The effect of actuation frequency on clot integration with the Tigertriever device: A preliminary in vitro study.

BACKGROUND: The Tigertriever stent retriever (Rapid Medical) can be actively expanded and contracted by the operator, which allows for several actuation-related parameters to be optimized to potentially improve device efficacy. These parameters have not yet been evaluated. We conducted a benchtop study to evaluate the effect of actuation frequency on clot integration within the stent. METHODS: A Tigertriever 17 device was deployed within a biological clot analog placed in a straight tube. The device was actuated between the maximally contracted and maximally expanded states with three different frequencies: passive (one-time opening, n = 6), slow (20 s/cycle, n = 6), and fast (5 s/cycle, n = 7). A flat-detector CT scan was acquired, the clot and stent wires were segmented, and the boundaries of the clot and stent wires were calculated on each axial slice. The intersection between the stent and clot boundaries throughout the volume was defined as the volume of clot integrated within the stent. The clot integration factor (ratio of integrated clot volume to total clot volume) was then statistically compared between the three frequencies as an estimate of clot capture efficiency. RESULTS: The clot integration factor was significantly higher (23% increase, p = 0.01) with the fast actuation as compared to the passive and slow actuations, with a post hoc test showing no difference (p > 0.05) between the passive and slow groups. CONCLUSIONS: Faster actuation frequencies may result in improved clot integration with the Tigertriever device. This effect needs to be validated by clinical data.

In vitro comparison of middle meningeal artery embolization with Squid liquid embolic agent and Contour polyvinyl alcohol particles.

BACKGROUND: Liquid embolic agents and polyvinyl alcohol (PVA) particles have been used for the embolization of the middle meningeal artery (MMA) for the treatment of chronic subdural hematomas. However, the vascular penetration and distribution of these embolic agents have not yet been compared. The current study compares distribution of a liquid embolic agent (Squid) to PVA particles (Contour) in an in vitro model of the MMA. METHODS: MMA models were embolized with Contour PVA particles 45-150 µm, Contour PVA particles 150-250 µm, and Squid-18 liquid embolic agent (n=5 each). The models were scanned and every vascular segment with embolic agent was manually marked on the images. Embolized vascular length as a percentage of control, average embolized vascular diameter, and embolization time were compared between the groups. RESULTS: The 150-250 µm Contour particles primarily accumulated close to the microcatheter tip, yielding proximal branch occlusions. The 45-150 µm Contour particles achieved a more distal distribution, but in a patchy segmental pattern. However, the models embolized with Squid-18 had a consistently distal, near-complete and homogenous distribution. Embolized vascular length was significantly higher (76±13% vs 5±3%, P=0.0007) and average embolized vessel diameter was significantly smaller (405±25 µm vs 775±225 µm, P=0.0006) with Squid than with Contour. Embolization time with Squid was also lower (2.8±2.4 min vs 6.4±2.7 min, P=0.09). CONCLUSIONS: Squid-18 liquid results in a considerably more consistent, distal and homogeneous pattern of embolysate distribution than Contour PVA particles in an anatomical model of the MMA tree.

Liquid embolic surface area as a predictor of chronic subdural hematoma resolution in middle meningeal artery embolization.

BACKGROUND: Liquid embolic agents (LEAs) such as ethylene vinyl alcohol (EVOH) are utilized for middle meningeal artery embolization (MMAE) for chronic subdural hematomas (cSDH). LEAs may be advantageous for MMAE as they are permanent and can penetrate the microvasculature of the subdural membranes. LEA surface area (SA) can quantify this penetration. The segmentation of LEA SA is not described in the literature and may be of interest in refining MMAE technique. METHODS: We retrospectively collected computerized tomography (CT) scans from 74 patients (with 95 cSDH) who underwent first-line MMAE with EVOH. Non-contrast head CTs were acquired pre-embolization, immediately post-embolization and at 1-, 3-, and 6 month follow-up. A 3D-Slicer was used to segment hematoma volumes and the liquid embolic cast. We hypothesized that greater LEA SA would be correlated with greater improvements in cSDH volumetric resolution. RESULTS: There was significant resolution in cSDH volumes over the follow-up period compared to preoperative volume (p<0.0001). The LEA SA was significantly correlated with the rate of cSDH resolution at 3 months (R2=0.08, p=0.03), and 6 months (R2=0.14, p=0.01). CONCLUSIONS: The correlation of LEA surface area with hematoma resolution at 3-months and 6-months suggests greater LEA penetration may improve radiographic outcomes. This study uniquely provides a quantitative radiological perspective on the effect of LEA penetration on cSDH resolution.

A novel angiographic method to estimate arterial blood flow rates using contrast reflux: Effect of injection parameters.

BACKGROUND: Contrast reflux, which is the retrograde movement of contrast against flow direction, is commonly observed during angiography. Despite a vast body of literature on angiography, the hemodynamic factors affecting contrast reflux have not been studied. Numerous methods have been developed to extract flow from angiography, but the reliability of these methods is not yet sufficient to be of routine clinical use. PURPOSE: To evaluate the effect of baseline blood flow rates and injection conditions on the extent of contrast reflux. To estimate arterial flow rates based on measurement of contrast reflux length. MATERIALS AND METHODS: Iodinated contrast was injected into an idealized tube as well as a physiologically accurate model of the cervico-cerebral vasculature. A total of 194 high-speed angiograms were acquired under varying "blood" flow rates and injection conditions (catheter size, injection rate, and injection time). The length of contrast reflux was compared to the input variables and to dimensionless fluid dynamics parameters at the catheter-tip. Arterial blood flow rates were estimated using contrast reflux length as well as a traditional transit-time method and compared to measured flow rates. RESULTS: Contrast reflux lengths were significantly affected by contrast injection rate (p < 0.0001), baseline blood flow rate (p = 0.0004), and catheter size (p = 0.04), but not by contrast injection time (p = 0.4). Reflux lengths were found to be correlated to dimensionless fluid dynamics parameters by an exponential function (R2  = 0.6-0.99). When considering the entire dataset in unison, flow estimation errors with the reflux-length method (39% ± 33%) were significantly higher (p = 0.003) than the transit-time method (33% ± 36%). However, when subgrouped by catheter, the error with the reflux-length method was substantially reduced and was significantly lower (14% ± 14%, p < 0.0001) than the transit-time method. CONCLUSION: Results show correlations between contrast reflux length and baseline hemodynamic parameters that have not been reported previously. Clinically relevant blood flow rate estimation is feasible by simple measurement of reflux length. In vivo and clinical studies are required to confirm these correlations and to refine the methodology of estimating blood flow by reflux.

Immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent.

OBJECTIVE: Flow-diverting stents with a resorbable component have significant theoretical benefits over full metal stents, although currently there are none in clinical use. In this study, the authors sought to determine the immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent. METHODS: Bioresorbable stents were deployed into glass tube models to determine porosity and pore density. In vitro flow diversion behavior was evaluated using high frame rate angiography under pulsatile flow conditions in a patient-specific silicone aneurysm model treated with the resorbable stent as well as the Surpass Evolve stent. In vivo flow diversion was characterized by deployment into 20 rabbit saccular aneurysm models, and grading was based on the O'Kelly-Marotta scale and the 4F-flow diversion predictive score. RESULTS: Porosities and pore densities of the bioresorbable stent were in the flow-diverting range for all target vessel diameters. Quantified results of immediate angiography after placement of the bioresorbable stent into a silicone aneurysm model demonstrated greater flow diversion compared to the Evolve stent. Bioresorbable stent placement in saccular aneurysm models resulted in an immediate O'Kelly-Marotta grade of A3 or better and a 4F-flow diversion predictive score of 4 or better in all cases. CONCLUSIONS: The bioresorbable stent has immediate flow-diversion characteristics that are comparable to commercially available metal stents. Longer-term studies are underway to determine the ability of the resorbable fibers to act as a neointimal scaffold and result in long-term aneurysm occlusion.

An in vitro study of pressure increases during contrast injections in diagnostic cerebral angiography.

BACKGROUND: During diagnostic cerebral angiography, the contrast bolus injected into a vessel can cause substantial changes in baseline pressures and flows. One potential, and serious complication is the re-rupture of aneurysms due to these injections. The goals of this in vitro study were to evaluate the effect of injection conditions on intraneurysmal pressure changes during angiography. METHODS: A silicone replica of a complete circle of Willis model with ophthalmic, anterior communicating, and basilar tip aneurysms was connected to a physiologically accurate flow pump. Contrast injections were performed under different conditions (carotid or vertebral vessel imaging, catheter diameter, injection rate, injection time, and arterial blood flow rate) and the pressure in each aneurysm was recorded before and during each injection. The effect of injection conditions on percentage increase in aneurysm pressures was statistically assessed. Additionally, the effect of the distance between the aneurysm and the catheter-tip on aneurysmal pressures was assessed. RESULTS: Mean intraneurysmal pressures during injection (84.5 ± 10.8 mmHg) were significantly higher than pre-injection pressures (80.4 ± 10.6 mmHg, p < 0.0001). Only 3 of the 5 conditions - carotid injections, higher injection rates, and smaller catheter diameters - significantly increased intraneurysmal pressures. The catheter-tip distance showed no correlation to pressure increases. CONCLUSIONS: Increasing contrast injection rates and decreasing catheter diameters are correlated to intraneurysmal pressure increases during angiography irrespective of the distance to the catheter tip. Future in vivo studies are required to confirm these findings and determine whether the amplitude of pressure increases with commonly used injection rates can be clinically detrimental.

Endovascular Ultraviolet Laser-Facilitated Reversal of Vasospasm Induced by Subarachnoid Hemorrhage in Canines.

BACKGROUND: Because treatments for cerebral arterial spasm-a delayed consequence of subarachnoid hemorrhage (SAH)-are clinically inconsistent, we describe here a new method for reversal of arterial spasm, possibly extensible to nitric oxide (NO)-sensitive microvasculature. METHODS: We subjected dogs to the intracisternal double-hemorrhage model of SAH (autologous blood injection on days 1 and 3) and began endovascular treatment of the spasmed basilar artery (BA) on Day 4. A conical-tip fused silica optical fiber was introduced via a microcatheter (inserted femorally) into the proximal vicinity of the spasmed BA. After local saline flushing of blood, an ultraviolet (UV) pulsed laser beam (355 nm Nd:YAG) was focused into the optical fiber and converted into a concentric ring beam, which facilitated endovascular irradiation for 30 s at intensities of 12-20 W/cm2. BA diameters were measured angiographically using a semiautomated routine over the entire BA length as well as the proximal, medial, and distal segments. RESULTS: On Day 4 the BAs had constricted by 21 ± 11%. After UV laser irradiation on Day 4, the constricted BAs dilated to 93 ± 15% of their normal diameters within minutes, and the dilation (91 ± 12%) persisted on Day 5. Most BA segments recovered to their respective baselines after UV irradiation, even when the UV beam was located considerably proximal to the BA origin. At days 4 and 5, the percent BA dilation normalized to Day 4 pre-treatment decreased linearly (by scatter plot, p < 0.02) over a range of about 60 mm from the UV irradiation site. CONCLUSIONS: We conjecture that the vasodilator nitric oxide, produced at high local concentration from its vascular storage forms (chiefly nitrites) by UV laser-induced photoscission, stimulates a wave of arterial dilation, possibly by longitudinal propagation of transnitrosation reactions in the arterial wall, which reverses cerebral vasospasm semi-locally and thus avoids the deleterious effects of systemic treatment.

Preliminary in vitro angiographic comparison of the flow diversion behavior of Evolve and Pipeline devices.

BACKGROUND AND PURPOSE: Flow diverters are increasingly used to treat a broad category of cerebral aneurysms. We conducted an in vitro study to angiographically compare the flow diversion effect of Surpass Evolve from Stryker Neurovascular with the Pipeline Shield Embolization Device from Medtronic Neurovascular. METHODS: Three copies each of three carotid aneurysm geometries were manufactured from silicone. Evolve and Pipeline flow diverters were deployed in one copy of each geometry; the third copy was used as Control. High-speed angiography was acquired under pulsatile flow in each replica, contrast concentration-time curves within the aneurysms were recorded, and the curves were quantified with six parameters. The parameters were statistically evaluated to compare the flow diversion effect of both devices. RESULTS: The Evolve showed greater flow diversion trends in almost all intra-geometry comparisons than the Pipeline. When aggregated over the three geometries, the Evolve was statistically significantly better than the Pipeline in four of the six parameters, and about the same or better (not statistically significant) than the Pipeline in the other two parameters. CONCLUSIONS: The Evolve device demonstrated greater in vitro flow diversion effects than Pipeline. Comparative efficacy of the devices will need to be adjudicated based on clinical outcomes.

Angiographic assessment of the efficacy of flow diverter treatment for cerebral aneurysms.

BACKGROUND: The recent growth of neuro-endovascular treatment has rekindled interest in the use of angiographic techniques for flow assessment. Aneurysm treatment with flow diverters is particularly amenable to such analysis. We analyze contrast time-density curves - recorded within aneurysms before (pre) and immediately after (post) flow diverter implantation to estimate six-month treatment outcomes. METHODS: Fifty-six patients with 65 aneurysms were treated with flow diverters at two institutions. A region of interest was drawn around the aneurysm perimeter in image sequences taken both pre and post angiography, and the temporal variation in grayscale intensity within the aneurysm (time-density curve) was recorded. Eleven parameters were quantified from each time-density curve. Aneurysm occlusion status was recorded six months post treatment. The change in parameters from pre to post treatment was statistically evaluated between aneurysm occluded and non-occluded groups. RESULTS: Of the 11 parameters, eight were significantly different before and immediately after flow diversion. Considering the entire data set, none of the parameters was statistically different between the occluded and non-occluded groups. However, subgroup analyses showed that four variables were significantly different between the aneurysm occluded and non-occluded groups. The sensitivity of these variables to predict aneurysm occlusion at six months ranged from 60% to 89%, while the specificity ranged from 55% to 70%. CONCLUSIONS: Device-induced intra-aneurysmal flow alterations quantified by simple aneurysmal time-density curves can potentially be used to predict long-term outcomes of flow diversion. Large multi-center studies will be required to confirm these findings. Patient-to-patient variability in coagulation may need to be incorporated for clinically relevant predictive values.

Realistic Vascular Replicator for TAVR Procedures.

Transcatheter aortic valve replacement (TAVR) is an over-the-wire procedure for treatment of severe aortic stenosis (AS). TAVR valves are conventionally tested using simplified left heart simulators (LHS). While those provide baseline performance reliably, their aortic root geometries are far from the anatomical in situ configuration, often overestimating the valves' performance. We report on a novel benchtop patient-specific arterial replicator designed for testing TAVR and training interventional cardiologists in the procedure. The Replicator is an accurate model of the human upper body vasculature for training physicians in percutaneous interventions. It comprises of fully-automated Windkessel mechanism to recreate physiological flow conditions. Calcified aortic valve models were fabricated and incorporated into the Replicator, then tested for performing TAVR procedure by an experienced cardiologist using the Inovare valve. EOA, pressures, and angiograms were monitored pre- and post-TAVR. A St. Jude mechanical valve was tested as a reference that is less affected by the AS anatomy. Results in the Replicator of both valves were compared to the performance in a commercial ISO-compliant LHS. The AS anatomy in the Replicator resulted in a significant decrease of the TAVR valve performance relative to the simplified LHS, with EOA and transvalvular pressures comparable to clinical data. Minor change was seen in the mechanical valve performance. The Replicator showed to be an effective platform for TAVR testing. Unlike a simplified geometric anatomy LHS, it conservatively provides clinically-relevant outcomes and complement it. The Replicator can be most valuable for testing new valves under challenging patient anatomies, physicians training, and procedural planning.

Pressure and Flow Rate Changes During Contrast Injections in Cerebral Angiography: Correlation to Reflux Length.

Cerebral angiography involves the antegrade injection of contrast media through a catheter into the vasculature to visualize the region of interest under X-ray imaging. Depending on the injection and blood flow parameters, the bolus of contrast can propagate in the upstream direction and proximal to the catheter tip, at which point contrast is said to have refluxed. In this in vitro study, we investigate the relationship of fundamental hemodynamic variables to this phenomenon. Contrast injections were carried out under steady and pulsatile flow using various vessel diameters, catheter sizes, working fluid flow rates, and injection rates. The distance from the catheter tip to the proximal edge of the contrast bolus, called reflux length, was measured on the angiograms; the relation of this reflux length to different hemodynamic parameters was evaluated. Results show that contrast reflux occurs when the pressure distal to the catheter tip increases to be greater than the pressure proximal to the catheter tip. The ratio of this pressure difference to the baseline flow rate, called reflux resistance here, was linearly correlated to the normalized reflux length (reflux length/vessel diameter). Further, the ratio of blood flow to contrast fluid momentums, called the Craya-Curtet number, was correlated to the normalized reflux length via a sigmoid function. A sigmoid function was also found to be representative of the relationship between the ratio of the Reynolds numbers of blood flow to contrast and the normalized reflux length. As described by previous reports, catheter based contrast injections cause substantial increases in local flow and pressure. Contrast reflux should generally be avoided during standard antegrade angiography. Our study shows two specific correlations between contrast reflux length and baseline and intra-injection parameters that have not been published previously. Further studies need to be conducted to fully characterize the phenomena and to extract reliable indicators of clinical utility. Parameters relevant to cerebral angiography are studied here, but the essential principles are applicable to all angiographic procedures involving antegrade catheter injections.

In vitro measurement of the permeability of endovascular coils deployed in cerebral aneurysms.

BACKGROUND AND PURPOSE: Aneurysm recurrence is the primary limitation of endovascular coiling treatment for cerebral aneurysms. Coiling is currently quantified by a volumetric porosity measure called packing density (pd). Blood flow through a coil mass depends on the permeability of the coil mass, and not just its pd. The permeability of coil masses has not yet been quantified. Here we measure coil permeability with a traditional falling-head permeameter modified to incorporate idealized aneurysms. METHODS: Silicone replicas of idealized aneurysms were manufactured with three different aneurysm diameters (4, 5, and 8 mm). Four different coil types (Codman Trufill Orbit, Covidien Axium, Microvention Microplex 10, and Penumbra 400) were deployed into the aneurysms with a target pd of 35%. Coiled replicas were installed on a falling-head permeameter setup and the time taken for a column of fluid above the aneurysm to drop a certain height was recorded. Permeability of the samples was calculated based on a simple modification of the traditional permeameter equation to incorporate a spherical aneurysm. RESULTS: The targeted 35% pd was achieved for all samples (35%±1%, P=0.91). Coil permeabilities were significantly different from each other (P<0.001) at constant pd. Microplex 10 coils had the lowest permeability of all coil types. Data suggest a trend of increasing permeability with thicker coil wire diameter (not statistically significant). CONCLUSIONS: A simple in vitro setup was developed to measure the permeabilities of coil masses based on traditional permeametry. Coil permeability should be considered when evaluating the hemodynamic efficacy of coiling instead of just packing density. Coils made of thicker wires may be more permeable, and thus less effective, than coils made from thinner wires. Whether aneurysm recurrence is affected by coil wire diameter or permeability needs to be confirmed with clinical trials.

In vitro angiographic comparison of the flow-diversion performance of five neurovascular stents.

Background and purpose Data differentiating flow diversion properties of commercially available low- and high-porosity stents are limited. This in vitro study applies angiographic analysis of intra-aneurysmal flow to compare the flow-diversion performance of five neurovascular devices in idealized sidewall and bifurcation aneurysm models. Methods Five commercial devices (Enterprise, Neuroform, LVIS, FRED, and Pipeline) were implanted in silicone sidewall and bifurcation aneurysm models under physiological average flow of blood analog fluid. High-speed angiographic images were acquired pre- and post-device implantation and contrast concentration-time curves within the aneurysm were recorded. The curves were quantified with five parameters to assess changes in contrast transport, and thus aneurysm hemodynamics, due to each device. Results Inter-device flow-diversion performance was more easily distinguished in the sidewall model than the bifurcation model. There were no obvious overall statistical trends in the bifurcation parameters but the Pipeline performed marginally better than the other devices. In the sidewall geometry, overall evidence suggests that the LVIS performed better than the Neuroform and Enterprise. The Pipeline and FRED devices were statistically superior to the three stents and Pipeline was superior to FRED in all sidewall parameters evaluated. Conclusions Based on this specific set of experiments, lower-porosity flow diverters perform significantly better in reducing intra-aneurysmal flow activity than higher-porosity stents in sidewall-type geometries. The LVIS device is potentially a better flow diverter than the Neuroform and Enterprise devices, while the Pipeline is potentially better than the FRED.

Hemodynamics of Flow Diverters.

Cerebral aneurysms are pathological focal evaginations of the arterial wall at and around the junctions of the circle of Willis. Their tenuous walls predispose aneurysms to leak or rupture leading to hemorrhagic strokes with high morbidity and mortality rates. The endovascular treatment of cerebral aneurysms currently includes the implantation of fine-mesh stents, called flow diverters, within the parent artery bearing the aneurysm. By mitigating flow velocities within the aneurysmal sac, the devices preferentially induce thrombus formation in the aneurysm within hours to days. In response to the foreign implant, an endothelialized arterial layer covers the luminal surface of the device over a period of days to months. Organization of the intraneurysmal thrombus leads to resorption and shrinkage of the aneurysm wall and contents, eventually leading to beneficial remodeling of the pathological site to a near-physiological state. The devices' primary function of reducing flow activity within aneurysms is corollary to their mesh structure. Complete specification of the device mesh structure, or alternately device permeability, necessarily involves the quantification of two variables commonly used to characterize porous media-mesh porosity and mesh pore density. We evaluated the flow alteration induced by five commercial neurovascular devices of varying porosity and pore density (stents: Neuroform, Enterprise, and LVIS; flow diverters: Pipeline and FRED) in an idealized sidewall aneurysm model. As can be expected in such a model, all devices substantially reduced intraneurysmal kinetic energy as compared to the nonstented case with the coarse-mesh stents inducing a 65-80% reduction whereas the fine-mesh flow diverters induced a near-complete flow stagnation (∼98% reduction). We also note a trend toward greater device efficacy (lower intraneurysmal flow) with decreasing device porosity and increasing device pore density. Several such flow studies have been and are being conducted in idealized as well as patient-derived geometries with the overarching goals of improving device design, facilitating treatment planning (what is the optimal device for a specific aneurysm), and predicting treatment outcome (will a specific aneurysm treated with a specific device successfully occlude over the long term). While the results are generally encouraging, there is poor standardization of study variables between different research groups, and any consensus will only be reached after standardized studies are conducted on collectively large datasets. Biochemical variables may have to be incorporated into these studies to maximize predictive values.

IN VITRO QUANTIFICATION OF THE SIZE DISTRIBUTION OF INTRASACCULAR VOIDS LEFT AFTER ENDOVASCULAR COILING OF CEREBRAL ANEURYSMS.

PURPOSE: Endovascular coiling of cerebral aneurysms remains limited by coil compaction and associated recanalization. Recent coil designs which effect higher packing densities may be far from optimal because hemodynamic forces causing compaction are not well understood since detailed data regarding the location and distribution of coil masses are unavailable. We present an in vitro methodology to characterize coil masses deployed within aneurysms by quantifying intra-aneurysmal void spaces. METHODS: Eight identical aneurysms were packed with coils by both balloon- and stent-assist techniques. The samples were embedded, sequentially sectioned and imaged. Empty spaces between the coils were numerically filled with circles (2D) in the planar images and with spheres (3D) in the three-dimensional composite images. The 2D and 3D void size histograms were analyzed for local variations and by fitting theoretical probability distribution functions. RESULTS: Balloon-assist packing densities (31±2%) were lower (p=0.04) than the stent-assist group (40±7%). The maximum and average 2D and 3D void sizes were higher (p=0.03 to 0.05) in the balloon-assist group as compared to the stent-assist group. None of the void size histograms were normally distributed; theoretical probability distribution fits suggest that the histograms are most probably exponentially distributed with decay constants of 6-10 mm. Significant (p<=0.001 to p=0.03) spatial trends were noted with the void sizes but correlation coefficients were generally low (absolute r<=0.35). CONCLUSION: The methodology we present can provide valuable input data for numerical calculations of hemodynamic forces impinging on intra-aneurysmal coil masses and be used to compare and optimize coil configurations as well as coiling techniques.

Physical factors effecting cerebral aneurysm pathophysiology.

Many factors that are either blood-, wall-, or hemodynamics-borne have been associated with the initiation, growth, and rupture of intracranial aneurysms. The distribution of cerebral aneurysms around the bifurcations of the circle of Willis has provided the impetus for numerous studies trying to link hemodynamic factors (flow impingement, pressure, and/or wall shear stress) to aneurysm pathophysiology. The focus of this review is to provide a broad overview of such hemodynamic associations as well as the subsumed aspects of vascular anatomy and wall structure. Hemodynamic factors seem to be correlated to the distribution of aneurysms on the intracranial arterial tree and complex, slow flow patterns seem to be associated with aneurysm growth and rupture. However, both the prevalence of aneurysms in the general population and the incidence of ruptures in the aneurysm population are extremely low. This suggests that hemodynamic factors and purely mechanical explanations by themselves may serve as necessary, but never as necessary and sufficient conditions of this disease's causation. The ultimate cause is not yet known, but it is likely an additive or multiplicative effect of a handful of biochemical and biomechanical factors.

Comparison of the in vitro hemodynamic performance of new flow diverters for bypass of brain aneurysms.

One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p > 0.05).

Endoluminal scaffolds for vascular reconstruction and exclusion of aneurysms from the cerebral circulation.

The latest class of neuroendovascular devices being evaluated is intended to treat cerebral aneurysms. In addition to inducing flow stasis-mediated thrombosis of aneurysms and thus at times being referred to as flow diverters, these devices reconstitute pathologic arterial segments to near-physiologic normalcy. The successful implementation of such an endoluminal scaffold for vascular reconstruction in the cerebral circulation requires careful consideration of various factors drawn from engineering, physics, and biological sciences. Here we review some of these factors.

The mixability of angiographic contrast with arterial blood.

PURPOSE: Angiographic contrast that is routinely injected into arteries is used not only to evaluate arterial geometry but also in many cases to assess perfusion. The authors conducted two experiments to examine the dispersion of angiographic contrast injected antegradely into an artery under conditions similar to those found in selective (carotid artery) or superselective (circle of Willis) angiography in order to determine the distance from the catheter tip at which the contrast can be considered fully mixed with the blood. A third experiment investigated whether the contrast once mixed with blood will separate from the mixture under the gravitational field due to a density mismatch. METHODS: Experiment I--Under high-speed angiographic acquisition, a bolus of contrast was injected through a catheter along the flow direction of a blood analog fluid flowing through a straight, long, cylindrical tube. The variation in grayscale intensity along the length of the tube was acquired and modeled as the step response to a second-order system. The distance from the catheter tip at which the contrast mixes with the working fluid, the mixing length, was determined as the length along the tube after which the step response settles to within 3% of the steady state value. Experiment II--A bolus of angiographic contrast was injected at rates varying from 0.1 to 1 cc/s through three different catheter sizes in the left common carotid artery of three rabbits. The average cross-sectional grayscale intensity over one cardiac cycle was calculated at four locations along the artery: Immediately distal to the catheter tip, at location of maximum grayscale intensity, and at 10 and 20 arterial diameters from the catheter tip. The status of mixing within 10 arterial diameters was assessed by differences between the grayscale value at this location and that at the maximum and 20 arterial diameter location. Experiment III--Angiographic contrast was premixed by agitation in three separate vials containing normal saline, canine blood, and glycerol/distilled-water mixture. The vials were then stationed vertically and angiographic images obtained every 5 min for 1 h. The average intensity of contrast along the vertical length of each vial was obtained for every time point to record any changes in the distribution of contrast over time. RESULTS: The first experiment shows that angiographic contrast completely mixes with steady flowing blood analog fluid within about eight tube diameters of the injection site. The second experiment shows that contrast completely mixes with blood within ten arterial diameters under appropriate injection parameters. The third experiment shows that angiographic contrast does not separate from, or settle out of, contrast-carrying fluid mixtures for a period of 1 h. CONCLUSIONS: The results demonstrate that under typical injection conditions in the clinical setting, contrast issuing from the catheter completely mixes with the blood within ten artery diameters downstream of the catheter tip. Once mixed, it does not separate from the blood due to gravity.