Topological Data Analysis and Use of Mapper for Cerebral Aneurysm Rupture Status Discrimination Based on 3-Dimensional Shape Analysis.

BACKGROUND AND OBJECTIVES: Topological data analysis (TDA), which identifies patterns in data through simplified topological signatures, has yet to be applied to aneurysm research. We investigate TDA Mapper graphs (Mapper) for aneurysm rupture discrimination. METHODS: Two hundred sixteen bifurcation aneurysms (90 ruptured) from 3-dimensional rotational angiography were segmented from vasculature and evaluated for 12 size/shape and 18 enhanced radiomics features. Using Mapper, uniformly dense aneurysm models were represented as graph structures and described by graph shape metrics. Mapper dissimilarity scores (MDS) were computed between pairs of aneurysms based on shape metrics. Lower MDS described similar shapes, whereas high MDS represented shapes that do not share common characteristics. Ruptured/unruptured average MDS scores (how "far" an aneurysm is shape-wise to ruptured/unruptured data sets, respectively) were evaluated for each aneurysm. Rupture status discrimination univariate and multivariate statistics were reported for all features. RESULTS: The average MDS for pairs of ruptured aneurysms were significantly larger compared with unruptured pairs (0.055 ± 0.027 vs 0.039 ± 0.015, P < .0001). Low MDS suggest that, in contrast to ruptured aneurysms, unruptured aneurysms have similar shape characteristics. An MDS threshold value of 0.0417 (area under the curve [AUC] = 0.73, 80% specificity, 60% sensitivity) was identified for rupture status classification. Under this predictive model, MDS scores <0.0417 would identify unruptured status. MDS statistical performance in discriminating rupture status was similar to that of nonsphericity and radiomics Flatness (AUC = 0.73), outperforming other features. Ruptured aneurysms were more elongated ( P < .0001), flatter ( P < .0001), and showed higher nonsphericity ( P < .0001) compared with unruptured. Including MDS in multivariate analysis resulted in AUC = 0.82, outperforming multivariate analysis on size/shape (AUC = 0.76) and enhanced radiomics (AUC = 0.78) alone. CONCLUSION: A novel application of Mapper TDA was proposed for aneurysm evaluation, with promising results for rupture status classification. Multivariate analysis incorporating Mapper resulted in high accuracy, which is particularly important given that bifurcation aneurysms are challenging to classify morphologically. This proof-of-concept study warrants future investigation into optimizing Mapper functionality for aneurysm research.

Aneurysm presence at the anterior communicating artery bifurcation is associated with caliber tapering of the A1 segment.

OBJECTIVE: Vessel tapering results in blood flow acceleration at downstream bifurcations (firehose nozzle effect), induces hemodynamics predisposing to aneurysm initiation, and has been associated with middle cerebral artery (MCA) aneurysm presence and rupture status. The authors sought to determine if vessel caliber tapering is a generalizable predisposing factor by evaluating upstream A1 segment profiles in association with aneurysm presence in the anterior communicating artery (ACoA) complex, the most prevalent cerebral aneurysm location associated with a high rupture risk. METHODS: Three-dimensional rotational angiographic studies were analyzed for 68 patients with ACoA aneurysms, 37 nonaneurysmal contralaterals, and 53 healthy bilateral controls (211 samples total). A1 segments were determined to be dominant, codominant, or nondominant based on flow and size. Equidistant cross-sectional orthogonal cuts were generated along the A1 centerline, and cross-sectional area (CSA) was evaluated proximally and distally, using intensity-invariant edge detection filtering. The relative tapering of the A1 segment was evaluated as the tapering ratio (distal/proximal CSA). Computational fluid dynamics was simulated on ACoA parametric models with and without tapering. RESULTS: Aneurysms occurred predominantly on dominant (79%) and codominant (17%) A1 segments. A1 segments leading to unruptured ACoA aneurysms had significantly greater tapering compared to nonaneurysmal contralaterals (0.69 ± 0.13 vs 0.80 ± 0.17, p = 0.001) and healthy controls (0.69 ± 0.13 vs 0.83 ± 0.16, p < 0.001), regardless of dominance labeling. There was no statistically significant difference in tapering values between contralateral A1 and healthy A1 controls (0.80 ± 0.17 vs 0.83 ± 0.16, p = 0.56). Hemodynamically, A1 segment tapering induces high focal pressure, high wall shear stress, and high velocity at the ACoA bifurcation. CONCLUSIONS: Aneurysmal, but not contralateral or healthy control, A1 segments demonstrated significant progressive vascular tapering, which is associated with aneurysmogenic hemodynamic conditions at the ACoA complex. Demonstration of the upstream tapering effect in the communicating ACoA segment is consistent with its prior detection in the noncommunicating MCA bifurcation, which together form more than 50% of intracranial aneurysms. The mechanistic characterization of this upstream vascular tapering phenomenon is warranted to understand its clinical relevance and devise potential therapeutic strategies.

Vortex formation and associated aneurysmogenic transverse rotational shear stress near the apex of wide-angle cerebral bifurcations.

OBJECTIVE: Aneurysm formation preferentially occurs at the site of wide-angle cerebral arterial bifurcations, which were recently shown to have a high longitudinal positive wall shear stress (WSS) gradient that promotes aneurysm formation. The authors sought to explore the other components of the hemodynamic environment that are altered with increasing bifurcation angle in the apical region and the effects of these components on WSS patterns on the vessel wall that may modulate aneurysm genesis and progression. METHODS: Parametric models of symmetrical and asymmetrical bifurcations were created with increasing bifurcation angles (45°-240°), and 3D rotational angiography models of 13 middle cerebral artery (MCA) bifurcations (7 aneurysmal, 6 controls) were analyzed using computational fluid dynamics. For aneurysmal bifurcations, the aneurysm was digitally removed to uncover hemodynamics at the apex. WSS vectors along cross-sectional planes distal to the bifurcation apex were decomposed as orthogonal projections to the cut plane into longitudinal and transverse (tangential to the cross-sectional plane) components. Transverse rotational WSS (TRWSS) and TRWSS gradients (TRWSSGs) were sampled and evaluated at the apex and immediately distal from the apex. RESULTS: In parametric models, increased bifurcation angle was associated with transverse flow vortex formation with emergence of an associated apical high TRWSS with highly aneurysmogenic positive TRWSSGs. While TRWSS decayed rapidly away from the apex in narrow-angle bifurcations, it remained greatly elevated for many radii downstream in aneurysm-prone wider bifurcations. In asymmetrical bifurcations, TRWSS was higher on the aneurysm-prone daughter vessel associated with the wider angle. Patient-derived models with aneurysmal bifurcations had wider angles (149.33° ± 12.56° vs 98.17° ± 8.67°, p < 0.001), with significantly higher maximum TRWSS (1.37 ± 0.67 vs 0.48 ± 0.23 Pa, p = 0.01) and TRWSSG (1.78 ± 0.92 vs 0.76 ± 0.50 Pa/mm, p = 0.03) compared to control nonaneurysmal bifurcations. CONCLUSIONS: Wider vascular bifurcations are associated with a novel and to the authors' knowledge previously undescribed transverse component rotational wall shear stress associated with a positive (aneurysmogenic) spatial gradient. The resulting hemodynamic insult, demonstrated in both parametric models and patient-based anatomy, is noted to decay rapidly away from the protection of the medial pad in healthy narrow-angle bifurcations but remain elevated distally downstream of wide-angle aneurysm-prone bifurcations. This TRWSS serves as a new contribution to the hemodynamic environment favoring aneurysm formation and progression at wide cerebral bifurcations and may have clinical implications favoring interventions that reduce bifurcation angle.

Moments of Intra-Dome Velocity Distribution as Robust Predictors of Rupture Status in Cerebral Aneurysms.

BACKGROUND: Wall shear stress (WSS), the spatial gradient of flow velocity at luminal surface, has been employed for aneurysmal hemodynamic analysis, but it is sensitive to surface irregularities and noise. We devised a volumetric approach to evaluate discriminant power of intra-dome flow velocity distribution and modal analysis in rupture status determination compared with previously described WSS analysis. METHODS: Catheter three-dimensional rotational angiographic datasets matched for volume were segmented in 20 sidewall aneurysms (10 ruptured), computational fluid dynamics simulations were performed, and velocity distributions were extracted from mesh-independent isometric sampling followed by moment analysis (mean, variance, skewness, and kurtosis). Univariate and multivariate analysis was used to evaluate discriminant performance of velocity moments. Sensitivity of velocity moments and WSS was evaluated to bleb presence and surface irregularity using digital bleb removal and surface noise addition. RESULTS: Velocity moments of ruptured aneurysms showed higher skewness (2.45 ± 0.57 vs. 1.36 ± 0.82, P = 0.003) and kurtosis (11.83 ± 4.77 vs. 6.05 ± 4.65, P = 0.01) with lower mean (0.019 ± 0.01 vs. 0.038 ± 0.02, P = 0.03) compared with unruptured lesions; in multivariate modeling, skewness alone emerged as best predictor (area under the curve = 0.88). Bleb removal increased low WSS by 548%, and surface noise decreased it by 85.8% while having a smaller (<7%) effect on velocity skewness and kurtosis. CONCLUSIONS: High aneurysm dome flow velocity skewness and kurtosis suggest an exponential distribution in ruptured lesions, with high peaks at low velocities, consistent with areas of slow flow. In contrast to WSS-based techniques, this approach is robust against surface variations, with promising improved rupture status discriminant performance that requires further validation in expanded future studies.

Enhanced Radiomics for Prediction of Rupture Status in Cerebral Aneurysms.

BACKGROUND: Radiomics is a powerful tool for automatic extraction of morphological features, but when applied to cerebral aneurysms, it is inferior to established descriptors in classifying rupture status. We sought a strategy to recover neck orientation and parent vessel caliber to enhance Radiomics performance and facilitate its adoption for aneurysm risk stratification. METHODS: We analyzed 135 sidewall (32 ruptured) and 216 bifurcation (90 ruptured) aneurysms from three-dimensional rotational catheter angiography datasets. Clinical three-dimensional rotational catheter angiography defined in arbitrary orientation underwent affine transformations enabling aneurysm neck alignment to XY plane before analysis in PyRadiomics, facilitating automatic extraction of aneurysm height and width, previously not possible with random alignment. Additionally, parent vessel size was estimated from aneurysm location and incorporated into enhanced Radiomics (height, width, height/width, size ratio). Rupture status classification was compared across methodologies for 31 automatically computed conventional Radiomics, enhanced Radiomics, and established size/shape descriptors using univariate, multivariate, and area under the curve (AUC) statistics. RESULTS: Enhanced Radiomics-derived height/width and size ratio were significantly higher in both ruptured subsets. Using multivariate analysis in sidewall lesions, enhanced Radiomics (AUC = 0.85) matched established features (AUC = 0.86) and outperformed conventional Radiomics (AUC = 0.82); in bifurcation lesions, enhanced Radiomics (AUC = 0.78) outperformed both established features (AUC = 0.76) and conventional Radiomics (AUC = 0.74). CONCLUSIONS: Enhanced Radiomics incorporating neck orientation and parent vessel estimate is an efficient operator-independent methodology that offers superior rupture status classification for both sidewall and bifurcation aneurysms and should be considered a strong candidate for larger-scale multicenter and multimodality validation.

Performance of Radiomics derived morphological features for prediction of aneurysm rupture status.

BACKGROUND: Morphological differences between ruptured and unruptured cerebral aneurysms represent a focus of neuroimaging researchfor understanding the mechanisms of aneurysmal rupture. We evaluated the performance of Radiomics derived morphological features, recently proposed for rupture status classification, against automatically measured shape and size features previously established in the literature. METHODS: 353 aneurysms (123 ruptured) from three-dimensional rotational catheter angiography (3DRA) datasets were analyzed. Based on a literature review, 13 Radiomics and 13 established morphological descriptors were automatically extracted per aneurysm, and evaluated for rupture status prediction using univariate and multivariate statistical analysis, yielding an area under the curve (AUC) metric of the receiver operating characteristic. RESULTS: Validation of overlapping descriptors for size/volume using both methods were highly correlated (p<0.0001, R 2=0.99). Univariate analysis selected AspectRatio (p<0.0001, AUC=0.75), Non-sphericity Index (p<0.0001, AUC=0.75), Height/Width (p<0.0001, AUC=0.73), and SizeRatio (p<0.0001, AUC=0.73) as best among established descriptors, and Elongation (p<0.0001, AUC=0.71) and Flatness (p<0.0001, AUC=0.72) among Radiomics features. Radiomics Elongation correlated best with established Height/Width (R 2=0.52), whereas Radiomics Flatness correlated best with Ellipticity Index (R 2=0.54). Radiomics Sphericity correlated best with Undulation Index (R 2=0.65). Best Radiomics performers, Elongation and Flatness, were highly correlated descriptors (p<0.0001, R 2=0.75). In multivariate analysis, established descriptors (Height/Width, SizeRatio, Ellipticity Index; AUC=0.79) outperformed Radiomics features (Elongation, Maximum3Ddiameter; AUC=0.75). CONCLUSION: Although recently introduced Radiomics analysis for aneurysm shape and size evaluation has the advantage of being an efficient operator independent methodology, it currently offers inferior rupture status discriminant performance compared with established descriptors. Future research is needed to extend the current Radiomics feature set to better capture aneurysm shape information.

Increased focal internal carotid artery angulation in patients with posterior communicating artery aneurysms.

BACKGROUND: Aneurysms at the posterior communicating artery (PCOM) origin represent the most common location on the internal carotid artery (ICA), and are associated with greater recurrence following endovascular treatment. We evaluate the association between ICA angulation in three-dimensional (3D) space and PCOM aneurysmal development, using high-resolution 3D rotational angiography (3DRA) studies. METHODS: 3DRA datasets were evaluated in 70 patients with PCOM aneurysms, 31 non-aneurysmal contralateral, and 86 healthy controls (187 total). The local angle formed by upstream and downstream ICA segments at the PCOM origin, αICA@PCOM, was measured using 3DRA multiplanar reconstruction. Computational fluid dynamics (CFD) analysis was performed on parametric and patient-based models. RESULTS: αICA@PCOM was significantly larger in aneurysm-bearing ICA segments (68.14±11.91°) compared with non-aneurysmal contralateral (57.17±10.76°, p<0.001) and healthy controls (48.13±13.68°, p<0.001). A discriminant threshold αICA@PCOM value of 61° (87% specificity, 80% sensitivity) was established (area under the curve (AUC)=0.88). Ruptured PCOM aneurysms had a significantly larger αICA@PCOM compared to unruptured (72.65±15.16° vs 66.35±9.94°, p=0.04). In parametric and patient-based CFD analysis, a large αICA@PCOM induces high focal pressure at the PCOM origin, relatively low wall shear stress (WSS), and high proximal WSS spatial gradients (WSSG). CONCLUSION: ICA angulation at PCOM origin is significantly higher in vessels harboring PCOM aneurysms compared with contralateral and healthy ICAs. This sharper bend in the ICA leads to high focal pressure at the aneurysm neck, low focal WSS and high proximal WSSG. These findings underline the importance of morphological ICA variations and the likelihood of PCOM aneurysm, an association which can inform clinical decisions and may serve in predictive analytics.

Proximal Parent Vessel Tapering is Associated With Aneurysm at the Middle Cerebral Artery Bifurcation.

BACKGROUND: Cerebral aneurysm initiation and evolution have been linked to hemodynamic and morphological factors. Stenotic morphology upstream to a bifurcation can alter hemodynamic patterns and lead to destructive vessel wall remodeling and aneurysm initiation. The effect of more subtle proximal variations in vessel diameter on bifurcation aneurysm development has not been evaluated. OBJECTIVE: To investigate whether vessel tapering is associated with aneurysmal presence at the middle cerebral artery (MCA) bifurcation. METHODS: Bilateral catheter three-dimensional rotational angiographic datasets from 33 patients with unilateral unruptured MCA aneurysms and 44 datasets from healthy patients were analyzed. Equidistant cross-sectional cuts were generated along the MCA M1 segment with cross-sectional area measurement using edge-detection filtering. Relative tapering of the M1 segment was evaluated as the TaperingRatio. Computational fluid dynamics (CFD) simulations were performed on bilateral patient models and parametric MCAs of constant and tapered inflow vessel. RESULTS: MCA leading to aneurysms had significantly lower TaperingRatio (0.88 ± 0.15) compared to contralateral (1.00 ± 0.16, P = .002) and healthy MCAs (1.00 ± 0.15, P > .001, area under the curve = 0.73), which showed little to no tapering. CFD simulations showed that vessel tapering leads to flow acceleration with higher wall shear stress (WSS) and WSS gradients at the bifurcation apex. CONCLUSION: Aneurysmal but not contralateral or control MCA M1 segments demonstrate a previously undescribed progressive distal tapering phenomenon. This upstream vessel narrowing leads to flow acceleration that accentuates WSS and spatial gradients at the bifurcation apex, a pattern previously shown to favor aneurysm initiation and progression.

Induction of aneurysmogenic high positive wall shear stress gradient by wide angle at cerebral bifurcations, independent of flow rate.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cerebrovascular network registration via an efficient attributed graph matching technique.

Registration of vascular networks is an indispensable element of prognostic and diagnostic studies that require structural analysis and comparison over time, among different samples, and to a gold standard. However, vascular networks manifest low spatial texture and sparse structural content so that even small variations in their location can make the intensity-based registration inefficient and prone to errors. Motivated by geometrical graph-based models developed in our prior work, we use the shape information in the graph topology sense to enhance the registration performance. An efficient feature-based registration is presented that seeks correspondence of the bifurcations and branches in a graph matching scheme. Since the graph matching is originally posed a NP-hard quadratic assignment problem (QAP) in the literature, we have designed a node signature that incorporates edge correspondences indirectly. This allows removing the quadratic term in the QAP to recast the problem as a linear assignment problem (LAP) to relieve the computational burden. The LAP is efficiently solvable and is scalable to data with graph representation of larger size. The performance is tested and validated using clinical 3-D angiography images of the human cerebrovasculature as well as synthetic datasets. This method proves to be robust in the face of different structural and algorithm's parameters. Quality of inter-subject and multimodal matching of clinical data has also been confirmed.

Critical role of angiographic acquisition modality and reconstruction on morphometric and haemodynamic analysis of intracranial aneurysms.

BACKGROUND: Subtracted 3-D rotational angiography (3DRA) and cone-beam computed tomography angiography (CBCT-A) are often used in assessing cerebral aneurysm shape and haemodynamic profile. We sought to evaluate the effect of imaging modality, reconstruction parameters, and kernel selection on patient-derived aneurysm morphology and computational fluid dynamic (CFD) analysis to assess its potential contribution to inter-study variability. METHODS: Four patients (five aneurysms) underwent concurrent 3DRA followed by high-resolution CBCT-A. Six models were reconstructed per aneurysm: 3DRA reconstructed with 0.28 and 0.14 mm voxel sizes (large and small volume of interest (VOI) respectively), and two kernel types (normal/smooth). CBCT-A was reconstructed over small VOI using normal/sharp kernel. Maximal dome dimension, neck diameter and dome/neck ratio were evaluated in 3D. Wall shear stress (WSS) magnitude was evaluated on the entire aneurysm dome and in the 5% dome areas covered by lowest (LWSS) and highest (HWSS) WSS. Parameters were evaluated with pairwise t-test analysis. RESULTS: Smaller VOI reconstructions resulted in smaller Dmax (P value=0.03) and Dmax/neck (P value=0.006) and in larger LWSS (P value=0.03). Use of sharp kernel led to narrower neck (P value=0.04) and higher Dmax/neck values (P value=0.02). CBCT-A resulted in statistically different aneurysm shape (up to 24% difference) and haemodynamics (up to 97% difference) compared with 3DRA. CONCLUSION: The choice of catheter 3D angiographic modality and reconstruction kernel has a critical impact on derived aneurysm morphological and haemodynamic analysis. The resultant variability can confound and obscure underlying differences within patient populations and between studies performed at different centres using divergent techniques, compromising the accuracy of quantitative aneurysm analysis.

Proximal Stenosis Is Associated with Rupture Status in Middle Cerebral Artery Aneurysms.

BACKGROUND: Hemodynamic factors impact cerebral aneurysm development and progression. Parent vessel architectural features, such as caliber, curvature, and angle, can affect downstream pressure and shear stress. OBJECTIVE: To investigate the association between proximal parent vessel stenosis and aneurysm rupture status at the middle cerebral artery (MCA) bifurcation. METHODS: Catheter 3-dimensional rotational angiographic datasets from 69 Japanese patients with MCA aneurysms (58 unruptured/11 ruptured) were analyzed. The narrowest cross-sectional area of the M1 segment was evaluated through equidistant cross-sectional plane cuts along the M1 length. The degree of stenosis relative to M1 size (StenosisIndex) and the distance from stenosis to the aneurysm neck (StenosisAnDist) were statistically evaluated. The effects of StenosisIndex and StenosisAnDist were determined in parametric aneurysm models with/without stenosis using computational fluid dynamic and fluid-structure interaction simulations. RESULTS: MCA harboring ruptured aneurysms had significantly greater StenosisIndex (0.31 ± 0.21 vs. 0.17 ± 0.14, P = 0.01), indicative of greater narrowing, and shorter StenosisAnDist (4.26 ± 1.91 vs. 6.94 ± 4.06 mm, P = 0.02) compared with unruptured aneurysms. Multivariate analysis combining StenosisIndex and StenosisAnDist resulted in P = 0.003, area under the curve = 0.81 (80% sensitivity, 74% specificity). Computational fluid dynamic and fluid-structure interaction simulations identified a synergetic effect of high stenosis and short StenosisAnDist in inducing greater aneurysm inflow velocity and deeper jet penetration, greater dome pressure, and greater tensile stress in the aneurysm wall. CONCLUSIONS: Ruptured status in bifurcation MCA aneurysms was associated with severity of proximal M1 stenosis and its proximity to the aneurysm neck, a novel risk factor, which acts by increasing aneurysm dome wall tension, and should be considered in investigations of rupture risk stratification.

Benefit of cone-beam CT angiography in visualizing aneurysm shape and identification of exact rupture site.

While high-resolution cone-beam computational tomographic (CBCT) angiography has gained use in intracranial vascular imaging, digital subtraction angiography (DSA) and 3-dimensional-rotational angiography (3D-RA) remain the preferred acquisition modalities for intracranial aneurysm imaging. This case report highlights the utility of the greater spatial resolution afforded by CBCT for cerebral aneurysm imaging. A 54-year-old man presenting with subarachnoid hemorrhage was confirmed to harbor a ruptured anterior communicating artery aneurysm by conventional angiography. Due to varying contrast opacification captured by different acquisition methods, dramatic aneurysm shape difference was observed between 2- and 3-dimensional-angiographic and CBCT models. The greater resolution of CBCT revealed in an unequivocal fashion the exact site of rupture on the aneurysm dome, visualized as a discrete irregular and elongated bleb that was not seen on either 3D-RA or DSA. High-resolution CBCT visualized the shape of the target aneurysm in greater detail than the more conventional 2D-DSA and 3D-RA, enabling more precise computational fluid dynamics (CFD) simulations. Given that aneurysms most likely change shape either prior to rupture or upon rupture, future studies evaluating fluid dynamics using computer reconstructions should be cognizant of the differences in resolution provided by various imaging modalities.

Realistic non-Newtonian viscosity modelling highlights hemodynamic differences between intracranial aneurysms with and without surface blebs.

Most computational fluid dynamic (CFD) simulations of aneurysm hemodynamics assume constant (Newtonian) viscosity, even though blood demonstrates shear-thinning (non-Newtonian) behavior. We sought to evaluate the effect of this simplifying assumption on hemodynamic forces within cerebral aneurysms, especially in regions of low wall shear stress, which are associated with rupture. CFD analysis was performed for both viscosity models using 3D rotational angiography volumes obtained for 26 sidewall aneurysms (12 with blebs, 12 ruptured), and parametric models incorporating blebs at different locations (inflow/outflow zone). Mean and lowest 5% values of time averaged wall shear stress (TAWSS) computed over the dome were compared using Wilcoxon rank-sum test. Newtonian modeling not only resulted in higher aneurysmal TAWSS, specifically in areas of low flow and blebs, but also showed no difference between aneurysms with or without blebs. In contrast, for non-Newtonian analysis, bleb-bearing aneurysms showed significantly lower 5% TAWSS compared to those without (p=0.005), despite no significant difference in mean dome TAWSS (p=0.32). Non-Newtonian modeling also accentuated the differences in dome TAWSS between ruptured and unruptured aneurysms (p<0.001). Parametric models further confirmed that realistic non-Newtonian viscosity resulted in lower bleb TAWSS and higher focal viscosity, especially when located in the outflow zone. The results show that adopting shear-thinning non-Newtonian blood viscosity in CFD simulations of intracranial aneurysms uncovered hemodynamic differences induced by bleb presence on aneurysmal surfaces, and significantly improved discriminant statistics used in risk stratification. These findings underline the possible implications of using a realistic model of blood viscosity in predictive computational hemodynamics.

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.

Curvature effect on hemodynamic conditions at the inner bend of the carotid siphon and its relation to aneurysm formation.

Although high-impact hemodynamic forces are thought to lead to cerebral aneurysmal change, little is known about the aneurysm formation on the inner aspect of vascular bends such as the internal carotid artery (ICA) siphon where wall shear stress (WSS) is expected to be low. This study evaluates the effect of vessel curvature and hemodynamics on aneurysm formation along the inner carotid siphon. Catheter 3D-rotational angiographic volumes of 35 ICA (10 aneurysms, 25 controls) were evaluated in 3D for radius of curvature and peak curvature of the siphon bend, followed by univariate statistical analysis. Computational fluid dynamic (CFD) simulations were performed on patient-derived models after aneurysm removal and on synthetic variants of increasing curvature. Peak focal siphon curvature was significantly higher in aneurysm bearing ICAs (0.36 ± 0.045 vs. 0.30 ± 0.048 mm(-1), p=0.003), with no difference in global radius of curvature (p=0.36). In CFD simulations, increasing parametric curvature tightness (from 5 to 3mm radius) resulted in dramatic increase of WSS and WSS gradient magnitude (WSSG) on the inner wall of the bend. In patient-derived data, the location of aneurysms coincided with regions of low WSS (<4 Pa) flanked by high WSS and WSSG peaks. WSS peaks correlated with the aneurysm neck. In contrast, control siphon bends displayed low, almost constant, WSS and WSSG profiles with little spatial variation. High bend curvature induces dynamically fluctuating high proximal WSS and WSSG followed by regions of flow stasis and recirculation, leading to local conditions known to induce destructive vessel wall remodeling and aneurysmal initiation.

Superior performance of cone-beam CT angiography in characterization of intracranial atherosclerosis.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Benefit of a sharp computed tomography angiography reconstruction kernel for improved characterization of intracranial aneurysms.

BACKGROUND: Computed tomography angiography (CTA) is the first-line imaging modality used for cerebral aneurysms because of its speed and sensitivity for detection, although digital subtraction angiography is often required for more detailed aneurysm shape delineation. OBJECTIVE: To determine whether a sharper CTA reconstruction kernel can better characterize an aneurysm and improve decision-making before intervention. METHODS: Fifteen patients presenting with aneurysmal subarachnoid hemorrhage underwent 64-row CTA. CTA data were reconstructed using the default H20f smooth kernel and a H60f sharp kernel and compared with contemporaneous catheter 3-dimensional rotational angiography (3DRA). Aneurysm neck, width, and aspect ratio measurements were made using intensity line plots of identical projections on all imaging datasets and compared by matched-pair statistics. RESULTS: Aneurysm neck measurements from the H20f smooth kernel revealed overestimation compared with both the sharp kernel (greater by 0.64 ± 0.21 mm, P < .01) and 3DRA (greater by 0.68 ± 0.19 mm, P < .01). There was no statistically significant difference between 3DRA and the sharp kernel CTA measurements. Neck measurements correlated well between the H60f kernel and 3DRA but not between the H20f Kernel and 3DRA (R 0.97 vs 0.86). CONCLUSION: H60f sharp CTA kernel reconstruction provides more accurate anatomic characterization of cerebral aneurysms than the H20f smooth kernel at the expense of less visually pleasing reconstructions. Because it does not require additional contrast, radiation, or imaging hardware and is more similar to 3DRA, it may aid in selecting the appropriate treatment strategy before to evaluation by catheter-based angiography.