Intracranial aneurysm is a relatively common cerebrovascular disease resulting from pathological weakness of the intracranial artery wall, leading to gradual abnormal bulging under the impact of blood flow and other factors. Non-traumatic subarachnoid hemorrhage (SAH) is mainly caused by the rupture of intracranial aneurysms and accounts for 75%−85% of cases (1). Owing to the hazardous nature of intracranial aneurysms, they frequently have grave consequences. The fatality rate for initial hemorrhage is as high as 35%, and even after survival, most patients still suffer from severe disability, resulting in significant clinical and socioeconomic burdens (2). With the continuous advancement and widespread application of non-invasive imaging technology, the detection rate of intracranial aneurysms has been steadily increasing annually. The prevalence of unruptured intracranial aneurysms (UIA) is as high as 7% in the population; however, the actual risk of rupture is <1% (3, 4). Prophylactic treatment for these UIAs may lead to surgery-related complications such as intraoperative rupture and infarction. On the other hand, conservative treatment carries the risk of late rupture. Determining the higher risk between treatment and rupture is a major challenge for clinicians. Therefore, precise and timely differentiation between unstable and stable UIAs as well as accurate intervention are crucial components in the field of cerebrovascular disease diagnosis and treatment.

Recently, numerous risk factors for intracranial aneurysms with a high risk of rupture have been reported. These include general clinical characteristics of patients, such as gender, age, smoking, and hypertension (5), as well as morphological features of intracranial aneurysms, such as maximum diameter and aspect ratio (AR) (6, 7). Observational studies on unruptured intracranial aneurysms have demonstrated that the morphological characteristics associated with aneurysm rupture undergo significant changes during aneurysm growth, resulting in a marked increase in annual rupture rates (8, 9). The blood flow between the aneurysm and the parent artery is continuous, resulting in changes in morphology with each pulsation of the parent artery. We postulate that aneurysm pulsation during the cardiac cycle induces morphological changes, which is also associated with aneurysm rupture. With recent advancements in imaging technology, it has become feasible to monitor the dynamic changes in aneurysms caused by pulse pressure from the beating artery of the heart. Current dynamic studies primarily focus on the significance of irregular pulses in aneurysms and predicting the risk of rupture during clipping. However, there is a dearth of research examining dynamic morphological changes in aneurysms for risk assessment purposes (10–12). Four-dimensional computed tomography angiography (4D-CTA) was used in this study to examine the correlation between morphological changes in intracranial aneurysms during the cardiac cycle and aneurysm rupture, aiming to explore potential factors associated with intracranial aneurysms rupture.

This was a retrospective study of 4D-CTA for intracranial aneurysm detection. We found that both the rate of dome height change and the rate of aneurysm volume change were independently associated with rupture, and the aneurysm volume change rate demonstrated a good ability to analyze aneurysm rupture. Our findings suggest that the rate of morphological changes detected using 4D-CTA in aneurysms may be a potential clinical indicator associated with aneurysm rupture.

Morphology provides an important foundation for studying the risk of aneurysm rupture, but most studies on aneurysm morphology are static (13, 14). Given that blood flow within intracranial aneurysms is subject to changes in response to cardiac contraction and relaxation, a dynamic study of their morphological alterations would be more advantageous. Univariate analysis revealed that the rate of morphological changes during the cardiac cycle was associated with aneurysm rupture compared with other factors. Furthermore, the ruptured group exhibited a consistently higher rate of morphological changes than the unruptured group. The results of multivariate and ROC analyses demonstrated that the change rate of aneurysm height and volume were independent factors associated with the ruptured status, with a certain ability to analyze the factors contributing to aneurysm rupture, especially for the change rate of volume, which showed superior sensitivity.

The rates of dome height and aneurysm volume changes reflect the degree of morphological changes in a cardiac cycle, which can alter intraluminal hemodynamics, an important factor in the occurrence, growth, and rupture of intracranial aneurysms (15–17).

This study found a negative correlation between the rate of change in dome height and aneurysm rupture, suggesting that a higher rate of change in dome height was associated with a lower aneurysm rupture. Blood entering the aneurysm from the parent artery produces wall shear stress (WSS), which increases with blood flow velocity. The blood flow velocity and WSS were the highest at the ostium of the aneurysm. Slow blood rheology within the aneurysm cavity results in decreased WSS, with the slowest blood flow velocity at the top of the aneurysm corresponding to the lowest WSS values. Both high and low WSS can contribute to aneurysm formation and rupture (18–20). The greater the rate of change in aneurysm height, the more obvious the change in height becomes. The distance from the ostium to the top of the aneurysm increased, resulting in a greater degree of velocity change in blood flow. Although WSS at the top of the aneurysm decreases, there is a fluctuation range owing to the dynamic change in height; therefore, WSS will not be too high or too low. Additionally, the pumping of blood by the heart causes a series of changes in blood flow that leads to fluctuations in the aneurysm height. Generally, WSS variation at the apex of an aneurysm oscillates within a narrow range, creating a corresponding buffer to prevent rupture caused by abrupt changes in WSS at this location.

Kuroda first proposed cardiac cycle-related volume changes in intracranial aneurysms and evaluated the relationship between intracranial aneurysms and the movement of normal intracranial arteries in one cardiac cycle. Although no significant difference existed between unruptured aneurysms and normal intracranial arteries, there was still a slight distinction (21). 4D-CTA is a feasible method for quantitatively analyzing the volume changes of aneurysms during a cardiac cycle, providing a theoretical basis for further research (22, 23). In this study, the comparison between ruptured and unruptured aneurysms revealed a significant difference in volume change rate between the two groups. Furthermore, there is a positive correlation between aneurysm volume change rate and rupture risk, indicating that higher volume change rates increase the likelihood of aneurysm rupture. A study on the pathological changes of intracranial aneurysms found that compared to the normal vascular wall, the aneurysm wall showed the absence of a multilayered vessel wall structure-elastic compartment with an increase in permeability, endothelial cell damage and produces areas of inflammation, and chronic increased inflammation further exacerbates vessel wall defects (24–27). The destruction of elastic fibers is most pronounced at the weak point of the tumor wall, where the expansion rate exceeds that of the normal vessel wall, and rupture is more likely to occur. Some studies suggest that the rupture point of an aneurysm is the same as its pulsatile point on 4D-CTA or the weak point observed during surgery, and an aneurysm with a pulsatile point is more likely to rupture (10, 28, 29). The pulsation point was defined as a protrusion observed in the same area of the aneurysm on at least three consecutive images during the cardiac cycle. The appearance of an abnormal pulsation must be accompanied by an increase in volume change. After a rupture, although small blood clots may temporarily protect by attaching to the site of rupture, the aneurysm wall in this area is always weaker than in other parts and more susceptible to expansion due to the pulsation of blood flow. Therefore, for aneurysms with a high-volume change rate, an early warning indicates the possibility of rupture and necessitates prompt treatment.

Additionally, this study revealed a higher incidence of intracranial aneurysms in women than in men. Some scholars believe that the female gender is not only a risk factor for aneurysm formation but also a risk factor for SAH, which is related to the potential protective participation of sex steroids (6). The aneurysms in the present study occurred at the three most common sites of ruptured aneurysms (MCa, ACoA, and PCoA), possibly because the blood flow changes significantly at the bifurcation of blood vessels, making it easier to form aneurysms (30). Our study accurately reflects the distribution of aneurysms; however, due to the small sample size, no significant difference was observed between the two groups.

This study had several limitations. First, it was a retrospective study conducted at a single center, and most patients included were candidates for preventive therapy, which inevitably led to a selection bias. Second, in the ruptured group, the aneurysm had already ruptured at the time of diagnosis, and 4D-CTA was performed after the rupture. Changes in aneurysm morphology may result from its rupture rather than a causal relationship. These factors are associated with the ruptured status and represent important findings, but they do not necessarily increase the risk of rupture. Consequently, our conclusion may deviate from the actual circumstances. Third, the sample size of the study was limited. The optimal approach would entail a multicenter, large-scale study wherein the same patient is monitored from the initial detection of unruptured aneurysms until rupture, with a comprehensive recording of all morphological data for prospective comparative analysis.

The rates of change in dome height and aneurysm volume may serve as factors associated with rupture, and the influence of volume change rate is more significant. These influencing factors have the potential to become predictive indicators for intracranial aneurysm rupture.

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

The studies involving humans were approved by Ethics Committee of the Fourth Affiliated Hospital of Harbin Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin in accordance with the national legislation and institutional requirements.

BW and CS wrote the manuscript contributed equally to the article. ZS and XN collected and analyze data. JZ, SQ, and YL conducted the work. All authors contributed to the article and approved the submitted version.