Kyehan Rhee

Changes of Flow Characteristics by Stenting in Aneurysm Models: Influence of Aneurysm Geometry and Stent Porosity

AbstractAn endovascular technique using a stent has been developed and successfully applied in the treatment of wide neck aneurysms. A stent can facilitate thrombosis in the aneurysm pouch while maintaining biocompatible passage of the parent artery. Insertion of the stent changes the flow characteristics inside the aneurysm pouch, which can affect the intra-aneurysmal embolization process. The purpose of this study is to clarify the velocity and wall shear stress changes that are caused by stenting in fusiform and lateral aneurysm models. We used a flow visualization technique that incorporated a photochromic dye in order to observe the flow fields and measure the wall shear rates. The intra-aneurysmal flow motion was significantly reduced in the stented aneurysm models. Coherent inflow along the distal wall of the aneurysm was diminished and inflow was distributed along the pores of the stent wall in the stented models. Also, sluggish intra-aneurysmal vortex motion was well maintained in the stented aneurysm models during the deceleration phase. A less porous stent generally reduced the intraneurysmal fluid motion further, but the porosity effect was not significant. The magnitude and pulsatility of the wall shear rate were reduced by stenting, and the reductions were more significant in the lateral aneurysm models compared to the fusiform aneurysm models. The hemodynamic changes that were observed in our study can help explain the efficacy of in vivo thrombus formation caused by stenting.

A new atherosclerotic lesion probe based on hydrophobically modified chitosan nanoparticles functionalized by the atherosclerotic plaque targeted peptides

We developed a new imaging probe for atherosclerotic lesion imaging by chemically conjugating an atherosclerotic plaque-homing peptide (termed the AP peptide) to hydrophobically modified glycol chitosan (HGC) nanoparticles. The AP peptide was previously discovered by using an in vivo phage display screening method. HGC nanoparticles were labeled with the near-infrared (NIR) fluorophore Cy5.5, yielding nanoparticles 314 nm in diameter. The binding characteristics of nanoparticles to cytokine (TNF-alpha)-activated bovine aortic endothelial cells (BAECs) were studied in vitro under static conditions and in a dynamic flow environment. AP-tagged HGC-Cy5.5 nanoparticles (100 microg/ml, 2 h incubation) bound more avidly to TNF-alpha-activated BAECs than to unactivated BAECs. Nanoparticles were mostly located in the membranes of BAECs, although some were taken up by the cells and were visible in the cytoplasm, suggesting that the AP peptides in HGC nanoparticles retained target selectivity for activated BAECs. Binding selectivity of AP-tagged HGC-Cy5.5 nanoparticles was also studied in vivo. NIR fluorescence imaging demonstrated that AP-tagged HGC-Cy5.5 nanoparticles bound better to atherosclerotic lesions in a low-density lipoprotein receptor-deficient (Ldlr(-/-)) atherosclerotic mouse than to such lesions in a normal mouse. These results suggest that the newly designed AP-tagged HGC-Cy5.5 nanoparticles may be useful for atherosclerotic lesion imaging, and may also be employed to elucidate pathophysiological changes, at the molecular level, on atherosclerotic endothelium.

Hemodynamics of cerebral aneurysms: computational analyses of aneurysm progress and treatment.

The progression of a cerebral aneurysm involves degenerative arterial wall remodeling. Various hemodynamic parameters are suspected to be major mechanical factors related to the genesis and progression of vascular diseases. Flow alterations caused by the insertion of coils and stents for interventional aneurysm treatment may affect the aneurysm embolization process. Therefore, knowledge of hemodynamic parameters may provide physicians with an advanced understanding of aneurysm progression and rupture, as well as the effectiveness of endovascular treatments. Progress in medical imaging and information technology has enabled the prediction of flow fields in the patient-specific blood vessels using computational analysis. In this paper, recent computational hemodynamic studies on cerebral aneurysm initiation, progress, and rupture are reviewed. State-of-the-art computational aneurysmal flow analyses after coiling and stenting are also summarized. We expect the computational analysis of hemodynamics in cerebral aneurysms to provide valuable information for planning and follow-up decisions for treatment.

Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis

Targeting ligands to dysfunctional or activated endothelial cells overlying atherosclerotic plaques could provide tools for selective drug delivery to atherosclerotic lesions. To identify peptides selectively targeting dysfunctional endothelial cells, a phage library was screened against tumor necrosis factor-alpha (TNF-alpha) activated bovine aortic endothelial cells (BAECs). Five rounds of biopanning were carried out and the phage clones selected were examined for their DNA inserts. A phage clone displaying the CLWTVGGGC sequence occurred most frequently and was found to bind specifically to TNF-alpha activated BAECs over untreated cells. On the other hand, bindings of the phage clone to human umbilical vein endothelial cells, lymphatic endothelial cells, and epithelial cells were minimal. Flow cytometric and fluorescence microscopic studies showed the preferential binding of the CLWTVGGGC peptide to TNF-alpha activated BAECs compared to untreated cells. In vivo studies demonstrated selective homing and co-localization of the CLWTVGGGC peptide to dysfunctional endothelial cells overlying atherosclerotic plaques in low-density lipoprotein receptor-deficient mice. These results demonstrate that the CLWTVGGGC peptide could specifically recognize dysfunctional endothelial cells at atherosclerotic plaques and be used as a targeting ligand for drug delivery and imaging of atherosclerosis.

Intraaneurysmal flow changes affected by clip location and occlusion magnitude in a lateral aneurysm model

In order to study the flow dynamic changes inside an aneurysm sac due to the partial occlusion of the aneurysm neck, velocity fields were measured using a particle image velocitimeter (PIV) in in vitro aneurysm models under the physiological flow waveform. Lateral aneurysm models arising from the curved parent vessel with different occlusion ratios and sites-e.g. no clip, 50% proximal and distal clip, and 75% proximal and distal clip-were tested. Reduced inflow and intraaneurysmal velocities may provide a better hemodynamic environment for aneurysm embolization. Comparing inflow rates and averaged intraaneurysmal velocities in the proximal and the distal clip model, they were lower in the distal clip model in cases of 50% neck occlusion, but they were lower in the proximal clip model in cases of 75% occlusion. These results suggest that clipping sites for reduced inflow and intraaneurysmal flow velocities may differ for different residual neck sizes. Less effective inflow blocking in the 75% distally clipped model may be due to the curvature of the parent artery. Therefore, not only the residual neck size and clipping site but the geometry of parent vessel significantly affect the flow fields inside the aneurysm, and subsequently the success of the aneurysm treatment.

Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles

Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue.

The hemodynamic alterations induced by the vascular angular deformation in stent-assisted coiling of bifurcation aneurysms

The hemodynamic changes induced by stent deployment and vascular remodeling in bifurcation aneurysms were investigated using computational fluid dynamics. The stent deployment reduced the intra-aneurysmal flow activity by decreasing the mean velocity, mean kinetic energy, mean wall shear stress, and mean vorticity. These hemodynamic parameters increased with an increase in the branching angle because of the vessel deformation caused by stent straightening. The maximum wall shear stress and its spatial gradient occurred near the neck of the aneurysm in the stented left daughter vessel, whereas a maximum oscillatory shear index was detected near the neck of the right aneurysm of the right daughter vessel. Theses parameters, which might be related to the recurrence of aneurysms, were also increased by stent-induced vessel deformation.

Effects of framing coil shape, orientation, and thickness on intra-aneurysmal flow

To study the effects of the geometrical characteristics of a framing coil on aneurysm thromboembolization efficacy, the hemodynamics in lateral aneurysms filled with coils having a different shape, orientation, and thickness were analyzed using computational fluid dynamics. The aneurysms packed with vortex and cage-shaped coils were modeled using three different coil orientations: transverse, parallel, and orthogonal. The orthogonal orientation of a vortex coil and parallel orientation of a cage-shaped coil showed higher inflow, vorticity, and wall shear stress in the dome region, which provide an unfavorable hemodynamic environment for thromboembolization. Thicker coils also produced unfavorable hemodynamic conditions compared to normal coils having the same shape, orientation, and total coil volume. Though the effects of coil shape and orientation on the hemodynamic parameters of interest were not consistent, the open area at the distal half of the mid-transverse plane of an aneurysm showed significant positive correlation with flow into the dome region and mean vorticity in the dome region. Therefore, blocking the distal mid-transverse plane of an aneurysm using coils would effectively reduce the intra-aneurysmal flow activity and provide a more efficient hemodynamic environment for thromboembolization.

Time-delay control of ionic polymer metal composite actuator

This paper presents the control of an ionic polymer metal composite (IPMC) strip, which is an electro-active polymer actuator. IPMC can produce mechanical bending motion in response to an electrical excitation. Although IPMC has many beneficial properties, such as low power consumption, large deformation, and bi-directional actuation, it is very challenging to control because of its time-varying and nonlinear properties. Time-delay control (TDC) was applied to an IPMC strip in order to obtain a robust and precise tracking performance. The TDC scheme has shown good tracking performance with exceptional robustness in many other applications, in addition to having a simple and efficient structure and design process. A first-order filter was applied to the control input to reduce the sensor noise. An anti-windup scheme was also used because of its inherent integral effect. The simulation and experimental results of an IPMC strip controlled by TDC showed good performance in the steady state and transient responses. Furthermore, the control output responses tracked the desired model even when the IPMC parameters varied in repetitive experiments. In addition, it was shown through Nyquist analysis that the stability of the IPMC strip controlled by TDC is always maintained with the time-varying parameters. These results demonstrate that the TDC law applied to a time-varying and nonlinear IPMC provides robustness in performance and stability, while yielding precise transient and steady state tracking performance.

Effects of radial wall motion and flow waveform on the wall shear rate distribution in the divergent vascular graft.

AbstractAmong the hemodynamic factors influencing intimal hyperplasia in the anastomotic region of a vascular graft, wall shear rate is believed to be one of the most important. We would like to study the effects radial wall motion on the wall shear rate distribution in the end-to-end anastomosis model of an artery and a divergent graft. Rigid and elastic models are constructed and the wall shear rate distributions are measured along the anastomosis using photochromic flow visualization method for carotid and femoral flow waveform. The mean and peak of shear rate decrease along the divergent graft, and the decreases are more significant in the elastic model. The shear rate waves are decomposed using the Fourier transform in order to separate the effects of radial wall motion and geometry. The percentage reductions of mean wall shear rates compared to steady shear rates at mean flow are calculated, and additional 8% (carotid) and 22% (femoral) reductions are observed in the elastic models near the end of the divergent graft. Also radial wall motion decreases the amplitudes of higher harmonics of wall shear rates in the elastic models. Since radial wall motion may affect the flow field differently for different geometry, wall elasticity should be considered in studying arterial hemodynamics.