Characterization of aerosol plumes from singing and playing wind instruments associated with the risk of airborne virus transmission.

The exhalation of aerosols during musical performances or rehearsals posed a risk of airborne virus transmission in the COVID-19 pandemic. Previous research studied aerosol plumes by only focusing on one risk factor, either the source strength or convective transport capability. Furthermore, the source strength was characterized by the aerosol concentration and ignored the airflow rate needed for risk analysis in actual musical performances. This study characterizes aerosol plumes that account for both the source strength and convective transport capability by conducting experiments with 18 human subjects. The source strength was characterized by the source aerosol emission rate, defined as the source aerosol concentration multiplied by the source airflow rate (brass 383 particle/s, singing 408 particle/s, and woodwind 480 particle/s). The convective transport capability was characterized by the plume influence distance, defined as the sum of the horizontal jet length and horizontal instrument length (brass 0.6 m, singing 0.6 m and woodwind 0.8 m). Results indicate that woodwind instruments produced the highest risk with approximately 20% higher source aerosol emission rates and 30% higher plume influence distances compared with the average of the same risk indicators for singing and brass instruments. Interestingly, the clarinet performance produced moderate source aerosol concentrations at the instrument's bell, but had the highest source aerosol emission rates due to high source airflow rates. Flute performance generated plumes with the lowest source aerosol emission rates but the highest plume influence distances due to the highest source airflow rate. Notably, these comprehensive results show that the source airflow is a critical component of the risk of airborne disease transmission. The effectiveness of masking and bell covering in reducing aerosol transmission is due to the mitigation of both source aerosol concentrations and plume influence distances. This study also found a musician who generated approximately five times more source aerosol concentrations than those of the other musicians who played the same instrument. Despite voice and brass instruments producing measurably lower average risk, it is possible to have an individual musician produce aerosol plumes with high source strength, resulting in enhanced transmission risk; however, our sample size was too small to make generalizable conclusions regarding the broad musician population.

4D magnetic resonance flow imaging for estimating pulmonary vascular resistance in pulmonary hypertension.

PURPOSE: To develop an estimate of pulmonary vascular resistance (PVR) using blood flow measurements from 3D velocity-encoded phase contract magnetic resonance imaging (here termed 4D MRI). MATERIALS AND METHODS: In all, 17 patients with pulmonary hypertension (PH) and five controls underwent right heart catheterization (RHC), 4D and 2D Cine MRI (1.5T) within 24 hours. MRI was used to compute maximum spatial peak systolic vorticity in the main pulmonary artery (MPA) and right pulmonary artery (RPA), cardiac output, and relative area change in the MPA. These parameters were combined in a four-parameter multivariate linear regression model to arrive at an estimate of PVR. Agreement between model predicted and measured PVR was also evaluated using Bland-Altman plots. Finally, model accuracy was tested by randomly withholding a patient from regression analysis and using them to validate the multivariate equation. RESULTS: A decrease in vorticity in the MPA and RPA were correlated with an increase in PVR (MPA: R(2) = 0.54, P < 0.05; RPA: R(2) = 0.75, P < 0.05). Expanding on this finding, we identified a multivariate regression equation that accurately estimates PVR (R(2) = 0.94, P < 0.05) across severe PH and normotensive populations. Bland-Altman plots showed 95% of the differences between predicted and measured PVR to lie within 1.49 Wood units. Model accuracy testing revealed a prediction error of ∼20%. CONCLUSION: A multivariate model that includes MPA relative area change and flow characteristics, measured using 4D and 2D Cine MRI, offers a promising technique for noninvasively estimating PVR in PH patients. J. MAGN. RESON. IMAGING 2016;44:914-922.

Vorticity is a marker of right ventricular diastolic dysfunction.

Right ventricular diastolic dysfunction (RVDD) is an important prognostic indicator in pulmonary arterial hypertension (PAH). RV vortex rings have been observed in healthy subjects, but their significance in RVDD is unknown. Vorticity, the local spinning motion of an element of fluid, may be a sensitive measure of RV vortex dynamics. Using four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we investigated the relationship between right heart vorticity with echocardiographic indexes of RVDD. Thirteen (13) PAH subjects and 10 controls underwent same-day 4D flow CMR and echocardiography. RV diastolic function was assessed using trans-tricuspid valve (TV) early (E) and late (A) velocities, E/A ratio, and e' and a' tissue Doppler velocities. RV and right atrial (RA) integrated mean vorticity was calculated for E and A-wave filling periods using 4D datasets. Compared with controls, A-wave vorticity was significantly increased in RVDD subjects in both the RV [2343 (1,559-3,295) vs. 492 (267-2,649) 1/s, P = 0.028] and RA [30 (27-44) vs. 9 (5-27) 1/s, P = 0.005]. RA E vorticity was significantly decreased [13 (7-22) vs. 28 (15-31) 1/s, P = 0.038] in RVDD. E-wave vorticity correlated TV e', E-,and TV E/A (P < 0.05), and A-wave vorticity associated with both TV A and E/A (P < 0.02). RVDD is associated with alterations in E- and A-wave vorticity, and vorticity correlates with multiple echocardiographic markers of RVDD. Vorticity may be a robust noninvasive research tool for the investigation of RV fluid and tissue mechanical interactions in PAH.

Measurements and Simulations of Aerosol Released while Singing and Playing Wind Instruments.

Outbreaks from choir performances, such as the Skagit Valley Choir, showed that singing brings potential risk of COVID-19 infection. There is less known about the risks of airborne infection from other musical performances, such as playing wind instruments or performing theater. In addition, it is important to understand methods that can be used to reduce infection risk. In this study, we used a variety of methods, including flow visualization, aerosol and CO2 measurements, and computational fluid dynamics (CFD) modeling to understand the different components that can lead to transmission risk from musical performance and risk mitigation. This study was possible because of a partnership across academic departments and institutions and collaboration with the National Federation of State High School Associations and the College Band Directors National Association. The interdisciplinary team enabled us to understand the various aspects of aerosol transmission risk from musical performance and to quickly implement strategies in music classrooms during the COVID-19 pandemic. We found that plumes from musical performance were highly directional, unsteady and varied considerably in time and space. Aerosol number concentration measured at the bell of the clarinet was comparable to that of singing. Face and bell masks attenuated plume velocities and lengths and decreased aerosol concentrations measured in front of the masks. CFD modeling showed differences between indoor and outdoor environments and that the lowest risk of airborne COVID-19 infection occurred at less than 30 min of exposure indoors and less than 60 min outdoors.

Development of a custom-designed echo particle image velocimetry system for multi-component hemodynamic measurements: system characterization and initial experimental results.

We have recently developed an ultrasound-based velocimetry technique, termed echo particle image velocimetry (Echo PIV), to measure multi-component velocity vectors and local shear rates in arteries and opaque fluid flows by identifying and tracking flow tracers (ultrasound contrast microbubbles) within these flow fields. The original system was implemented on images obtained from a commercial echocardiography scanner. Although promising, this system was limited in spatial resolution and measurable velocity range. In this work, we propose standard rules for characterizing Echo PIV performance and report on a custom-designed Echo PIV system with increased spatial resolution and measurable velocity range. Then we employed this system for initial measurements on tube flows, rotating flows and in vitro carotid artery and abdominal aortic aneurysm (AAA) models to acquire the local velocity and shear rate distributions in these flow fields. The experimental results verified the accuracy of this technique and indicated the promise of the custom Echo PIV system in capturing complex flow fields non-invasively.

4D Flow Assessment of Vorticity in Right Ventricular Diastolic Dysfunction.

Diastolic dysfunction, a leading cause of heart failure in the US, is a complex pathology which manifests morphological and hemodynamic changes in the heart and circulatory system. Recent advances in time-resolved phase-contrast cardiac magnetic resonance imaging (4D Flow) have allowed for characterization of blood flow in the right ventricle (RV) and right atrium (RA), including calculation of vorticity and qualitative visual assessment of coherent flow patterns. We hypothesize that right ventricular diastolic dysfunction (RVDD) is associated with changes in vorticity and right heart blood flow. This paper presents background on RVDD, and 4D Flow tools and techniques used for quantitative and qualitative analysis of cardiac flows in the normal and disease states. In this study, 20 patients with RVDD and 14 controls underwent cardiac 4D Flow and echocardiography. A method for determining the time-step for peak early diastole using 4D Flow data is described. Spatially integrated early diastolic vorticity was extracted from the RV, RA, and combined RV/RA regions of each subject using a range of vorticity thresholding and scaling methods. Statistically significant differences in vorticity were found in the RA and combined RA/RV in RVDD subjects compared to controls when vorticity vectors were both thresholded and scaled by cardiac index.

Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast Magnetic Resonance Imaging.

Measurement of hemodynamic wall shear stress (WSS) is important in investigating the role of WSS in the initiation and progression of atherosclerosis. Echo particle image velocimetry (echo PIV) is a novel ultrasound-based technique for measuring WSS in vivo that has previously been validated in vitro using the standard optical PIV technique. We evaluated the repeatability and reproducibility of echo PIV for measuring WSS in the human common carotid artery. We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56 ± 12 y). Echo PIV was highly repeatable, with an intra-observer variability of 1.0 ± 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5 dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was reproducible, with a low inter-observer variability (max: 2.0 ± 0.2 dyn/cm2, mean: 1.3 ± 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter-scan (test-retest) variability (max: 7.1 ± 2.3 dyn/cm2, mean: 2.9 ± 0.4 dyn/cm2, min: 1.5 ± 0.1 dyn/cm2). We compared echo PIV with the reference method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p < 0.05). Significant differences were observed in some WSS measurements (echo PIV vs. PC-MRI): WSS at peak systole: 21 ± 7.0 dyn/cm2 vs. 15 ± 5.0 dyn/cm2; time-averaged WSS: 8.9 ± 3.0 dyn/cm2 vs. 7.1 ± 3.0 dyn/cm2 (p < 0.05); WSS at end diastole: 3.8 ± 2.8 dyn/cm2 vs. 3.9 ± 2 dyn/cm2 (p > 0.05). For the first time, we report that echo PIV can measure WSS with good repeatability and reproducibility in adult humans with a broad age range. Echo PIV is feasible in humans and offers an easy-to-use, ultrasound-based, quantitative technique for measuring WSS in vivo in humans with good repeatability and reproducibility.

Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension.

Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m(2); P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = -0.74, P < 0.001), mean pulmonary pressure (ρ = -0.64, P = 0.006), and elastance (ρ = -0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = -0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR-based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH.

Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension.

Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e'). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = -0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e' (Rho = 0.63, P = 0.001), and lateral e' (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e' (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency.

Extraction of pulmonary vascular compliance, pulmonary vascular resistance, and right ventricular work from single-pressure and Doppler flow measurements in children with pulmonary hypertension: a new method for evaluating reactivity: in vitro and clinical studies.

BACKGROUND: Current evaluation of pulmonary hypertension (PH) in children involves measurement of pulmonary vascular resistance (PVR); however, PVR neglects important pulsatile components. Pulmonary artery (PA) input impedance and ventricular power (VP) include mean and pulsatile effects and have shown promise as alternative measures of vascular function. Here we report the utility of pulsed-wave (PW) Doppler-measured instantaneous flow and pressure measurements for estimation of input impedance and VP and use this method to develop a novel parameter: reactivity in compliance. METHODS AND RESULTS: An in vitro model of the general pulmonary vasculature was used to obtain impedance and VP, measured by PW Doppler and a reference flow meter. The method was then tested in a preliminary clinical study in subjects with normal PA hemodynamics (n=4) and patients with PH undergoing reactivity evaluation (8 patients; 23 data points). In vitro results showed good agreement between the impedance spectra computed from both flow-measurement methods. Excellent correlation was seen in vitro between actual resistance and the zero-frequency (Z(o)) impedance value (r2=0.984). Excellent agreement was also found between Z(o) and PVR in the clinical measurements (y=1.075x+0.73; r=0.993). Furthermore, total VP and VP/cardiac output increased significantly with hypertension (128.73 to 365.91 mW and 2.42 to 6.69 mW x mL(-1) x s(-1), respectively). The first-harmonic value of impedance (Z1) was used as a measure of compliance reactivity; older patients exhibited markedly less compliance reactivity than did younger patients. CONCLUSIONS: Input impedance and VP calculated from Doppler measurements and a single-catheter pressure measurement provide comprehensive characterization of PH and reactivity.

Advantages in using multifrequency excitation of contrast microbubbles for enhancing echo particle image velocimetry techniques: initial numerical studies using rectangular and triangular waves.

Accurate measurement of velocity profiles, multiple velocity vectors and local shear stress in arteries is very important for a variety of cardiovascular diseases. We have recently developed an ultrasound based velocimetry technique, termed echo particle image velocimetry (echo PIV). This method takes advantage of the nonlinear backscatter characteristics of ultrasound contrast microbubbles when exposed to certain ultrasonic forcing conditions. Preliminary in vitro, animal and clinical studies have shown significant promise of this method for measuring multiple velocity components with good temporal (up to 2 ms) and spatial (<1 mm) resolution. However, there is still difficulty in maximizing the nonlinearity of bubble backscatter using conventional Gaussian-pulse excitation techniques because: (1) significant harmonic components may not be produced at modest pressure amplitudes; and (2) the higher incident pressure amplitudes required to induce nonlinear behavior may cause bubble destruction. We present here a potential solution to this problem through the use of multifrequency excitation, where rectangular and triangular pulses with four harmonics are used to drive the bubble. The nonlinear behavior of the microbubble, as well as fragility and backscatter, were studied through numerical modeling via a modified Rayleigh-Plesset equation. Results show that the rectangular wave is effective in improving the visibility of microbubbles, with effective scattering cross-section area significantly higher (up to 35 times) than the widely-used Gaussian waveform. However, velocity and acceleration analysis of the bubble wall shows that the rectangular wave may threaten bubble stability. Due to lower wall velocity and acceleration, the triangular wave should decrease the potential for bubble destruction yet maintain relatively high second harmonic backscatter components. The impact of higher harmonics was studied by examining backscatter differences from incident rectangular and triangular pulses with four and two harmonics. Results indicate that a two-frequency excitation (which may be easier to implement practically) may be sufficient to induce nonlinear behavior of the microbubbles at modest incident pressures. These predictions provide support for the use of multifrequency driving to enhance echo PIV applications.

Computational simulations of the total cavo-pulmonary connection: insights in optimizing numerical solutions.

The Fontan procedure is a palliative surgical technique that is used to treat patients with congenital heart defects that include complex lesions such as those with a hypoplastic ventricle. In vitro, in vivo, and computational models of a set of modifications to the Fontan procedure, called the total cavopulmonary connection (TCPC), have been developed. Using these modeling methods, attempts have been made at finding the most energy efficient TCPC circuit. Computational modeling has distinct advantages to other modeling methods. However, discrepancies have been found in validation studies of TCPC computational models. There is little in the literature available to help explain and correct for such discrepancies. Differences in computational results can occur when choosing between steady flow versus transient flow numerical solvers. In this study transient flow solver results were shown to be more consistent with results from previous TCPC in vitro experiments. Using a transient flow solver we found complex fluctuating flow patterns can exist with steady inflow boundary conditions in computational models of the TCPC. To date such findings have not been reported in the literature. Furthermore, our computational modeling results suggest fluctuating flow patterns as well as the magnitudes of these secondary flow structures diminish if the TCPC offset between vena cavae is increased or if flanged connections are added. An association was found between these modifications and improvements in TCPC circuit flow efficiencies. In summary, development of accurate computational simulations in the validation process is critical to efforts in finding the most efficient TCPC circuits, efforts aimed at potentially improving the long term outcome for Fontan patients.

Use of intravascular ultrasound to measure local compliance of the pediatric pulmonary artery: in vitro studies.

BACKGROUND: The accurate measurement of local pulmonary artery compliance in pediatric pulmonary hypertension is an important step toward further understanding the biomechanical and hemodynamic aspects of the disease. The emergence of intravascular ultrasound (IVUS) imaging techniques promises the ability to make such measurements clinically. However, the use of IVUS for compliance measurements has not been validated. Furthermore, confusion exists regarding the most appropriate method to measure compliance. METHODS: This study validated IVUS measurements against a laser micrometer standard for 4 elastic tubes of varying compliance. Two methods of quantifying local compliance were explored: The pressure-strain modulus (E(p)), (E(p)(g/cm(2)) = DeltaP x R(d)/DeltaR (Where DeltaP is pulse pressure, R(d) is diastolic radius, and DeltaR is systolic minus diastolic radii) and the dynamic compliance (C(dyn)), (C(dyn)(%/100 mm Hg) = [DeltaD/(DeltaP x D(d))] x 10(4) Where DeltaD is systolic minus diastolic diameters and D(d) is diastolic diameter. RESULTS: IVUS diameter measurements agreed well with laser micrometer data although slight overestimation (mean = 3.67% +/- 2.78%) was present. Mean values of E(p) ranged from 353.3 g/cm(2) to 2676.0 g/cm(2); mean C(dyn) values ranged from 5.7% diametric change/100 mm Hg to 39.5% diametric change/100 mm Hg for all tube models. Although mean values of E(p) and C(dyn) could be distinguished among the various tubes, the extremely large measurement uncertainty for E(p) precluded statistical differentiation. The uncertainty in E(p) increased inversely with the diametric change, indicating a potential limitation of E(p) associated with stiffening arteries. CONCLUSIONS: We conclude that C(dyn) is a more robust mean of quantifying pediatric pulmonary artery compliance, especially as arteries stiffen with chronic pulmonary hypertension.

Numerical modeling of microbubble backscatter to optimize ultrasound particle image velocimetry imaging: initial studies.

We have developed a promising non-invasive ultrasound-based method for performing particle image velocimetry (PIV) in vivo. This method, termed echo PIV, provides multi-component blood velocity data with good ( approximately 2 ms) temporal resolution. The method takes advantage of the non-linear ultrasound backscatter characteristics of small gas-filled microbubbles (ultrasound contrast) that are seeded into the blood stream. In this study, we use a numerical model to explore potential areas to focus future work in echo PIV. Ultrasound backscatter from encapsulated microbubbles was modeled using a modified Rayleigh-Plesset equation (Church model, 1995), taking into account the protein/lipid shell layer as a thick, mass-conserving incompressible fluid surrounded by incompressible blood-like fluid. The equation of motion was solved numerically to characterize the fundamental and second harmonic components of the backscattered pressure. Results show a significant advantage in using the second harmonic component for echo PIV, especially for small bubble sizes less than 3 microm in diameter at 2.2 MHz frequency. The effect of the shell thickness ranging from 10 to 500 nm on the vibration amplitude of the bubble was examined and it is shown that the presence of the shell requires mechanical index (MI) > 0.2 of incident pressure amplitude to improve bubble detectability. Analysis of the effect of pulse length shows a tradeoff between axial resolution (short pulse length) and bubble detectability (longer pulse length) will most likely be required. The effect of varying MI between 0.1 and 0.6 was also studied at a center frequency of 2.2 MHz and the results indicate that the resonance of the second harmonic is maximized for bubbles with diameter of approximately 2.75 microm. Bubble non-linearities at MI > 0.2 induced a resonant frequency shift away from the integer multiple of the incident frequency in the second harmonic backscatter. For a given bubble size, there is a combination of optimal incident frequency and mechanical index range that maximizes the ratio of the second harmonic compared to the fundamental. This resonant frequency decreases with increasing bubble radius. Further, a narrow bandwidth pulse is shown to increase signal strength. Both of these effects may cause conflict with factors governing spatial resolution. Optimization of the incident frequency, microbubble size and mechanical index to enhance bubble detectability will depend on the particular clinical application. These theoretical predictions provide further understanding of the physics behind our echo PIV technique, and should be useful for guiding the design of echo PIV systems.

Stiffening-induced high pulsatility flow activates endothelial inflammation via a TLR2/NF-κB pathway.

Stiffening of large arteries is increasingly used as an independent predictor of risk and therapeutic outcome for small artery dysfunction in many diseases including pulmonary hypertension. The molecular mechanisms mediating downstream vascular cell responses to large artery stiffening remain unclear. We hypothesize that high pulsatility flow, induced by large artery stiffening, causes inflammatory responses in downstream pulmonary artery endothelial cells (PAECs) through toll-like receptor (TLR) pathways. To recapitulate the stiffening effect of large pulmonary arteries that occurs in pulmonary hypertension, ultrathin silicone tubes of variable mechanical stiffness were formulated and were placed in a flow circulatory system. These tubes modulated the simulated cardiac output into pulsatile flows with different pulsatility indices, 0.5 (normal) or 1.5 (high). PAECs placed downstream of the tubes were evaluated for their expression of proinflammatory molecules (ICAM-1, VCAM-1, E-selectin and MCP-1), TLR receptors and intracellular NF-κB following flow exposure. Results showed that compared to flow with normal pulsatility, high pulsatility flow induced proinflammatory responses in PAECs, enhanced TLR2 expression but not TLR4, and caused NF-κB activation. Pharmacologic (OxPAPC) and siRNA inhibition of TLR2 attenuated high pulsatility flow-induced pro-inflammatory responses and NF-κB activation in PAECs. We also observed that PAECs isolated from small pulmonary arteries of hypertensive animals exhibiting proximal vascular stiffening demonstrated a durable ex-vivo proinflammatory phenotype (increased TLR2, TLR4 and MCP-1 expression). Intralobar PAECs isolated from vessels of IPAH patients also showed increased TLR2. In conclusion, this study demonstrates for the first time that TLR2/NF-κB signaling mediates endothelial inflammation under high pulsatility flow caused by upstream stiffening, but the role of TLR4 in flow pulsatility-mediated endothelial mechanotransduction remains unclear.

Initial experience with the development and numerical and in vitro studies of a novel low-pressure artificial right ventricle for pediatric Fontan patients.

The Fontan operation, an efficient palliative surgery, is performed for patients with single-ventricle pathologies. The total cavopulmonary connection is a preferred Fontan procedure in which the superior and inferior vena cava are connected to the left and right pulmonary artery. The overall goal of this work is to develop an artificial right ventricle that can be introduced into the inferior vena cava, which would act to reverse the deleterious hemodynamics in post-Fontan patients. We present the initial design and computational analysis of a micro-axial pump, designed with the particular hemodynamics of Fontan physiology in mind. Preliminary in vitro data on a prototype pump are also presented. Computational studies showed that the new design can deliver a variety of advantageous operating conditions, including decreased venous pressure through proximal suction, increased pressure rise across the pump, increased pulmonary flows, and minimal changes in superior vena cava pressures. In vitro studies on a scaled prototype showed trends similar to those seen computationally. We conclude that a micro-axial flow pump can be designed to operate efficiently within the low-pressure, low-flow environment of cavopulmonary flows. The results provide encouragement to pursue this design to for in vitro studies and animal studies.

Regression analysis for vortex ring characteristics during left ventricular filling.

A new technique to determine ventricular function is being developed from non-invasive measurements of centerline mitral flow, using color M-mode (CMM) ultrasound. Based on the hypothesis that vortex rings accompanying mitral flow are significant indicators of ventricular filling, we present a technique to determine characteristics of vortex rings created by mitral inflow, including diameter, position and circulation from the CMM derived centerline velocity data. The rings are modeled as vortex filament loops, which induce axial flow. A quasi-Newtonian regression was performed on the velocity data to determine model ring characteristics. Performance of the technique was determined using a synthetic data set with known vortex ring parameters. The algorithm is shown to be insensitive to initial estimates for ring parameters. However, noise in the data can lead to inaccuracy in the derived ring parameters. Further work to increase the accuracy of the regression algorithm and decrease effect of data uncertainty is ongoing.

Characterizing vortex ring behavior during ventricular filling with Doppler echocardiography: an in vitro study.

Doppler ultrasound color M-mode imaging (CMM) has been proposed as a noninvasive means of quantifying diastolic function by measuring flow propagation into the left ventricle. However, the relationship between CMM-derived parameters and underlying fluid dynamics is still unclear. The purpose of this study was to couple high-resolution velocimetry measurements with ultrasound Doppler and CMM measurements in order to shed light on the relationship between CMM flow propagation and inflow dynamics using a simple yet highly reproducible in vitro model of left ventricular inflow. Two Reynolds number conditions were analyzed: 4000 and 6000. Both conditions produced starting jets that formed vortex rings. Average (N = 5) CMM centerline velocities were in agreement with DPIV centerline velocities, although large uncertainty in CMM data was present (uncertainty +/- 10 cm s(-1)). Two flow propagation parameters were extracted from the CMM data: the first utilized an isovelocity as the marker of flow propagation; the second used local peak velocity as the marker. The isovelocity technique followed the flow proximal to the vortex (wavefront) while the peak velocity method followed peak vorticity, and therefore vortex propagation, closely. We conclude that CMM imaging, while limited in measuring absolute velocities, can be utilized to assess inflow vortex ring properties, and thereby provide useful information on diastolic function.