The interrelated effects of 2D angiographic morphological variables and aneurysm rupture

Discussion

The present retrospective study demonstrated that rupture occurrence in cerebral aneurysm patients correlated with complex and interrelated morphological factors that could be best expressed by utilizing calculated 2D morphological parameters as well as maximum diameter (Dmax), maximum height (Hmax), and inflow angle. The current study indicates that specific morphological characteristics of ruptured aneurysms and unruptured aneurysms in a single patient have distinct characteristics. Though further research will be required to determine potential relationships between clinical variables, such as smoking, hypertension, arteriosclerosis, or even genetic predisposition, and aneurysm rupture, this study indicates that in a single patient, aneurysm rupture risk can be distinguished. These findings potentially indicate that morphological variation, with consideration for clinical variables, is a potentially effective approach for clinical stratification of these patients.

Conventionally, the primary indicator of rupture risk was a large maximum diameter (Dmax), defined by Wiebers et al17 as larger than 10 mm; however, a recent proliferation of inconsistent reports of methods to indicate aneurysm rupture have appeared in the literature.14 For aneurysms with Dmax larger than 10 mm, it has been reported that there is only a 0.05% per year risk of rupture.3,4 Conversely, Baharoglu et al18 reported that though aneurysms larger than 7.76 mm were likely to rupture, Dmax was of no significant use in predicting rupture due to the wide variation in aneurysm type. These findings are consistent with the current results, which indicate that aneurysms of ~6 mm and ~3.5 mm were sometimes subject to rupture, though Dmax was not the most significant predictor of these events. Because the size of aneurysms is closely associated with the geometry of the parent artery diameter,19 it is unsurprising that assessment of maximum aneurysm diameter yields inconsistent results. Sato et al19 demonstrated that the variant aneurysm shapes and configurations, including ratio of aneurysm height to neck diameter and torsion angle of the aneurysm to the upstream parent artery, played a role in determining the shear wall stress. In fact, artery failure was more closely related to these parameters, in terms of materials failure theory, than artery curvature, or aneurysm size or shape.19 Thus, aneurysms must be more carefully considered on an individual basis in order to determine artery wall failure leading to rupture, and more appropriate clinical guidelines should be developed.

Based on the need for better clinical guidelines for aneurysm rupture, researchers have recently proposed aspect ratio, bottleneck factor, size ratio, height-width ratio, and inflow angle as critical measurements of rupture risk.14 Rahman et al20 reported that size ratio was the most significant discriminant of rupture status, while Hoh et al11 reported that bottleneck factor and height-width ratio were most consistently associated with rupture.21 In yet another report, Baharoglu et al18 published that inflow angle was the most significant discriminant of rupture status in sidewall-type aneurysms, potentially due to high-energy transmission of the dome. The current study, however, suggests that size ratio and height-width ratio were the most significant discriminant for rupture, though aspect ratio, bottleneck factor, and inflow angle were also related to rupture risk. The discrepancies between these studies may indicate a need to more carefully consider the geometry of not just the aneurysm, but also the surrounding artery.19 Furthermore, there is an urgent need for better clinical typing of aneurysms.18

In the current study, bifurcation and sidewall aneurysms were mixed despite previous indications that these 2 aneurysm types have very different failure properties.18 Particularly for inflow angle, aspect ratio, and bottleneck factor,18 this may interfere with accurate assessment of the relationship between these parameters and rupture. For the same reason, these parameters may not be broadly applicable to all aneurysm types, necessitating better aneurysm typing in order for more appropriate assessments of rupture risk to be widely implemented. Fortunately, modern angiography has allowed for reliable and consistent centerline techniques for examining artery and aneurysm characteristics.21 Notably, aspect ratio can describe satisfactorily lengthways stretch aneurysm but cannot describe satisfactorily transverse stretch aneurysm; comparatively, bottleneck factor can satisfactorily describe transverse stretch aneurysm, but cannot satisfactorily describe lengthways stretch aneurysm.21 Using the directions suggested in centerline angiography techniques coupled with the current findings and this brief review of the literature, we propose that aneurysms can be classified broadly into 2 types based on stretch direction: lengthwise and transverse. By applying modern CT angiography, rather than DSA,22 it may be possible to distinguish characteristics of these aneurysms more effectively, thereby allowing improved rupture risk assessment and prevention in clinical patients.

More specifically, neck width, dome width, aneurysm shape, aspect ratio (height/neck width), and bottleneck factor (dome width/neck width) have been examined. Among these, aspect ratio has shown the greatest promise as a parameter to associate with rupture risk.14,23,24 Carter et al25 demonstrated that ruptured intracranial aneurysms originating from distal blood vessels were smaller than ruptured intracranial aneurysms originating from proximal, larger blood vessels. Thus, size ratio is useful because it is representative of aneurysm stretch character relative to parent artery. Similarly, Rahman et al20 reported that patients that experienced rupture exhibited significantly larger size ratios compared with patients that did not experience rupture, suggesting that size ratios may be a practical tool for gauging stretch and, thereby, assessing rupture in clinical aneurysm patients. Furthermore, height-width ratio increases with increasing Dmax and Hmax, increasing bottleneck factor and increasing the size ration in ruptured aneurysms but not in unruptured aneurysms, thereby indicating stretch. Thus, aneurysm stretch character more significantly correlates with expansion of the aneurysm in irregular aneurysms that will undergo rupture, unlike other parameters. It is, thus, important to consider than height-width ratio, size ratio, aspect ratio are all interrelated, describing aneurysm characteristics and stretch in different but important ways.

Anther variable, bulge location increases with increasing aspect ratio, increasing bottleneck factor, increasing size ration, and increasing Dmax and Hmax in unruptured aneurysms, but does not correlate to any variables in ruptured aneurysms, which indicates that with larger aneurysm volume the largest transverse may be closer to the tip the aneurysm in unruptured aneurysms. But, it does not happen in ruptured aneurysm, owing to the more irregular sphere.

The relatively small patient group and lack of differentiation between bifurcation and sidewall aneurysm hemodynamics may limit the broad applicability of these results. Further study is required to relate clinical variables to these diverse morphological variables before clinical recommendations can be made. Additionally, further prospective studies will be required to confirm these results, particularly to allow proper blinding and avoid study bias. Thus, these findings can only provide a basis for further study, instead of providing a quantitative clinical standard. More extensive and comprehensive multivariate analysis of both clinical and morphological parameters will be required to generate useful clinical guidelines for aneurysm patient stratification by rupture risk.

In conclusion, this retrospective case-control analysis of multiple aneurysm patients with and without rupture indicates that morphological parameters are useful in predicting rupture leading to acute subarachnoid hemorrhage. In particular, maximum diameter (Dmax), aneurysm height (Hmax), inflow angle, aspect ratio, bottleneck factor, bulge location, size ratio, and height-width ratio was associated with rupture by univariate analyses. Notably, only size ratio and height-width ratio was significantly associated with ruptured aneurysms in binary logistic analyses. Thus, the stretch character of aneurysms is more significantly correlated with expansion in ruptured aneurysms. These findings, however, require confirmation in larger future larger studies that also consider diverse clinical variables as well as morphological characteristics.