Differences Between Ruptured Aneurysms With and Without Blebs: Mechanistic Implications.

PURPOSE: Blebs are known risk factors for intracranial aneurysm (IA) rupture. We analyzed differences between IAs that ruptured with blebs and those that ruptured without developing blebs to identify distinguishing characteristics among them and suggest possible mechanistic implications. METHODS: Using image-based models, 25 hemodynamic and geometric parameters were compared between ruptured IAs with and without blebs (n = 673), stratified by location. Hemodynamic and geometric differences between bifurcation and sidewall aneurysms and for aneurysms at five locations were also analyzed. RESULTS: Ruptured aneurysms harboring blebs were exposed to higher flow conditions than aneurysms that ruptured without developing blebs, and this was consistent across locations. Bifurcation aneurysms were exposed to higher flow conditions than sidewall aneurysms. They had larger maximum wall shear stress (WSS), more concentrated WSS distribution, and larger numbers of critical points than sidewall aneurysms. Additionally, bifurcation aneurysms were larger, more elongated, and had more distorted shapes than sidewall aneurysms. Aneurysm morphology was associated with aneurysm location (p < 0.01). Flow conditions were different between aneurysm locations. CONCLUSION: Aneurysms at different locations are likely to develop into varying morphologies and thus be exposed to diverse flow conditions that may predispose them to follow distinct pathways towards rupture with or without bleb development. This could explain the diverse rupture rates and bleb presence in aneurysms at different locations.

Prediction of bleb formation in intracranial aneurysms using machine learning models based on aneurysm hemodynamics, geometry, location, and patient population.

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.

Hemodynamic conditions that favor bleb formation in cerebral aneurysms.

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.

Analysis of hemodynamic changes from aneurysm inception to large sizes.

While previous studies have identified many risk factors for the progression and rupture of cerebral aneurysms, the changes in aneurysm flow characteristics during its evolution are not fully understood. This work analyzes the changes in the aneurysm hemodynamic environment from its initial development to later stages when the aneurysm has substantially enlarged. A total of 88 aneurysms at four locations were studied with image based computational fluid dynamics (CFD). Two synthetic sequences representing the aneurysm geometry at three earlier stages were generated by shrinking the aneurysm sac while keeping the neck fixed or shrinking the neck simultaneously. The flow conditions were then quantitatively compared between these two modes of evolution. As aneurysms enlarged, the inflow rate increased in growing neck sequences, but decreased in fixed neck sequences. The inflow jet became more concentrated in both sequences. The mean aneurysm flow velocity and wall shear stress decreased in both sequences, but they decreased faster in enlarging aneurysms if the neck was fixed. Additionally, the intra-aneurysmal flows became more complex and more unstable, wall shear stress distribution became more oscillatory, and the area under low wall shear stress increased for both sequences. The evolution of flow characteristics of aneurysms with fixed and growing necks are different. The observed trends suggest that fixed neck aneurysms may evolve towards a flow environment characteristic of stable aneurysms faster than aneurysms with growing necks, which could also evolve towards a more disfavorable environment.

Hemodynamics in aneurysm blebs with different wall characteristics.

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.

Blebs in intracranial aneurysms: prevalence and general characteristics.

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.