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In recent years, endovascular treatments, in which a treatment device such as a catheter is inserted into a blood vessel to directly approach a lesion, have become increasingly popular worldwide. For safer treatment and further optimization of medical devices, a deeper understanding of the vascular biotribology of the medical devices, biomodels, and blood vessels and an appropriate evaluation method are required. This review paper presents the current state of research on the evaluation of the friction between an intravascular device and a vascular biomodel. We review the experimental conditions, including the sample shape, sliding speed, contact pressure, lubricant, materials, and temperature. Standardized methods should be established for evaluating the friction between an intravascular device and a vascular biomodel.

Abstract Computational fluid dynamics is widely used to simulate droplet-spreading behavior due to respiratory events. However, droplet generation inside the body, such as the number, mass, and particle size distribution, has not been quantitatively analyzed. The aim of this study was to identify quantitative characteristics of droplet generation during coughing. Airflow simulations were performed by coupling the discrete phase model and Eulerian wall film model to reproduce shear-induced stripping of airway mucosa. An ideal airway model with symmetric bifurcations was constructed, and the wall domain was covered by a mucous liquid film. The results of the transient airflow simulation indicated that the droplets had a wide particle size distribution of 0.1–400 µm, and smaller droplets were generated in larger numbers. In addition, the total mass and number of droplets generated increased with an increasing airflow. The total mass of the droplets also increased with an increasing mucous viscosity, and the largest number and size of droplets were obtained at a viscosity of 8 mPa s. The simulation methods used in this study can be used to quantify the particle size distribution and maximum particle diameter under various conditions.

As an approach to maintain patency in femoropopliteal stenting, a helical stent configuration was proposed, which showed improved patency in clinical trials. However, the effects of helical stent placement on the flow have not been quantitatively analyzed. The purpose of this study was to estimate flow velocities to quantify the influence of helical stent placement. Helical and straight stents were implanted in three healthy pigs, and the flow velocities were estimated using the time-intensity curve (TIC) in the angiography images. The angiographic images indicated thinning of the leading edge of the contrast medium through the helically deformed artery, which was not observed in the straight stent. The slower rise of the TIC peak in the helical stent indicated faster travel of this thinner edge. Arterial expansion due to stenting was observed in all cases, and the expansion rate varied according to location. All cases of helical stent implantation showed that velocity was maintained (55.0%–71.3% velocity retention), unlike for straight stent implantation (43.0%–68.0% velocity retention); however, no significant difference was observed.

This study investigates the non-invasive monitoring of the endocrine ovarian activities of captive female golden takins (Budorcas taxicolor bedfordi) based on long-term fecal sex steroid hormone metabolite dynamics. Fecal progesterone (P4) metabolite dynamics were monitored in nine females for 0.5–15 years between 2004 and 2022. Fecal estradiol-17β (E2) and estrone (E1) metabolites were measured during certain estrous cycles, and fecal E1 metabolite concentrations were measured during all gestation periods. The breeding season of the captive animals was mainly between May and December, and they were polyestrous animals whose breeding season begins during the long-day period. The onset of the breeding season occurred slightly earlier as age increased. The mean age (±SD) at puberty based on fecal P4 metabolite dynamics was 4.1 ± 2.9 years. The first conception ages ranged from 2.3–10.2 years. The mean estrous cycle period (±SEM) was 25.4 ± 1.1 days, and mounting and mating occurred in periods of low fecal P4 metabolite levels during the breeding season. The mean gestation period (±SD) from the estimated mating date to the calving date was 253.9 ± 5.7 days, and the fecal P4 metabolite distribution during pregnancy was bimodal. Fecal estrone metabolite levels gradually increased 21 weeks before delivery, peaked during the week of delivery, and then markedly decreased in the first week after delivery. Estrus resumed in the first April–August period after delivery (mean ± SD; 103.5 ± 40.9 days) or in May of the year after delivery (421.0 ± 16.5 days). This study revealed that the estrous cycle and pregnancy of female golden takins can be determined by fecal progesterone metabolite dynamics and that fecal estrone metabolite dynamics increases toward parturition and are useful for predicting the date of delivery. This endocrinological information is important for planned breeding efforts for the golden takins.

Detecting abnormal blood flow is possible through transcranial Doppler (TCD) ultrasound by measuring blood velocity in cerebral arteries. Velocity measurements are at the highest precision when the direction of blood flow coincides with the ultrasound beam. However, because TCD is typically performed blindly (i.e., without a B-mode), a 0° interrogation angle is usually assumed. This leads to a common issue of angular mismatch. This study quantitatively shows the angular mismatch effects on the measured velocities using a TCD ultrasound flow phantom compared with the velocities measured by optical particle image velocimetry (PIV) as control. Resulting errors with and without ultrasound machine angular correction were also considered. An ultrasound phantom developed by combining polyvinyl alcohol hydrogel (PVA-H), quartz glass as a scatterer, and a gypsum plate as a skull bone was utilized to approximate the middle cerebral artery TCD measurement from the temporal window. The PVA-H and quartz glass compositions were controlled to achieve transparency and enable PIV velocity measurement. Then, TCD velocity measurement was conducted on several interrogation and mismatch angles. Comparison results revealed that without an ultrasound machine angle correction, all measurements yielded underestimation with 73.9% at the highest in the 80° interrogation window at the 130 mL/min flow. On the other hand, with the correction, the errors in almost all angles were comparatively lower; however, at 80° at the 124 mL/min flow, a maximum overestimation rate of 113.7% was found, showing a larger error magnitude. Therefore, we find that angular mismatch, especially in larger angles, leads to inaccurate velocity measurements in TCD. Our results suggest that despite angle correction, velocity errors may still occur when the interrogation angle changes.

BackgroundStent is widely regarded as the main treatment for curing cardiovascular diseases such as stenosis. Previous research has revealed that the damage of endothelial cells (EC), i.e., the components of endothelium, during stent implantation, could lead to severe complications, such as restenosis. To prevent restenosis, enhancements have been made to surface biocompatibility to accelerate the stent endothelialization process. Anodization on the Ni-Ti is a simple and efficient surface modification method to improve the biocompatibility of the Ni-Ti stent surfaces by enhancing the surface hydrophilicity, leading to an increase in the EC activities. The EC activity is known to be affected by the blood flow. Flow change by stent structure may result in EC dysfunctions, thereby leading to restenosis. It is thus essential to investigate the EC activities resulting from the anodization on the Ni-Ti surface under flow conditions.ObjectiveTo study the influence of the endothelialization process on the Ni-Ti stent surface through anodization. The EC attachment and morphology on the anodized stent strut were observed under both with and without the flow conditions.MethodA parallel plate flow chamber was designed to generate a constant wall shear stress (WSS) to study the flow effect on the EC behavior. The hydrophilicity of the Ni-Ti stent strut surface was enhanced by a TiO2 layer fabricated via anodization. The EC distribution on the surface of the anodized nitinol stent strut was observed after 24 h of static (without flow) and flow exposure (with flow) experiment.ResultsUnder the static condition, the EC density on the surface of the anodized Ni-Ti stent strut was higher compared with the control. Under the flow condition, the enhancement of the EC density on the surface of the stent strut with anodization was reduced. The EC demonstrates a long and thin spindle-shaped morphology under the flow condition.ConclusionUnlike the static condition, the EC is demonstrating a long and thin morphology in response to the flow under the flow condition. By improving the surface hydrophilicity, the anodization could enhance the EC migration onto the strut surface, and subsequently, accelerate the Ni-Ti stent endothelialization process. The improvement of the surface hydrophilicity is lower under the flow conditions when compared with the static conditions.

Esophageal intramural pseudodiverticulosis (EIPD) is a rare disorder characterized by an abnormal, cyst-like dilatation of the excretory ducts of esophageal submucosal glands. We aimed to elucidate the histopathological features and immunohistochemical properties of the epithelial lining of the cyst-like lesions in EIPD. We performed a histopathological and immunohistochemical study of 2 cases (one autopsy and one surgical) of EIPD. The ductal walls consisted of inner ductal cells, which were cytokeratin (CK) 7-positive and CK5/6-negative, and outer basal cells, which were CK7-negative and CK5/6-positive. The ductal epithelium frequently showed squamous metaplasia and rarely simulated a false diverticulum. Immunohistochemistry for CK7 was useful for distinction between the conditions because the surface epithelium was negative for CK7. We also confirmed that myoepithelial cells in the acinar portion of submucosal glands were well-preserved in EIPD, the finding that explained the periodic opening and closing movements of orifices of cyst-like lesions in this disorder. The immunohistochemical properties of the epithelial lining of cyst-like lesions in EIPD were essentially similar to those of the normal ducts of submucosal glands.

A national questionnaire survey on guidewire penetration accidents by the Japanese Society for Neuroendovascular Therapy reported examples of perforation accidents occurring “during catheter introduction” (75.2% of accidents). In this study, we evaluated the behavior of a guidewire and a catheter during catheter introduction by numerical simulations, based on the results of the national survey. Using the contact force between the medical devices and the vessel wall, and the medical device position as criteria, we investigated the mechanism and the risk of penetration by the device tip during device introduction. We also evaluated the effects of the insertion velocity of the guidewire and the catheter. The contact force gradually increased during insertion of the guidewire, and the maximum contact force was observed after the guidewire passed through a bend in the blood vessel. After that, when introducing a catheter along the guidewire at the bend in the blood vessel, the guidewire imparted a greater load on the vessel wall than when the guidewire itself was introduced. This is the same tendency seen in our previous study and the national survey. One reason for the force increase during catheter introduction is a decrease in the contact area, which concentrates the contact force. Another reason for the force increase is that the bending stiffness of the guidewire covered by the catheter is the sum of the stiffnesses of the two devices, which is larger than that of only the guidewire. Different from guidewire introduction, as the insertion velocity of the catheter increased, the maximum contact force decreased under the influence of the bend shape and the contact force distribution. Moreover, the guidewire oscillated considerably when the catheter was introduced, and this oscillation increased as the insertion velocity increased, leading to a risk of mistakenly straying into a perforating branch.

Anzai et al. propose a deep learning approach to estimate the 3D hemodynamics of complex aorta-coronary artery geometry in the context of coronary artery bypass surgery. Their method reduces the calculation time 600-fold, while allowing high resolution and similar accuracy as traditional computational fluid dynamics (CFD) method.

Stent implantation has been a primary treatment for stenosis and other intravascular diseases. However, the struts expansion procedure might cause endothelium lesion and the structure of the struts could disturb the blood flow environment near the wall of the blood vessel. These changes could damage the vascular innermost endothelial cell (EC) layer and pose risks of restenosis and post-deployment thrombosis. This research aims to investigate the effect of flow alterations on EC distribution in the presence of gap between two struts within the parallel flow chamber. To study how the gap presence impacts EC migration and the endothelialization effect on the surface of the struts, two struts were placed with specific orientations and positions on the EC layer in the flow chamber. After a 24-h exposure under wall shear stress (WSS), we observed the EC distribution conditons especially in the gap area. We also conducted computational fluid dynamics (CFD) simulations to calculate the WSS distribution. High EC-concentration areas on the bottom plate corresponded to the high WSS by the presence of gap between the two struts. To find the relation between the WSS and EC distributions on the fluorescence images, WSS condition by CFD simulation could be helpful for the EC distribution. The endothelialization rate, represented by EC density, on the downstream sides of both struts was higher than that on the upstream sides. These observations were made in the flow recirculation at the gap area between two struts. On two side surfaces between the gaps, meaning the downstream at the first and the upstream at the second struts, EC density differences on the downstream surfaces of the first strut were higher than on the upstream surfaces of the second strut. Finally, EC density varied along the struts when the struts were placed at tilted angles. These results indicate that, by the presence of gap between the struts, ECs distribution could be predicted in both perpendicular and tiled positions. And tiled placement affect ECs distribution on the strut side surfaces.

Background: Whilst intravascular endoscopy can be used to identify lesions and assess the deployment of endovascular devices, it requires temporary blockage of the local blood flow during observation, posing a serious risk of ischaemia.Objective: To aid the design of a novel flow-blockage-free intravascular endoscope, we explored changes in the haemodynamic behaviour of the flush flow with respect to the flow injection speed and the system design.Methods: We first constructed the computational models for three candidate endoscope designs (i.e., Model A, B, and C). Using each of the three endoscopes, flow patterns in the target vessels (straight, bent, and twisted) under three different sets of boundary conditions (i.e., injection speed of the flush flow and the background blood flowrate) were then resolved through use of computational fluid dynamics and in vitro flow experiments. The design of endoscope and its optimal operating condition were evaluated in terms of the volume fraction within the vascular segment of interest, as well as the percentage of high-volume-fraction area (PHVFA) corresponding to three cross-sectional planes distal to the microcatheter tip.Results: With a mild narrowing at the endoscope neck, Model B exhibited the highest PHVFA, irrespective of location of the cross-sectional plane, compared with Models A and C which, respectively, had no narrowing and a moderate narrowing. The greatest difference in the PHVFA between the three models was observed on the cross-sectional plane 2 mm distal to the tip of the microcatheter (Model B: 33% vs. Model A: 18%). The background blood flowrate was found to have a strong impact on the resulting volume fraction of the flush flow close to the vascular wall, with the greatest difference being 44% (Model A).Conclusion: We found that the haemodynamic performance of endoscope Model B outperformed that of Models A and C, as it generated a flush flow that occupied the largest volume within the vascular segment of interest, suggesting that the endoscope design with a diameter narrowing of 30% at the endoscope neck might yield images of a better quality.

To ensure safe coil embolization for cerebral aneurysms, it is important to investigate the contact force between a coil and an aneurysm wall. Therefore, in our previous study, we developed an experimental system for measuring the contact force between a coil and an aneurysm biomodel. However, because the aneurysm model was made of silicone rubber, its physical properties, such as the friction coefficient, differed from those of aneurysms in vivo. Therefore, in this study, we made an aneurysm model using poly (vinyl alcohol) hydrogel (PVA-H) and evaluated the effect of the model material on the contact force. In addition, we acquired images during the experiment and evaluated the behavior of the coil and catheter and the relationship between the catheter movement and the contact force. A commercially available coil was inserted through a catheter into two types of aneurysm models (silicone rubber and PVA-H), and the effects of the model material and the catheter tip position (near dome, at the center, and near neck) were evaluated. The contact force and the total movement of the catheter tip for the PVA-H model were smaller than those for the silicone rubber model. The contact force (total catheter movement) was greater (smaller) when the catheter tip was inserted deeper into the silicone rubber model. These results suggest that the state of contact between the aneurysm and the coil affects the contact force and the catheter movement and that these two values are related.

The vascular endothelial cells constitute the innermost layer. The cells are exposed to mechanical stress by the flow, causing them to express their functions. To elucidate the functions, methods involving seeding endothelial cells as a layer in a chamber were studied. The chambers are known as parallel plate, T-chamber, step, cone plate, and stretch. The stimulated functions or signals from endothelial cells by flows are extensively connected to other outer layers of arteries or organs. The coculture layer was developed in a chamber to investigate the interaction between smooth muscle cells in the middle layer of the blood vessel wall in vascular physiology and pathology. Additionally, the microfabrication technology used to create a chamber for a microfluidic device involves both mechanical and chemical stimulation of cells to show their dynamics in in vivo microenvironments. The purpose of this study is to summarize the blood flow (flow inducing) for the functions connecting to endothelial cells and blood vessels, and to find directions for future chamber and device developments for further understanding and application of vascular functions. The relationship between chamber design flow, cell layers, and microfluidics was studied.

Decades after its introduction, endovascular aneurysm repair remains a challenging procedure with risks of collateral patency failure. Here, we investigate the ability of a porous stent, the Multilayer Flow Modulator (MFM), to maintain renal perfusion after a single or overlapping case. Silicone models representing an ideal infrarenal AAA geometry were used to analyze and compare three cases (control, single MFM and two overlapped MFMs). Micro-computed tomography was used to image the deployed MFM devices geometry and evaluate pore size and density along with porosity in both two (planimetric) and three dimensions (gravimetric). Laser particle image velocimetry (PIV) experiments were performed to image velocity and vorticity fields at the aorta-renal bifurcation. Flow experiments revealed renal arteries perfusion preservation in both single and overlapped cases. Microstructure analysis revealed an uneven distribution of wires in the MFM devices leading to local change in planimetric porosity and pore size. Overlap of a second MFM device led to a significant decrease in those 2D metrics but did not affect the gravimetric porosity and the branch perfusion. This first microstructure evaluation of MFM device combined with flow experiments revealed the ability of the device to preserve collateral flow thanks to a highly porous microstructure.

During an angioscopy operation, a transparent liquid called dextran is sprayed out from a catheter to flush the blood away from the space between the camera and target. Medical doctors usually inject dextran at a constant flow rate. However, they often cannot obtain clear angioscopy visibility because the flushing out of the blood is insufficient. Good flushing conditions producing clear angioscopy visibility will increase the rate of success of angioscopy operations. This study aimed to determine a way to improve the clarity for angioscopy under different values for the parameters of the injection waveform, endoscope position, and catheter angle. We also determined the effect of a stepwise waveform for injecting the dextran only during systole while synchronizing the waveform to the cardiac cycle. To evaluate the visibility of the blood-vessel walls, we performed a computational fluid dynamics (CFD) simulation and calculated the visible area ratio (VAR), representing the ratio of the visible wall area to the total area of the wall at each point in time. Additionally, the normalized integration of the VAR called the area ratio (ARVAR) represents the ratio of the visible wall area as a function of the dextran injection period. The results demonstrate that the ARVAR with a stepped waveform, bottom endoscope, and three-degree-angle catheter results in the highest visibility, around 25 times larger than that under the control conditions: a constant waveform, a center endoscope, and 0 degrees. This set of conditions can improve angioscopy visibility.

ObjectivesTreating intracranial aneurysms with flow-diverting stents sometimes requires deployment of a second device. Herein we quantify the sizing effects of devices in dual-stent treatments upon the final stent microstructure and the post-treatment aneurysmal haemodynamics.MethodsFifteen sidewall ICA aneurysm geometries were included. Using a virtual stenting technique, we implanted either one or two stents for each aneurysm treatment considered, with each stent specified as one of two different sizes, yielding a total of two single-stent and fouir dual-stent treatment scenarios for each aneurysm. Three stent microstructural parameters and nine aneurysmal haemodynamic parameters were quantified and systematically compared across the 90 treatment scenarios.ResultsDeployment of a second stent further reduced the aneurysmal inflow rate (IR) and energy loss (EL) by, respectively, 14 ± 11% (p = 0.001) and 9 ± 12% (p = 0.056), relative to the untreated condition. Sizing effects of the earlier-deployed stent led to largest differences of 6.9% for the final IR reduction and 11.1% for the EL, whereas sizing effects from the later-deployed stent were minor (≤2.1%). The change in stent pore size was the only microstructural parameter demonstrating a strong correlation with the reduction in the post-treatment aneurysmal haemodynamics, in terms of the IR (r = 0.50, p < 0.001) and pressure drop (r = 0.63, p < 0.001).ConclusionSize of the earlier-deployed stent has substantial effects on the final haemodynamic outcomes after dual-stent treatment. The average pore size of stent wires at the aneurysm orifice shows promise as a potential index for predicting the efficacy of flow-diversion treatments.

Coronary artery bypass grafts (CABGs), including saphenous vein grafts (SVGs) or left internal mammary artery (LIMA) grafts, are recently applied to treat coronary artery aneurysm (CAA). Surgical outcomes are considered to be related to surgical strategies (types of the bypass graft and whether CAA ligated or not) and the size of the CAA (usually characterized by diameter). However, the understanding of the relationship between the surgical outcomes and the abovementioned factors is limited. Previous studies related to CABG treatments have shown hemodynamic studies could help evaluate surgical outcomes through graft mass flow rate, wall shear stress (WSS), and oscillatory shear index (OSI). It is believed that the hemodynamic study of applying CABGs to CAA, which is not studied yet, could help us understand the different CABG surgeries. The aim of the study was to evaluate the hemodynamic differences among different surgical methods. To do this, eight three-dimensional models were constructed, representing application of SVGs and LIMA grafts to CAAs (whether ligated or not) with diameters two, three, and five times the normal diameter, to perform computational fluid dynamics (CFD) simulation. The lumped-parameter model (LPM) was coupled to the boundary of the 3D models which increase the complexity of the simulation, but it can ensure the stability of the simulation boundary conditions. The results show that SVG (no matter whether ligated or not) hemodynamic characteristics are positive, with an average high graft mass flow rate of 70 ml/min, an average WSS of 0.479 Pa, and a low OSI of 0.001. LIMA with CAA ligation has the same characteristics with higher WSS (average 1.701 Pa). The hemodynamic characteristics of LIMA without CAA ligation are negative, including high reverse mass flow rate and high OSI (0.367). The results indicate that the surgical outcomes of LIMA with CAA ligation are likely to be the best among these models. The surgical outcomes of LIMA without CAA ligation seem to be undesirable due to the high reverse mass flow and high OSI. The CAA diameter may not have a significant effect on surgical outcomes.

Coronary artery aneurysms (CAAs) have been reported to associate with an increased risk for thrombosis. Distinct to the brain aneurysm, which can cause a rupture, CAA’s threat is more about its potential to induce thrombosis, leading to myocardial infarction. Case reports suggest that thrombosis risk varied with the different CAA diameters and hemodynamics effects (usually wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT)) may relate to the thrombosis risk. However, currently, due to the rareness of the disease, there is limited knowledge of the hemodynamics effects of CAA. The aim of the study was to estimate the relationship between hemodynamic effects and different diameters of CAAs. Computational fluid dynamics (CFD) provides a noninvasive means of hemodynamic research. Four three-dimensional models were constructed, representing coronary arteries with a normal diameter (1x) and CAAs with diameters two (2x), three (3x), and five times (5x) that of the normal diameter. A lumped parameter model (LPM) which can capture the feature of coronary blood flow supplied the boundary conditions. WSS in the aneurysm decreased 97.7% apparently from 3.51 Pa (1x) to 0.08 Pa (5x). OSI and RRT in the aneurysm were increased apparently by two orders of magnitude from 0.01 (1x) to 0.30 (5x), and from 0.38 Pa−1 (1x) to 51.59 Pa−1 (5x), separately. Changes in the local volume of the CAA resulted in dramatic changes in local hemodynamic parameters. The findings demonstrated that thrombosis risk increased with increasing diameter and was strongly exacerbated at larger diameters of CAA. The 2x model exhibited the lowest thrombosis risk among the models, suggesting the low-damage (medication) treatment may work. High-damage (surgery) treatment may need to be considered when CAA diameter is 3 times or higher. This diameter classification method may be a good example for constructing a more complex hemodynamic-based risk stratification method and could support clinical decision-making in the assessment of CAA.

Abstract Biomodels made of poly(vinyl alcohol) (PVA) are demanded because they can represent the geometries and mechanical properties of human tissues realistically. Injecting and molding, commonly used in three-dimensional (3D) modeling, help to represent the blood vessels accurately. However, these techniques sometimes require higher pressures than the upper pressure limit of the dispensers for pouring in high viscosity materials; the material viscosity should therefore be lower. Moreover, the mechanical properties of the biomodels should be reproduced. This study proposes a PVA solution through the addition of xanthan gum (XG) for 3D modeling, which lowers liquid viscosity while maintaining the mechanical properties of biomodels. XG is known to facilitate the achievement of non-Newtonian fluidity; however, the effects of XG on a PVA solution and PVA hydrogel (PVA-H) are not confirmed. The viscosity measurement using 15 wt% PVA with XG solution (PVA/XG) shows that it will provide easier pouring than 17 wt% PVA solution. The tensile test using the PVA-H of PVA(15 wt%)/XG(0.2 wt%) reveals that the gel is comparable in Young’s modulus to 17 wt% PVA-H. X-ray diffraction shows the crystalline structures of the PVA/XG gel and PVA-H are identical. Thus, this PVA/XG would be useful for fabricating biomodels using injection molding techniques.

Purpose: To report the limited usefulness of polymerase chain reaction (PCR)-based immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement analysis in diagnosing primary ocular adnexal lymphomas (OAL) treated with corticosteroids before biopsy. Observations: This was a case series of two patients: a 47-year-old woman and a 43-year-old man, who both presented with impaired visual acuity and ophthalmoplegia of the involved eyes. Both patients had previously received non-diagnostic biopsy and had been subsequently treated with corticosteroids. The visual acuity and ophthalmoplegia progressively worsened after a variable duration of remission. Ocular magnetic resonance imaging revealed gadolinium-enhancing intra- and extraconal lesions. Systemic evaluations did not reveal any other lesions outside of the orbit. Differential diagnoses were lymphoproliferative disorders, including undiagnosed primary OALs, and idiopathic ocular inflammation. Both patients were exposed to repeated biopsies. The biopsied tissue demonstrated marked lymphocytolysis due to corticosteroid usage; therefore, histology and immunophenotype were non-diagnostic. EuroClonality/BIOMED-2 PCR-based gene rearrangement analyses detected genetic clonalities of Ig and TCR and suggested diagnoses of primary OALs of B-cell and T-cell origins, respectively. An OAL of B-cell origin was treated with radiotherapy; an OAL of a rare T-cell origin was treated with high-dose methotrexate-based chemotherapy and adjuvant radiotherapy. Both patients remained progression free for more than 36 months. Conclusions and importance: PCR-based gene rearrangement analysis can be of limited usefulness in suggesting a diagnosis of primary OAL in patients receiving pre-biopsy corticosteroid treatment. Identification of genetic clonality is of clinical importance to provide treatment options for undiagnosed OALs. Keywords: Ocular adnexal lymphomas, Corticosteroids, B-cell, T-cell, Polymerase chain reaction, Gene rearrangement, Immunoglobulin, T-cell receptor

Background: Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. Methods: This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. Results: Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. Conclusions: In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients.

In a recent paper published in Materials (Castro et al., 2019), the permeability evaluation of triple periodic minimum surface samples was carried out experimentally. Darcy’s law was used under unsuitable conditions, resulting in an underestimation of the results. In this comment, we highlight the problem and propose a new estimation of the permeability using the Forchheimer equation, which is better suited to the experimental conditions.

Various catheter simulators using a computer or blood vessel biomodels have been developed for training of medical students and young physicians. Moreover, we have developed a system to simulate a guidewire in blood vessels that uses both numerical analysis and experimental observation for the quantitative analysis of treatment technique, surgical planning, intra-operative assistance, and to facilitate the design of new guidewires. However, not limited to our group, there is a lack of studies evaluating the motions of both the guidewire and catheter and their interaction in a blood vessel. Therefore, in the present study, we modified our computer-based system and experimental apparatus to evaluate the catheter motion and compared both results. First, we added a mechanism to the experimental apparatus to move and evaluate the catheter in a poly (vinyl alcohol) hydrogel blood vessel model. Second, we added a new catheter model to the calculation. We subsequently evaluated the behaviors of the medical devices (the guidewire and the catheter) by measuring the three-dimensional position and the contact force between the medical devices and the vessel wall. Comparison of the calculation and experimental results showed that the trajectories and the contact forces of both the experimental and numerically analyzed medical devices had the same tendencies. By considering the flexibility of the catheter in both the experimental and numerical analysis methods, we could reproduce the phenomena seen in clinical situations, such as movement of the catheter during the insertion or removal of the guidewire, and movement of the guidewire during the insertion of the catheter.

Biological materials that make up the body organs and tissues are soft, wet and visco-elastic. Hydrogels can mimic these aspects and show promise for bio-medical applications. Their tribological properties are very important for promising applications such as artificial cartilage and bio-models for endovascular surgery training. The present study investigates the friction of polyvinyl alcohol (PVA) hydrogel against nine different metallic and non-metallic bio-compatible engineering materials likely to occur as countermaterials in these two applications. All the materials exhibited a characteristic velocity-dependent peak friction coefficient. Comparing the peaks, we find that lowest peak friction coefficient is produced by ceramics and glass (μ < 0.05), followed by metal alloys (μ < 0.05-0.08) and highest for polymers (0.4 < μ < 1.5), including PTFE which typically has very low-adhesion. Our results suggest that to achieve low friction, polymers should be avoided as a counter-material to PVA-hydrogels. It is also shown that PVA surface roughness is critical for achieving early transition to elasto-hydrodynamic lubrication and low friction, as shown in our comparative calculations with two different values of surface roughness of the gel. In the mixed lubrication region, the general trend is for friction to increase with roughness of the counterbody, but internal damping properties and adhesion also play important role, as shown by a simple linear model fit.

Staphylococcal γ-hemolysin (Hlg) is a two-component cytolysin, which consists of LukF (Hlg1) and Hlg2. Our previous study has suggested that LukF and Hlg2 are alternatively arranged on the human erythrocyte membrane and form a ring-shaped heterooligomeric transmembrane pore with a functional diameter of approximately 2 nm. Quantitative image analyses using high-resolution transmission electron microscopy have revealed that LukF and Hlg2 tend to be arranged in several mismatch patterns. Several previous studies have reported that the LukF component has a binding pocket for phosphatidylcholine. In the present study, membranedamaging activities by Hlg were investigated by using carboxyfluoresceine (CF)-loading liposomes consisting of mammalian erythrocyte phospholipids or one kind of phospholipid. Our results revealed that Hlg shows membrane-damaging activities on horse, rabbit and human erythrocyte total phospholipid liposomes. Such activity was closely related to the ratio of phosphatidylcholine. Hlg showed membrane-damaging activity against phosphatidylcholine liposome by formation of ring-shaped pore complex and cluster. Besides, it was revealed that Hlg could target cardiolipin, which is not included in the mammalian erythrocyte membrane, but exists in the bacterial cytoplasmic membrane and in the inner mitochondrial membrane of mammal cell. The results suggest that Hlg has the potential to recognize several phospholipids in both erythrocyte and non-erythrocyte membranes and induce cytolysis not only of mammalian cells but also of bacterial cells by the formation of pores and clusters. These novel findings will contribute to the elucidation of mutual actions between cytotoxicity protein and phospholipids, and eventually lead to the development of a treatment for staphylococcal infection.

Staphylococcal γ-hemolysin (Hlg), consists of two separate proteins, Hlg1 (LukF) of 34 kDa and Hlg2 of 32 kDa, which cooperatively lyse mammalian erythrocytes. Hlg is an illustrative molecule for the study of the assembly and membrane insertion of transmembrane proteins having the unique characteristic of being composed of two separate proteins. Our previous studies revealed that LukF and Hlg2 assemble alternately on a membrane to form ring-shaped heteroheptameric transmembrane pores, which form funnel-shaped structure with a subunit mismatch arrangement in which the distance between two of the adjacent subunits is significant larger than the others. In the present study, further analysis of the subunit mismatch arrangement in Hlg heteroheptameric pores was conducted by two-dimensional (2-D) image analysis. The distances between two adjacent subunits were numbered according to the size of the distance between adjacent subunits, and how each distance was arranged in the pore was investigated. As a result, the following results were clarified: (1) Not all distances between two adjacent subunits are even. This indicates that a mismatch arrangement exists at not only one site but also at other sites. (2) There is a high probability leading several patterns of mismatch arrangement. (3) These mismatch patterns tend to be polarized into a region in which the distance between subunits is great and a region in which such distance is small. The probabilistic analysis used in this study revealed that there is the intrinsic geometry with subunit arrangements in the heteroheptameric pore consists of two differential subunits.

Vascular diseases, such as ischemic heart disease, infarction, aneurysms, stroke and stenosis are a leading cause of serious long-term disability and their mortality rate is as high as that of cancers in many countries. Recently, neurovascular intervention using catheters is a minimally-invasive endovascular technique used to treat vascular disease of the brain, and a navigation system for catheters has been developed to facilitate surgical planning and to provide intra-operative assistance. Since the mechanical properties of a catheter play an important role in reaching the targeted disease, tracking of catheter movement during endovascular treatment may be useful to increase confirmation of the rate of successful operation. In this study, we developed an in vitro tracking system for catheter motion using poly (vinyl alcohol) hydrogel (PVA-H) to mimic an arterial wall. The employed models were made of PVA-H, which is sufficiently transparent to permit observation of catheter movement in the artery. This system is expected to contribute to validation of computer-based navigation systems for surgical assistance.

Background and purpose: Stenting is one of the treatment options for carotid artery stenosis. To show the effectiveness of the treatment, computational fluid dynamics (CFD) has been performed for the last several decades. The inlet/outlet boundary conditions are important in CFD, and several researchers have used various inlet/outlet boundary conditions. In this paper, we compared the blood flow with various inlet/outlet boundary conditions and the measurement data obtained by an ultrasound device.Methods: Blood flow speed was measured in the internal carotid artery (ICA), the external carotid artery (ECA), and the common carotid artery (CCA) using an ultrasound device. A carotid artery was reconstructed by computed tomography (CT). Mesh in the integrated data was generated to perform flow dynamics using a commercial code. CFD for blood flow was performed using the reconstructed carotid artery. Five cases of inlet and outlet boundary conditions (I/O B.C.) were used for the CFD. The simulation results were compared with the ultrasound data on the blood flow speed in the vicinity of the center of the ICA and the ECA.Results: Various blood flow speeds were obtained from the five cases. The case of adjustment of pressures in ICA and ECA is the nearest flow speed to the ultrasound data.Conclusion: The flow speed depends on the I/O B.C.. The I/O B.C. may be necessary for the measurement data obtained by ultrasound device or magnetic resonance imaging (MRI).

In vitro blood vessel biomodeling with realistic mechanical properties and geometrical structures is helpful for training in surgical procedures, especial those used in endovascular treatment. Poly (vinyl alcohol) hydrogel (PVA-H), which is made of Poly (vinyl alcohol) (PVA) and water, may be useful as a material for blood vessel biomodeling due to its low surface friction resistance and good transparency. In order to simulate the mechanical properties of blood vessels, measurements of mechanical properties of PVA-H were carried out with a dynamic mechanical analyzer, and the storage modulus (G’) and loss modulus (G”) of PVA-H were obtained. PVA-Hs were prepared by the low-temperature crystallization method. They were made of PVA with various concentrations (C) and degrees of polymerization (DP), and made by blending two kinds of PVA having different DP or saponification values (SV). The G’ and G” of PVA-H increased, as the C or DP of PVA increased, or as the proportion of PVA with higher DP or SV increased. These results indicate that it is possible to obtain PVA-H with desirable dynamic viscoelasticity. Furthermore, it is suggested that PVA-H is stable in the temperature range of 0°C to 40°C, indicating that biomodeling made of PVA-H should be available at 37°C, the physiological temperature. The dynamic viscoelasticity of PVA-H obtained was similar to that of the dog blood vessel measured in previous reports. In conclusion, PVA-H is suggested to be useful as a material of blood vessel biomodeling.

Cardiovascular diseases are closely related to blood flow. Ultrasonic-Measurement-Integrated (UMI) simulation, in which results of ultrasonic measurement are fed back to the flow simulation, was proposed in a previous study in order to reproduce the real blood flow accurately and efficiently. The usability of the UMI simulation was confirmed by numerical experiment, but the effectiveness of this simulation was strongly affected by the accuracy of the ultrasonic measurement. In this paper, we examined the accuracy of a commercial ultrasonic measurement device by an experiment with a PVA-H straight tube phantom. By analyzing the measured color Doppler images for a developed laminar flow inside the phantom, we obtained the relationship between the color Doppler value and the Doppler velocity (C-V relationship). It was revealed that the original C-V relationship provided in the device as a color bar was not suitable for quantitative evaluation of Doppler velocity to be used in UMI simulation. Compared with the original C-V relationship, the present C-V relationship results are in far better agreement with the analytic solution. Investigation of the normalized error confirmed that the result obtained with the present C-V relationship was reliable in cases of relatively high Reynolds number in the flow domain except near the wall. The two signal conditioning factors of the device had little influence on the Doppler velocity. Finally, we investigated the effect of temporal and spatial averaging of ultrasonic measurement data to clarify the relation between the number of averagings and the level of agreement with the analytic solution.

We are pleased to present the issue “Biomedical Flow Dynamics.” Biomedical engineering has been globally recognized as an engineering field for biomedical applications. From now, the combination of biomedical engineering with flow dynamics will unravel a new research field for engineering and science in biomedical applications. This transdisciplinary research that combines flow dynamics and biomedical engineering will enable the progress of research pertaining to cells and bodies under the emerging biological, computational simulations, and experimental engineering techniques. Therefore, this special issue tries to cover various research topics. We think that the papers are of great significance to all fields. Moreover, we believe that the researches will directly influence the quality of life. We sincerely appreciate the wonderful opportunity given to us by the JBSE's editorial board members. Furthermore, we would like to express our sincere gratitude to all the authors and reviewers for their excellent contributions and making this special issue fruitful. Finally, we are thankful to the JBSE editorial office for their technical assistance.

In previous published research, the deployment of flow-diversion increases the intra-aneurysmal pressure by 20 mmHg in the case with a pre-aneurysm stenosis. The purpose of this study is to learn the influence to the aneurysm when a pre-aneurysm stenosis exists which may threaten people's health even more severely. In the present research, idealized models of straight and curved blood vessels with both aneurysm and pre-aneurysm stenosis were established, with altering the degree of stenosis, the distance between stenosis and aneurysm and the curvature of parent artery. As the degree of stenosis increases, the reattachment length increases in straight vessels. Different positions of reattachment points to aneurysm neck affect the flow pattern inside the aneurysm. In the model with higher degree of stenosis and smaller distance between stenosis and aneurysm, the flow pattern and the direction of vortexes inside the aneurysm are affected by the recirculation after stenosis. Driven by inertial force, reattachment length decreases as the curvature of the parent artery increases, and stream inside the aneurysm is affected only when the distance between stenosis and aneurysm is short enough. In all models, the pressure drop inside the aneurysm increases as the degree of stenosis increases, creating a lower pressure environment in the aneurysm.