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.

Predicting the growth of middle cerebral artery bifurcation aneurysms using differences in the bifurcation angle and inflow coefficient

J Neurosurg 138:1357–1365, 2023

Growing intracranial aneurysms (IAs) are prone to rupture. Previous cross-sectional studies using postrupture morphology have shown the morphological or hemodynamic features related to IA rupture. Yet, which morphological or hemodynamic differences of the prerupture status can predict the growth and rupture of smaller IAs remains unknown. The purpose of this longitudinal study was to investigate the effects of morphological features and the hemodynamic environment on the growth of IAs at middle cerebral artery (MCA) bifurcations during the follow-up period.

METHODS One hundred two patients with MCA M1–2 bifurcation saccular IAs who underwent follow-up for more than 2 years at the authors’ institutions between 2011 and 2019 were retrospectively identified. During the follow-up period, cases involving growth of MCA IAs were assigned to the event group, and those with MCA IAs unchanged in size were assigned to the control group. The morphological parameters examined were aneurysmal neck length, dome height, aspect ratio and volume, M1 and M2 diameters and their ratio, and angle configurations among M1, M2, and the aneurysm. Hemodynamic parameters were flow rate and wall shear stress in M1, M2, and the aneurysm, including the aneurysmal inflow rate coefficient (AIRC), defined as the ratio of the aneurysmal inflow rate to the M1 flow rate. Those parameters were compared statistically between the two groups. Correlations between morphological and hemodynamic parameters were also examined.

RESULTS Eighty-three of 102 patients were included: 25 with growing MCA IAs (event group) and 58 with stable MCA IAs (control group). The median patient age at initial diagnosis was 66.9 (IQR 59.8–72.3) years. The median follow-up period was 48.5 (IQR 36.5–65.6) months. Both patient age and the AIRC were significant independent predictors of the growth of MCA IAs. Moreover, the AIRC was strongly correlated with sharper bifurcation and inflow angles, as well as wider inclination angles between the M1 and M2 arteries.

CONCLUSIONS The AIRC was a significant independent predictor of the growth of MCA IAs. Sharper bifurcation and inflow angles and wider inclination angles between the M1 and M2 arteries were correlated with the AIRC. MCA IAs with such a bifurcation configuration are more prone to grow and rupture.

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.

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.

Numerical Analysis of Bifurcation Angles and Branch Patterns in Intracranial Aneurysm Formation

Neurosurgery 85 (1): E31–E39. 2019

Hemodynamic factors, especially wall shear stress (WSS), are generally thought to play an important role in intracranial aneurysm (IA) formation. IAs frequently occur at bifurcation apices, where the vessels are exposed to the impact of WSS.

OBJECTIVE: To elucidate the relationship between bifurcation geometry and WSS for IA formation.

METHODS: Twenty-one bifurcation models varying in branch angles and branch diameters were made with 3-dimensional computer-aided design software. In all models, the value of maximum WSS (WSSMAX), the area of high WSS (AREA), and the magnitude of wall shear force over AREA (|Fw |) were investigated by the steady-flow simulation of computational fluid dynamics.

RESULTS: On the basis of statistical analysis, WSSMAX tended to be high when the bifurcation angle and/or branch diameter was small. AREA and |F⃗ | significantly increase as the bifurcation and/or the branch angle became larger.

CONCLUSION: The magnitude of WSS strongly correlated with bifurcation geometry. In addition to high WSS, AREA and |F⃗ | were thought to affect IA formation. Observed bifurcation geometry may predict IA formation. Large branch angles and small branch may increase the risk of IA formation.

Hemodynamic features of offending vessels at neurovascular contact in patients with trigeminal neuralgia and hemifacial spasm

J Neurosurg 130:1870–1876, 2019

Offending vessels at the site of neurovascular contact (NVC) in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS) may have specific hemodynamic features. The purpose of this study was to investigate the wall shear stress (WSS) of offending vessels at NVCs by conducting a computational fluid dynamics (CFD) analysis.

METHODS The authors retrospectively analyzed the cases of 20 patients (10 with TN and 10 with HFS) evaluated by 3D CT angiography and used the imaging findings for analysis of the hemodynamic parameters. The 3D CFD images were directly compared with the NVCs determined by simulated multifusion images of CT angiogram and MR cisternogram, and operative photos. The magnitudes of the WSS (WSSm) at the proximal (WSSm-p), just-beginning (WSSm-j), contact site (WSSm-s), and distal (WSSm-d) areas of each NVC were analyzed. The ratios of the WSSm-j, WSSm-s, and WSSm-d areas to the WSSm-p area were calculated individually. The direction of the WSS (WSSv) and its temporal variation (WSSvV) were depicted and morphologically compared with the NVC confirmed by simulated images and operative findings.

RESULTS The ratios of WSSm at the just-beginning and the contact site to the proximal area of the NVCs (WSSm-j/ WSSm-p and WSSm-s/WSSm-p) were both significantly higher than that at the distal area (WSSm-d/WSSm-p) (p < 0.05). The WSSv and WSSvV at the NVCs showed small variation in a single cardiac cycle, especially along the areas that were in contact with the affected nerve.

CONCLUSIONS Areas of relatively high WSSm and temporal variation of WSSm (WSSmV) were observed at the NVCs. Less mobility of the WSSv and WSSvV was detected along the side of the vessels in contact with the nerves. These findings may be consistent with the actual area of the NVC. Hemodynamic features of the site of NVC can be added to the preoperative simulation for MVD surgery, which may be useful for the diagnosis and treatment planning of TN and HFS.

 

Morphological and Hemodynamic Differences Between Aneurysmal Middle Cerebral Artery Bifurcation and Contralateral Nonaneurysmal Anatomy

Neurosurgery 81:779–786, 2017

The morphological and hemodynamic features differ between middle cerebral artery (MCA) bifurcations with and without aneurysms.

OBJECTIVE: To investigate the morphological and hemodynamic differences between aneurysmal MCA bifurcation and contralateral nonaneurysmal anatomy.

METHODS: Computed tomography angiography of 36 patients with unilateral small saccular MCA bifurcation aneurysms was evaluated. The parent–daughter angles (ϕ1 for larger branch and ϕ2 for smaller branch), bifurcation angle (ϕ = ϕ1 + ϕ2), inclination angle (γ angle), and their relationships with the MCA bifurcation locations were analyzed. Computational fluid dynamics simulation was performed in 6 cases to explore the hemodynamics influenced by the bifurcation morphology.

RESULTS: The ϕ angle was significantly higher in aneurysmal than contralateral nonaneurysmal bifurcations (160.8◦ ± 31.0◦ vs 99.0◦ ± 19.2◦, respectively; P = .000); the ϕ1, ϕ2, and γ angles were also higher. However, by regression analysis combined with MCA bifurcation locations, only the ϕ angle might be associated with the aneurysm presence (odds ratio = 1.120, 95% confidence interval = 1.059-1.185) and a ϕ angle cut-off of 124.8◦ was established. Computational fluid dynamics simulation demonstrated that flow resistance of the wider aneurysmal MCA bifurcation was significantly higher than that on the contralateral side.

CONCLUSION: A larger ϕ angle was more prevalent in aneurysmal than nonaneurysmal MCA bifurcations, and the higher flow resistance caused by the larger ϕ angle might be a potential hemodynamic factor associated with MCA aneurysm presence.

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.

Increasing Flow Diversion for Cerebral Aneurysm Treatment Using a Single Flow Diverter

Increasing Flow Diversion for Cerebral Aneurysm Treatment Using a Single Flow Diverter

Neurosurgery 75:286–294, 2014

A neurovascular flow diverter (FD), aiming at inducing embolic occlusion of cerebral aneurysms through hemodynamic changes, can produce variable mesh densities owing to its flexible mesh structure.

OBJECTIVE: To explore whether the hemodynamic outcome would differ by increasing FD local compaction across the aneurysm orifice.

METHODS: We investigated deployment of a single FD using 2 clinical strategies: no compaction (the standard method) and maximum compaction across the aneurysm orifice (an emerging strategy). Using an advanced modeling technique, we simulated these strategies applied to a patient-specific wide-necked aneurysm model, resulting in a relatively uniform mesh with no compaction (C1) and maximum compaction (C2) at the aneurysm orifice. Pre- and posttreatment aneurysmal hemodynamics were analyzed using pulsatile computational fluid dynamics. Flow-stasis parameters and blood shear stress were calculated to assess the potential for aneurysm embolic occlusion.

RESULTS: Flow streamlines, isovelocity, and wall shear stress distributions demonstrated enhanced aneurysmal flow reduction with C2. The average intra-aneurysmal flow velocity was 29% of pretreatment with C2 compared with 67% with C1. Aneurysmal flow turnover time was 237% and 134% of pretreatment for C2 and C1, respectively. Vortex core lines and oscillatory shear index distributions indicated that C2 decreased the aneurysmal flow complexity more than C1. Ultrahigh blood shear stress was observed near FD struts in inflow region for both C1 and C2.

CONCLUSION: The emerging strategy of maximum FD compaction can double aneurysmal flow reduction, thereby accelerating aneurysm occlusion. Moreover, ultrahigh blood shear stress was observed through FD pores, which could potentially activate platelets as an additional aneurysmal thrombosis mechanism.

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.

Intracranial Aneurysms Occur More Frequently at Bifurcation Sites That Typically Experience Higher Hemodynamic Stresses

ANEURYSM SUSCEPTIBILITY AND HEMODYNAMIC STRESS

Neurosurgery 73:497–505, 2013 

Intracranial aneurysms (IAs) occur more frequently at certain bifurcations than at others. Hemodynamic stress, which promotes aneurysm formation in animal models, also differs among bifurcations, depending on flow and vessel geometry.

OBJECTIVE: To determine whether locations that are more likely to develop IAs experience different hemodynamic stresses that might contribute to higher IA susceptibility.

METHODS: We characterized the hemodynamic microenvironment at 10 sites in or around the circle of Willis where IAs commonly occur and examined statistical relationships between hemodynamic factors and the tendency for a site to form IAs. The tendency for each site to develop IAs was quantified on the basis of the site distribution from systematic literature analysis of 19 reports including 26 418 aneurysms. Hemodynamic parameters for these sites were derived from image-based computational fluid dynamics of 114 cerebral bifurcations from 31 individuals. Wall shear stress and its spatial gradient were calculated in the impact zone surrounding the bifurcation apex. Linear and exponential regression analyses evaluated correlations between the tendency for IA formation and the typical hemodynamics of a site.

RESULTS: IA susceptibility significantly correlated with the magnitudes of wall shear stress and positive wall shear stress gradient within the hemodynamic impact zone calculated for each site.

CONCLUSION: IAs occur more frequently at cerebral bifurcations that typically experience higher hemodynamic shear stress and stronger flow acceleration, conditions previously shown to promote aneurysm initiation in animals.

Characterization of Cyclic CSF Flow in the Foramen Magnum and Upper Cervical Spinal Canal with MR Flow Imaging and Computational Fluid Dynamics

AJNR Am J Neuroradiol 31:997–1002.DOI 10.3174/ajnr.A1995

CSF flow has been shown to exhibit complex patterns in MR images in both healthy subjects and in patients with Chiari I. Abnormal CSF flow oscillations, according to prevailing opinion, cause syringomyelia and other clinical manifestations that affect some patients with the Chiari I malformation.

For this article, we reviewed the literature on PC MR of CSF flow, collected the published CFD studies relevant to CSF flow, and performed flow simulations. PC MR creates cine and still images of CSF flow and measurements of flow velocities. CFD, a technique used to compute flow and pressure in liquid systems, simulates the CSF flow patterns that occur in a specific geometry or anatomy of the SAS and a specific volume of flow.

Published PC MR studies show greater peak CSF velocities and more complex flow patterns in patients with Chiari I than in healthy subjects, with synchronous bidirectional flow one of the characteristic markers of pathologic flow. In mathematic models of the SAS created from high-resolution MR images, CFD displays complex CSF flow patterns similar to those shown in PC MR in patients. CFD shows that the pressure and flow patterns vary from level to level in the upper spinal canal and differ between patients with Chiari and healthy volunteers. In models in which elasticity and motion are incorporated, CFD displays CSF pressure waves in the SAS.

PC MR and CFD studies to date demonstrate significant alterations of CSF flow and pressure patterns in patients with Chiari I. CSF flow has nonlaminar complex spatial and temporal variations and associated pressure waves and pressure gradients. Additional simulations of CSF flow supplemented by PC MR will lead to better measures for distinguishing pathologic flow abnormalities that cause syringomyelia, headaches, and other clinical manifestations in Chiari I malformations.

CFD  computational fluid dynamics; PC MR  phase-contrast cardiac-gated MR studies; SAS  subarachnoid space