A new methodology for determining the central pressure waveform from peripheral measurement using Fourier-based machine learning.

Radial applanation tonometry is a well-established technique for hemodynamic monitoring and is becoming popular in affordable non-invasive wearable healthcare electronics. To assess the central aortic pressure using radial-based measurements, there is an essential need to develop mathematical approaches to estimate the central pressure waveform. In this study, we propose a new Fourier-based machine learning (F-ML) methodology to transfer non-invasive radial pressure measurements to the central pressure waveform. To test the method, collection of tonometry recordings of the radial and carotid pressure measurements are used from the Framingham Heart Study (2640 individuals, 55 % women) with mean (range) age of 66 (40-91) years. Method-derived estimates are significantly correlated with the measured ones for three major features of the pressure waveform (systolic blood pressure, r=0.97, p < 0.001; diastolic blood pressure, r=0.99, p < 0.001; and mean blood pressure, r=0.99, p < 0.001). In all cases, the Bland-Altman analysis shows negligible bias in the estimations and error is bounded to 5.4 mmHg. Findings also suggest that the F-ML approach reconstructs the shape of the central pressure waveform accurately with the average normalized root mean square error of 5.5 % in the testing population which is blinded to all stages of machine learning development. The results show that the F-ML transfer function outperforms the conventional generalized transfer function, particularly in terms of reconstructing the shape of the central pressure waveform morphology. The proposed F-ML transfer function can provide accurate estimates for the central pressure waveform, and ultimately expand the usage of non-invasive devices for central hemodynamic assessment.

Assessing pressure wave components for aortic stiffness monitoring through spectral regression learning.

Aims: The ageing process notably induces structural changes in the arterial system, primarily manifesting as increased aortic stiffness, a precursor to cardiovascular events. While wave separation analysis is a robust tool for decomposing the components of blood pressure waveform, its relationship with cardiovascular events, such as aortic stiffening, is incompletely understood. Furthermore, its applicability has been limited due to the need for concurrent measurements of pressure and flow. Our aim in this study addresses this gap by introducing a spectral regression learning method for pressure-only wave separation analysis. Methods and results: Leveraging data from the Framingham Heart Study (2640 individuals, 55% women), we evaluate the accuracy of pressure-only estimates, their interchangeability with a reference method based on ultrasound-derived flow waves, and their association with carotid-femoral pulse wave velocity (PWV). Method-derived estimates are strongly correlated with the reference ones for forward wave amplitude ( R 2 = 0.91 ), backward wave amplitude ( R 2 = 0.88 ), and reflection index ( R 2 = 0.87 ) and moderately correlated with a time delay between forward and backward waves ( R 2 = 0.38 ). The proposed pressure-only method shows interchangeability with the reference method through covariate analysis. Adjusting for age, sex, body size, mean blood pressure, and heart rate, the results suggest that both pressure-only and pressure-flow evaluations of wave separation parameters yield similar model performances for predicting carotid-femoral PWV, with forward wave amplitude being the only significant factor (P < 0.001; 95% confidence interval, 0.056-0.097). Conclusion: We propose an interchangeable pressure-only wave separation analysis method and demonstrate its clinical applicability in capturing aortic stiffening. The proposed method provides a valuable non-invasive tool for assessing cardiovascular health.

Validation of a Suprasystolic Cuff System for Static and Dynamic Representation of the Central Pressure Waveform.

BACKGROUND: Noninvasive pulse waveform analysis is valuable for central cardiovascular assessment, yet controversies persist over its validity in peripheral measurements. Our objective was to compare waveform features from a cuff system with suprasystolic blood pressure hold with an invasive aortic measurement. METHODS AND RESULTS: This study analyzed data from 88 subjects undergoing concurrent aortic catheterization and brachial pulse waveform acquisition using a suprasystolic blood pressure cuff system. Oscillometric blood pressure (BP) was compared with invasive aortic systolic BP and diastolic BP. Association between cuff and catheter waveform features was performed on a set of 15 parameters inclusive of magnitudes, time intervals, pressure-time integrals, and slopes of the pulsations. The evaluation covered both static (subject-averaged values) and dynamic (breathing-induced fluctuations) behaviors. Peripheral BP values from the cuff device were higher than catheter values (systolic BP-residual, 6.5 mm Hg; diastolic BP-residual, 12.4 mm Hg). Physiological correction for pressure amplification in the arterial system improved systolic BP prediction (r2=0.83). Dynamic calibration generated noninvasive BP fluctuations that reflect those invasively measured (systolic BP Pearson R=0.73, P<0.001; diastolic BP Pearson R=0.53, P<0.001). Static and dynamic analyses revealed a set of parameters with strong associations between catheter and cuff (Pearson R>0.5, P<0.001), encompassing magnitudes, timings, and pressure-time integrals but not slope-based parameters. CONCLUSIONS: This study demonstrated that the device and methods for peripheral waveform measurements presented here can be used for noninvasive estimation of central BP and a subset of aortic waveform features. These results serve as a benchmark for central cardiovascular assessment using suprasystolic BP cuff-based devices and contribute to preserving system dynamics in noninvasive measurements.

A Pneumatic Low-Pass Filter for High-Fidelity Cuff-Based Pulse Waveform Acquisition.

Cuff-based pulse waveform acquisition (CBPWA) devices are reliable solutions for non-invasive cardiovascular diagnostics. However, poor signal resolution has limited clinical applications. This study aims to demonstrate the improved signal quality of CBPWA devices by implementing passive pneumatic low-pass filters (pLPF). Conventionally, pressure sensor output resolution is a percentage of the operating range. Therefore, measurement of small pressure changes in a large range must sacrifice signal resolution to accommodate for the large mean pressures. We design a pLPF to obtain the running mean pressure and combine it with a high-resolution differential pressure sensor for isolating the signal's pulsatile component. Thirty-one volunteers participated in a device proof-of-concept study at Caltech. Volunteers were measured at rest in the supine position on the left arm. The filtering behavior is mathematically modeled and experimentally verified, showing good agreement between measured and predicted cutoff frequencies. In the human study, the device successfully captured high-fidelity pulse waveform measurements for all volunteers: a blood pressure (BP) reading was followed by inflate-and-hold acquisition in diastolic BP (DBP), mean arterial pressure (MAP), and supra systolic BP (sSBP). The study demonstrated the reliability and high signal resolution of pLPF for CBPWA. Considering the widespread use of the brachial cuff, a system for high-resolution CBPWA motivates the clinical implementation of non-invasive pulse waveform analysis (PWA).

Multi-Modal Mobility Morphobot (M4) with appendage repurposing for locomotion plasticity enhancement.

Robot designs can take many inspirations from nature, where there are many examples of highly resilient and fault-tolerant locomotion strategies to navigate complex terrains by recruiting multi-functional appendages. For example, birds such as Chukars and Hoatzins can repurpose wings for quadrupedal walking and wing-assisted incline running. These animals showcase impressive dexterity in employing the same appendages in different ways and generating multiple modes of locomotion, resulting in highly plastic locomotion traits which enable them to interact and navigate various environments and expand their habitat range. The robotic biomimicry of animals' appendage repurposing can yield mobile robots with unparalleled capabilities. Taking inspiration from animals, we have designed a robot capable of negotiating unstructured, multi-substrate environments, including land and air, by employing its components in different ways as wheels, thrusters, and legs. This robot is called the Multi-Modal Mobility Morphobot, or M4 in short. M4 can employ its multi-functional components composed of several actuator types to (1) fly, (2) roll, (3) crawl, (4) crouch, (5) balance, (6) tumble, (7) scout, and (8) loco-manipulate. M4 can traverse steep slopes of up to 45 deg. and rough terrains with large obstacles when in balancing mode. M4 possesses onboard computers and sensors and can autonomously employ its modes to negotiate an unstructured environment. We present the design of M4 and several experiments showcasing its multi-modal capabilities.

The Influence of Valve Leaflet Stiffness Variability on Aortic Wall Shear Stress.

Aortic stenosis is a common cardiac condition that impacts the aorta's hemodynamics downstream of the affected valve. We sought to better understand how non-uniform stiffening of a stenotic aortic valve would affect the wall shear stress (WSS) experienced by the walls of the aorta and the residence time near the valve. Several experimental configurations were created by individually stiffening leaflets of a polymer aortic valve. These configurations were mounted inside an in vitro experimental setup. Digital particle image velocimetry (DPIV) was used to measure velocity profiles inside a model aorta. The DPIV results were used to estimate the WSS and residence time. Our analysis suggests that leaflet asymmetry greatly affects the amount of WSS by vectoring the systolic jet and stiffened leaflets have an increased residence time. This study indicates that valve leaflets with different stiffness conditions can have a more significant impact on wall shear stress than stenosis caused by the uniform increase in all three leaflets (and the subsequent increased systolic velocity) alone. This finding is promising for creating customizable (patient-specific) prosthetic heart valves tailored to individual patients.

Intrinsic Frequencies of Carotid Pressure Waveforms Predict Heart Failure Events: The Framingham Heart Study.

Intrinsic frequencies (IFs) derived from arterial waveforms are associated with cardiovascular performance, aging, and prevalent cardiovascular disease (CVD). However, prognostic value of these novel measures is unknown. We hypothesized that IFs are associated with incident CVD risk. Our sample was drawn from the Framingham Heart Study Original, Offspring, and Third Generation Cohorts and included participants free of CVD at baseline (N=4700; mean age 52 years, 55% women). We extracted 2 dominant frequencies directly from a series of carotid pressure waves: the IF of the coupled heart and vascular system during systole (ω1) and the IF of the decoupled vasculature during diastole (ω2). Total frequency variation (Δω) was defined as the difference between ω1 and ω2. We used Cox proportional hazards regression models to relate IFs to incident CVD events during a mean follow-up of 10.6 years. In multivariable models adjusted for CVD risk factors, higher ω1 (hazard ratio [HR], 1.14 [95% CI], 1.03-1.26]; P=0.01) and Δω (HR, 1.16 [95% CI, 1.03-1.30]; P=0.02) but lower ω2 (HR, 0.87 [95% CI, 0.77-0.99]; P=0.03) were associated with higher risk for incident composite CVD events. In similarly adjusted models, higher ω1 (HR, 1.23 [95% CI, 1.07-1.42]; P=0.004) and Δω (HR, 1.26 [95% CI, 1.05-1.50]; P=0.01) but lower ω2 (HR, 0.81 [95% CI, 0.66-0.99]; P=0.04) were associated with higher risk for incident heart failure. IFs were not significantly associated with incident myocardial infarction or stroke. Novel IFs may represent valuable markers of heart failure risk in the community.

Thermal Effects on Fluid Mixing in the Eye.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the developed world. Wet AMD can be managed through serial intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. However, sometimes the treatment is ineffective. Given that the half-life of the drug is limited, inefficient mixing of the injected drug in the vitreous chamber of the eye may contribute to the ineffectiveness. Here, we introduce thermal heating as a means of enhancing the mixing-process in the vitreous chamber and investigate parameters that potentially influence its effectiveness. Our in vitro studies reveal the importance of the heating location on the eye. A significant increase in the mixing and delivery of drugs to the targeted area (the macula) could be achieved by placing heating pads to induce a current, against gravity, in the vitreous. The presented results can potentially help in the development of a better strategy for intravitreal injection, subsequently improving the quality of patient care.

Honeybees use their wings for water surface locomotion.

Honeybees display a unique biolocomotion strategy at the air-water interface. When water's adhesive force traps them on the surface, their wetted wings lose ability to generate aerodynamic thrust. However, they adequately locomote, reaching a speed up to 3 body lengths·s-1 Honeybees use their wetted wings as hydrofoils for their water surface propulsion. Their locomotion imparts hydrodynamic momentum to the surrounding water in the form of asymmetric waves and a deeper water jet stream, generating ∼20-µN average thrust. The wing kinematics show that the wing's stroke plane is skewed, and the wing supinates and pronates during its power and recovery strokes, respectively. The flow under a mechanical model wing mimicking the motion of a bee's wing further shows that nonzero net horizontal momentum is imparted to the water, demonstrating net thrust. Moreover, a periodic acceleration and deceleration of water are observed, which provides additional forward movement by "recoil locomotion." Their water surface locomotion by hydrofoiling is kinematically and dynamically distinct from surface skimming [J. H. Marden, M. G. Kramer, Science 266, 427-430 (1994)], water walking [J. W. M. Bush, D. L. Hu, Annu. Rev. Fluid Mech. 38, 339-369 (2006)], and drag-based propulsion [J. Voise, J. Casas, J. R. Soc. Interface 7, 343-352 (2010)]. It is postulated that the ability to self-propel on a water surface may increase the water-foraging honeybee's survival chances when they fall on the water.

Experimental trajectory optimization of a flapping fin propulsor using an evolutionary strategy.

The experimental optimization of bio-inspired flapping fin trajectories are demonstrated for potential applications as a side or a rear propulsor of an autonomous underwater vehicle. The trajectories are scored based upon their difference from a force set-point and upon their efficiency and are parameterized by 10 variables inspired by fish swimming. The flapping fin is a generic rectangular rigid flat plate with a tapered edge. Optimization occurs as follows. First, a generation of trajectories is created. Second, the trajectories are executed by a spherical parallel manipulator, during which the forces are acquired. Third, the trajectories are scored and a new generation of trajectories is created using the covariance matrix adaptive evolutionary strategy. This loop repeats ad-infinitum until the search converges. Within the first set of searches, two trajectories for optimal side-force generation are found, one is fully three-dimensional while the other is artificially constrained to a line, and one trajectory for optimal thrust generation is found. All searches demonstrate good convergence properties and match the desired force set-point almost immediately. Additional generations primarily improve the efficiency of the maneuver. The two trajectories for generating side-force have a similar efficiency, which shows potential in utilizing a simple trajectory limited to a line. Comparison between the trajectories for generating side-force and thrust suggests that side-force generation is more efficient around Re ~1000, based on the average tip velocity and length of the fin. The second set of searches explores the behavior of the optimal trajectories for generating side-force at a lower force set-point and the third set of searches explores the sensitivity and repeatability of the optimization.

Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer.

Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardiography for assessment of cardiac function [left ventricular ejection fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference).Experimental Design: Cross-sectional study design was used. Concurrent evaluation of EF was performed using Vivio, two-dimensional (2D) echocardiography, and CMR. Differences in mean EF (2D echocardiography vs. CMR; Vivio vs. CMR) were compared using Bland-Altman plots. Linear regression was used to evaluate proportional bias.Results: A total of 191 consecutive survivors participated [50.7% female; median time from diagnosis: 15.8 years (2-44); median anthracycline dose: 225 mg/m2 (25-642)]. Echocardiography overestimated mean EF by 4.9% (P < 0.001); linear regression analysis confirmed a proportional bias, when compared with CMR (t = 3.1, P < 0.001). There was no difference between mean EF derived from Vivio and from CMR (-0.2%, P = 0.68). The detection of cardiac dysfunction via echocardiography was poor when compared with CMR [Echo EF < 45% (sensitivity 14.3%), Echo EF < 50% (sensitivity 28.6%)]. Sensitivity was substantially better for Vivio-based measurements [EF < 45% or EF < 50% (sensitivity 85.7%)].Conclusions: This accessible technology has the potential to change the day-to-day practice of clinicians caring for the large number of patients diagnosed with cardiac dysfunction and heart failure each year, allowing real-time monitoring and management of their disease without the lag-time between imaging and interpretation of results. Clin Cancer Res; 24(13); 3119-25. ©2018 AACR.

Asymmetry in the jet opening: underwater jet vectoring mechanism by dragonfly larvae.

Aquatic Anisopteran dragonfly larvae achieve respiration and propulsion by repetitive water jets flowing through their anal openings. Previous studies have shown that the tri-leaflet anal valves modulate the emerging jet by varying the opening size. We discovered that the valves are also capable of controlling the opening asymmetry by independent retraction of a leaflet. This study shows the effects of their valve asymmetry control on the respiratory and propulsive flows. Furthermore, the effects of size variation are re-evaluated using fluid momentum and power equations. Synchronized dual cameras recorded the valve movement and the flow generated by Aeshnidae sp. During the respiratory jetting, retraction of a single leaflet positions the opening in an off-centred locale, from which diagonally deflected jets emerge. The resulting flow field, together with the opening size modulation, implicates a reduction in the reinhalation of the exhaled jet and partial powering of the refilling process. Instead, during the propulsive jetting, concurrent partial retraction of the three leaflets results in the centred opening. The resulting jet flows straight, which has an implication for lowering form drag. Additionally, the propulsive aperture size control suggests improved thrust production. Our study highlights the significant influence that an asymmetrically positioned jet opening can have on biological jet flow. The findings inspire a new mechanism for jet vectoring that may prove useful for application in the broader engineering field.

Experimental Investigation of the Effect of Non-Newtonian Behavior of Blood Flow in the Fontan Circulation.

The Fontan procedure for univentricular heart defects creates a unique circulation where all pulmonary blood flow is passively supplied directly from systemic veins. Computational simulations, aimed at optimizing the surgery, have assumed blood to be a Newtonian fluid without evaluating the potential error introduced by this assumption. We compared flow behavior between a non-Newtonian blood analog (0.04% xanthan gum) and a control Newtonian fluid (45% glycerol) in a simplified model of the Fontan circulation. Particle image velocimetry was used to examine flow behavior at two different cardiac outputs and two caval blood flow distributions. Pressure and flow rates were measured at each inlet and outlet. Velocity, shear strain, and shear stress maps were derived from velocity data. Power loss was calculated from pressure, flow, and velocity data. Power loss was increased in all test conditions with xanthan gum vs. glycerol (mean 10±2.9% vs. 5.6±1.3%, p=0.032). Pulmonary blood flow distribution differed in all conditions, more so at low cardiac output. Caval blood flow mixing patterns and shear stress were also qualitatively different between the solutions in all conditions. We conclude that assuming blood to be a Newtonian fluid introduces considerable error into simulations of the Fontan circulation, where low-shear flow predominates.

On the role of tip curvature on flapping plates.

During the flapping motion of a fish's tail, the caudal fin exhibits antero-posterior bending and dorso-ventral bending, the latter of which is referred to as chord-wise bending herein. The impact of chord-wise tip curvature on the hydrodynamic forces for flapping plates is investigated to explore potential mechanisms to improve the maneuverability or the performance of autonomous underwater vehicles. First, actuated chord-wise tip curvature is explored. Comparison of rigid curved geometries to a rigid flat plate as a baseline suggests that an increased curvature decreases the generated forces. An actuated plate with a dynamic tip curvature is created to illustrate a modulation of this decrease in forces. Second, the impact of curvature is isolated using curved plates with an identical planform area. Comparison of rigid curved geometries as a baseline corroborates the result that an increased curvature decreases the generated forces, with the exception that presenting a concave geometry into the flow increases the thrust and the efficiency. A passively-actuated plate is designed to capitalize on this effect by presenting a concave geometry into the flow throughout the cycle. The dynamically and passively actuated plates show potential to improve the maneuverability and the efficiency of autonomous underwater vehicles, respectively.

Toroidal plasmoid generation via extreme hydrodynamic shear.

Saint Elmo's fire and lightning are two known forms of naturally occurring atmospheric pressure plasmas. As a technology, nonthermal plasmas are induced from artificially created electromagnetic or electrostatic fields. Here we report the observation of arguably a unique case of a naturally formed such plasma, created in air at room temperature without external electromagnetic action, by impinging a high-speed microjet of deionized water on a dielectric solid surface. We demonstrate that tribo-electrification from extreme and focused hydrodynamic shear is the driving mechanism for the generation of energetic free electrons. Air ionization results in a plasma that, unlike the general family, is topologically well defined in the form of a coherent toroidal structure. Possibly confined through its self-induced electromagnetic field, this plasmoid is shown to emit strong luminescence and discrete-frequency radio waves. Our experimental study suggests the discovery of a unique platform to support experimentation in low-temperature plasma science.

Noninvasive iPhone Measurement of Left Ventricular Ejection Fraction Using Intrinsic Frequency Methodology.

OBJECTIVE: The study is based on previously reported mathematical analysis of arterial waveform that extracts hidden oscillations in the waveform that we called intrinsic frequencies. The goal of this clinical study was to compare the accuracy of left ventricular ejection fraction derived from intrinsic frequencies noninvasively versus left ventricular ejection fraction obtained with cardiac MRI, the most accurate method for left ventricular ejection fraction measurement. DESIGN: After informed consent, in one visit, subjects underwent cardiac MRI examination and noninvasive capture of a carotid waveform using an iPhone camera (The waveform is captured using a custom app that constructs the waveform from skin displacement images during the cardiac cycle.). The waveform was analyzed using intrinsic frequency algorithm. SETTING: Outpatient MRI facility. SUBJECTS: Adults able to undergo MRI were referred by local physicians or self-referred in response to local advertisement and included patients with heart failure with reduced ejection fraction diagnosed by a cardiologist. INTERVENTIONS: Standard cardiac MRI sequences were used, with periodic breath holding for image stabilization. To minimize motion artifact, the iPhone camera was held in a cradle over the carotid artery during iPhone measurements. MEASUREMENTS AND MAIN RESULTS: Regardless of neck morphology, carotid waveforms were captured in all subjects, within seconds to minutes. Seventy-two patients were studied, ranging in age from 20 to 92 years old. The main endpoint of analysis was left ventricular ejection fraction; overall, the correlation between ejection fraction-iPhone and ejection fraction-MRI was 0.74 (r = 0.74; p < 0.0001; ejection fraction-MRI = 0.93 × [ejection fraction-iPhone] + 1.9). CONCLUSIONS: Analysis of carotid waveforms using intrinsic frequency methods can be used to document left ventricular ejection fraction with accuracy comparable with that of MRI. The measurements require no training to perform or interpret, no calibration, and can be repeated at the bedside to generate almost continuous analysis of left ventricular ejection fraction without arterial cannulation.

Analyzing the effect of geometric factors on designing neutron radiography system.

Neutron radiography is one of the main applications of research reactors. It is a powerful tool to conduct nondestructive testing of materials. The parameters that affect the quality of a radiographic image must be considered during the design of a neutron radiography system. Hence, this study aims to investigate the effect of geometric factors on the quality of the neutron radiography system. The results show that the performance of the mentioned system can be increased by regulating the geometric factors.