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Background It is thought that aneurysms evolve as the result of progressive degradation of the wall in response to abnormal hemodynamics characterized by either high or low wall shear stress (WSS). Objective To investigate the effects of these two different hemodynamic pathways in a series of cerebral aneurysms with known rupture sites. Methods Nine aneurysms in which the rupture site could be identified in three-dimensional images were analyzed. The WSS distribution was obtained from computational fluid dynamics (CFD) simulations. Internal wall stresses were computed using structural wall models under hemodynamic loads determined by the CFD models. Wall properties (thickness and stiffness) were modulated with the WSS distribution (increased or decreased in regions of high or low WSS) to test possible wall degradation pathways. Rupture probability indices (RPI) were calculated to compare different wall models. Results Most rupture sites aligned with the intrasaccular flow stream and downstream of the primary impaction zone. The model that best explained the rupture site (produced higher RPI) in eight of the nine aneurysms (89%) had thinner and stiffer walls in regions of abnormally high WSS. The remaining case (11%) was best explained by a model with thinner and stiffer walls in regions of abnormally low WSS. Conclusions Aneurysm rupture seems to be caused by localized degradation and weakening of the wall in response to abnormal hemodynamics. Image-based computational models assuming wall thinning and stiffening in regions of abnormally high WSS were able to explain most of the observed rupture sites. [ABSTRACT FROM AUTHOR]

SUMMARY Understanding the flow alteration in side branches during flow diversion treatment of cerebral aneurysms is important to prevent ischemic complications and improve device designs. Flow diverters were placed in the aorta of four rabbits crossing the origin of side arteries. Subject-specific computational models were constructed from 3D angiographies and Doppler ultrasounds (DUSs). Flow simulations were run before and after virtually deploying the flow diverters, assuming distal resistances remained unchanged after treatment. All jailed arteries remained patent angiographically 8 weeks after treatment. The computational models estimated decreases compared to pretreatment in the mean flow rates between 2% and 20% and in peak flow rates between 5% and 36%. The major changes were observed during systole. Flow patterns did not exhibit recirculation zones before treatment. Implantation of the flow diverters altered the flow structure only locally near the device wires. No major recirculation regions were created or destroyed. Flow diverters seem safe with respect to perforator or side branch occlusion. Relatively small changes in flow rates through jailed arteries are expected, even for moderate to large degrees of coverage of their origins. These results seem consistent with previous clinical experiences where no or very few complications related to perforator occlusion have been reported.Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY Quantification and characterization of the hemodynamic environment created after flow diversion treatment of cerebral aneurysms is important to understand the effects of flow diverters and their interactions with the biology of the aneurysm wall and the thrombosis process that takes place subsequently. This paper describes the construction of multi-modality image-based subject-specific CFD models of experimentally created aneurysms in rabbits and subsequently treated with flow diverters. Briefly, anatomical models were constructed from 3D rotational angiography images, flow conditions were derived from Doppler ultrasound measurements, stent models were created and virtually deployed, and the results were compared with in vivo digital subtraction angiography and Doppler ultrasound images. The models were capable of reproducing in vivoobservations, including velocity waveforms measured in the parent artery, peak velocity values measured in the aneurysm, and flow structures observed with digital subtraction angiography before and after deployment of flow diverters. The results indicate that regions of aneurysm occlusion after flow diversion coincide with slow and smooth flow patterns, whereas regions still permeable at the time of animal sacrifice were observed in parts of the aneurysm exposed to larger flow activity, that is, higher velocities, more swirling, and more complex flow structures. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Embedded mesh, immersed body or fictitious domain techniques have been used for many years as a way to discretize geometrically complex domains with structured grids. The use of such techniques within adaptive, unstructured grid solvers is relatively recent. The combination of body-fitted functionality for some portion of the domain, together with embedded mesh or immersed body functionality for another portion of the domain offers great advantages, which are increasingly being exploited. The present paper reviews the methodologies pursued so far, addresses implementational issues and shows the possibilities such techniques offer. [Copyright &y& Elsevier]

Hemodynamic factors are thought to be implicated in the progression and rupture of intracranial aneurysms. Current efforts aim to study the possible associations of hemodynamic chars acteristics such as complexity and stability of intra-aneurysmal flow patterns, size and location of the region of flow impingement with the clinical history of aneurysmal rupture. However, there are no reliable methods for measuring blood flow patterns in vivo. In this paper, an efficient methodology for patient-specific modeling and characterization of the hemodynamics in cerebral aneurysms from medical images is described. A sensitivity analysis of the hemodynamic characteristics with respect to variations of several variables over the expected physiologic range of conditions is also presented. This sensitivity analysis shows that although changes in the velocity fields can be observed, the characterization of the intra-aneurysmal flow patterns is not altered when the mean input flow, the flow division, the viscosity model, or mesh resolution are changed. It was also found that the variable that has the greater impact on the computed flow fields is the geometry of the vascular structures. We conclude that with the proposed modeling pipeline clinical studies involving large numbers cerebral aneurysms are feasible. [ABSTRACT FROM AUTHOR]

The simulation of blood flow past endovascular devices such as coils and stents is a challenging problem due to the complex geometry of the devices. Traditional unstructured grid computational fluid dynamics relies on the generation of finite element grids that conform to the boundary of the computational domain. However, the generation of such grids for patient-specific modeling of cerebral aneurysm treatment with coils or stents is extremely difficult and time consuming. This paper describes the application of an adaptive grid embedding technique previously developed for complex fluid structure interaction problems to the simulation of endovascular devices. A hybrid approach is used: the vessel walls are treated with body conforming grids and the endovascular devices with an adaptive mesh embedding technique. This methodology fits naturally in the framework of image-based computational fluid dynamics and opens the door for exploration of different therapeutic options and personalization of endovascular procedures. [ABSTRACT FROM AUTHOR]

Virtual bronchoscopy reconstructions of the airway noninvasively provide useful morphologic information of structural abnormalities such as stenoses and masses. In this paper, we show how virtual bronchoscopy can be used to perform aerodynamic calculations in anatomically realistic models. Pressure and flow patterns in a human airway were computed noninvasively. These showed decreased pressure and increased shear stress in the region of a stenosis. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient‐specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier–Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low‐shear environments can contribute to aneurysm pathology through distinct mechanisms. [ABSTRACT FROM AUTHOR]

The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient‐specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient‐specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high‐flow in ACom with thin blebs at impingement sites and low‐flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure—high‐flow and low‐flow conditions—highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient‐specific characteristics impact these processes, which need further investigation. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) are localized enlargements of cerebral blood vessels that cause substantial rates of mortality and morbidity in humans. The rupture possibility of these aneurysms is a critical medical challenge for physicians during treatment planning. This treatment planning while assessing the rupture potential of aneurysms becomes more complicated when they are constrained by an adjacent structure such as optic nerve tissues or bones, which is not widely studied yet. In this work, we considered and studied a constitutive model to investigate the bio-mechanical response of image-based patient-specific IA data using cardiovascular structural mechanics equations. We performed biomechanical modeling and simulations of four different patient-specific aneurysms' data (three middle cerebral arteries and one internal carotid artery) to assess the rupture potential of those aneurysms under a plane contact constraint. Our results suggest that aneurysms with plane contact constraints produce less or almost similar maximum wall effective stress compared to aneurysms with no contact constraints. In our research findings, we observed that a plane contact constraint on top of an internal carotid artery might work as a protective wall due to the 16.6% reduction in maximum wall effective stress than that for the case where there is no contact on top of the aneurysm. [ABSTRACT FROM AUTHOR]

Introduction: Connecting local hemodynamics, biomechanics, and tissue properties in cerebral aneurysms is important for understanding the processes of wall degeneration and subsequent aneurysm progression and rupture. This challenging problem requires integration of data from multiple sources. Methods: This paper describes the tools and techniques developed to integrate data from multiple sources, including clinical information, 3D imaging, intraoperative videos, ex vivo micro–computed tomography (CT), and multiphoton microscopy. Central to this approach is a 3D tissue model constructed from micro‐CT images of aneurysm samples resected during neurosurgery. This model is aligned to vascular models constructed from 3D clinical images and is used to map and compare flow, biomechanics, and tissue data. Results: The approach is illustrated with data of three human intracranial aneurysms. These case studies demonstrated the ability of this approach to study relationships between different factors affecting the aneurysm wall and produced provocative observations that will be further studied with larger series. For instance, "atherosclerotic" and "hyperplastic" looking parts of the aneurysm corresponded to thicker walls and occurred in regions of recirculating flow and low wall shear stress (WSS); thin regions were associated with inflow jets, flow impingement, and high WSS; blebs had walls of varying structures, including calcified, thin, or hyperplastic walls. Conclusions: The current approach enables the study of interactions of multiple factors thought to be responsible for the progressive degradation and weakening of the aneurysm wall during its evolution. This paper describes the tools and techniques for integrating data from multiple sources, including clinical information, 3D imaging, intraoperative videos, ex vivo micro‐CT, and multiphoton microscopy. Central is a micro‐CT–based 3D tissue model of aneurysm samples resected during neurosurgery. This model is aligned to vascular models from 3D clinical images and used to map and compare flow, biomechanics, and tissue data. This enables studying interactions of multiple factors thought to be responsible for the progressive wall degradation and weakening. [ABSTRACT FROM AUTHOR]

The author reflects on the use of image-based computational fluid dynamics (CFD) in bioengineering and clinical problems. He notes the efforts in evaluating computational models such as model verification and sensitivity analysis. He notes that CFD method is used in understanding diseases, risk assessment, treatment planning, device design and optimization. Moreover, he discusses the used of the method in patient evaluation and treatment planning for vascular diseases.

The goal of this study was to test if CFD‐based virtual angiograms could be used to automatically discriminate between intracranial aneurysms (IAs) with and without flow stagnation. Time density curves (TDC) were extracted from patient digital subtraction angiography (DSA) image sequences by computing the average gray level intensity inside the aneurysm region and used to define injection profiles for each subject. Subject‐specific 3D models were reconstructed from 3D rotational angiography (3DRA) and computational fluid dynamics (CFD) simulations were performed to simulate the blood flow inside IAs. Transport equations were solved numerically to simulate the dynamics of contrast injection into the parent arteries and IAs and then the contrast retention time (RET) was calculated. The importance of gravitational pooling of contrast agent within the aneurysm was evaluated by modeling contrast agent and blood as a mixture of two fluids with different densities and viscosities. Virtual angiograms can reproduce DSA sequences if the correct injection profile is used. RET can identify aneurysms with significant flow stagnation even when the injection profile is not known. Using a small sample of 14 IAs of which seven were previously classified as having flow stagnation, it was found that a threshold RET value of 0.46 s can successfully identify flow stagnation. CFD‐based prediction of stagnation was in more than 90% agreement with independent visual DSA assessment of stagnation in a second sample of 34 IAs. While gravitational pooling prolonged contrast retention time it did not affect the predictive capabilities of RET. CFD‐based virtual angiograms can detect flow stagnation in IAs and can be used to automatically identify aneurysms with flow stagnation even without including gravitational effects on contrast agents. [ABSTRACT FROM AUTHOR]

SUMMARY Because of its ability to deal with any geometry, image-based computational fluid dynamics (CFD) has been progressively used to investigate the role of hemodynamics in the underlying mechanisms governing the natural history of cerebral aneurysms. Despite great progress in methodological developments and many studies using patient-specific data, there are still significant controversies about the precise governing processes and divergent conclusions from apparently contradictory results. Sorting out these issues requires a global vision of the state of the art and a unified approach to solving this important scientific problem. Towards this end, this paper reviews the contributions made using patient-specific CFD models to further the understanding of these mechanisms, and highlights the great potential of patient-specific computational models for clinical use in the assessment of aneurysm rupture risk and patient management. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Bolus tracking magnetic resonance imaging (MRI) is a powerful technique for measuring perfusion, and is playing an increasing role in the investigation of acute stroke. However, limitations have been reported when assessing patients with steno-occlusive disease. The presence of a steno-occlusive disease in the artery may cause bolus dispersion, which has been shown to introduce significant errors in cerebral blood flow (CBF) quantification. Bolus dispersion is commonly described by a vascular transport function, but the function that properly characterizes the dispersion is unknown. A novel method to quantify bolus dispersion errors on perfusion measurements is presented. A realistic patient-specific model is constructed from anatomical and physiologic MR data, and the arterial blood flow pattern and the transport of the bolus of contrast agent are computed using finite element analysis. The methodology presented was used also to evaluate the accuracy of three simple vascular models. The methodology was tested on MR data from two normal subjects and two subjects with mild carotid artery stenosis. The estimated CBF errors were of the order of 15% to 20%. However, the presence of stenosis did not necessarily introduce larger dispersion (not only the geometrical model but also the particular physiologic conditions influence the degree of bolus dispersion). The method described will contribute to a better understanding of errors introduced by dispersion effects, to the assessment and validation of vascular models, and to the development of new methods for the correction of dispersion errors in CBF quantification. [Copyright &y& Elsevier]

While previous studies have identified many risk factors for the progression and rupture of cerebral aneurysms, the changes in aneurysm flow characteristics during its evolution are not fully understood. This work analyzes the changes in the aneurysm hemodynamic environment from its initial development to later stages when the aneurysm has substantially enlarged. A total of 88 aneurysms at four locations were studied with image based computational fluid dynamics (CFD). Two synthetic sequences representing the aneurysm geometry at three earlier stages were generated by shrinking the aneurysm sac while keeping the neck fixed or shrinking the neck simultaneously. The flow conditions were then quantitatively compared between these two modes of evolution. As aneurysms enlarged, the inflow rate increased in growing neck sequences, but decreased in fixed neck sequences. The inflow jet became more concentrated in both sequences. The mean aneurysm flow velocity and wall shear stress decreased in both sequences, but they decreased faster in enlarging aneurysms if the neck was fixed. Additionally, the intra‐aneurysmal flows became more complex and more unstable, wall shear stress distribution became more oscillatory, and the area under low wall shear stress increased for both sequences. The evolution of flow characteristics of aneurysms with fixed and growing necks are different. The observed trends suggest that fixed neck aneurysms may evolve towards a flow environment characteristic of stable aneurysms faster than aneurysms with growing necks, which could also evolve towards a more disfavorable environment. [ABSTRACT FROM AUTHOR]

Background: Hemodynamic patterns have been associated with cerebral aneurysm instability. For patient-specific computational fluid dynamics (CFD) simulations, the inflow rates of a patient are typically not known. The aim of this study was to analyze the influence of inter- and intra-patient variations of cerebral blood flow on the computed hemodynamics through CFD simulations and to incorporate these variations into statistical models for aneurysm rupture prediction. Methods: Image data of 1820 aneurysms were used for patient-specific steady CFD simulations with nine different inflow rates per case, capturing inter- and intra-patient flow variations. Based on the computed flow fields, 17 hemodynamic parameters were calculated and compared for the different flow conditions. Next, statistical models for aneurysm rupture were trained in 1571 of the aneurysms including hemodynamic parameters capturing the flow variations either by defining hemodynamic "response variables" (model A) or repeatedly randomly selecting flow conditions by patients (model B) as well as morphological and patient-specific variables. Both models were evaluated in the remaining 249 cases. Results: All hemodynamic parameters were significantly different for the varying flow conditions (p < 0.001). Both the flow-independent "response" model A and the flow-dependent model B performed well with areas under the receiver operating characteristic curve of 0.8182 and 0.8174 ± 0.0045, respectively. Conclusions: The influence of inter- and intra-patient flow variations on computed hemodynamics can be taken into account in multivariate aneurysm rupture prediction models achieving a good predictive performance. Such models can be applied to CFD data independent of the specific inflow boundary conditions. [ABSTRACT FROM AUTHOR]

Purpose: The mechanisms of cerebral aneurysm rupture are not fully understood. We analyzed the associations of hemodynamics, morphology, and patient age and gender with aneurysm rupture stratifying by location.Methods: Using image-based models, 20 hemodynamic and 17 morphological parameters were compared in 1931 ruptured and unruptured aneurysms with univariate logistic regression. Rupture rates were compared between males and females as well as younger and older patients and bifurcation versus sidewall aneurysms for different aneurysm locations. Subsequently, associations between hemodynamics and morphology and patient as well as aneurysm characteristics were analyzed for aneurysms at five locations.Results: Compared to unruptured aneurysms, ruptured aneurysms were characterized by a more irregular shape and were exposed to a more adverse hemodynamic environment described by faster flow, higher wall shear stress, more oscillatory shear, and more unstable and complex flows. These associations with rupture status were consistent for different aneurysm locations. Rupture rates were significantly higher in males at the internal carotid artery (ICA) bifurcation, ophthalmic ICA, and the middle cerebral artery (MCA) bifurcation. At the anterior communicating artery (ACOM) and MCA bifurcation, they were significantly higher for younger patients. Bifurcation aneurysms had significantly larger rupture rates at the MCA and posterior communicating artery (PCOM). In these groups with higher rupture rates, aneurysms were characterized by adverse hemodynamics and more complex shapes.Conclusion: Hemodynamic and morphological differences between ruptured and unruptured aneurysms are consistent across locations. Adverse morphology and hemodynamics are related to rupture as well as younger age, male gender, and bifurcation aneurysms. [ABSTRACT FROM AUTHOR]

Background: For a treatment decision of unruptured cerebral aneurysms, physicians and patients need to weigh the risk of treatment against the risk of hemorrhagic stroke caused by aneurysm rupture. The aim of this study was to externally evaluate a recently developed statistical aneurysm rupture probability model, which could potentially support such treatment decisions.Methods: Segmented image data and patient information obtained from two patient cohorts including 203 patients with 249 aneurysms were used for patient-specific computational fluid dynamics simulations and subsequent evaluation of the statistical model in terms of accuracy, discrimination, and goodness of fit. The model’s performance was further compared to a similarity-based approach for rupture assessment by identifying aneurysms in the training cohort that were similar in terms of hemodynamics and shape compared to a given aneurysm from the external cohorts.Results: When applied to the external data, the model achieved a good discrimination and goodness of fit (area under the receiver operating characteristic curve AUC = 0.82), which was only slightly reduced compared to the optimism-corrected AUC in the training population (AUC = 0.84). The accuracy metrics indicated a small decrease in accuracy compared to the training data (misclassification error of 0.24 vs. 0.21). The model’s prediction accuracy was improved when combined with the similarity approach (misclassification error of 0.14).Conclusions: The model’s performance measures indicated a good generalizability for data acquired at different clinical institutions. Combining the model-based and similarity-based approach could further improve the assessment and interpretation of new cases, demonstrating its potential use for clinical risk assessment. [ABSTRACT FROM AUTHOR]

Background: Intracranial aneurysms at the posterior communicating artery (PCOM) are known to have high rupture rates compared to other locations. We developed and internally validated a statistical model discriminating between ruptured and unruptured PCOM aneurysms based on hemodynamic and geometric parameters, angio-architectures, and patient age with the objective of its future use for aneurysm risk assessment.Methods: A total of 289 PCOM aneurysms in 272 patients modeled with image-based computational fluid dynamics (CFD) were used to construct statistical models using logistic group lasso regression. These models were evaluated with respect to discrimination power and goodness of fit using tenfold nested cross-validation and a split-sample approach to mimic external validation.Results: The final model retained maximum and minimum wall shear stress (WSS), mean parent artery WSS, maximum and minimum oscillatory shear index, shear concentration index, and aneurysm peak flow velocity, along with aneurysm height and width, bulge location, non-sphericity index, mean Gaussian curvature, angio-architecture type, and patient age. The corresponding area under the curve (AUC) was 0.8359. When omitting data from each of the three largest contributing hospitals in turn, and applying the corresponding model on the left-out data, the AUCs were 0.7507, 0.7081, and 0.5842, respectively.Conclusions: Statistical models based on a combination of patient age, angio-architecture, hemodynamics, and geometric characteristics can discriminate between ruptured and unruptured PCOM aneurysms with an AUC of 84%. It is important to include data from different hospitals to create models of aneurysm rupture that are valid across hospital populations. [ABSTRACT FROM AUTHOR]

Objective The detailed mechanisms of cerebral aneurysm evolution are poorly understood but are important for objective aneurysm evaluation and improved patient management. The purpose of this study was to identify hemodynamic conditions that may predispose aneurysms to growth. Methods A total of 33 intracranial unruptured aneurysms longitudinally followed with three-dimensional imaging were studied. Patient-specific computational fluid dynamics models were constructed and used to quantitatively characterize the hemodynamic environments of these aneurysms. Hemodynamic characteristics of growing (n=16) and stable (n=17) aneurysms were compared. Logistic regression statistical models were constructed to test the predictability of aneurysm growth by hemodynamic features. Results Growing aneurysms had significantly smaller shear rate ratios (p=0.01), higher concentration of wall shear stress (p=0.03), smaller vorticity ratios (p=0.01), and smaller viscous dissipation ratios (p=0.01) than stable aneurysms. They also tended to have larger areas under low wall shear stress (p=0.06) and larger aspect ratios (p=0.18), but these trends were not significant. Mean wall shear stress was not significantly different between growing and stable aneurysms. Logistic regression models based on hemodynamic variables were able to discriminate between growing and stable aneurysms with a high degree of accuracy (94-100%). Conclusions Growing aneurysms tend to have complex intrasaccular flow patterns that induce non-uniform wall shear stress distributions with areas of concentrated high wall shear stress and large areas of low wall shear stress. Statistical models based on hemodynamic features seem capable of discriminating between growing and stable aneurysms. [ABSTRACT FROM AUTHOR]

With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial!temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneutysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Panticipants were free to choose boundaty conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (P1V) were carried out in a silicone model of one of the provided aneutysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peaksystolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that white a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneuiysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneuiysm. [ABSTRACT FROM AUTHOR]

Purpose To assess hemodynamic differences between aneurysms that occlude rapidly and those occluding in delayed fashion after flow diversion in rabbits. Methods Thirty-six elastase-induced aneurysms in rabbits were treated with flow diverting devices. Aneurysm occlusion was assessed angiographically immediately before they were sacrificed at 1 (n=6), 2 (n=4), 4 (n=8) or 8 weeks (n=18) after treatment. The aneurysms were classified into a fast occlusion group if they were completely or near completely occluded at 4 weeks or earlier and a slow occlusion group if they remained incompletely occluded at 8 weeks. The immediate post-treatment flow conditions in aneurysms of each group were quantified using subject-specific computational fluid dynamics and statistically compared. Results Nine aneurysms were classified into the fast occlusion group and six into the slow occlusion group. Aneurysms in the fast occlusion group were on average significantly smaller (fast=0.9 cm, slow=1.393 cm, p=0.024) and had smaller ostia (fast=0.144 cm2, slow=0.365 cm2, p=0.015) than aneurysms in the slow occlusion group. They also had a lower mean posttreatment inflow rate (fast=0.047 mL/s, slow=0.155 mL/s, p=0.0239), kinetic energy (fast=0.519 erg, slow=1.283 erg, p=0.0468), and velocity (fast=0.221 cm/s, slow=0.506 cm/s, p=0.0582). However, the differences in the latter two variables were only marginally significant. Conclusions Hemodynamic conditions after flow diversion treatment of cerebral aneurysms in rabbits are associated with the subsequent aneurysm occlusion time. Specifically, smaller inflow rate, kinetic energy, and velocity seem to promote faster occlusions, especially in smaller and small-necked aneurysms. These results are consistent with previous studies based on clinical series. [ABSTRACT FROM AUTHOR]

Background Evaluation of flow diversion treatment of intracranial aneurysms is difficult owing to lack of knowledge of the target hemodynamic environment. Objective To identify hemodynamic conditions created after flow diversion that induce fast aneurysm occlusion. Methods Two groups of aneurysms treated with flow diverters alone were selected: (a) aneurysms completely occluded at 3 months (fast occlusion), and (b) aneurysms patent or incompletely occluded at 6 months (slow occlusion). A total of 23 aneurysms were included in the study. Patient-specific computational fluid dynamics models were constructed and used to characterize the hemodynamic environment immediately before and after treatment. Average post-treatment hemodynamic conditions between the fast and slow occlusion groups were statistically compared. Results Aneurysms in the fast occlusion group had significantly lower post-treatment mean velocity (fast=1.13cm/s, slow=3.11cm/s, p=0.02), inflow rate (fast=0.47mL/s, slow=1.89mL/s, p=0.004) and shear rate (fast=20.52 1/s, slow=32.37 1/s, p=0.02) than aneurysms in the slow occlusion group. Receiver operating characteristics analysis showed that mean post-treatment velocity, inflow rate, and shear rate below a certain threshold could discriminate between aneurysms of the fast and slow occlusion groups with good accuracy (84%, 77%, and 76%, respectively). Conclusions The occlusion time of cerebral aneurysms treated with flow diverters can be predicted by the hemodynamic conditions created immediately after device implantation. Specifically, low post-implantation flow velocity, inflow rate, and shear rate are associated with fast occlusion times. [ABSTRACT FROM AUTHOR]

SUMMARY Morphometric information of the brain vascularization is valuable for a variety of clinical and scientific applications. In particular, this information is important when creating arterial tree models for imposing boundary conditions in numerical simulations of the brain hemodynamics. The purpose of this work is to provide quantitative descriptions of arterial branches, bifurcation patterns, shape, and geographical distribution of the arborization of the main cerebral arteries as well as estimations of the corresponding vascular territories. For this purpose, subject-specific digital reconstructions of the brain vascular network created from 3T magnetic resonance angiography images of healthy volunteers are used to derive population-averaged morphometric characteristics of the cerebral arterial trees. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY Quantifying the hemodynamic environment within aneurysms and its change after deployment of flow diverting devices is important to assess the device efficacy and understand their long-term effects. The purpose of this study was to estimate deviations in the quantification of the relative change of hemodynamic variables during flow diversion treatment of cerebral aneurysms due to changing physiologic flow conditions. Computational fluid dynamics calculations were carried out on three patient-specific geometries. Three flow diverters were virtually implanted in each geometry and simulations were performed under five pulsatile flow conditions. Hemodynamic variables including aneurysm inflow rate, mean velocity, shear rate, and wall shear stress were quantified before and after stenting. Deviations in the relative change of these variables due to varying flow conditions were calculated. The results indicate that a change in the mean flow of the parent artery of approximately 30-50% can induce large deviations in the relative change of hemodynamic variables in the range of 30-80%. Thus, quantification of hemodynamic changes during flow diversion must be carried out carefully. Variations in the inflow conditions during the procedure may induce large deviations in the quantification of these changes. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Characterization of the complex branching architecture of cerebral arteries across a representative sample of the human population is important for diagnosing, analyzing, and predicting pathological states. Brain arterial vasculature can be visualized by magnetic resonance angiography (MRA). However, most MRA studies are limited to qualitative assessments, partial morphometric analyses, individual (or small numbers of) subjects, proprietary datasets, or combinations of the above limitations. Neuroinformatics tools, developed for neuronal arbor analysis, were used to quantify vascular morphology from 3T time-of-flight MRA high-resolution (620μm isotropic) images collected in 61 healthy volunteers (36/25 F/M, average age=31.2±10.7, range=19–64years). We present in-depth morphometric analyses of the global and local anatomical features of these arbors. The overall structure and size of the vasculature did not significantly differ across genders, ages, or hemispheres. The total length of the three major arterial trees stemming from the circle of Willis (from smallest to largest: the posterior, anterior, and middle cerebral arteries; or PCAs, ACAs, and MCAs, respectively) followed an approximate 1:2:4 proportion. Arterial size co-varied across individuals: subjects with one artery longer than average tended to have all other arteries also longer than average. There was no net right–left difference across the population in any of the individual arteries, but ACAs were more lateralized than MCAs. MCAs, ACAs, and PCAs had similar branch-level properties such as bifurcation angles. Throughout the arterial vasculature, there were considerable differences between branch types: bifurcating branches were significantly shorter and straighter than terminating branches. Furthermore, the length and meandering of bifurcating branches increased with age and with path distance from the circle of Willis. All reconstructions are freely distributed through a public database to enable additional analyses and modeling (cng.gmu.edu/brava). [Copyright &y& Elsevier]

SUMMARY Hemodynamics is thought to be a fundamental factor in the formation, progression, and rupture of cerebral aneurysms. Understanding these mechanisms is important to improve their rupture risk assessment and treatment. In this study, we analyze the blood flow field in a growing cerebral aneurysm using experimental particle image velocimetry (PIV) and computational fluid dynamics (CFD) techniques. Patient-specific models were constructed from longitudinal 3D computed tomography angiography images acquired at 1-y intervals. Physical silicone models were constructed from the computed tomography angiography images using rapid prototyping techniques, and pulsatile flow fields were measured with PIV. Corresponding CFD models were created and run under matching flow conditions. Both flow fields were aligned, interpolated, and compared qualitatively by inspection and quantitatively by defining similarity measures between the PIV and CFD vector fields. Results showed that both flow fields were in good agreement. Specifically, both techniques provided consistent representations of the main intra-aneurysmal flow structures and their change during the geometric evolution of the aneurysm. Despite differences observed mainly in the near wall region, and the inherent limitations of each technique, the information derived is consistent and can be used to study the role of hemodynamics in the natural history of intracranial aneurysms. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: A role for high shear stress in plaque destabilization has been postulated. We investigate this potential effect by correlating carotid plaque morphology directly with in vivo wall shear stress measurements. Materials and Methods: Carotid endarterectomy patients were enrolled in an IRB approved study using magnetic resonance angiography (MRA) to measure in vivo wall shear stress. After endarterectomy, the specimen was oriented, cross sectioned for histology at 2 mm intervals, and photographed. The shear stress correlating with each histologic segment of vessel was calculated from presurgical MRA using Navier-Stokes finite element analysis. The plaque regions were evaluated quantitatively for area of necrosis, calcification, hemorrhage and inflammation; fibrous cap and intimal thickness, plaque erosion, rupture or thrombosis. Results: Complete analysis with shear stress correlation has been performed on twenty fields of plaque. No erosion, rupture or thrombosis was noted. Low shear stress areas had a thinner plaque (1.42 vs 230) and thinner fibrous cap (11 vs 35). Intraplaque hemorrhage was significantly more prevalent in high shear stress (p=0.001, as was calcification (p=0.04), but inflammation and necrosis were not. Conclusion: We can correlate quantitative and qualitative morphologic features and eventually proteomic and genomic alterations within areas of low and high shear stress in atherosclerotic plaques. Our quantitative data supports the concept that high shear stress leads to destabilization of the plaque indicated predominantly by more intraplaque hemorrhage. [ABSTRACT FROM AUTHOR]

Assessing the risk of rupture of intracranial aneurysms is important for clinicians because the natural rupture risk can be exceeded by the small but significant risk carried by current treatments. To this end numerous investigators have used image-based computational fluid dynamics models to extract patient-specific hemodynamics information, but there is no consensus on which variables or hemodynamic characteristics are the most important. This paper describes a computational framework to study and characterize the hemodynamic environment of cerebral aneurysms in order to relate it to clinical events, such as growth or rupture. In particular, a number of hemodynamic quantities are proposed to describe the most salient features of these hemodynamic environments. Application to a patient population indicates that ruptured aneurysms tend to have concentrated inflows, concentrated wall shear stress distributions, high maximal wall shear stress, and smaller viscous dissipation ratios than unruptured aneurysms. Furthermore, these statistical associations are largely unaffected by the choice of physiologic flow conditions. This confirms the notion that hemodynamic information derived from image-based computational models can be used to assess aneurysm rupture risk, to test hypotheses about the mechanisms responsible for aneurysm formation, progression, and rupture, and to answer specific clinical questions. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The study of hemodynamics in arterial models constructed from patient-specific medical images requires the solution of the incompressible flow equations in geometries characterized by complex branching tubular structures. The main challenge with this kind of geometries is that the convergence rate of the pressure Poisson solver is dominated by the graph depth of the computational grid. This paper presents a deflated preconditioned conjugate gradients (DPCG) algorithm for accelerating the pressure Poisson solver. A subspace deflation technique is used to approximate the lowest eigenvalues along the tubular domains. This methodology was tested with an idealized cylindrical model and three patient-specific models of cerebral arteries and aneurysms constructed from medical images. For these cases, the number of iterations decreased by up to a factor of 16, while the total CPU time was reduced by up to 4 times when compared with the standard PCG solver. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: A deflated preconditioned conjugate gradient technique has been developed for the solution of the Pressure–Poisson equation within an incompressible flow solver. The deflation is done using a region-based decomposition of the unknowns, making it extremely simple to implement. The procedure has shown a considerable reduction in the number of iterations. For grids with large graph-depth the savings exceed an order of magnitude. Furthermore, the technique has shown a remarkable insensitivity to the number of groups/regions chosen, and to the way the groups are formed. [Copyright &y& Elsevier]

Modeling the flow dynamics in cerebral aneurysms after the implantation of intrasaccular devices is important for understanding the relationship between flow conditions created immediately posttreatment and the subsequent outcomes. This information, ideally available a priori based on computational modeling prior to implantation, is valuable to identify which aneurysms will occlude immediately and which aneurysms will likely remain patent and would benefit from a different procedure or device. In this report, a methodology for modeling the hemodynamics in intracranial aneurysms treated with intrasaccular flow diverting devices is described. This approach combines an image‐guided, virtual device deployment within patient‐specific vascular models with an immersed boundary method on adaptive unstructured grids. A partial mesh refinement strategy that reduces the number of mesh elements near the aneurysm dome where the flow conditions are largely stagnant was compared with the full refinement strategy that refines the mesh everywhere around the device wires. The results indicate that using the partial mesh refinement approach is adequate for analyzing the posttreatment hemodynamics, at a reduced computational cost. The results obtained on a series of four cerebral aneurysms treated with different intrasaccular devices were in good qualitative agreement with angiographic observations. Promising results were obtained relating posttreatment flow conditions and outcomes of treatments with intrasaccular devices, which need to be confirmed on larger series. [ABSTRACT FROM AUTHOR]