Blood-mimicking Fluid Research Articles

Correlation between subretinal tissue plasminogen activator and air injection rates with pressure in a retina mimicking model

By investigating the correlation between the injection rate and pressure of subretinal tissue plasminogen activator (tPA) and air using a standard Viscous Fluid Control (VFC) system with a 38-gauge cannula, we aimed to establish guidelines for stable injections. We fabricated a retina mimicking model (RMM) with 0.25% agarose solution and an aluminum plate, and substituted submacular hemorrhage (SMH) and tPA with blood-mimicking fluid (BMF) and balanced salt solution (BSS), respectively. The diameter of the pre-bleb mimicking SMH in RMM was 1.30 ± 0.16 cm, increasing to 1.98 ± 0.24 cm and 1.83 ± 0.22 cm after bleb propagation with BSS and air, respectively. BSS injection rates were 2.86 ± 0.04 µl/sec, 6.74 ± 0.48 µl/sec and 8.55 ± 0.16 µl/sec at 8, 12, and 16 psi, respectively. Air injection rates were 37.98 ± 3.11 µl/sec, 79.01 ± 5.13 µl/sec and 156.06 ± 13.72 µl/sec at 2, 3 and 4 psi, respectively. By experimenting with different pressures in the RMM, we found 12 psi to be the minimum for proper BSS injection and 2 psi for air. These findings provide crucial parameters for safer surgery to prevent irreversible damage.

Exploring the relationship between embolic acute stroke distribution and supra-aortic vessel patency: key findings from an in vitro model study

BackgroundWe investigated differences in intracranial embolus distribution through communicating arteries in relation to supra-aortic vessel (SAV) patency.MethodsFor this experimental analysis, we created a silicone model of the extracranial and intracranial...

Production and characterization of a blood analogue based on alginate microparticles

This work addresses the need for a universal blood substitute by focusing on developing alginate-based microparticles engineered to replicate the mechanical properties of red blood cells (RBCs). Alginate, known for its biocompatibility and tunable mechanical properties, is used to create microparticles that closely resemble RBCs in size and shape. These alginate microparticles are produced through premix membrane emulsification (PME), ensuring a uniform size distribution. The viscosity ratio and the size of the filter pores influence the final size of the microparticles. Filters with pores of 20 µm were used to produce 5 wt% alginate microparticles with a diameter of 7.81 µm ± 0.77, and filters with pores of 30 µm were used to produce 0.5 wt% alginate microparticles with a diameter of 8.69 µm ± 3.30. The Deformability Index (DI) of the alginate microparticles follows the correlation that microparticles with higher elastic modulus exhibit lower DI values. The DI found for 0.5 wt% alginate microparticles solution is higher than the DI found for 5 wt% alginate microparticles. The DI of RBCs is higher than the ones found for the alginate microparticles, however the value is in the range of the experimental error. Rheological studies reveal that suspensions of 25–30 wt% alginate microparticles exhibit a shear-thinning behavior similar to human blood. The DI of the alginate microparticles shows little influence on the rheology of the suspensions. Furthermore, the Cell-Free Layer (CFL) of alginate microparticles is close to that of RBCs, reinforcing the potential of alginate as a suitable material for blood substitute development. The alginate microparticles produced in this work show a great potential to contribute to creating a blood-mimicking fluid for applications in medical treatments and research.

Robust adversarial learning model to segment non-speckle regions in blood flow echo

In our previous study, we analyzed the contrast of blood flow echo, and non-speckle regions were more frequently detected in the porcine blood with the high flow velocity. However, this contrast method is dependent on the degree of smoothing and threshold for outliers. This study developed a new U-Net model incorporating domain adaptation with both in silico and experimental data. This model segments blood flow echo into speckle and non-speckle regions. The performance of the developed U-Net model with several conditions of scatterer number density from 0.1 to 1.5 scatterers mm−3 and scatterer amplitude from 2 to 50 times against the speckle component was assessed using in silico data and experimental data with blood-mimicking fluid. The results indicated that the developed U-Net model with adversarial learning could stably detect non-speckle regions compared to the model without the adversarial learning and the contrast analysis method, in both in silico and experimental data.

Delineating the effects of morphological changes on retinal hemodynamics in diabetic human retinas: An invitro investigation

Diabetes-related vascular abnormalities are commonly encountered in the retinal vasculature, the most common being the increased tortuosity and reduced lumen diameter. These morphological changes significantly affect the underlying hemodynamics and remain unexplored. The current study examines the changes produced by the altered morphology on the blood flow velocity and wall shear stress (WSS) using particle streak velocimetry (PSV) experiments and numerical simulations and compares it with the healthy scenario. The diabetic and healthy retinal arteries are extracted from patient-specific fundus images and transparently printed using stereolithography (SLA) in three dimensions. Flow visualization experiments are performed using the blood-mimicking fluid (BMF) with three different flow rates, whose values are evaluated using the similarity analysis. Experimental and simulation results illustrate a significant reduction in the average axial velocity and WSS due to tortuosity with maximum percentage reductions of 10% and 11%, respectively, compared to healthy. Additionally, a strong correlation is observed between a particular artery's local tortuosity and the WSS, with a higher tortuosity index leading to the development of low-shear regions inside the diabetic artery. A 14% diameter reduction in the diabetic arteries leads to approximately 65% and 63% increase in the velocity and WSS, respectively, compared to healthy. Moreover, the experiments also capture the effect of decreased blood viscosity on the WSS in the case of diabetic arteries, illustrating a significant decrease in WSS values. The experiments performed in the current study may help ophthalmologists estimate the induced damage that the arterial morphological changes may create and facilitate an accurate prognosis of retinal vascular diseases.

Study of the blood flow structure in personalized models of graft branch from the femoral artery

The paper presents the methodology and results of calculating the pulsating flow of blood-mimicking fluid in three personalized models of proximal anastomosis of the femo-ral artery after femoral popliteal bypass surgery performed using synthetic grafts. Per-sonalized models were built based on computed tomography data and ultrasound meas-urements of blood flow velocity in the common femoral artery and in the graft. The char-acteristics of the pulsating flow of blood-mimicking fluid were calculated by numerically solving the three-dimensional unsteady Navier-Stokes equations. Comparison of the calculated velocity field obtained for one of the personalized models with clinical meas-urement data using ultrasonic high-speed vector imaging (applying the V Flow technol-ogy implemented in the Mindray scanner) showed satisfactory agreement of the results. A comparative analysis of the flow structure in two personalized models built for the sec-ond patient one and seven months after surgery is given. It was established that the nar-rowing of the flow sections of the vascular bed, detected after seven months, due to the growth of neointima in the common femoral artery (immediately before the anastomosis) and in the initial section of the graft, led to a significant increase in gradients of the ve-locity field and the time-averaged wall shear stress (TAWSS) in the area of the anastomo-sis; at the same time, the value of the oscillatory shear index (OSI) on the wall throughout the entire anastomosis area decreased. It was also revealed that at a distance of several calibers from the anastomosis, a single-vortex, weakly swirling flow is formed in the graft, the direction of swirl in which is determined by the individual geometry of the anastomo-sis area.

A Mechatronic Cardiovascular Simulation System for Jugular Venous Echo-Doppler Training

Echo-doppler examination of the jugular vessel is a powerful tool for the early diagnosis of cardiovascular disorders that can be further related to central nervous system diseases. Unfortunately, the ultrasound technique is strongly operator-dependent, so the quality of the scan, the accuracy of the measurement, and therefore the rapidity and robustness of the diagnosis reflect the degree of training. The paper presents the development of a mechatronic simulation system for improving the skill of novice physicians in echo-doppler procedures. The patient is simulated by a silicone manikin whose materials are designed to have a realistic ultrasound response. Two tubes allow blood-mimicking fluid to flow inside the manikin, simulating the hemodynamics of the internal jugular vein. The mechatronic system is designed for controlling the flow waveform, to reproduce several clinical cases of interest for diagnosis. The experiments investigate the accuracy of the echo-doppler measurements performed on the proposed system by novice operators using a real ultrasound scanner.

A phantom study: Evaluation of a novel three-lumen balloon catheter for potential treatment of intractable limb ischemia.

Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease (PAD) which induces extremity rest pain, extremity gangrene or ulcers that mostly might lead to limb loss. One of the most common criteria of CLI is 50 mmHg or less systolic ankle arterial pressure. In this study, a custom made three-lumen catheter (9 Fr) including a distal inflatable balloon in between the inflow and outflow lumen holes was designed and fabricated based on the patented design of Hyper Perfusion Catheter. The proposed catheter design aims to increase ankle systolic pressure to 60 mmHg or more to promote healing and/or alleviating severe pain due to intractable ischemia for patients with CLI. To simulate the blood circulation of related anatomy, in vitro CLI model phantom was designed and constructed by using a modified hemodialysis circuit, a hemodialysis pump and a tube set for cardio-pulmonary bypass surgery. A blood mimicking fluid (BMF) with dynamic viscosity of 4.1 mPa.s was used at 22 ºC to prime the phantom. The data was collected by a custom-made circuit design in real time and all measurements were verified with commercial certificated medical devices. The results of in vitro CLI model phantom experiments have shown that it is feasible to elevate the pressure distal to the occlusion (representing ankle pressure) above 80 mmHg without affecting the systemic pressure.

Validation of 4D flow cardiovascular magnetic resonance in TIPS stent grafts using a 3D-printed flow phantom

BackgroundFour-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is feasible for portal blood flow evaluation after placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with liver cirrhosis. However, clinical acceptance of 4D flow CMR in TIPS patients is limited due to the lack of validation studies. The purpose of this study was to validate 4D flow CMR-derived measurements in TIPS stent grafts using a three-dimensional (3D)-printed flow phantom. MethodsA translucent flow phantom of the portal vasculature was 3D-printed. The phantom consisted of the superior mesenteric vein and the splenic vein draining into the portal vein, the TIPS-tract, and the hepatic vein. A TIPS stent graft (Gore® Viatorr®) was positioned within the TIPS-tract. Superior mesenteric vein and splenic vein served as inlets for blood-mimicking fluid. 4D flow CMR acquisitions were performed at 3T at preset flow rates of 0.8 to 2.8 l/min using velocity encoding of both 1.0 and 2.0 m/s. Flow rates and velocities were measured at predefined levels in the portal vasculature and within the stent graft. Accuracy of 4D flow CMR was assessed through linear regression with reference measurements obtained by flow sensors and two-dimensional (2D) phase contrast (PC) CMR. Intra- and interobserver agreement were assessed through Bland–Altman analyses. ResultsAt a velocity encoding of 2.0 m/s, 4D flow CMR-derived flow rates and velocities showed an excellent correlation with preset flow rates and 2D PC CMR-derived flow velocities at all vascular levels and within the stent graft (all r ≥ 0.958, p ≤ 0.003). At a velocity encoding of 1.0 m/s, aliasing artifacts were present within the stent graft at flow rates ≥ 2.0 l/min. 4D flow CMR-derived measurements revealed high intra- and interobserver agreement. ConclusionsThe in vitro accuracy and precision of 4D flow CMR is unaffected by the presence of TIPS stent grafts, suggesting that 4D flow CMR may be used to monitor TIPS patency in patients with liver cirrhosis.

Wall Shear Stress Measurement in Carotid Artery Phantoms with Variation in Degree of Stenosis Using Plane Wave Vector Doppler

Wall shear stress (WSS) plays an important role in the formation, growth, and rupture of atherosclerotic plaques in arteries. This study measured WSS in diseased carotid artery phantoms with degrees of stenosis varying from 0 to 60% with both steady and pulsatile flow. Experiments were performed using in silico and real flow phantoms. Blood velocities were estimated using plane wave (PW) vector Doppler. Wall shear stress was then estimated from the velocity gradient near the wall multiplied by the viscosity of a blood-mimicking fluid. The estimated WSS using the in silico phantom agreed within 10% of the ground-truth values (root-mean-square error). The phantom experiment showed that the mean WSS and maximum WSS increased with the increasing degree of stenosis. The simulation and experiment results provide the necessary validation data to give confidence in WSS measurements in patients using the PW vector Doppler technique.

Characterization of blood mimicking fluid with ultrafast ultrasonic and optical image velocimeters

A blood mimicking fluid (BMF) is imperative for the evaluation of Doppler ultrasound. Doppler ultrasound still causes errors due to some artifacts such as aliasing and presence of grating lobes. One of the other velocimeters is the optical particle image velocimeter (PIV). This study initially developed an in vitro measurement system for analyzing flowing BMF with ultrasonic and optical PIVs. The acoustic properties such as speed of sound, attenuation, and backscatter coefficient of BMF equivalent to the human blood, used for both ultrasonic and optical PIVs were analyzed in a frequency range of 4–12 MHz. The velocity profiles were estimated by ultrasonic and optical PIVs using a block matching method. A difference between velocities obtained by ultrasonic and optical data was within 4.0% using BMF with 20 μm polyamide particle at 0.2% concentration that realized the acoustic properties and speckle patterns similar to those in ultrafast ultrasound blood flow imaging.

Experimental Investigation of Blood Mimicking Fluid Viscosity for Application in 3D-Printed Medical Simulator

Blood mimicking fluid (BMF) is blood that accurately mimics human blood. BMF is commonly used in 3D printed medical simulators for pre-surgical planning and simulation or intraoperative orientation to assist surgeons on cardiac surgical procedures. This research aims to develop a newly formulated BMF containing polysaccharide particles via varying the percent composition of xanthan gum-starch-water-glycerol-contrast agent mixture. The viscosity of the formulated BMF is compared with human blood and observed. A total of 10 BMF samples consisting of different components and composition ratios is prepared and the viscosity of each sample is measured at shear rates ranging from 0s−1 to 1000s−1. The results are tabulated and compared with human blood. Based on the results of the experiments conducted, the addition of polysaccharide particles was found to affect the viscosity of the BMF. The BMF sample with a composition of water 59.98 vol%, glycerol 40 vol%, 0.01 wt% xanthan gum and 0.01 wt% starch shows the smallest viscosity percentage difference when compared to the viscosity of actual blood. Viscosity plateau values was found at 3.71± 0.34 mPa.s which is within the range of actual normal human whole blood viscosity.

Human “live cadaver” neurovascular model for proximal and distal mechanical thrombectomy in stroke

BackgroundPreclinical testing platforms that accurately replicate complex human cerebral vasculature are critical to advance neurointerventional knowledge, tools, and techniques. Here, we introduced and validated a human “live cadaveric” head-and-neck neurovascular...

Creating patient-specific vein models to characterize wall shear stress in hemodialysis population

End-Stage Renal Disease (ESRD) patients require arteriovenous fistulas (AVF) that allow a mature vein to withstand hemodialysis. Unfortunately, venous thrombosis and stenosis in the cephalic vein arch after AVF placement is common and heavily influenced by hemodynamics. To better assess forces and flow behavior in the cephalic arch, we have built patient-specific millifluidic models that allow us to explore the complex interplay between patient-specific vein geometry and fluctuating hemodynamics. These 3D models were created from patient-specific intravascular ultrasound and venogram images obtained three- and twelve-months post AVF creation and fabricated into soft elastomer-based millifluidic devices. Geometric validation of fabricated phantom millifluidic device shows successful replication of original computational 3D model. Millifluidic devices were perfused with a blood-mimicking fluid containing fluorescent tracer beads under steady-state physiologic cephalic vein flow conditions (20 mL/min). Particle image velocimetry was employed to calculate wall shear stress (WSS) across the cephalic arches. Experimental WSS profile evaluation reveals that the physiologic cephalic arch model yields WSS values within physiologic range [76–760 mPa]. Moreover, upon comparing WSS profiles across all models, it is noticeable that WSS values increase as vein diameter decreases, which further supports employed experimental and analysis strategy. The presented millifluidic devices show promise for experimental WSS characterization under pathologic flow conditions to contrast from calculated physiologic hemodynamics and better understand WSS influence on thrombosis and stenosis in hemodialysis patients.

PIV methodology for small scale measurement

Measurement of velocity fields by PIV method is often limited by the scale of the measured model. This is doubly true for the stereo PIV method. Problems of measurement in small (but still macroscopic) scales are associated with optical distortions in the optical path of the camera. Additionally, there is a calibration problem for stereo PIV. Therefore, this paper is devoted to the description of PIV methodology for measurement in small geometrical scales. The idealized transparent model of hemodialysis vascular access was used in this paper. This model had realistic vascular access dimensions (6 mm in diameter). A special working blood-mimicking fluid (BMF) was mixed with a refractive index matching that of the model. The refraction and distortion of light passing through the interface between the model and the fluid was so small, that it was possible to calibrate the stereo PIV outside the measured model. The accuracy of this calibration is discussed and verified by measuring the velocity field on a straight section of the vascular access model for laminar flow.

A Review of Blood-mimicking Fluid Properties Using Doppler Ultrasound Applications.

Doppler imaging ultrasound characterization and standardization requires blood that is called blood mimicking fluid for the exam. With recognized internal properties, acoustic and physical features of this artificial blood. Both acoustical and physical merits set in the International Electrotechnical Commission (IEC) scale are determined as regular values, where the components utilized in the artificial blood preparation must have values identical to the IEC values. An artificial blood is commercially available in the medical application and may not be suitable in the mode of ultrasonic device or for rate of new imaging technique. It is sometimes qualified to have the strength to produce sound features and simulate blood configuration for particular implementations. In the current review article, appropriate artificial blood components, fluids, and measurements are described that have been created using varied materials and processes that have modified for medical applications.

Projection-based stereolithography for direct 3D printing of heterogeneous ultrasound phantoms.

Modern ultrasound (US) imaging is increasing its clinical impact, particularly with the introduction of US-based quantitative imaging biomarkers. Continued development and validation of such novel imaging approaches requires imaging phantoms that recapitulate the underlying anatomy and pathology of interest. However, current US phantom designs are generally too simplistic to emulate the structure and variability of the human body. Therefore, there is a need to create a platform that is capable of generating well-characterized phantoms that can mimic the basic anatomical, functional, and mechanical properties of native tissues and pathologies. Using a 3D-printing technique based on stereolithography, we fabricated US phantoms using soft materials in a single fabrication session, without the need for material casting or back-filling. With this technique, we induced variable levels of stable US backscatter in our printed materials in anatomically relevant 3D patterns. Additionally, we controlled phantom stiffness from 7 to >120 kPa at the voxel level to generate isotropic and anisotropic phantoms for elasticity imaging. Lastly, we demonstrated the fabrication of channels with diameters as small as 60 micrometers and with complex geometry (e.g., tortuosity) capable of supporting blood-mimicking fluid flow. Collectively, these results show that projection-based stereolithography allows for customizable fabrication of complex US phantoms.

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.

Validation of a novel ultrasound Doppler monitoring device (earlybird) for measurements of volume flow rate in arteriovenous fistulas for hemodialysis.

Controversy exists regarding surveillance of arteriovenous fistulas for hemodialysis to increase patency. A significant reduction in volume flow rate (VFR) should lead to diagnostic evaluation and eventually intervention. Several methods are available for VFR measurements, but all of them are associated with low reproducibility. VFR trend analysis is suggested as an improved solution. It is therefore a need to find user-friendly, cost and time-effective modalities. We present a novel Doppler ultrasound device (earlybird) which could bridge this gap. It includes an easy-to-use and light-weight single element transducer. In an experimental and clinical setting, we compared earlybird to duplex ultrasound to assess VFR. In a closed circuit of blood-mimicking fluid, 36 paired calculations of calibrated, duplex ultrasound and earlybird VFR was measured. In addition, 23 paired recordings of duplex ultrasound and earlybird VFR was measured in 16 patients with underarm arteriovenous fistulas. Pearson correlation, intraclass correlation coefficient, root-mean-square and Bland-Altman plots were analyzed. Strong correlation (r = 0.991, p < 0.001), and excellent level of agreement (ICC = 0.970 (95% CI 0.932 - 0.985), p < 0.001) between earlybird and the calibrated VFR was found in the experimental setup. This was confirmed in the clinical setting, with a strong correlation (r = 0.781, p < 0.001) and moderate to good level of agreement (ICC = 0.750 (95% CI 0.502-0.885), p < 0.001) between earlybird and duplex ultrasound VFR measured at the arteriovenous fistulas outflow veins. In the Bland-Altman plot-analysis for the experimental setup, we found smaller limits of agreement, a smaller consistent and proportional bias, as well as greater accuracy of earlybird than DUS when compared to the calibrated VFR. Earlybird is a feasible tool for VFR measurements and could be a future promising device for easy assessment and surveillance of AVF for hemodialysis.

A Pulsed Wave Doppler Ultrasound Blood Flowmeter by PMUTs

This letter describes a blood flowmeter by the pulsed wave Doppler (PWD) ultrasound detection procedure utilizing piezoelectric micromachined ultrasonic transducers (pMUTs) with the aluminum nitride (AlN) film as the piezoelectric material. The transceiver electronics for the PWD scheme are constructed for system control and signal processing, and a blood-mimicking fluid (BMF) is synthesized for flow velocity tests. Both the average Doppler frequency-shift and Doppler power spectrum density (PSD) shift with respect to the flow velocity have been characterized and validated, and the flow direction can also be recognized. Finally, a real-time pulsatile flow measurement is demonstrated to emulate the feasibility of monitoring blood flows in practice. [2021-0077]