Competing pathways of intracranial aneurysm growth: linking regional growth distribution and hemodynamics

J Neurosurg 142:1741–1750, 2025

This study analyzes intracranial aneurysm growth, revealing two main mechanisms: high-flow impingement causing wall thinning (mainly in ACom aneurysms) and slow, oscillatory flow leading to wall thickening (mainly in MCA aneurysms). Findings support personalized monitoring and interventions based on regional hemodynamic environments.

• Intracranial aneurysm growth is driven by complex interactions of hemodynamic forces and wall remodeling mechanisms.

• Growth most commonly occurs in the aneurysm body and central flow regions, with patterns varying by location and morphology.

• Two main growth pathways are identified: high-flow impingement (causing wall thinning/degeneration, mainly in ACom aneurysms) and low-flow oscillatory conditions (causing wall thickening/remodeling, mainly in MCA aneurysms).

• High-flow impingement regions (neck, body, inflow) show higher wall shear stress (WSS) and are linked to wall degeneration and rupture risk.

• Low-flow regions (dome, central) have low WSS, high oscillatory shear index, and promote wall remodeling and thickening.

• Distinct growth patterns by aneurysm type suggest targeted monitoring and interventions could reduce rupture risk.

• Findings challenge the simplistic view that only one flow condition drives growth or rupture, emphasizing the need for personalized treatment strategies.

• Study limitations include model assumptions (rigid walls, Newtonian blood), subjective region labeling, and exclusion of nonhemodynamic factors.

Stability of unruptured intracranial aneurysms in the anterior circulation: nomogram models for risk assessment

J Neurosurg 137:675–684, 2022

The probable stability of the lesion is critical in guiding treatment decisions in unruptured intracranial aneurysms (IAs). The authors aimed to develop multidimensional predictive models for the stability of unruptured IAs.

METHODS Patients with unruptured IAs in the anterior circulation were prospectively enrolled and regularly followed up. Clinical data were collected, IA morphological features were assessed, and adjacent hemodynamic features were quantified with patient-specific computational fluid dynamics modeling. Based on multivariate logistic regression analyses, nomograms incorporating these factors were developed in a primary cohort (patients enrolled between January 2017 and February 2018) to predict aneurysm rupture or growth within 2 years. The predictive accuracies of the nomograms were compared with the population, hypertension, age, size, earlier rupture, and site (PHASES) and earlier subarachnoid hemorrhage, location, age, population, size, and shape (ELAPSS) scores and validated in the validation cohort (patients enrolled between March and October 2018).

RESULTS Among 231 patients with 272 unruptured IAs in the primary cohort, hypertension, aneurysm location, irregular shape, size ratio, normalized wall shear stress average, and relative resident time were independently related to the 2-year stability of unruptured IAs. The nomogram including clinical, morphological, and hemodynamic features (C+M+H nomogram) had the highest predictive accuracy (c-statistic 0.94), followed by the nomogram including clinical and morphological features (C+M nomogram; c-statistic 0.89), PHASES score (c-statistic 0.68), and ELAPSS score (c-statistic 0.58). Similarly, the C+M+H nomogram had the highest predictive accuracy (c-statistic 0.94) in the validation cohort (85 patients with 97 unruptured IAs).

CONCLUSIONS Hemodynamics have predictive values for 2-year stability of unruptured IAs treated conservatively. Multidimensional nomograms have significantly higher predictive accuracies than conventional risk prediction scores.

 

Computational fluid dynamic analysis of the initiation of cerebral aneurysms

J Neurosurg 137:335–343, 2022

Relationships between aneurysm initiation and hemodynamic factors remain unclear since de novo aneurysms are rarely observed. Most previous computational fluid dynamics (CFD) studies have used artificially reproduced vessel geometries before aneurysm initiation for analysis. In this study, the authors investigated the hemodynamic factors related to aneurysm initiation by using angiographic images in patients with cerebral aneurysms taken before and after an aneurysm formation.

METHODS The authors identified 10 cases of de novo aneurysms in patients who underwent follow-up examinations for existing cerebral aneurysms located at a different vessel. The authors then reconstructed the vessel geometry from the images that were taken before aneurysm initiation. In addition, 34 arterial locations without aneurysms were selected as control cases. Hemodynamic parameters acting on the arterial walls were calculated by CFD analysis.

RESULTS In all de novo cases, the aneurysmal initiation area corresponded to the highest wall shear stress divergence (WSSD point), which indicated that there was a strong tensile force on the arterial wall at the initiation area. The other previously reported parameters did not show such correlations. Additionally, the pressure loss coefficient (PLc) was statistically significantly higher in the de novo cases (p < 0.01). The blood flow impact on the bifurcation apex, or the secondary flow accompanied by vortices, resulted in high tensile forces and high total pressure loss acting on the vessel wall.

CONCLUSIONS Aneurysm initiation may be more likely in an area where both tensile forces acting on the vessel wall and total pressure loss are large.

Aneurysm Wall Enhancement Is Associated With Decreased Intrasaccular IL-10 and Morphological Features of Instability

Neurosurgery 89:664–671, 2021

High-resolution vessel wall imaging plays an increasingly important role in assessing the risk of aneurysm rupture.

OBJECTIVE: To introduce an approach toward the validation of the wall enhancement as a direct surrogate parameter for aneurysm stability.

METHODS: A total of 19 patients harboring 22 incidental intracranial aneurysms were enrolled in this study. The aneurysms were dichotomized according to their aneurysm to- pituitary stalk contrast ratio using a cutoff value of 0.5 (nonenhancing < 0.5; enhancing ≥ 0.5). We evaluated the association of aneurysm wall enhancement with morphological characteristics, hemodynamic features, and inflammatory chemokines directly measured inside the aneurysm.

RESULTS: Differences in plasma concentration of chemokines and inflammatory molecules, morphological, and hemodynamic parameters were analyzed using the Welch test or Mann-Whitney U test. The concentration  IL-10 in the lumen of intracranial aneurysms with low wall enhancement was significantly increased compared to aneurysms with strong aneurysm wall enhancement (P = .014). The analysis of morphological and hemodynamic parameters showed significantly increased values for aneurysm volume (P=.03), aneurysm area (P=.044), maximal diameter (P=.049), and nonsphericity index (P=.021) for intracranial aneurysms with strong aneurysm wall enhancement. None of the hemodynamic parameters reached statistical significance; however, the total viscous shear force computed over the region of low wall shear stress showed a strong tendency toward significance (P = .053).

CONCLUSION: Aneurysmal wall enhancement shows strong associations with decreased intrasaccular IL-10 and established morphological indicators of aneurysm instability.

 

A Simple Flow Classification Parameter Can Discriminate Rupture Status in Intracranial Aneurysms

Neurosurgery 2020 DOI:10.1093/neuros/nyaa189

A simple dimensionless aneurysm number (An), which depends on geometry and flow pulsatility, was previously shown to distinguish the flow mode in intracranial aneurysms (IA): vortex mode with a dynamic vortex formation/evolution if An > 1, and cavity mode with a steady shear layer if An < 1.

OBJECTIVE: To hypothesize that An > 1 can distinguish rupture status because vortex mode is associated with high oscillatory shear index, which, in turn, is statistically associated with rupture.

METHODS: The above hypothesis is tested on a retrospective, consecutively collected database of 204 patient-specific IAs. The first 119 cases are assigned to training and the remainder to testing dataset. An is calculated based on the pulsatility index (PI) approximated either from the literature or solving an optimization problem (denoted as PI). Student’s t-test and logistic regression (LR) are used for hypothesis testing and data fitting, respectively.

RESULTS: An can significantly discriminate ruptured and unruptured status with 95% confidence level (P<.0001). An (using PI) and An (usingPI) significantly predict the ruptured IAs (for training dataset An: AUC = 0.85, An: AUC = 0.90, and for testing dataset An: sensitivity = 94%, specificity = 33%,An: sensitivity = 93.1%, specificity = 52.85%).

CONCLUSION: An > 1 predicts ruptured status. Unlike traditional hemodynamic parameters such as wall shear stress and oscillatory shear index, An has a physical threshold of one (does not depend on statistical analysis) and does not require time-consuming flow simulations. Therefore, An is a simple, practical discriminator of IA rupture status.

The biophysical role of hemodynamics in the pathogenesis of cerebral aneurysm formation and rupture

Neurosurg Focus 47 (1):E11, 2019

The pathogenesis of intracranial aneurysms remains complex and multifactorial. While vascular, genetic, and epidemio- logical factors play a role, nascent aneurysm formation is believed to be induced by hemodynamic forces. Hemodynamic stresses and vascular insults lead to additional aneurysm and vessel remodeling. Advanced imaging techniques allow us to better define the roles of aneurysm and vessel morphology and hemodynamic parameters, such as wall shear stress, oscillatory shear index, and patterns of flow on aneurysm formation, growth, and rupture. While a complete understand- ing of the interplay between these hemodynamic variables remains elusive, the authors review the efforts that have been made over the past several decades in an attempt to elucidate the physical and biological interactions that govern aneurysm pathophysiology. Furthermore, the current clinical utility of hemodynamics in predicting aneurysm rupture is discussed.

External validation of cerebral aneurysm rupture probability model with data from two patient cohorts

Acta Neurochirurgica (2018) 160:2425–2434

For a treatment decision of unruptured cerebral aneurysms, physicians and patients need to weigh the risk of treatment against the risk of hemorrhagic stroke caused by aneurysm rupture. The aim of this study was to externally evaluate a recently developed statistical aneurysm rupture probability model, which could potentially support such treatment decisions.

Methods Segmented image data and patient information obtained from two patient cohorts including 203 patients with 249 aneurysms were used for patient-specific computational fluid dynamics simulations and subsequent evaluation of the statistical model in terms of accuracy, discrimination, and goodness of fit. The model’s performance was further compared to a similaritybased approach for rupture assessment by identifying aneurysms in the training cohort that were similar in terms of hemodynamics and shape compared to a given aneurysm from the external cohorts.

Results When applied to the external data, the model achieved a good discrimination and goodness of fit (area under the receiver operating characteristic curve AUC = 0.82), which was only slightly reduced compared to the optimism-corrected AUC in the training population (AUC = 0.84). The accuracy metrics indicated a small decrease in accuracy compared to the training data (misclassification error of 0.24 vs. 0.21). The model’s prediction accuracy was improved when combined with the similarity approach (misclassification error of 0.14).

Conclusions The model’s performance measures indicated a good generalizability for data acquired at different clinical institutions. Combining the model-based and similarity-based approach could further improve the assessment and interpretation of new cases, demonstrating its potential use for clinical risk assessment.

Development of a statistical model for discrimination of rupture status in posterior communicating artery aneurysms

Acta Neurochirurgica (2018) 160:1643–1652

Intracranial aneurysms at the posterior communicating artery (PCOM) are known to have high rupture rates compared to other locations. We developed and internally validated a statistical model discriminating between ruptured and unruptured PCOM aneurysms based on hemodynamic and geometric parameters, angio-architectures, and patient age with the objective of its future use for aneurysm risk assessment.

Methods A total of 289 PCOM aneurysms in 272 patients modeled with image-based computational fluid dynamics (CFD) were used to construct statistical models using logistic group lasso regression. These models were evaluated with respect to discrimination power and goodness of fit using tenfold nested cross-validation and a split-sample approach to mimic external validation.

Results The final model retained maximum and minimum wall shear stress (WSS), mean parent artery WSS, maximum and minimum oscillatory shear index, shear concentration index, and aneurysm peak flow velocity, along with aneurysm height and width, bulge location, non-sphericity index, mean Gaussian curvature, angio-architecture type, and patient age. The corresponding area under the curve (AUC) was 0.8359. When omitting data from each of the three largest contributing hospitals in turn, and applying the corresponding model on the left-out data, the AUCs were 0.7507, 0.7081, and 0.5842, respectively.

Conclusions Statistical models based on a combination of patient age, angio-architecture, hemodynamics, and geometric characteristics can discriminate between ruptured and unruptured PCOM aneurysms with an AUC of 84%. It is important to include data from different hospitals to create models of aneurysm rupture that are valid across hospital populations.

Is there an inherited anatomical conformation favoring aneurysmal formation of the anterior communicating artery?

J Neurosurg 126:1598–1605, 2017

The pathophysiological mechanisms responsible for the formation of intracranial aneurysms (IAs) remain only partially elucidated. However, current evidence suggests a genetic component. The purpose of this study was to investigate the specific anatomical variations in the arterial complex that are associated with the presence of anterior communicating artery (ACoA) aneurysms in the familial forms of IAs.

METHODS This multicenter study investigated bifurcation IAs in patients who had a sporadic ACoA IA without a family history of IA (SACAA group), in patients who had an ACoA IA with a family history of IA (FACAA group), and in their healthy first-degree relatives (HFDRs). Through the use of MR angiography (MRA) reconstructions, the symmetry of the A1 segments and the angle between the A1 and A2 segments were analyzed on 3D models for each group. These measurements were then compared among the 3 groups.

RESULTS Twenty-four patients with SACAA, 24 patients with FACAA, and 20 HFDRs were included in the study. Asymmetrical configuration of the A1 segments was more frequent in the FACAA group than in the HFDR group (p = 0.002). The aneurysm-side A1-A2 angle was lower in the FACAA group (p = 0.003) and SACAA group (p = 0.007) than in the HFDR group. On the contralateral side, there was no difference in A1-A2 angles between groups.

CONCLUSIONS The anatomical shape of the ACoA complex seems to be similarly associated with the presence of ACoA IAs in both the FACAA and SACAA groups. This highlights the role played by hemodynamic constraints in aneurysm formation and questions the hypothesis of the hereditary character of these anatomical shapes.

Hemodynamic and morphological characteristics of unruptured posterior communicating artery aneurysms with oculomotor nerve palsy

Hemodynamic and morphological characteristics of unruptured posterior communicating artery aneurysms with oculomotor nerve palsy

J Neurosurg 125:264–268, 2016

Unruptured posterior communicating artery (PCoA) aneurysms with oculomotor nerve palsy (ONP) have a very high risk of rupture. This study investigated the hemodynamic and morphological characteristics of intracranial aneurysms with high rupture risk by analyzing PCoA aneurysms with ONP.

Methods: Fourteen unruptured PCoA aneurysms with ONP, 33 ruptured PCoA aneurysms, and 21 asymptomatic unruptured PCoA aneurysms were included in this study. The clinical, morphological, and hemodynamic characteristics were compared among the different groups.

Results: The clinical characteristics did not differ among the 3 groups (p > 0.05), whereas the morphological and hemodynamic analyses showed that size, aspect ratio, size ratio, undulation index, nonsphericity index, ellipticity index, normalized wall shear stress (WSS), and percentage of low WSS area differed significantly (p < 0.05) among the 3 groups. Furthermore, multiple comparisons revealed that these parameters differed significantly between the ONP group and the asymptomatic unruptured group and between the ruptured group and the asymptomatic unruptured group, except for size, which differed significantly only between the ONP group and the asymptomatic unruptured group (p = 0.0005). No morphological or hemodynamic parameters differed between the ONP group and the ruptured group.

Conclusions: Unruptured PCoA aneurysms with ONP demonstrated a distinctive morphological-hemodynamic pattern that was significantly different compared with asymptomatic unruptured PCoA aneurysms and was similar to ruptured PCoA aneurysms. The larger size, more irregular shape, and lower WSS might be related to the high rupture risk of PCoA aneurysms.

Association of Hemodynamic Factors With Intracranial Aneurysm Formation and Rupture

Association of Hemodynamic Factors With Intracranial Aneurysm Formation and Rupture

Neurosurgery 78:510–520, 2016

Recent evidence suggests a link between the magnitude and distribution of hemodynamic factors and the formation and rupture of intracranial aneurysms. However, there are many conflicting results.

OBJECTIVE: To quantify the effect of hemodynamic factors on aneurysm formation and their association with ruptured aneurysms.

METHODS: We performed a systematic review and meta-analysis through October 2014. Analysis of the effects of hemodynamic factors on aneurysm formation was performed by pooling the results of studies that compared geometrical models of intracranial aneurysms and “preaneurysm” models where the aneurysm was artificially removed. Furthermore, we calculated pooled standardized mean differences between ruptured and unruptured aneurysms to quantify the association of hemodynamic factors with ruptured aneurysms. Standard PRISMA guidelines were followed.

RESULTS: The hemodynamic factors that showed high positive correlations with location of aneurysm formation were high wall shear stress (WSS) and high gradient oscillatory number, with pooled proportions of 78.8% and 85.7%, respectively. Positive correlations were largely seen in bifurcation aneurysms, whereas negative correlations were seen in sidewall aneurysms. Mean and normalized WSS were significantly lower and low shear area significantly higher in ruptured aneurysms.

CONCLUSION: Pooled analyses of computational fluid dynamics models suggest that an increase in WSS and gradient oscillatory number may contribute to aneurysm formation, whereas low WSS is associated with ruptured aneurysms. The location of the aneurysm at the bifurcation or sidewall may influence the correlation of these hemodynamic factors.

Computational Fluid Dynamic Analysis of Intracranial Aneurysmal Bleb Formation

Computational Fluid Dynamic Analysis of Intracranial Aneurysmal Bleb Formation

Neurosurgery 73:1061–1069, 2013

The management of unruptured aneurysms is controversial, with the decision to treat influenced by aneurysm characteristics including size and morphology. Aneurysmal bleb formation is thought to be associated with an increased risk of rupture.

OBJECTIVE: To correlate computational fluid dynamic (CFD) indices with bleb formation.

METHODS: Anatomic models were constructed from 3-dimensional rotational angiography data in 27 patients with cerebral aneurysms harboring a single bleb. Additional models representing the aneurysm before bleb formation were constructed by digitally removing the bleb. We characterized hemodynamic features of models both with and without the blebs using CFDs. Flow structure, wall shear stress (WSS), pressure, and oscillatory shear index (OSI) were analyzed.

RESULTS: There was a statistically significant association between bleb location at or adjacent to the point of maximal WSS (74%, P = .019), irrespective of rupture status. Aneurysmal blebs were related to the inflow or outflow jet in 89% of cases (P < .001), whereas 11% were unrelated. Maximal wall pressure and OSI were not significantly related to bleb location. The bleb region attained a lower WSS after its formation in 96% of cases (P < .001) and was also lower than the average aneurysm WSS in 86% of cases (P < .001).

CONCLUSION: Cerebral aneurysm blebs generally form at or adjacent to the point of maximal WSS and are aligned with major flow structures. Wall pressure and OSI do not contribute to determining bleb location. The measurement of WSS using CFD models may potentially predict bleb formation and thus improve the assessment of rupture risk in unruptured aneurysms.

The A1-A2 Diameter Ratio May Influence Formation and Rupture Potential of Anterior Communicating Artery Aneurysms

AComAA

Neurosurgery 73:845–853, 2013

Specific morphological factors contribute to the hemodynamics of the anterior communicating artery (AComA). No study has examined the role of the A2 segment on AComA aneurysm presence and rupture.

OBJECTIVE: To examine the possibility that the ratio between A1 and A2 segments (A1-2 ratio) represents an independent risk factor for presence and rupture of AComA aneurysms (AComAAs).

METHODS: A retrospective review of an institutional aneurysm database was performed; patients with ruptured and unruptured AComAAs were identified. Two control groups were selected: group A (posterior circulation aneurysms) and group B (patients without intracranial aneurysms or other vascular malformations). Measurements of A1 and A2 diameters were obtained from digital subtraction angiography (64.1% of 3-D rotational digital subtraction angiography), and the A1-2 ratio calculated.

RESULTS: From January 2009 to April 2011, 156 patients were identified (52 AComAAs, 54 control group A, and 50 control group B). Mean age at the time of presentation was 56.09 years. Compared with both control groups, patients with AComAAs had greater A1 diameter (P < .01) and A1-2 ratio (P < .001) and smaller A2 diameter (P < .01). The A1-2 ratio correlated positively with the presence of AComAAs (P < .001). Ruptured AComAAs were smaller than unruptured ones (5.91 mm vs 9.25 mm, P = .02) and associated with a higher A1-2 Ratio (P = .02). The presence of a dominant A1 did not predict AComAA rupture (P = .15). The A1-2 ratio correlated positively with the presence of ruptured AComAAs (P = .04).

CONCLUSION: A1-2 ratio correlates positively with the presence and rupture of AComAAs and may facilitate treatment decision in cases of small, unruptured AComAAs.

Aneurysm Volume-to-Ostium Area Ratio: A Parameter Useful for Discriminating the Rupture Status of Intracranial Aneurysms

Neurosurgery 68:310–318, 2011 DOI: 10.1227/NEU.0b013e3182010ed0

Slow or stagnant flow is a hemodynamic feature that has been linked to the risk of aneurysm rupture.

OBJECTIVE: To assess the potential value of the ratio of the volume of an aneurysm to the area of its ostium (VOR) as an indicator of intra-aneurysmal slow flow and, thus, in turn, the risk of rupture.

METHODS: Using a sample defined from internal databases, a retrospective analysis of aneurysm size, aspect ratio (AR), and VOR was performed on a series of 155 consecutive aneurysms having undergone 3-dimensional digital subtraction angiography as a part of their evaluation. Measurements were obtained from 3-dimensional digital subtraction angiography studies using commercial software. Aneurysm size, AR, and VOR were correlated with rupture status (ruptured or unruptured). A multiple logistic regression model that best correlated with rupture status was generated to evaluate which of these parameters was the most useful to discriminate rupture status. This model was validated using an independent database of 62 consecutive aneurysms acquired outside the retrospective study interval.

RESULTS: VOR showed better discrimination for rupture status than did size and AR. The best logistic regression model, which included VOR rather than size or AR, determined rupture status correctly in 80.6% of subjects. The reproducibility calculating AR and VOR was excellent.

CONCLUSION: Determination of VOR was easily done and reproducible using widely available commercial equipment. It may be a more robust parameter to discriminate rupture status than AR.