Markus Tremmel

Hemodynamic–Morphologic Discriminants for Intracranial Aneurysm Rupture

Background and Purpose— The purpose of this study was to identify significant morphological and hemodynamic parameters that discriminate intracranial aneurysm rupture status using 3-dimensional angiography and computational fluid dynamics. Methods— One hundred nineteen intracranial aneurysms (38 ruptured, 81 unruptured) were analyzed from 3-dimensional angiographic images and computational fluid dynamics. Six morphological and 7 hemodynamic parameters were evaluated for significance with respect to rupture. Receiver operating characteristic analysis identified area under the curve (AUC) and optimal thresholds separating ruptured from unruptured aneurysms for each parameter. Significant parameters were examined by multivariate logistic regression analysis in 3 predictive models—morphology only, hemodynamics only, and combined—to identify independent discriminants, and the AUC receiver operating characteristic of the predicted probability of rupture status was compared among these models. Results— Morphological parameters (size ratio, undulation index, ellipticity index, and nonsphericity index) and hemodynamic parameters (average wall shear stress [WSS], maximum intra-aneurysmal WSS, low WSS area, average oscillatory shear index, number of vortices, and relative resident time) achieved statistical significance (P<0.01). Multivariate logistic regression analysis demonstrated size ratio to be the only independently significant factor in the morphology model (AUC, 0.83; 95% CI, 0.75 to 0.91), whereas WSS and oscillatory shear index were the only independently significant variables in the hemodynamics model (AUC, 0.85; 95% CI, 0.78 to 0.93). The combined model retained all 3 variables, size ratio, WSS, and oscillatory shear index (AUC, 0.89; 95% CI, 0.82 to 0.96). Conclusion— All 3 models—morphological (based on size ratio), hemodynamic (based on WSS and oscillatory shear index), and combined—discriminate intracranial aneurysm rupture status with high AUC values. Hemodynamics is as important as morphology in discriminating aneurysm rupture status.

Morphology parameters for intracranial aneurysm rupture risk assessment.

OBJECTIVEThe aim of this study is to identify image-based morphological parameters that correlate with human intracranial aneurysm (IA) rupture. METHODSFor 45 patients with terminal or sidewall saccular IAs (25 unruptured, 20 ruptured), three-dimensional geometries were evaluated for a range of morphological parameters. In addition to five previously studied parameters (aspect ratio, aneurysm size, ellipticity index, nonsphericity index, and undulation index), we defined three novel parameters incorporating the parent vessel geometry (vessel angle, aneurysm [inclination] angle, and [aneurysm-to-vessel] size ratio) and explored their correlation with aneurysm rupture. Parameters were analyzed with a two-tailed independent Students t test for significance; significant parameters (P < 0.05) were further examined by multivariate logistic regression analysis. Additionally, receiver operating characteristic analyses were performed on each parameter. RESULTSStatistically significant differences were found between mean values in ruptured and unruptured groups for size ratio, undulation index, nonsphericity index, ellipticity index, aneurysm angle, and aspect ratio. Logistic regression analysis further revealed that size ratio (odds ratio, 1.41; 95% confidence interval, 1.03–1.92) and undulation index (odds ratio, 1.51; 95% confidence interval, 1.08–2.11) had the strongest independent correlation with ruptured IA. From the receiver operating characteristic analysis, size ratio and aneurysm angle had the highest area under the curve values of 0.83 and 0.85, respectively. CONCLUSIONSize ratio and aneurysm angle are promising new morphological metrics for IA rupture risk assessment. Because these parameters account for vessel geometry, they may bridge the gap between morphological studies and more qualitative location-based studies.

Comparison of Two Stents in Modifying Cerebral Aneurysm Hemodynamics

There is a general lack of quantitative understanding about how specific design features of endovascular stents (struts and mesh design, porosity) affect the hemodynamics in intracranial aneurysms. To shed light on this issue, we studied two commercial high-porosity stents (Tristar stent™ and Wallstent®) in aneurysm models of varying vessel curvature as well as in a patient-specific model using Computational Fluid Dynamics. We investigated how these stents modify hemodynamic parameters such as aneurysmal inflow rate, stasis, and wall shear stress, and how such changes are related to the specific designs. We found that the flow damping effect of stents and resulting aneurysmal stasis and wall shear stress are strongly influenced by stent porosity, strut design, and mesh hole shape. We also confirmed that the damping effect is significantly reduced at higher vessel curvatures, which indicates limited usefulness of high-porosity stents as a stand-alone treatment. Finally, we showed that the stasis-inducing performance of stents in 3D geometries can be predicted from the hydraulic resistance of their flat mesh screens. From this, we propose a methodology to cost-effectively compare different stent designs before running a full 3D simulation.

Characterization of Critical Hemodynamics Contributing to Aneurysmal Remodeling at the Basilar Terminus in a Rabbit Model

Background and Purpose— Hemodynamic insult by bilateral common carotid artery ligation has been shown to induce aneurysmal remodeling at the basilar terminus in a rabbit model. To characterize critical hemodynamics that initiate this remodeling, we applied a novel hemodynamics–histology comapping technique. Methods— Eight rabbits received bilateral common carotid artery ligation to increase basilar artery flow. Three underwent sham operations. Hemodynamic insult at the basilar terminus was assessed by computational fluid dynamics. Bifurcation tissue was harvested on day 5; histology was comapped with initial postligation hemodynamic fields of wall shear stress (WSS) and WSS gradient. Results— All bifurcations showed internal elastic lamina loss in periapical regions exposed to accelerating flow with high WSS and positive WSS gradient. Internal elastic lamina damage happened 100% of the time at locations where WSS was >122 Pa and WSS gradient was >530 Pa/mm. The degree of destructive remodeling accounting for internal elastic lamina loss, medial thinning, and luminal bulging correlated with the magnitude of the hemodynamic insult. Conclusions— Aneurysmal remodeling initiates when local hemodynamic forces exceed specific limits at the rabbit basilar terminus. A combination of high WSS and positive WSS gradient represents dangerous hemodynamics likely to induce aneurysmal remodeling.

Influence of Intracranial Aneurysm-to-Parent Vessel Size Ratio on Hemodynamics and Implication for Rupture: Results from a Virtual Experimental Study

OBJECTIVEThe effectiveness of intracranial aneurysm (IA) size as a predictor for rupture has been debated. We recently performed a retrospective analysis of IA morphology and found that a new index, namely, aneurysm-to-parent vessel size ratio (SR), was strongly correlated with IA rupture, with 77% of ruptured IAs showing an SR of more than 2, and 83% of unruptured IAs showing an SR of 2 or less. As hemodynamics have been implicated in both IA development and rupture, we examine how varying SR influences intra-aneurysmal hemodynamics. METHODSOne sidewall and 1 terminal IA were virtually reconstructed from patient 3-dimensional angiographic images. In 2 independent in silico experiments, the SR was varied from 1.0 to 3.5 by virtually changing either aneurysm size or vessel diameter while keeping the other parameter constant. Pulsatile computational fluid dynamics simulations were performed on each model for hemodynamics analysis. RESULTSLow SR (≤2) aneurysm morphology consistently demonstrated simple flow patterns with a single intra-aneurysmal vortex, whereas higher SR (>2) aneurysm morphology presented multiple vortices and complex flow patterns. The aneurysm luminal area that was exposed to low wall shear stress increased with increasing SR. Complex flow, multiple vortices, and low aneurysmal wall shear stress have been associated with ruptured IAs in previous studies. CONCLUSIONHigher SR, irrespective of aneurysm type and absolute aneurysm or vessel size, gives rise to flow patterns typically observed in ruptured IAs. These results provide hemodynamic support for the existing correlation of SR with rupture risk.

Newtonian viscosity model could overestimate wall shear stress in intracranial aneurysm domes and underestimate rupture risk

Objective Computational fluid dynamics (CFD) simulations of intracranial aneurysm hemodynamics usually adopt the simplification of the Newtonian blood rheology model. A study was undertaken to examine whether such a model affects the predicted hemodynamics in realistic intracranial aneurysm geometries. Methods Pulsatile CFD simulations were carried out using the Newtonian viscosity model and two non-Newtonian models (Casson and Herschel-Bulkley) in three typical internal carotid artery saccular aneurysms (A, sidewall, oblong-shaped with a daughter sac; B, sidewall, quasi-spherical; C, near-spherical bifurcation). For each aneurysm model the surface distributions of shear rate, blood viscosity and wall shear stress (WSS) predicted by the three rheology models were compared. Results All three rheology models produced similar intra-aneurysmal flow patterns: aneurysm A had a slowly recirculating secondary vortex near the dome whereas aneurysms B and C contained only a large single vortex. All models predicted similar shear rate, blood viscosity and WSS in parent vessels of all aneurysms and in the sacs of B and C. However, large discrepancies in shear rate, viscosity and WSS among predictions by the various rheology models were found in the dome area of A where the flow was relatively stagnant. Here the Newtonian model predicted higher shear rate and WSS values and lower blood viscosity than the two non-Newtonian models. Conclusions The Newtonian fluid assumption can underestimate viscosity and overestimate shear rate and WSS in regions of stasis or slowly recirculating secondary vortices, typically found at the dome in elongated or complex-shaped saccular aneurysms as well as in aneurysms following endovascular treatment. Because low shear rates and low WSS in such flow conditions indicate a high propensity for thrombus formation and rupture, CFD based on the Newtonian assumption may underestimate the propensity of these events.

In vivo assessment of rapid cerebrovascular morphological adaptation following acute blood flow increase

OBJECT Pathological extremes in cerebrovascular remodeling may contribute to basilar artery (BA) dolichoectasia and fusiform aneurysm development. Factors regulating cerebrovascular remodeling are poorly understood. To better understand hemodynamic influences on cerebrovascular remodeling, we examined BA remodeling following common carotid artery (CCA) ligation in an animal model. METHODS Rabbits were subjected to sham surgery (3 animals), unilateral CCA ligation (3 animals), or bilateral CCA ligation (5 animals). Transcranial Doppler ultrasonography and rotational angiography were used to compute BA flow, diameter, wall shear stress (WSS), and a tortuosity index on Days 0, 1, 4, 7, 14, 28, 56, and 84. Basilar artery tissues were stained and analyzed at Day 84. Statistical analysis was performed using orthogonal contrast analysis, repeated measures analysis of variance, or mixed regression analysis of repeated measures. Statistical significance was defined as a probability value < 0.05. RESULTS Basilar artery flow and diameter increased significantly after the procedure in both ligation groups, but only the bilateral CCA ligation group demonstrated significant differences between groups. Wall shear stress significantly increased only in animals in the bilateral CCA ligation group and returned to baseline by Day 28, with 52% of WSS correction occurring by Day 7. Only the bilateral CCA ligation group developed significant BA tortuosity, occurring within 7 days postligation. Unlike the animals in the sham and unilateral CCA ligation groups, the animals in the bilateral CCA ligation group had histological staining results showing a substantial internal elastic lamina fragmentation. CONCLUSIONS Increased BA flow results in adaptive BA remodeling until WSS returns to physiological baseline levels. Morphological changes occur rapidly following flow alteration and do not require chronic insult to affect substantial and significant structural transformation. Additionally, it appears that there exists a flow-increase threshold that, when surpassed, results in significant tortuosity.

Size ratio for clinical assessment of intracranial aneurysm rupture risk

Abstract Objectives: We previously used three-dimensional (3D) volumetric analysis to identify a novel intracranial aneurysm (IA) morphological metric, aneurysm-to-parent vessel size ratio (SR), which strongly correlated with aneurysm rupture. However, complex 3D analysis is not easily obtained, and ubiquitous IA risk assessment is traditionally performed with two-dimensional (2D) imaging, typically with size being the sole considered morphometric. Because only easily applicable 2D measurements will be of clinical value, we sought to investigate the correlation of SR determined from 2D angiography with IA rupture status. Methods: SR and traditional aspect ratio (AR) and aneurysm size parameters were measured in a retrospective cohort of 38 IA cases (16 ruptured) with 2D rotational angiographic images. These parameters were analysed for correlation with IA rupture status. Students t-test or Wilcoxon rank-sum test was used for normally or non-normally distributed data respectively. Logistic regression was performed for independently statistically significant parameters to generate an effect size estimate (odds ratio). Area-under-the-curve (AUC) calculated from the receiver-operating-characteristic curve was additionally obtained for each index to describe differentiating capabilities. Results: Only SR achieved statistical significance (p=0·05) in Wilcoxon rank-sum test. Logistic regression generated an SR odds ratio of 3·52 (p=0·04; 95% confidence interval: 1·035–11·938) for every doubling of SR value. The AUC value of SR (0·688) was higher than that of AR (0·642) and size (0·585). Conclusions: SR had the strongest correlation with IA rupture and was demonstrated to be a valuable parameter in 2D, where it can be easily obtained from angiographic images. When eventually evaluated in a prospective data set, SR may prove to be an important tool for aneurysm rupture-risk assessment.

High Wall Shear Stress and Positive Wall Shear Stress Gradient Trigger the Initiation of Intracranial Aneurysms

While the pathogenesis of an intracranial aneurysm (IA) is poorly understood, it has been generally postulated to be related to hemodynamic insult. IAs are predominantly located at apices of arterial bifurcations or outer curves on or near the Circle of Willis, suggesting a potential role of the specific hemodynamics at such locations characterized by high wall shear stress (WSS). Clinically, new IA formation has been observed following local flow increase.Copyright

Role of Hemodynamics in Initiation of Aneurysmal Remodeling

Hemodynamic insult has long been speculated to be a key factor in intracranial aneurysm (IA) formation,1 but the specifics of hemodynamic insult contributing to this process are not understood. Despite other risk factors, IAs are predominantly found at locations associated with unique hemodynamic stress such as at the apices of arterial bifurcations or outer curves, prominent in high wall shear stress (WSS) and wall shear stress gradients (WSSG).2 Furthermore, it appears that increased flow at these locations is required to trigger the initiation of aneurysmal remodeling.3 We have previously shown that increasing flow in the rabbit basilar artery (BA), secondary to common carotid artery (CCA) ligation, resulted in nascent aneurysm development at the basilar terminus (BT).4 However, it is unclear if certain hemodynamic stress thresholds must be exceeded to trigger aneurysmal remodeling, and whether sustained insult is necessary.Copyright