Biomechanical wall properties of human intracranial aneurysms resected following surgical clipping (IRRAs Project)

Background and purposeIndividual rupture risk assessment of intracranial aneurysms is a major issue in the clinical management of asymptomatic aneurysms. Aneurysm rupture occurs when wall tension exceeds the strength limit of the wall tissue. At present, aneurysmal wall mechanics are poorly understood and thus, risk assessment involving mechanical properties is inexistent. Aneurysm computational hemodynamics studies make the assumption of rigid walls, an arguable simplification. We therefore aim to assess mechanical properties of ruptured and unruptured intracranial aneurysms in order to provide the foundation for future patient-specific aneurysmal risk assessment. This work also challenges some of the currently held hypotheses in computational flow hemodynamics research.MethodsA specific conservation protocol was applied to aneurysmal tissues following clipping and resection in order to preserve their mechanical properties. Sixteen intracranial aneurysms (11 female, 5 male) underwent mechanical uniaxial stress tests under physiological conditions, temperature, and saline isotonic solution. These represented 11 unruptured and 5 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a 3-parameter (C₁₀, C₀₁, C₁₁) Mooney–Rivlin hyperelastic model. Each aneurysm was classified according to its biomechanical properties and (un)rupture status.ResultsTissue testing demonstrated three main tissue classes: Soft, Rigid, and Intermediate. All unruptured aneurysms presented a more Rigid tissue than ruptured or pre-ruptured aneurysms within each gender subgroup. Wall thickness was not correlated to aneurysmal status (ruptured/unruptured). An Intermediate subgroup of unruptured aneurysms with softer tissue characteristic was identified and correlated with multiple documented risk factors of rupture.ConclusionThere is a significant modification in biomechanical properties between ruptured aneurysm, presenting a soft tissue and unruptured aneurysms, presenting a rigid material. This finding strongly supports the idea that a biomechanical risk factor based assessment should be utilized in the to improve the therapeutic decision making.     

Nonlinear anisotropic stress analysis of anatomically realistic cerebral aneurysms

BACKGROUND: Static deformation analysis and estimation of wall stress distribution of patient-specific cerebral aneurysms can provide useful insights into the disease process and rupture. METHOD OF APPROACH: The three-dimensional geometry of saccular cerebral aneurysms from 27 patients (18 unruptured and nine ruptured) was reconstructed based on computer tomography angiography images. The aneurysm wall tissue was modeled using a nonlinear, anisotropic, hyperelastic material model (Fung-type) which was incorporated in a user subroutine in ABAQUS. Effective material fiber orientations were assumed to align with principal surface curvatures. Static deformation of the aneurysm models were simulated assuming uniform wall thickness and internal pressure load of 100 mm Hg. RESULTS: The numerical analysis technique was validated by quantitative comparisons to results in the literature. For the patient-specific models, in-plane stresses in the aneurysm wall along both the stiff and weak fiber directions showed significant regional variations with the former being higher. The spatial maximum of stress ranged from as low as 0.30 MPa in a small aneurysm to as high as 1.06 MPa in a giant aneurysm. The patterns of distribution of stress, strain, and surface curvature were found to be similar. Sensitivity analyses showed that the computed stress is mesh independent and not very sensitive to reasonable perturbations in model parameters, and the curvature-based criteria for fiber orientations tend to minimize the total elastic strain energy in the aneurysms wall. Within this small study population, there were no statistically significant differences in the spatial means and maximums of stress and strain values between the ruptured and unruptured groups. However, the ratios between the stress components in the stiff and weak fiber directions were significantly higher in the ruptured group than those in the unruptured group. CONCLUSIONS: A methodology for nonlinear, anisotropic static deformation analysis of geometrically realistic aneurysms was developed, which can be used for a more accurate estimation of the stresses and strains than previous methods and to facilitate prospective studies on the role of stress in aneurysm rupture.     

Further evidence for the dynamic stability of intracranial saccular aneurysms

It has long been thought that intracranial saccular aneurysms enlarge and rupture because of mechanical instabilities. Recent nonlinear analyses suggest, however, that at least certain sub-classes of aneurysms do not exhibit quasi-static limit point instabilities or dynamic instabilities in response to periodic loading, and consequently, that the natural history of these lesions is likely governed by growth and remodeling processes. In this paper, we present additional results that support the finding that one particular sub-class of saccular aneurysms is dynamically stable. Specifically, we extended recent results of Shah and Humphrey, which are based on the assumption that some saccular aneurysms can be modeled as spherical elastic membranes surrounded by a viscous cerebrospinal fluid, to account for a viscohyperelastic behavior of the aneurysm. It is shown that inclusion of a "short-term" viscoelastic contribution to the mechanical behavior of an aneurysm serves to increase its dynamic stability against various disturbances.     

Morphological and Hemodynamic Discriminators for Rupture Status in Posterior Communicating Artery Aneurysms

Background and Purpose

The conflicting findings of previous morphological and hemodynamic studies on intracranial aneurysm rupture may be caused by the relatively small sample sizes and the variation in location of the patient-specific aneurysm models. We aimed to determine the discriminators for aneurysm rupture status by focusing on only posterior communicating artery (PCoA) aneurysms.

Materials and Methods

In 129 PCoA aneurysms (85 ruptured, 44 unruptured), clinical, morphological and hemodynamic characteristics were compared between the ruptured and unruptured cases. Multivariate logistic regression analysis was performed to determine the discriminators for rupture status of PCoA aneurysms.

Results

While univariate analyses showed that the size of aneurysm dome, aspect ratio (AR), size ratio (SR), dome-to-neck ratio (DN), inflow angle (IA), normalized wall shear stress (NWSS) and percentage of low wall shear stress area (LSA) were significantly associated with PCoA aneurysm rupture status. With multivariate analyses, significance was only retained for higher IA (OR = 1.539, p < 0.001) and LSA (OR = 1.393, p = 0.041).

Conclusions

Hemodynamics and morphology were related to rupture status of intracranial aneurysms. Higher IA and LSA were identified as discriminators for rupture status of PCoA aneurysms.     

Flow instability detected in ruptured versus unruptured cerebral aneurysms at the internal carotid artery

Flow instability has emerged as a new hemodynamic metric hypothesized to have potential value in assessing the rupture risk of cerebral aneurysms. However, diverse findings have been reported in the literature. In the present study, high-resolution hemodynamic simulations were performed retrospectively on 35 aneurysms (10 ruptured & 25 unruptured) located at the internal carotid artery (ICA). Simulated hemodynamic parameters were statistically compared between the ruptured and unruptured aneurysms, with emphasis on examining the correlation of flow instability with the status of aneurysm rupture. Pronounced flow instability was detected in 20% (2 out of 10) of the ruptured aneurysms, whereas in 44% (11 out of 25) of the unruptured aneurysms. Statistically, the flow instability metric (quantified by the temporally and spatially averaged fluctuating kinetic energy over the aneurysm sac) did not differ significantly between the ruptured and unruptured aneurysms. In contrast, low wall shear stress area (LSA) and pressure loss coefficient (PLC) exhibited significant correlations with the status of aneurysm rupture. In conclusion, the present study suggests that the presence of flow instability may not correlate closely with the status of aneurysm rupture, at least for ICA aneurysms. On the other hand, the retrospective nature of the study and the small sample size may have to some extent compromised the reliability of the conclusion, and therefore large-scale prospective studies would be needed to further address the issue.     

Correlation Between the Rupture Risk and 3D Geometric Parameters of Saccular Intracranial Aneurysms

The purpose of this study is to evaluate the association of the location and geometric parameters of intracranial aneurysm with the risk of rupture. A retrospective study consisted of 284 patients diagnosed with saccular intracranial aneurysm between January 2009 and May 2013 at Wuxi Third People’s Hospital was conducted. 3D digital subtraction angiography images from all patients (240 ruptured, 44 unruptured) were obtained and analyzed. The location of the aneurysms and the 3D geometric parameters including the aneurysm depth, the neck size, diameter of the parent artery, aneurysm angle, aspect radio, size ratio, and the neck-to-parent-artery ratio (NPR) were compared between ruptured and unruptured groups. Results: In ruptured group, anterior communicating artery, posterior communicating artery (PCoA), and the bifurcation of internal carotid artery (ICA) were the top three locations for aneurysm occurrence, accounting for 40.00, 30.42, and 12.08 % respectively. While in the unruptured group, top three locations were PCoA (36.36 %), posterior cerebral circulation (18.18 %), and the bifurcation of the ICA (15.91 %). Distribution of aneurysm location is significantly different (p < 0.05) between ruptured and unruptured aneurysms. For the 3D geometric parameters characterizing aneurysm, aneurysm depth (p < 0.05), parent artery diameter (p < 0.05), aneurysm angle (p < 0.01), aspect ratio (p < 0.01), and size ratio (p < 0.01) all showed a significant difference between ruptured and unruptured group. No difference was found in the neck size and the NPR ratio between the two groups. 3D geometric parameters such as aneurysm depth, parent artery diameter, aneurysm angle, aspect ratio, and size ratio can be helpful in evaluating the rupture risk of saccular intracranial aneurysm for a better prevention and prognosis.     

Growth rate and rupture rate of unruptured intracranial aneurysms: a population approach

Background  

Understanding aneurysm growth rate allows us to predict not only the current rupture risk, but also accumulated rupture risk in the future. However, determining growth rate of unruptured intracranial aneurysms often requires follow-up of patients for a long period of time so that significant growth can be observed and measured. We investigate a relationship between growth rate and rupture rate and develop a theoretical model that can predict average behavior of unruptured intracranial aneurysms based on existing clinical data.     

Hemodynamic stress in lateral saccular aneurysms

The flow velocities in glass and silastic lateral aneurysm models were quantitatively measured with the non-invasive laser Doppler method. The influences of the elasticity of the wall, the pulse wave and the properties of the perfusion medium on the intra-aneurysmal circulation were investigated. As shown previously, the inflow into the aneurysm arose from the downstream lip and was directed toward the center of the fundus. Backflow to the parent vessel took place along the walls of the fundus. With non-pulsatile perfusion, flow velocities in the center of the standardized aneurysms varied between 0.4 and 2% of the maximum velocity in the parent vessel. With pulsatile perfusion, flow velocities in the center of the fundus ranged between 8 and 13% of the flow velocity in the axis of the parent vessel. Flow velocities in the aneurysms were slower with a polymer suspension with blood-like properties compared to a glycerol/water solution. Flow velocity measurements near the aneurysmal wall allowed the estimation of the shear stresses at critical locations. The maximum shear stresses at the downstream lip of the aneurysm were in the range of the stresses measured at the flow divider of an arterial bifurcation. The present results suggest that in human saccular aneurysms intra-aneurysmal flow and shear stress on the wall are directly related to the pulsatility of perfusion, i.e. the systolic/diastolic pressure difference and that the tendency to spontaneous thrombosis depends on the viscoelastic properties of the blood, namely the hematocrit.     

An approach to quantitative assessment of hemodynamic differences between unruptured and ruptured ophthalmic artery aneurysms

Background and purpose: Hemodynamic parameters are important in the pathogenesis, evolution and rupture of intracranial aneurysm. Energy loss (EL) has been applied for the rupture risk prediction of artery aneurysms recently. We proposed a new EL and further investigate its effects on the rupture of aneurysms. Materials and methods: Sixty-four patient-specific ophthalmic aneurysm datasets were divided into ruptured and unruptured groups based on their clinical history. Based on patient-specific 3D-DSA data, realistic models were retrospectively reconstructed and then analyzed by using computational fluid dynamic method. Results: The flow field feature EL in ruptured cases was significantly higher than that in unruptured cases. The average wall shear stress (WSS) and the maximum WSS in ruptured cases were higher than those in unruptured cases. Modified pressure loss coefficient (PLC_M) in ruptured cases was slight higher than that in unruptured cases but the difference has no statistical significance. Multivariate logistic regression analysis demonstrated flow field feature EL (p < 0.05) and the maximum WSS (p < 0.05) were the only independently significant variables to predict rupture of ophthalmic aneurysm. There were no differences in PLC_M, the maximum oscillatory shear index (OSI), the average OSI and AR between the two groups. Conclusion: Flow field feature EL may be a reliable factor to predict the rupture risk of aneurysms.     

Parameterization of the shape of intracranial saccular aneurysms using Legendre polynomials

Our recent studies of the nonlinear mechanics of saccular aneurysms suggest that it is unlikely that these lesions enlarge or rupture via material (limit point) or dynamic (resonance) instabilities. Rather, there is a growing body of evidence from both vascular biology and biomechanical analyses that implicate mechanosensitive growth and remodeling processes. There is, therefore, a pressing need to quantify regional multiaxial wall stresses which, because of the membrane-like behavior of many aneurysms, necessitates better information on the applied loads and regional surface curvatures. Herein, we present and illustrate a method whereby regional curvatures can be estimated easily for sub-classes of human aneurysms based on clinically available data from magnetic resonance angiography (MRA). Whereas Legendre polynomials are used to illustrate this approach, different functions may prove useful for different sub-classes of lesions.     

Finite strain elastodynamics of intracranial saccular aneurysms.

Various investigators suggest that intracranial saccular aneurysms are dynamically unstable, that they resonate in response to pulsatile blood flow. This hypothesis is based on linearized analyses or experiments on rubber "models", however, and there is a need for a more critical examination. Toward this end, we (a) derive a new nonlinear equation of motion for a pulsating spherical aneurysm that is surrounded by cerebral spinal fluid and whose behavior is described by a Fung-type pseudostrain-energy function that fits data on human lesions, and (b) use methods of nonlinear dynamics to examine the stability of such lesions against perturbations to both in vivo and in vitro conditions. The numerical results suggest that this sub-class of lesions is dynamically stable. Moreover, with the exception of transients associated with initial perturbations, inertial effects appear to be insignificant for fundamental forcing frequencies less than 10 Hz and hence for typical physiologic and laboratory conditions. We submit, therefore, that further study of the mechanics of saccular aneurysms should be focused on quasi-static stress analyses that investigate the roles of lesion geometry and material properties, including growth and remodeling.     

Influence of morphology and hemodynamic factors on rupture of multiple intracranial aneurysms: matched-pairs of ruptured-unruptured aneurysms located unilaterally on the anterior circulation

Background

The authors evaluated the impact of morphological and hemodynamic factors on the rupture of matched-pairs of ruptured-unruptured intracranial aneurysms on one patient’s ipsilateral anterior circulation with 3D reconstruction model and computational fluid dynamic method simulation.

Methods

20 patients with intracranial aneurysms pairs on the same-side of anterior circulation but with different rupture status were retrospectively collected. Each pair was divided into ruptured-unruptured group. Patient-specific models based on their 3D-DSA images were constructed and analyzed. The relative locations, morphologic and hemodynamic factors of these two groups were compared.

Results

There was no significant difference in the relative bleeding location. The morphological factors analysis found that the ruptured aneurysms more often had irregular shape and had significantly higher maximum height and aspect ratio. The hemodynamic factors analysis found lower minimum wall shear stress (WSSmin) and more low-wall shear stress-area (LSA) in the ruptured aneurysms than that of the unruptured ones. The ruptured aneurysms more often had WSSmin on the dome.

Conclusions

Intracranial aneurysms pairs with different rupture status on unilateral side of anterior circulation may be a good disease model to investigate possible characteristics linked to rupture independent of patient characteristics. Irregular shape, larger size, higher aspect ratio, lower WSSmin and more LSA may indicate a higher risk for their rupture.

     

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.     

Posterior Cerebral Artery Angle and the Rupture of Basilar Tip Aneurysms

Since the initial publication of the International Study of Unruptured Intracranial Aneurysms (ISUIA), management of unruptured intracranial aneurysms has been mainly based on the size of the aneurysm. The contribution of morphological characteristics to treatment decisions of unruptured aneurysms has not been well studied in a systematic and location specific manner. We present a large sample of basilar artery tip aneurysms (BTA) that were assessed using a diverse array of morphological variables to determine the parameters associated with ruptured aneurysms. Demographic and clinical risk factors of aneurysm rupture were obtained from chart review. CT angiograms (CTA) were evaluated with Slicer, an open source visualization and image analysis software, to generate 3-D models of the aneurysms and surrounding vascular architecture. Morphological parameters examined in each model included aneurysm volume, aspect ratio, size ratio, aneurysm angle, basilar vessel angle, basilar flow angle, and vessel to vessel angles. Univariate and multivariate analyses were performed to determine statistical significance. From 2008–2013, 54 patients with BTA aneurysms were evaluated in a single institution, and CTAs from 33 patients (15 ruptured, 18 unruptured) were available and analyzed. Aneurysms that underwent reoperation, that were associated with arteriovenous malformations, or that lacked preoperative CTA were excluded. Multivariate logistic regression revealed that a larger angle between the posterior cerebral arteries (P1-P1 angle, p = 0.037) was most strongly associated with aneurysm rupture after adjusting for other morphological variables. In this location specific study of BTA aneurysms, the larger the angle formed between posterior cerebral arteries was found to be a new morphological parameter significantly associated with ruptured BTA aneurysms. This is a physically intuitive parameter that can be measured easily and readily applied in the clinical setting.     

Automated methodology for determination of stress distribution in human abdominal aortic aneurysm

Knowledge of impending abdominal aortic aneurysm (AAA) rupture can help in surgical planning. Typically, aneurysm diameter is used as the indicator of rupture, but recent studies have hypothesized that pressure-induced biomechanical stress may be a better predictor Verification of this hypothesis on a large study population with ruptured and unruptured AAA is vital if stress is to be reliably used as a clinical prognosticator for AAA rupture risk. We have developed an automated algorithm to calculate the peak stress in patient-specific AAA models. The algorithm contains a mesh refinement module, finite element analysis module, and a postprocessing visualization module. Several aspects of the methodology used are an improvement over past reported approaches. The entire analysis may be run from a single command and is completed in less than 1 h with the peak wall stress recorded for statistical analysis. We have used our algorithm for stress analysis of numerous ruptured and unruptured AAA models and report some of our results here. By current estimates, peak stress in the aortic wall appears to be a better predictor of rupture than AAA diameter. Further use of our algorithm is ongoing on larger study populations to convincingly verify these findings.     

Analysis of Morphological Parameters to Differentiate Rupture Status in Anterior Communicating Artery Aneurysms

In contrast to size, the association of morphological characteristics of intracranial aneurysms with rupture has not been established in a systematic manner. We present an analysis of the morphological variables that are associated with rupture in anterior communicating artery aneurysms to determine site-specific risk variables. One hundred and twenty-four anterior communicating artery aneurysms were treated in a single institution from 2005 to 2010, and CT angiograms (CTAs) or rotational angiography from 79 patients (42 ruptured, 37 unruptured) were analyzed. Vascular imaging was evaluated with 3D Slicer© to generate models of the aneurysms and surrounding vasculature. Morphological parameters were examined using univariate and multivariate analysis and included aneurysm volume, aspect ratio, size ratio, distance to bifurcation, aneurysm angle, vessel angle, flow angle, and parent-daughter angle. Multivariate logistic regression revealed that size ratio, flow angle, and parent-daughter angle were associated with aneurysm rupture after adjustment for age, sex, smoking history, and other clinical risk factors. Simple morphological parameters such as size ratio, flow angle, and parent-daughter angle may thus aid in the evaluation of rupture risk of anterior communicating artery aneurysms.