Blood Analog Research Articles

Electro-fluid-mechanics of the heart

This article presents an overview of the dynamics of the human heart and the main goal is the discussion of its fluid mechanic features. We will see, however, that the flow in the heart can not be fully described without considering its electrophysiology and elastomechanics as well as the interaction with the systemic and pulmonary circulations with which it is strongly connected. Biologically, the human heart is similar to that of all warm-blooded mammals and it satisfies the same allometric laws. Since the Paleolithic Age, however, humans have improved their living conditions, have modified the environment to satisfy their needs and, more recently, have developed advanced medical knowledge which has allowed triple the number of heartbeats with respect to other mammals. In the last century, effective diagnostic tools, reliable surgical procedures and prosthetic devices have been developed and refined leading to substantial progress in cardiology and heart surgery with routine clinical practice which nowadays cures many disorders, once lethal. Pulse duplicators have been built to reproduce the pulsatile flow and ‘blood analogues’, have been realized. Heart phantoms, can attain deformations similar to the real heart although the active contraction and the tissue anisotropy still can not be replicated. Numerical models have also become a viable alternative for cardiovascular research: they do not suffer from limitations of material properties and device technologies, thus making possible the realization of truly digital twins. Unfortunately, a high-fidelity model for the whole heart consists of a system of coupled, nonlinear partial differential equations with a number of degrees of freedom of the order of a billion and computational costs become the bottleneck. An additional challenge comes from the inherent human variability and the uncertainty of the heart parameters whose statistical assessment requires a campaign of simulations rather than a single deterministic calculation; reduced and surrogate models can be employed to alleviate the huge computational burden and all possibilities are currently being pursued. In the era of big data and artificial intelligence, cardiovascular research is also advancing by exploiting the latest technologies: equation-based augmented reality, virtual surgery and computational prediction of disease progression are just a few examples among many that will become standard practice in the forthcoming years.

Improved quantification of coronary artery luminal stenosis in the presence of heavy calcifications using photon-counting detector CT.

Coronary CT Angiography (cCTA) is commonly used to detect and quantify luminal stenoses in patients with coronary artery disease (CAD). However, its use is limited in patients with heavy coronary calcifications due to calcium blooming, which is caused by insufficient spatial resolution. This study evaluated the ability of a photon-counting-detector (PCD) CT in quantifying luminal stenosis in the presence of heavy calcifications relative to an energy-integrating-detector (EID) CT. Cylindrical rods of 4.5 mm diameter (with 3 mm lumen), which contained calcium hydroxyapatite (CaHA) to emulate calcifications of varying shapes and sizes and an iodine or blood analog to emulate the coronary lumen, were placed within an anthropomorphic thorax phantom and scanned at matched dose on an EID-CT and a PCD-CT scanner. Stenoses were qualitatively evaluated and quantified using commercial software. Measured percent area stenosis was compared to reference values. PCD-CT provided better visualization of calcium plaques and the patent lumen, and more accurate stenosis quantification for all plaques. In one rod (75% occlusion with ring-shaped plaque), only PCD-CT was able to determine that the vessel was not fully obstructed. The phantom results indicate luminal stenoses that were previously considered non-assessable due to the presence of heavily-calcified plaques can be assessed using PCD-CT. Clinical studies to support these conclusions are underway.

Severe MAC increases shear stresses on particles traversing the mitral valve: an in vitro study

Abstract Funding Acknowledgements Type of funding sources: None. Background Mitral annular calcification (MAC) is a strong predictor of stroke but mechanism(s) are poorly defined. Severe MAC can produce a gradient across the mitral valve (MV) and, when studied in vitro, disturbs normal flow across the valve resulting in increased viscous energy dissipation. Purpose We hypothesized that severe MAC would increase shear stress on particles traveling across the MV into the left ventricle (LV). Given that shear stresses cause platelet activation this might represent a mechanism by which MAC could increase stroke risk. Methods A silicone model MV was created using a 3D TEE dataset. 3D printed calcium phantoms were incorporated into the valve simulate severe MAC. The valve was tested in a left heart duplicator under rest and exercise conditions and compared with a duplicate valve without the calcium phantoms. Fine particles suspended in a water/glycerol blood analogue allowed for measurement of vortex formation and shear stresses using particle image velocimetry (PIV). Particle residence time (PRT) maps were created to assess how long blood particles would remain in the LV. Particle residence index (PRI - ratio of remaining particles in LV/initial number of particles) is a more quantitative measure of how fast particles leave the LV. These calculations were used to approximate viscous shear stresses on blood particles. For each particle the induced viscous shear stress was evaluated for the entire duration of residence in the LV. Results For the normal MV all released particles left the LV by the 3rd cycle; with severe MAC particles completely left the LV shortly after the 7th cycle. PRI measurements confirmed that particles remained longer in the LV in the presence of severe MAC (figure 1). MAC also induced a shift in the accumulated shear stress levels from the high range > 0.4 Pa.s and the low range < 0.1 towards the middle region (0.16-0.32 Pa.s, figure 2). As shear stress is reported for one cycle, one may expect MAC to lead to higher accumulated higher viscous stresses as particles reside in the LV for a longer time. Conclusions In the presence of severe MAC blood particles remain longer in the LV and are exposed to greater cumulative shear stresses vs the normal situation. Given that shear stress is known to cause platelet activation this may be a mechanism by which MAC increases risk of ischemic stroke. Abstract Figure 1 Abstract Figure 2

A particulate blood analogue based on artificial viscoelastic blood plasma and RBC-like microparticles at a concentration matching the human haematocrit.

There has been enormous interest in the production of fluids with rheological properties similar to those of real blood over the last few years. Application fields range from biomicrofluidics (microscale) to forensic science (macroscale). The inclusion of flexible microparticles in blood analogue fluids has been demonstrated to be essential in order to reproduce the behaviour of blood flow in these fields. Here, we describe a protocol to produce a whole human blood analogue composed of a proposed plasma analogue and flexible spherical microparticles that mimic the key structural attributes of RBCs (size and mechanical properties), at a concentration matching the human haematocrit (∼42% by volume). Polydimethylsiloxane (PDMS) flexible microparticles were used to mimic RBCs, whose capability to deform is tunable by means of the mixing ratio of the PDMS precursor. Their flow through glass micronozzles allowed us to find the appropriate mixing ratio of PDMS to have approximately the same Young's modulus (E) as that exhibited by real RBCs. Shear and extensional rheology and microrheology techniques were used to match the properties exhibited by human plasma and whole blood at body temperature (37 °C). Finally, we study the flow of our proposed fluid through a microfluidic channel, showing the in vitro reproduction of the multiphase flow effects taking place in the human microcirculatory system, such as the cell-free layer (CFL) and the Fåhræus-Lindqvist effect. A macroscale application in the field of forensic science is also presented, concerning the impact of our blood analogue droplets on a solid surface for bloodstain pattern analysis.

In vitro flow study in a compliant abdominal aorta phantom with a non-Newtonian blood-mimicking fluid

In vitro aortic flow simulators allow studying hemodynamics with a wider range of flow visualization techniques compared to in vivo medical imaging and without the limitations of invasive examinations. This work aims to develop an experimental bench to emulate the pulsatile circulation in a realistic aortic phantom. To mimic the blood shear thinning behavior, a non-Newtonian aqueous solution is prepared with glycerin and xanthan gum polymer. The flow is compared to a reference flow of Newtonian fluid. Particle image velocimetry is carried out to visualize 2D velocity fields in a phantom section. The experimental loop accurately recreates flowrates and pressure conditions and preserves the shear-thinning properties of the non-Newtonian fluid. Velocity profiles, shear rate, and shear stress distribution maps show that the Newtonian fluid tends to dampen the observed velocities. Preferential asymmetrical flow paths are observed in a diameter narrowing region and amplified in the non-Newtonian case. Wall shear stresses are about twice higher in the non-Newtonian case. This study shows new insights on flow patterns, velocity and shear stress distributions compared to rigid and simplified geometry aorta phantom with Newtonian fluid flows studies. The use of a non-Newtonian blood analog shows clear differences in flows compared to the Newtonian one in this compliant patient-specific geometry. The development of this aortic simulator is a promising tool to better analyze and understand aortic hemodynamics and to aid in clinical decision-making.

Extensional Magnetorheology of Viscoelastic Human Blood Analogues Loaded with Magnetic Particles.

This study represents a pioneering work on the extensional magnetorheological properties of human blood analogue fluids loaded with magnetic microparticles. Dynabeads M-270 particles were dispersed in Newtonian and viscoelastic blood analogue fluids at 5% wt. Capillary breakup experiments were performed, with and without the influence of an external magnetic field aligned with the flow direction. The presence of the particles increased the viscosity of the fluid, and that increment was larger when embedded within a polymeric matrix. The application of an external magnetic field led to an even larger increment of the viscosity of the working fluids, as the formation of small aggregates induced an increment in the effective volume fraction of particles. Regarding the liquid bridge stability, the Newtonian blood analogue fluid remained as a Newtonian liquid exhibiting a pinch-off at the breakup time in any circumstance. However, in the case of the viscoelastic blood analogue fluid, the presence of the particles and the simultaneous application of the magnetic field enhanced the formation of the beads-on-a-string structure, as the Ohnesorge number remained basically unaltered, whereas the time of the experiment increased due to its larger viscosity, which resulted in a decrease in the Deborah Number. This result was confirmed with fluids containing larger concentrations of xanthan gum.

Transition to Turbulence Downstream of a Stenosis for Whole Blood and a Newtonian Analog Under Steady Flow Conditions.

Blood, a multiphase fluid comprised of plasma, blood cells, and platelets, is known to exhibit a shear-thinning behavior at low shear rates and near-Newtonian behavior at higher shear rates. However, less is known about the impact of its multiphase nature on the transition to turbulence. In this study, we experimentally determined the critical Reynolds number at which the flow began to transition to turbulence downstream of eccentric stenosis for whole porcine blood and a Newtonian blood analog (water-glycerin mixture). Velocity profiles for both fluids were measured under steady-state flow conditions using an ultrasound Doppler probe placed 12 diameters downstream of eccentric stenosis. Velocity was recorded at 21 locations along the diameter at 11 different flow rates. Normalized turbulent kinetic energy was used to determine the critical Reynolds number for each fluid. Blood rheology was measured before and after each experiment. Tests were conducted on five samples of each fluid inside a temperature-controlled in vitro flow system. The viscosity at a shear rate of 1000 s-1 was used to define the Reynolds number for each fluid. The mean critical Reynolds numbers for blood and water-glycerin were 470 ± 27.5 and 395 ± 10, respectively, indicating a ∼19% delay in transition to turbulence for whole blood compared to the Newtonian fluid. This finding is consistent with a previous report for steady flow in a straight pipe, suggesting some aspect of blood rheology may serve to suppress, or at least delay, the onset of turbulence in vivo.

Development of Inspired Therapeutics Pediatric VAD: Benchtop Evaluation of Impeller Performance and Torques for MagLev Motor Design.

Despite the availability of first-generation extracorporeal mechanical circulatory support (MCS) systems that are widely used throughout the world, there is a need for the next generation of smaller, more portable devices (designed without cables and a minimal number of connectors) that can be used in all in-hospital and transport settings to support patients in heart failure. Moreover, a system that can be universally used for all indications for use including cardiopulmonary bypass (CPB), uni- or biventricular support (VAD), extracorporeal membrane oxygenation (ECMO) and respiratory assist that is suitable for use for adult, neonate, and pediatric patients is desirable. Providing a single, well designed, universal technology could reduce the incidence of human errors by limiting the need for training of hospital staff on a single system for a variety of indications throughout the hospital rather than having to train on multiple complex systems. The objective of this manuscript is to describe preliminary research to develop the first prototype pump for use as a ventricular assist device for pediatric patients with the Inspired Universal MCS technology. The Inspired VAD Universal System is an innovative extracorporeal blood pumping system utilizing novel MagLev technology in a single portable integrated motor/controller unit which can power a variety of different disposable pump modules intended for neonate, pediatric, and adult ventricular and respiratory assistance. A prototype of the Inspired Pediatric VAD was constructed to determine the hemodynamic requirements for pediatric applications. The magnitude/range of hydraulic torque of the internal impeller was quantified. The hydrodynamic performance of the prototype pump was benchmarked using a static mock flow loop model containing a heated blood analogue solution to test the pump over a range of rotational speeds (500-6000 RPM), flow rates (0-3.5L/min), and pressures (0 to ~420 mmHg). The device was initially powered by a shaft-driven DC motor in lieu of a full MagLev design, which was also used to calculate the fluid torque acting on the impeller. The pediatric VAD produced flows as high as 4.27L/min against a pressure of 127 mmHg at 6000 RPM and the generated pressure and flow values fell within the desired design specifications. The empirically determined performance and torque values establish the requirements for the magnetically levitated motor design to be used in the Inspired Universal MagLev System. This next step in our research and development is to fabricate a fully integrated and functional magnetically levitated pump, motor and controller system that meets the product requirement specifications and achieves a state of readiness for acute ovine animal studies to verify safety and performance of the system.

Long-Term Stability of 13 Fentanyl Analogs in Blood.

Fentanyl analogs continue to play a major role in proliferating the opioid epidemic in the USA. With high rates of overdose deaths, forensic laboratories experience backlogs, which may lead to false-negative results due to drug instability. To address this issue, a quantitative method was validated for fentanyl analogs (3-methylfentanyl, 4-anilino-N-phenethylpiperidine (4-ANPP), 4-fluoro-isobutyrylfentanyl (4-FIBF), acetylfentanyl, acrylfentanyl, butyrylfentanyl, carfentanil, cyclopropylfentanyl, fentanyl, furanylfentanyl, methoxyacetylfentanyl, p-fluorofentanyl and valerylfentanyl) in blood using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) and used to assess long-term stability under various temperature conditions (-20°C, 4°C, ∼25°C and 35°C) for 9 months. Authentic specimens were also analyzed 6 months apart for applicability to postmortem blood. Method validation resulted in calibration ranges of 1-100 ng/mL and limits of detection of 0.5 ng/mL. Precision and bias were acceptable (within ±7.2% coefficient of variation (CV) and ±15.2%, respectively). Matrix effects exhibited ion enhancement for all analytes, except carfentanil and 4-ANPP in low-quality control (>25%). For long-term stability, fentanyl analogs (except acrylfentanyl) remained stable under room temperature and refrigerated conditions at low and high concentrations (81.3-112.5% target) for 9 months. While most fentanyl analogs remained stable frozen, degradation was observed after 2 weeks (four freeze/thaw cycles). At elevated temperatures, most analytes were stable for 1 week (74.2-112.6% target). Acrylfentanyl was unstable after 24 h under elevated (70% loss) and room temperatures (53-60% loss), 48-72 h when refrigerated (28-40% loss) and 4 weeks when frozen (22% loss). In authentic bloods (n = 7), initial furanylfentanyl (FuF) and 4-ANPP concentrations were 1.1-3.6 and 1.4-6.4 ng/mL, respectively. Percentage loss of FuF and 4-ANPP over 6 months were 16.3-37.4% and 0.2-26.8%, respectively. Samples suspected to contain fentanyl analogs are recommended to be stored refrigerated or frozen with limited freeze/thaw cycles. Due to instability, in the event of an acrylfentanyl overdose, samples should be analyzed immediately or stored frozen with analysis within 1 month.

Blood Particulate Analogue Fluids: A Review.

Microfluidics has proven to be an extraordinary working platform to mimic and study blood flow phenomena and the dynamics of components of the human microcirculatory system. However, the use of real blood increases the complexity to perform these kinds of in vitro blood experiments due to diverse problems such as coagulation, sample storage, and handling problems. For this reason, interest in the development of fluids with rheological properties similar to those of real blood has grown over the last years. The inclusion of microparticles in blood analogue fluids is essential to reproduce multiphase effects taking place in a microcirculatory system, such as the cell-free layer (CFL) and Fähraeus–Lindqvist effect. In this review, we summarize the progress made in the last twenty years. Size, shape, mechanical properties, and even biological functionalities of microparticles produced/used to mimic red blood cells (RBCs) are critically exposed and analyzed. The methods developed to fabricate these RBC templates are also shown. The dynamic flow/rheology of blood particulate analogue fluids proposed in the literature (with different particle concentrations, in most of the cases, relatively low) is shown and discussed in-depth. Although there have been many advances, the development of a reliable blood particulate analogue fluid, with around 45% by volume of microparticles, continues to be a big challenge.

Energy loss associated with in-vitro modeling of mitral annular calcification.

IntroductionStudy aims were to compare hemodynamics and viscous energy dissipation (VED) in 3D printed mitral valves–one replicating a normal valve and the other a valve with severe mitral annular calcification (MAC). Patients with severe MAC develop transmitral gradients, without the commissural fusion typifying rheumatic mitral stenosis (MS), and may have symptoms similar to classical MS. A proposed mechanism relates to VED due to disturbed blood flow through the diseased valve into the ventricle.MethodsA silicone model of a normal mitral valve (MV) was created using a transesophageal echocardiography dataset. 3D printed calcium phantoms were incorporated into a second valve model to replicate severe MAC. The synthetic MVs were tested in a left heart duplicator under rest and exercise conditions. Fine particles were suspended in a water/glycerol blood analogue for particle image velocimetry calculation of VED.ResultsCatheter mean transmitral gradients were slightly higher in the MAC valve compared to the normal MV, both at rest (3.2 vs. 1.3 mm Hg) and with exercise (5.9 vs. 5.0 mm Hg); Doppler gradients were 2.7 vs. 2.1 mm Hg at rest and 9.9 vs 8.2 mm Hg with exercise. VED was similar between the two valves at rest. During exercise, VED increased to a greater extent for the MAC valve (240%) versus the normal valve (127%).ConclusionMAC MS is associated with slightly increased transmitral gradients but markedly increased VED during exercise. These energy losses may contribute to the exercise intolerance and exertional dyspnea present in MAC patients.

A microparticle blood analogue suspension matching blood rheology.

The handling of blood in vitro is demanding because of ethical, economical and safety issues. Although several Newtonian and non-Newtonian blood analogues are found in the literature, few studies have used particles to mimic red blood cells (RBCs) and built an analogue with similar rheological properties of blood. This work reports the development of a blood analogue suspension composed of polydimethylsiloxane (PDMS) microparticles with an average diameter of ∼7 μm. High throughput production of PDMS particles is possible using a multi-stage membrane emulsification process; up to ∼6 mL of microparticles are manufactured in 3 hours. PDMS particles at a concentration of around 21% (w/w) at 20 °C present steady, oscillatory and extensional rheologies very similar to those of blood under physiological conditions (37 °C and ∼41% hematocrit), making them a good candidate whole blood analogue. Also, flow studies were performed in microchannels with contraction to study the cell-free layer (CFL) formation and particle deformation, achieving good qualitative results. Using the procedure developed, it is possible to obtain blood analogue fluids with a shelf life of at least 6 months.

Numerical investigation of volute tongue design on hemodynamic characteristics and hemolysis of the centrifugal blood pump

In the design of rotary blood pumps, the optimization of design parameters plays an essential role in enhancing the hydrodynamic performance and hemocompatibility. This study investigates the influence of the volute tongue angle as a volute geometric parameter on the hemodynamic characteristics of a blood pump. A numerical investigation on five different versions of volute designs is carried out by utilizing a computational fluid dynamics (CFD) software ANSYS-FLUENT. The effect of volute tongue angle is evaluated regarding the hydrodynamic performance, circumferential pressure distribution, the radial force, and the blood damage potential. A series of volute configurations are constructed with a fixed radial gap (5%), but varying tongue angles ranging from 10 to 50°. The relative hemolysis is assessed with the Eulerian based empirical power-law blood damage model. The pressure-flow rate characteristics of the volute designs at a range of rotational speeds are obtained from the experimental measurements by using the blood analog fluid. The results indicate an inverse relationship between hydraulic performance and the tongue angle; at higher tongue angles, a decrease in performance was observed. However, a higher tongue angle improves the net radial force acting on the impeller. The pump achieves the optimized performance at 20° of the tongue angle with the relatively high hydrodynamic performance and minor blood damage risk.

In vitro Biomodels in Stenotic Arteries to Perform Blood Analogues Flow Visualizations and Measurements: A Review

Cardiovascular diseases are one of the leading causes of death globally and the most common pathological process is atherosclerosis. Over the years, these cardiovascular complications have been extensively studied by applyingin vivo,in vitroand numerical methods (in silico).In vivostudies represent more accurately the physiological conditions and provide the most realistic data. Nevertheless, these approaches are expensive, and it is complex to control several physiological variables. Hence, the continuous effort to find reliable alternative methods has been growing. In the last decades, numerical simulations have been widely used to assess the blood flow behavior in stenotic arteries and, consequently, providing insights into the cardiovascular disease condition, its progression and therapeutic optimization. However, it is necessary to ensure its accuracy and reliability by comparing the numerical simulations with clinical and experimental data. For this reason, with the progress of thein vitroflow measurement techniques and rapid prototyping, experimental investigation of hemodynamics has gained widespread attention. The present work reviews state-of-the-artin vitromacro-scale arterial stenotic biomodels for flow measurements, summarizing the different fabrication methods, blood analogues and highlighting advantages and limitations of the most used techniques.

Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective.

Hemorheological alterations in the majority of metabolic diseases are always connected with blood rheology disturbances, such as the increase of blood and plasma viscosity, cell aggregation enhancement, and reduction of the red blood cells (RBCs) deformability. Thus, the visualizations and measurements of blood cells deformability flowing in microfluidic devices (point-of-care devices) can provide vital information to diagnose early symptoms of blood diseases and consequently to be used as a fast clinical tool for early detection of biomarkers. For instance, RBCs rigidity has been correlated with myocardial infarction, diabetes mellitus, hypertension, among other blood diseases. In order to better understand the blood cells behavior in microfluidic devices, rheological properties analysis is gaining interest by the biomedical committee, since it is strongly dependent on the interactions and mechanical cells proprieties. In addition, the development of blood analogue fluids capable of reproducing the rheological properties of blood and mimic the RBCs behavior at in vitro conditions is crucial for the design, performance and optimization of the microfluidic devices frequently used for personalized medicine. By combining the unique features of the hemorheology and microfluidic technology for single-cell analysis, valuable advances in personalized medicine for new treatments and diagnosis approach can be achieved.

Fast, flexible and low-cost multiphase blood analogue for biomedical and energy applications

During the last two decades, several kinds of particulate blood analogue fluids have been proposed, but none of those were able to mimic the multiphase effects of real blood. Hence, it is clear that it is crucial to develop a simple multiphase blood analogue to be used for in vitro experiments at both macro- and microscale level. To the best of our knowledge, the present work shows for the first time a straightforward and extremely stable blood analogue fluid able to mimic multiphase blood flow phenomena. The present work proposes a simple, low-cost and stable multiphase blood analogue with the ability to mimic microscale blood flow phenomena. The proposed analogue fluid is composed of Brij L4 surfactant micelles suspended in pure water and is extremely easy to be produced. To investigate the ability of this analogue to mimic microscale blood flow phenomena, flow visualizations were performed in a microchannel constriction. In vitro blood phenomena were compared with the measurements performed with the proposed analogue fluid. Additionally, rheological measurements of the multiphase blood analogue were acquired by means of a stress-controlled rheometer and compared with in vitro blood sample viscosity curves. Overall, the results indicate that it is possible to produce a stable particulate fluid with geometrical, mechanical and flow properties similar to in vitro blood. Hence, the proposed analogue has a great potential to be used in flow experiments from macro- to nanoscale levels.

Effects of passive, active, and mixed playing strategies on external and internal loads in female tennis players.

This study aimed to investigate the effects of different playing strategies on external and internal loads in female tennis players during match play. Also, the underlying effects on the technical-tactical actions and activity profiles were examined. Twelve well-trained female players (age: 25±5 years; maximum oxygen uptake: 40.9±4.3 ml/kg/min) played points against an opponent of similar ability outdoors on red-clay courts. The players played points over five playing conditions. Before each condition, the players were instructed to apply either a passive, an active, or their own playing strategy (free play) to succeed. The five conditions were played in a randomized order, whereas the condition with the own strategy was always played first and served as control. During play, the external and internal loads were investigated by 10 Hz global positioning system, 100 Hz inertial measurement unit, short-range telemetry, capillary blood, and visual analog scale procedures. A 25 Hz video camera was used to examine the technical-tactical actions and activity profiles. Compared to the control condition, the passive, active, and mixed playing strategy conditions induce up to large effects on the external loads (running distances with high acceleration and deceleration), up to moderate effects on the internal loads (energy expenditures spent with high metabolic power, lactate concentration, and rating of effort), and up to very large effects on the technical-tactical actions (number of ground strokes and errors) and activity profiles (strokes per rally, rally duration, work to rest ratio, and effective playing time). Our study shows that passive, active, and mixed playing strategies have an impact on the external and internal loads, technical-tactical actions, and activity profiles of female tennis players during match play. This finding should be considered for practical purposes like match analyses and training procedures in the tennis environment.

Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

Abstract Transit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

3D manufacturing of intracranial aneurysm biomodels for flow visualizations: Low cost fabrication processes

There is a continuous search for better and more complete in vitro models with mechanical properties closer to in vivo conditions. In this work a manufacturing process, based on a lost core casting technique, is herein reported to produce aneurysm biomodels to perform experimental hemodynamic studies. By using real artery images combined with a lost core casting technique, three materials were tested: paraffin, beeswax and glycerin-based soap. All in vitro biomodels were compared according to their transparency and final structure. Additionally, comparisons between experimental and numerical flow studies were also performed. The results have shown that the biomodels produced with beeswax and glycerine-based soap were the most suitable in vitro models to perform direct flow visualizations of particulate blood analogue fluids. The biomodels proposed in this works, have the potential to provide further insights into the complex blood flow phenomena happening at different kinds of pathologies and answer to important hemodynamics questions that otherwise cannot be tackled with the existing in vitro models.

Identification of viscoelastic properties of Dacron aortic grafts subjected to physiological pulsatile flow

In vascular surgery, most synthetic vascular grafts currently used for large vessels replacements are made of Dacron (polyethylene terephthalate; PET). In this study, the dynamic response of these synthetic arterial substitutes to physiological pulsatile conditions is investigated in depth. Experiments were performed on a mock circulatory loop developed to replicate physiological pulsatile pressure and flow. Two different models of Dacron grafts (branched and straight) were tested at various heart rate conditions. Results are presented in terms of cyclic axisymmetric diameter changes, hysteretic loops of the pressure-diameter change, and viscoelastic parameters, such as loss factor and storage modulus that are identified from the hysteresis loop. The amplitude of cyclic diameter change of the Dacron graft was found to be always below 0.2% for all the heart rates considered (from 57 to 187 bpm). The loss factor of the Dacron graft slightly increased with the heart rate; almost no effect of the pulse rate was observed on the storage modulus, which was identified to be around 100 MPa. Both glycerol-water mixture (i.e. the blood analogue fluid) and saline solution were used in the circulatory loop and results did not present significant differences between the two cases. This shows that the effect of the shear load on the dynamic response of Dacron grafts is negligible. A comparison between Dacron vascular implants and human thoracic aortas shows a large mismatch in their viscoelastic mechanical properties.