). Multivariate analysis determined that a shorter left CIA (OR 1.07, 95% CI 1.01 to 1.1, p=0.016) and a smaller total aneurysm volume (OR 1.007, CI. 1.001 to 1.014, p=0.016) were associated with intact AAA. After a ROC curve analysis, left CIA length <50 mm demonstrated a lower incidence of rupture (sensitivity 60% and specificity 78%), while total aneurysm volume <380 mL had 60% sensitivity and specificity. Conclusion: Large rAAAs seem to have different anatomical characteristics than similarly sized intact AAAs. Large intact AAAs have lower total aneurysm volumes and shorter left CIAs, with higher ILT/aneurysm volume rates. [ABSTRACT FROM AUTHOR]

Purpose: Abdominal aortic aneurysm (AAA) growth after endovascular aneurysm repair (EVAR) is still unpredictable. The issue of optimal frequency of computed tomography angiography for surveillance and its measurement method accuracy remain unclear. We aimed to assess the value of abdominal aneurysm sac volume measurement for detecting expansions and the association of preprocedural intraluminal thrombus (ILT) volume with aneurysm sac growth following EVAR. Material and methods: A total of 107 patients underwent elective EVAR. Inclusion criteria provided a cohort of 39 patients. Changes of postoperative maximum aneurysm sac diameter and AAA volume were calculated. Volumetric AAA changes and demographic data of the cases with clinically irrelevant AAA diameter enlargement were evaluated. Preoperative ILT volumes were collected. ILT and AAA sac volume ratio was calculated. Statistical data analysis was performed using standard methods. Results: The mean changes of maximum AAA diameter and volume in percentage after EVAR were -5.08 ± 8.20 mm and -13.39 ± 23.32%, respectively. A moderate positive linear correlation between those changes was found (R2 = 0.731; p < 0.0001). The mean relative AAA volume increase in cases without clinically relevant diameter enlargement was 11.50 ± 8.27%. The means of ILT and AAA sac ratios were 0.59 ± 0.17 and 0.52 ± 1.8 in growing AAA sac and in stable or shrinking AAA sac groups, respectively (p = 0.308). Conclusions: Volumetric AAA measurement may be useful as an additional method to diameter measurement after EVAR to identify clinically relevant sac growth. Preoperative volume of ILT may not significantly affect the growth rate of AAA after EVAR. [ABSTRACT FROM AUTHOR]

Intraluminal thrombus (ILT) is a relatively rare cause of stroke. MRI/MRA is increasingly used for stroke patients eligible for acute treatment. Radiological ILT characteristics have never been studied systematically on MRA. We aimed to analyse signal changes and other radiological characteristics of ILT in the acute phase on MRA in a case series of ILT patients. Consecutive stroke patients registered in our stroke database between January 2013 and September 2022 were screened for supra-aortic ILT on MRA, in whom MRA was the first supra-aortic vessel imaging performed. Twelve patients were included for analysis. Radiological analysis on MRA included ILT localisation, diameter of the free-floating ILT component, total ITL length, degree of stenosis caused by ILT, and ILT signal intensity. Median age was 65 years and 92% were men. Median time interval between stroke onset and MRA was 0.5 days. Atherosclerosis was the underlying ILT aetiology in half of the patients. The most frequent ILT localisation was the internal carotid artery, always involving the C1 segment. Median ILT diameter was 4.35 mm, median length 20.9 mm, median stenosis 65%, and with a homogeneous hypointensity of the ILT in 67% and a mixed hypo-hyperintensity in 33% (with ILT showing central hyperintensity surrounded by peripheral hypointensity). When observed on MRA, ILT showed a homogeneous hypointensity in two-thirds and a mixed hypo-hyperintensity in one third of patients. In future studies, follow-up MRA scans should be performed to analyse whether these signal changes are time-related or influenced by antithrombotic treatment for ILT. [ABSTRACT FROM AUTHOR]

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