Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. OBJECTIVES: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review). SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. DATA COLLECTION AND ANALYSIS: Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE. MAIN RESULTS: We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias.  Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence).  Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence). AUTHORS' CONCLUSIONS: The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines.

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.

PURPOSE: The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS: All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE: Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS: This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.

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.

Deviation from optimal vascular caliber control at middle cerebral artery bifurcations harboring aneurysms.

Cerebral aneurysms form preferentially at arterial bifurcations. The vascular optimality principle (VOP) decrees that minimal energy loss across bifurcations requires optimal caliber control between radii of parent (r0) and daughter branches (r1 and r2): r0(n)=r1(n)+r2(n), with n approximating three. VOP entails constant wall shear stress (WSS), an endothelial phenotype regulator. We sought to determine if caliber control is maintained in aneurysmal intracranial bifurcations. Three-dimensional rotational angiographic volumes of 159 middle cerebral artery (MCA) bifurcations (62 aneurysmal) were processed using 3D gradient edge-detection filtering, enabling threshold-insensitive radius measurement. Radius ratio (RR)=r0(3)/(r1(3)+r2(3)) and estimated junction exponent (n) were compared between aneurysmal and non-aneurysmal bifurcations using Student t-test and Wilcoxon rank-sum analysis. The results show that non-aneurysmal bifurcations display optimal caliber control with mean RR of 1.05 and median n of 2.84. In contrast, aneurysmal bifurcations had significantly lower RR (0.76, p<.0001) and higher n (4.28, p<.0001). Unexpectedly, 37% of aneurysmal bifurcations revealed a daughter branch larger than its parent vessel, an absolute violation of optimality, not witnessed in non-aneurysmal bifurcations. The aneurysms originated more often off the smaller daughter (52%) vs. larger daughter branch (16%). Aneurysm size was not statistically correlated to RR or n. Aneurysmal males showed higher deviation from VOP. Non-aneurysmal MCA bifurcations contralateral to aneurysmal ones showed optimal caliber control. Aneurysmal bifurcations, in contrast to non-aneurysmal counterparts, disobey the VOP and may exhibit dysregulation in WSS-mediated caliber control. The mechanism of this focal divergence from optimality may underlie aneurysm pathogenesis and requires further study.

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 (γ) 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 γ (median 57.8° versus 15.4°; P<0.0001). Seventy-five percent of aneurysmal MCAs had γ >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.

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.

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to dissolution of the blood clot at the site of aneurysm rupture by natural fibrinolytic activity. This review is an update of a previously published Cochrane review. OBJECTIVES: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (1948 to December 2012), and EMBASE (1947 to December 2012). In an effort to identify further published, unpublished, and ongoing studies we searched reference lists and trial registers, performed forward tracking of relevant references and contacted drug companies. SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the data. Three review authors assessed trial quality. For the primary outcome we converted the outcome scales between good and poor outcome for the analysis. We scored death from any cause and rates of rebleeding, cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. MAIN RESULTS: We included 10 trials involving 1904 participants. The risk of bias was low in six studies. Four studies were open label and were rated as high risk of performance bias. One of these studies was also rated as high risk for attrition bias. Four trials reported on poor outcome (death, vegetative state, or severe disability) with a pooled risk ratio (RR) of 1.02 (95% confidence interval (CI) 0.91 to 1.15). All trials reported on death from all causes with a pooled RR of 1.00 (95% CI 0.85 to 1.18). In a trial that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for cerebral ischaemia the RR for poor outcome was 0.85 (95% CI 0.64 to 1.14). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up (RR 0.65, 95% CI 0.44 to 0.97; 78 per 1000 participants), but there was heterogeneity (I² = 62%) between the trials. The pooled RR for reported cerebral ischaemia was 1.41 (95% CI 1.04 to 1.91, 83 per 1000 participants), again with heterogeneity between the trials (I² = 52%). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in five trials (RR 1.11, 95% CI 0.90 to 1.36). AUTHORS' CONCLUSIONS: The current evidence does not support the use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage, even in those who have concomitant treatment strategies to prevent cerebral ischaemia. Results on short-term treatment are promising, but not conclusive. Further randomised trials evaluating short-term antifibrinolytic treatment are needed to evaluate its effectiveness.

Overriding role of parent over daughter vessel dimension in size ratio detection performance of bifurcation aneurysms ruptured status.

OBJECTIVE: Aneurysm-to-vessel size ratio (SR) predicts rupture status based on the premise that large aneurysms on small vessels are more likely to rupture compared to small aneurysms on larger vessels. While simpler for sidewall-type (function of proximal vessel [PV] only), SR methodology for bifurcation aneurysms requires the overhead of daughter vessels measurement. This study sets to evaluate SR performance on bifurcation aneurysms, and determine the added value of including daughters' measurements. METHODS: Catheter 3D-rotational angiograms of 154 bifurcation aneurysms (54 ruptured) were available. Aneurysms were evaluated for height (H) and maximal size (Dmax). Vessel size was evaluated as PV, daughter vessels average (DV), and parent and daughter vessels average (PDV). First, SR was evaluated as SR1(PDV) = H/PDV and SR2(PDV) = Dmax/PDV. Second, SR function of the parent vessel only was evaluated as SR1(PV) = H/PV and SR2(PV) = Dmax/PV. Statistical significance was assumed for P < 0.05. Area under the curve (AUC) was evaluated. RESULTS: Unexpectedly, parent vessel only definitions, SR1(PV) (P < 0.001, AUC = 0.69) and SR2(PV) (P = 0.002, AUC = 0.64), performed marginally better as rupture status discriminators compared to the corresponding parent and daughter vessels definitions, SR1(PDV) (P = 0.001, AUC = 0.67) and SR2(PDV) (P = 0.01, AUC = 0.63), respectively. Parameters including daughter vessel measurements (DV, PDV, DV/PV) were not significant. CONCLUSION: Not only is the inclusion of daughter measurements not statistically justified, it may be detrimental to SR performance. Parent-only SR definitions simplify the aneurysmal morphological evaluation at no performance loss. It is reasonable to employ a unified approach regardless of sidewall/bifurcation labeling, by defining SR as aneurysm size to parent vessel ratio and omitting the measurements of the daughter branches.

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.

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 (ß(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 ß 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.

Size ratio performance in detecting cerebral aneurysm rupture status is insensitive to small vessel removal.

BACKGROUND: The variable definition of size ratio (SR) for sidewall (SW) vs bifurcation (BIF) aneurysms raises confusion for lesions harboring small branches, such as carotid ophthalmic or posterior communicating locations. These aneurysms are considered SW by many clinicians, but SR methodology classifies them as BIF. OBJECTIVE: To evaluate the effect of ignoring small vessels and SW vs stringent BIF labeling on SR ruptured aneurysm detection performance in borderline aneurysms with small branches, and to reconcile SR-based labeling with clinical SW/BIF classification. METHODS: Catheter rotational angiographic datasets of 134 consecutive aneurysms (60 ruptured) were automatically measured in 3-dimensional. Stringent BIF labeling was applied to clinically labeled aneurysms, with 21 aneurysms switching label from SW to BIF. Parent vessel size was evaluated both taking into account, and ignoring, small vessels. SR was defined accordingly as the ratio between aneurysm and parent vessel sizes. Univariate and multivariate statistics identified significant features. The square of the correlation coefficient (R(2)) was reported for bivariate analysis of alternative SR calculations. RESULTS: Regardless of SW/BIF labeling method, SR was equally significant in discriminating aneurysm ruptured status (P < .001). Bivariate analysis of alternative SR had a high correlation of R(2) = 0.94 on the whole dataset, and R = 0.98 on the 21 borderline aneurysms. CONCLUSION: Ignoring small branches from SR calculation maintains rupture status detection performance, while reducing postprocessing complexity and removing labeling ambiguity. Aneurysms adjacent to these vessels can be considered SW for morphometric analysis. It is reasonable to use the clinical SW/BIF labeling when using SR for rupture risk evaluation.

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.

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.

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 (D(max)) 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 D(max)/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 D(max) (AUC = 0.77). Multivariate statistics failed to support SR as an incremental independent parameter from PV, D(max), 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 D(max) individual component measurements could not be validated, suggesting prior findings of its utility to be the result of aneurysm-type selection bias.

Rupture status discrimination in intracranial aneurysms using the centroid-radii model.

Intracranial aneurysms are localized, abnormal arterial dilatations with a variable risk of rupture, leading to medical conditions associated with high morbidity and mortality. Predicting their risk of rupture, especially for incidental asymptomatic aneurysms, is a challenging task. The size of the aneurysm sac is traditionally used to assess the risk, but shape analysis has emerged as a promising differentiator of rupture likelihood. The centroid-radii model (CRM) is introduced here to describe both the size and the shape of the aneurysms, and determine rupture status. The entropy of CRM is proposed as an aneurysm descriptor which is easy to compute, robust to noise and segmentation, and accurate in rupture status discrimination. Analysis is performed on 154 patient-derived saccular aneurysms. The aneurysms are further classified as sidewall and bifurcation, and the shape analysis is performed separately on the two subtypes. Using the entropy of CRM resulted in 80.3% and 70.5% classification accuracy of status rupture in sidewall and bifurcation aneurysms, respectively. When compared to the accuracy of some commonly used size and shape indexes, the entropy of the CRM proved to be a more accurate single index associated with rupture in intracranial aneurysms, for both sidewall and bifurcation subtypes.

3D shape analysis of intracranial aneurysms using the writhe number as a discriminant for rupture.

Intracranial aneurysms are polymorphic focal arterial dilations, which harbor a variable risk of rupture leading to high morbidity and mortality. Increased detection of incidental aneurysms by non-invasive imaging has created a need for rupture risk stratification tools, in addition to simple aneurysm size, to guide optimal treatment strategy. To this end, shape analysis has emerged as a possible differentiator of rupture likelihood. A novel set of morphological parameters based on the writhe number are introduced here to describe aneurysms and discriminate rupture status. Classification in 117 saccular aneurysms (52 ruptured and 65 unruptured) is based on statistical analysis of writhe number distribution on the aneurysm surface. Aneurysms are analyzed both in isolation and including a portion of their parent vessel. Sidewall and bifurcation aneurysm subtypes were found to be best described by disjoint sets of shape parameters, yielding a morphological dichotomy between the two aneurysm classes. Writhe number analysis results in 86.7% accuracy on sidewall (SW) aneurysms and 71.2% accuracy on bifurcation (BF) aneurysms. This represents a 12% accuracy increase for both subtypes compared to the performance of seven established 2D and 3D indexes. The results support the utility of writhe number aneurysm shape analysis, with potential clinical value in rupture risk stratification.

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 degrees+/-26.5 degrees versus 105.8 degrees+/-18.5 degrees, 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.