Alexandra Lauric, James E. Hippelheuser and Adel M. Malek
Endothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide branching angles with aneurysm presence, the authors evaluated the effect of bifurcation geometry on local apical hemodynamics.
Computational fluid dynamics simulations were performed on parametric bifurcation models with increasing angles having: 1) symmetrical geometry (bifurcation angle 60°–180°), 2) asymmetrical geometry (daughter angles 30°/60° and 30°/90°), and 3) curved parent vessel (bifurcation angles 60°–120°), all at baseline and double flow rate. Time-dependent and time-averaged apical WSS and WSSG were analyzed. Results were validated on patient-derived models.
Narrow symmetrical bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles ≥ 85°. Asymmetrical bifurcations develop positive WSSG on the more obtuse daughter branch. A curved parent vessel leads to positive apical WSSG on the side corresponding to the outer curve. All simulations revealed wider apical area coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation angle and higher flow rate. Flow rate did not affect the angle threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex, in a dynamic fashion and in an angle-dependent manner.
Apical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The development of aneurysmogenic positive WSSG as a function of angular geometry provides a mechanotransductive link for the association of wide bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the associated aneurysmal degeneration.
Merih I. Baharoglu, Alexandra Lauric, Bu-Lang Gao and Adel M. Malek
Prediction of aneurysm rupture likelihood is clinically valuable, given that more unruptured aneurysms are being discovered incidentally with the increased use of imaging. The authors set out to evaluate the relative performance of morphological features for rupture status discrimination in the context of the divergent geometrical and hemodynamic characteristics of sidewall- and bifurcation-type aneurysms.
Catheter 3D rotational angiographic images of 271 consecutive aneurysms (101 ruptured, 135 bifurcation type) were used to assess the following parameters in 3D: maximum diameter (Dmax), height, height/width ratio, aspect ratio, size ratio, nonsphericity index, and inflow angle. Univariate statistics applied to the bifurcation, sidewall, and combined (bifurcation + sidewall) sets identified significant features for inclusion in multivariate analysis yielding area under the curve (AUC) and optimal thresholds in the receiver-operating characteristic. Furthermore, a computational fluid dynamics analysis was performed to evaluate the flow and wall shear stress conditions inside sidewall and bifurcation aneurysms at different inflow angles.
The mean Dmax, height, and inflow angle were significantly greater in ruptured sidewall aneurysms than in unruptured sidewall aneurysms, but showed no difference between ruptured and unruptured bifurcation lesions. There was a statistically significant difference between ruptured and unruptured aneurysms for all measured features in the combined set. Multivariate analysis identified the following: 1) nonsphericity index as the only rupture status discriminator in bifurcation lesions (AUC = 0.67); 2) height/width ratio, size ratio, and inflow angle as strong discriminators in sidewall lesions (AUC = 0.87); and 3) height/width ratio, inflow angle, and size ratio as intermediate discriminators in the combined group (AUC = 0.76). Computational fluid dynamics analysis showed that although increasing inflow angle in a sidewall model led to deeper penetration of flow, higher velocities, and higher wall shear stress inside the aneurysm dome, it produced the exact opposite results in a bifurcation model.
Retrospective morphological and hemodynamic analysis point to a dichotomy between sidewall and bifurcation aneurysms with respect to performance of shape and size parameters in identifying rupture status, suggesting the need for aneurysm type–based analyses in future studies. The current most commonly used clinical risk assessment metric, Dmax, was found to be of no value in differentiating between ruptured and unruptured bifurcation aneurysms.
Mina G. Safain, Jason P. Rahal, Samir Patel, Alexandra Lauric, Edward Feldmann and Adel M. Malek
Intracranial atherosclerotic disease (ICAD) carries a high risk of stroke. Evaluation of ICAD has focused on assessing the absolute degree of stenosis, although plaque morphology has recently demonstrated increasing relevance. The authors provide the first report of the use of ultra-high-resolution C-arm cone-beam CT angiography (CBCT-A) in the evaluation of vessel stenosis as well as plaque morphology.
Between August 2009 and July 2012, CBCT-A was used in all patients with ICAD who underwent catheter-based angiography at the authors' institution (n = 18). Lesions were evaluated for maximum degree of stenosis as well as plaque morphological characteristics (ulcerated, calcified, dissected, or spiculated) via digital subtraction angiography (DSA), 3D-rotational angiography (3DRA), and CBCT-A. The different imaging modalities were compared in their assessment of absolute stenosis as well as their ability to resolve different plaque morphologies.
Lesions were found to have similar degrees of stenosis when utilizing CBCT-A compared with 3DRA, but both 3DRA and CBCT-A differed from DSA in their assessment of the absolute degree of stenosis. CBCT-A provided the most detailed resolution of plaque morphology, identifying a new plaque characteristic in 61% of patients (n = 11) when compared with DSA and 50% (n = 9) when compared with 3DRA. CBCT-A identified all lesion characteristics visualized on DSA and 3DRA.
CBCT-A provides detailed spatial resolution of plaque morphology and may add to DSA and 3DRA in the evaluation of ICAD. Further prospective study is warranted to determine any benefit CBCTA-A may provide in clinical decision making and risk stratification over existing conventional imaging modalities.
Fatih Tütüncü, Sarah Schimansky, Merih I. Baharoglu, Bulang Gao, Daniel Calnan, James Hippelheuser, Mina G. Safain, Alexandra Lauric and Adel M. Malek
Arterial bifurcations represent preferred locations for aneurysm formation, especially when they are associated with variations in divider geometry. The authors hypothesized a link between basilar apex aneurysms and basilar bifurcation (α) and vertebrobasilar junction (VBJ) angles.
The α and VBJ angles were measured in 3D MR and rotational angiographic volumes using a coplanar 3-point technique. Angle α was compared between age-matched cohorts in 45 patients with basilar artery (BA) aneurysms, 65 patients with aneurysms in other locations (non-BA), and 103 nonaneurysmal controls. Additional analysis was performed in 273 nonaneurysmal controls. Computational fluid dynamics (CFD) simulations were performed on parametric BA models with increasing angles.
Angle α was significantly wider in patients with BA aneurysms (146.7° ± 20.5°) than in those with non-BA aneurysms (111.7° ± 18°) and in controls (103° ± 20.6°) (p < 0.0001), whereas no difference was observed for the VBJ angle. A wider angle α correlated with BA aneurysm neck width but not dome size, which is consistent with CFD results showing a widening of the impingement zone at the bifurcation apex. BA bifurcations hosting even small aneurysms (< 5 mm) had a significantly larger α angle compared with matched controls (p < 0.0001). In nonaneurysmal controls, α increased with age (p < 0.0001), with a threshold effect above 35 years of age and a steeper dependence in females (p = 0.002) than males (p = 0.04).
The α angle widens with age during adulthood, especially in females. This angular widening is associated with basilar bifurcation aneurysms and may predispose individuals to aneurysm initiation by diffusing the flow impingement zone away from the protective medial band region of the flow divider.