Fusiform versus Saccular Intracranial Aneurysms-Hemodynamic Evaluation of the Pre-Aneurysmal, Pathological, and Post-Interventional State.

Minimally-invasive therapies are well-established treatment methods for saccular intracranial aneurysms (SIAs). Knowledge concerning fusiform IAs (FIAs) is low, due to their wide and alternating lumen and their infrequent occurrence. However, FIAs carry risks like ischemia and thus require further in-depth investigation. Six patient-specific IAs, comprising three position-identical FIAs and SIAs, with the FIAs showing a non-typical FIA shape, were compared, respectively. For each model, a healthy counterpart and a treated version with a flow diverting stent were created. Eighteen time-dependent simulations were performed to analyze morphological and hemodynamic parameters focusing on the treatment effect (TE). The stent expansion is higher for FIAs than SIAs. For FIAs, the reduction in vorticity is higher (Δ35-75% case 2/3) and the reduction in the oscillatory velocity index is lower (Δ15-68% case 2/3). Velocity is reduced equally for FIAs and SIAs with a TE of 37-60% in FIAs and of 41-72% in SIAs. Time-averaged wall shear stress (TAWSS) is less reduced within FIAs than SIAs (Δ30-105%). Within this study, the positive TE of FDS deployed in FIAs is shown and a similarity in parameters found due to the non-typical FIA shape. Despite the higher stent expansion, velocity and vorticity are equally reduced compared to identically located SIAs.

Standardized viscosity as a source of error in computational fluid dynamic simulations of cerebral aneurysms.

BACKGROUND: Computational fluid dynamics (CFD) simulations are a powerful tool for studying cerebral aneurysms, capable of evaluating hemodynamics in a way that is infeasible with imaging alone. However, the difficulty of incorporating patient-specific information and inherent obstacles of in vivo validation have limited the clinical usefulness of CFD of cerebral aneurysms. In this work we investigate the effect of using standardized blood viscosity values in CFD simulations of cerebral aneurysms when compared to simulations of the same aneurysms using patient-specific viscosity values derived from hematocrit measurements. PURPOSE: The objective of this work is to determine the level of error, on average, that is, caused by using standardized values of viscosity in CFD simulations of cerebral aneurysms. By quantifying this error, we demonstrate the need for incorporating patient-specific viscosity in future CFD investigations of cerebral aneurysms. METHODS: CFD simulations of forty-one cerebral aneurysms were conducted using patient-specific boundary conditions. For each aneurysm two simulations were conducted, one utilizing patient-specific blood viscosity derived from hematocrit measurements and another using a standardized value for blood viscosity. Hemodynamic parameters such as wall shear stress (WSS), wall shear stress gradient (WSSG), and the oscillatory shear index (OSI) were calculated for each of the simulations for each aneurysm. Paired t-tests for differences in the time-averaged maps of these hemodynamic parameters between standardized and patient-specific viscosity simulations were conducted for each aneurysm. Bland-Altman analysis was used to examine the cohort-wide changes in the hemodynamic parameters. Subjects were broken into two groups, those with higher than standard viscosity and those with lower than standard viscosity. An unpaired t-test was used to compare the percent change in WSS, WSSG, and OSI between patient-specific and standardized viscosity simulations for the two cohorts. The percent changes in hemodynamic parameters were correlated against the direction and magnitude of percent change in viscosity, aneurysm size, and aneurysm location. For all t-tests, a Bonferroni-corrected significance level of 0.0167 was used. RESULTS: 63.2%, 41.5%, and 48.7% of aneurysms showed statistically significant differences between patient-specific and standardized viscosity simulations for WSS, WSSG, and OSI respectively. No statistically significant difference was found in the percent changes in WSS, WSSG, and OSI between the group with higher than standard viscosity and those with lower than standard viscosity, indicating an increase in viscosity can cause either an increase or decrease in each of the hemodynamic parameters. On a study-wide level no significant bias was found in either direction for WSS, WSSG, or OSI between the simulation groups due to the bidirectional effect of changing viscosity. No correlation was found between percent change of viscosity and percent change of WSS, WSSG, or OSI, meaning an after-the-fact correction for patient-specific viscosity is not feasible. CONCLUSION: Standardizing viscosity values in CFD of cerebral aneurysms has a large and unpredictable impact on the calculated WSS, WSSG, and OSI when compared to CFD simulations of the same aneurysms using a patient-specific viscosity. We recommend implementing hematocrit-based patient-specific blood viscosity values for all CFD simulations of cerebral aneurysms.

Improving the accuracy of computational fluid dynamics simulations of coiled cerebral aneurysms using finite element modeling.

Cerebral aneurysms are a serious clinical challenge, with ∼half resulting in death or disability. Treatment via endovascular coiling significantly reduces the chances of rupture, but the techniquehas failure rates of ∼20 %. This presents a pressing need to develop a method fordetermining optimal coildeploymentstrategies. Quantification of the hemodynamics of coiled aneurysms using computational fluid dynamics (CFD) has the potential to predict post-treatment outcomes, but representing the coil mass in CFD simulations remains a challenge. We use the Finite Element Method (FEM) for simulating patient-specific coil deployment for n = 4 ICA aneurysms for which 3D printed in vitro models were also generated, coiled, and scanned using ultra-high resolution synchrotron micro-CT. The physical and virtual coil geometries were voxelized onto a binary structured grid and porosity maps were generated for geometric comparison. The average binary accuracy score is 0.8623 and the average error in porosity map is 4.94 %. We then conduct patient-specific CFD simulations of the aneurysm hemodynamics using virtual coils geometries, micro-CT generated oil geometries, and using the porous medium method to represent the coil mass. Hemodynamic parameters including Neck Inflow Rate (Qneck) and Wall Shear Stress (WSS) were calculated for each of the CFD simulations. The average relative error in Qneck and WSS from CFD using FEM geometry were 6.6 % and 21.8 % respectively, while the error from CFD using a porous media approximation resulted in errors of 55.1 % and 36.3 % respectively; demonstrating a marked improvement in the accuracy of CFD simulations using FEM generated coil geometries.

Towards Prediction of Blood Flow in Coiled Aneurysms Before Treatment: A Porous Media Approach.

Modeling blood flow in aneurysms treated with coils could be used to understand the complete embolization of the aneurysm, through thrombus formation that fills the entire sac. Modeling of the endovascular coil mass as a porous medium is a technique that allows for study of aneurysm hemodynamics, efficiently for patient-specific treatment outcome predictions. Models in the literature use mean porosity of coils in the aneurysmal volume, proving inadequate for outcome prediction. However, models that consider heterogeneous porosity distribution have shown more accurate hemodynamics. We recently published the porous crown model, considering the heterogeneous coil mass distribution, validated on two patients. This study aims (i) to validate the porous crown model for a larger cohort (eight patients), and (ii) to propose a porous medium model translatable to clinical practice in treatment planning. We analyzed the porosity distribution of the endovascular coils deployed inside the cerebral aneurysm phantoms of eight patients using 3D x-ray synchrotron images. The permeability and inertial factor of the porous crown model are calculated using previously published methodology. We propose a new "bilinear" porous model, that uses the same hypothesis, but the permeability and inertial factor can be defined from just basic information available in the neuro-suite, i.e., the aneurysmal sac volume and the coil volume fraction targeted by the neurosurgeon. These two models are compared to the coil-resolved simulations, considered as the gold standard. The results show that both the porous crown model and the bilinear model produce similarly accurate hemodynamics in the aneurysm. The error in the standard (mean porosity) porous model is 66%, whereas the error of the bilinear model is 26%, compared to the coil-resolved. The bilinear model is promising as a means of treatment outcome prediction at time of intervention.

Assessment of the flow-diverter efficacy for intracranial aneurysm treatment considering pre- and post-interventional hemodynamics.

Endovascular treatment of intracranial aneurysms with flow diverters (FD) has become one of the most promising interventions. Due to its woven high-density structure they are particularly applicable for challenging lesions. Although several studies have already conducted realistic hemodynamic quantification of the FD efficacy, a comparison with morphologic post-interventional data is still missing. This study analyses the hemodynamics of ten intracranial aneurysm patients treated with a novel FD device. Based on pre- and post-interventional 3D digital subtraction angiography image data, patient-specific 3D models of both treatment states are generated applying open source threshold-based segmentation methods. Using a fast virtual stenting approach, the real stent positions available in the post-interventional data are virtually replicated and both treatment scenarios were characterized using image-based blood flow simulations. The results show FD-induced flow reductions at the ostium by a decrease in mean neck flow rate (51%), inflow concentration index (56%) and mean inflow velocity (53%). Intraluminal reductions in flow activity for time-averaged wall shear stress (47%) and kinetic energy (71%) are present as well. However, an intra-aneurysmal increase in flow pulsatility (16%) for the post-interventional cases can be observed. Patient-specific FD simulations demonstrate the desired flow redirection and activity reduction inside the aneurysm beneficial for thrombosis formation. Differences in the magnitude of hemodynamic reduction exist over the cardiac cycle which may be addressed in a clinical setting by anti-hypertensive treatment in selected cases.

Modeling Flow in Cerebral Aneurysm After Coils Embolization Treatment: A Realistic Patient-Specific Porous Model Approach.

PURPOSE: Computational fluid dynamics (CFD) has been used to evaluate the efficiency of endovascular treatment in coiled cerebral aneurysms. The explicit geometry of the coil mass cannot typically be incorporated into CFD simulations since the coil mass cannot be reconstructed from clinical images due to its small size and beam hardening artifacts. The existing methods use imprecise porous medium representations. We propose a new porous model taking into account the porosity heterogeneity of the coils deployed in the aneurysm. METHODS: The porosity heterogeneity of the coil mass deployed inside two patients' cerebral aneurysm phantoms is first quantified based on 3D X-ray synchrotron images. These images are also used to compute the permeability and the inertial factor arising in porous models. A new homogeneous porous model (porous crowns model), considering the coil's heterogeneity, is proposed to recreate the flow within the coiled aneurysm. Finally, the validity of the model is assessed through comparisons with coil-resolved simulations. RESULTS: The strong porosity gradient of the coil measured close to the aneurysmal wall is well captured by the porous crowns model. The permeability and the inertial factor values involved in this model are closed to the ideal homogeneous porous model leading to a mean velocity in the aneurysmal sac similar as in the coil-resolved model. CONCLUSION: The porous crowns model allows for an accurate description of the mean flow within the coiled cerebral aneurysm.

Endothelial Responses to Curvature-Induced Flow Patterns in Engineered Cerebral Aneurysms.

Hemodynamic factors have long been associated with clinical outcomes in the treatment of cerebral aneurysms. Computational studies of cerebral aneurysm hemodynamics have provided valuable estimates of the mechanical environment experienced by the endothelium in both the parent vessel and aneurysmal dome walls and have correlated them with disease state. These computational-clinical studies have recently been correlated with the response of endothelial cells (EC) using either idealized or patient-specific models. Here, we present a robust workflow for generating anatomic-scale aneurysm models, establishing luminal cultures of ECs at physiological relevant flow profiles, and comparing EC responses to curvature mediated flow. We show that flow patterns induced by parent vessel curvature produce changes in wall shear stress (WSS) and wall shear stress gradients (WSSG) that are correlated with differences in cell morphology and cellular protein localization. Cells in higher WSS regions align better with the flow and display strong Notch1-extracellular domain (ECD) polarization, while, under low WSS, differences in WSSG due to curvature change were associated with less alignment and attenuation of Notch1-ECD polarization in ECs of the corresponding regions. These proof-of-concept results highlight the use of engineered cellularized aneurysm models for connecting computational fluid dynamics to the underlying endothelial biology that mediates disease.

Modeling the Mechanical Microenvironment of Coiled Cerebral Aneurysms.

Successful occlusion of cerebral aneurysms using coil embolization is contingent upon stable thrombus formation, and the quality of the thrombus depends upon the biomechanical environment. The goal of this study was to investigate how coil embolization alters the mechanical micro-environment within the aneurysm dome. Inertialess particles were injected in three-dimensional, computational simulations of flow inside patient aneurysms using patient-specific boundary conditions. Coil embolization was simulated as a homogenous porous medium of known permeability and inertial constant. Lagrangian particle tracking was used to calculate the residence time and shear stress history for particles in the flow before and after treatment. The percentage of particles entering the aneurysm dome correlated with the neck surface area before and after treatment (pretreatment: R2 = 0.831, P < 0.001; post-treatment: R2 = 0.638, P < 0.001). There was an inverse relationship between the change in particles entering the dome and coil packing density (R2 = 0.600, P < 0.001). Following treatment, the particles with the longest residence times tended to remain within the dome even longer while accumulating lower shear stress. A significant correlation was observed between the treatment effect on residence time and the ratio of the neck surface area to porosity (R2 = 0.390, P = 0.007). The results of this study suggest that coil embolization triggers clot formation within the aneurysm dome via a low shear stress-mediated pathway. This hypothesis links independently observed findings from several benchtop and clinical studies, furthering our understanding of this treatment strategy.

Lagrangian Trajectory Simulation of Platelets and Synchrotron Microtomography Augment Hemodynamic Analysis of Intracranial Aneurysms Treated With Embolic Coils.

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.

Can Endovascular Treatment of Fusiform Intracranial Aneurysms Restore the Healthy Hemodynamic Environment?-A Virtual Pilot Study.

Numerous studies assess intracranial aneurysm rupture risk based on morphological and hemodynamic parameter analysis in addition to clinical information such as aneurysm localization, age, and sex. However, intracranial aneurysms mostly occur with a saccular shape located either lateral to the parent artery or at a bifurcation. In contrast, fusiform intracranial aneurysms (FIAs), i.e., aneurysms with a non-saccular, dilated form, occur in approximately 3-13% of all cases and therefore have not yet been as thoroughly studied. To improve the understanding of FIA hemodynamics, this pilot study contains morphological analyses and image-based blood flow simulations in three patient-specific cases. For a precise and realistic comparison to the pre-pathological state, each dilation was manually removed and the time-dependent blood flow simulations were repeated. Additionally, a validated fast virtual stenting approach was applied to evaluate the effect of virtual endovascular flow-diverter deployment focusing on relevant hemodynamic quantities. For two of the three patients, post-interventional information was available and included in the analysis. The results of this numerical pilot study indicate that complex flow structures, i.e., helical flow phenomena and the presence of high oscillating flow features, predominantly occur in FIAs with morphologically differing appearances. Due to the investigation of the individual healthy states, the original flow environment could be restored which serves as a reference for the virtual treatment target. It was shown that the realistic deployment led to a considerable stabilization of the individual hemodynamics in all cases. Furthermore, a quantification of the stent-induced therapy effect became feasible for the treating physician. The results of the morphological and hemodynamic analyses in this pilot study show that virtual stenting can be used in FIAs to quantify the effect of the planned endovascular treatment.

Platelet Dynamics and Hemodynamics of Cerebral Aneurysms Treated with Flow-Diverting Stents.

Flow-diverting stents (FDS) are used to treat cerebral aneurysms. They promote the formation of a stable thrombus within the aneurysmal sac and, if successful, isolate the aneurysmal dome from mechanical stresses to prevent rupture. Platelet activation, a mechanism necessary for thrombus formation, is known to respond to biomechanical stimuli, particularly to the platelets' residence time and shear stress exposure. Currently, there is no reliable method for predicting FDS treatment outcomes, either a priori or after the procedure. Eulerian computational fluid dynamic (CFD) studies of aneurysmal flow have searched for predictors of endovascular treatment outcome; however, the hemodynamics of thrombus formation cannot be fully understood without considering the platelets' trajectories and their mechanics-triggered activation. Lagrangian analysis of the fluid mechanics in the aneurysmal vasculature provides novel metrics by tracking the platelets' residence time (RT) and shear history (SH). Eulerian and Lagrangian parameters are compared for 19 patient-specific cases, both pre- and post-treatment, to assess the degree of change caused by the FDS and subsequent treatment efficacy.