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Biomedical subjects

Robin Shandas

Publications and source records attributed to Robin Shandas.

At least 19 recordsLinked to original sources

Efficiency differences in computational simulations of the total cavo-pulmonary circulation with and without compliant vessel walls.

The Fontan operation is a palliative surgical procedure performed on children born with congenital defects of the heart that have yielded only a single functioning ventricle. The total cavo-pulmonary connection (TCPC) is the most popular variant of the Fontan procedure. The objective of the study was to quantify and compare the efficiency of numerical models of the TCPC with rigid versus elastic vessel wall models. The pressure drop and power loss through both type TCPC models was measured. Significant differences in efficiencies exist between rigid versus elastic numerical models. We have shown incorporating elasticity into numerical models of the total cavo-pulmonary connection is important when determining circuit efficiencies.

Blood Flow Velocity↗

Theoretical predictions of harmonic generation from submicron ultrasound contrast agents for nonlinear biomedical ultrasound imaging.

Submicron ultrasound contrast agents have aroused attention for their significant promise in ultrasonic contrast/molecular imaging, targeted therapy and echo particle imaging velocimetry. However, nonlinear acoustic properties of submicron encapsulated gas bubbles for ultrasonic applications are still not clearly understood. In this paper, nonlinear acoustic emission characteristics from submicron bubbles were examined using a numerical study. The modified RP equation incorporating viscosity, acoustic radiation, thermal effects and encapsulated shell was used to study single bubble dynamics. Further, a size integration method, shown previously to be useful in prediction of backscatter spectra from groups of bubbles, was applied to analyse response from a bubble population. We show that bubbles with radii (200-500 nm) produce significant subharmonic and ultraharmonic components of the backscatter spectrum, while smaller bubbles (<200 nm) provide substantial second harmonic components. Additionally, nanoscale bubbles (<100 nm) produce very low backscatter amplitudes and thus may not be useful with the use of current ultrasound technology. Analysing optimal ultrasound driving pressures and bubbles size ranges for maximal subharmonic and ultraharmonic signals showed that sub and ultraharmonic mode nonlinear imaging methods may be potentially competitive for larger size bubbles (>200 nm) in providing proper contrast-to-tissue signal ratios.

Acoustics↗

Use of myocardial performance index in pediatric patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: The myocardial performance index (MPI) correlates with clinical status in adults with idiopathic pulmonary arterial (PA) hypertension (IPAH). This pediatric study used MPI to assess response to bosentan therapy. METHODS: The study included 12 children with IPAH and 12 healthy control subjects. MPI was correlated with catheterization data at initiation of bosentan and at a median follow-up of 9 months. Therapy responders were defined by a greater than 20% decrease in mean PA pressure. RESULTS: Right ventricular MPI for patients with IPAH was 0.64 +/- 0.30 versus 0.28 +/- 0.03 in control subjects (P < .01). It had a strong correlation with mean PA pressure (R = 0.94; P < .001). Right ventricular MPI decreased significantly in responders (range 20%-44%, mean 25%) with a 5% increase in nonresponders. CONCLUSIONS: Right ventricular MPI in pediatric IPAH correlates with mean PA pressure and response to therapy. This study suggests that this noninvasive Doppler index may be useful to follow up children with IPAH, particularly when tricuspid regurgitation data are insufficient.

Adolescent↗

Noninvasive Doppler tissue measurement of pulmonary artery compliance in children with pulmonary hypertension.

BACKGROUND: We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). METHODS: Dynamic compliance (C(dyn)) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. C(dyn) was calculated as: [(D(s) - D(d))/(D(d) x P(s))] x 10(4); where D(s) = systolic diameter, D(d) = diastolic diameter, and P(s) = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. C(dyn) was also measured in an additional 13 patients undergoing reactivity studies. RESULTS: Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, C(dyn) calculated by CMM DTI agreed with C(dyn) calculated using invasive techniques (23.4 +/- 16.8 vs 29.1 +/- 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower C(dyn) values than control subjects (P < .01). C(dyn) values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress-strain behavior of these arteries. Reactivity in C(dyn) agreed with reactivity measured using impedance techniques. CONCLUSION: The C(dyn) method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension.

Adolescent↗

Predicting backscatter characteristics from micron- and submicron-scale ultrasound contrast agents using a size-integration technique.

In this paper, a computationally, inexpensive, size-integration method based on a modified Rayleigh-Plesset model is developed to predict backscatter spectra from groups of bubbles with various size distributions, incident acoustic amplitudes, and driving frequencies. The method was validated using experimentally measured spectra from contrast bubbles of various sizes: Optison, Levovist, ST68 microbubbles, and submicron bubbles. This method provides a computationally inexpensive means of examining backscatter spectrum from multiple bubbles, especially in predicting occurrence and relative amplitude of subharmonics and second harmonics.

Algorithms↗

Simulations of congenital septal defect closure and reactivity testing in patient-specific models of the pediatric pulmonary vasculature: A 3D numerical study with fluid-structure interaction.

Clinical imaging methods are highly effective in the diagnosis of vascular pathologies, but they do not currently provide enough detail to shed light on the cause or progression of such diseases, and would be hard pressed to foresee the outcome of surgical interventions. Greater detail of and prediction capabilities for vascular hemodynamics and arterial mechanics are obtained here through the coupling of clinical imaging methods with computational techniques. Three-dimensional, patient-specific geometric reconstructions of the pediatric proximal pulmonary vasculature were obtained from x-ray angiogram images and meshed for use with commercial computational software. Two such models from hypertensive patients, one with multiple septal defects, the other who underwent vascular reactivity testing, were each completed with two sets of suitable fluid and structural initial and boundary conditions and used to obtain detailed transient simulations of artery wall motion and hemodynamics in both clinically measured and predicted configurations. The simulation of septal defect closure, in which input flow and proximal vascular stiffness were decreased, exhibited substantial decreases in proximal velocity, wall shear stress (WSS), and pressure in the post-op state. The simulation of vascular reactivity, in which distal vascular resistance and proximal vascular stiffness were decreased, displayed negligible changes in velocity and WSS but a significant drop in proximal pressure in the reactive state. This new patient-specific technique provides much greater detail regarding the function of the pulmonary circuit than can be obtained with current medical imaging methods alone, and holds promise for enabling surgical planning.

Blood Flow Velocity↗

Thermomechanics of the shape memory effect in polymers for biomedical applications.

We examine the shape memory effect in polymer networks intended for biomedical, and specifically cardiovascular, applications. The polymers were synthesized by photopolymerization from a tert-butyl acrylate monomer with a diethyleneglycol diacrylate crosslinker. Three-point flexural tests were used to systematically investigate the thermomechanics of shape storage (predeformation) and shape recovery. The glass transition temperature, T(g), of the polymers was determined to be approximately 65 degrees C. The polymers show 100% strain recovery, at low and high predeformation temperatures, up to maximum strains of approximately 80%. The polymers show a sigmoidal free strain recovery response as a function of increasing temperature at a constant heating rate. Free strain recovery was determined to depend on the temperature during predeformation; lower predeformation temperatures (T < T(g)) decreased the temperature required for free strain recovery. Constrained stress recovery shows a complex evolution as a function of temperature and also depends on the temperature during predeformation. Stress recovery after low-temperature predeformation (T < T(g)) shows a peak in the generated recovery stress, whereas stress recovery after high-temperature predeformation (T > T(g)) is sigmoidal. The isothermal free strain recovery rate was found to increase with increasing temperature or decreasing predeformation temperature. The thermomechanical results are discussed in light of potential biomedical applications, and a prototype device is presented.

Biocompatible Materials↗

Aortic input impedance increases with age in healthy men and women.

Aortic input impedance represents the hydraulic load presented by the systemic circulation to the left ventricle of the heart and is increased in patients with cardiovascular disease. Aging is a strong independent risk factor for cardiovascular disease and could exert this effect partly through an increase in modulus of aortic input impedance. We used a novel noninvasive technique to determine aortic input impedance in 71 healthy men and women aged 20 to 69 years. We found that the aortic input impedance spectrum was shifted rightward with advancing age, characterized by a 37% increase in the frequency of the minimum modulus between the third and seventh decade (P<0.0001). The frequency of the minimum modulus correlated with age in all subjects (r=0.48; P<0.0001), in men (r=0.43; P<0.005), and in women (r=0.53; P=0.001). Although several physical characteristics were associated with the frequency of the minimum modulus (bivariate correlation), a regression model that included age and these physical characteristics showed that age was the only independent predictor of the frequency of the minimum modulus. We conclude that aortic input impedance increases with advancing age in healthy men and women. This increase in aortic input impedance may be an important mechanism by which age increases the risk of cardiovascular disease in humans.

Adult↗

A microstructural hyperelastic model of pulmonary arteries under normo- and hypertensive conditions.

This work represents the first application of a statistical mechanics based microstructural orthotropic hyperelastic model to pulmonary artery mechanics under normotensive and hypertensive conditions. The model provides an analogy between the entangled network of long molecular chains and the structural protein framework seen in the medial layer, and relates the mechanical response at macro-level to the deformation (entropy change) of individual molecular chains at the micro-level. A finite element approach was adopted to implement the model. Material parameters were determined via comparing model output to measured pressure-stretch results from normotensive and hypertensive trunks and branches obtained from a rat model of pulmonary arterial hypertension. Results from this initial study show that this model appears reasonable for the study of hyperelastic and anisotropic pulmonary artery mechanics. Typical tangent modulus values ranged from 200 to 800 kPa for normotensive arteries-this increased to beyond 1 MPa for hypertensive vessels. Our study also provokes the hypothesis that increase of cross-linking density may be one mechanism by which the pulmonary artery stiffens in hypertension.

Animals↗

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.

Blood Flow Velocity↗

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.

Acoustics↗

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.

Adolescent↗

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.

Blood Flow Velocity↗

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.

Blood Flow Velocity↗

Noninvasive measurement of steady and pulsating velocity profiles and shear rates in arteries using echo PIV: in vitro validation studies.

Although accurate measurement of velocity profiles, multiple velocity vectors, and shear stress in arteries is important, there is still no easy method to obtain such information in vivo. We report on the utility of combining ultrasound contrast imaging with particle image velocimetry (PIV) for noninvasive measurement of velocity vectors. This method (echo PIV) takes advantage of the strong backscatter characteristics of small gas-filled microbubbles (contrast) seeded into the flow. The method was tested in vitro. The steady flow analytical solution and optical PIV measurements (for pulsatile flow) were used for comparison. When compared to the analytical solution, both echo PIV and optical PIV resolved the steady velocity profile well. Error in shear rate as measured by echo PIV (8%) was comparable to the error of optical PIV (6.5%). In pulsatile flow, echo PIV velocity profiles agreed well with optical PIV profiles. Echo PIV followed the general profile of pulsatile shear stress across the artery but underestimated wall shear at certain time points. However, error in shear from echo PIV was an order of magnitude less than error from current shear measurement methods. These studies indicate that echo PIV is a promising technique for noninvasive measurement of velocity profiles and shear stress.

Animals↗

Dynamic three-dimensional reconstruction and modeling of cardiovascular anatomy in children with congenital heart disease using biplane angiography.

Modeling and simulation of cardiovascular biomechanics and fluid dynamics from patient-specific data is a continuing topic of research investigation. Several methodologies utilizing CT, MRI and ultrasound to re-create the three-dimensional anatomy of the cardiovascular system have been examined. Adaptation of these models to pediatric applications has not been studied as extensively. There is significant need for such techniques in pediatric congenital heart disease since local anatomy may exhibit highly unusual geometry, and three-dimensional information would be of significant use for surgical and interventional planning, biomechanical and fluid dynamic simulation, and patient counseling. We report here on the adaptation and application of a three-dimensional reconstruction technique that utilizes bi-plane angiographic images as the base data sets. The method has been validated in a variety of adult imaging situations including coronary artery imaging and intervention. The method uses a skeletonization approach whereby local centerline, diameter, branching and tortuosity of the vasculature are obtained to create the three-dimensional model. Ten patients with a variety of etiology were imaged and 3D reconstructions were obtained. Excellent images were obtained of complex anatomy including the highly branched pulmonary vasculature and Fontan surgical connections. The data were then translated into solid and surface models to facilitate viewing, export into computational fluid dynamic grids, and into files suitable for stereo lithography fabrication (STL). This method appears promising for the dynamic study of complex cardiovascular anatomy found in congenital heart disease. Optimization of the method to facilitate on-line reconstruction and simulation are currently ongoing.

Algorithms↗

Stress and strain in rat pulmonary artery material during a biaxial bubble test.

A biaxial bubble test has been designed to ascertain the mechanical properties of rat pulmonary arteries. The analytical procedure used to estimate stress and strain from the resulting test data is presented along with some analytical results. The bubble test was performed by loading a flat piece of rat pulmonary artery into a test fixture beneath a circular opening; the material was subsequently pressurized from below, producing a "bubble" of deformed material. Due to the anisotropy of the rat pulmonary artery, the resulting bubble was ellipsoidal in shape. Test results were recorded in the form of side-view images taken from various angles at incremental values of pressure. Average strains were estimated with the use of image analysis to measure changes in the bubble perimeter during inflation. Formulations for isotropic materials were applied to estimate stresses based on the anisotropic geometry of the bubbles produced during testing; some results of this preliminary analysis are presented here. Results from this analysis show differences in mechanical properties of the rat pulmonary artery from those of healthy versus hypertensive rats.

Animals↗

Simulation of branching blood flows on parallel computers.

We present a fully parallel nonlinearly implicit algorithm for the numerical simulation of some branching blood flow problems, which require efficient and robust solver technologies in order to handle the high nonlinearity and the complex geometry. Parallel processing is necessary because of the large number of mesh points needed to accurately discretize the system of differential equations. In this paper we introduce a parallel Newton-Krylov-Schwarz based implicit method, and software for distributed memory parallel computers, for solving the nonlinear algebraic systems arising from a Q2-Q1 finite element discretization of the incompressible Navier-Stokes equations that we use to model the blood flow in the left anterior descending coronary artery.

Arteries↗