Woorak Choi

Fluid-dynamic optimal design of helical vascular graft for stenotic disturbed flow.

Although a helical configuration of a prosthetic vascular graft appears to be clinically beneficial in suppressing thrombosis and intimal hyperplasia, an optimization of a helical design has yet to be achieved because of the lack of a detailed understanding on hemodynamic features in helical grafts and their fluid dynamic influences. In the present study, the swirling flow in a helical graft was hypothesized to have beneficial influences on a disturbed flow structure such as stenotic flow. The characteristics of swirling flows generated by helical tubes with various helical pitches and curvatures were investigated to prove the hypothesis. The fluid dynamic influences of these helical tubes on stenotic flow were quantitatively analysed by using a particle image velocimetry technique. Results showed that the swirling intensity and helicity of the swirling flow have a linear relation with a modified Germano number (Gn*) of the helical pipe. In addition, the swirling flow generated a beneficial flow structure at the stenosis by reducing the size of the recirculation flow under steady and pulsatile flow conditions. Therefore, the beneficial effects of a helical graft on the flow field can be estimated by using the magnitude of Gn*. Finally, an optimized helical design with a maximum Gn* was suggested for the future design of a vascular graft.

Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats

Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.

Beneficial fluid-dynamic features of pulsatile swirling flow in 45° end-to-side anastomosis

Although a large number of vascular grafts are surgically implanted annually, approximately 10-15% of these grafts fail in the first year after operation and about 50% are only effective for five to ten years. Surgical implantation of a vascular graft modifies the inherent hemodynamic environment in blood vessels; hence, fluid dynamic characteristics of pathological blood flow are highly related to the performance of the vascular graft. In this study, pathological fluid-dynamic characteristics in a 45° end-to-side anastomosis were experimentally investigated using a particle image velocimetry technique. In particular, the effect of the pulsatile swirling inlet flow in the vascular graft on the improvement of pathological hemodynamic features was systematically investigated. Introducing the pulsatile swirling flow equalizes the asymmetric distribution of wall shear stress and reduces oscillatory shear index and the size of flow separation because the flow disturbs the formation of Dean-type vortices and suppresses secondary flow collision. The fluid dynamic features of the pulsatile swirling flow are expected to be beneficial in designing vascular grafts that can suppress pathological hemodynamic characteristics in the recipient host vessel.

Effect of swirling blood flow on vortex formation at post-stenosis

Various clinical observations reported that swirling blood flow is a normal physiological flow pattern in various vasculatures. The swirling flow has beneficial effects on blood circulation through the blood vessels. It enhances oxygen transfer and reduces low-density lipoprotein concentration in the blood vessel by enhancing cross-plane mixing of the blood. However, the fluid-dynamic roles of the swirling flow are not yet fully understood. In this study, inhibition of material deposition at the post-stenosis region by the swirling flow was observed. To reveal the underlying fluid-dynamic characteristics, pathline flow visualization and time-resolved particle image velocimetry measurements were conducted. Results showed that the swirling inlet flow increased the development of vortices at near wall region of the post-stenosis, which can suppress further development of stenosis by enhancing transport and mixing of the blood flow. The fluid-dynamic characteristics obtained in this study would be useful for improving hemodynamic characteristics of vascular grafts and stents in which the stenosis frequently occurred. Moreover, the time-resolved particle image velocimetry measurement technique and vortex identification method employed in this study would be useful for investigating the fluid-dynamic effects of the swirling flow on various vascular environments.

Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish

Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS) that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV) technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis.

Homocysteine-induced peripheral microcirculation dysfunction in zebrafish and its attenuation by L-arginine

Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter V¯CV/ V¯PCV, where V¯CV and V¯PCV represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively. The ratio of the peripheral microcirculation perfusion to the systemic perfusion is largely decreased due to peripheral accumulation of neutrophils, while the systemic perfusion is relatively preserved by increased blood supply from subintestinal vein. Pretreatment with L-arginine attenuates the effects of Hcy on peripheral microcirculation and reduces the peripheral accumulation of neutrophils. Given its convenience, high reproducibility of the observation site, non-invasiveness, and the ease of drug treatment, the present zebrafish model with the proposed parameters will be used as a useful drug screening platform for investigating the pathophysiology of Hcy-induced microvascular diseases.Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter V¯CV/V¯PCV, where V¯CV and V¯PCV represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively. The ratio of the peripheral microcirculation perfusion to the systemic perfusion is largely decreased due to peripheral accumulation of neutrophils, while the systemic perfusion is relatively preserved by increased blood supply from subintestinal vein. Pretreatment with L-arginine attenuates the effects of Hcy on peripheral microcirculation and reduces the peripheral accumulation of neutrophils. Given its convenience, high reproducibility of the observation site, non-invasiveness, and the ease of drug treatment, the present zebrafish model with the proposed parameters will be used as a useful drug screening platform for investigating the pathophysiology of Hcy-induced microvascular diseases.

Variation in wall shear stress in channel networks of zebrafish models

Physiological functions of vascular endothelial cells (ECs) vary depending on wall shear stress (WSS) magnitude, and the functional change affects the pathologies of various cardiovascular systems. Several in vitro and in vivo models have been used to investigate the functions of ECs under different WSS conditions. However, these models have technical limitations in precisely mimicking the physiological environments of ECs and monitoring temporal variations of ECs in detail. Although zebrafish (Danio rerio) has several strategies to overcome these technical limitations, zebrafish cannot be used as a perfect animal model because applying various WSS conditions on blood vessels of zebrafish is difficult. This study proposes a new zebrafish model in which various WSS can be applied to the caudal vein. The WSS magnitude is controlled by blocking some parts of blood-vessel networks. The accuracy and reproducibility of the proposed method are validated using an equivalent circuit model of blood vessels in zebrafish. The proposed method is applied to lipopolysaccharide (LPS)-stimulated zebrafish as a typical application. The proposed zebrafish model can be used as an in vivo animal model to investigate the relationship between WSS and EC physiology or WSS-induced cardiovascular diseases.

Hemodynamic characteristics of flow around a deformable stenosis

Clinical studies reported that some vulnerable stenoses deformed their shape in a blood vessel based on flow condition. However, the effects of shape variation on flow characteristics remain unclear. The flow characteristics are known to affect vulnerable stenosis rupture and fractional flow reserve (FFR) value which has been widely used as a diagnostic tool for stenosis. Vulnerable stenosis rupture occurs when the structural stress exerted on a fibrous cap exceeds its tolerable threshold. The stress magnitude is determined from the spatial distribution of static pressure around the stenosis. In the present study, the static pressure distribution and the FFR value in deformable stenosis were investigated with related other flow characteristics. Two phantom models were fabricated to mimic deformable and nondeformable stenoses using polydimethylsiloxane. The flow characteristics were observed under a steady-flow condition at three Reynolds numbers (Re=500, 1000, 1500) using a particle image velocimetry. The pressure drop across the stenosis models were measured using a pressure sensor to determine effects of shape deformation on FFR value. Shape variations and jet deflections were clearly observed in the deformable stenosis model, and the effective severity of the stenosis increased up to 17.2%. The shape variations of deformable stenosis model increased the static pressure difference at the upstream and downstream sides of the stenosis. The pressure drop across the deformable stenosis model was significantly higher than that of the nondeformable stenosis model. The present results substantiate that stenosis deformability should be carefully considered to diagnose the rupture of vulnerable stenosis.

Flow characteristics around a deformable stenosis under pulsatile flow condition

A specific portion of a vulnerable stenosis is deformed periodically under a pulsatile blood flow condition. Detailed analysis of such deformable stenosis is important because stenotic deformation can increase the likelihood of rupture, which may lead to sudden cardiac death or stroke. Various diagnostic indices have been developed for a nondeformable stenosis by using flow characteristics and resultant pressure drop across the stenosis. However, the effects of the stenotic deformation on the flow characteristics remain poorly understood. In this study, the flows around a deformable stenosis model and two different rigid stenosis models were investigated under a pulsatile flow condition. Particle image velocimetry was employed to measure flow structures around the three stenosis models. The deformable stenosis model was deformed to achieve high geometrical slope and height when the flow rate was increased. The deformation of the stenotic shape enhanced jet deflection toward the opposite vessel wall of the...