Pericallosal artery aneurysms (PAAs), also known as distal anterior cerebral artery (DACA) aneurysms, are defined as intracranial aneurysms (IAs) located on the anterior cerebral artery (ACA) distal to the anterior communicating artery (Dinc et al., 2017; Petr et al., 2017). Aneurysm rupture lead to subarachnoid hemorrhage (SAH), a devastating condition with a high mortality rate of 30–40% (Morita et al., 2012; Li et al., 2013; Molyneux et al., 2015). Despite accounting for only a small percentage (1–9%) of all IAs, PAAs merit special attention due to their considerably high propensity to rupture (Lehecka et al., 2008b; Gross et al., 2014; Thompson et al., 2015; Korja et al., 2017). Multiple previous studies have reported that the odds ratio for a proportion of ruptured PAAs compared with IAs at all other locations is in the range of 2.5–4.7, indicating the higher rupture risk of PAAs (Weir et al., 2002; Bijlenga et al., 2013; Gross et al., 2014). Therefore, identifying high-rupture-risk PAAs and subsequently providing selective therapy are of critical importance to these patients.

Unfortunately, knowledge of the risk factors of PAAs for rupture remains limited due to the rarity of these lesions. Previous studies demonstrated that certain morphological parameters, e.g., aneurysm diameter, aspect ratio (AR), size ratio (SR), and irregular shape, are highly correlated with IA rupture (Ryu et al., 2011; Kashiwazaki et al., 2013; Greving et al., 2014; Wang et al., 2021). Degenerative remodeling of the artery wall caused by abnormal hemodynamics is believed to play an important role in the progression and rupture of IAs (Meng et al., 2007, 2014; Kulcsar et al., 2011; Tanaka et al., 2018). Thus, rupture risk evaluation based on morphological and hemodynamic parameters is critical for the identification of patients with PAAs at high risk for rupture.

We previously reported our initial experiences of morphological risk factor analysis for PAAs based on manual morphological measurements, which provided a solid basis for further exploration (Zhai et al., 2020). The present study goes a step further by providing a more detailed analysis of rupture risk factors for PAAs based on more advanced morphological computer-assisted semiautomated measurement (CASAM) and hemodynamic analysis.

The mean age of the patients in the PAA cohort was 57.65 ± 9.97 years (range: 33–84 years). A total of 59.4% (19/32) of the PAAs were located at the bifurcation of the callosomarginal artery in the A3 segment, and no significant difference in baseline and morphological characteristics was detected between the ruptured and unruptured groups. Overall, there was little significant difference in the baseline and morphologic characteristics between ruptured and unruptured PAAs, and only AR was significantly higher in the ruptured group than in the unruptured group (P = 0.045) (Table 1).

According to the results of the quantitative hemodynamic analysis shown in Table 2, the mean OSI was significantly higher in the ruptured group than in the unruptured group (P = 0.035), and the mean NWSS was significantly lower in the ruptured group than in the unruptured group (P = 0.012). ROC curve analysis was performed to evaluate the predictive value of the variables for the rupture of PAAs (Figure 2). The largest AUC was that of the mean OSI (AUC = 0.808), and the AUC of mean NWSS (AUC = 0.733) ranked second, followed by the AUC of the AR (AUC = 0.712). The optimal threshold for mean OSI was 0.009875 with 75.0% sensitivity and 85.0% specificity. The optimal threshold for the mean NWSS was 0.78, which provided 91.7% sensitivity and 55.0% specificity. The optimal threshold for AR was 0.82, with a sensitivity of 75% and specificity of 65%. Factors in univariate analysis with P < 0.05 were subsequently used in a multivariable binary logistic regression analysis, including AR, mean NWSS, and mean OSI. The results of the multivariate analysis indicated that a high mean OSI was significantly associated with PAA rupture (OR = 6.45, 95% CI 1.37–30.32, P = 0.018). Multiple vital hemodynamic parameters are compared between several typical ruptured and unruptured typical PAAs in Figure 3.

To the best of our knowledge, this is the first study that assess hemodynamics and morphology simultaneously to evaluate the rupture risk of PAAs. In the present study, the results of the univariate analysis revealed that ruptured PAAs had significantly higher AR, mean NWSS, and mean OSI values than unruptured PAAs. AR represents the diameter-to-neck ratio, high AR of ruptured PAAs means that they have a relatively small neck area that limits the blood flow in the aneurysm sac and induces relatively slow and inconsistent flow in the aneurysm sac (Nader-Sepahi et al., 2004; Tateshima et al., 2010). As AR increases, vortices gradually appear in the aneurysm sac, and the flow velocity decreases (Ujiie et al., 1999; Tykocki et al., 2014). Most previous studies have indicated that AR is positively correlated with the risk of aneurysm rupture, consistent with our results (Ryu et al., 2011; Soldozy et al., 2019).

WSS is the frictional force induced by blood flow acting on the endothelium of the vessel wall, whose direction is parallel to local blood flow (Soldozy et al., 2019). For comparisons among different patients, NWSS was calculated for the hemodynamic analysis; this variable is defined as the WSS of the aneurysm wall divided by that of the parent artery wall. Low WSS was usually considered to be associated with aneurysm rupture (Miura et al., 2013; Soldozy et al., 2019), consistent with our finding that ruptured PAAs had significantly lower NWSS. OSI is a non-dimensional parameter that is defined as the directional change in WSS during the cardiac cycle; this frequency-based parameter has been used to quantify IA rupture (Soldozy et al., 2019). Our results indicated that a high mean OSI was an independent risk factor for PAA rupture (OR = 6.45, 95% CI 1.37–30.32, P = 0.018). OSI reflects the temporal variation in the blood flow direction, and the temporal variations in blood flow can be illustrated by the continuously emerging and disappearing vortices of blood flow throughout the cardiac cycle (Can and Du, 2016; Soldozy et al., 2019). OSI reflects the shape of the aneurysm and its parent artery because aneurysmal geometry and hemodynamics are intertwined, consistent with our finding (see above) that ruptured PAAs tend to have a relatively elongated shape as well as inconsistent flow.

Despite comprehensive screen, in an aneurysm cohort of 2141 patients, only 2.20% of them had PAAs. The primary limitation of this study was the small sample size, which might limit its generalizability. Second, the 3D DSA examination used for the hemodynamic study was not administered to all patients with PAAs, which caused a certain degree of selective bias. To overcome these limitations, further analysis with more adequate data is warranted in the future.

This study suggested that there were morphological and hemodynamic differences between ruptured and unruptured PAAs. In particular, a high mean OSI is an independent risk factor for PAA rupture. These findings should be considered preliminary until confirmed in larger studies.

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 human participants were reviewed and approved by the Ethics Committee of Xuanwu Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

XZ, JG, CZ, CL, JY, NJ, SX, GF, PH, and HZ contributed to the conception, design, analysis, and interpretation of the data as well as to drafting the manuscript and revising it critically. All authors have read and approved the final version of the manuscript.

GF was employed by the company UnionStrong (Beijing) Technology Co., Ltd. The remaining 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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