Identification of Small, Regularly Shaped Cerebral Aneurysms Prone to Rupture.

BACKGROUND AND PURPOSE: Many small, regularly shaped cerebral aneurysms rupture; however, they usually receive a low score based on current risk-assessment methods. Our goal was to identify patient and aneurysm characteristics associated with rupture of small, regularly shaped aneurysms and to develop and validate predictive models of rupture in this aneurysm subpopulation. MATERIALS AND METHODS: Cross-sectional data from 1079 aneurysms smaller than 7 mm with regular shapes (without blebs) were used to train predictive models for aneurysm rupture using machine learning methods. These models were based on the patient population, aneurysm location, and hemodynamic and geometric characteristics derived from image-based computational fluid dynamics models. An independent data set with 102 small, regularly shaped aneurysms was used for validation. RESULTS: Adverse hemodynamic environments characterized by strong, concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns were associated with rupture in small, regularly shaped aneurysms. Additionally, ruptured aneurysms were larger and more elongated than unruptured aneurysms in this subset. A total of 5 hemodynamic and 6 geometric parameters along with aneurysm location, multiplicity, and morphology, were used as predictive variables. The best machine learning rupture prediction-model achieved a good performance with an area under the curve of 0.84 on the external validation data set. CONCLUSIONS: This study demonstrated the potential of using predictive machine learning models based on aneurysm-specific hemodynamic, geometric, and anatomic characteristics for identifying small, regularly shaped aneurysms prone to rupture.

Evaluation of Outcome Prediction of Flow Diversion for Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Identifying and predicting which aneurysms are likely to quickly occlude and which ones are likely to remain open following treatment with flow-diverting devices is important to develop optimal patient management strategies. The purpose of this study was to evaluate predictions based on computational fluid dynamics models using the elastase rabbit aneurysm model. MATERIALS AND METHODS: A series of 13 aneurysms created in rabbits were treated with flow diverters, and outcomes were angiographically assessed at 8 weeks' follow-up. Computational fluid dynamics models were constructed from pretreatment 3D rotational angiograms and Doppler ultrasound flow velocity measurements. Postimplantation mean aneurysm inflow rate and flow velocity were used to prospectively predict aneurysm occlusion blinded to the actual outcomes. Specifically, if both variables were below their corresponding thresholds, fast occlusion was predicted, while if one of them was above the threshold, slow or incomplete occlusion was predicted. RESULTS: Of the 13 aneurysms included, 8 were incompletely occluded 8 weeks after treatment, and 5 were completely occluded. A total of 10 computational fluid dynamics-based predictions agreed with the angiographic outcome, reaching 77% accuracy, 80% sensitivity, and 75% specificity. Posttreatment mean velocity alone was able to achieve the same predictive power as the combination of inflow rate and velocity. CONCLUSIONS: Subject-specific computational fluid dynamics models of the hemodynamic conditions created immediately after implantation of flow-diverting devices in experimental aneurysms created in rabbits are capable of prospectively predicting, with a reasonable accuracy, which aneurysms will completely occlude and which ones will remain incompletely occluded.

Regional Aneurysm Wall Enhancement is Affected by Local Hemodynamics: A 7T MRI Study.

BACKGROUND AND PURPOSE: Aneurysm wall enhancement has been proposed as a biomarker for inflammation and instability. However, the mechanisms of aneurysm wall enhancement remain unclear. We used 7T MR imaging to determine the effect of flow in different regions of the wall. MATERIALS AND METHODS: Twenty-three intracranial aneurysms imaged with 7T MR imaging and 3D angiography were studied with computational fluid dynamics. Local flow conditions were compared between aneurysm wall enhancement and nonenhanced regions. Aneurysm wall enhancement regions were subdivided according to their location on the aneurysm and relative to the inflow and were further compared. RESULTS: On average, wall shear stress was lower in enhanced than in nonenhanced regions (P = .05). Aneurysm wall enhancement regions at the neck had higher wall shear stress gradients (P = .05) with lower oscillations (P = .05) than nonenhanced regions. In contrast, aneurysm wall enhancement regions at the aneurysm body had lower wall shear stress (P = .01) and wall shear stress gradients (P = .008) than nonenhanced regions. Aneurysm wall enhancement regions far from the inflow had lower wall shear stress (P = .006) than nonenhanced regions, while aneurysm wall enhancement regions close to the inflow tended to have higher wall shear stress than the nonenhanced regions, but this association was not significant. CONCLUSIONS: Aneurysm wall enhancement regions tend to have lower wall shear stress than nonenhanced regions of the same aneurysm. Moreover, the association between flow conditions and aneurysm wall enhancement seems to depend on the location of the region on the aneurysm sac. Regions at the neck and close to the inflow tend to be exposed to higher wall shear stress and wall shear stress gradients. Regions at the body, dome, or far from the inflow tend to be exposed to uniformly low wall shear stress and have more aneurysm wall enhancement.

Quantitative bone SPECT analysis of mandibular condyles in an asymptomatic population: an approach to normal reference values.

Bone scintigraphy is an extremely valuable technique in diagnosis and treatment planning for patients with condylar hyperplasia (CH). The main objective of this study was to develop an approach to determine normal activity values in the mandibular condyles, adjusted to age and sex, through quantitative analysis of bone single-photon emission computed tomography (SPECT) on a condyle-by-condyle basis and to compare these values with those of a control group comprising patients with confirmed CH. Technetium 99 m-methylene diphosphonate (99mTc-MDP) SPECT studies of the mandibular condyles were performed in patients with no mandibular pathology for quantitative analysis. Regions of interest were drawn on slices representing the upper, middle, and inferior thirds of each condyle and on the summation of transaxial slices representing the whole condyle (three-dimensional approach). The clivus was used for internal validation and the condyle to clivus ratios were calculated. These ratios were compared between 'normal' and 'diseased' condyles. A total 144 condyles in normal patients and 25 in confirmed CH patients were analysed. Differences between the ratios were evaluated through the coefficient of variation. In normal patients, the ratios to the clivus on the summed condyle image showed the lowest variability: range 0.3-1.28 (median 0.74). The quantile regression model showed significant differences with respect to sex, but not to age. The Mann-Whitney test showed significant differences in the ratios to clivus between normal and diseased condyles (P<0.0001).

Analysis of Flow Dynamics and Outcomes of Cerebral Aneurysms Treated with Intrasaccular Flow-Diverting Devices.

BACKGROUND AND PURPOSE: Intrasaccular flow diversion offers a promising treatment option for complex bifurcation aneurysms. The purpose of this study was to compare the flow conditions between successfully occluded and incompletely occluded aneurysms treated with intrasaccular devices. MATERIALS AND METHODS: The hemodynamics in 18 completely occluded aneurysms after treatment with intrasaccular devices was compared against 18 that were incompletely occluded at follow-up. Hemodynamic and geometric parameters were obtained from computational fluid dynamics models constructed from 3D angiographies. Models of the intrasaccular devices were created and interactively deployed within the vascular models using posttreatment angiography images for guidance. Hemodynamic and geometric variables were compared using the Mann-Whitney test and univariate logistic regression analysis. RESULTS: Incomplete occlusion was associated with large posttreatment mean aneurysm inflows (P = .02) and small reductions in the mean inflow rate (P = .01) and inflow concentration index (P = .03). Incompletely occluded aneurysms were larger (P = .002) and had wider necks (P = .004) than completely occluded aneurysms and tended to have more complex flow patterns, though this trend was not significant after adjusting for multiple testing. CONCLUSIONS: The outcome of cerebral aneurysm treatment with intrasaccular flow diverters is associated with flow conditions created immediately after device implantation. Flow conditions unfavorable for immediate and complete occlusion seem to be created by improper positioning or orientation of the device. Complete occlusion is more difficult to achieve in larger aneurysms, aneurysms with wider necks, and aneurysms with stronger and more complex flows.

Identification of Hostile Hemodynamics and Geometries of Cerebral Aneurysms: A Case-Control Study.

BACKGROUND AND PURPOSE: Hostile hemodynamic conditions and geometries are thought to predispose aneurysms for instability and rupture. This study compares stable, unstable, and ruptured aneurysms while controlling for location and patient characteristics. MATERIALS AND METHODS: The hemodynamics and geometries of 165 stable, 65 unstable, and 554 ruptured aneurysms were compared. Hemodynamics was modeled using image-based computational fluid dynamics. Case-control pairs were selected matching aneurysm location, patient age, and sex. Paired Wilcoxon tests were used to compare hemodynamic and geometric variables among different aneurysm groups. The pairing was repeated 100 times, and the combined P values were calculated and adjusted for multiple testing. RESULTS: Ruptured aneurysms had lower minimum wall shear stress (P = .03), higher maximum wall shear stress (P = .03), more concentrated (P = .03) and mean oscillatory shear stress (P = .03), higher maximum velocity (P = .03), and more complex flows (vortex core-line length, P = .03) than stable aneurysms. Similarly, unstable aneurysms had more concentrated shear stress (P = .04) and more complex flows (vortex core-line length, P = .04) than stable aneurysms. Compared with stable aneurysms, ruptured aneurysms were larger (size ratio, aneurysm size/vessel size, P = .03), more elongated (aspect ratio, P = .03), and irregular (nonsphericity index, P = .03). Similarly, unstable aneurysms were larger (size ratio, P = .04), more elongated (aspect ratio, P = .04), and irregular (bulge location, P = .04; area-weighted Gaussian curvature; P = .04) than stable aneurysms. No significant differences were found between unstable and ruptured aneurysms. CONCLUSIONS: Unstable and ruptured aneurysms have more complex flows with concentrated wall shear stress and are larger, more elongated, and irregular than stable aneurysms, independent of aneurysm location and patient sex and age.

Uso adecuado de las pruebas no invasivas de isquemia para guiar la toma de decisión sobre revascularización tras un infarto agudo de miocardio con elevación del segmento ST en países iberoamericanos: Resultados de la reunión de un panel de expertos de la International Atomic Energy Agency / Appropriate use of noninvasive ischemia testing to guide revascularization decision making following acute ST elevation myocardial infarction in Latin American countries: Results from an expert panel meeting of the International Atomic Energy Agency

En los países iberoamericanos y caribeños las cardiopatías, y en especial las cardiopatías isquémicas, constituyen la causa principal de muerte tanto en varones como en mujeres. En muchos de estos países los esfuerzos sobre salud pública y comunitaria tratan de definir las estrategias de cuidados que sean efectivas desde los puntos de vista clínico y de costes, promuevan la prevención primaria y secundaria, y redunden en la mejora de los resultados de los pacientes. El enfoque óptimo para el tratamiento de episodios agudos tales como el infarto de miocardio con elevación del segmento ST (IAMCEST) es una cuestión controvertida; sin embargo, el papel de la valoración de la carga isquémica residual en los pacientes de IAMCEST tras una intervención coronaria percutánea primaria se encuentra en expansión. Aunque los ensayos clínicos aleatorizados han establecido el valor de la revascularización guiada por la reserva de flujo fraccional escalonada, el uso de técnicas de imagen funcionales no invasivas puede jugar un papel similar a mucho menor coste. Para los pacientes iberoamericanos y caribeños, podrían aplicarse las técnicas disponibles de imágenes de estrés para definir la isquemia residual en la arteria no infartada y orientar la revascularización en un procedimiento escalonado tras una intervención coronaria percutánea primaria. El uso de imagen cardíaca nuclear, respaldado por su disponibilidad relativamente amplia, coste moderado y capacidades cuantitativas sólidas, puede servir de guía a una atención efectiva y reducir los episodios cardíacos subsiguientes en pacientes con cardiopatía coronaria. Esta técnica no invasiva puede evitar las cuestiones de seguridad potenciales de los procedimientos invasivos prolongados y repetidos, y servir de referencia para las pruebas subsiguientes de estrés tras el episodio de IAMCEST inicial. Este documento de consenso fue diseñado por la reunión del panel de expertos de la International Atomic Energy Agency y destaca la evidencia disponible centrada en la utilidad de la imagen de perfusión miocárdica de estrés en pacientes post-IAMCEST. El documento podría servir como guía para el uso prudente y adecuado de la imagen nuclear orientada a la gestión terapéutica, a fin de evitar los procedimientos invasivos innecesarios en los países iberoamericanos y caribeños, en los que los recursos podrían ser escasos

Across Latin American and Caribbean countries, cardiovascular disease and especially ischemic heart disease is currently the main cause of death both in men and in women. For most Latin American and Caribbean countries, public and community health efforts aim to define care strategies which are both clinically and cost effective and promote primary and secondary prevention, resulting in improved patient outcomes. The optimal approach to deal with acute events such as ST-elevation myocardial infarction (STEMI) is a matter of controversy; however, there is an expanding role for assessing residual ischemic burden in STEMI patients following primary percutaneous coronary intervention. Although randomized clinical trials have established the value of staged fractional flow reserve-guided revascularization, the use of noninvasive functional imaging modalities may play a similar role at a much lower cost. For LAC, available stress imaging techniques could be applied to define residual ischemia in the non-infarct related artery and to target revascularization in a staged procedure after primary percutaneous coronary intervention The use of nuclear cardiac imaging, supported by its relatively wide availability, moderate cost, and robust quantitative capabilities, may serve to guide effective care and to reduce subsequent cardiac events in patients with coronary artery disease. This noninvasive approach may avert potential safety issues with repeat and lengthy invasive procedures, and serve as a baseline for subsequent follow-up stress testing following the index STEMI event. This consensus document was devised from an expert panel meeting of the International Atomic Energy Agency, highlighting available evidence with a focus on the utility of stress myocardial perfusion imaging in post-STEMI patients. The document could serve as guidance to the prudent and appropriate use of nuclear imaging for targeting therapeutic management and avoiding unnecessary invasive procedures within Latin American and Caribbean countries, where resources could be scarce

Appropriate use of noninvasive ischemia testing to guide revascularization decision making following acute ST elevation myocardial infarction in Latin American countries: Results from an expert panel meeting of the International Atomic Energy Agency. / Uso adecuado de las pruebas no invasivas de isquemia para guiar la toma de decisión sobre revascularización tras un infarto agudo de miocardio con elevación del segmento ST en países iberoamericanos: Resultados de la reunión de un panel de expertos de la International Atomic Energy Agency.

Across Latin American and Caribbean countries, cardiovascular disease and especially ischemic heart disease is currently the main cause of death both in men and in women. For most Latin American and Caribbean countries, public and community health efforts aim to define care strategies which are both clinically and cost effective and promote primary and secondary prevention, resulting in improved patient outcomes. The optimal approach to deal with acute events such as ST-elevation myocardial infarction (STEMI) is a matter of controversy; however, there is an expanding role for assessing residual ischemic burden in STEMI patients following primary percutaneous coronary intervention. Although randomized clinical trials have established the value of staged fractional flow reserve-guided revascularization, the use of noninvasive functional imaging modalities may play a similar role at a much lower cost. For LAC, available stress imaging techniques could be applied to define residual ischemia in the non-infarct related artery and to target revascularization in a staged procedure after primary percutaneous coronary intervention The use of nuclear cardiac imaging, supported by its relatively wide availability, moderate cost, and robust quantitative capabilities, may serve to guide effective care and to reduce subsequent cardiac events in patients with coronary artery disease. This noninvasive approach may avert potential safety issues with repeat and lengthy invasive procedures, and serve as a baseline for subsequent follow-up stress testing following the index STEMI event. This consensus document was devised from an expert panel meeting of the International Atomic Energy Agency, highlighting available evidence with a focus on the utility of stress myocardial perfusion imaging in post-STEMI patients. The document could serve as guidance to the prudent and appropriate use of nuclear imaging for targeting therapeutic management and avoiding unnecessary invasive procedures within Latin American and Caribbean countries, where resources could be scarce.

Hemodynamic Characteristics of Ruptured and Unruptured Multiple Aneurysms at Mirror and Ipsilateral Locations.

BACKGROUND AND PURPOSE: Different hemodynamic patterns have been associated with aneurysm rupture. The objective was to test whether hemodynamic characteristics of the ruptured aneurysm in patients with multiple aneurysms were different from those in unruptured aneurysms in the same patient. MATERIALS AND METHODS: Twenty-four mirror and 58 ipsilateral multiple aneurysms with 1 ruptured and the others unruptured were studied. Computational fluid dynamics models were created from 3D angiographies. Case-control studies of mirror and ipsilateral aneurysms were performed with paired Wilcoxon tests. RESULTS: In mirror pairs, the ruptured aneurysm had more oscillatory wall shear stress (P = .007) than the unruptured one and tended to be more elongated (higher aspect ratio), though this trend achieved only marginal significance (P = .03, 1-sided test). In ipsilateral aneurysms, ruptured aneurysms had larger maximum wall shear (P = .05), more concentrated (P < .001) and oscillatory wall shear stress (P < .001), stronger (P < .001) and more concentrated inflow jets (P < .001), larger maximum velocity (P < .001), and more complex flow patterns (P < .001) compared with unruptured aneurysms. Additionally, ruptured aneurysms were larger (P < .001) and more elongated (P < .001) and had wider necks (P < .001) and lower minimum wall shear stress (P < .001) than unruptured aneurysms. CONCLUSIONS: High wall shear stress oscillations and larger aspect ratios are associated with rupture in mirror aneurysms. Adverse flow conditions characterized by high and concentrated inflow jets; high, concentrated, and oscillatory wall shear stress; and strong, complex and unstable flow patterns are associated with rupture in ipsilateral multiple aneurysms. In multiple ipsilateral aneurysms, these unfavorable flow conditions are more likely to develop in larger, more elongated, more wide-necked, and more distal aneurysms.

Angioarchitectures and Hemodynamic Characteristics of Posterior Communicating Artery Aneurysms and Their Association with Rupture Status.

BACKGROUND AND PURPOSE: Intracranial aneurysms originating at the posterior communicating artery are known to have high rupture risk compared with other locations. We tested the hypothesis that different angioarchitectures (ie, branch point configuration) of posterior communicating artery aneurysms are associated with aneurysm hemodynamics, which in turn predisposes aneurysms to rupture. MATERIALS AND METHODS: A total of 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) were studied with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Hemodynamic characteristics were compared between ruptured and unruptured aneurysms, as well as among aneurysms with different angioarchitectures. RESULTS: Angioarchitecture was associated with rupture (P = .003). Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions (maximum wall shear stress, P < .001; shear concentration index, P < .001; mean oscillatory shear index, P < .001), stronger and more concentrated inflow jets (represented as Q, P = .01; inflow concentration index, P < .001), and more complex and unstable flow patterns (vortex core length, P < .001; proper orthogonal decomposition entropy, P < .001) compared with unruptured aneurysms. These adverse conditions were more common in aneurysms with bifurcation-type angioarchitectures compared with those with lateral or sidewall angioarchitectures. Interestingly, ruptured aneurysms also had lower normalized mean wall shear stress (P = .02) and minimum wall shear stress (P = .002) than unruptured aneurysms. CONCLUSIONS: High-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. These characteristics include strong and concentrated inflow jets, concentrated regions of elevated wall shear stress, oscillatory wall shear stress, lower normalized wall shear stress, and complex and unstable flow patterns.

Understanding Angiography-Based Aneurysm Flow Fields through Comparison with Computational Fluid Dynamics.

BACKGROUND AND PURPOSE: Hemodynamics is thought to be an important factor for aneurysm progression and rupture. Our aim was to evaluate whether flow fields reconstructed from dynamic angiography data can be used to realistically represent the main flow structures in intracranial aneurysms. MATERIALS AND METHODS: DSA-based flow reconstructions, obtained during interventional treatment, were compared qualitatively with flow fields obtained from patient-specific computational fluid dynamics models and quantitatively with projections of the computational fluid dynamics fields (by computing a directional similarity of the vector fields) in 15 cerebral aneurysms. RESULTS: The average similarity between the DSA and the projected computational fluid dynamics flow fields was 78% in the parent artery, while it was only 30% in the aneurysm region. Qualitatively, both the DSA and projected computational fluid dynamics flow fields captured the location of the inflow jet, the main vortex structure, the intrasaccular flow split, and the main rotation direction in approximately 60% of the cases. CONCLUSIONS: Several factors affect the reconstruction of 2D flow fields from dynamic angiography sequences. The most important factors are the 3-dimensionality of the intrasaccular flow patterns and inflow jets, the alignment of the main vortex structure with the line of sight, the overlapping of surrounding vessels, and possibly frame rate undersampling. Flow visualization with DSA from >1 projection is required for understanding of the 3D intrasaccular flow patterns. Although these DSA-based flow quantification techniques do not capture swirling or secondary flows in the parent artery, they still provide a good representation of the mean axial flow and the corresponding flow rate.

Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with Inflammation and Degenerative Changes of the Aneurysm Wall.

BACKGROUND AND PURPOSE: Saccular intracranial aneurysm is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with saccular intracranial aneurysm rupture. We investigated how saccular intracranial aneurysm hemodynamics is associated with wall remodeling and inflammation of the saccular intracranial aneurysm wall. MATERIALS AND METHODS: Tissue samples resected during a saccular intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT angiographies. RESULTS: More stable and less complex flows were associated with thick, hyperplastic saccular intracranial aneurysm walls, while slower flows with more diffuse inflow were associated with degenerated and decellularized saccular intracranial aneurysm walls. Wall degeneration (P = .041) and rupture were associated with increased inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate (P = .046) were associated with increased inflammation. Inflammation was also associated with lack of an intact endothelium (P = .034) and the presence of organized luminal thrombosis (P = .018), though overall organized thrombosis was associated with low minimum wall shear stress (P = .034) and not with the flow conditions associated with inflammation. CONCLUSIONS: Flow conditions in the saccular intracranial aneurysm are associated with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is related to high flow activity, including elevated wall shear stress. Endothelial injury may be a mechanism by which flow induces inflammation in the saccular intracranial aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular intracranial aneurysms at risk of developing inflammation, a potential biomarker for rupture.

Mechanistic Studies on the Self-Assembly of PLGA Patchy Particles and Their Potential Applications in Biomedical Imaging.

Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the molecular mechanisms involved in the formation of these particles. We have been studying in depth the formation of patchy polymeric particles. These particles are made of PLGA and lipid-polymer functional groups. They have unique patch-core-shell structural features: hollow or solid hydrophobic cores and a patchy surface. Previously, we identified the shear stress as the most important parameter in a patchy particle's formation. Here, we investigated in detail the role of shear stress in the patchy particle's internal and external structure using an integrative experimental and computational approach. By cross-sectioning the multipatch particles, we found lipid-based structures embedded in the entire PLGA matrix, which represents a unique finding in the PLGA field. By developing novel computational fluid dynamics and molecular dynamics simulations, we found that the shear stress determines the internal structure of the patchy particles. Equally important, we discovered that these particles emit a photoacoustic (PA) signal in the optical clinical imaging window. Our results show that particles with multiple patches emit a higher PA signal than single-patch particles. This phenomenon most likely is due to the fact that multipatchy particles absorb more heat than single-patchy particles as shown by differential scanning calorimetry analysis. Furthermore, we demonstrated the use of patchy polymeric particles as photoacoustic molecular probes both in vitro and in vivo studies. The fundamental studies described here will help us to design more effective PLGA carriers for a number of medical applications as well as to accelerate their medical translation.

Strategy for modeling flow diverters in cerebral aneurysms as a porous medium.

Simulations using the patient-specific geometry of the aneurysm may help in a better planning of the treatment and in a consequent reduction of the associated risks. We propose, evaluate, and implement a methodology for the simulation of flow diverter (FD) devices in intracranial aneurysms by using a porous medium method (PMM), which greatly reduces the computational cost of these simulations compared with immersed method (IMM) approaches used to model complex FDs. The method relies on parameters from an empirical correlation derived from experimental observations in wire screens, consistent with CFD simulations. The verification of our PMM strategy was carried out by comparing the results of simulations in different (patient-specific) geometries and FDs, to those obtained under identical conditions by the IMM. Overall, both quantitative and qualitative results are consistent between IMM and PMM in cases where the local porosity remains roughly uniform throughout the neck, with differences in the reduction of the observables lower than 10%. This PMM strategy is up to 10 times faster than the IMM, which allows for a runtime of hours instead of days, bringing it closer for its application in the clinic.

Analysis of hemodynamics and aneurysm occlusion after flow-diverting treatment in rabbit models.

BACKGROUND AND PURPOSE: Predicting the outcome of flow diversion treatment of cerebral aneurysms remains challenging. Our aim was to investigate the relationship between hemodynamic conditions created immediately after flow diversion and subsequent occlusion of experimental aneurysms in rabbits. MATERIALS AND METHODS: The hemodynamic environment before and after flow-diversion treatment of elastase-induced aneurysms in 20 rabbits was modeled by using image-based computational fluid dynamics. Local aneurysm occlusion was quantified by using a voxelization technique on 3D images acquired 8 weeks after treatment. Global and local voxel-by-voxel hemodynamic variables were used to statistically compare aneurysm regions that later thrombosed to regions that remained patent. RESULTS: Six aneurysms remained patent at 8 weeks, while 14 were completely or nearly completely occluded. Patent aneurysms had statistically larger neck sizes (P = .0015) and smaller mean transit times (P = .02). The velocity, vorticity, and shear rate were approximately 2.8 times (P < .0001) larger in patent regions-that is, they had larger "flow activity" than regions that progressed to occlusion. Statistical models based on local hemodynamic variables were capable of predicting local occlusion with good precision (84% accuracy), especially away from the neck (92%-94%). Predictions near the neck were poorer (73% accuracy). CONCLUSIONS: These results suggests that the dominant healing mechanism of occlusion within the aneurysm dome is related to slow-flow-induced thrombosis, while near the neck, other processes could be at play simultaneously.

Quantifying the large-scale hemodynamics of intracranial aneurysms.

BACKGROUND AND PURPOSE: Hemodynamics play an important role in the mechanisms that govern the initiation, growth, and possible rupture of intracranial aneurysms. The purpose of this study was to objectively characterize these dynamics, classify them, and connect them to aneurysm rupture. MATERIALS AND METHODS: Image-based computational fluid dynamic simulations were used to re-create the hemodynamics of 210 patient-specific intracranial aneurysm geometries. The hemodynamics were then classified according to their spatial complexity and temporal stability by using quantities derived from vortex core lines and proper orthogonal decomposition. RESULTS: The quantitative classification was compared with a previous qualitative classification performed by visual inspection. Receiver operating characteristic curves provided area-under-the-curve estimates for spatial complexity (0.905) and temporal stability (0.85) to show that the 2 classifications were in agreement. Statistically significant differences were observed in the quantities describing the hemodynamics of ruptured and unruptured intracranial aneurysms. Specifically, ruptured aneurysms had more complex and more unstable flow patterns than unruptured aneurysms. Spatial complexity was more strongly associated with rupture than temporal stability. CONCLUSIONS: Complex-unstable blood flow dynamics characterized by longer core line length and higher entropy could induce biologic processes that predispose an aneurysm for rupture.

Effects of flow-diverting device oversizing on hemodynamics alteration in cerebral aneurysms.

BACKGROUND AND PURPOSE: Flow-diverting devices are increasingly being considered for large or giant aneurysms with wide necks, which are difficult to treat with coils or clips. These devices are often oversized to achieve good positioning against the artery wall. The objective of this study was to analyze the effect of oversized flow-diverting devices in altering aneurysmal flows and creating hemodynamic environments favorable for thrombosis and aneurysm occlusion. MATERIALS AND METHODS: Patient-specific computational fluid dynamics models of 3 cerebral aneurysms were constructed from 3D angiography images. Numeric simulations of the hemodynamics after implanting stents of increasing diameters were performed. The corresponding modifications of hemodynamic variables such as aneurysm inflow rate, average velocity, shear rate, and wall shear stress were calculated and compared. RESULTS: The results indicate that because the devices are oversized, the stent cells stretch in the direction of the vessel axis, change cell angles, and result in larger cells. This change in the cell geometry causes a diminution of the hemodynamic performance of the stent. Quantitatively, stent oversizing results in larger values of aneurysm inflow rates, average velocity, shear rate, and wall shear stress compared with nonoversizing cases. CONCLUSIONS: The efficacy of flow-diverting devices in modifying intra-aneurysmal flow can be substantially reduced by oversizing the devices. As the level of device oversize increases, aneurysmal hemodynamic variables are significantly less affected.

Clinical Application of Image-Based CFD for Cerebral Aneurysms.

During the last decade, the convergence of medical imaging and computational modeling technologies has enabled tremendous progress in the development and application of image-based computational fluid dynamics modeling of patient-specific blood flows. These techniques have been used for studying the basic mechanisms involved in the initiation and progression of vascular diseases, for studying possible ways to improve the diagnosis and evaluation of patients by incorporating hemodynamics information to the anatomical data typically available, and for the development of computational tools that can be used to improve surgical and endovascular treatment planning. However, before these technologies can have a significant impact on the routine clinical practice, it is still necessary to demonstrate the connection between the extra information provided by the models and the natural progression of vascular diseases and the outcome of interventions. This paper summarizes some of our contributions in this direction, focusing in particular on cerebral aneurysms.

Aneurysm rupture following treatment with flow-diverting stents: computational hemodynamics analysis of treatment.

BACKGROUND AND PURPOSE: Flow-diverting approaches to intracranial aneurysm treatment had many promising early results, but recent apparently successful treatments have been complicated by later aneurysm hemorrhage. We analyzed 7 cases of aneurysms treated with flow diversion to explore the possible rupture mechanisms. MATERIALS AND METHODS: CFD analysis of pre- and posttreatment conditions was performed on 3 giant aneurysms that ruptured after treatment and 4 successfully treated aneurysms. Pre- and posttreatment hemodynamics were compared including WSS, relative blood flows, vascular resistances, and pressures, to identify the effects of flow-diverter placements. RESULTS: Expected reductions in aneurysm velocity and WSS were obtained, indicating effective flow diversion from the sac into the parent artery, consistent with periprocedural observations. In each case with postaneurysm rupture, the result of flow diversion led to an increase in pressure within the aneurysm. This pressure increase is related to larger effective resistance in the parent artery from placement of the devices and, in 2 cases, the reduction of a preaneurysm stenosis. CONCLUSIONS: Flow-diversion devices can cause intra-aneurysmal pressure increases, which can potentially lead to rupture, especially for giant aneurysms. This relates both to changes in the parent artery configuration, such as reduction of a proximal stenosis, and to the flow diversion into higher resistance parent artery pathways combined with cerebral autoregulation, leading to higher pressure gradients. These may be important effects that should be considered when planning interventions. Potentially dangerous cases could be identified with angiography and/or patient-specific CFD models.

Quantitative characterization of the hemodynamic environment in ruptured and unruptured brain aneurysms.

BACKGROUND AND PURPOSE: Hemodynamics are thought to play an important role in the mechanisms of aneurysm pathogenesis, progression, and rupture. The purpose of this study was to define quantitative measures related to qualitative flow characteristics previously analyzed and to investigate their relationship to aneurysm rupture. MATERIALS AND METHODS: The hemodynamic environments in 210 cerebral aneurysms were analyzed by using image-based CFD under different flow conditions. Quantitative hemodynamic variables were defined and extracted from the simulation results. A statistical analysis of the relationship to the previous history of aneurysm rupture was performed, and the variability with flow conditions was assessed. RESULTS: Ruptured aneurysms were more likely to have larger inflow concentrations, larger MWSS, larger shear concentrations, and lower viscous dissipation ratios than unruptured aneurysms. Areas under low WSS and measures of abnormally low shear force distributions of ruptured and unruptured aneurysms were not statistically different. Although the values of hemodynamic quantities changed with different flow conditions, the statistical differences or ratios between their mean values over the ruptured and unruptured groups were maintained, for both pulsatile and steady flows. CONCLUSIONS: Concentrated inflow streams and WSS distributions with elevated levels of MWSS and low aneurysmal viscous dissipation are statistically associated with a clinical history of prior aneurysm rupture. In contrast, the area and total viscous shear force applied in the aneurysm region subjected to abnormally low WSS levels are not. This study highlights the potential for image-based CFD for investigating aneurysm-evolution mechanisms and for clinical assessment of aneurysm risks.