Flow Rate Waveforms Research Articles

Performance Assessment of an Electrostatic Filter-Diverter Stent Cerebrovascular Protection Device: Evaluation of a Range of Potential Electrostatic Fields Focusing on Small Particles

Silent Brain Infarction (SBI) is increasingly recognized in patients with cardiac conditions, particularly Atrial Fibrillation (AF) in elderly patients and those undergoing Transcatheter Aortic Valve Implantation (TAVI). While these infarcts often go unnoticed due to a lack of acute symptoms, they are associated with a threefold increase in stroke risk and are considered a precursor to ischemic stroke. Moreover, accumulating evidence suggests that SBI may contribute to the development of dementia, depression, and cognitive decline, particularly in the elderly population. The burden of SBI is substantial, with studies showing that up to 11 million Americans may experience a silent stroke annually. In AF patients, silent brain infarcts are common and can lead to progressive brain damage, even in those receiving anticoagulation therapy. The use of cerebral embolic protection devices (CEPDs) during TAVI has been explored to mitigate the risk of stroke; however, their efficacy remains under debate. Despite advancements in TAVI technology, cerebrovascular events, including silent brain lesions, continue to pose significant challenges, underscoring the need for improved preventive strategies and therapeutic approaches. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by atrial fibrillation, thromboembolism, or dislodged debris of varying potential TAVI patients. The study has been carried out in two stages. Both are based on computational fluid dynamics (CFD) coupled with the Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flow rate waveforms characteristic of healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flow rates and pressures in a patient’s aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming from the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: (1) while the smallest particles are deflected by electrostatic repulsion, avoiding micro embolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients.

Induction of Controllable Vortical Flow in a Dual-Stenosis Aorta Model: A Replication of Disordered Eddies Flow in Aneurysms.

This paper presents a two-stenosis aorta model mimicking vortical flow in vascular aneurysms. More specifically, we propose to virtually induce two adjacent stenoses in the abdominal aorta to develop various vortical flow zones post stenoses. Computational fluid dynamics (CFD) simulations were conducted for the virtual two-stenosis model based on physiological and anatomical data (i.e., diameters, flow rate waveforms) from adult rabbits. The virtual model includes adult rabbits' infra-renal portion of the aorta and iliac arteries. 3D CFD simulations in five different dual-stenosis configurations were performed using a commercial CFD package (FLUENT). In-house software assessed the evolution of flow vortices. Notably, spatial-temporally averaged wall shear stress (STA-WSS) and oscillatory shear index (OSI), the total volume of vortex flow, the number of vortices, and the phase-to-phase overlap of vortex flow within each region were evaluated. In all models, we found consistent patterns of the vortex flow parameters, indicating that the adjacent stenoses induced three different hemodynamic zones, namely, stable vortical flow (after the first stenosis), transient vortical flow (after the second stenosis), and unstable vortical flow (further distal to the second stenosis). Also, different degrees of flow disturbance can be achieved in these three zones. It is significant to note that, although the 'dual-stenosis' geometry is completely hypothetical, it allows us to create various vortical flows in consecutive vessel segments for the first time. As a result, if implemented as a pre-clinical model, the proposed two-stenosis model offers an attractive, tunable environment to investigate the interplays between subject-specific hemodynamics and vascular remodeling. This aspect remains in our future directions.

Perfusion Bioreactor Conditioning of Small-diameter Plant-based Vascular Grafts.

Vascular grafts are mainly composed of synthetic materials, but are prone to thrombosis and intimal hyperplasia at small diameters. Decellularized plant scaffolds have emerged that provide promising alternatives for tissue engineering. We previously developed robust, endothelialized small-diameter vessels from decellularized leatherleaf viburnum. This is the first study to precondition and analyze plant-based vessels under physiological fluid flow and pressure waveforms. Using decellularized leatherleaf viburnum as tissue-engineered grafts for implantation can have profound impacts on healthcare due to their biocompatibility and cost-effective production. A novel perfusion bioreactor was designed, capable of accurately controlling fluid flow rate and pressure waveforms for preconditioning of small-diameter vascular grafts. A closed-loop system controlled pressure waveforms, mimicking physiological values of 50-120mmHg at a frequency of 8.75Hz for fluid flow reaching 5mL/min. Plant-based vascular grafts were recellularized with endothelial and vascular smooth muscle cells and cultured for up to 3weeks in this bioreactor. Cell density, scaffold structure and mechanics, thrombogenicity, and immunogenicity of grafts were evaluated. Bioreactor treatment with fluid flow significantly increased luminal endothelial cell density, while pressure waveforms reduced thrombus formation and maintained viable vascular smooth muscle cells within inner layers of grafts compared to static controls. Suture retention of grafts met transplantation standards and white cell viability was suitable for vascular remodeling. Low thrombogenicity of endothelialized leatherleaf viburnum holds great potential for vascular repair. This study provides insight into benefits of conditioning plant-based materials with hemodynamic forces at higher frequencies that have not previously been investigated.

Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI

Background and objectiveThe evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. MethodsA complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. ResultsThe analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. ConclusionsThe findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Manufacturing an artificial arterial tree using 3D printing

Models of the arterial network are useful in studying mechanical cardiac assist devices as well as complex pathological states that are difficult to investigate in-vivo otherwise. Earlier work of artificial arterial tree (AAT) have been constructed to include some of the major arteries and their branches for in-vitro experiments which focused on the aorta, using dipping or painting techniques, which resulted in inaccuracies and inconsistent wall thickness. Therefore, the aim of this work is to use 3D printing for manufacturing AAT based on physiologically correct dimensions of the largest 45 segments of the human arterial tree. A volume ratio mix of silicone rubber (98 %) and a catalyst (2 %) was used to create the walls of the AAT. To validate, the AAT was connected at its inlet to a piston pump that mimicked the heart and capillary tubes at the outlets that mimicked arterial resistances. The capillary tubes were connected to a reservoir that collected the water which was the fluid used in testing the closed-loop hydraulic system. Young's modulus of the AAT walls was determined using tensile testing of different segments of various wall thickness. The developed AAT produced pressure, diameter and flow rate waveforms that are similar to those observed in-vivo. The technique described here is low cost, may be used for producing arterial trees to facilitate testing mechanical cardiac assist devices and studying hemodynamic investigations.

Adaptive design of experiments to fit surrogate Gaussian process regression models allows fast sensitivity analysis of the input waveform for patient-specific 3D CFD models of liver radioembolization

Background and objectivePatient-specific 3D computational fluid dynamics (CFD) models are increasingly being used to understand and predict transarterial radioembolization procedures used for hepatocellular carcinoma treatment. While sensitivity analyses of these CFD models can help to determine the most impactful input parameters, such analyses are computationally costly. Therefore, we aim to use surrogate modelling to allow relatively cheap sensitivity analysis. As an example, we compute Sobol's sensitivity indices for three input waveform shape parameters. MethodsWe extracted three characteristic shape parameters from our input mass flow rate waveform (peak systolic mass flow rate, heart rate, systolic duration) and defined our 3D input parameter space by varying these parameters within 75 %-125 % of their nominal values. To fit our surrogate model with a minimal number of costly CFD simulations, we developed an adaptive design of experiments (ADOE) algorithm. The ADOE uses 100 Latin hypercube sampled points in 3D input space to define the initial design of experiments (DOE). Subsequently, we re-sample input space with 10,000 Latin Hypercube sampled points and cheaply estimate the outputs using the surrogate model. In each of 27 equivolume bins which divide our input space, we determine the most uncertain prediction of the 10,000 points, compute the true outputs using CFD, and add these points to the DOE. For each ADOE iteration, we calculate Sobol's sensitivity indices, and we continue to add batches of 27 samples to the DOE until the Sobol indices have stabilized. ResultsWe tested our ADOE algorithm on the Ishigami function and showed that we can reliably obtain Sobol's indices with an absolute error <0.1. Applying ADOE to our waveform sensitivity problem, we found that the first-order sensitivity indices were 0.0550, 0.0191 and 0.407 for the peak systolic mass flow rate, heart rate, and the systolic duration, respectively. ConclusionsAlthough the current study was an illustrative case, the ADOE allows reliable sensitivity analysis with a limited number of complex model evaluations, and performs well even when the optimal DOE size is a priori unknown. This enables us to identify the highest-impact input parameters of our model, and other novel, costly models in the future.

Effects of Coronary Stenosis on Coronary Vascular Impedance

Introduction: The impedance analysis for circulation system is a powerful tool to comprehensively measure the afterload of the entire circulation system. The spectrum of vascular mechanical parameters derived from the impedance analysis can reveal the compliance and resistance changes in proximal and distal vessels, as well as the wave reflections. However, the similar investigation in the opposition of the coronary circulation is limited, and it is unknown how coronary stenosis affects the vascular impedance of the coronary circulation. In this study, we aimed to quantify and compare the changes in the vascular impedance of coronary circulation from the dynamic pressure and flow relations in healthy and patients with stenosis. Method: The pressure and flow rate waveforms from the main coronary artery were obtained from a lumped-parameter computational model that coupled the systemic circulation with the coronary perfusion within a closed system. Both healthy and diseased (coronary stenosis) pressure-flow relations were examined. A Fourier transform was performed to analyze the pressure and flow data, and the resistance (Z0), characteristic impedance (ZC), wave reflections (RW), total arterial compliance (C), and other hemodynamic parameters were derived. Results: Compared to the healthy subject, the diseased subject presented an increased resistance (Z0 was elevated from 0.44 mmHg ▪ min/ml to 0.59 mmHg ▪ min/ml), increased characteristic impedance (ZC was elevated from 0.07 mmHg ▪ min/ml to 0.14 mmHg ▪ min/ml), and reduced wave reflection (RW was decreased from 0.72 to 0.6). These changes indicate elevated distal arteries and arterioles narrowing and proximal artery stiffening in the entire coronary vasculature. Moreover, the coronary flow and the total arterial compliance (stroke volume divided by pulse pressure) were reduced with the disease progression. These data suggest a reduced coronary perfusion and stiffening of the artery in the coronary circulation. Discussion: The impedance analysis has been widely used for systemic and pulmonary circulations previously to quantify the total afterload of the left and right ventricles, respectively. The distribution of the impedance in different frequencies reflects the anatomical and mechanical properties of the vasculature in the circulation system. This study originally found that the coronary artery impedance is altered by coronary stenosis. The key characteristics include the narrowing of distal coronary arteries and stiffening of proximal coronary arteries. However, since both proximal and distal arteries are altered, the wave reflection was reduced, and this may explain a reduced pulse pressure observed in the diseased subject. The reduction in overall coronary perfusion indicates an impaired blood supply to the ventricle and may be responsible for the dysfunction of the heart. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Induction of Controllable Vortex Flow in a New Aorta Stenosis Model for Potential Aorta Mechanobiology Study: A Flow Simulation Platform

Background: Abdominal aortic aneurysms (AAA) are common, particularly among individuals over age 65, with a prevalence of 9%. To better understand the natural history of AAAs, one critical knowledge gap must be filled to elucidate the role of vortical flow in vascular degradation and thrombosis formation. We aimed to induce various types of vortical flow with aneurysm-like hemodynamic environments using a novel aorta stenosis model. Such a model will enable us to investigate the interplays between disturbed hemodynamics and vascular pathological remodeling. Methods: In this study, the hemodynamics and geometry of the aorta in rabbits were used to simulate the physiological flow conditions after two adjacent stenoses were created virtually with varying degrees of area reduction (30-70%) and spacing (5-6.8 mm). A physiological blood flow (rate) waveform measured in rabbits using ultrasound Doppler (normalized to 3.0 mL/s) was prescribed to the inlet (i.e., descending aorta), and zero pressure boundary conditions were applied at two outlets (i.e., iliac arteries). 3D computational fluid dynamics (CFD) simulation in five different stenosis configurations was performed using commercial software (Fluent, Version 20, Ansys Inc., PA). In-house software assessed the evolution of flow vortices over three distinct regions post stenosis using an established method. The total volume of vortex flow, the number of vortices, and the phase-to-phase overlap of vortex flows within different post-stenosis regions were derived to characterize the vortex flow. Results: Quantitative and qualitative flow assessments were performed for all five CFD models. Firstly, in all models, we found consistent patterns of the three vortex flow parameters, indicating that the adjacent stenoses induced three different hemodynamic zones in the post-stenosis regions, namely, stable vortical flow (after first stenosis), transient flow (after second stenosis), unstable vortical flow (further distal to second stenosis). Moreover, increased stenosis degree or reduced spacing led to reduced vortex flow number but increased total volume of vortex flow. The distinctions of the three regions were most significant in the model with 50% and then 30% stenoses, and with a 5 mm (center-to-center) spacing between two stenoses. Conclusions: CFD simulations can offer a powerful tool to predict complex flows using subject-specific vasculature. Such a flow simulation platform is valuable for guiding experimental design or therapy in various diseases. We demonstrated that it is feasible to adjust and achieve multiple types of vortical flows with the novel stenosis model. The three zones with distinct hemodynamic environments allow us to investigate the vascular remodeling regulated by the specifics of the eddies. Our ongoing work is implementing optimized aorta stenosis models to preclinical or in vitro studies to reveal the interplays between varying disturbed flow and aneurysm remodeling. We acknowledge funding support from NIH/NIBIB (R01-EB029570A1) and the Health Research Institute of Michigan Technological University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Performance assessment of an electrostatic filter-diverter stent cerebrovascular protection device. Is it possible not to use anticoagulants in atrial fibrilation elderly patients?

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients.

A Vector Fitting Approach for the Automated Estimation of Lumped Boundary Conditions of 1D Circulation Models.

The choice of appropriate boundary conditions is a crucial step in the development of cardiovascular models for blood flow simulations. The three-element Windkessel model is usually employed as a lumped boundary condition, providing a reduced order representation of the peripheral circulation. However, the systematic estimation of the Windkessel parameters remains an open problem. Moreover, the Windkessel model is not always adequate to model blood flow dynamics, which often require more elaborate boundary conditions. In this study, we propose a method for the estimation of the parameters of high order boundary conditions, including the Windkessel model, from pressure and flow rate waveforms at the truncation point. Moreover, we investigate the effect of adopting higher order boundary conditions, corresponding to equivalent circuits with more than one storage element, on the accuracy of the model. The proposed technique is based on Time-Domain Vector Fitting, a modeling algorithm that, given samples of the input and output of a system, such as pressure and flow waveforms, can derive a differential equation approximating their relation. The capabilities of the proposed method are tested on a 1D circulation model consisting of the 55 largest human systemic arteries, to demonstrate its accuracy and its usefulness to estimate boundary conditions with order higher than the traditional Windkessel models. The proposed method is compared to other common estimation techniques, and its robustness in parameter estimation is verified in presence of noisy data and of physiological changes of aortic flow rate induced by mental stress. Results suggest that the proposed method is able to accurately estimate boundary conditions of arbitrary order. Higher order boundary conditions can improve the accuracy of cardiovascular simulations, and Time-Domain Vector Fitting can automatically estimate them.

Hemodynamic simulation in the aortic arch with the lattice Boltzmann method

Aortic diseases have high mortality rates, wherein wall shear stress (WSS) and oscillatory shear index play important roles. Previous studies focused on describing the WSS distribution; however, no report has investigated how hemodynamic parameters determine the distribution of WSS. This study investigates the parameters affecting the WSS distribution and determines the variations of these parameters. A realistic healthy aortic geometry is reconstructed from computed tomography medical images, and a flow simulation is performed using the lattice Boltzmann method. The inlet velocity waveform from the Doppler ultrasound measurement is imposed as the inlet boundary condition, whereas the three-element Windkessel model is used as the outlet boundary condition. The measured outlet flow rate waveforms are used to validate the simulation. A good agreement is found between the outlet flow rate waveform obtained from the measurement and that from the simulation: the descending artery, innominate artery, left common carotid, and left subclavian artery receive 63.42%, 24.01%, 4.14%, and 8.46%, respectively, of the total inlet flow rate over the cardiac cycle in the measurements and 62.17%, 24.61%, 4.7%, and 8.44%, respectively, in the simulation. The simulation shows that the temporal and spatial distributions of the WSS are separately determined by the flow rate and impacting angle. The flow rate ratio between the inlet and outlet decreases with an increase in Re. This relation can be fitted well by the exponential function. Moreover, the impacting angle between the blood flow and the vessel centerline is determined by the vessel geometry only.

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns.

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (-16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3-5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.

Network-Based Characterization of Blood Large-Scale Coherent Motion in the Healthy Human Aorta With 4D Flow MRI.

The need for distilling the hemodynamic complexity of aortic flows into clinically relevant quantities resulted in a loss of the information hidden in 4D aortic fluid structures. To reduce information loss, this study proposes a network-based approach to identify and characterize in vivo the large-scale coherent motion of blood in the healthy human aorta. The quantitative paradigm of the aortic flow as a "social network" was applied on 4D flow MRI acquisitions performed on forty-one healthy volunteers. Correlations between the aortic blood flow rate waveform at the proximal ascending aorta (AAo), assumed as one of the drivers of aortic hemodynamics, and the waveforms of the axial velocity in the whole aorta were used to build "one-to-all" networks. The impact of the driving flow rate waveform and of aortic geometric attributes on the transport of large-scale coherent fluid structures was investigated. The anatomical length of persistence of large-scale coherent motion was the 29.6% of the healthy thoracic aorta length (median value, IQR 23.1%-33.9%). Such length is significantly influenced by the average and peak-to-peak AAo blood flow rate values, suggesting a remarkable inertial effect of the AAo flow rate on the transport of large-scale fluid structures in the distal aorta. Aortic geometric attributes such as curvature, torsion and arch shape did not influence the anatomical length of persistence. The proposed in vivo approach allowed to quantitatively characterize the transport of large-scale fluid structures in the healthy aorta, strengthening the definition of coherent hemodynamic structures and identifying flow inertia rather than geometry as one of its main determinants. The findings on healthy aortas may be used as reference values to investigate the impact of aortic disease or implanted devices in disrupting/restoring the physiological spatiotemporal coherence of large-scale aortic flow.

Non-invasive estimation of the parameters of a three-element windkessel model of aortic arch arteries in patients undergoing thoracic endovascular aortic repair.

Background: Image-based computational hemodynamic modeling and simulations are important for personalized diagnosis and treatment of cardiovascular diseases. However, the required patient-specific boundary conditions are often not available and need to be estimated. Methods: We propose a pipeline for estimating the parameters of the popular three-element Windkessel (WK3) models (a proximal resistor in series with a parallel combination of a distal resistor and a capacitor) of the aortic arch arteries in patients receiving thoracic endovascular aortic repair of aneurysms. Pre-operative and post-operative 1-week duplex ultrasound scans were performed to obtain blood flow rates, and intra-operative pressure measurements were also performed invasively using a pressure transducer pre- and post-stent graft deployment in arch arteries. The patient-specific WK3 model parameters were derived from the flow rate and pressure waveforms using an optimization algorithm reducing the error between simulated and measured pressure data. The resistors were normalized by total resistance, and the capacitor was normalized by total resistance and heart rate. The normalized WK3 parameters can be combined with readily available vessel diameter, brachial blood pressure, and heart rate data to estimate WK3 parameters of other patients non-invasively. Results: Ten patients were studied. The medians (interquartile range) of the normalized proximal resistor, distal resistor, and capacitor parameters are 0.10 (0.07-0.15), 0.90 (0.84-0.93), and 0.46 (0.33-0.58), respectively, for common carotid artery; 0.03 (0.02-0.04), 0.97 (0.96-0.98), and 1.91 (1.63-2.26) for subclavian artery; 0.18 (0.08-0.41), 0.82 (0.59-0.92), and 0.47 (0.32-0.85) for vertebral artery. The estimated pressure showed fairly high tolerance to patient-specific inlet flow rate waveforms using the WK3 parameters estimated from the medians of the normalized parameters. Conclusion: When patient-specific outflow boundary conditions are not available, our proposed pipeline can be used to estimate the WK3 parameters of arch arteries.

The Ability of Doppler Uterine Artery Ultrasound to Predict Premature Birth.

Demonstration of the predictive capacity of Doppler Uterine Artery (UtA) on preterm birth (PB) by serial measurement at various ages of pregnancy. The prospective study included a group of 116 pregnant women, of whom 85 gave birth prematurely and 31 pregnant women gave birth at term, constituting the control group. UtA Doppler measurement was performed by the abdominal approach. Quantitative wave evaluations were performed by the pulsatility index (PI), the systole/diastole ratio (S/D), as well as the qualitative analysis of the flow rate waveform (notch). UtA Doppler evaluation was performed in 3 pregnancy periods: 18.0-22.6 weeks, 28.0-31.6 weeks, and 32.0-35.6 weeks. Only at the third examination, at 32.0-35.5 weeks of gestation, was there a statistically significant difference between the S/D-UtA ratio and PI-UtA correlated with the risk of premature birth (p<0.05). Although there was an association between UtA Doppler and late preterm birth, the predictive ability was low. Also, UtA Doppler was not statistically significant for preterm birth before 32 weeks of gestation. Although we did not find a statistical association between second-trimester UtA Doppler and preterm birth, we do suggest a closer look at women with abnormal UtA Doppler in the second trimester. We believe that, according to the results obtained, UtA Doppler can predict especially iatrogenic premature birth depending on the prediction of the most severe complications, severe preeclampsia, and SGA.

Performance testing for different peak expiratory flow meters.

Peak expiratory flow meters (PEFMs) have emerged as primary tools used for diagnosing and monitoring a range of respiratory diseases including asthma and chronic obstructive pulmonary disease, and the performance of these meters will thus impact disease evaluation. The aim of this study was therefore to assess the technical performance of mechanical and electronic PEFMs commonly used in clinical practice. The accuracy, repeatability, airflow resistance, frequency response, and linearity of five electronic and seven mechanical PEFMs were measured using a standard flow/volume simulator in accordance with nine A-waveforms and three B-waveforms defined in ISO 23747:2015 issued by the International Standards Organization (ISO). The accuracy, repeatability, linearity, airflow resistance, and frequency response pass rates for these 12 different PEFM brands were 41.67%, 75.00%, 50.00%, 75.00%, and 25.00%, respectively. Just 16.67% (2/12) of the tested PEFMs met all evaluated criteria, whereas the remaining PEFMs partially met these criteria. There were no significant differences between the two tested PEFM types in the low flow rate waveform test (P> 0.05), although there were significant differences in the medium and high flow rate waveform test (P< 0.05). In addition, the overall PEFMs test had poor accuracy and good repeatability, although most of the repeatability errors occurred in the BTPS state. PEFMs commonly used in clinical settings exhibit variable technical performance, and relevant departments need to strengthen PEFM quality control and management in China.

CARD21: In Vitro Investigation Of The Timing Of The LVAD Pulsatility Event On Intraventricular Hemodynamics

Background: To reduce in-pump thrombosis and potentially improve left ventricular (LV) washout, pulsatility events (i.e., periodic LVAD speed modulation) have been introduced in 3rd generation LVADs. However, this pseudo-pulsatility of the centrifugal continuous flow pumps is not synchronized with native LV residual contractility. This study investigates the effect of timing of pulsatility events, with respect to LV pressure variations along the cardiac cycle, on intraventricular hemodynamics. Methods: Time-resolved stereo particle image velocimetry measurements were performed in a patient-derived quasirigid LV silicon model implanted with an LVAD. The residual LV contractility was modelled as a periodic variation in intraventricular pressure (IVP). Velocity fields in two orthogonal planes were measured for 7.5 cardiac cycles (including 3 occurrences of the pulsatility events, which happen every two seconds), for 3 LVAD speeds and 4 different synchronicities of pulsatility: at maximum/ minimum IVP and during increasing/decreasing IVP. Instantaneous measurements of the flowrate through the LVAD, with a time-resolution of 1 ms, were collected during the entire experiment. Ventricle stagnation index (VSI) was computed for each measurement plane and all experimental conditions studied. Results: Despite maintaining a constant average flowrate, the synchronicity of the LVAD pulsatility with the oscillatory IVP strongly influenced the flow rate waveforms, especially the peak and minimum instantaneous flow rates. A strong effect of the timing of pulsatility was also observed on intraventricular hemodynamics: pulsatility events taking place during decreasing IVP (diastole) resulted in higher VSI than other timing of pulsatility. Overall, these high resolution, instantaneous measurements of LVAD flow rate and pressure also highlighted the complex interrelations between LVAD speed, peripheral resistance, IVP and flow rate. Conclusion: This in vitro study elucidates the effect of LVAD pulsatility event synchronicity with the cardiac cycle on flowrate and LV flow patterns.

Hemodynamics of anterior circulation intracranial aneurysms with daughter blebs: investigating the multidirectionality of blood flow fields

Recent advances in diagnostic neuroradiological imaging, allowed the detection of unruptured intracranial aneurysms (IAs). The shape – irregular or multilobular – of the aneurysmal dome, is considered as a possible rupture risk factor, independently of the size, the location and patient medical background. Disturbed blood flow fields in particular is thought to play a key role in IAs progression. However, there is an absence of widely-used hemodynamic indices to quantify the extent of a multi-directional disturbed flow. We simulated blood flow in twelve patient-specific anterior circulation unruptured intracranial aneurysms with daughter blebs utilizing the spectral/hp element framework Nektar++. We simulated three cardiac cycles using a volumetric flow rate waveform while we considered blood as a Newtonian fluid. To investigate the multidirectionality of the blood flow fields, besides the time-averaged wall shear stress (TAWSS), we calculated the oscillatory shear index (OSI), the relative residence time (RRT) and the time-averaged cross flow index (TACFI). Our CFD simulations suggest that in the majority of our vascular models there is a formation of complex intrasaccular flow patterns, resulting to low and highly oscillating WSS, especially in the area of the daughter blebs. The existence of disturbed multi-directional blood flow fields is also evident by the distributions of the RRT and the TACFI. These findings further support the theory that IAs with daughter blebs are linked to a potentially increased rupture risk.

Cardiovascular Response to Posture Changes: Multiscale Modeling and in vivo Validation During Head-Up Tilt

In spite of cardiovascular system (CVS) response to posture changes have been widely studied, a number of mechanisms and their interplay in regulating central blood pressure and organs perfusion upon orthostatic stress are not yet clear. We propose a novel multiscale 1D-0D mathematical model of the human CVS to investigate the effects of passive (i.e., through head-up tilt without muscular intervention) posture changes. The model includes the main short-term regulation mechanisms and is carefully validated against literature data and in vivo measures here carried out. The model is used to study the transient and steady-state response of the CVS to tilting, the effects of the tilting rate, and the differences between tilt-up and tilt-down. Passive upright tilt led to an increase of mean arterial pressure and heart rate, and a decrease of stroke volume and cardiac output, in agreement with literature data and present in vivo experiments. Pressure and flow rate waveform analysis along the arterial tree together with mechano-energetic and oxygen consumption parameters highlighted that the whole system approaches a less stressed condition at passive upright posture than supine, with a slight unbalance of the energy supply-demand ratio. The transient dynamics is not symmetric in tilt-up and tilt-down testing, and is non-linearly affected by the tilting rate, with stronger under- and overshoots of the hemodynamic parameters as the duration of tilt is reduced. By enriching the CVS response to posture changes, the present modeling approach shows promise in a number of applications, ranging from autonomic system disorders to spaceflight deconditioning.

Hemodynamics and stresses in numerical simulations of the thoracic aorta: Stochastic sensitivity analysis to inlet flow-rate waveform

Numerical simulations of the blood flow inside a patient-specific thoracic aorta in presence of an aneurysm are considered. We focus on the impact on the numerical predictions of the inlet flow-rate waveform. First, the results obtained by using an idealized and a MRI-measured flow-rate waveform are compared. The measured boundary condition produces significantly higher wall shear stresses than those obtained in the idealized case. Discrepancies are reduced but they are still present even if the idealized inlet waveform is rescaled in order to match the stroke volume.This motivates a systematic sensitivity analysis of numerical predictions to the shape of the inlet flow-rate waveform that is carried out in the second part of the paper. Two parameters are selected to describe the inlet waveform: the stroke volume and the period of the cardiac cycle. A stochastic approach based on the generalized Polynomial Chaos (gPC) approach, in which continuous response surfaces of the quantities of interest in the parameter space can be obtained from a limited number of simulations, is used. For both selected uncertain parameters, we use beta PDFs reproducing clinical data. The two selected input parameters appear to have a significant influence on wall shear stresses as well as on the velocity distribution in vessel regions characterized by large curvature. This confirms the need of using patient-specific inlet conditions to obtain reliable hemodynamic predictions.