Merih I. Baharoglu

Aneurysm Inflow-Angle as a Discriminant for Rupture in Sidewall Cerebral Aneurysms Morphometric and Computational Fluid Dynamic Analysis

Background and Purpose— The ability to discriminate between ruptured and unruptured cerebral aneurysms on a morphological basis may be useful in clinical risk stratification. The objective was to evaluate the importance of inflow-angle (IA), the angle separating parent vessel and aneurysm dome main axes. Methods— IA, maximal dimension, height–width ratio, and dome–neck aspect ratio were evaluated in sidewall-type aneurysms with respect to rupture status in a cohort of 116 aneurysms in 102 patients. Computational fluid dynamic analysis was performed in an idealized model with variational analysis of the effect of IA on intra-aneurysmal hemodynamics. Results— Univariate analysis identified IA as significantly more obtuse in the ruptured subset (124.9°±26.5° versus 105.8°±18.5°, P=0.0001); similarly, maximal dimension, height–width ratio, and dome–neck aspect ratio were significantly greater in the ruptured subset; multivariate logistic regression identified only IA (P=0.0158) and height–width ratio (P=0.0017), but not maximal dimension or dome–neck aspect ratio, as independent discriminants of rupture status. Computational fluid dynamic analysis showed increasing IA leading to deeper migration of the flow recirculation zone into the aneurysm with higher peak flow velocities and a greater transmission of kinetic energy into the distal portion of the dome. Increasing IA resulted in higher inflow velocity and greater wall shear stress magnitude and spatial gradients in both the inflow zone and dome. Conclusions— Inflow-angle is a significant discriminant of rupture status in sidewall-type aneurysms and is associated with higher energy transmission to the dome. These results support inclusion of IA in future prospective aneurysm rupture risk assessment trials.

Stent-Assisted Coiling of Intracranial Bifurcation Aneurysms Leads to Immediate and Delayed Intracranial Vascular Angle Remodeling

BACKGROUND AND PURPOSE: Wide-neck bifurcating aneurysms are increasingly treated with intracranial stent-assisted coiling by using shape-memory alloy microstents. We sought to investigate the short- and long-term effects of intracranial stent implantation on the geometry and angular conformation of the stent-coiled vascular bifurcation. MATERIALS AND METHODS: Thirty patients underwent stent-mediated coiling for 31 bifurcation aneurysms by using 31 self-expanding Neuroform (n = 14) and Enterprise (n = 17) stents (17 women; mean age, 56 years). The angle (δ) between the stented mother and daughter vessels at the bifurcation was measured by using multiplanar imaging of reconstructed rotational conventional angiography volumes and was compared by using matched-pair statistics. Neuroform and Enterprise longitudinal stent stiffness was measured in vitro at an increasing bending angle θ (θ = 180°− δ). RESULTS: Stent deployment increased the bifurcation angle δ from 101.5° to 119.8° postprocedurally and to 137.3° (P < .0001) at latest follow-up, resulting in effective straightening; the angular remodeling was greater in distal-versus-proximal arteries (anterior cerebral > MCA > BA > ICA), inversely proportional to mother-vessel diameter and proportional to pretreatment bending angle θ. At follow-up, angle δ continued to significantly expand, with remodeling being greater in the early period (1–6 versus >7 months) and more pronounced with the longitudinally stiffer closed-cell Enterprise compared with the open-cell Neuroform stent. CONCLUSIONS: Stent placement across bifurcation aneurysms leads to a significant biphasic angular remodeling related to stent type and vessel caliber, altering morphology to mimic sidewall lesions, a phenomenon needing consideration during procedural planning. Future work is needed to uncover the hemodynamic implications of this structural change and any possible effect on aneurysm-recurrence rates.

Identification of a dichotomy in morphological predictors of rupture status between sidewall- and bifurcation-type intracranial aneurysms.

OBJECT 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. METHODS 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 (D(max)), 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. RESULTS The mean D(max), 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. CONCLUSIONS 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, D(max), was found to be of no value in differentiating between ruptured and unruptured bifurcation aneurysms.

Y-stent coiling of basilar bifurcation aneurysms induces a dynamic angular vascular remodeling with alteration of the apical wall shear stress pattern.

BACKGROUND Although wide-necked basilar bifurcation aneurysms are treated with Y-stent coiling, the effect of this intervention on vessel configuration and hemodynamics is unknown. OBJECTIVE To investigate the immediate and delayed effects of Y-stenting using self-expanding microstents on basilar bifurcation architecture and hemodynamics. METHODS Fifteen patients underwent basilar Y-stent coiling and imaging with rotational angiography. Vascular angles were measured between proximal P1 segments of the posterior cerebral arteries (α) and between the basilar artery and each P1 segment (β(1,2)) in the anteroposterior and γ(1,2) sagittal planes. Patient-specific computational fluid dynamic analysis was used to estimate wall shear stress (WSS) changes with treatment. RESULTS In the anteroposterior plane, Y-stenting significantly decreased angle α and increased β angles immediately after stent coiling (P < .05 and P < .01, respectively) in a continued dynamic remodeling that progressed further in later months; sagittal γ angles also decreased (P < .0001). This novel stent-induced geometric progressive remodeling resulted in effective straightening and narrowing of the basilar bifurcation angle α (150.0 degrees vs 113 degrees, P < .0001) with significant correlation (r = 0.39, P < .05) between pretreatment proximal P1 angles and maximal angular change. Computational fluid dynamic analysis showed the angular remodeling led to significant narrowing of the WSS interpeak at the apex, redirecting high WSS away from the neck transition zone with native vessel toward the inert coil mass. CONCLUSION Y-configuration stent coiling induced immediate and, more significantly, a previously undefined delayed cerebrovascular remodeling. This progressive stent-induced angular remodeling alters perianeurysmal hemodynamics, independent of the flow-diverting properties of stent struts, thus shifting the balance of hemodynamic forces affecting aneurysm development and evolution.

Angular remodeling in single stent-assisted coiling displaces and attenuates the flow impingement zone at the neck of intracranial bifurcation aneurysms.

BACKGROUND Self-expanding intracranial stent-assisted coiling of bifurcation aneurysms has recently been shown to straighten target cerebral vessels, a phenomenon with unknown hemodynamic effect. OBJECTIVE To investigate the impact of angular remodeling in aneurysms treated with single stent-assisted coiling with the use of computational fluid dynamic techniques. METHODS Fourteen patients (7 women, mean age 55) who underwent stent coiling of 14 wide-necked bifurcation aneurysms were included based on the availability of high-resolution 3-dimensional rotational angiography. Pretreatment data sets underwent virtual aneurysm removal to isolate the effect of stenting. Wall shear stress and pressure profiles obtained from constant flow input computational fluid dynamic analysis were analyzed for apical hemodynamic changes. RESULTS Stenting increased the bifurcation angle with significant straightening immediately after treatment and at follow-up (107.3° vs. 144.9°, P < .001). The increased stented angle at follow-up led to decreased pressure drop at the bifurcation apex (12.2 vs. 9.9 Pa, P < .003) and migration of the flow impingement zone (FIZ) toward the contralateral nonstented daughter branch by a mean of 1.48 ± 0.2 mm. Stent-induced angular remodeling decreased FIZ width separating peak apical wall shear stress (3.4 vs. 2.5 mm, P < .004). Analysis of FIZ distance measured from the parent vessel centerline showed it to be linearly (r = .58, P < .002) and FIZ width inversely correlated (r = .46, P < .02) to vessel bifurcation angle. CONCLUSION Stent-induced angular remodeling significantly altered bifurcation apex hemodynamics in a favorable direction by blunting apical pressure and inducing the narrowing and migration of the FIZ, a novel response to intracranial stenting that should be added to intimal hyperplasia and flow diversion.

Variation in Restarting Antithrombotic Drugs at Hospital Discharge After Intracerebral Hemorrhage

Background and Purpose— Whether intracerebral hemorrhage (ICH) survivors should restart antithrombotic drugs is unknown. We analyzed the frequency of restarting antithrombotic drugs in ICH survivors who had taken prophylactic antithrombotic drugs in atrial fibrillation or after thromboembolic disease in 5 cohorts and explored factors associated with doing so. Methods— We compared the characteristics and proportions of patients taking antithrombotic drugs at ICH onset and discharge in 4 hospital-based cohorts (Lille, France, n=542; Utrecht, The Netherlands, n=389; multicenter Clinical Relevance of Microbleeds in Stroke-2 (CROMIS-2) ICH, United Kingdom, n=667; and Amsterdam, The Netherlands, n=403) and 1 community-based study (Lothian, Scotland, n=137), using bivariate analyses. We sought characteristics associated with restarting using bivariate and multivariable logistic regression analyses. Results— A total of 942 (44%) patients with ICH took antithrombotic drugs at hospital admission (no difference between cohorts). Antithrombotic drugs were restarted in 96 (20%) of the 469 survivors who had taken antithrombotic drugs for secondary prevention or atrial fibrillation, but this proportion differed when stratified by the cohort of origin (Lille, 18%; Utrecht, 45%; Lothian, 15%; CROMIS-2 ICH, 11%; Amsterdam, 20%; P<0.001) and by type of antithrombotic drug pre-ICH (14% in patients with previous antiplatelet drugs versus 26% in patients with previous vitamin K antagonists and 41% in patients with both drugs; P<0.001). We did not find other consistent, independent associations with restarting antithrombotic drugs. Conclusions— The variation in clinical practice and lack of consistent associations with restarting antithrombotic drugs after ICH reflect current knowledge and support the need for randomized controlled trials to resolve this dilemma.

Ruptured Status Discrimination Performance of Aspect Ratio, Height/Width, and Bottleneck Factor Is Highly Dependent on Aneurysm Sizing Methodology

BACKGROUND Numerous size and shape parameters have historically been used to describe cerebral aneurysms and to correlate rupture status. These parameters are often inconsistently defined. OBJECTIVE To evaluate the impact of definition variation on rupture status detection performance. METHODS Catheter rotational angiographic data sets of 134 consecutive aneurysms (60 ruptured) were automatically measured in 3 dimensions with a validated algorithm. According to the literature, aneurysm height was assessed as both maximal and orthogonal distances from dome to neck. Maximal and orthogonal widths were defined perpendicular to height definitions. Neck size was evaluated as minimum, maximum, and average diameter of the neck plane. Aspect ratio (AR; height/neck), height/width ratio (HW), and bottleneck factor (BNF; width/neck) were evaluated for alternative definitions of each size variable. Univariate statistics were used to identify significant features and to compute the area under the curve (AUC) of the receiver-operating characteristic. RESULTS The AR, HW, and BNF showed significant dependence on parameter definition. Statistical significance and performance varied widely, depending on alternative definitions: AR, AUC range of 0.59 to 0.75; HW, AUC range of 0.48 to 0.72; and BNF, AUC range of 0.57 to 0.72. Using maximal height, orthogonal width, and minimum neck resulted in the best AR, HW, and BNF performances. Compared with HW, AR and BNF were less sensitive to alternative definitions. CONCLUSION Alternative aneurysm size definitions have a significant impact on prediction performance and optimal threshold values. Adoption of standard methodology and sizing nomenclature appears critical to ensure rupture detection performance and reproducibility across studies.

Widening and High Inclination of the Middle Cerebral Artery Bifurcation Are Associated With Presence of Aneurysms

Background and Purpose— The middle cerebral artery (MCA) bifurcation is a preferred site for aneurysm formation. Wider bifurcation angles have been correlated with increased risk of aneurysm formation. We hypothesized a link between the presence of MCA aneurysms and the angle morphology of the bifurcation. Methods— Three-dimensional rotational angiography volumes of 146 MCA bifurcations (62 aneurysmal) were evaluated for angle morphology: parent–daughter angles (larger daughter Ф1, smaller daughter Ф2), bifurcation angle (Ф1+Ф2), and inclination angle (&ggr;) between the parent vessel axis and the plane determined by daughter vessel axes. Statistics were evaluated using Wilcoxon rank-sum analysis and area under the receiver operator characteristic curve. Results— Aneurysmal bifurcations had wider inclination angle &ggr; (median 57.8° versus 15.4°; P<0.0001). Seventy-five percent of aneurysmal MCAs had &ggr; >10°, compared with 25% nonaneurysmal. Ф1 and Ф2, but especially Ф1+Ф2, were significantly larger in aneurysmal bifurcations (median 171.3° versus 98.1°; P<0.0001). Sixty-seven percent of aneurysmal bifurcations had Ф1+Ф2 >161°, compared with 0% nonaneurysmal MCAs. An optimal threshold of 140° was established for Ф1+Ф2 (area under the curve, 0.98). Sixty-eight percent of aneurysms originated off the daughter branches. Seventy-six percent of them originated off the branch with the largest branching angle, specifically if this was the smaller daughter branch. Wider Ф1+Ф2 correlated with aneurysm neck width, but not dome size. Conclusions— MCA bifurcations harboring aneurysms have significantly larger branching angles and more often originate off the branch with the largest angle. Wider inclination angle is strongly correlated with aneurysm presence, a novel finding. The results point to altered wall shear stress regulation as a possible factor in aneurysm development and progression.

Incremental Contribution of Size Ratio as a Discriminant for Rupture Status in Cerebral Aneurysms: Comparison With Size, Height, and Vessel Diameter

BACKGROUND: Aneurysm size ratio (SR), variably defined as the ratio of dome height (H) or maximal dimension (Dmax) over average parent vessel diameter (PV) diameter, has been proposed as a promising aneurysm rupture status predictor. OBJECTIVE: To evaluate the incremental contribution of SR to retrospective rupture status determination in a large high-resolution aneurysm database. METHODS: Measurements were performed on catheter 3D-rotational angiographic volumetric datasets for 267 aneurysms (98 ruptured). SR was computed both as H/PV (SR1) and as Dmax/PV (SR2), and its discriminant performance was evaluated on the whole dataset, on aneurysm-type subsets (bifurcation [BIF] vs sidewall [SW]), and at specific aneurysm locations. Univariate and multivariate statistical analyses were performed by the use of area under the curve (AUC) of the receiver-operating characteristics. RESULTS: Neither SR1 nor SR2 were statistically correlated to rupture status in the BIF group, where only PV (AUC = 0.61) achieved significance. All parameters were statistically significant in the combined group, but with modest performance (AUC range, 0.62-0.74). SR1 (AUC = 0.84) and SR2 (AUC = 0.78) were strong predictors in the SW group, similar to H (AUC = 0.83) and Dmax (AUC = 0.77). Multivariate statistics failed to support SR as an incremental independent parameter from PV, Dmax, and H. CONCLUSION: SR provides an uneven performance that depends strongly on the BIF/SW distribution of the data and is not useful for bifurcation lesions. In the SW subset, the incremental contribution of the SR over its H or Dmax individual component measurements could not be validated, suggesting prior findings of its utility to be the result of aneurysm-type selection bias.

Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex

OBJECT 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.