Computational Study on the Effects of Valve Orientation on the Hemodynamics and Leaflet Dynamics of Bioprosthetic Pulmonary Valves.

Pulmonary valves do not display a fibrous annulus as do other valves in the heart; thus, pulmonary valves can be implanted at multiple orientations and locations within the right ventricular outflow tract (RVOT). This gives surgeons more freedom when implanting the valve but it also results in uncertainties regarding placement, particularly with respect to valve orientation. We investigate the pulmonary artery hemodynamics and valve leaflet dynamics of PVRs with various orientations via fluid-structure interaction models. A canonical model of the branching pulmonary artery is coupled with a dynamic model of a pulmonary valve and from this, we quantify the effect of valve implant orientation on the post-valvular hemodynamics and leaflet dynamics. Metrics such as turbulent kinetic energy, branch pulmonary artery flow distributions, projected valve opening area, and pressure differentials across the valve leaflets are analyzed. Our results indicate that off-axis orientation results in higher pressure forces and flow and energy asymmetry, which potentially have implications for long term durability of implanted bioprosthetic valves.

Effect of schooling on flow generated sounds from carangiform swimmers.

Computational models are used to examine the effect of schooling on flow generated noise from fish swimming using their caudal fins. We simulate the flow as well as the far-field hydrodynamic sound generated by the time-varying pressure loading on these carangiform swimmers. The effect of the number of swimmers in the school, the relative phase of fin flapping of the swimmers, and their spatial arrangement is examined. The simulations indicate that the phase of the fin flapping is a dominant factor in the total sound radiated into the far-field by a group of swimmers. For small schools, a suitable choice of relative phase between the swimmers can significantly reduce the overall intensity of the sound radiated to the far-field. The relative positioning of the swimmers is also shown to have an impact on the total radiated noise. For a larger school, even highly uncorrelated phases of fin movement between the swimmers in the school are very effective in significantly reducing the overall intensity of sound radiated into the far-field. The implications of these findings for fish ethology as well as the design and operation of bioinspired vehicles are discussed.

Changes in aorta hemodynamics in Left-Right Type 1 bicuspid aortic valve patients after replacement with bioprosthetic valves: An in-silico study.

Bicuspid aortic valve (BAV) is the most common cardiac congenital abnormality with a high rate of concomitant aortic valve and ascending aorta (AAo) pathologic changes throughout the patient's lifetime. The etiology of BAV-related aortopathy was historically believed to be genetic. However, recent studies theorize that adverse hemodynamics secondary to BAVs also contribute to aortopathy, but their precise role, specifically, that of wall shear stress (WSS) magnitude and directionality remains controversial. Moreover, the primary therapeutic option for BAV patients is aortic valve replacement (AVR), but the role of improved post-AVR hemodynamics on aortopathy progression is also not well-understood. To address these issues, this study employs a computational fluid dynamics model to simulate personalized AAo hemodynamics before and after TAVR for a small cohort of 6 Left-Right fused BAV patients. Regional distributions of five hemodynamic metrics, namely, time-averaged wall shear stress (TAWSS) and oscillating shear index (OSI), divergence of wall shear (DWSS), helicity flux integral & endothelial cell activation potential (ECAP), which are hypothesized to be associated with potential aortic injury are computed in the root, proximal and distal ascending aorta. BAVs are characterized by strong, eccentric jets, with peak velocities exceeding 4 m/s and axially circulating flow away from the jets. Such conditions result in focused WSS loading along jet attachment regions on the lumen boundary and weaker, oscillating WSS on other regions. The jet attachment regions also show alternating streaks of positive and negative DWSS, which may increase risk for local tissue stretching. Large WSS magnitudes, strong helical flows and circumferential WSS have been previously implicated in the progression of BAV aortopathy. Post-intervention hemodynamics exhibit weaker, less eccentric jets. Significant reductions are observed in flow helicity, TAWSS and DWSS in localized regions of the proximal AAo. On the other hand, OSI increases post-intervention and ECAP is observed to be low in both pre- and post-intervention scenarios, although significant increases are also observed in this ECAP. These results indicate a significant alleviation of pathological hemodynamics post AVR.

In silico modelling of the effect of pyloric intervention procedures on gastric flow and emptying in a stomach with gastroparesis.

Pyloric interventions are surgical procedures employed to increase the gastric emptying rate in gastroparesis patients. In this study, we use an in silico model to investigate the consequences of pyloric intervention on gastric flow and emptying for two phenotypes of gastroparesis: antral hypomotility and decreased gastric tone. The transpyloric pressure gradient predicted by the in silico model, based on viscous fluid flow equations, is compared against in vivo measurements. Both phenotypes exhibit a similar pre-procedural emptying rate reduction, but after pyloric surgery, antral hypomotility case with preserved gastric tone shows significant improvements in emptying rates, up to 131%, accompanied by bile reflux from the duodenum into the stomach. Conversely, severely reduced gastric tone cases exhibited a post-procedural reduction in the net emptying rate due to the relatively larger bile reflux. In cases with a combination of antral hypomotility and reduced gastric tone, post-procedural improvements were observed only when both conditions were mild. Our findings highlight the pivotal role of the relative increase in pyloric orifice diameter in determining post-operative emptying rates. The study suggests a possible explanation for the selective response of patients toward these procedures and underscores the potential of in silico modelling to generate valuable insights to inform gastric surgery.

Pancreatic duct pressure: A review of technical aspects and clinical significance.

Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP.

Reconstructing the pressure field around swimming fish using a physics-informed neural network.

Fish detect predators, flow conditions, environments and each other through pressure signals. Lateral line ablation is often performed to understand the role of pressure sensing. In the present study, we propose a non-invasive method for reconstructing the instantaneous pressure field sensed by a fish's lateral line system from two-dimensional particle image velocimetry (PIV) measurements. The method uses a physics-informed neural network (PINN) to predict an optimized solution for the pressure field near and on the fish's body that satisfies both the Navier-Stokes equations and the constraints put forward by the PIV measurements. The method was validated using a direct numerical simulation of a swimming mackerel, Scomber scombrus, and was applied to experimental data of a turning zebrafish, Danio rerio. The results demonstrate that this method is relatively insensitive to the spatio-temporal resolution of the PIV measurements and accurately reconstructs the pressure on the fish's body.

Towards Longitudinal Monitoring of Leaflet Mobility in Prosthetic Aortic Valves via In-Situ Pressure Sensors: In-Silico Modeling and Analysis.

BACKGROUND: Transcatheter aortic valves (TAVs) are susceptible to leaflet thrombosis which may lead to thromboembolic events, and early detection and intervention are believed to be the key to avoiding such adverse outcomes. An embedded sensor system installed on the valve stent, coupled with an appropriate machine learning-based continuous monitoring algorithm can facilitate early detection to predict severity of reduced leaflet motion (RLM) and avoid adverse outcomes. METHODS: We present a data-driven, in silico, proof-of-concept analysis of a pressure microsensor based system for quantifying RLM in TAVs. We generate a dataset of 21 high-fidelity transvalvular flow simulations with healthy and mildly stenotic TAVs to train a logistic regression model to correlate individual leaflet mobility in each simulation with principal components of corresponding hemodynamic pressure recorded at strategic locations of the TAV stent. A separate test dataset of 7 simulations is also generated for prospective assessment of model performance. RESULTS: An array of 6 sensors embedded on the TAV stent, with two sensors tracking individual leaflet, successfully correlates leaflet mobility with recorded pressure. The sensors are placed along leaflet centerlines, one in the sinus, and the other at the sino-tubular junction. The regression model is tuned using cross-validation to achieve high accuracy on both training (R2 = 0.93) and test (R2 = 0.77) sets. CONCLUSION: Discrete blood pressure recordings on TAV stents can be successfully correlated with individual leaflet mobility. Further development of this technology can enable longitudinal monitoring of TAVs and early detection of valve failure.

Quantifying the Effect of Body Habitus on Cardiac Auscultation Via Computational Hemoacoustics.

The effect of body habitus on auscultation of heart murmurs is investigated via computational hemoacoustic modeling. The source of the heart murmur is first obtained from a hemodynamic simulation of blood flow through a stenosed aortic valve. This sound source is then placed at the aortic valve location in four distinct human thorax models, and the propagation of the murmur in each thorax model is simulated by solving the elastic wave equations in the time-domain. Placing the same sound source in different thorax models allows for the disambiguation of the effect of body habitus on cardiac auscultation. The surface acceleration resulting from the murmur on each subject's chest surface shows that subjects with higher body-mass index and thoracic cross-sectional area yield smaller acceleration values for the S1 sound. Moreover, the spectral analysis of the signal shows that slope from linear regression in the normal heart sound frequency range (10-150 Hz) is larger for children at the aortic, pulmonic, and mitral auscultation points compared to that for adults. The slope in the murmur frequency range (150-400 Hz) was larger for female subjects at the mitral point compared to that for male subjects. The trends from the results show the potential of the proposed computational method to provide quantitative insights regarding the effect of various anatomical factors on cardiac auscultation.

Effect of stomach motility on food hydrolysis and gastric emptying: Insight from computational models.

The peristaltic motion of stomach walls combines with the secretion of digestive enzymes to initiate the process that breaks down food. In this study, the mixing, breakdown, and emptying of a liquid meal containing protein is simulated in a model of a human stomach. In this model, pepsin, the gastric enzyme responsible for protein hydrolysis, is secreted from the proximal region of the stomach walls and allowed to react with the contents of the stomach. The velocities of the retropulsive jet induced by the peristaltic motion, the emptying rate, and the extent of hydrolysis are quantified for a control case as well as for three other cases with reduced motility of the stomach, which may result from conditions such as diabetes mellitus. This study quantifies the effect of stomach motility on the rate of food breakdown and its emptying into the duodenum and we correlate these observations with the mixing in the stomach induced by the wall motion.

Improved swimming performance in schooling fish via leading-edge vortex enhancement.

The hydrodynamics of schooling fish has been the subject of continued investigation over the last 50 years; fish schools exhibit a variety of arrangements and several distinct mechanisms have been proposed to explain the hydrodynamic benefits of schooling. In the current study, we use direct numerical simulations to show that a caudal fin swimmer trailing another similar swimmer can significantly improve its swimming performance by positioning itself such that the wake-induced flow of the leading fish, enhances the leading-edge vortex (LEV) on the fin of the trailing fish. Improvements of up to 12% in both the thrust and efficiency of the trailing fish are possible with this mechanism. The mechanisms underlying these interactional effects are quantitatively analyzed by applying the force partitioning method, a powerful data-driven method that partitions the pressure forces on the fish into mechanistically distinct components. The analysis reveals that the LEV on the fin dominates the overall thrust production for these swimmers and its enhancement therefore provides an effective and robust means for harnessing fish-fish hydrodynamic interactions in a school. In addition to confirming the potential energetic benefits of schooling, the LEV enhancement mechanism could be exploited in coordinated swimming of bioinspired multi-vehicle or multi-foil flapping foil propulsion systems.

In vitro assessment of the biocompatibility of chemically treated silicone materials with human lens epithelial cells.

Cytotoxicity testing is a regulatory requirement for safety testing of new ocular implants. In vitro toxicity tests determine whether toxic chemicals are present on a material surface or leach out of the material matrix. A method of evaluating the cytotoxicity of ocular implants was developed using fluorescent viability dyes. To assess the assay's sensitivity in detecting toxic substances on biomaterials, zinc diethydithiocarbamate (ZDEC) and benzalkonium chloride (BAK) were deposited on silicone surfaces at different concentrations. Human lens epithelial cells (HLEC) were added to the surface of these treated silicone surfaces and were assessed for viability. The viability of both the adherent and non-adherent cells was determined using confocal microscopy with, annexin V, ethidium homodimer, and calcein. Cell metabolism was also evaluated using resazurin and the release of inflammatory cytokines was quantified using a multiplex Mesoscale Discovery platform. Confocal microscopy was shown to be a sensitive assay for evaluating material toxicity, as significant toxicity (p < 0.05) from ZDEC and BAK-treated surfaces compared to the untreated silicone control was detected. Patterns of cytokine release from cells varied depending on the toxin evaluated and the toxin concentration and did not directly correlate with the reduction in cell metabolic activity measured by alamarBlue.

A Noninvasive Assessment of Flow Based on Contrast Dispersion in Computed Tomography Angiography: A Computational and Experimental Phantom Study.

Transluminal attenuation gradient (TAG), defined as the gradient of the contrast agent attenuation drop along the vessel, is an imaging biomarker that indicates stenosis in the coronary arteries. The transluminal attenuation flow encoding (TAFE) equation is a theoretical platform that quantifies blood flow in each coronary artery based on computed tomography angiography (CTA) imaging. This formulation couples TAG (i.e., contrast dispersion along the vessel) with fluid dynamics. However, this theoretical concept has never been validated experimentally. The aim of this proof-of-principle phantom study is to validate TAFE based on CTA imaging. Dynamic CTA images were acquired every 0.5 s. The average TAFE estimated flow rates were compared against four predefined pump values in a straight (20, 25, 30, 35, and 40 ml/min) and a tapered phantom (25, 35, 45, and 55 ml/min). Using the TAFE formulation with no correction, the flow rates were underestimated by 33% and 81% in the straight and tapered phantoms, respectively. The TAFE formulation was corrected for imaging artifacts focusing on partial volume averaging and radial variation of contrast enhancement. After corrections, the flow rates estimated in the straight and tapered phantoms had an excellent Pearson correlation of r = 0.99 and 0.87 (p < 0.001), respectively, with only a 0.6%±0.2 mL/min difference in estimation of the flow rate. In this proof-of-concept phantom study, we corrected the TAFE formulation and showed a good agreement with the actual pump values. Future clinical validations are needed for feasibility of TAFE in clinical use.

Computational Modeling of Aortic Stenosis With a Reduced Degree-of-Freedom Fluid-Structure Interaction Valve Model.

In this study, a novel reduced degree-of-freedom (rDOF) aortic valve model is employed to investigate the fluid-structure interaction (FSI) and hemodynamics associated with aortic stenosis. The dynamics of the valve leaflets are determined by an ordinary differential equation with two parameters and this rDOF model is shown to reproduce key features of more complex valve models. The hemodynamics associated with aortic stenosis is studied for three cases: a healthy case and two stenosed cases. The focus of the study is to correlate the hemodynamic features with the source generation mechanism of systolic murmurs associated with aortic stenosis. In the healthy case, extremely weak flow fluctuations are observed. However, in the stenosed cases, simulations show significant turbulent fluctuations in the ascending aorta, which are responsible for the generation of strong wall pressure fluctuations after the aortic root mostly during the deceleration phase of the systole. The intensity of the murmur generation increases with the severity of the stenosis, and the source locations for the two diseased cases studied here lie around 1.0 inlet duct diameters (Do) downstream of the ascending aorta.

Prosthetic Valve Monitoring via In Situ Pressure Sensors: In Silico Concept Evaluation using Supervised Learning.

PURPOSE: Patients receiving transcatheter aortic valve replacement (TAVR) can benefit from continuous, longitudinal monitoring of valve prosthesis to prevent leaflet thrombosis-related complications. We present a computational proof-of-concept study of a novel, non-invasive and non-toxic valve monitoring technique for TAVs which uses pressure measurements from microsensors embedded on the valve stent. We perform a data-driven analysis to determine the signal processing and machine learning required to detect reduced mobility in individual leaflets. METHODS: We use direct numerical simulations to describe hemodynamic differences in transvalvular flow in ascending aorta models with healthy and stenotic valves. A Cartesian-grid flow solver and a reduced-order valve model simulate the complex dynamics of blood flow and leaflet motion, respectively. The two-way fluid-structure interaction coupling is achieved using a sharp interface immersed boundary method. RESULTS: From a dataset of 21 simulations, we show leaflets with reduced mobility result in large, asymmetric pressure fluctuations in their vicinity, particularly in the region extending from the aortic sinus to the sino-tubular junction (STJ). We train a linear classifier algorithm by correlating sinus and STJ pressure measurements on the stent surface to individual leaflet status. The algorithm was shown to have >90% accuracy for prospective detection of individual leaflet dysfunction. CONCLUSIONS: We demonstrate that using only two discrete pressure measurements, per leaflet, on the TAV stent, individual leaflet status can be accurately predicted. Such a sensorized TAV system could enable safe and inexpensive detection of prosthetic valve dysfunction.

Detecting Aortic Valve Anomaly From Induced Murmurs: Insights From Computational Hemodynamic Models.

Patients who receive transcatheter aortic valve replacement are at risk for leaflet thrombosis-related complications, and can benefit from continuous, longitudinal monitoring of the prosthesis. Conventional angiography modalities are expensive, hospital-centric and either invasive or employ potentially nephrotoxic contrast agents, which preclude their routine use. Heart sounds have been long recognized to contain valuable information about individual valve function, but the skill of auscultation is in decline due to its heavy reliance on the physician's proficiency leading to poor diagnostic repeatability. This subjectivity in diagnosis can be alleviated using machine learning techniques for anomaly detection. We present a computational and data-driven proof-of-concept analysis of a novel, auscultation-based technique for monitoring aortic valve, which is practical, non-invasive, and non-toxic. However, the underlying mechanisms leading to physiological and pathological heart sounds are not well-understood, which hinders development of such a technique. We first address this by performing direct numerical simulations of the complex interactions between turbulent blood flow in a canonical ascending aorta model and dynamic valve motion in 29 cases with healthy and stenotic valves. Using the turbulent pressure fluctuations on the aorta lumen boundary, we model the propagation of heart sounds, as elastic waves, through the patient's thorax. The heart sound may be recorded on the epidermal surface using a stethoscope/phonocardiograph. This approach allows us to correlate instantaneous hemodynamic phenomena and valve motion with the acoustic response. From this dataset we extract "acoustic signatures" of healthy and stenotic valves based on principal components of the recorded sound. These signatures are used to train a linear discriminant classifier by maximizing correlation between recorded heart sounds and valve status. We demonstrate that this classifier is capable of accurate prospective detection of anomalous valve function and that the principal component-based signatures capture prominent audible features of heart sounds, which have been historically used by physicians for diagnosis. Further development of such technology can enable inexpensive, safe and patient-centric at-home monitoring, and can extend beyond transcatheter valves to surgical as well as native valves.

Determining the Toxicity of UV Radiation and Chemicals on Primary and Immortalized Human Corneal Epithelial Cells.

This article describes the methods of measuring the toxicity of ultraviolet (UV) radiation and ocular toxins on primary (pHCEC) and immortalized (iHCEC) human corneal epithelial cell cultures. Cells were exposed to UV radiation and toxic doses of benzalkonium chloride (BAK), hydrogen peroxide (H2O2), and sodium dodecyl sulfate (SDS). Metabolic activity was measured using a metabolic assay. The release of inflammatory cytokines was measured using a multi-plex interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) assay, and cells were evaluated for viability using fluorescent dyes. The damaging effects of UV on cell metabolic activity and cytokine release occurred at 5 min of UV exposure for iHCEC and 20 min for pHCEC. Similar percent drops in metabolic activity of the iHCEC and pHCEC occurred after exposure to BAK, H2O2, or SDS, and the most significant changes in cytokine release occurred for IL-6 and IL-8. Microscopy of fluorescently stained iHCEC and pHCEC BAK-exposed cells showed cell death at 0.005% BAK exposure, although the degree of ethidium staining was greater in the iHCECs than pHCECs. Utilizing multiple methods of assessing toxic effects using microscopy, assessments of metabolic activity, and cytokine production, the toxicity of UV radiation and chemical toxins could be determined for both primary and immortalized cell lines.

Mosquitoes buzz and fruit flies don't-a comparative aeroacoustic analysis of wing-tone generation.

Crepuscular mosquitoes, which swarm in low light conditions, exhibit a range of adaptations including large aspect-ratio wings, high flapping frequencies and small stroke amplitudes that taken together, facilitate the generation of wing-tones that are well-suited for acoustic communication. In the current study, we employ computational aeroacoustic modeling to conduct a comparative study of wing-tone and flight efficiency in a mosquito (maleCulex) and a similar sized flying insect: a fruit fly (Drosophila). Based on this analysis, we show that pound-for-pound, a mosquito generates wing-tones that are a factor of about 3.4 times more intense than a fruit fly, and the mosquito is more efficient by a factor of about 3.7 in converting mechanical power into acoustic power. The wing-tones for the mosquito are also more tilted in the forward direction, a characteristic that would be more conducive for acoustic signaling during a mate chase. The simulation data also shows that the specific power (mechanical power over mean lift) of the mosquito is nearly equal to that of the fruit fly, indicating that the adaptations that facilitate wing-tone based communication in mosquitoes, do not seem to compromise their flight efficiency.

A computational study of the hemodynamics of bioprosthetic aortic valves with reduced leaflet motion.

We employ a reduced degree-of-freedom aortic valve model to investigate the flow physics associated with early-stage reduced leaflet motion in bioprosthetic aortic valves. The model is coupled with a sharp-interface immersed boundary based incompressible flow solver to efficiently simulate the fluid-structure interaction. A total of 19 cases of flow through aortic valves with varying degrees of reduced leaflet motion (RLM) are considered. The characteristics of the aortic jet and the consequent aorta wall loading patterns are analyzed. Our results show that asymmetric RLM tilts the aortic jet and leads to large reverse and recirculating flow regions downstream from leaflets with restricted mobility. The changes in flow patterns increase wall pressure and shear stress fluctuations, and result in asymmetric oscillating shear on the aorta wall. These findings have implications for auscultation based diagnosis of this condition as well as the health of the aorta.

Flow physics and mixing quality in a confined impinging jet mixer.

Due to their ability to provide efficient mixing at small scales, confined impinging jet mixers (CIJMs) are employed widely in nanoparticle assembly processes such as flash nanoprecipitation and flash nanocomplexation, which require rapid mixing. In this mixing device, two jets from opposite directions impinge directly on each other forming a thin shear layer that breaks down rapidly into small flow structures. This enables effective mixing of the species transported by each jet by drastically reducing the diffusion distance. In the present study, the mixing performance of a commonly used cylindrical CIJM is examined by direct numerical simulations. Analysis of the simulation results indicates that the interaction of the shear layer with the inner walls of the CIJM is critical in inducing a range of instabilities in the impinging jet flow. By examining flow structures, statistical quantities, and metrics, we have characterized and quantified the mixing quality of a binary mixture in the CIJM. Product uniformity in processes such as precipitation and complexation is expected to depend on the residence time of the constituents, and this quantity is also calculated and compared for the cases with different jet Reynolds numbers. The jet Reynolds numbers of Re = 200, 600, and 1000 are considered, and the simulation results show that the CIJM achieves very good mixing for the Re = 600 and Re = 1000 cases. It is also found that the Re = 600 case performs slightly better than the other cases in terms of uniformity of the residence time. These quantitative analyses offer useful insights into the mechanism of nanoparticle size control and uniformity afforded by the unique flow physics and mixing characteristics in the CIJMs.