Left ventricular flow is intrinsically complex, three-dimensional and unsteady. Its features are susceptible to cardiovascular pathology and treatment, in particular to surgical interventions involving the valves (mitral valve replacement). To improve our understanding of intraventricular fluid mechanics and the impact of various types of prosthetic valves thereon, we have developed a custom-designed versatile left ventricular phantom with anatomically realistic moving left ventricular membrane. A biological, a tilting disc and a bileaflet valve (in two different orientations) were mounted in the mitral position and tested under the same settings. To investigate 3D flow within the phantom, a four-view tomographic particle image velocimetry setup has been implemented. The results compare side-by-side the evolution of the 3D flow topology, vortical structures and kinetic energy in the left ventricle domain during the cardiac cycle. Except for the tilting disc valve, all tested prosthetic valves induced a crossed flow path, where the outflow crosses the inflow path, passing under the mitral valve. The biological valve shows a strong jet with a peak velocity about twice as high compared to all mechanical heart valves, which makes it easier to penetrate deeply into the cavity. Accordingly, the peak kinetic energy in the left ventricle in case of the biological valve is about four times higher than the mechanical heart valves. We conclude that the tomographic particle imaging velocimetry setup provides a useful ground truth measurement of flow features and allows a comparison of the effects of different valve types on left ventricular flow patterns.@en

Microbubbles (MBs) have been shown to create transient or lethal pores in cell membranes under the influence of ultrasound, known as ultrasound-mediated sonoporation. Several studies have reported enhanced drug delivery or local cell death induced by MBs that are either targeted to a specific biomarker (targeted microbubbles, tMBs) or that are not targeted (non-targeted microbubbles, ntMBs). However, both the exact mechanism and the optimal acoustic settings for sonoporation are still unknown. In this study we used real-time uptake patterns of propidium iodide, a fluorescent cell impermeable model drug, as a measure for sonoporation. Combined with high-speed optical recordings of MB displacement and ultra-high-speed recordings of MB oscillation, we aimed to identify differences in MB behavior responsible for either viable sonoporation or cell death. We compared ntMBs and tMBs with identical shell compositions exposed to long acoustic pulses (500–50,000 cycles) at various pressures (150–500 kPa). Propidium iodide uptake highly correlated with cell viability; when the fluorescence intensity still increased 120 s after opening of the pore, this resulted in cell death. Higher acoustic pressures and longer cycles resulted in more displacing MBs and enhanced sonoporation. Non-displacing MBs were found to be the main contributor to cell death, while displacement of tMBs enhanced reversible sonoporation and preserved cell viability. Consequently, each therapeutic application requires different settings: non-displacing ntMBs or tMBs are advantageous for therapies requiring cell death, especially at 500 kPa and 50,000 cycles, whereas short acoustic pulses causing limited displacement should be used for drug delivery.@en

Microbubbles (MBs) have been shown to create transient or lethal pores in cell membranes under the influence of ultrasound, known as ultrasound-mediated sonoporation. Several studies have reported enhanced drug delivery or local cell death induced by MBs that are either targeted to a specific biomarker (targeted microbubbles, tMBs) or that are not targeted (non-targeted microbubbles, ntMBs). However, both the exact mechanism and the optimal acoustic settings for sonoporation are still unknown. In this study we used real-time uptake patterns of propidium iodide, a fluorescent cell impermeable model drug, as a measure for sonoporation. Combined with high-speed optical recordings of MB displacement and ultra-high-speed recordings of MB oscillation, we aimed to identify differences in MB behavior responsible for either viable sonoporation or cell death. We compared ntMBs and tMBs with identical shell compositions exposed to long acoustic pulses (500–50,000 cycles) at various pressures (150–500 kPa). Propidium iodide uptake highly correlated with cell viability; when the fluorescence intensity still increased 120 s after opening of the pore, this resulted in cell death. Higher acoustic pressures and longer cycles resulted in more displacing MBs and enhanced sonoporation. Non-displacing MBs were found to be the main contributor to cell death, while displacement of tMBs enhanced reversible sonoporation and preserved cell viability. Consequently, each therapeutic application requires different settings: non-displacing ntMBs or tMBs are advantageous for therapies requiring cell death, especially at 500 kPa and 50,000 cycles, whereas short acoustic pulses causing limited displacement should be used for drug delivery.@en

Power Doppler (PD) imaging has become a staple in high frame rate ultrasound imaging due to its ability to image small vessels and slow-moving flows, such as in the case of imaging blood flow in the brain. Alternatively, color Doppler (CD) can be used to determine the one-dimensional directional information of the blood scatterers. This can help determine if the flow is arterial or venous, or distinguish between adjacent flows that have an opposite direction. Current methods for estimating 2D blood velocity vectors rely mostly on trigonometric solutions using synthetic apertures or, large plane-wave angles in transmission and sub-apertures in receive to be able to resolve the 2D vector. Relative to PD or CD techniques, these methods are more computationally expensive and have not been successfully used to image blood flow direction within micrometer sized vasculature. In this paper, we propose to use the orientations of the vessels derived from a directional spatial filter in combination with the CD signal to enhance the PD images with directional information. This approach was tested on simulated data as well as on a 2D image containing brain vasculature of a mouse.@en

Echocardiographic determination of multi-component blood flow dynamics in the left ventricle remains a challenge. In this study we compare contrast enhanced, high frame rate (1000 fps) echo particle image velocimetry (ePIV) against optical particle image velocimetry (oPIV, gold standard), in a realistic left ventricular phantom. We find that ePIV compares well to oPIV, even for the high velocity inflow jet (normalized RMSE = 9 ?1%). Additionally, we perform the method of Proper Orthogonal Decomposition, to better qualify and quantify the differences between the two modalities. We show that ePIV and oPIV resolve very similar flow structures, especially for the lowest order mode with a cosine similarity index of 86%. The coarser resolution of ePIV does result in increased variance and blurring of smaller flow structures when compared to oPIV. However, both modalities are in good agreement with each other for the modes that constitute the bulk of the kinetic energy. We conclude that high frame rate ePIV can accurately estimate the high velocity diastolic inflow jet and the high energy flow structures in a left ventricular setting.@en

Ultrafast contrast enhanced ultrasound, combined with echo particle image velocimetry (ePIV), can provide accurate, multidimensional hemodynamic flow field measurement. However, the use of ultrasound contrast agent (UCA) still prevents this method from becoming a truly versatile and non-invasive diagnostic tool. In this study, we investigate the use of native blood instead of UCA backscatter for ePIV measurements and compare their accuracy in vitro. Additionally, the effect of measurement depth is experimentally assessed. Blood mimicking fluid (BMF) was pumped through a 10 mm diameter tube producing parabolic flow profiles, adding UCA in the case of contrast imaging. Plane wave imaging at 5000 framesper-second was performed with a Verasonics Vantage system and a linear array. The tube was imaged at three different depths: 25, 50 and 100 mm. Singular value decomposition (SVD) was assessed for clutter suppression against mean background subtraction. PIVlab was used as a PIV implementation. With SVD, BMF provided almost equal ePIV accuracy as UCA, except at 100 mm depth where UCA provided better accuracy. Use of clutter suppression greatly improved ePIV results, but minimal differences in ePIV accuracy were noted between mean and SVD filtered groups (BMF or UCA). Accuracy decreased with increasing depth, likely due to reduced elevation resolution, resulting in out-of-plane smoothing of velocity gradients.@en

S.S. Khalafvand, J.D. Voorneveld, H.W. Mulder, A. Haak, F.J.H. Gijsen, J.G. Bosch, N. de Jong, S. Kenjeres (2016), “Numerical modelling of 4D left ventricular blood flow using computed tomography imaging and computational fluid dynamics”, Proceedings of the Virtual physiology human conference, Amsterdam, The Netherlands, September 26-28, 2016, Poster Presentation. @en

Investigation of the complex intra-ventricular flow patterns in the left ventricle (LV) remains a challenge in clinical ultrasound. Echo-particle image velocimetry (ePIV) is able to estimate 2D flow from 2D images, but it is known to underestimate the high velocity flows present during the filling and ejection periods of the cardiac cycle[1], [2]. High frame rate (HFR) ultrasound imaging has been shown to improve the dynamic range of velocities resolvable by ePIV[3]. However, HFR ePIV has yet to be verified in the complex flow environment of the LV. In this study we compare HFR ePIV against the gold standard optical PIV (oPIV) in a realistic geometry dynamic LV phantom.@en