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The autorotation and energy harvesting potential of bladeless turbine models are tested in a confined water stream with Reynolds numbers from 20 K to 40 K. Mini bladeless turbine models of various ...

BackgroundBlebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites.MethodsBlebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs.ResultsThin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%.ConclusionsNot all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.

BackgroundAlthough it is generally believed that blebs represent weaker spots in the walls of intracranial aneurysms (IAs), it is largely unknown which aneurysm characteristics favor their development.ObjectiveTo investigate possible associations between aneurysm hemodynamic and geometric characteristics and the development of blebs in intracranial aneurysms.MethodsA total of 270 IAs in 199 patients selected for surgical clipping were studied. Blebs were visually identified and interactively marked on patient-specific vascular models constructed from presurgical images. Blebs were then deleted from the vascular reconstruction to approximate the aneurysm before bleb formation. Computational fluid dynamics studies were performed in these models and in cases without blebs. Hemodynamic and geometric characteristics of aneurysms with and without blebs were compared.ResultsA total of 173 aneurysms had no blebs, while 97 aneurysms had a total of 122 blebs. Aneurysms favoring bleb formation had stronger (pConclusionsStrong and concentrated inflow jets, high-speed, complex, and unstable flow patterns, and concentrated, oscillatory, and heterogeneous WSS patterns favor the formation of blebs in IAs. Blebs are more likely to form in large, elongated, and irregularly shaped aneurysms. These adverse characteristics could be considered signs of aneurysm instability when evaluating aneurysms for conservative observation or treatment.

This study is devoted to the investigation of optimal conditions for flow-induced autorotation of a hinged cylinder in a direction perpendicular to the flow in a water tunnel. Previous studies of h...

Objective: Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 μm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I—only calcification, no lipid pools (20/51, 39%), Type II—calcification and lipid pools, not colocalized (19/51, 37%), Type III—calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. Conclusions: Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.

Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

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.

BackgroundBlebs are rupture risk factors in intracranial aneurysms (IAs), but their prevalence, distribution, and associations with clinical factors as well as their causes and effects on aneurysm vulnerability remain unclear.MethodsA total of 122 blebs in 270 IAs selected for surgery were studied using patient-specific vascular reconstructions from 3D angiographic images. Bleb geometry, location on the aneurysm, and frequency of occurrence in aneurysms at different locations were analyzed. Associations between gender, age, smoking, hypertension, hormone therapy, dental infection, and presence of blebs were investigated.ResultsOf all aneurysms with blebs, 77% had a single bleb and 23% had multiple blebs. Only 6% of blebs were at the neck, while 46% were in the body and 48% in the dome. Aneurysms with blebs were larger (pConclusionsBlebs are common in IAs, and most aneurysms harboring blebs have a single bleb. Blebs in the aneurysm neck are rare, but they are equally common in the body and dome. The presence of blebs in IAs was associated with dental infection, and negatively associated with hormone replacement therapy.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: A total of 88 aneurysms at four locations were studied with image based 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. RESULTS: 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. CONCLUSION: 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.

Background and purposeVertebrobasilar dolichoectatic and fusiform aneurysms (VBDAs) are known to have a poor natural history, with high rates of growth, rupture, and stroke. The purpose of this study was to identify hemodynamic characteristics that differ between VBDAs associated with growth, rupture, and stroke.Materials and methodsVBDAs with CT angiography or MR angiography followed longitudinally without treatment were studied. Unstable aneurysms were defined as those that grew or ruptured during follow-up. Aneurysms associated with stroke were defined as those associated with posterior circulation infarct at follow-up. Baseline data, including demographics, comorbidities, and aneurysm morphology and size were collected. Image based computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups (stable vs unstable and no stroke vs stroke) using the Wilcoxon test.ResultsA total of 37 VBDAs were included (24 stable, 13 unstable; 30 no stroke, 7 stroke). Unstable aneurysms had lower shear rates (P=0.05), blood flow velocity (P=0.03), and lower vorticity (P=0.049) than stable aneurysms. In addition, unstable aneurysms had higher mean oscillatory shear indices (P=0.001). There were no differences in the hemodynamic characteristics of aneurysms in the stroke group compared with the non-stroke group.ConclusionThis small study suggests there may be hemodynamic differences between unstable and stable VBDAs. Unstable VBDAs appear to be under lower flow conditions with lower velocity, vorticity, and shear rates, and have more oscillatory flow. There was no difference in the hemodynamic characteristics of aneurysms in the stroke and no stroke group.

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 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.

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 P P P = .01; inflow concentration index, P P P 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.

BACKGROUND AND PURPOSE: Cerebral aneurysms in the posterior circulation are known to have a higher rupture risk than those in the anterior circulation. We sought to test the hypothesis that differences in hemodynamics can explain the difference in rupture rates. MATERIALS AND METHODS: A total of 117 aneurysms, 63 at the tip of the basilar artery (27 ruptured, 36 unruptured, rupture rate = 43%) and 54 at the bifurcation of the internal carotid artery (11 ruptured, 43 unruptured, rupture rate = 20%) were analyzed with image-based computational fluid dynamics. Several hemodynamic variables were compared among aneurysms at each location and between ruptured and unruptured aneurysms at each location. RESULTS: On average, aneurysms at the basilar tip had more concentrated inflow (P < .001), a larger inflow rate (P < .001), a larger maximum oscillatory shear index (P = .003), more complex flows (P = .033), and smaller areas under low wall shear stress (P < .001) than aneurysms at the bifurcation of the internal carotid artery. In general, ruptured aneurysms had larger inflow concentration (P = .02), larger shear concentration (P = .02), more complex flows (P < .001), and smaller minimum wall shear stress (P = .003) than unruptured aneurysms. CONCLUSIONS: High flow conditions, characterized by large and concentrated inflow jets, complex and oscillatory flow patterns, and wall shear stress distributions with focalized regions of high shear and large regions of low shear, are associated with aneurysm rupture, especially for basilar tip aneurysms. The higher flow conditions in basilar tip aneurysms could explain their increased rupture risk compared with internal carotid bifurcation aneurysms.

Symmetric bodies such as cylinders and spheroidal bodies, in their terminal stable states, are long known to have their long axis align themselves perpendicular to the direction of the flow. This property has been confirmed in primarily sedimentation based theoretical, experimental and numerical techniques and the transition to a terminal stable state is believed to coincide with the onset of significant inertial effects in the flow. However, the threshold at which this transition occurs is yet unknown. We conduct modified experiments with hinged bodies and a CFD study to examine the nature of the transition of prolate spheroids and cylinders of various aspect ratios, from initial to their terminal stable equilibrium. Our experiments and numerics, both reveal the presence of intermediate metastable states which are sensitive to the flow Reynolds number and physical attributes of the immersed body and gradually lead to the stable state.

This paper investigates the mechanics of clearance of an embedded particle in a lubrication layer of viscoelastic fluid. We show theoretically that in a slider bearing domain containing a viscoelastic fluid, the oscillating shearing motion of a wall aids in transporting away any embedded particle towards the moving boundary. The impact of geometry and material properties of the fluid layer are explored by coupling theoretical and numerical methods. Our approach suggests a possible mechanism by which the human eye could clear out any debris beneath the eyelid, under responsive blinking. Our simplified analysis brings to bear interesting approaches from physics and engineering upon a very complex biological problem and could provide essential clues about the physiological design of the tear film.

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.

PurposeAssessing the rupture probability of intracranial aneurysms (IAs) remains challenging. Therefore, hemodynamic simulations are increasingly applied toward supporting physicians during treatment planning. However, due to several assumptions, the clinical acceptance of these methods remains limited.MethodsTo provide an overview of state-of-the-art blood flow simulation capabilities, the Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was conducted. Seventeen research groups from all over the world performed segmentations and hemodynamic simulations to identify the ruptured aneurysm in a patient harboring five IAs. Although simulation setups revealed good similarity, clear differences exist with respect to the analysis of aneurysm shape and blood flow results. Most groups (12/71%) included morphological and hemodynamic parameters in their analysis, with aspect ratio and wall shear stress as the most popular candidates, respectively.ResultsThe majority of groups (7/41%) selected the largest aneurysm as being the ruptured one. Four (24%) of the participating groups were able to correctly select the ruptured aneurysm, while three groups (18%) ranked the ruptured aneurysm as the second most probable. Successful selections were based on the integration of clinically relevant information such as the aneurysm site, as well as advanced rupture probability models considering multiple parameters. Additionally, flow characteristics such as the quantification of inflow jets and the identification of multiple vortices led to correct predictions.ConclusionsMATCH compares state-of-the-art image-based blood flow simulation approaches to assess the rupture risk of IAs. Furthermore, this challenge highlights the importance of multivariate analyses by combining clinically relevant metadata with advanced morphological and hemodynamic quantification.

OBJECTIVEIncidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors’ goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data.METHODSPatient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm’s shape and hemodynamics. Next, the previously developed model’s discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data.RESULTSThe US model’s AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10.CONCLUSIONSDeveloping an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

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.

The evolution of intracranial aneurysms (IAs) is thought to be driven by progressive wall degradation in response to abnormal hemodynamics. Previous studies focused on the relationship between global hemodynamics and wall properties. However, hemodynamics, wall structure and mechanical properties of cerebral aneurysms can be non-uniform across the aneurysm wall. Therefore, the aim of this work is to introduce a methodology for mapping local hemodynamics to local wall structure in resected aneurysm specimens. This methodology combines image-based computational fluid dynamics, tissue resection, micro-CT imaging of resected specimens mounted on 3D-printed aneurysm models, alignment to 3D vascular models, multi-photon microscopy of the wall, and regional mapping of hemodynamics and wall properties. This approach employs a new 3D virtual marking tool for surgeons to delineate the location of the resected specimen directly on the 3D model, while in the surgical suite. The case of a middle cerebral artery aneurysm is used to illustrate the application of this methodology to the assessment of the relationship between local wall shear stress and local wall properties including collagen fiber organization and wall geometry. This methodology can similarly be used to study the relationship between local intramural stresses and local wall structure.

BackgroundWhile clinical and angiographic risk factors for intracranial aneurysm instability are well established, it is reasonable to postulate that intra-aneurysmal hemodynamics also have a role in aneurysm instability.ObjectiveTo identify hemodynamic characteristics that differ between radiologically unstable and stable unruptured intracranial aneurysms.Materials and methods12 pairs of unruptured intracranial aneurysms with a 3D rotational angiographic set of images and followed up longitudinally without treatment were studied. Each pair consisted of one stable aneurysm (no change on serial imaging) and one unstable aneurysm (demonstrated growth of at least 1 mm diameter or ruptured during follow-up) of matching size (within 10%) and locations. Patient-specific computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups using the paired Wilcoxon test.ResultsThe area of the aneurysm under low wall shear stress (low shear stress area (LSA)) was 2.26 times larger in unstable aneurysms than in stable aneurysms (p=0.0499). The mean aneurysm vorticity was smaller by a factor of 0.57 in unstable aneurysms compared with stable aneurysms (p=0.0499). No statistically significant differences in geometric variables or shape indices were found.ConclusionsThis pilot study suggests there may be hemodynamic differences between unstable and stable unruptured cerebral aneurysms. In particular, the area under low wall shear stress was larger in unstable aneurysms. These findings should be considered tentative until confirmed by future larger studies.

This paper is devoted to the study and classification of vortex-induced oscillation and the wake structure of flow past finite cylinders. Experiments were performed in a water tunnel using cylindrical particles hinged in the center of the test section while allowing them one degree of rotational freedom. The speed of flow and aspect ratio of the cylinders were used to vary the Reynolds number in the study between 100 and 5000. The cylinders display different responses to the fluid flow depending upon the Re, ranging from steady orientation, periodic oscillation to autorotation. A hydrogen bubble flow visualization technique was used to examine the vortex structure and supported by image analysis techniques. Specific features of the wake structure such as length of the primary vortex, its frequency and amplitude were analyzed as a function of Re. Our investigations indicate that the frequency of oscillation of the cylinder and the vortex shedding increases monotonically with the Reynolds number. Also, the length of the primary vortex versus Re shows interesting features and reveals possible critical points in the flow when vortex structure changes. In order to better understand qualitative aspects of the cylinder’s dynamics that go beyond experiments, a simplistic forced nonlinear pendulum toy model was employed and seen to capture qualitative aspects of the cylinder’s dynamics.

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 ten-fold 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.

PURPOSE: The mechanisms of cerebral aneurysm rupture are not fully understood. We analyzed the associations of hemodynamics, morphology, 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.

INTRODUCTION: Modeling the flow dynamics in cerebral aneurysms after the implantation of intra-saccular devices is important for understanding the relationship between flow conditions created immediately post-treatment 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. METHODS: In this report a methodology for modeling the hemodynamics in intracranial aneurysms treated with intra-saccular 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 to the full refinement strategy that refines the mesh everywhere around the device wires. RESULTS: The results indicate that using the partial mesh refinement approach is adequate for analyzing the post-treatment hemodynamics, at a reduced computational cost. The results obtained on a series of four cerebral aneurysms treated with different intra-saccular devices were in good qualitative agreement with angiographic observations. CONCLUSIONS: Promising results were obtained relating post-treatment flow conditions and outcomes of treatments with intra-saccular devices, which need to be confirmed on larger series.

A computational scheme using the Chimera grid method is presented for simulation of three-dimensional motion and aggregation of two red blood cells (RBCs) in a narrow tube. The cells are modelled as rigid ellipsoidal particles; the computational scheme is applicable to deformable fluid-filled particles. Attractive energy between two RBCs is modelled by a depletion interaction theory and used for simulating aggregation of two cells. Through the simulation, we show that the Chimera grid method is applicable to the simulation of three-dimensional motion and aggregation of multiple RBCs in a microvessel and microvascular network.

Computational fluid dynamics (CFD) has been used for several years to identify mechanical risk factors associated with aneurysmal evolution and rupture as well as to understand flow characteristics before and after surgical treatments in order to help the clinical decision making process. We used the keywords, "CFD" and "aneurysms" to search recent publications since about 2000, and categorized them into (i) studies of rupture risk factors and (ii) investigations of pre- and post-evaluations of surgical treatment with devices like coils and flow diverters (FD). This search enables us to examine the current status of CFD as a clinical tool and to determine if CFD can potentially become an important part of the routine clinical practice for the evaluation and treatment of aneurysms in near future. According to previous reports, it has been argued that CFD has become a quite robust non-invasive tool for the evaluation of surgical devices, especially in the early stages of device design and it has also been applied successfully to the study of rupture risk assessment. However, we find that due to the large number of pre-processing inputs further efforts of validation and reproducibility of CFD with larger clinical datasets are still essential to identify standardized mechanical risk factors. As a result, we identify the following needs to have a robust CFD tool for clinical use: (i) more reliability tests through validation studies, (ii) analyses of larger generalized clinical datasets to find converging universal risk parameters, (iii) fluid structure interaction (FSI) analyses to better understand the detailed vascular remodeling processes associated with aneurysm growth, evolution and rupture, and (iv) better coordinated and organized communications and collaborations between engineers and clinicians.

The terminal orientation of a rigid body in a moving fluid is an example of a dissipative system, out of thermodynamic equilibrium and therefore a perfect testing ground for the validity of the maximum entropy production principle (MaxEP). Thus far, dynamical equations alone have been employed in studying the equilibrium states in fluid-solid interactions, but these are far too complex and become analytically intractable when inertial effects come into play. At that stage, our only recourse is to rely on numerical techniques which can be computationally expensive. In our past work, we have shown that the MaxEP is a reliable tool to help predict orientational equilibrium states of highly symmetric bodies such as cylinders, spheroids and toroidal bodies. The MaxEP correctly helps choose the stable equilibrium in these cases when the system is slightly out of thermodynamic equilibrium. In the current paper, we expand our analysis to examine i) bodies with fewer symmetries than previously reported, for instance, a half-ellipse and ii) when the system is far from thermodynamic equilibrium. Using two-dimensional numerical studies at Reynolds numbers ranging between 0 and 14, we examine the validity of the MaxEP. Our analysis of flow past a half-ellipse shows that overall the MaxEP is a good predictor of the equilibrium states but, in the special case of the half-ellipse with aspect ratio much greater than unity, the MaxEP is replaced by the Min-MaxEP, at higher Reynolds numbers when inertial effects come into play. Experiments in sedimentation tanks and with hinged bodies in a flow tank confirm these calculations.

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.

Introduction: Inflammation has been proposed as a possible mechanism involved in the degradation and weakening of the walls of intracranial aneurysms. Hypothesis: Abnormal wall shear stress (WSS) levels induce wall inflammation which then affects the wall structure and mechanics Methods: A total of 20 aneurysms which underwent surgical clipping were studied. Patient-specific computational fluid dynamics models were constructed from pre-surgical CTA images. Numerical simulations were carried out using pulsatile flows. After clipping the aneurysm, a tissue sample was resected from the dome and analyzed histologically with CD45 to search for evidence of wall inflammation. For analysis, the aneurysm series was divided in two different manners. First, aneurysms were classified into an “inflammation” group if the number of CD45+ cells was larger than the median of CD45+ cells in the entire sample of 20 aneurysms; otherwise they were classified as “no-inflammation”. Hemodynamic variables were then statistically compared between these two groups. Secondly, aneurysms were subdivided into three groups according to their mean WSS: 1) “low WSS” if WSS2*median(WSS), and 3) “mid WSS” otherwise. The numbers of CD45+ cells in each group were then statistically compared. Results: Aneurysms in the “inflammation” group had significantly larger mean WSS (p=0.018), shear rate (p=0.015), vorticity (p=0.018), and viscous dissipation (p=0.015) than aneurysms in the “no-inflammation” group. Conversely, aneurysms in the “high WSS” group had significantly larger numbers of CD45+ cells (p=0.0046) than the “mid WSS” and “low WSS” groups. Interestingly, aneurysms with stable flow patterns also tended to have larger numbers of inflammatory cells (p=0.040) than aneurysms with unstable flows. Conclusion: These preliminary results suggest that there is a connection between intra-aneurysmal flow characteristics and wall inflammation in cerebral aneurysms. In particular, inflamed walls seem to be associated with higher levels of wall shear stress.

In this paper, we explain some well known experimental observations in fluid solid interaction from a thermodynamic perspective. In particular we use the extremum of the rate of entropy production to establish the stability of specific patterns observed in single and multiparticle sedimentation in an infinite fluid and the sedimentation of spheres in the presence of walls. While these phenomena have been explained numerically, there is no known rigorous theoretical argument to establish the stability of the observed configurations. We provide a very convincing theoretical basis using entropy based arguments that are considered by several scientists as the underlying theme of nature, life and evolution. In the absence of many rigorous examples for the entropy production principle, our paper advances this argument and lends it much credibility. In addition to looking at the rate of entropy production, we also put forth a very plausible heuristic argument based on the thermal gradients in the systems being studied, which could be the underlying causal principle for many known patterns in nature.

We study a slowly moving sphere in fluids where the viscosity depends upon factors such as shear-rate, temperature and pressure, with the flow field approximated by the Stokes flow past a sphere. We derive an expression for the stresses generated in the fluid due to these various factors. This gives us information about both, the force imposed by the fluid upon the sphere and also the reaction force due to the sphere upon the fluid, referred to as the stress density. The values of the force and stress density are numerically computed in each of the cases and analyzed for various values of the flow and material parameters. Our computations show interesting variations in the distribution of stress density in the fluid for the various cases and also give us valuable information about the effect of walls. Our calculations also indicate that particle heating or cooling can serve as a significant control parameter since the drag force upon the sphere increases dramatically for a cold particle and can be reduced considerably upon heating it.

We study the steady terminal orientation of a fore-aft symmetric body as it settles in a viscous fluid. An optimal principle for the settling behavior is discussed based upon entropy production in the system, both in the Stokes limit and the case of near equilibrium states when inertial effects emerge. We show that in the Stokes limit, the entropy production in the system is zero allowing any possible terminal orientation while in the presence of inertia, the particle assumes a horizontal position which coincides with the state of maximum entropy production. Our results are seen to agree well with experimental observations.

BACKGROUND AND PURPOSE: Aneurysm progression and rupture is thought to be governed by progressive degradation and weakening of the wall in response to abnormal hemodynamics. Our goal was to investigate the relationship between the intra-aneurysmal hemodynamic conditions and wall mechanical properties in human aneurysms. MATERIALS AND METHODS: A total of 8 unruptured aneurysms were analyzed. Computational fluid dynamics models were constructed from preoperative 3D rotational angiography images. The aneurysms were clipped, and the domes were resected and mechanically tested to failure with a uniaxial testing system under multiphoton microscopy. Linear regression analysis was performed to explore possible correlations between hemodynamic quantities and the failure characteristics and stiffness of the wall. RESULTS: The ultimate strain was correlated negatively to aneurysm inflow rate ( P = .021), mean velocity ( P = .025), and mean wall shear stress ( P = .039). It was also correlated negatively to inflow concentration, oscillatory shear index, and measures of the complexity and instability of the flow; however, these trends did not reach statistical significance. The wall stiffness at high strains was correlated positively to inflow rate ( P = .014), mean velocity ( P = .008), inflow concentration ( P = .04), flow instability ( P = .006), flow complexity ( P = .019), wall shear stress ( P = .002), and oscillatory shear index ( P = .004). CONCLUSIONS: In a study of 8 unruptured intracranial aneurysms, ultimate strain was correlated negatively with aneurysm inflow rate, mean velocity, and mean wall shear stress. Wall stiffness was correlated positively with aneurysm inflow rate, mean velocity, wall shear stress, flow complexity and stability, and oscillatory shear index. These trends and the impact of hemodynamics on wall structure and mechanical properties should be investigated further in larger studies.

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 aneurysms 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. Participants were free to choose boundary 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 (PIV) were carried out in a silicone model of one of the provided aneurysms. 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 peak-systolic 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 while 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 aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.

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 cm 2 , slow=0.365 cm 2 , p=0.015) than aneurysms in the slow occlusion group. They also had a lower mean post-treatment 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.

Parallel plate chambers are frequently used to examine the response of biological cells to a constant wall shear stress. However, the stress can vary more than 80% across the chamber due to end effects. Earlier estimates of the magnitude of this inhomogeneity used boundary layer theory and experiments. Here, the full equations for steady, three-dimensional flow in a novel parallel plate device were solved numerically and used to identify an active test region where the shear stress is within 5% of a constant value. Endothelial cells can be confined to this region to assure a nearly uniform shear stress exposure.

Intracranial aneurysms (ICA) are abnormal dilations of the cerebral arteries, most commonly located at the apices of bifurcations. The ability of the arterial wall, particularly the endothelial cells forming the inner lining of the wall, to respond appropriately to hemodynamic stresses is critical to arterial health. ICA initiation is believed to be caused by a breakdown in this homeostatic mechanism leading to wall degradation. Due to the complex nature of this process, there is a need for both controlled in vitro and in vivo studies. Chung et al. developed an in vitro chamber for analyzing the response of biological cells to the hemodynamic wall shear stress fields generated by the impinging flows found at arterial bifurcations [7, 6]. Here, we build on this work and design an in vitro flow chamber that can be used to reproduce specific magnitudes of wall shear stress (WSS) and gradients of wall shear stress. Particular attention is given to reproducing spatial distributions of these functions that have been shown to induce pre-aneurysmal changes in vivo [38]. We introduce a measure of the gradient of the wall shear stress vector (WSSVG) which is appropriate for complex 3D flows and reduces to expected measures in simple 2D flows. The WSSVG is a scalar invariant and is therefore appropriate for use in constitutive equations for vessel remodeling in response to hemodynamic loads [34, 35].