Wall Shear Rate Research Articles

Prediction of the extent of thrombus formation in the parent artery after endovascular occlusion of a distal anterior cerebral artery aneurysm using computational fluid dynamics

Endovascular coiling of a cerebral aneurysm and coil occlusion of the parent artery have been occasionally performed to treat cerebral aneurysms; however, it is difficult to predict the accurate extent of thrombus formation in the parent artery proximal to the coiled aneurysm and the coil-occluded parent artery preoperatively, and unexpected occlusion of the arterial branches can occur by thrombus extension into or in the parent artery. The authors describe a case of a distal anterior cerebral artery (ACA) aneurysm treated by endovascular parent artery occlusion (PAO) with preoperative computational fluid dynamics (CFD) prediction of the extent of thrombus formation. A 73-year-old woman presented with subarachnoid hemorrhage and an aneurysm that was located on the right pericallosal artery distal to the paracentral artery bifurcation. Endovascular coiling of the aneurysm and the pericallosal artery was planned. In advance of the treatment, CFD was performed to predict the extent of thrombus formation with specific wall shear stress and shear rate thresholds. The hemodynamic results indicated that coiling of the aneurysm resulted in thrombus formation in the pericallosal artery up to just distal to the paracentral artery ostium; therefore, the treatment was implemented according to the CFD prediction. Postoperative digital subtraction angiography revealed that the extent of thrombus formation was consistent with the preoperative CFD prediction. This technique may prevent unexpected occlusion of arterial branches.

Effects of Exercise Training and Statin Use in People Living with Human Immunodeficiency Virus with Dyslipidemia.

To evaluate the effects of the combination of exercise training (ET) and statins in people living with human immunodeficiency virus. This was a randomized, double-blind, placebo-controlled clinical trial. Eighty-three people living with human immunodeficiency virus were assigned to either placebo (PL), statins (STA), PL + ET (PLET) or STA + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-wk follow-up, the volunteers underwent to anthropometric assessment and blood collection to evaluate lipid profile, cardiovascular markers, inflammatory profile; a Doppler ultrasound examination, muscle strength (MS) and cardiorespiratory fitness (CF) tests were performed. There was a decrease in total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, fibrinogen, interleukin (IL)-1β and right carotid intima-media thickness in the STA, PLET, and STAET groups compared with PL group (P < 0.001). Furthermore, there was a decrease in total cholesterol, triglycerides, low-density lipoprotein, IL-1β, IL-6, and IL-8 levels and in left and right carotid intima-media thickness and an increase in HDL-c levels in the STAET groups compared with the STA (P ≤ 0.001) and PLET groups (P ≤ 0.001). There was an increase in IL-10 levels, peak-systolic velocity, end-diastolic velocity, wall shear rate in the PLET and STAET groups compared with the PL (P ≤ 0.001) and STA groups (P ≤ 0.001). The PLET and STAET groups reduced body fat mass, body fat percentage and increased lean body mass, MS and CF compared with PL (P ≤ 0.001) and STA (P ≤ 0.001) groups. The combination of ET and statins is useful to enhance lipid and inflammatory profiles, reduce cardiovascular disease markers, and improve Doppler ultrasound findings, MS and CF in people living with HIV.

Reduced model to predict thrombin and fibrin during thrombosis on collagen/tissue factor under venous flow: Roles of γ'-fibrin and factor XIa.

During thrombosis, thrombin generates fibrin, however fibrin reversibly binds thrombin with low affinity E-domain sites (KD = 2.8 μM) and high affinity γ’-fibrin sites (KD = 0.1 μM). For blood clotting on collagen/tissue factor (1 TF-molecule/μm2) at 200 s-1 wall shear rate, high μM-levels of intraclot thrombin suggest robust prothrombin penetration into clots. Setting intraclot zymogen concentrations to plasma levels (and neglecting cofactor rate limitations) allowed the linearization of 7 Michaelis-Menton reactions between 6 species to simulate intraclot generation of: Factors FXa (via TF/VIIa or FIXa), FIXa (via TF/FVIIa or FXIa), thrombin, fibrin, and FXIa. This reduced model [7 rates, 2 KD’s, enzyme half-lives~1 min] predicted the measured clot elution rate of thrombin-antithrombin (TAT) and fragment F1.2 in the presence and absence of the fibrin inhibitor Gly-Pro-Arg-Pro. To predict intraclot fibrin reaching 30 mg/mL by 15 min, the model required fibrinogen penetration into the clot to be strongly diffusion-limited (actual rate/ideal rate = 0.05). The model required free thrombin in the clot (~100 nM) to have an elution half-life of ~2 sec, consistent with measured albumin elution, with most thrombin (>99%) being fibrin-bound. Thrombin-feedback activation of FXIa became prominent and reached 5 pM FXIa at >500 sec in the simulation, consistent with anti-FXIa experiments. In predicting intrathrombus thrombin and fibrin during 15-min microfluidic experiments, the model revealed “cascade amplification” from 30 pM levels of intrinsic tenase to 15 nM prothrombinase to 15 μM thrombin to 90 μM fibrin. Especially useful for multiscale simulation, this reduced model predicts thrombin and fibrin co-regulation during thrombosis under flow.

Quantitative assessment of the conjunctival microcirculation using a smartphone and slit-lamp biomicroscope

PurposeThe conjunctival microcirculation is a readily-accessible vascular bed for quantitative haemodynamic assessment and has been studied previously using a digital charge-coupled device (CCD). Smartphone video imaging of the conjunctiva, and haemodynamic parameter quantification, represents a novel approach. We report the feasibility of smartphone video acquisition and subsequent haemodynamic measure quantification via semi-automated means. MethodsUsing an Apple iPhone 6 s and a Topcon SL-D4 slit-lamp biomicroscope, we obtained videos of the conjunctival microcirculation in 4 fields of view per patient, for 17 low cardiovascular risk patients. After image registration and processing, we quantified the diameter, mean axial velocity, mean blood volume flow, and wall shear rate for each vessel studied. Vessels were grouped into quartiles based on their diameter i.e. group 1 (<11 μm), 2 (11–16 μm), 3 (16–22 μm) and 4 (>22 μm). ResultsFrom the 17 healthy controls (mean QRISK3 6.6%), we obtained quantifiable haemodynamics from 626 vessel segments. The mean diameter of microvessels, across all sites, was 21.1μm (range 5.8–58 μm). Mean axial velocity was 0.50mm/s (range 0.11–1mm/s) and there was a modestly positive correlation (r 0.322) seen with increasing diameter, best appreciated when comparing group 4 to the remaining groups (p < .0001). Blood volume flow (mean 145.61pl/s, range 7.05–1178.81pl/s) was strongly correlated with increasing diameter (r 0.943, p < .0001) and wall shear rate (mean 157.31 s−1, range 37.37–841.66 s−1) negatively correlated with increasing diameter (r − 0.703, p < .0001). ConclusionsWe, for the first time, report the successful assessment and quantification of the conjunctival microcirculatory haemodynamics using a smartphone-based system.

Arterial wall shear rate response to reactive hyperaemia is markedly different between young and older humans.

The vasodilatory response to reactive hyperaemia is impaired with advancing age, but it is unclear whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response. Using new technology that allows detailed WSR measurement, we assessed the WSR-FMD response in healthy older people. Our data show that older people have a markedly altered and diminished WSR response to reactive hyperaemia compared to young people, but reduced WSR alone does not fully explain reduced FMD. In young people, WSR appears to be coupled to FMD but, by age ∼65 years, the arterial vasodilatory response has begun to uncouple from the WSR stimulus. These findings point to the importance and utility of comprehensively characterizing the WSR-FMD response when using reactive hyperaemia to assess vascular function, as well as giving new insight into the age-related alteration in vascular function. The vasodilatory response to reactive hyperaemia is impaired with age, but it is unknown whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response to the WSR stimulus. Inherent difficulties in measuring blood flow velocity close to the arterial wall have prevented detailed assessment of the WSR-FMD response. Using an enhanced multigate spectral Doppler ultrasound system (ultrasound advanced open platform), we aimed to produce new data on the WSR-FMD relationship in healthy older adults. Sixty healthy people, comprising 28 young (27.5±5.5years) and 32 older (64.9±3.7years) individuals, underwent FMD assessment. Raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The data revealed that older people have a much altered and diminished WSR response to reactive hyperaemia compared to younger people [e.g. WSR peak: 622 (571-673) vs. 443 (396-491) 1/s in young and older respectively; P<0.05]. However, reduced WSR alone does not appear to fully explain the reduced FMD response in older people because associations between WSR and FMD were few and weak. This was in contrast to young adults, where associations were strong. We conclude that WSR during FMD is much altered and diminished in older people, and there appears to be an 'uncoupling' of WSR from FMD in older people that may reflect a loss of precision in the reactive hyperaemia stimulus-response relationship. These findings also point to the importance and utility of comprehensively characterizing the WSR-FMD response when using reactive hyperaemia to assess vascular function.

A Theoretical Analysis of Receptor-Mediated Endocytosis of Nanoparticles in Wall Shear Flow

This study theoretically investigates receptor–ligand-mediated endocytosis of nanoparticles (NPs) in wall shear flow. The endocytosis is modeled as a birth–death process and relationships between coefficients in the model and the wall shear rate have been derived to deal with the effects of the shear flow. Model predictions show that flow-induced alteration in bond formation rates does not affect the endocytosis significantly, and the suppression of hydrodynamic load on endocytosis is eminent only when diameters of NPs are large (around 700[Formula: see text]nm) and the shear rate is sufficiently high. In the latter case, it is shown that the hydrodynamic load suppresses the initial attachment of NPs to cells more than the following internalization. The model also predicts that shear-promoted expression of certain ligands can lead to observable increase in the number of endocytozed NPs in typical flow-chamber experiments, and the promotion can also cause selective endocytosis of NPs by cells at high shear rate regions if the ligand surface density on NPs or the original expression of receptors on cells in the absence of flow is low.

Carotid Wall Shear Rate as a Marker of Systemic Atherosclerosis and Atherosclerotic Cardiovascular Disease

to assess possibility of the use of carotid wall shear rate (WSR) as a marker of systemic atherosclerosis and atherosclerotic cardiovascular disease (ASCVD). We included into this study 200 patients with different cardiovascular risk (142 patients already had one or more ASCVD). All patients underwent ultrasound scanning of carotid and lower limb arteries with measurement of the ankle-brachial index. Carotid WSR was determined during ultrasonic scanning of carotid arteries in accordance with the Hagen-Poiseuille law. Mean WSR value in this cohort of patients was 434±139 s-1. Based on the results of the ROCanalysis, it was found that WSR below the threshold value of 300 s-1 allowed to predict the presence of ASCVD with sensitivity of 97.1 % and specificity of 84.6 %. WSR &lt;300 s-1 was associated with relative risk (RR) of ASCVD presence 11.2 (95 % CI 1.26-99.3, p=0.03), adjusted for factors such as sex, age, smoking, obesity, hypertension, estimated glomerular filtration rate (eGFR), low density lipoprotein cholesterol, and high sensitivity C-reactive protein, carotid intima-media thickness. The model which included carotid WSR, as well as factors such as the presence of type 2 diabetes, obesity, sex, age, eGFR, allowed to diagnose combined atherosclerotic lesions of peripheral arteries with a sensitivity of 73.1 % and a specificity of 90.3 %. Evaluation of the carotid WSR allows to diagnose with satisfactory sensitivity and specificity the presence of combined atherosclerosis of peripheral arteries and ASCVD.

Coagulopathy implications using a multiscale model of traumatic bleeding matching macro- and microcirculation.

Quantifying the relationship between vascular injury and the dynamic bleeding rate requires a multiscale model that accounts for changing and coupled hemodynamics between the global and microvascular levels. A lumped, global hemodynamic model of the human cardiovascular system with baroreflex control was coupled to a local 24-level bifurcating vascular network that spanned diameters from the muscular artery scale (0.1-1.3 mm) to capillaries (5-10 μm) via conservation of momentum and conservation of mass boundary conditions. For defined injuries of severing all vessels at each nth-level, the changing pressures and flowrates were calculated using prescribed shear-dependent hemostatic clot growth rates (normal or coagulopathic). Key results were as follows: 1) the upstream vascular network rapidly depressurizes to reduce blood loss; 2) wall shear rates at the hemorrhaging wound exit are sufficiently high (~10,000 s-1) to drive von Willebrand factor unfolding; 3) full coagulopathy results in >2-liter blood loss in 2 h for severing all vessels of 0.13- to 0.005-mm diameter within the bifurcating network, whereas full hemostasis limits blood loss to <100 ml within 2 min; and 4) hemodilution from transcapillary refill increases blood loss and could be implicated in trauma-induced coagulopathy. A sensitivity analysis on length-to-diameter ratio and branching exponent demonstrated that bleeding was strongly dependent on these tissue-dependent network parameters. This is the first bleeding model that prescribes the geometry of the injury to calculate the rate of pressure-driven blood loss and local wall shear rate in the presence or absence of coagulopathic blood. NEW & NOTEWORTHY We developed a multiscale model that couples a lumped, global hemodynamic model of a patient to resolved, single-vessel wounds ranging from the small artery to capillary scale. The model is able to quantify wall shear rates, seal rates, and blood loss rates in the presence and absence of baroreflex control and hemodilution.

Experimental investigation of Taylor-Couette-Poiseuille flow at low Taylor and Reynolds numbers.

Flow patterns of a Taylor-Couette-Poiseuille flow were studied at low axial Reynolds and rotational Taylor numbers (Re ≤ 10.5, Ta ≤ 319). The radius ratio of the inner and outer cylinders was 0.804 and the ratio of the length of the annulus to the gap width was 44.5. Complete map of the studied flow regimes was elaborated. The axial and azimuthal components of the wall shear rate γ were measured at the outer fixed cylinder using a three-segment electrodiffusion probe. The components of the wall shear rate of helices have never been measured in previous investigations. Spatio-temporal description of multiple flow patterns was obtained using flow visualizations and simultaneous measurements of wall shear rate components. The flow structures include Taylor vortices, helices winding in the same direction as the base flow or in the opposite direction, helices that were stagnant or moving in the axial direction, smooth or with superposed azimuthal waves, among others. The influence of different flow structures on the wall shear stress components is discussed with and without axial base flow. It was found that the wall shear stress is a function of Ta but no significant dependence on Re was observed for the studied flow regimes and that the mean wall shear stress increases with the number of azimuthal waves. It was also noted that the ED probes provide a more detailed information about flow patterns than torque measurements and visualizations described in the literature.

Association between ultrasound morphology of carotid plaque and carotid wall shear rate in patients with atherosclerosis of peripheral arteries

Aim– to investigate the relationship between the values of the carotid endothelial shear rate and ultrasound morphology of atherosclerotic plaques in carotid arteries.Material and methods. The study involved 70 patients with carotid atherosclerosis, including 43 males and 27 females. The average age of patients was (61.1±8.54) years. All patients underwent ultrasound triplex scanning of carotid arteries. Ultrasonic plaque morphology was evaluated using several ultrasonographic characteristics: uniformity of echotexture and echogenicity. We used the classification of G. Geraulakos et al. (1993). Endothelial shear rate in the common carotid artery was determined in accordance with the law of Hagen – Poiseuille.Results. Most patients (30) had a plaque type I, less frequently occurred plaque II (15) and III (20 patients) types. Homogeneous echo positive plaques corresponding to «stable» phenotype were found in 5 patients. In patients with plaque type I and II, endothelial shear rate values were 373 (305; 481) s–1 and 311 (282; 419) s–1 respectively. In the groups of patients with plaque– type III and IV endothelial shear rate was significantly higher – 500 (429; 556) s–1 and 470 (440; 512) s–1 respectively. Among patients with plaque with a predominance of echolucent component, more patients with type 2 diabetes mellitus were found (p=0.006).Conclusion. Carotid endothelial shear rate was significantly lower in patients with carotid atherosclerosis and echolucent plaques compared to those having predominantly hyperechoic plaque. Prevalence of diabetes mellitus type 2 was significantly higher in the group of patients with unstable plaque and low carotid endothelial shear rate.

Variations in pulsatile flow around stenosed microchannel depending on viscosity.

In studying blood flow in the vessels, the characteristics of non-Newtonian fluid are important, considering the role of viscosity in rheology. Stenosis, which is an abnormal narrowing of the vessel, has an influence on flow behavior. Therefore, analysis of blood flow in stenosed vessels is essential. However, most of them exist as simulation outcomes. In this study, non-Newtonian fluid was observed in stenosed microchannels under the pulsatile flow condition. A polydimethylsiloxane channel with 60% stenosis was fabricated by combining an optic fiber and a petri dish, resembling a mold. Three types of samples were prepared by changing the concentrations of xanthan gum, which induces a shear thinning effect (phosphate buffered saline (PBS) solution as the Newtonian fluid and two non-Newtonian fluids mimicking normal blood and highly viscous blood analog). The viscosity of the samples was measured using a Y-shaped microfluidic viscometer. Thereafter, velocity profiles were analyzed under the pulsatile flow condition using the micro-particle image velocimetry (PIV) method. For the Newtonian fluid, the streamline was skewed more to the wall of the channel. The velocity profile of the non-Newtonian fluid was generally blunter than that of the Newtonian fluid. A highly oscillating wall shear stress (WSS) during the pulsatile phase may be attributed to such a bluntness of flow under the same wall shear rate condition with the Newtonian fluid. In addition, a highly viscous flow contributes to the variation in the WSS after passing through the stenosed structures. A similar tendency was observed in simulation results. Such a variation in the WSS was associated with plaque instability or rupture and damage of the tissue layer. These results, related to the influence on the damage to the endothelium or stenotic lesion, may help clinicians understand relevant mechanisms.

Experimental observation of heat transfer characteristics in turbulent Couette-Poiseuille flows

Turbulent Couette-Poiseuille flows between horizontal plates heated from below are investigated experimentally at low bulk Reynolds number Reb=1500 and low bulk Richardson number Ri=0.001 using stereo PIV, thermocouple, heat flux sensor and hot-wire thermometer. In the experimental apparatus the flow is driven by a moving plate and a blower. The lower hot plate (seamless belt) moves at several values of speed while the upper cold plate is at rest, and a bulk mean velocity is kept constant. It is found that heat transfer exhibits a local maximum at the lower plate speed for which a wall shear rate is null. In this specific condition turbulence decays in the vicinity of the lower hot plate so that vortical structures stemming from the upper cold plate may attain to the vicinity of the lower plate to carry low-temperature fluids, enhancing heat transfer. In the experiment, this phenomenon is observed by intermittent low-temperature fluctuation in the vicinity of the lower plate.

Continuous Simultaneous Recording of Brachial Artery Distension and Wall Shear Rate: A New Boost for Flow-Mediated Vasodilation.

Vascular ultrasound has been extensively applied in the clinical setting to noninvasively assess the endothelial function by means of the so-called brachial artery flow mediated dilation (FMD). Despite the usefulness in large-scale epidemiological studies, this approach has revealed some pitfalls for assessing vascular physiology and health in individual subjects. Mainly, a reliable FMD examination should be based on the simultaneous and reliable measurement of both the stimulus, i.e., the wall shear rate (WSR), and the response, i.e., the diameter change. However, multiple technical, practical, and methodological challenges must be faced to meet this goal. In this work, we present the technical developments needed to implement a system to enable the extensive and reliable clinical ultrasound FMD examination. It integrates both a hardware part, i.e., an upgraded version of the ultrasound advanced open platform (ULA-OP), and a software part, i.e., a signal processing and data analysis platform. The system was applied for a two-center pilot clinical study on 35 young and healthy volunteers. Therefore, we present here the results of a statistical analysis on magnitude, time-course, and kinetic parameters of WSR and diameter trends that allowed us to accurately explore the vasodilatory response to the dynamic WSR changes. Our observations demonstrate that a direct and accurate estimation of WSR stimulus by multigate spectral Doppler allows understanding brachial artery vasodilatory response to reactive hyperemia. Drawing inferences on WSR stimulus from the diameter response along with an inaccurate estimation of WSR may cause further uncertainties for the accurate interpretation of the FMD response.

Immunocapture of Escherichia coli in a fluoropolymer microcapillary array

This study presents novel experimental insights into the direct quantitation and immunocapture of bacteria cells in a fluoropolymer microcapillary array, using Escherichia coli as work model, a pathogen responsible for around 80% of urinary tract infections (UTIs). In spite of the current clinical demand for sensitive tests for rapid identification and quantitation of pathogens in human samples, portable diagnostic tests developed to date lack the specificity, limit of detection and speed for effective implementation in bacteria detection at point-of-care. The ‘open microfluidic’ approach presented in this work directly addresses those challenges. We report for the first time evidence of immunocapture of bacteria using polyclonal antibodies immobilized on the inner surface of an inexpensive 10-bore, 200 μm internal diameter FEP-Teflon® MicroCapillary Film, with a limit of detection (LoD) of at just 1 colony forming unit (CFU). In capillaries coated with less than a full monolayer of capture antibody, we observed a first order equilibrium, with bacteria captured (in CFUs/ml) linearly proportional to the CFU/ml in the incubated sample. We captured up to 100% of E. coli cells, with clear evidence of immunospecificity as demonstrated by testing with a different bacteria specie (in this case Bacillus subtillis). We noticed gravity settling of bacteria within the capillaries created a gradient of concentration which on the overall enhanced the capturing of cells up to 6 orders of magnitude beyond the theoretic full monolayer (∼4.5 × 104 CFUs/ml), with washings having an unnoticeable effect. Our data particularly highlights quantitatively the relevance of interrogation volume in respect to the miniaturisation of bacteria quantitation, which cannot be solved with the most sophisticated imaging equipment. A further set of continuous flow experiments at a flow rate of just ∼1 μl/min (corresponding to a wall shear rate of ∼101 s−1 and superficial flow velocity ∼53 μm/s) showed a degree of flow focusing, yet the mobility, antibody affinity capturing and gravity settling of bacteria cells enabled successful capturing in the microcapillaries. These results will inform the future development of effective microfluidic approaches for rapid point-of-care quantitation of bacterial pathogens and in particular rule-in of E. coli in UTIs.

Diagnostics of the fluctuating wall shear rate components using an uncalibrated three-segment electrodiffusion sensor

An inverse problem is used to significantly improve the frequency response of a three-segment electrodiffusion (ED) sensor subjected to strong inertial effects in high-amplitude unsteady flows. It is shown that the fluctuating component of the wall shear rate’s magnitude and direction can be accurately determined when both variables exhibit simultaneous large-amplitude variations, even when using an uncalibrated probe. Measurements are performed in the vicinity of a rotating cylinder in motion in a highly viscous fluid with poor electrochemical diffusivity, thus establishing a harsh environment for an ED sensor. Results using the inverse problem showed strong concordance with PIV complementary measurements in most cases and further expose the potential of this non-intrusive technique for thorough wall shear stress diagnostics.

Flow-rate based method for velocity of fully developed laminar flow in tubes

This work proposes an explicit method to determine velocity profiles of non-Newtonian fluids flowing in the laminar fully developed regime through a straight tube with a circular cross section. An integral expression for local velocity is derived by introducing the concept of a core-flow rate at a point in the tube as the rate of the partial flow passing through a coaxially centered circular cross section with a radius equal to the radial position of that point. In this approach, the velocity is expressed as the difference between the mean core velocity from the core-flow rate and the mean velocity of the flow through a virtual tube with its wall at the corresponding radial position. First, this method has been verified using velocities for the Newtonian and power law models. Then, it has been applied to velocity calculations for fluids obeying the Carreau, Cross, and Phan–Thien–Tanner (PTT) models. Moreover, the velocity result for the Carreau model has been applied to the viscosity reconstruction by the inverse parameter estimation from the measured velocity. Specifically, for the PTT model case, the slip boundary condition has also been considered. The mean velocity of the virtual tube flow can be determined by the difference between the measured and the core velocities. Therefore, a measured velocity profile allows the acquisition of the apparent shear rates of many virtual tube flows. These virtual tube flows have different wall shear stresses because of the differences in radii despite having the same pressure gradient. With the apparent shear rate and the wall shear stress, the Rabinowitsch correction has been conducted to retrieve the true wall shear rate, which facilitates accurate estimation of the viscosity and the Reynolds number. It has been found that the obtained Reynolds number closely follows the generalized Reynolds number.

Effect of processing conditions on crystallization kinetics during materials extrusion additive manufacturing

Material extrusion additive manufacturing processes force molten polymer through a printer nozzle at high (>100 s−1) wall shear rates prior to cooling and crystallization. These high shear rates can lead to flow-induced crystallization in common polymer processing techniques, but the magnitude and importance of this effect is unknown for additive manufacturing. A significant barrier to understanding this process is the lack of in situ measurement techniques to quantify crystallinity after polymer filament extrusion. To address this issue, we use a combination of infrared thermography and Raman spectroscopy to measure the temperature and percent crystallinity of extruded polycaprolactone during additive manufacturing. We quantify crystallinity as a function of time for the nozzle temperatures and filament feed rates accessible to the apparatus. Crystallization is shown to occur faster at higher shear rates and lower nozzle temperatures, which shows that processing conditions can have a dramatic effect on crystallization kinetics in additive manufacturing.

Estimating hemodynamic shear stress in murine peripheral collateral arteries by two-photon line scanning.

Changes in wall shear stress of blood vessels are assumed to be an important component of many physiological and pathophysiological processes. However, due to technical limitations experimental in vivo data are rarely available. Here, we investigated two-photon excitation fluorescence microscopy as an option to measure vessel diameter as well as blood flow velocities in a murine hindlimb model of arteriogenesis (collateral artery growth). Using line scanning at high frequencies, we measured the movement of blood cells along the vessel axis. We found that peak systolic blood flow velocity averaged 9mm/s and vessel diameter 42µm in resting collaterals. Induction of arteriogenesis by femoral artery ligation resulted in a significant increase in centerline peak systolic velocity after 1day with an average of 51mm/s, whereas the averaged luminal diameter of collaterals (52µm) changed much less. Thereof calculations revealed a significant fourfold increase in hemodynamic wall shear rate. Our results indicate that two-photon line scanning is a suitable tool to estimate wall shear stress e.g., in experimental animal models, such as of arteriogenesis, which may not only help to understand the relevance of mechanical forces in vivo, but also to adjust wall shear stress in ex vivo investigations on isolated vessels as well as cell culture experiments.

Association between Carotid Wall Shear Rate and Arterial Stiffness in Patients with Hypertension and Atherosclerosis of Peripheral Arteries.

Aim To evaluate carotid wall shear rate (WSR) in association with local and regional vascular stiffness in patients with hypertension (HTN) and atherosclerosis of peripheral arteries and to study the pattern of change of WSR in patients with HTN with increasing severity of peripheral artery atherosclerosis. Materials and Methods Study involved 133 patients with HTN, 65 men and 48 women, aged in average 57.9±10.8 years. All patients were divided into four groups in accordance with ultrasound morphologic classification of vessel wall. Duplex scanning of carotid and lower limb arteries was performed. Carotid-femoral (cfPWV) and carotid-radial (crPWV) pulse wave velocity (PWV) were measured. Local carotid stiffness was evaluated by carotid ultrasound. Results WSR of patients with plaques without and with hemodynamic disturbance was 416±128 s−1 and 405±117 s−1, respectively, which was significantly less than the WSR in patients with intact peripheral arteries – 546±112 s−1. Decreased carotid WSR was associated with increased crPVW, cfPWV, Peterson's elastic modulus, decreased distensibility, and distensibility coefficient. Conclusion In patients with HTN and atherosclerotic lesions of peripheral arteries, it is registered that the carotid WSR decreased with increasing severity of atherosclerosis. Decreased carotid WSR is associated with increased local carotid stiffness, regional vascular stiffness of muscular, and elastic vessels.

Simulation of the nodal flow of mutant embryos with a small number of cilia: comparison of mechanosensing and vesicle transport hypotheses.

Left–right (L-R) asymmetry in the body plan is determined by nodal flow in vertebrate embryos. Shinohara et al. (Shinohara K et al. 2012 Nat. Commun. 3, 622 (doi:10.1038/ncomms1624)) used Dpcd and Rfx3 mutant mouse embryos and showed that only a few cilia were sufficient to achieve L-R asymmetry. However, the mechanism underlying the breaking of symmetry by such weak ciliary flow is unclear. Flow-mediated signals associated with the L-R asymmetric organogenesis have not been clarified, and two different hypotheses—vesicle transport and mechanosensing—are now debated in the research field of developmental biology. In this study, we developed a computational model of the node system reported by Shinohara et al. and examined the feasibilities of the two hypotheses with a small number of cilia. With the small number of rotating cilia, flow was induced locally and global strong flow was not observed in the node. Particles were then effectively transported only when they were close to the cilia, and particle transport was strongly dependent on the ciliary positions. Although the maximum wall shear rate was also influenced by ciliary position, the mean wall shear rate at the perinodal wall increased monotonically with the number of cilia. We also investigated the membrane tension of immotile cilia, which is relevant to the regulation of mechanotransduction. The results indicated that tension of about 0.1 μN m−1 was exerted at the base even when the fluid shear rate was applied at about 0.1 s−1. The area of high tension was also localized at the upstream side, and negative tension appeared at the downstream side. Such localization may be useful to sense the flow direction at the periphery, as time-averaged anticlockwise circulation was induced in the node by rotation of a few cilia. Our numerical results support the mechanosensing hypothesis, and we expect that our study will stimulate further experimental investigations of mechanotransduction in the near future.