Christian Poelma

Measurements of the wall shear stress distribution in the outflow tract of an embryonic chicken heart

In order to study the role of blood–tissue interaction in the developing chicken embryo heart, detailed information about the haemodynamic forces is needed. In this study, we present the first in vivo measurements of the three-dimensional distribution of wall shear stress (WSS) in the outflow tract (OFT) of an embryonic chicken heart. The data are obtained in a two-step process: first, the three-dimensional flow fields are measured during the cardiac cycle using scanning microscopic particle image velocimetry; second, the location of the wall and the WSS are determined by post-processing flow velocity data (finding velocity gradients at locations where the flow approaches zero). The results are a three-dimensional reconstruction of the geometry, with a spatial resolution of 15–20 µm, and provides detailed information about the WSS in the OFT. The most significant error is the location of the wall, which results in an estimate of the uncertainty in the WSS values of 20 per cent.

Particle-fluid interactions in grid-generated turbulence

The effect of small particles on decaying grid-generated turbulence is studied experimentally. Using a two-camera system, instantaneous fluid-phase and particlephase measurements can be obtained simultaneously. The data obtained with this system are used to study the decay behaviour of the turbulent flow. The role of particle size, particle density and volume load is studied in a number of different cases. These cases are chosen so that the individual role of these parameters can systematically be evaluated. Addition of particles to the flow has significant effects on the decaying turbulence: first, the onset of the turbulent decay appears to shift upstream; second, the flow becomes anisotropic as it develops downstream. The latter is observed as an increase in integral length scale in the vertical direction. The rate at which the flow becomes anisotropic can be predicted using a new parameter: the product of the non-dimensional number density and the Stokes number (referred to as the ‘Stokes load’). This parameter, combining the relevant fluid and particle characteristics, is a measure for the energy redistribution leading to anisotropy. In addition to redistributing energy, the particles also produce turbulence. However, this only becomes evident when the grid-generated turbulence has decayed sufficiently, relatively far downstream of the grid. The turbulence production by particles can also account for the observed decrease in slope of the power spectrum, which leads to a ‘cross-over’ effect. The production of turbulence by the particles can be predicted using a model for the momentum deficit of the particle wakes. The validity of this approach is confirmed using conditional sampling of the fluid velocity field around the particles.

Fluid Shear Stress and Inner Curvature Remodeling of the Embryonic Heart. Choosing the Right Lane

Cardiovascular development is directed or modulated by genetic and epigenetic factors. The latter include blood flow-related shear stress and blood pressure-related circumferential strain. This review focuses on shear stress and its effects on endothelial cells lining the inner surfaces of the heart and blood vessels. Flow characteristics of the embryonic blood, like velocity, viscosity and periodicity, are taken into account to describe the responses of endothelial cells to shear stress and the sensors for this friction force. The primary cilium, which is an integral part of the shear sensor, connects to the cytoskeletal microtubules and transmits information about the level and direction of blood flow into the endothelial cell. When the heart remodels from a more or less straight into a c-shaped tube the sharp curvature, in combination with the small vessel dimensions and high relative viscosity, directs the highest shear stress to the inner curvature of this pump. This proves to be an important epigenetic modulator of cardiac morphogenesis because when shear stress is experimentally altered inner curvature remodeling is affected which leads to the development of congenital cardiovascular anomalies. The best of both worlds, mechanics and biology, are used here to describe early cardiogenesis.

Complex flow patterns in a real-size intracranial aneurysm phantom: phase contrast MRI compared with particle image velocimetry and computational fluid dynamics

The aim of this study was to validate the flow patterns measured by high‐resolution, time‐resolved, three‐dimensional phase contrast MRI in a real‐size intracranial aneurysm phantom. Retrospectively gated three‐dimensional phase contrast MRI was performed in an intracranial aneurysm phantom at a resolution of 0.2 × 0.2 × 0.3 mm3 in a solenoid rat coil. Both steady and pulsatile flows were applied. The phase contrast MRI measurements were compared with particle image velocimetry measurements and computational fluid dynamics simulations. A quantitative comparison was performed by calculating the differences between the magnitude of the velocity vectors and angles between the velocity vectors in corresponding voxels. Qualitative analysis of the results was executed by visual inspection and comparison of the flow patterns. The root‐mean‐square errors of the velocity magnitude in the comparison between phase contrast MRI and computational fluid dynamics were 5% and 4% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 16° and 14° for the steady and pulsatile measurements, respectively. In the phase contrast MRI and particle image velocimetry comparison, the root‐mean‐square errors were 12% and 10% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 19° and 15° for the steady and pulsatile measurements, respectively. Good agreement was found in the qualitative comparison of flow patterns between the phase contrast MRI measurements and both particle image velocimetry measurements and computational fluid dynamics simulations. High‐resolution, time‐resolved, three‐dimensional phase contrast MRI can accurately measure complex flow patterns in an intracranial aneurysm phantom. Copyright

Tgfβ/Alk5 signaling is required for shear stress induced klf2 expression in embryonic endothelial cells

Endothelial cells (EC) translate biomechanical forces into functional and phenotypic responses that play important roles in cardiac development. Specifically, EC in areas of high shear stress, i.e., in the cardiac outflow tract and atrioventricular canal, are characterized by high expression of Krüppel‐like factor 2 (Klf2) and by transforming growth factor‐beta (Tgfβ)‐driven endothelial‐to‐mesenchymal transition. Extraembryonic venous obstruction (venous clip model) results in congenital heart malformations, and venous clip‐induced alterations in shear stress‐related gene expression are suggestive for an increase in cardiac shear stress. Here, we study the effects of shear stress on Klf2 expression and Tgfβ‐associated signaling in embryonic EC in vivo using the venous clip model and in vitro by subjecting cultured EC to fluid flow. Cellular responses were assessed by analysis of Klf2, Tgfβ ligands, and their downstream signaling targets. Results show that, in embryonic EC, shear stress activates Tgfβ/Alk5 signaling and that induction of Klf2 is an Alk5 dependent process. Developmental Dynamics 240:1670–1680, 2011.

Particle-Turbulence Interaction in a Homogeneous, Isotropic Turbulent Suspension

A review is given of numerical, analytical, and experimental research regarding the two-way coupling effect between particles and fluid turbulence in a homogeneous, isotropic turbulent suspension. The emphasis of this review is on the effect of the suspended particles on the spectrum of the carrier fluid, in order to explain the physical mechanisms that are involved. An important result of numerical simulations and analytical models (neglecting the effect of gravity) is that, for a homogeneous and isotropic suspension with particles with a response time much larger than the Kolmogorov time scale, the main effect of the particles is suppression of the energy of eddies of all sizes. However for a suspension with particles with a response time comparable to or smaller than the Kolmogorov time, the Kolmogorov length scale will decrease and the turbulence energy of (nearly) all eddy sizes increases. For a suspension with particles with a response time in between the two limiting cases mentioned above the energy of the larger eddies is suppressed, whereas the energy of the smaller ones is enhanced. Attention is paid to several physical mechanisms that were suggested in the literature to explain this influence of the particles on the turbulence. In some of the experimental studies, certain results from simulations and models have, indeed, been confirmed. However, in other experiments these results were not found. This is attributed to the role of gravity, which leads to turbulence production by the particles. Additional research effort is needed to fully understand the physical mechanisms causing the two-way coupling effect in a homogeneous, isotropic, and turbulently flowing suspension. This review contains 47 references.

Accurate Blood Flow Measurements: Are Artificial Tracers Necessary?

Imaging-based blood flow measurement techniques, such as particle image velocimetry, have become an important tool in cardiovascular research. They provide quantitative information about blood flow, which benefits applications ranging from developmental biology to tumor perfusion studies. Studies using these methods can be classified based on whether they use artificial tracers or red blood cells to visualize the fluid motion. We here present the first direct comparison in vivo of both methods. For high magnification cases, the experiments using red blood cells strongly underestimate the flow (up to 50% in the present case), as compared to the tracer results. For medium magnification cases, the results from both methods are indistinguishable as they give the same underestimation of the real velocities (approximately 33%, based on in vitro reference measurements). These results suggest that flow characteristics reported in literature cannot be compared without a careful evaluation of the imaging characteristics. A method to predict the expected flow averaging behavior for a particular facility is presented.

An experimental study of transitional pulsatile pipe flow

The transitional regime of a sinusoidal pulsatile flow in a straight, rigid pipe is investigated using particle image velocimetry. The main aim is to investigate how the critical Reynolds number is affected by different pulsatile conditions, expressed as the Womersley number and the oscillatory Reynolds number. The transition occurs in the region of Re?=?2250-3000 and is characterized by an increasing number of isolated turbulence structures. Based on velocity fields and flow visualizations, these structures can be identified as puffs, similar to those observed in steady flow transition. Measurements at different Womersley numbers yield similar transition behavior, indicating that pulsatile effects do not play a role in the regime that is investigated. Variations of the oscillatory Reynolds number also appear to have little effect, so that the transition here seems to be determined only by the mean Reynolds number. For larger mean Reynolds numbers, a second regime is observed: here, the flow remains turbulent throughout the cycle. The turbulence intensity varies during the cycle, but has a phase shift with respect to the mean flow component. This is caused by a growth of kinetic energy during the decelerating part and a decay during the accelerating part of the cycle. Flow visualization experiments reveal that the flow develops localized turbulence at several random axial positions. The structures quickly grow to fill the entire pipe in the decelerating phase and (partially) decay during the accelerating phase.

Transitional flow in aneurysms and the computation of haemodynamic parameters

Haemodynamic forces appear to play an influential role in the evolution of aneurysms. This has led to numerous studies, usually based on computational fluid dynamics. Their focus is predominantly on the wall shear stress (WSS) and associated derived parameters, attempting to find correlations between particular patterns of haemodynamic indices and regions subjected to disease formation and progression. The indices are generally determined by integration of flow properties over a single cardiac cycle. In this study, we illustrate that in some cases the transitional flow in aneurysms can lead to significantly different WSS distributions in consecutive cardiac cycles. Accurate determination of time-averaged haemodynamic indices may thus require simulation of a large number of cycles, which contrasts with the common approach to determine parameters using data from a single cycle. To demonstrate the role of transitional flow, two exemplary cases are considered: flow in an abdominal aortic aneurysm and in an intracranial aneurysm. The key differences that are observed between these cases are explained in terms of the integral timescale of the transitional flows in comparison with the cardiac cycle duration: for relatively small geometries, transients will decay before the next cardiac cycle. In larger geometries, transients are still present when the systolic phase produces new instabilities. These residual fluctuations serve as random initial conditions and thus seed different flow patterns in each cycle. To judge whether statistics are converged, the derived indices from at least two successive cardiac cycles should be compared.

Quantitative measurement of the lifetime of localized turbulence in pipe flow

Transition to turbulence in a pipe is characterized by the increase of the characteristic lifetimes of localized turbulent spots (‘puffs’) with increasing Reynolds number (Re). Previous experiments are based on visualization or indirect measurements of the lifetime probability. Here we report quantitative direct measurements of the lifetimes based on accurate pressure measurements combined with laser Doppler anemometry (LDA). The characteristic lifetime is determined directly from the lifetime probability. It is shown that the characteristic lifetime does not diverge at finite Re, and follows an exponential scaling for the observed range 1725<Re<1955. Over this small Re range the lifetime increases over four orders of magnitude. The results show that the puff velocity is not constant, and the rapid disintegration of puffs occurs within 20–70 pipe diameters.