Hiroyuki Kosukegawa

High fidelity virtual stenting (HiFiVS) for intracranial aneurysm flow diversion: in vitro and in silico.

A flow diverter (FD) is a flexible, densely braided stent-mesh device placed endoluminally across an intracranial aneurysm to induce its thrombotic occlusion. FD treatment planning using computational virtual stenting and flow simulation requires accurate representation of the expanded FD geometry. We have recently developed a high fidelity virtual stenting (HiFiVS) technique based on finite element analysis to simulate detailed FD deployment processes in patient-specific aneurysms (Ma et al.J. Biomech. 45:2256–2263, 2012). This study tests if HiFiVS simulation can recapitulate real-life FD implantation. We deployed two identical FDs (Pipeline Embolization Device) into phantoms of a wide-necked segmental aneurysm using a clinical push–pull technique with different delivery wire advancements. We then simulated these deployment processes using HiFiVS and compared results against experimental recording. Stepwise comparison shows that the simulations precisely reproduced the FD deployment processes recorded in vitro. The local metal coverage rate and pore density quantifications demonstrated that simulations reproduced detailed FD mesh geometry. These results provide validation of the HiFiVS technique, highlighting its unique capability of accurately representing stent intervention in silico.

Friction Properties of Medical Metallic Alloys on Soft Tissue–Mimicking Poly(Vinyl Alcohol) Hydrogel Biomodel

In order to investigate the tribological behavior of medical devices in contact with tissue, friction tests for four kinds of medical metallic alloys (316L stainless steel, CoCr, NiTi and TiMoSn) on soft tissue–mimicking poly(vinyl alcohol) hydrogel (PVA-H) biomodel were carried out at low normal load. XPS analysis and wettability tests for them were prepared to understand the difference in friction. According to the surface oxide compositions, these alloys can be divided into two groups: “Fe/Cr-oxide-surface alloys” for 316L and CoCr, and “Ti-oxide-surface alloys” for NiTi and TiMoSn. From the wettability test, Fe/Cr-oxide-surface alloys show lower polar components of surface free energy than Ti-oxide-surface alloys. Fe/Cr-oxide-surface alloys show higher friction coefficients in the elastic friction domain than those of Ti-oxide-surface alloys, while there was no significant difference in the hydrodynamic lubrication. Since elastic friction is governed by the adsorption of hydrogel polymer on counterbody, the surface characteristic of alloys plays an important role in friction. A tentative explanation for this tendency is expressed by linking two different theories describing the adsorption force of hydrogel and wettability of countermaterial.

Development of a Methodology for Adaptation of Refractive Index Under Controlling Kinematic Viscosity for PIV

Blood vessel diseases such as ischemic cardiac disease or cerebral aneurysm are life-threatening disorders and as large a cause of death as cancer in many countries. The rupture of a cerebral aneurysm usually causes subarachnoidal hemorrhage the mortality of which is very high. Previous studies have proved that the genesis and growth of aneurysm are related to hemodynamics. Especially, in endovascular therapy for cerebral aneurysms using medical devices such as coils or stents, hemodynamics in an aneurysm are related to thrombosis formation in the aneurysm and to its repair. In vascular research using a biomodel (blood vessel phantom with mechanical properties similar to a human artery) for treating cerebral aneurysm, the working fluid, termed Blood-Mimicking Fluid (BMF), should mimic human blood with respect to viscosity so as to obtain realistic blood flow modeling in in vitro measurements. Moreover, refractive indices of BMF must be adjusted to fit biomodel materials because the materials used for Particle Image Velocimetry, one of the best tools for measurement of flow, have various refractive indices. For simultaneous adjustment of the two parameters, i.e. kinematic viscosity and refractive index, an aqueous mixture of glycerol and sodium iodide has been used in previous research. In this paper, we develop a systematic way to precisely find the two targeted parameters of BMF by showing the measurement values of the refractive index and the viscosity of the two aqueous solutions. The refractive index to light of fluorescent was measured with a critical angle refractometer while temperature of sample was also measured. And a vibration-type viscometer was used to obtain the dynamic viscosity under the same condition as refractive index measurement. These measurements were carried out at room temperature and pressure, respectively. As a result of detailed measurements at various proportions, refractive indices of the aqueous solution of glycerol (Gly. aq.) increase monotonically. On the one hand, the kinematic viscosity of Gly. aq. increases very slightly with its proportion and that of the aqueous solution of sodium iodide (NaI aq.) exhibits unique behavior. The results of combining Gly. aq. and NaI aq. indicate that the mixture has a wide range of kinematic viscosity, including the value of blood (around 3.8 mm2 /s), at the targeted refractive index. In conclusion, this mixing method is useful for BMF preparation with the adjustment of refractive index and kinematic viscosity.Copyright

Mechanical Properties of Tube-Shaped Poly (Vinyl Alcohol) Hydrogel Blood Vessel Biomodel

Biomodels, which mimic the shape and motion of blood vessels, have been developed for clinical training in endovascular intervention and for the technical development of interventional devices such as stents. The present authors have developed a biomodel made of poly (vinyl alcohol) hydrogel (PVA-H), which has good transparency, low surface friction, and dynamic viscoelasticity similar to that of arteries. However, evaluation of its behavior as an arterial biomodel has not been carried out. In order to develop a PVA-H biomodel which can accurately mimic the motion of blood vessels, it is necessary to measure and match its mechanical properties in a tube shape mimicking blood vessels. In this study, tube-shaped PVA-H biomodels were prepared, and their mechanical properties were evaluated as to pulse wave velocity (PWV), compliance, and transfer function. PWV was calculated with Young’s modulus and dimensions of the biomodels. A tube-shaped PVA-H model and a model made of commercial silicone were set in a pulsatile flow path apparatus filled pure water (23°C). Sinusoidal pulsatile waves of various frequencies generated by a screw pump were released into flow path. The flow rate, the inner pressure, and the diameter of the biomodels were measured. The compliance of a biomodel was calculated with changing pressures and diameters. The transfer function was obtained as the ratio of the amplitude of the pressure in front of a biomodel and that behind it. The two kinds of biomodels studied showed PWV similar to that of real arteries: PVA-H shows lower PWV which younger arteries tend to show, while silicone shows higher PWV, similar to the case of aged arteries. In compliance, PVA-H shows a value similar to that of arteries in the lower pressure range, whereas silicone shows a value similar to that of arteries at higher pressure. A difference of transfer function in relation to the pulsatile frequencies was observed. This phenomenon is similar to that of real blood vessels and explainable in terms of the theory of the forced vibration in single-degree-of-freedom systems with attenuation. The transfer function is affected by mechanical properties of the wall, and the difference between biomodels is due to the viscoelasticity of the biomodels. With PVA-H, these parameters can be gradually changed by adjusting factors such as concentration. These findings indicate that PVA-H would be useful for the development of biomodels.Copyright

Induction of Neurite Outgrowth in PC12 Cells Treated with Temperature-Controlled Repeated Thermal Stimulation

To promote the functional restoration of the nervous system following injury, it is necessary to provide optimal extracellular signals that can induce neuronal regenerative activities, particularly neurite formation. This study aimed to examine the regulation of neuritogenesis by temperature-controlled repeated thermal stimulation (TRTS) in rat PC12 pheochromocytoma cells, which can be induced by neurotrophic factors to differentiate into neuron-like cells with elongated neurites. A heating plate was used to apply thermal stimulation, and the correlation of culture medium temperature with varying surface temperature of the heating plate was monitored. Plated PC12 cells were exposed to TRTS at two different temperatures via heating plate (preset surface temperature of the heating plate, 39.5°C or 42°C) in growth or differentiating medium for up to 18 h per day. We then measured the extent of growth, neuritogenesis, or acetylcholine esterase (AChE) activity (a neuronal marker). To analyze the mechanisms underlying the effects of TRTS on these cells, we examined changes in intracellular signaling using the following: tropomyosin-related kinase A inhibitor GW441756; p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580; and MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 with its inactive analog, U0124, as a control. While a TRTS of 39.5°C did not decrease the growth rate of cells in the cell growth assay, it did increase the number of neurite-bearing PC12 cells and AChE activity without the addition of other neuritogenesis inducers. Furthermore, U0126, and SB203580, but not U0124 and GW441756, considerably inhibited TRTS-induced neuritogenesis. These results suggest that TRTS can induce neuritogenesis and that participation of both the ERK1/2 and p38 MAPK signaling pathways is required for TRTS-dependent neuritogenesis in PC12 cells. Thus, TRTS may be an effective technique for regenerative neuromedicine.

Deformation of Stenotic Blood Vessel Model Made From Poly (Vinyl Alcohol) Hydrogel by Hydrostatic Pressure

Vascular plaque deformation reduces blood flow, increases arterial embolism risk, and may lead to ischemic stroke. Plaque stiffness varies widely and is an important factor influencing both plaque and parent artery deformation. These geometric changes affect local hemodynamics, which impact plaque initiation influencing disease progression. However, most previous studies used non-elastic stenotic vessel models. For more realistic analysis, we constructed a stenosis model comprising an elastic poly (vinyl alcohol) hydrogel (PVA-H) parent artery and plaque of variable stiffness. Our previous study using this flexible model demonstrated substantial effects of hydrostatic pressure. Here ultrasonography was conducted under changing hydrostatic pressure to measure geometric changes at the narrowest cross section. PVA-H specimens were constructed with the stiffness of a hard lipid core, smooth muscle, and plaque, as estimated by tensile tests using 5, 12, and 15 wt% PVA, respectively. The change in cross-sectional aspect ratio (height/face length) at the narrowest site is largest (∼1.3) for the 5 wt% PVA-H plaque and smallest (∼1.2) for the 12 wt% PVA-H plaque. Stenotic artery deformation depends on both artery and plaque elasticity. Hydrostatic pressure has a substantial effect on both vessel and plaque geometries, which markedly alter blood flow.Copyright

Control of Wall Thickness of Blood Vessel Biomodel Made of Poly (Vinyl Alcohol) Hydrogel by a Three-Dimensional-Rotating Spin Dip-Coating Method

To control the thickness of a PVA-H biomodel of human arteries and veins (150 to 800 μm in thickness), a three-dimensional-rotating spin dip-coating apparatus was fabricated. A straight aluminum cylinder (Ra = 0.16 μm) was employed as substrate. Spin dip-coating was carried out in a cooling chamber at 10°C for 1 hour, and then the substrate was quenched at −30°C for gelation of PVA. The thickness of the deposited PVA-H was measured by using a confocal laser displacement meter. Under the experimental conditions employed, PVA-H with a thickness over 30 μm was obtained. The thickness linearly increased with repeated dippings. The thickness of PVA-H depends on the dipping withdrawal speed, the viscosity of the PVA solution, and the diameter of the substrate. Furthermore, the thickness of PVA-H was found to be almost the same when the viscosity of the PVA solution was constant, regardless of the concentrations of PVA. These results indicate that a tube-shaped PVA-H biomodel with desired thickness and physical properties can be obtained by using a spin dip-coating technique and that PVA-H can mimic the wall thickness of various arteries and veins.Copyright

Evaluation of Compliance of Poly (vinyl alcohol) Hydrogel for Development of Arterial Biomodeling

An in vitro blood vessel biomodeling with realistic mechanical properties and geometrical structures will be helpful for the training of intervention, preoperative simulation, and realizing the same physical conditions of blood flow. Poly (vinyl alcohol) hydrogel (PVA-H) with low surface friction, good transparency, and similar elasticity to blood vessel has been developed and accepted as a good material for biomodeling. However, the compliance of PVA-H vessel model has not been measured. In this study, we changed the elasticity and measured the compliance of a box-typed PVA-H biomodeling, to represent the similar compliance to a real artery. PVA powders were dissolved in a mixture of water and organic solvent so that PVA solutions of 12, 18 wt% were prepared. The model was subjected to hydrostatic pressure by adding distilled water and the inner diameter was measured using an ultrasound system. The compliance of each model was calculated from the strain of inner diameter and the inner pressure. The inner diameter of model increases linearly as the inner pressure increases. The compliance of PVA-H model is constant according to pressure change, while that of a real blood vessel changes nonlinearly. This difference may depend on the isotropic characteristics of PVA-H, whereas a real blood vessel is anisotropic. These results indicate that adding anisotropy, such as orientation of PVA, to model would be necessary to represent the compliance of a real artery.