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Breigh N. Roszelle1 Daniel Felix Ritchie School of Engineering and Computer Science, Department of Mechanical and Materials Engineering, University of Denver, Clarence M. Knudson Hall, 2390 South York Street #200, Denver, CO 80208 e-mail: [email protected] Priya Nair School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287 L. Fernando Gonzalez Department of Neurological Surgery, Jefferson Medical College, Philadelphia, PA 19107 M. Haithem Babiker School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287 Justin Ryan School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287 David Frakes School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287; School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ 85287 Comparison Among Different High Porosity Stent Configurations: Hemodynamic Effects of Treatment in a Large Cerebral Aneurysm Whether treated surgically or with endovascular techniques, large and giant cerebral aneurysms are particularly difficult to treat. Nevertheless, high porosity stents can be used to accomplish stent-assisted coiling and even standalone stent-based treatments that have been shown to improve the occlusion of such aneurysms. Further, stent assisted coiling can reduce the incidence of complications that sometimes result from embolic coiling (e.g., neck remnants and thromboembolism). However, in treating cerebral aneurysms at bifurcation termini, it remains unclear which configuration of high porosity stents will result in the most advantageous hemodynamic environment. The goal of this study was to compare how three different stent configurations affected fluid dynamics in a large patient-specific aneurysm model. Three common stent configurations were deployed into the model: a half-Y, a full-Y, and a crossbar configuration. Particle image velocimetry was used to examine post-treatment flow patterns and quantify root-mean-squared velocity magnitude (V RMS ) within the aneurysmal sac. While each configuration did reduce V RMS within the aneurysm, the full-Y configuration resulted in the greatest reduction across all flow conditions (an average of 56% with respect to the untreated case). The experimental results agreed well with clinical follow up after treatment with the full-Y configuration; there was evidence of thrombosis within the sac from the stents alone before coil embolization was performed. A computational simulation of the full-Y configuration aligned well with the experimental and in vivo findings, indicating potential for clinically useful prediction of post-treatment hemodynamics. This study found that applying different stent configurations resulted in considerably different fluid dynamics in an anatomically accurate aneurysm model and that the full-Y configuration performed best. The study indicates that knowledge of how stent configurations will affect post-treatment hemodynamics could be important in interventional planning and demonstrates the capability for such planning based on novel computational tools. [DOI: 10.1115/1.4026257] Introduction Treatments for cerebral aneurysms have improved dramatically over the past few decades; however, large and giant aneurysms remain notoriously difficult to treat [1]. Large aneurysms are those with a sac diameter of >10 mm while giant aneurysms are often defined as having a sac diameter of >25 mm [2,3]. Because of increased complications during and after treatment, such as hemorrhage, cerebral compression, and thromboembolism, giant aneurysms account for the highest mortality rates among cerebral aneurysms [4]. An analysis of mortality and morbidity of patients who underwent clipping surgery on unruptured cerebral aneurysms by Raaymakers et al. showed that the mortality rate of patients with posterior circulation nongiant aneurysms was 3.0%, while the mortality rate of patients with posterior circulation giant aneurysms was 9.6% [5]. Because surgical clipping has achieved such limited success in treating giant aneurysms, other techniques 1 Corresponding author. Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received September 2, 2013; final manuscript received December 11, 2013; accepted manuscript posted December 16, 2013; published online February 5, 2014. Editor: Victor H. Barocas. Journal of Biomechanical Engineering including parent artery occlusion (PAO) have emerged. The goal of PAO is to reduce blood flow into the aneurysmal sac, and the technique can be executed either surgically or with endovascular devices such as detachable balloons and/or coils [6]. Over the past decade, embolic coiling has become the gold standard for treating cerebral aneurysms. Coiling is less invasive than traditional surgical methods and also more effective according to the International Subarachnoid Aneurysm Trial [7]. Unfortunately, large and giant aneurysms, especially those with neck sizes of over 5 mm, are difficult to treat even with the most advanced coiling techniques [8]. Larger aneurysms treated with coiling demonstrate increased incidence of poor initial occlusion, high rates of neck remnants, poor coil stability, and recanalization rates of over 50% [9]. However, flexible high porosity stents can be used to aid in the coil embolization of large and giant aneurysms. The stents are deployed directly into the lumen of the diseased parent vessel, across the aneurysmal neck. This provides a bridging scaffold to both support coils and serve as a nidus for neointimal growth over the aneurysmal neck [10]. Because treating giant aneurysms with coiling alone often results in neck remnants, the use of a stent or stents to support the coils and maintain the patency of the parent vessel can be highly C 2014 by ASME Copyright V FEBRUARY 2014, Vol. 136 / 021013-1 Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use beneficial [11]. However, it remains unclear which configuration of stents is most beneficial in addressing aneurysms at bifurcation termini. During stent-assisted coiling, stents are deployed first in order to keep coils in place as they are deployed. In some cases coiling is performed immediately after stenting, but in other cases the two steps may be staged over days or even months as separate interventions [12]. During the time between staged stenting and coiling, there is often some thrombosis within the aneurysmal sac, indicating that stents alone can effect hemodynamic changes that facilitate aneurysmal exclusion [13]. It is also noteworthy that the later coiling stage of stent-assisted coiling can in some cases fail, making the earlier stenting stage the effective conclusion of the treatment. Accordingly, the configuration of deployed stents can have considerable impact on the overall outcome of treatment. Determining the best stent configuration to promote beneficial hemodynamics is, thus, an important consideration in treatment design. Currently, there is no consensus as to which stent configuration is best for treating aneurysms at bifurcation termini [14]. When dealing with basilar tip aneurysms, the characteristic vascular geometry allows for several different configurations to be deployed within the branching arteries. These include the half-Y, full-Y, and crossbar configurations, all of which are shown in Fig. 1. A previous study by our group investigated different stent configurations in an idealized wide-neck aneurysm model both experimentally and computationally, and it was clear that each configuration led to different flow patterns [15]. Because the study examined only a single idealized model, characterizing flows in additional anatomical models may help improve understanding of the effects that stent configuration has under more clinically realistic conditions. Therefore, this study considered a model of a large patientspecific aneurysm to further explore the flow characteristics effected by three different stent configurations. Specifically, we used particle image velocimetry (PIV) to assess fluid dynamic outcomes after treatment with the different stent configurations and then compared the experimental findings to clinical follow up with favorable agreement. We also applied novel finite element (FE) models and computational fluid dynamics to simulate the course of treatment pursued in vivo, thereby, demonstrating potential for interventional planning. Methodology In Vitro Experiments Modeling. The basilar tip aneurysm examined in this study was selected because of its large sac and neck sizes, which made it a very poor candidate for coil embolization alone. Specifically, the aneurysm had a maximum sac diameter of 14.3 mm and a minimum neck diameter of 5.4 mm at the parent vessel. It was also selected because post-treatment clinical follow up data (imagebased and otherwise) were available. A three-dimensional model of the aneurysm is shown in Fig. 2. In order to reconstruct the aneurysmal geometry, computed tomography image data were first enhanced and segmented using custom MATLAB code (Mathworks, Natuck, MA) [16,17]. Thresholding and region growing segmentation operations were then performed within Mimics software (Materialize, Ann Arbor, MI) to form a 3D computational model of the aneurysm and associated vessels. The computational model was translated into a physical core model made of wax using an R66þ Solidscape 3D printer (Solidscape, Merrimack, NH). The wax core was then recast to form a refined metallic core so as to achieve regulated smoothness along the vessel walls. A final in vitro flow model was then made by casting the refined metallic core in urethane and melting the core out, leaving a lost-core model suitable for optical experiments. Device Deployment. Three different configurations of Neuroform stents (Stryker, Freemont, CA) were investigated: the 021013-2 / Vol. 136, FEBRUARY 2014 Fig. 1 Illustrations of three different stent configurations: (a) half-Y, (b) crossbar, and (c) full-Y half-Y, full-Y, and crossbar configurations. Each configuration is shown in Fig. 1. Experiments were also run on the untreated case for comparison. Flow Measurement. In order to mimic in vivo flow conditions, a neurovascular flow loop apparatus was developed. The loop was filled with a blood analog comprised of water, aqueous sodium iodide, and glycerol designed to have a viscosity of 3.16 cP at a 25 C operating temperature. The refractive index of the fluid was matched to that of urethane to facilitate PIV measurements, and 8 lm fluorescent particles (Thermo Scientific, Waltham, MA) were seeded into the fluid. Flow within the loop was driven by a peristaltic pump (Harvard Apparatus, Holliston, MA) through flexible polyvinyl chloride Transactions of the ASME Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use Computational Simulations Fig. 2 Computational model of the patient-specific aneurysm tubing. Both steady and pulsatile conditions were investigated at flow rates of 3, 4, and 5 ml/s. During steady flow experiments, the fluid was directed through a compliance chamber to remove pulsatile effects. During pulsatile flow experiments, the chamber was removed and the pump was configured to reproduce a vertebral flow waveform from literature [18]. In both cases, the flow rate through the loop was continuously monitored with a flow meter (Omega Engineering, Inc., Stamford, CT). Inflow to the aneurysm model was also monitored using a fluid-filled pressure transducer (Harvard Apparatus, Holliston, MA) attached to the tubing directly upstream of the model. The pressure transducer was connected to an amplifier unit (Harvard Apparatus, Holliston, MA) and waveform measurements were monitored using an oscilloscope. PIV was performed using a Flowmaster 3D stereo PIV system (LaVision, Ypsilanti, MI) comprising a 532 nm wavelength Solo PIV III dual cavity pulsed YAG laser (New Wave Research, Fremont, CA) and two Imager Intense cross correlation CCD cameras. A thickness of 0.5 mm was maintained for the laser light sheet. The fluorescent particles illuminated by the laser in the working fluid experience peak excitation and emission at 542 and 618 nm, respectively. Because stents can cause intense laser reflections, low-pass optical filters with a 572 nm cutoff (Omega Optical, Brattle Bro, VT) were installed on the cameras. During data collection, a total of seven parallel planes were measured, each 1 mm apart. The test section of the aneurysm selected for measurement allowed for complete coverage of the aneurysmal neck. Experimental Flow Data Processing and Analysis. Two hundred image pairs were acquired (at a rate of 5 Hz) at each imaging plane and for each flow condition. Flow velocity vectors were calculated using a cross correlation algorithm within DaVis software (Lavision, Ypsilanti, MI). Interrogation windows with an initial size of 32 by 32 pixels and a final size of 16 by 16 pixels were used. An overlap of 50% was specified between neighboring windows. A single velocity flow field was then averaged within each measurement plane for each flow condition. Root-mean-squared velocity magnitude (V RMS ) was used to describe flow conditions inside the aneurysm. Since the metric considers all data points measured within the aneurysmal sac, a reduction in V RMS indicates a reduction in overall fluid dynamic activity within the aneurysm. V RMS is calculated as sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi n 1X V rms ¼ jV i j2 n i¼1 where n is the number of data points within the aneurysmal sac and |Vi| indicates the flow velocity magnitude at point i. Journal of Biomechanical Engineering Finite Element Device Deployments. In order to demonstrate and assess interventional planning capabilities, FE modeling was used to simulate deployment of the full-Y stent configuration (which was the course of treatment pursued in vivo). A computational model of the Neuroform stent was first designed in Pyformex2. A description of the computational stent geometry can be found in Babiker et al. [15]. The computational stent was imported into Abaqus (Simulia, Providence, RI) where it was meshed using 28,503 four-node linear quadrilateral shell elements of Abaqus element type S4R. Shell elements were chosen because they are computationally less expensive to simulate than conventional 3D solid elements. Shell elements also perform similarly to 3D solid elements, as demonstrated by Hall and Kasper who showed good agreement between stents modeled with shell and 3D solid elements during stent expansion simulations [19]. An artificial shell thickness of 70 lm was applied to the shell elements in Abaqus. Superelastic Nitinol material behavior was also imposed using a user defined subroutine in Abaqus, which is described by Gong and Pelton [20] and Auricchio et al. [21]. A material density of 6.8 g/ cm3 was specified in order to match Nitinol. Stent deployment in the computational aneurysm model was simulated in Abaqus/Explicit by (1) crimping the stent into a microcatheter, (2) advancing the microcatheter to the site of the aneurysm, and (3) unsheathing the stent in a step-by-step process. This technique is similar to the one reported in a previous study by our group [22]. The aneurysm was modeled as a rigid body with 18,557 quadrilateral elements. The crimper was modeled as a cylindrical shell with 10,653 quadrilateral elements and the material properties of steel. A radial displacement boundary condition was imposed on the crimper to uniformly compress the stent into a 0.54 mm microcatheter. The microcatheter was also modeled as a cylindrical sheath with 27,189 shell elements, a 30 GPa elastic modulus, a 0.3 Poisson ratio, and a 7 g/cm3 density. After crimping, the microcatheter was advanced along the vessel centerline to the site of the aneurysm, as shown in Fig. 3 (panes 1 and 2 and 6 and 7). Microcatheter advancement was performed through the kinematic coupling of a control point with circular nodes lining the microcatheter tip. Displacements were imposed onto the reference point to guide the microcatheter through the vessel centerline, which is similar to the technique used by Ma et al. [23]. This approach simulates microcatheter navigation in the clinic, where a guidewire is used to direct the microcatheter to the site of the aneurysm. After microcatheter advancement, the stent was divided into eight subsets and radial constraints were applied to each in order to constrain the stent radius to that of the microcatheter. Step-bystep, the radial constraints on each subset were relaxed and the stent subset was allowed to expand, as shown in Fig. 3 (panes 3–5). This approach simulates stent unsheathing in the clinic where the stent is fixed in place using a pusher and the microcatheter is slowly pulled back to unsheath the stent. Surface-to-surface contacts were modeled using the “general contact” algorithm in Abaqus/Explicit. Stent-to-microcatheter, microcatheter-to-vessel, stent-to-vessel, and stent-to-stent contact interactions were modeled using frictional coefficients of 0.07, 0.1, 0.07, and 0.07, respectively. The frictional coefficients were estimated from the literature [24–26]. Computational Fluid Dynamic Simulations. After simulating stent deployment in Abaqus, deployed stent geometries were shelled in Geomagic studio (Raindrop Geomagic, Research Triangle Park, NC) with a 70 lm thickness and merged. The shelled stent geometries and the original computational aneurysm model were then imported into ANSYS ICEM (ANSYS, Canonsburg, PA), where the inlet and outlets of the aneurysm model were extruded. A mesh density function was applied near the stents and the Octree algorithm was used to discretize the stent and blood 2 Please see pyformex.berlios.de. FEBRUARY 2014, Vol. 136 / 021013-3 Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use Fig. 3 Image sequence showing the simulated deployment of two Neuroform stents in a full-Y configuration. The final FE simulation result (pane 8) was used in a fluid dynamic simulation. specify the pressure-velocity coupling. A steady flat 4 ml/s flow profile was applied at the inlet of the model, and zero pressure boundary conditions were imposed at the outlets. Although physiologically accurate boundary conditions can be critically important, we propose that zero pressure conditions are appropriate here based on the assumptions of equal flow resistance across the outflow branches and that high porosity stent deployment effects minimal changes in vascular resistance (the latter assumption is supported by a previous experimental study from our group [27]). The overall CFD approach has been described previously by Babiker et al. [15]. Results In Vitro Results Effects of Stent Configuration on Aneurysmal Flow. V RMS reductions within the aneurysmal volume for each treatment (with respect to the untreated case) are shown in Fig. 4. There was a reduction in V RMS of at least 25% after any stent treatment regardless of flow conditions. Under steady flow conditions (Fig. 4(a)), the half-Y configuration was consistently least effective. The crossbar and full-Y configurations led to similar V RMS reductions of 50% or above. The full-Y configuration led to the highest V RMS reductions at 4 and 5 ml/s steady flow rates; however, the crossbar configuration led to the greatest reduction at 3 ml/s (66.9%). Under pulsatile flow conditions (Fig. 4(b)), the half-Y and crossbar configurations led to similar V RMS reductions of 25–30%. The full-Y configuration led to the greatest reductions for all three pulsatile flow rates, with a maximum reduction of 62% at 3 ml/s. Fig. 4 Reductions in VRMS for all flow conditions explored. The percentages shown in each column are the reductions in VRMS with respect to the untreated case. volumes into approximately 16 106 tetrahedrons. The final mesh was imported into ANSYS Fluent where the blood volume was assumed to comprise a Newtonian fluid with the same density and viscosity as the blood analog solution used in experiments. The stent volume was modeled as solid. The vessel wall and stent surfaces were assumed to be rigid, and a no-slip boundary condition was applied at the walls. The SIMPLE algorithm was used to 021013-4 / Vol. 136, FEBRUARY 2014 Aneurysmal Flow Patterns. Flow patterns varied after deployment of each stent configuration as expected. Figure 5 highlights the flow patterns within a plane near the middle of the measurement volume at 4 ml/s steady flow. Under untreated conditions, there was a high velocity jet within the aneurysmal sac near the lower branch vessel, and a region of flow recirculation near the top branching vessel. Both features are shown in Fig. 5(a). Figure 5(b) shows that the half-Y configuration led to a similar area of recirculation when compared to the untreated case (near the top branching vessel corresponding to the unstented side). The half-Y configuration also led to a high velocity flow region; however, that region was shifted to the side of the unstented vessel in contrast to the untreated case. The crossbar configuration, as shown in Fig. 5(c), led to a jet that originated from the parent vessel and continued on into the center of the aneurysmal sac. Lastly, the Transactions of the ASME Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use Fig. 5 Velocity vector flow patterns within the aneurysm for each stent deployment configuration at 4 ml/s steady flow Fig. 6 Velocity vector flow patterns within the aneurysm for each stent deployment configuration at 4 ml/s pulsatile flow flow patterns for the full-Y configuration are shown in Fig. 5(d). That configuration led to a reduction in overall flow velocity and, unlike the other configurations, did not generate any high velocity jets. The flow patterns during peak systole of pulsatile flow at 4 ml/s are shown in Fig. 6. The results are similar to those seen during steady flow. As shown in Fig. 6(b), there was high velocity flow into the aneurysm for the half-Y configuration, which is similar to the untreated case shown in Fig. 6(a). For the crossbar configuration, flow into the aneurysm from the neck plane is reduced in comparison to the untreated case, as shown in Fig. 6(c). However, the full-Y configuration as shown in Fig. 6(d) led to greater reductions in flow velocities than either of the other configurations. Computational Results. Three-dimensional streamtraces for the untreated and full-Y configurations are presented in Figs. 7(a) and 7(b), respectively. Figure 7(a) shows a concentrated flow jet impinging on the aneurysmal fundus that transitions into a recirculating flow pattern near the center of the aneurysm. The impinging Journal of Biomechanical Engineering flow jet was noticeably dispersed after the full-Y deployment and velocity magnitudes within the aneurysm were considerably reduced, as shown in Fig. 7(b). The reduction in V RMS with respect to the untreated case was 35.7%. Wall shear stress (WSS) and spatial wall shear stress gradient (WSSG) contour plots are presented in Figs. 8 and 9. In the Figures, WSS and WSSG magnitudes show considerable reductions after treatment. The largest reductions were observed along the left side of the posterior wall of the aneurysm (oriented as the right side of the aneurysmal sac in the figures), as shown in panes in Figs. 8(c) and 8(d) and 9(c) and 9(d). Clinical Results. The aneurysm we examined was treated clinically with a full-Y configuration. Figure 10(a) shows the aneurysm immediately after treatment; the markers indicating stent endpoints can be seen in the parent and outlet vessels. The aneurysm was then coiled a month after stenting. During the time between coiling and stenting, considerable thrombosis FEBRUARY 2014, Vol. 136 / 021013-5 Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use Fig. 7 Fluid dynamic simulation results showing 3D streamtraces for the untreated case (a) and the full-Y configuration (b) at 4 ml/s steady flow Fig. 9 Simulated contour plot of the WSSG gradient for the untreated case (a) and the full-Y configuration (b). Contour plots are shown for the posterior view of the aneurysm (view 1—(a) and (b)) and anterior view (view 2—(c) and (d)). Fig. 8 Simulated WSS contour plots for the untreated case (a) and the full-Y configuration (b). Contour plots are shown for the posterior view of the aneurysm (view 1—(a) and (b)) and the anterior view (view 2—(c) and (d)). (approximately 50% by clinical standards) occurred on the left side of the aneurysmal sac as shown in Fig. 10(b). That partial occlusion facilitated subsequent coil embolization, which led to a successful treatment outcome. The one-year post-treatment angiogram shown in Fig. 10(c) indicated complete aneurysmal exclusion without any rebleeding. Discussion Whether treated surgically or with endovascular techniques, large and giant cerebral aneurysms are particularly difficult to treat [4,5]. Fortunately, stent-assisted coiling has shown promise in recent years as an effective treatment for such aneurysms [28]. However, the best stent configuration for treating aneurysms at bifurcation termini remains a subject of clinical debate [14]. A previous study by our group showed that considerable differences in aneurysmal fluid dynamics resulted after treatment with different stent configurations in an idealized aneurysm model [15]. The primary goal of this study was to further understanding of the fluid dynamics that different stent configurations effect under more clinically realistic experimental conditions. The study also demonstrated potential for interventional planning based on novel computational tools, which were used here to simulate posttreatment flow conditions that agreed well with clinical outcomes. Differences in Aneurysmal Fluid Dynamics Among Stent Configurations. In Vitro experiments revealed considerable differences among aneurysmal fluid dynamics after treatment with 021013-6 / Vol. 136, FEBRUARY 2014 different stent configurations. In that regard, the findings agree with previous in vitro studies by our group that investigated simpler aneurysm models as well as computational studies by others involving anatomical models [29,15]. In this study, even in cases where the reductions in V RMS effected by different stent configurations were similar, the underlying aneurysmal flow patterns were quite different. For example, under steady flow conditions, the crossbar and full-Y configurations led to similar reductions in V RMS ; however, the crossbar configuration led to a concentrated jet through the aneurysmal neck, which was not observed after treatment with the full-Y configuration. These two different stent configurations and the dissimilar flow patterns they effect could, therefore, lead to important differences in clinical outcomes. In Vitro results showed that the full-Y configuration led to the most advantageous fluid dynamic environment among the different stent configurations we considered. Specifically, results showed that the full-Y led to the largest reductions in V RMS as compared to the untreated case for all of the flow conditions examined (with one exception). Further, flow patterns for the fullY showed an overall reduction in high flow velocities, a lack of concentrated flow jets, and larger regions of low flow velocity within the aneurysm. Such regions have been correlated with thrombus formation sites, which can facilitate aneurysmal exclusion, in prior studies [30]. Influence of Aneurysmal Geometry on Post-Treatment Fluid Dynamics. One critically important factor in determining the optimal stent configuration is the geometry of the aneurysm being treated. While the full-Y configuration led to the most advantageous fluid dynamic environment for the geometry we examined, results may differ for other geometries. For example, a case study by Cross et al. found that the full-Y configuration was a poor choice for treating one patient’s basilar tip aneurysm because the intersection of the two stents did not reach the midpoint of the aneurysmal neck, which reduced stent coverage there and increased the risk of coil herniation into the parent vessel [14]. The importance of geometry is also highlighted when comparing the patient-specific model from this study to the idealized model examined by Babiker et al. [15]. Figure 11 compares in vitro reductions in V RMS with respect to the untreated case, for each stent configuration, between the patient-specific and idealized aneurysm geometries. Some similarities can be observed between the two models. For example, the half-Y configuration was consistently least effective in reducing V RMS within the aneurysm. Further, the crossbar configuration led to a flow jet Transactions of the ASME Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use Fig. 10 Digital subtraction angiography images of the large aneurysm at different stages of treatment: (a) immediately after stent treatment, (b) one month after stent treatment, before coiling (note the partial occlusion of the sac), and (c) one year after stent assisted coiling Fig. 11 Comparison of VRMS reductions associated with all three stent configurations in both the patient-specific anatomical model and a previously examined idealized model originating from the aneurysmal neck in both cases whereas the full-Y configuration led to better dissipation of the flow jet. Significant lower recanalization was observed after comparing standalone coiling to half Y and even less need for retreatment after the Y configuration. Non significant but lower recanalization and need for retreatment has been shown after a “Y” configuraltion compared to half Y. However, while similarities do exist, the two models also effected many fluid dynamic differences. For example, the crossbar configuration was more effective in reducing V RMS for the idealized case. Further, the half-Y configuration had a minimal effect on V RMS in the idealized model but reduced V RMS by more than 24% in the patient-specific case. Therefore, the geometry of the aneurysm and parent vessel clearly influence the hemodynamic effects of each stent configuration. Although they are not a focal point of this study, the considerable effects that experimental inflow conditions had on posttreatment fluid dynamics should also be noted. For example, the crossbar configuration reduced V RMS by the greatest degree for one of the steady flow rates, but was far from best under any pulsatile flow conditions. Like the effects that geometry can have on post-treatment flows, the considerable effects that inflow conditions can have further underscore the critical importance of patient-specificity for realistic interventional planning. Comparisons Among Experimental, Simulated, and Clinical Results. Although experiments were the primary source of data used in this study to evaluate three different stent configurations, a simulation of the full-Y configuration was also performed and Journal of Biomechanical Engineering clinical data describing that configuration’s use in vivo were gathered. Accordingly, three different characterizations of fluid dynamics affected by the full-Y were available. In comparing the experimental and simulated characterizations of the full-Y, results agreed well. Both demonstrated reductions in V RMS , similarly localized regions of low velocity flow, and dissipation of the impingement jet observed in the untreated model; however, the experimental model demonstrated greater dissipation and lower overall flow velocities. Differences between the results can be attributed to several factors, one of which is that the stent deployments were not matched exactly in terms of rotation and/or absolute endpoints (such matching is extremely if not prohibitively difficult). Other potential sources of differences between the experimental and simulated results include that the outflow boundary conditions were different (although symmetric in each case), and that the aneurysmal volumes used to calculate V RMS were slightly different due to spatial limitations on data collected in vitro. Nevertheless, the many strong similarities between the experimental and simulated cases (quantitative and otherwise) provide confidence that the simulations generated reliable data. In comparing the experimental and simulated results to in vivo data, both agreed well with the limited information provided by clinical follow up. Specifically, digital subtraction angiography images acquired 3 months after initial treatment with stents showed partial thrombosis on one side of the aneurysmal sac. That region is identified in Fig. 8(b). Flow patterns observed in the experimental and simulated data shown in Figs. 6(d) and 7(b) show greatly reduced aneurysmal velocities toward both sides of the aneurysmal sac, including the site where thrombus formed in vivo (note the presence of low velocity regions below 0.05 m/s in Fig. 6(d) and the absence of high velocity streamtraces above 0.18 m/s in Fig. 7(b), toward the sides of the aneurysm in each case). The simulated data also show lower post-treatment WSS and WSSG magnitudes at the region where thrombus formed. Areas of low WSS have been proposed as sites where thrombus is likely to form [31]. While this study was limited to comparing across experimental, computational, and clinical results for only one of the stent configurations that was considered, all of the results matched well for that configuration. Implications for Interventional Planning. The different fluid dynamic outcomes of treatment that were observed in this study underscore the important roles that both experiments and simulations can play in the design of effective interventions by facilitating selection of the best stent configuration among alternatives for example. Although it would be impractical to perform an experimental study for every patient-specific case prior to treatment, experiments provide well founded but more general knowledge of the hemodynamics that different stent configurations will promote. Simulations, on the other hand, can build upon the fundamental knowledge that experiments contribute and complement such knowledge with patient-specific predictions of posttreatment hemodynamics that can be generated on timescales FEBRUARY 2014, Vol. 136 / 021013-7 Downloaded From: http://biomechanical.asmedigitalcollection.asme.org/ on 09/16/2015 Terms of Use: http://www.asme.org/about-asme/terms-of-use compatible with clinical workflows. Together, parallel bench top experiments and computational simulations can, thus, provide a well-rounded foundation to aid physicians in patient-specific interventional planning. For example, understanding that the full-Y configuration typically promotes low velocity flow regions toward the lateral boundaries of a bifurcation aneurysm becomes more meaningful when a patient-specific simulation (considering realistic geometric and inflow conditions) confirms that result. More detailed aspects of the deployment plan can then be finetuned with further simulations to optimize the prevalence and expanse of the low velocity flow regions or other potentially beneficial fluid dynamic features. One aim of future work is to apply the computational approaches used in this study to a larger patient population and, thereby, identify the hemodynamic predictors of clinical outcomes. Study Limitations. Several limitations of this study are noteworthy. First, only a single anatomical model was considered. However, results were compared to another model from previous work to add depth to the study. Second, both the experimental and computational aneurysm models we investigated were rigid wall models. Clearly more realistic moving wall boundaries would result in somewhat different fluid dynamic outcomes; however, previous studies have shown that aneurysmal fluid dynamics are dictated primarily by baseline geometry, which we recreated faithfully in this study for a patient-specific anatomical case [32]. Nevertheless, models with compliant vessel walls (both experimental and computational) have been used in our lab and will be considered in future work (this will include computational models with fluid structure interaction). Lastly, the comparisons that were made to clinical follow up data in this study were highly qualitative. That limitation is in large part due to the nature of the clinical follow up data available, but more quantitative comparisons to clinical follow up data will be included as available in future work. Conclusion This study characterized the considerable fluid dynamic differences that three different stent configurations affected in an anatomical basilar tip aneurysm model. Understanding of those differences is important because the hemodynamics that result from stenting alone may play an important role in the overall hemodynamic outcome of stent assisted coiling. Among the stent configurations investigated, the full-Y variant performed best. The aneurysm examined in this study was treated successfully in vivo with a full-Y configuration, and clinical follow up data agreed well with experimental results that demonstrated low velocity flow regions at the in vivo thrombus site. A computational simulation of the full-Y configuration predicted a low velocity flow region at that site as well, which indicates promise for interventional planning of endovascular treatments. The study also showed that aneurysmal geometry can have an important impact on the fluid dynamics effected by a given stent configuration. Future work will comprise examination of additional anatomical aneurysm models and endovascular devices, both in vitro and in silico, as well as further development of our computational tools for interventional planning. As the tools for interventional planning are developed, the long-term goal is to establish protocols and identify predictors from the modeling data that can be used to aid in optimizing the clinical outcomes of cerebral aneurysm treatments. Acknowledgment The authors acknowledge funding for this project from the following sources: Brain Aneurysm Foundation Research Grant, National Science Foundation CAREER Award, American Heart Association Beginning Grant in Aid, and Women in Philanthropy Society Category B Grant. 021013-8 / Vol. 136, FEBRUARY 2014 References [1] Lawton, M. T., and Spetzler, R. 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