Intracranial aneurysms (IAs) are vascular pathologies characterized by dilatation of the arterial wall in the brain. Previous research had observed IAs in ~2–5% of the adult population (1), and IAs at risk of rupture may result in a distinct disease known as subarachnoid hemorrhage (SAH), which is associated with high mortality and morbidity (2). These pieces of evidence imply that treating UIAs before they rupture could extremely be beneficial (3). Observational natural history studies of UIAs, on the other hand, have revealed that only a small percentage of all UIAs patients rupture (4), with a total rupture risk of 1.2% within 5 years of diagnosis (5). In this view, an individualized assessment of the rupture risk is essential for balancing the risks of operative treatment and observation.

Several studies have looked at risk factors for the rupture of IAs, including size, shape, location, age, hypertension, diabetes, smoking, and family history (6–8). These elements, however, have an extremely restricted capacity to predict whether IAs will rupture (9). Much consideration has been paid in recent years to the relationship between hemodynamics (10), vessel wall enhancement (11), radiomics (12), and aneurysm formation or rupture. Image-based computational fluid dynamics (CFD) modeling can help find both the hemodynamic value and the correlation of the value with ruptured IAs (13). The hemodynamics parameters may play an important role in the mechanisms underlying the rupture of cerebral aneurysms (14), though their precise role is still unknown and the results contradict each other sometimes (15). Therefore, a more accurate model to predict the rupture risk of IAs is warranted.

Clinical evidence shows the following as the most common preoperative classification of IAs by neurosurgeons: ruptured or unruptured, wide-necked or narrow-necked. Endovascular therapeutic strategies for ruptured and unruptured IAs have been recommended (16). Endovascular therapy for WNAs frequently necessitates stent-assisted coiling therapy (17), which has been linked to an increased risk of stroke due to stent thrombosis (18) and postoperative bleeding (19). However, we discovered that previous hemodynamic studies on aneurysms only looked at the risk of rupture and did not differentiate between WNAs and NNAs. Therefore, the purpose of this study was to compare the hemodynamic differences between WNAs and NNAs to assist neurosurgeons in developing more appropriate surgical strategies for IAs.

Subarachnoid hemorrhage caused by ruptured aneurysms can have serious consequences in terms of morbidity and mortality (2). Meanwhile, surgical treatment of aneurysms, whether clipping or endovascular treatment, has a high rate of complications that result in death or disability (30). Therefore, understanding how to accurately evaluate the rupture risk and balance the risk between operation and observation is critical for UIAs. The most common factors considered by neurosurgeons in developing surgical strategies were the rupture risk and whether the IAs was wide neck. Of note, WNAs had a significantly higher surgical risk than NNAs. Previous studies on the risk of aneurysm rupture did not differentiate between WNAs and NNAs (8, 31, 32). In this study, we discovered that the rupture ratio of WNAs was significantly higher than that of NNAs by analyzing the continuous data from aneurysms collected over the previous 2 year.

The rupture risk of wide-narrow neck aneurysms is still controversial. Some studies found that high AR was positively correlated with aneurysm rupture (33) or narrow-necked aneurysms had higher risk of rupture (34). Other studies shown that wide-necked aneurysms were more likely to rupture (35). By comparing the results of most studies, we found that the mean AR value of ruptured aneurysms was mostly about 1.6, all in the range of wide-neck (33, 36). Yin et al. latest research found that non-linearity relationship of AR correlation to IA rupture, in the AR range of 1.08–1.99, the prevalence of IA rupture was lower for increment in AR, the prevalence of IA rupture increased in the AR range of 3.42–4.08, no association between AR and the prevalence of IA rupture in the AR range of 1.99–3.42 (37). In clinical practice, the AR of narrow-necked aneurysms with size <10 mm is rarely >3.42. The growth of aneurysm was accompanied by the change of a series morphology such as AR and hemodynamic (38). These studies showed that the rupture of aneurysm was the result of multiple factors. There may be some bias to analyze the risk of aneurysm rupture regardless of the size and shape. This may be one of the reasons why the current prediction model of aneurysm rupture is not ideal. In this study, the aneurysms were divided into wide-neck and narrow-neck, and the size of the aneurysms were set between 3 and 10 mm, which may help to reduce the bias of prediction model.

Previous research found that most studies used 10 mm as the cutoff point for size among other classes of aneurysms and that aneurysms larger than 10 mm rapture at a significantly higher (39, 40). Aneurysms smaller than 3 mm in diameter with less rupture risk, which was consistent with previous research (41). Therefore, we also chose the most common diameter of aneurysms ranging from 3 to 10 mm to reduce the deviation of the results.

Moreover, we found that RIAs had significantly higher IAP, WSS, WSSG, and lower NWSS than UIAs. When the aneurysms were divided into WNAs and NNAs, the RWNAs were found to have significantly higher IAP, WSS, and lower NWSS than the UWNAs. The RNNAs had significantly higher IAP and Streamwise WSSG, and lower NWSS. The results provide evidence that WNAs and NNAs have different hemodynamics, which could explain why the rupture ratios differ.

CFD is a popular research tool for studying hemodynamics; it utilizes 3D imaging data to perform numerical analysis and simulate intravascular blood flow structure to solve and analyze fluid flow problems. WSS is the tangential friction caused by blood flow on the arterial lumen. Several previous studies had examined WSS playing an important role in the natural process of IAs, however the results of WSS studies were inconsistent. Cebral et al. (42) demonstrated a positive correlation of WSS with aneurysm rupture and found that aneurysms with high WSS were more likely to rupture. Elsewhere, Castro et al. (43) built models of 26 anterior communicating artery aneurysms and discovered significant correlations between elevated maximum WSS with IAs rupture. Other studies, however, have found a link between low WSS and aneurysm rupture. Miura et al. (44) analysis 106 patient-specific middle cerebral artery (MCA) aneurysms found that only lower WSS was significantly associated with rupture status. According to an analysis of 119 aneurysm 3D angiographic images, Xiang et al. (13) discovered lower MWSS and WSS in RIAs compared to UIAs. Conflicting studies have linked high and low WSS to aneurysm rupture, resulting in the high- and low-stress theories. The high-stress theory believes that high WSS causes endothelial cell damage and initiates the degeneration of the vascular wall. Compelling evidence shows that when exposed to high WSS, vascular endothelial cells overexpress nitric oxide (NO), causing abnormally low arterial tone and apoptosis of smooth muscle cells (SMC) (45, 46). According to the low stress theory, low WSS causes inflammation of endothelial cells. Endothelial cells produce reactive oxygen species, which increase the adhesion molecules and cytokines on the surface of vascular walls, increase luminal permeability, and reduce the ability to withstand physiological hemodynamic forces (47, 48).

However, none of the previous studies classified aneurysms based on their neck wide. Numerous contradictory hemodynamic results have greatly reduced the predictive accuracy of hemodynamic parameters in aneurysm rupture. In this study, the WSS of RIA was significantly higher than UIA when there was no distinction between the wide neck and narrow neck. However, the WSS of RWNAs was significantly higher than UWNAs when distinguishing between the wide neck and narrow neck. Furthermore, WSS can be used as an independent predictor of WNAs using binary logistic regression. There was no significant difference in WSS between ruptured and unruptured groups in NNAs. The important finding was that WSS in UWNAs was higher than in RNNAs. Therefore, when analyzing the relationship between aneurysm rupture and hemodynamics, there will be a significant deviation in the results if the aneurysm is not classified by wide-neck and narrow-neck first.

The forced energy with which blood strikes the inner wall of the aneurysm sac is referred to as IAP. The local pressure rises at a flow impingement point as fluid kinetic energy is converted to static wall pressure (49). A high IAP area on the aneurysm wall may result in subsequent aneurysmal growth by a 6-month follow-up examination (50), increasing the risk of ruptured aneurysms. When the IAP reaches the critical value for aneurysm wall dilatation, the aneurysm will gradually expand, potentially leading to aneurysm wall thinning and rupture (51). Research evidence has demonstrated the effect of IAP on aneurysm rupture. Strategies, including aneurysm clipping or embolization, stent implantation were used to reduce IAP, which avoided aneurysm rupture intraoperatively and reduced aneurysm recurrence and rupture postoperatively. Yu and colleagues (52) investigated the hemodynamic changes in pre-and-post stenting of aneurysms and found that stent placement can reduce IAP and WSS at the neck region in side-wall aneurysms. In another investigation (53), the 4 different stents (LVIS, LVIS Jr, Leo, Barrel VRD) showed IAP decreased significantly after stent implantation. These findings suggest a correlation of IAP with aneurysm rupture. However, in the past, IAP was not considered a hemodynamic parameter for predicting aneurysm rupture.

In the present study, the IAP of ruptured aneurysms was found to be significantly higher than that of unruptured aneurysms in both the WNAs and NNAs groups. Also, binary logistic regression analysis revealed that IAP was an independent predictor of aneurysm rupture in both WNAs and NNAs. At the same time, the ROC curve analysis demonstrated that IAP is highly sensitive to predict aneurysm rapture in WNAs groups and NNAs group. This sensitivity is significantly higher than that used to predict aneurysm rupture risk based on factors, including age, hypertension, history of subarachnoid hemorrhage, aneurysm size, and aneurysm location (54). Meanwhile, there was no significant difference in IAP between RNNAs and UWNAs, indicating that if an aneurysm is not divided into WNAs and NNAs, the statistical results will be skewed. This paper show that the previous contradictory results of hemodynamics may be caused by the inaccuracy of the prediction model. If aneurysms are divided into wide-neck and narrow-neck aneurysms before hemodynamic analysis, it may greatly reduce the deviation of hemodynamic results, so as to more accurately guide the clinical strategies of pre-operation.

Although the study provided ideal models for removing the effects of patient-related factors, some limitations influenced the reliability of this study. The aneurysm size interval of 3–10 mm was selected; the interval was assumed to have only a minor effect, but it may also have caused deviations in the obtained results. Furthermore, the study was a retrospective analysis, and the CFD simulation used a patient-specific model. The blood flow in the hemodynamic simulation is assumed to be laminar and Newtonian, the walls are assumed to be rigid, and the inlet and outlet boundary conditions are non-specific to patients, which may result in deviations. Moreover, because our research facility is a large medical referral center and the majority of cases are referred by subordinate hospitals, selection bias is possible. In this view, the findings cannot be applied to other populations. Last but not least, the sample size of the present study was relatively small; therefore, additional multicenter studies with a larger sample size are needed to validate the study results.

Wide-neck aneurysms and narrow-neck aneurysms have different hemodynamics, which could explain why they have different rupture ratios. This work has demonstrated that WSS and IAP are independent predictors of WNAs, but IAP is the only independent predictor of NNAs. These findings will assist neurosurgeons in developing more reasonable strategies for IAs before surgery.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Clinical Research Ethics Committee of Renmin Hospital. The patients/participants provided their written informed consent to participate in this study.

HW, QT, and ML contributed the conception, design, and drafted the manuscript. HW, KY, JW, PH, YG, WH, and WG contributed data acquisition and data analysis. HW, QT, YG, WH, and ML made the article preparation and editing and review. All authors contributed to the article and approved the submitted version.

This research was funded by National Natural Science Foundation of China (Grant Nos: 81971870 and 82172173).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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