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Background: The presence of blebs increases the rupture risk of intracranial aneurysms (IAs)., Objective: To evaluate whether cross-sectional bleb formation models can identify aneurysms with focalized enlargement in longitudinal series., Methods: Hemodynamic, geometric, and anatomical variables derived from computational fluid dynamics models of 2265 IAs from a cross-sectional dataset were used to train machine learning (ML) models for bleb development. ML algorithms, including logistic regression, random forest, bagging method, support vector machine, and K-nearest neighbors, were validated using an independent cross-sectional dataset of 266 IAs. The models' ability to identify aneurysms with focalized enlargement was evaluated using a separate longitudinal dataset of 174 IAs. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), the sensitivity and specificity, positive predictive value, negative predictive value, F1 score, balanced accuracy, and misclassification error., Results: The final model, with three hemodynamic and four geometrical variables, along with aneurysm location and morphology, identified strong inflow jets, non-uniform wall shear stress with high peaks, larger sizes, and elongated shapes as indicators of a higher risk of focal growth over time. The logistic regression model demonstrated the best performance on the longitudinal series, achieving an AUC of 0.9, sensitivity of 85%, specificity of 75%, balanced accuracy of 80%, and a misclassification error of 21%., Conclusions: Models trained with cross-sectional data can identify aneurysms prone to future focalized growth with good accuracy. These models could potentially be used as early indicators of future risk in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability., Objective: To develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population., Methods: Cross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy., Results: The final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%)., Conclusions: Based on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Blebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites., Methods: Blebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs., Results: Thin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%., Conclusions: Not all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Blebs are rupture risk factors in intracranial aneurysms (IAs), but their prevalence, distribution, and associations with clinical factors as well as their causes and effects on aneurysm vulnerability remain unclear., Methods: A total of 122 blebs in 270 IAs selected for surgery were studied using patient-specific vascular reconstructions from 3D angiographic images. Bleb geometry, location on the aneurysm, and frequency of occurrence in aneurysms at different locations were analyzed. Associations between gender, age, smoking, hypertension, hormone therapy, dental infection, and presence of blebs were investigated., Results: Of all aneurysms with blebs, 77% had a single bleb and 23% had multiple blebs. Only 6% of blebs were at the neck, while 46% were in the body and 48% in the dome. Aneurysms with blebs were larger (p<0.0001), more elongated (p=0.0002), and with wider necks than aneurysms without blebs. Bleb presence was associated with dental infection (p=0.0426) and negatively associated with hormone therapy (p=0.0426) in women. Anterior and posterior communicating arteries had larger percentages of aneurysms with blebs than internal carotid arteries. Patients with a history of hypertension tended to have a larger percentage of aneurysms with blebs. However, these trends did not reach significance in this sample., Conclusions: Blebs are common in IAs, and most aneurysms harboring blebs have a single bleb. Blebs in the aneurysm neck are rare, but they are equally common in the body and dome. The presence of blebs in IAs was associated with dental infection, and negatively associated with hormone replacement therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although it is generally believed that blebs represent weaker spots in the walls of intracranial aneurysms (IAs), it is largely unknown which aneurysm characteristics favor their development., Objective: To investigate possible associations between aneurysm hemodynamic and geometric characteristics and the development of blebs in intracranial aneurysms., Methods: A total of 270 IAs in 199 patients selected for surgical clipping were studied. Blebs were visually identified and interactively marked on patient-specific vascular models constructed from presurgical images. Blebs were then deleted from the vascular reconstruction to approximate the aneurysm before bleb formation. Computational fluid dynamics studies were performed in these models and in cases without blebs. Hemodynamic and geometric characteristics of aneurysms with and without blebs were compared., Results: A total of 173 aneurysms had no blebs, while 97 aneurysms had a total of 122 blebs. Aneurysms favoring bleb formation had stronger (p<0.0001) and more concentrated inflow jets (p<0.0001), higher flow velocity (p=0.0061), more complex (p<0.0001) and unstable (p=0.0157) flow patterns, larger maximum wall shear stress (WSS; p<0.0001), more concentrated (p=0.0005) and oscillatory (p=0.0004) WSS distribution, and a more heterogeneous WSS field (p<0.0001), than aneurysms without blebs. They were also larger (p<0.0001), more elongated (p<0.0001), had wider necks (p=0.0002), and more distorted and irregular shapes (p<0.0001)., Conclusions: Strong and concentrated inflow jets, high-speed, complex, and unstable flow patterns, and concentrated, oscillatory, and heterogeneous WSS patterns favor the formation of blebs in IAs. Blebs are more likely to form in large, elongated, and irregularly shaped aneurysms. These adverse characteristics could be considered signs of aneurysm instability when evaluating aneurysms for conservative observation or treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Semiquantitative scales correlate histopathologic findings in the walls of human aneurysms with rupture status., Objective: To apply a semiquantitative scale to the rabbit elastase-induced aneurysm model to determine whether rabbit histologic types mimic the full range of histologic subtypes of humans., Materials and Methods: Twenty-seven elastase-induced female rabbit aneurysms were studied, harvested at 2 weeks (n=5) and 12 weeks (n=22). Paraffin-embedded sections received hematoxylin-eosin and Verhoeff-Van Gieson staining. Immunohistochemistry was performed for α-smooth muscle actin and CD31 for endothelial cells. A semiquantitative scale was used for scoring based on human aneurysm tissue, divided into four subtypes according to cellular and extracellular matrix findings: type A, linear organized smooth muscle cells (SMCs) and intact endothelium; type B, thickened wall with disorganized, proliferating SMCs; type C, thick, collagenized and hypocellular wall with or without organizing thrombosis, and type D, extremely thin, hypocellular wall. Separate scoring was performed of the aneurysm neck and proximal and distal zones., Results: Findings compatible with all subtypes of human aneurysm tissue were identified. Types A and C were found in 13 (48%) and 11 (41%) of 27 aneurysms and in the proximal and distal wall at both time points. Type B was found in 16 aneurysms (59%), exclusively at the neck at both time points; type D, in 14 aneurysms (52%), exclusively at proximal and distal zones of 12-week aneurysms., Conclusions: The wall of elastase-induced rabbit aneurysm demonstrates histologic findings similar to the four categories of human cerebral aneurysms based on cellular and extracellular wall content., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)