Day-to-Day Variability in Measurements of Respiration Using Bioimpedance from a Non-Standard Location.

Non-invasive monitoring of pulmonary health may be useful for tracking several conditions such as COVID-19 recovery and the progression of pulmonary edema. Some proposed methods use impedance-based technologies to non-invasively measure the thorax impedance as a function of respiration but face challenges that limit the feasibility, accuracy, and practicality of tracking daily changes. In our prior work, we demonstrated a novel approach to monitor respiration by measuring changes in impedance from the back of the thigh. We reported the concept of using thigh-thigh bioimpedance measurements for measuring the respiration rate and demonstrated a linear relationship between the thigh-thigh bioimpedance and lung tidal volume. Here, we investigate the variability in thigh-thigh impedance measurements to further understand the feasibility of the technique for detecting a change in the respiratory status due to disease onset or recovery if used for long-term in-home monitoring. Multiple within-session and day-to-day impedance measurements were collected at 80 kHz using dry electrodes (thigh) and wet electrodes (thorax) across the five healthy subjects, along with simultaneous gold standard spirometer measurements for three consecutive days. The peak-peak bioimpedance measurements were found to be highly correlated (0.94 ± 0.03 for dry electrodes across thigh; 0.92 ± 0.07 for wet electrodes across thorax) with the peak-peak spirometer tidal volume. The data across five subjects indicate that the day-to-day variability in the relationship between impedance and volume for thigh-thigh measurements is smaller (average of 14%) than for the thorax (40%). However, it is affected by food and water and might limit the accuracy of the respiratory tidal volume.

Empirical and Computational Evaluation of Hemolysis in a Microfluidic Extracorporeal Membrane Oxygenator Prototype.

Microfluidic devices promise to overcome the limitations of conventional hemodialysis and oxygenation technologies by incorporating novel membranes with ultra-high permeability into portable devices with low blood volume. However, the characteristically small dimensions of these devices contribute to both non-physiologic shear that could damage blood components and laminar flow that inhibits transport. While many studies have been performed to empirically and computationally study hemolysis in medical devices, such as valves and blood pumps, little is known about blood damage in microfluidic devices. In this study, four variants of a representative microfluidic membrane-based oxygenator and two controls (positive and negative) are introduced, and computational models are used to predict hemolysis. The simulations were performed in ANSYS Fluent for nine shear stress-based parameter sets for the power law hemolysis model. We found that three of the nine tested parameters overpredict (5 to 10×) hemolysis compared to empirical experiments. However, three parameter sets demonstrated higher predictive accuracy for hemolysis values in devices characterized by low shear conditions, while another three parameter sets exhibited better performance for devices operating under higher shear conditions. Empirical testing of the devices in a recirculating loop revealed levels of hemolysis significantly lower (<2 ppm) than the hemolysis ranges observed in conventional oxygenators (>10 ppm). Evaluating the model's ability to predict hemolysis across diverse shearing conditions, both through empirical experiments and computational validation, will provide valuable insights for future micro ECMO device development by directly relating geometric and shear stress with hemolysis levels. We propose that, with an informed selection of hemolysis parameters based on the shear ranges of the test device, computational modeling can complement empirical testing in the development of novel high-flow blood-contacting microfluidic devices, allowing for a more efficient iterative design process. Furthermore, the low device-induced hemolysis measured in our study at physiologically relevant flow rates is promising for the future development of microfluidic oxygenators and dialyzers.

Next Generation Development of Hybrid Continuous Flow Pediatric Total Artificial Heart Technology: Design-Build-Test.

To address the unmet clinical need for pediatric circulatory support, we are developing an operationally versatile, hybrid, continuous-flow, total artificial heart ("Dragon Heart"). This device integrates a magnetically levitated axial and centrifugal blood pump. Here, we utilized a validated axial flow pump, and we focused on the development of the centrifugal pump. A motor was integrated to drive the centrifugal pump, achieving 50% size reduction. The motor design was simulated by finite element analysis, and pump design improvement was attained by computational fluid dynamics. A prototype centrifugal pump was constructed from biocompatible 3D printed parts for the housing and machined metal parts for the drive system. Centrifugal prototype testing was conducted using water and then bovine blood. The fully combined device ( i.e. , axial pump nested inside of the centrifugal pump) was tested to ensure proper operation. We demonstrated the hydraulic performance of the two pumps operating in tandem, and we found that the centrifugal blood pump performance was not adversely impacted by the simultaneous operation of the axial blood pump. The current iteration of this design achieved a range of operation overlapping our target range. Future design iterations will further reduce size and incorporate complete and active magnetic levitation.

A power amplification dyad in seahorses.

Throughout evolution, organisms repeatedly developed elastic elements to power explosive body motions, overcoming ubiquitous limits on the power capacity of fast-contracting muscles. Seahorses evolved such a latch-mediated spring-actuated (LaMSA) mechanism; however, it is unclear how this mechanism powers the two complementary functions necessary for feeding: rapidly swinging the head towards the prey, and sucking water into the mouth to entrain it. Here, we combine flow visualization and hydrodynamic modelling to estimate the net power required for accelerating the suction feeding flows in 13 fish species. We show that the mass-specific power of suction feeding in seahorses is approximately three times higher than the maximum recorded from any vertebrate muscle, resulting in suction flows that are approximately eight times faster than similar-sized fishes. Using material testing, we reveal that the rapid contraction of the sternohyoideus tendons can release approximately 72% of the power needed to accelerate the water into the mouth. We conclude that the LaMSA system in seahorses is powered by two elastic elements, the sternohyoideus and epaxial tendons. These elements jointly actuate the coordinated acceleration of the head and the fluid in front of the mouth. These findings extend the known function, capacity and design of LaMSA systems.

Channel impeller design for centrifugal blood pump in hybrid pediatric total artificial heart: Modeling, magnet integration, and hydraulic experiments.

BACKGROUND: The purpose of this research is to address ongoing device shortfalls for pediatric patients by developing a novel pediatric hybrid total artificial heart (TAH). The valveless magnetically-levitated MCS device (Dragon Heart) has only two moving parts, integrates an axial and centrifugal blood pump into a single device, and will occupy a compact footprint within the chest for the pediatric patient population. METHODS: Prior work on the Dragon Heart focused on the development of pump designs to achieve hemodynamic requirements. The impeller of these pumps was shaft-driven and thus could not be integrated for testing. The presented research leverages an existing magnetically levitated axial flow pump and focuses on centrifugal pump development. Using the axial pump diameter as a geometric constraint, a shaftless, magnetically supported centrifugal pump was designed for placement circumferentially around the axial pump domain. The new design process included the computational analysis of more than 50 potential centrifugal impeller geometries. The resulting centrifugal pump designs were prototyped and tested for levitation and no-load rotation, followed by in vitro testing using a blood analog. To meet physiologic demands, target performance goals were pressure rises exceeding 90 mm Hg for flow rates of 1-5 L/min with operating speeds of less than 5000 RPM. RESULTS: Three puck-shaped, channel impellers for the centrifugal blood pump were selected based on achieving performance and space requirements for magnetic integration. A quasi-steady flow analysis revealed that the impeller rotational position led to a pulsatile component in the pressure generation. After prototyping, the centrifugal prototypes (3, 4, and 5 channeled designs) demonstrated levitation and no-load rotation. Hydraulic experiments established pressure generation capabilities beyond target requirements. The pressure-flow performance of the prototypes followed expected trends with a dependence on rotational speed. Pulsatile blood flow was observed without pump-speed modulation due to rotating channel passage frequency. CONCLUSION: The results are promising in the advancement of this pediatric TAH. The channeled impeller design creates pressure-flow curves that are decoupled from the flow rate, a benefit that could reduce the required controller inputs and improve treatment of hypertensive patients.

Dependence of Skin-Electrode Contact Impedance on Material and Skin Hydration.

Dry electrodes offer an accessible continuous acquisition of biopotential signals as part of current in-home monitoring systems but often face challenges of high-contact impedance that results in poor signal quality. The performance of dry electrodes could be affected by electrode material and skin hydration. Herein, we investigate these dependencies using a circuit skin-electrode interface model, varying material and hydration in controlled benchtop experiments on a biomimetic skin phantom simulating dry and hydrated skin. Results of the model demonstrate the contribution of the individual components in the circuit to total impedance and assist in understanding the role of electrode material in the mechanistic principle of dry electrodes. Validation was performed by conducting in vivo skin-electrode contact impedance measurements across ten normative human subjects. Further, the impact of the electrode on biopotential signal quality was evaluated by demonstrating an ability to capture clinically relevant electrocardiogram signals by using dry electrodes integrated into a toilet seat cardiovascular monitoring system. Titanium electrodes resulted in better signal quality than stainless steel electrodes. Results suggest that relative permittivity of native oxide of electrode material come into contact with the skin contributes to the interface impedance, and can lead to enhancement in the capacitive coupling of biopotential signals, especially in dry skin individuals.

Microengineering 3D Collagen Hydrogels with Long-Range Fiber Alignment.

Aligned collagen I (COL1) fibers guide tumor cell motility, influence endothelial cell morphology, control stem cell differentiation, and are a hallmark of cardiac and musculoskeletal tissues. To study cell response to aligned microenvironments in vitro, several protocols have been developed to generate COL1 matrices with defined fiber alignment, including magnetic, mechanical, cell-based, and microfluidic methods. Of these, microfluidic approaches offer advanced capabilities such as accurate control over fluid flows and the cellular microenvironment. However, the microfluidic approaches to generate aligned COL1 matrices for advanced in vitro culture platforms have been limited to thin "mats" (<40 µm in thickness) of COL1 fibers that extend over distances less than 500 µm and are not conducive to 3D cell culture applications. Here, we present a protocol to fabricate 3D COL1 matrices (130-250 µm in thickness) with millimeter-scale regions of defined fiber alignment in a microfluidic device. This platform provides advanced cell culture capabilities to model structured tissue microenvironments by providing direct access to the micro-engineered matrix for cell culture.

The Modular µSiM Reconfigured: Integration of Microfluidic Capabilities to Study In Vitro Barrier Tissue Models under Flow.

Microfluidic tissue barrier models have emerged to address the lack of physiological fluid flow in conventional "open-well" Transwell-like devices. However, microfluidic techniques have not achieved widespread usage in bioscience laboratories because they are not fully compatible with traditional experimental protocols. To advance barrier tissue research, there is a need for a platform that combines the key advantages of both conventional open-well and microfluidic systems. Here, a plug-and-play flow module is developed to introduce on-demand microfluidic flow capabilities to an open-well device that features a nanoporous membrane and live-cell imaging capabilities. The magnetic latching assembly of this design enables bi-directional reconfiguration and allows users to conduct an experiment in an open-well format with established protocols and then add or remove microfluidic capabilities as desired. This work also provides an experimentally-validated flow model to select flow conditions based on the experimental needs. As a proof-of-concept, flow-induced alignment of endothelial cells and the expression of shear-sensitive gene targets are demonstrated, and the different phases of neutrophil transmigration across a chemically stimulated endothelial monolayer under flow conditions are visualized. With these experimental capabilities, it is anticipated that both engineering and bioscience laboratories will adopt this reconfigurable design due to the compatibility with standard open-well protocols.

Development of the Centrifugal Blood Pump for a Hybrid Continuous Flow Pediatric Total Artificial Heart: Model, Make, Measure.

Clinically-available blood pumps and total artificial hearts for pediatric patients continue to lag well behind those developed for adults. We are developing a hybrid, continuous-flow, magnetically levitated, pediatric total artificial heart (TAH). The hybrid TAH design integrates both an axial and centrifugal blood pump within a single, compact housing. The centrifugal pump rotates around the separate axial pump domain, and both impellers rotate around a common central axis. Here, we concentrate our development effort on the centrifugal blood pump by performing computational fluid dynamics (CFD) analysis of the blood flow through the pump. We also conducted transient CFD analyses (quasi-steady and transient rotational sliding interfaces) to assess the pump's dynamic performance conditions. Through modeling, we estimated the pressure generation, scalar stress levels, and fluid forces exerted on the magnetically levitated impellers. To further the development of the centrifugal pump, we also built magnetically-supported prototypes and tested these in an in vitro hydraulic flow loop and via 4-h blood bag hemolytic studies (n = 6) using bovine blood. The magnetically levitated centrifugal prototype delivered 0-6.75 L/min at 0-182 mmHg for 2,750-4,250 RPM. Computations predicted lower pressure-flow performance results than measured by testing; axial and radial fluid forces were found to be <3 N, and mechanical power usage was predicted to be <5 Watts. Blood damage indices (power law weighted exposure time and scalar stress) were <2%. All data trends followed expectations for the centrifugal pump design. Six peaks in the pressure rise were observed in the quasi-steady and transient simulations, correlating to the blade passage frequency of the 6-bladed impeller. The average N.I.H value (n = 6) was determined to be 0.09 ± 0.02 g/100 L, which is higher than desired and must be addressed through design improvement. These data serve as a strong foundation to build upon in the next development phase, whereby we will integrate the axial flow pump component.

Local extensional flows promote long-range fiber alignment in 3D collagen hydrogels.

Randomly oriented type I collagen (COL1) fibers in the extracellular matrix are reorganized by biophysical forces into aligned domains extending several millimeters and with varying degrees of fiber alignment. These aligned fibers can transmit traction forces, guide tumor cell migration, facilitate angiogenesis, and influence tissue morphogenesis. To create aligned COL1 domains in microfluidic cell culture models, shear flows have been used to align thin COL1 matrices (<50µm in height) in a microchannel. However, there has been limited investigation into the role of shear flows in aligning 3D hydrogels (>130µm). Here, we show that pure shear flows do not induce fiber alignment in 3D atelo COL1 hydrogels, but the simple addition of local extensional flow promotes alignment that is maintained across several millimeters, with a degree of alignment directly related to the extensional strain rate. We further advance experimental capabilities by addressing the practical challenge of accessing a 3D hydrogel formed within a microchannel by introducing a magnetically coupled modular platform that can be released to expose the microengineered hydrogel. We demonstrate the platform's capability to pattern cells and fabricate multi-layered COL1 matrices using layer-by-layer fabrication and specialized modules. Our approach provides an easy-to-use fabrication method to achieve advanced hydrogel microengineering capabilities that combine fiber alignment with biofabrication capabilities.

A biomimetic skin phantom for characterizing wearable electrodes in the low-frequency regime.

Advances in the integration of wearable devices in our daily life have led to the development of new electrode designs for biopotential monitoring. Historically, the development and testing of wearable electrodes for the acquisition of biopotential signals has been empirical, relying on experiments on human volunteers. However, the lack of explicit control on human variables, the intra-, and inter-subject variability complicates the understanding of the performance of these wearable electrodes. Herein, phantom mimicking the electrical properties of the skin in the low-frequency range (1 Hz-1000 Hz), which has the potential to be used as a platform for controlled benchtop experiments for testing electrode functionality, is demonstrated. The fabricated phantom comprises two layers representing the deeper tissues and stratum corneum. The lower layer of the phantom mimicking deeper tissues was realized using polyvinyl alcohol cryogel (PVA-c) prepared with 0.9% W/W saline solution by a freeze-thaw technique. The properties of the upper layer representing the stratum corneum were simulated using a 100µm thick layer fabricated by spin-coating a mixture of polydimethylsiloxane (PDMS), 2.5% W/W carbon black (CB) for conductance, and 40% W/W barium titanate (BaTiO3) as a dielectric. The hydration of the stratum corneum was modeled in a controlled way by varying porosity of the phantom's upper layer. Impedance spectroscopy measurements were carried out to investigate the electrical performance of the fabricated phantom and validated against the impedance response obtained across a physiological skin impedance range of five human subjects. The results indicated that the Bode plot depicting the impedance response obtained on the phantom was found to lie in the human skin range. Moreover, it was observed that the change of porosity provides control over the hydration and the phantom can be tuned as per the skin ranges among different individuals. Also, the phantom was able to mimic the impact of dry and hydrated skin on a simulated ECG signal in the time domain. The developed skin phantom is affordable, fairly easy to manufacture, stable over time, and can be used as a platform for benchtop testing of new electrode designs.

The effect of blood viscosity on shear-induced hemolysis using a magnetically levitated shearing device.

INTRODUCTION: Blood contacting medical devices, including rotary blood pumps, can cause shear-induced blood damage that may lead to adverse effects in patients. Due in part to an inadequate understanding of how cell-scale fluid mechanics impact red blood cell membrane deformation and damage, there is currently not a uniformly accepted engineering model for predicting blood damage caused by complex flow fields within ventricular assist devices (VADs). METHODS: We empirically investigated hemolysis in a magnetically levitated axial Couette flow device typical of a rotary VAD. The device is able to accurately control the shear rate and exposure time experienced by blood and to minimize the effects of other uncharacterized stresses. Using this device, we explored the effects of both hematocrit and plasma viscosity on shear-induced hemolysis to characterize blood damage based on the viscosity-independent shear rate, rather than on shear stress. RESULTS: Over a shear rate range of 20 000 - 80 000 1/s, the Index of Hemolysis (IH) was found to be dependent upon and well-predicted by the shear rate alone. IH was independent of hematocrit, bulk viscosity, or the suspension media viscosity and less correlated to shear stress (MSE = 0.46-0.75) than to shear rate (MSE = 0.06-0.09). CONCLUSION: This study recommends that future investigations of shear-induced blood damage report findings with respect to the viscosity-neutral term of shear rate, in addition to the bulk whole blood viscosity measured at an appropriate shear rate relevant to the flow conditions of the device.

Manufacturing Abdominal Aorta Hydrogel Tissue-Mimicking Phantoms for Ultrasound Elastography Validation.

Ultrasound (US) elastography, or elasticity imaging, is an adjunct imaging technique that utilizes sequential US images of soft tissues to measure the tissue motion and infer or quantify the underlying biomechanical characteristics. For abdominal aortic aneurysms (AAA), biomechanical properties such as changes in the tissue's elastic modulus and estimates of the tissue stress may be essential for assessing the need for the surgical intervention. Abdominal aortic aneurysms US elastography could be a useful tool to monitor AAA progression and identify changes in biomechanical properties characteristic of high-risk patients. A preliminary goal in the development of an AAA US elastography technique is the validation of the method using a physically relevant model with known material properties. Here we present a process for the production of AAA tissue-mimicking phantoms with physically relevant geometries and spatially modulated material properties. These tissue phantoms aim to mimic the US properties, material modulus, and geometry of the abdominal aortic aneurysms. Tissue phantoms are made using a polyvinyl alcohol cryogel (PVA-c) and molded using 3D printed parts created using computer aided design (CAD) software. The modulus of the phantoms is controlled by altering the concentration of PVA-c and by changing the number of freeze-thaw cycles used to polymerize the cryogel. The AAA phantoms are connected to a hemodynamic pump, designed to deform the phantoms with the physiologic cyclic pressure and flows. Ultra sound image sequences of the deforming phantoms allowed for the spatial calculation of the pressure normalized strain and the identification of mechanical properties of the vessel wall. Representative results of the pressure normalized strain are presented.

Inter-Laboratory Characterization of the Velocity Field in the FDA Blood Pump Model Using Particle Image Velocimetry (PIV).

PURPOSE: A credible computational fluid dynamics (CFD) model can play a meaningful role in evaluating the safety and performance of medical devices. A key step towards establishing model credibility is to first validate CFD models with benchmark experimental datasets to minimize model-form errors before applying the credibility assessment process to more complex medical devices. However, validation studies to establish benchmark datasets can be cost prohibitive and difficult to perform. The goal of this initiative sponsored by the U.S. Food and Drug Administration is to generate validation data for a simplified centrifugal pump that mimics blood flow characteristics commonly observed in ventricular assist devices. METHODS: The centrifugal blood pump model was made from clear acrylic and included an impeller, with four equally spaced, straight blades, supported by mechanical bearings. Particle Image Velocimetry (PIV) measurements were performed at several locations throughout the pump by three independent laboratories. A standard protocol was developed for the experiments to ensure that the flow conditions were comparable and to minimize systematic errors during PIV image acquisition and processing. Velocity fields were extracted at the pump entrance, blade passage area, back gap region, and at the outlet diffuser regions. A Newtonian blood analog fluid composed of sodium iodide, glycerin, and water was used as the working fluid. Velocity measurements were made for six different pump flow conditions, with the blood-equivalent flow rate ranging between 2.5 and 7 L/min for pump speeds of 2500 and 3500 rpm. RESULTS: Mean intra- and inter-laboratory variabilities in velocity were ~ 10% at the majority of the measurement locations inside the pump. However, the inter-laboratory variability increased to more than ~ 30% in the exit diffuser region. The variability between the three laboratories for the peak velocity magnitude in the diffuser region ranged from 5 to 25%. The bulk velocity field near the impeller changed proportionally with the rotational speed but was relatively unaffected by the pump flow rate. In contrast, flow in the exit diffuser region was sensitive to both the flow rate and the rotational speed. Specifically, at 3500 rpm, the exit jet tilted toward the inner wall of the diffuser at a flow rate of 2.5 L/min, but the jet tilted towards the outer wall when the flow rate was 7 L/min. CONCLUSIONS: Inter-laboratory experimental mean velocity data (and the corresponding variance) were obtained for the FDA pump model and are available for download at https://nciphub.org/wiki/FDA_CFD . Experimental datasets from the inter-laboratory characterization of benchmark flow models, including the blood pump model presented herein and our previous nozzle model, can be used for validating future CFD studies and to collaboratively develop guidelines on best practices for verification, validation, uncertainty quantification, and credibility assessment of CFD simulations in the evaluation of medical devices (e.g. ASME V&V 40 standards working group).

Detecting Regional Stiffness Changes in Aortic Aneurysmal Geometries Using Pressure-Normalized Strain.

Transabdominal ultrasound elasticity imaging could improve the assessment of rupture risk for abdominal aortic aneurysms by providing information on the mechanical properties and stress or strain states of vessel walls. We implemented a non-rigid image registration method to visualize the pressure-normalized strain within vascular tissues and adapted it to measure total strain over an entire cardiac cycle. We validated the algorithm's performance with both simulated ultrasound images with known principal strains and anatomically accurate heterogeneous polyvinyl alcohol cryogel vessel phantoms. Patient images of abdominal aortic aneurysm were also used to illustrate the clinical feasibility of our imaging algorithm and the potential value of pressure-normalized strain as a clinical metric. Our results indicated that pressure-normalized strain could be used to identify spatial variations in vessel tissue stiffness. The results of this investigation were sufficiently encouraging to warrant a clinical study measuring abdominal aortic pressure-normalized strain in a patient population with aneurysmal disease.

Clinical Implications of Physiologic Flow Adjustment in Continuous-Flow Left Ventricular Assist Devices.

There is increasing evidence for successful management of end-stage heart failure with continuous-flow left ventricular assist device (CF-LVAD) technology. However, passive flow adjustment at fixed CF-LVAD speed is susceptible to flow balancing issues as well as adverse hemodynamic effects relating to the diminished arterial pulse pressure and flow. With current therapy, flow cannot be adjusted with changes in venous return, which can vary significantly with volume status. This limits the performance and safety of CF-LVAD. Active flow adjustment strategies have been proposed to improve the synchrony between the pump and the native cardiovascular system, mimicking the Frank-Starling mechanism of the heart. These flow adjustment strategies include modulation by CF-LVAD pump speed by synchrony and maintenance of constant flow or constant pressure head, or a combination of these variables. However, none of these adjustment strategies have evolved sufficiently to gain widespread attention. Herein we review the current challenges and future directions of CF-LVAD therapy and sensor technology focusing on the development of a physiologic, long-term active flow adjustment strategy for CF-LVADs.

FDA Benchmark Medical Device Flow Models for CFD Validation.

Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal's Web site (www.asaiojournal.com) to listen.

A physics based approach to the pulse wave velocity prediction in compliant arterial segments.

Pulse wave velocity (PWV) quantification commonly serves as a highly robust prognostic parameter being used in a preventative cardiovascular therapy. Being dependent on arterial elastance, it can serve as a marker of cardiovascular risk. Since it is influenced by a blood pressure (BP), the pertaining theory can lay the foundation in developing a technique for noninvasive blood pressure measurement. Previous studies have reported application of PWV, measured noninvasively, for both the estimation of arterial compliance and blood pressure, based on simplified physical or statistical models. A new theoretical model for pulse wave propagation in a compliant arterial segment is presented within the framework of pseudo-elastic deformation of biological tissue undergoing finite deformation. An essential ingredient is the dependence of results on nonlinear aspects of the model: convective fluid phenomena, hyperelastic constitutive relation, large deformation and a longitudinal pre-stress load. An exact analytical solution for PWV is presented as a function of pressure, flow and pseudo-elastic orthotropic parameters. Results from our model are compared with published in-vivo PWV measurements under diverse physiological conditions. Contributions of each of the nonlinearities are analyzed. It was found that the totally nonlinear model achieves the best match with the experimental data. To retrieve individual vascular information of a patient, the inverse problem of hemodynamics is presented, calculating local orthotropic hyperelastic properties of the arterial wall. The proposed technique can be used for non-invasive assessment of arterial elastance, and blood pressure using direct measurement of PWV, with account of hyperelastic orthotropic properties.

Pulse Wave Velocity Prediction and Compliance Assessment in Elastic Arterial Segments.

Pressure wave velocity (PWV) is commonly used as a clinical marker of vascular elasticity. Recent studies have increased clinical interest in also analyzing the impact of heart rate, blood pressure, and left ventricular ejection time on PWV. In this article we focus on the development of a theoretical one-dimensional model and validation via direct measurement of the impact of ejection time and peak pressure on PWV using an in vitro hemodynamic simulator. A simple nonlinear traveling wave model was developed for a compliant thin-walled elastic tube filled with an incompressible fluid. This model accounts for the convective fluid phenomena, elastic vessel deformation, radial motion, and inertia of the wall. An exact analytical solution for PWV is presented which incorporates peak pressure, ejection time, ejection volume, and modulus of elasticity. To assess arterial compliance, the solution is introduced in an alternative form, explicitly determining compliance of the wall as a function of the other variables. The model predicts PWV in good agreement with the measured values with a maximum difference of 3.0%. The results indicate an inverse quadratic relationship ([Formula: see text]) between ejection time and PWV, with ejection time dominating the PWV shifts (12%) over those observed with changes in peak pressure (2%). Our modeling and validation results both explain and support the emerging evidence that, both in clinical practice and clinical research, cardiac systolic function related variables should be regularly taken into account when interpreting arterial function indices, namely PWV.

Morphology, Kinematics, and Dynamics: The Mechanics of Suction Feeding in Fishes.

Suction feeding is pervasive among aquatic vertebrates, and our understanding of the functional morphology and biomechanics of suction feeding has recently been advanced by combining experimental and modeling approaches. Key advances include the visualization of the patterns of flow in front of the mouth of a feeding fish, the measurement of pressure inside their mouth cavity, and the employment of analytical and computational models. Here, we review the key components of the morphology and kinematics of the suction-feeding system of anatomically generalized, adult ray-finned fishes, followed by an overview of the hydrodynamics involved. In the suction-feeding apparatus, a strong mechanistic link among morphology, kinematics, and the capture of prey is manifested through the hydrodynamic interactions between the suction flows and solid surfaces (the mouth cavity and the prey). It is therefore a powerful experimental system in which the ecology and evolution of the capture of prey can be studied based on first principals.