Jaehoon Seong

An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model.

Background and Purpose— The potential for successful treatment of intracranial aneurysms by flow diversion is gradually being recognized in the clinical setting; however, the devices currently available (stents) are not designed for flow diversion. We evaluate the long-term response of an appropriately designed flow diversion device in producing thrombotic occlusion of experimental aneurysms. Methods— Three different configurations of an original flow diversion device were implanted across thirty elastase-induced aneurysm models in rabbits. Ten animals per device configuration were followed-up for 3 weeks (n=3), 3 months (n=3), or 6 months (n=4), and tissue explanted postsacrifice was sent for histology. The temporal variation in angiographic contrast intensity within each aneurysm was fitted with a mathematical model to quantify the alteration in local hemodynamics caused by the implanted device. A predictive index, called the washout coefficient, was constructed to estimate long-term aneurysm occlusion probabilities immediately after treatment with any flow diversion device. Results— The device with a porosity of 70% and pore density of 18 pores/mm2 performed better at occluding aneurysms than devices with 70% porosity, 12 pores/mm2 and 65% porosity, 14 pores/mm2. A value of the washout coefficient less than 30 predicted greater than 97% angiographic aneurysm occlusion over a period of 6 months with a sensitivity of 73% and specificity of 82%. Conclusions— The flow diversion devices effected successful and stable aneurysm occlusion. Pore density, rather than porosity, may be the critical factor modulating efficacy of such devices.

In Vitro Evaluation of Flow Divertors in an Elastase-Induced Saccular Aneurysm Model in Rabbit

Endovascular coiling is an acceptable treatment of intracranial aneurysms, yet long term follow-ups suggest that endovascular coiling fails to achieve complete aneurysm occlusions particularly in wide-neck and giant aneurysms. Placing of a stentlike device across the aneurysm neck may be sufficient to occlude the aneurysm by promoting intra-aneurysmal thrombosis; however, conclusive evidence of its efficacy is still lacking. In this study, we investigate in vitro the efficacy of custom designed flow divertors that will be subsequently implanted in a large cohort of animals. The aim of this study is to provide a detailed database against which in vivo results can be analyzed. Six custom designed flow divertors were fabricated and tested in vitro. The design matrix included three different porosities (75%, 70%, and 65%). For each porosity, there were two divertors with one having a nominal pore density double than that of the other. To quantify efficacy, the divertors were implanted in a compliant elastomeric model of an elastase-induced aneurysm model in rabbit and intra-aneurysmal flow changes were evaluated by particle image velocimetry (PIV). PIV results indicate a marked reduction in intra-aneurysmal flow activity after divertor implantation in the innominate artery across the aneurysm neck. The mean hydrodynamic circulation after divertor implantation was reduced to 14% or less of the mean circulation in the control and the mean intra-aneurysmal kinetic energy was reduced to 29% or less of its value in the control. The intra-aneurysmal wall shear rate in this model is low and implantation of the flow divertor did not change the wall shear rate magnitude appreciably. This in vitro experiment evaluates the characteristics of local flow phenomena such as hydrodynamic circulation, kinetic energy, wall shear rate, perforator flow, and changes of these parameters as a result of implantation of stentlike flow divertors in an elastomeric replica of elastase-induced saccular aneurysm model in rabbit. These initial findings offer a database for evaluation of in vivo implantations of such devices in the animal model and help in further development of cerebral aneurysm bypass devices.

Treatment of Rabbit Elastase-Induced Aneurysm Models by Flow Diverters: Development of Quantifiable Indexes of Device Performance Using Digital Subtraction Angiography

It has been known for more than a decade that intracranial aneurysms can be successfully treated by deploying a porous meshed tube in the parent vessel of the aneurysm. Such devices are currently called flow diverters because they promote intraneurysmal flow stasis and thrombosis by diverting blood flow away from the aneurysm sac. The objective of this study was to use angiographic data to quantify and compare the performance of flow diverters of original design in successfully occluding an experimental aneurysm model. Three different configurations of a novel flow diverter with varying porosities and pore densities were implanted in 30 rabbit elastase-induced aneurysms. Temporal variations in angiographic contrast intensity within the aneurysms were fit to a mathematical model. Optimized model parameters were supplemented by the angiographic percentage aneurysm occlusion and an angiographic measure of device flexibility to derive composite scores of performance. Angiographic quantification further suggested a parameter, which could be employed to estimate long-term aneurysm occlusion probabilities immediately after treatment. Performance scores showed that the device with a porosity of 70% and pore density of 18 pores/mm2 performed better than devices with 65% porosity, 14 pores/mm2, and 70% porosity, 12 pores/mm2 with relative efficacies of 100%, 84%, and 76%, respectively. The pore density of flow diverters, rather than porosity, may thus be a critical factor modulating device efficacy. A value of the prognostic parameter of less than 30 predicted greater than 97% angiographic aneurysm occlusion over six months with a sensitivity of 73% and specificity of 82%.

Correlation Between Angiographic and Particle Image Velocimetry Quantifications of Flow Diverters in an In Vitro Model of Elastase-Induced Rabbit Aneurysms

The rupture of a cerebral aneurysm can result in a hemorrhagic stroke. A flow diverter, which is a porous tubular mesh, 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. By finding a correlation between particle image velocimetry (PIV) and digital subtraction angiography, a better assessment of how well an aneurysm is excluded from the parent artery can be made in the clinical setting. A model of a rabbit elastase-induced aneurysm was connected to a mock circulation loop. The model was then placed under angiography. Recorded angiograms were analyzed so that a contrast concentration-time curve based on the average grayscale intensity inside the aneurysm could be determined. That curve was then fitted to a mathematical model that quantifies the influence of convection and diffusion on contrast transport. Optimized parameters were correlated with the intraneurysmal mean kinetic energy measured by PIV in the same aneurysm model. A strong correlation was observed between the convection and diffusion time constants and the mean kinetic energy inside the aneurysm. Analyzing the flow of angiographic contrast into and out of the aneurysm after implantation of a flow diverter allows for prediction of the efficacy of the device in excluding the aneurysm. Correlating hydrodynamic measures obtained by angiography to those obtained by detailed techniques such as PIV increases confidence in such predictions.

Hemodynamics of Carotid Artery Atherosclerotic Occlusive Disease

Hemodynamic mechanisms for the initiation and progression of carotid bifurcation atherosclerotic occlusive disease have been extensively researched during the past few decades. Attention has focused on the carotid bulb, or sinus, where most atherosclerotic plaques are found. Herein, the authors review the seminal works that have led to an understanding of not only complex local hemodynamics but also the elicited specific biologic response. In addition, new analysis of the age-dependent morphologic maturation of the human carotid bifurcation is unveiled. Understanding the role of hemodynamics in atherogenesis may lead to the improvement of minimally invasive endovascular therapy and noninvasive strategies.

Angiographic assessment of the performance of flow divertors to treat cerebral aneurysms.

Past clinical and experimental evidence suggests that cerebral aneurysms can be successfully excluded from the circulation solely by the endovascular placement of a flow diverting device across the aneurysm neck. These devices promote intraaneurysmal flow stasis and concomitant thrombosis by redirecting flow away from the aneurysm. To comprehensively test the efficacy of such flow divertors, we are implanting devices with three different porosities in a large cohort of elastase-induced aneurysms in rabbits. Treatment efficacy is quantified by a mathematical model that is fit to aneurysmal angiographic contrast washout curves. Results from three animals implanted with different device porosities are presented here. The model competently captures the behavior of the aneurysmal washout curves and provides reliable indices of device efficacy. Preliminary analysis indicates that immediately after implantation, the device with medium porosity performs better than the devices with lower and higher porosities

Compliant Silicone Elastomer Models of Elastase-Induced Aneurysms in the Rabbit: Model Construction and Hemodynamics

An elastase-induced saccular aneurysm in the rabbit right common carotid artery was developed as a model of human cerebrovascular aneurysm, and used for testing various endovascular devices and therapies. The carotid artery of the rabbit approximates the size of the human middle cerebral artery. Therefore, the created aneurysm is similar to those found in humans around the main branches of the circle of Willis. To minimize the use of animals and gain more insight into the hemodynamics of this model, in addition to the ability to perform early testing of endovascular devices in vitro, we have developed a rapid prototyping technique to produce compliant elastomer replicas of such aneurysms. In this implementation, the geometry of the constructed aneurysm is a representative average. The rapid prototyping system reliably reproduces as many copies of the lumen of the arterial bed out of Polyacrylonitrile-butadiene-styrene (ABS). The ABS output of the prototyping system can be used as a core that is dipped a silicone elastomer and then spin coated until cured. Thereafter, the core is melted away to yield the elastomer replica of the arterial bed. This replica was included in a mock circulation loop for detailed hemodynamic investigation using particle image velocimetry (PIV).Copyright

Reduction of Intra-Aneurysmal Kinetic Energy by Intralumenal Flow Diverting Devices

Endovascular coiling is an acceptable treatment of intracranial aneurysms yet long term follow-ups suggest that endovascular coiling fails to achieve complete aneurysm occlusion particularly in wide-neck and giant aneurysms. Flow diverting devices can serve as an alternative to coils in endovascular bypass of human brain aneurysms for their exclusion from the cerebral circulation. They can redirect flow away from the aneurysm distally into the parent vessel thereby reestablishing physiological flow patterns. Placing of a flow diverting device across the aneurysm neck may be sufficient to occlude the aneurysm by promoting intra-aneurysmal thrombosis, however, conclusive evidence of its efficacy are still lacking. In this study [1], we investigated in vitro the efficacy of custom designed flow diverting devices and develop indices of their performance in an elastomeric model of the elastase-induced aneurysm in rabbit. The efficacy of custom designed flow divertors is investigated in terms of reducing the flow activity inside the sac. These custom made devices possess porosities that are similar to available stents, however, their pore densities are much higher. The results will help optimize the device that will be used in the animal model.Copyright

Treatment of Cerebral Aneurysms With Flow Divertors: Long Term Results in an In Vivo Model

Subarachnoid hemorrhagic stroke is a devastating illness with a 30-day mortality rate of 45% and is mostly caused due to the rupture of an intracranial aneurysm. Although these aneurysms are currently treated surgically by clipping, or, endovascularly by coiling and stent-assisted coiling, the feasibility of successfully treating aneurysms solely by the placement of an intravascular flow-diverting mesh across the aneurysm neck was established more than a decade ago [1]. Flow divertors disrupt the momentum exchange between the parent artery and aneurysm and significantly reduce intraaneurysmal hydrodynamic vorticity. The resultant flow stasis promotes thrombus formation within the aneurysm sac, which eventually matures into fibrotic tissue, leading to the exclusion of the aneurysm from the circulation. With the increased use of stents in the intracranial circulation, cases where coiling is not feasible, or is staged as a secondary procedure, are providing clinical evidence of the successful treatment of aneurysms with stents alone [2,3]. Such reports are sporadic and, moreover, the devices used are not designed to be flow divertors. Methodological evidence of the performance of appropriately designed flow divertors in treating cerebral aneurysms is currently unavailable.Copyright

Computational Investigation on the Dispersive Transport of Angiographic Contrast Injected Antegradely Into Flow in a Tube

In catheter-based angiography contrast is injected through a catheter into flowing arterial blood to attenuate the X-ray beam such that physicians can view vascular luminal morphology for diagnosis of vascular pathology [1]. Since real time angiography became available the transport of contrast could be visualized and numerous attempts have been made to relate the visualized transport of contrast to blood flow or blood velocity. Since the dispersion of contrast is a complex process and thorough understanding of contrast mixing with the flowing blood is missing, many physicians and researchers alike implicitly assume that mixing of contrast and blood is either instantaneously completed or that mixing does not take place at all during the short visualization period. In the former case many erroneously assume that the visualization of contrast transport directly reflect blood flow characteristics. Yet others attributed homogeneous mixing to turbulence even when the Reynolds number was as low as 77 [2]. In the latter case some reports suggested that since the two do not mix, the contrast, which is denser than blood, will tend to accumulate at low parts of the arterial system due to the gravity. The stereotypical concept is that under laminar flow conditions homogeneous mixing will take a long time and consequently a long distance. The fact that the angiographic contrast is a liquid tracer injected forcefully into the blood, generating an ejector effect is ignored. The velocity mismatch between the injected contrast and the flowing blood plays a major role in laminar mixing of the contrast. In this paper, we report our experimental investigation that was designed to find out how far distal to the catheter tip will the injected contrast reach homogeneous mixing with a blood analog fluid as evident by no further changes in the contrast density profiles measured downstream of the catheter tip.Copyright