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DOI: 10.1148/radiol.2311021741
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(Radiology 2004;231:272-276.)
© RSNA, 2004

Technical Developments

Measurement of Flow Modification in Phantom Aneurysm Model: Comparison of Coils and a Longitudinally and Axially Asymmetric Stent—Initial Findings1

Stephen Rudin, PhD, Zhou Wang, MS, Iacovos Kyprianou, MS, Kenneth R. Hoffmann, PhD, Ye Wu, MS, Hui Meng, PhD, Lee R. Guterman, PhD, MD, Balazs Nemes, MD, Daniel R. Bednarek, PhD, Jacek Dmochowski, PhD and L. Nelson Hopkins, MD

1 From the Depts of Radiology (S.R., D.R.B., L.N.H.), Neurosurgery (S.R., K.R.H., H.M., L.R.G., B.N., D.R.B., L.N.H.), Physics (S.R., I.K., K.R.H., Y.W., D.R.B.), Physiology and Biophysics (S.R., Z.W., K.R.H., D.R.B.), Mechanical and Aerospace Engineering (H.M.), and Social and Preventative Medicine (J.D.), Toshiba Stroke Research Center, State Univ of New York at Buffalo, 3435 Main St, Buffalo, NY 14214. From the 2002 RSNA scientific assembly. Received Dec 20, 2002; revision requested Feb 28, 2003; final revision received Aug 2; accepted Sep 8. Supported in part by National Institutes of Health grant R01NS38746, a grant from the John R. Oishei Foundation, and an equipment grant from Toshiba. Address correspondence to S.R. (e-mail: srudin@acsu.buffalo.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 Materials and Methods
 Results
 Discussion
 REFERENCES
 
Dye-dilution imaging sequences were performed and time-density curves were constructed in elastomer vessel aneurysm models to demonstrate the effectiveness of coils and an asymmetric stent in disrupting standard vortex flow. Compared with the use of coils, the use of stents led to marked flow modification, as seen with imaging sequences, and substantially slower inflow, as indicated by time-density curves, owing to the low-porosity region of the stent that covers the aneurysm orifice. These flow examination results indicate that potentially favorable flow modification features can be created by using the described asymmetric stent design, the use of which may lead to alternative methods of image-guided endovascular cerebral aneurysm therapy.

© RSNA, 2004

Index terms: Aneurysm, cerebral, 13.73 • Aneurysm, therapy, 13.1264, 13.1269 • Angiography, 13.125 • Blood, flow dynamics • Experimental study • Phantoms • Stents and prostheses, 13.1269


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
Materials and Methods
 Results
 Discussion
 REFERENCES
 
It is generally believed that cerebrovascular aneurysms develop as a result of hemodynamic phenomena and the interaction between flowing blood and vessel walls; however, the precise mechanism is not well understood. It has been stated that "between 90% and 95% of all intracranial aneurysms arise from hemodynamically induced degenerative vascular injury" (1), while elevated pulsatile shear stress has been correlated with the site of aneurysm growth (2,3).

The current endovascular treatment of choice for neurovascular aneurysms is not directly designed to be a blood flow modifier. Although embolization with use of detachable coils (4,5) that are wound to fill the volume of the aneurysm can disrupt the common vortex-like blood flow within the aneurysm, the substantial recurrence rate (6) associated with incomplete filling of the neck of aneurysms indicates the possibility that the original hemodynamic causes of aneurysms are not being addressed.

Other problems with coil deployment include the potential for rupture, the risk of herniation into the main vessel, inadequate endothelialization across the aneurysm neck (7,8), the time and costs required for multiple coil deployments, and the difficulty treating wide-necked and giant aneurysms.

An alternative endovascular device that potentially addresses flow modification directly is an asymmetric, variable-porosity stent (Fig 1). Unlike the design of the longitudinally asymmetric stents previously reported on (9), the design of this stent is longitudinally and axially asymmetric. The low-porosity patchlike region of the stent must be accurately positioned over the aneurysm orifice by using high-spatial-resolution radiologic guidance (10) to move the device along and rotate it around the catheter axis and consequently position it to divert and disrupt the aneurysmal vortex flow and to provide a host surface for vessel remodeling (11). Outside of the patchlike region, the stent is highly porous to prevent blockage or injury to perforating vessels. The purpose of our study was to demonstrate the effectiveness of coils and an asymmetric stent in disrupting standard vortex flow.



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  		Figure 1. Drawing illustrates asymmetric stent design, with the low-porosity region of the device placed at the neck of the aneurysm. This stent is a proposed alternative image-guided intervention to disrupt blood flow and induce stasis in aneurysms.

 

   Materials and Methods
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
Results
 Discussion
 REFERENCES
 
Although the actual clinical deployment of an asymmetric stent ultimately will have to be performed with radiologic guidance, for our initial tests of flow modification, video optical imaging was used.

Phantoms and Simulated Stent
Three elastomer phantoms (12), each with a 3-mm-diameter vessel lumen and a 7-mm aneurysm, were placed in a flow loop for testing. One of the aneurysms was not treated, one was filled with simulated coils, and one was treated with a developmental asymmetric stent that consisted of a mesh to cover the aneurysm orifice (Fig 2). It was not possible to use standard detachable coils because these, being composed of opaque metal, would not have transmitted an optical signal. Instead, the lengths of translucent Braunamid 2–0 polyamide thread suture material (Braun AESCULAP, Tuttlingen, Germany) were packed into the aneurysm phantom after they were coiled and heated so they would retain their shape. Although not ideally transparent, the suture material, unlike the more transparent nylon strands that were first tried, could be packed into the aneurysm. The aneurysm was filled with the material to 40% by volume, which in our clinical experience is the approximate filling density of detachable coils.



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  		Figure 2. Aneurysm phantoms that were not treated (top), filled with a threadlike suture material that simulated coils (middle), and treated with a low-porosity mesh held in place by a commercially available stent (bottom).

 
The developmental stent was simulated by using a patch of stainless steel mesh consisting of 200 wires per inch in each direction, with a 53-µm wire diameter separated by a 74-µm space; this composition resulted in 34% porosity when the ratio of open to total area was calculated. The mesh was held in place over the aneurysm orifice by using a commercially available, high-porosity, 3 x 18-mm coronary stent (Multi-Link Tristar; Guidant ACS, Temecula, Calif). Because there were no perforating vessel branches simulated in the phantom, it was not necessary to carefully limit the extent of the mesh to the diameter of the orifice, which was thus completely covered.

Experiments
The flow loop (Fig 3) into which the phantom was inserted enabled pulsatile flow. A 40% glycerin–60% water mixture was used to simulate the hydrodynamic properties of blood and to provide a refractive index that matched the elastomer phantom for best optical viewing. There was 36% forward flow at minimum compared with the maximum flow rate, as determined by using laser Doppler anemometry. A bolus of 5 mL of soluble dye (McCormick, Hunt Valley, Md) was manually injected into each of the three phantoms for 2 seconds while real-time, 30-frames-per-second digital video recordings of the aneurysmal flow were made by backlighting the flow phantoms.



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  		Figure 3. Drawing illustrates the flow loop into which aneurysm phantoms were placed and injected with optical dye.

 
After system response linearization of the video camera and the digitizing board, the flow patterns depicted by the dye images were compared and time-density data (13) were derived from an imaged region of interest that included most of the volume of the aneurysm but excluded the main channel; hence, the region of interest selection was not sensitive to the exact choice of size and location. Nevertheless, the region of interest in each of the three phantoms was a circled area that was selected by one of the authors (Z.W.) and was unchanged for each of the runs. Thus, the density plotted represented the optical dye integrated over the volume of the aneurysm and was derived on the basis of the decrease in digitized video signal recorded when the dye was introduced into the phantom.

The data were normalized to the inflow bolus peak in the main channel to compensate for small differences in the injection technique, and this normalization enabled a quantitative comparison of the time-density curves. The peak density (relative to the peak density in the untreated case); the time to peak density, which is the time from the injection to the time the density reaches its maximum; and the washout time, which is the fitting parameter for the tail of the curve when it is fit to an exponential decay with time, were calculated. Averaged parameters derived from the time-density curves for the nontreated (experiment repeated five times), coil-treated (experiment repeated three times), and mesh stent–treated (experiment repeated three times) aneurysm phantoms were compared.

Statistical Analyses
Three different outcomes (ie, responses)—relative peak density, time to peak density, and washout time—were compared in separate statistical analyses. For each response, three treatment methods—no treatment, coil placement, and mesh stent placement—were compared by using one-way analysis of variance. For every analysis, graphic diagnostic testing was performed to check the appropriateness of the analysis of variance. If any of the assumptions were violated, two approaches were taken: a search for a transformation of the response variable and a nonparametric one-way analysis of variance (Kruskal-Wallis method). If the null hypothesis of "equality of mean" responses for the different treatment methods was rejected, then pairwise comparisons were made by using the Tukey adjustment for multiple comparisons. Statistical software (SAS, version 8.02; SAS Institute, Cary, NC) was used to perform all statistical calculations.


   Results
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
 Results
Discussion
 REFERENCES
 
The time-density curves for dye transport and the dye imaging sequences revealed the different flow characteristics that resulted from the three aneurysm treatments (ie, no treatment, coil placement, and mesh stent deployment) (Fig 4). The values calculated from the time-density curves are summarized in the Table. For relative peak density and washout time, the null hypothesis of "equality of means" for the three methods was rejected (P < .001). For time to peak density, the variance of residuals was not constant; however, both the Kruskal-Wallis one-way analysis of variance results and the one-way analysis of variance results for log-transformed values rejected the null hypothesis of equal means (P < .001). For all three responses, each treatment method resulted in a different mean.



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  		Figure 4. Time-density curves normalized to inflow for the three types of aneurysm treatment (ie, nontreatment, coil placement, and low-porosity mesh stent placement) and derived from runs in which preinjection densities were subtracted from subsequent images, with the sample nonsubtracted images acquired with each sequence placed around each curve and cross-referenced (by letters a-h) to the location on each curve. The injection and flow of dye are illustrated from left to right, with the duration of the dye flow, beginning from the instance of injection, for each frame indicated. The arrows indicate how the imaging sequence progresses frame by frame.

 

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  		Values Calculated from Time-Density Curves

 
The following reported P values resulted when the Tukey adjustment was used for comparison; for peak density and washout time, raw means were used, whereas for time to peak density, log-transformed quantities were used. Differences in peak densities and washout times between the nontreated case and either the coil- or mesh stent–treated case were statistically significant (P < .001). The differences in time to peak density between the nontreated and coil-treated cases (P = .005), between the nontreated and mesh stent–treated cases (P < .001), and between the coil- and mesh stent–treated cases (P < .001) also were statistically significant.

In the nontreated aneurysm (Fig 4, top panel), vortex flow was observed and continued well after the bolus injection during the washout phase: The dye appeared to continue flowing in a circular whirling motion within the aneurysm. As illustrated in Figure 4 (top panel), with the dye imaging sequence, the bolus-induced density increase in the main channel could be seen to last between instances a and f, with continued vortex flow of the dye in the aneurysm after instance f. The peak density on the time-density curve occurred toward the end of the bolus injection, at instance f.

The coil-treated aneurysm (Fig 4, middle panel) demonstrated rapid distribution of the dye during the bolus injection (instances a–c), with the peak density occurring toward the end of the bolus injection, as was the case for the nontreated aneurysm.

The mesh stent–treated aneurysm (Fig 4, bottom panel) exhibited the slowest inflow pattern: The injection was completed by instance c, well before the peak density occurred between instances e and f. The dye appeared to seep somewhat uniformly through the mesh in a thick sheetlike distribution, with no apparent vorticity from instance b to instance e, when the distribution of the dye was viewed directly by the observers. Dye washout appeared as a similar seepage—of clear fluid. The clear fluid entered the aneurysm at instance e and eroded the somewhat uniform dye distribution in the aneurysmal volume, from instance f until the traces of dye remaining in the aneurysm formed a complex, dilute three-dimensional pattern that was not easily depicted on the two-dimensional projection images.


   Discussion
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
 Results
 Discussion
REFERENCES
 
In our phantom examinations, a comparison of the peak densities, times to peak density, and fitted washout rates revealed that both coil placement and mesh stent placement led to reduced peak densities (to 41% and 56%, respectively, of the peak density in the nontreated cases), although the distributions clearly were quite different, as previously described. The time to peak density for the aneurysm treated with simulated coils was 66% of that for the nontreated aneurysm. However, the time to peak density for the aneurysm treated with the mesh stent was more than 900% longer; this outcome clearly indicated the reduced flow into the aneurysm due to mesh stent placement.

The relative washout rate was derived by normalizing the data to the nontreated case. Although the relative washout in the aneurysm treated with the simulated coils was not significantly different from that in the aneurysm treated with the mesh stent, it was not possible to view the detailed distribution of the dye in the coil treatment case because of the lack of optical transparency of the suture material used for simulation. The low washout rate appeared to be due to the adhesion of the dye to the suture material used to simulate coils. This adherence appeared to be independent of the shape of the suture material or whether the suture was outside the aneurysm in the coil simulation; hence, repeated vigorous rinsing was required to completely eliminate the appearance of staining. Although this effect might be analogous to the thrombogenic features of actual coils, further investigations are needed to determine optimal coil simulation conditions and validate the associated washout rates.

Consideration was given to evaluating the flow reduction achieved with use of a mesh stent and simulated coils by using radiographic contrast material injections with angiographic sequences rather than the video optical imaging sequences used in this work. The potential advantage of using the described suture material is that unlike actual platinum coils, the suture material does not interfere with radiologic procedures. However, it has been previously demonstrated that because of the greater density and viscosity of contrast material, as compared with those of blood, the flow in aneurysms is not the same as the actual blood flow (14) in side-wall aneurysm models, in which there is shear-driven flow.

Also, the flow of a bolus of such contrast material depends on the orientation of the aneurysm with respect to gravity. The contrast material may undergo pooling, with a level of contrast material formed during inflow that can be visualized radiologically. This effect can greatly inflate the measured washout rates that are seen with the use of blood-equivalent fluid. However, in more realistic curved-vessel aneurysm models, in which there is pressure-driven flow directly into the aneurysm, there is less disparity between contrast material flow and actual blood flow (15). Any disparity between the flow of actual blood and that of radiographic contrast material for slow-flow conditions characteristic of treated aneurysms has not been fully investigated.

In addition to the limitations associated with using the phantom that were just described and those related to the fact that the phantom had no perforators, there were a number of other limitations in the experiments reported on herein. Although some characteristics of the pumping system were similar to those of the cerebrovasculature, the system was not designed to precisely mimic physiologic conditions. Our use of a Newtonian fluid, glycerin and water, as the carrier fluid might have resulted in differences with non-Newtonian blood, especially with the slow-flow conditions in the treated phantoms. Also, for practical reasons, the mesh stent that we used in the experiments was a simulation of a proposed asymmetric stent, and comparisons of the effects of flow were made by using suture material rather than actual opaque metallic coils. Once improved asymmetric prototype stents are made, we will plan experiments with use of animal models.

Further investigations are needed to advance the asymmetric stent design toward clinical application. First, the use of these stents to treat aneurysms at bifurcations may require reduced porosity away from the patchlike region that covers the aneurysm orifice so that the device does not interfere with blood flow in daughter vessels. Second, the probability of blockage of nearby perforating vessels will have to be evaluated, although high-spatial-resolution angiography may provide the guidance needed to avoid these vessels (10). Third, it is not yet known what flow modification is needed to perform satisfactory endovascular aneurysm therapy. It has been postulated that even giant aneurysms may not have to be completely filled with coils as long as the deployment of a few well-placed coils combined with a stent results in a sufficient change in blood flow (16).

In conclusion, optical flow examination results indicate that potentially favorable flow modification features can be created by using the described asymmetric stent design. The use of this stent design, either alone or in combination with coils or other embolic agents, may lead to alternative methods of image-guided endovascular cerebral aneurysm therapy.


   FOOTNOTES
 
Author contributions: Guarantor of integrity of entire study, S.R.; study concepts, S.R., Z.W., I.K., L.R.G.; study design, S.R., Z.W., I.K., K.R.H., H.M., B.N., D.R.B., L.N.H.; literature research, S.R., K.R.H., L.N.H.; experimental studies, S.R., Z.W., I.K., Y.W.; data acquisition, Z.W., I.K., Y.W.; data analysis/interpretation, S.R., Z.W., I.K., K.R.H., D.R.B.; statistical analysis, J.D., Z.W., I.K.; manuscript preparation, S.R., Z.W., I.K.; manuscript definition of intellectual content and editing, S.R., Z.W., I.K., K.R.H., D.R.B.; manuscript revision/review and final version approval, all authors


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
 Results
 Discussion
 REFERENCES
 

  1. Osborn AG, Tong KA. Intracranial aneurysms. Handbook of neuroradiology: brain and skull 2nd ed St Louis, Mo: Mosby-Year Book, 1996; 341.
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