Purpose: To study the feasibility of high-frame-rate (HFR) contrast material-enhanced (CE) ultrasound particle image velocimetry (PIV), or echo PIV, in the abdominal aorta. Materials and Methods: Fifteen healthy participants (six men; median age, 23 years [age range, 18-34 years]; median body mass index, 20.3 kg/m2 [range, 17.3-24.9 kg/m2]) underwent HFR CE US. US microbubbles were injected at incremental doses (0.25, 0.5, 0.75, and 1.5 mL), with each dose followed by US measurement to determine the optimal dosage. Different US mechanical index values were evaluated (0.09, 0.06, 0.03, and 0.01) in a diverging wave acquisition scheme. PIV analysis was performed via pairwise cross-correlation of all captured images. Participants also underwent phase-contrast MRI. The echo PIV and phase-contrast MRI velocity profiles were compared via calculation of similarity index and relative difference in peak velocity. Results: Visualization of the aortic bifurcation with HFR CE US was successful in all participants. Optimal echo PIV results were achieved with the lowest contrast agent dose of 0.25 mL in combination with the lowest mechanical indexes (0.01 or 0.03). Substantial bubble destruction occurred at higher mechanical indexes (>0.06). Flow patterns were qualitatively similar in the echo PIV and MR images. The echo PIV and MRI velocity profiles showed good agreement (similarity index, 0.98 and 0.99; difference in peak velocity, 8.5% and 17.0% in temporal and spatial profiles, respectively). Conclusion: Quantification of blood ow in the human abdominal aorta with US particle image velocimetry (echo PIV) is feasible. Use of echo PIV has potential in the clinical evaluation of aortic disease.@en

High-frame-rate (HFR) echo-particle image velocimetry (echoPIV) is a promising tool for measuring intracardiac blood flow dynamics. In this study, we investigate the optimal ultrasound contrast agent (UCA: SonoVue) infusion rate and acoustic output to use for HFR echoPIV (PRF = 4900 Hz) in the left ventricle (LV) of patients. Three infusion rates (0.3, 0.6, and 1.2 ml/min) and five acoustic output amplitudes (by varying transmit voltage: 5, 10, 15, 20, and 30 V - corresponding to mechanical indices of 0.01, 0.02, 0.03, 0.04, and 0.06 at 60-mm depth) were tested in 20 patients admitted for symptoms of heart failure. We assess the accuracy of HFR echoPIV against pulsed-wave Doppler acquisitions obtained for mitral inflow and aortic outflow. In terms of image quality, the 1.2-ml/min infusion rate provided the highest contrast-to-background ratio (CBR) (3-dB improvement over 0.3 ml/min). The highest acoustic output tested resulted in the lowest CBR. Increased acoustic output also resulted in increased microbubble disruption. For the echoPIV results, the 1.2-ml/min infusion rate provided the best vector quality and accuracy; mid-range acoustic outputs (corresponding to 15-20-V transmit voltages) provided the best agreement with the pulsed-wave Doppler. Overall, the highest infusion rate (1.2 ml/min) and mid-range acoustic output amplitudes provided the best image quality and echoPIV results.@en

Assessing the coronary circulation with contrast-enhanced echocardiography has high clinical relevance. However, it is not being routinely performed in clinical practice because the current clinical tools generally cannot provide adequate image quality. The contrast agent's visibility in the myocardium is generally poor, impaired by motion and nonlinear propagation artifacts. The established multipulse contrast schemes (MPCSs) and the more experimental singular value decomposition (SVD) filter also fall short to solve these issues. Here, we propose a scheme to process amplitude modulation/amplitude-modulated pulse inversion (AM/AMPI) echoes with higher order SVD (HOSVD) instead of conventionally summing the complementary pulses. The echoes from the complementary pulses form a separate dimension in the HOSVD algorithm. Then, removing the ranks in that dimension with dominant coherent signals coming from tissue scattering would provide the contrast detection. We performed both in vitro and in vivo experiments to assess the performance of our proposed method in comparison with the current standard methods. A flow phantom study shows that HOSVD on AM pulsing exceeds the contrast-to-background ratio (CBR) of conventional AM and an SVD filter by 10 and 14 dB, respectively. In vivo porcine heart results also demonstrate that, compared to AM, HOSVD improves CBR in open-chest acquisition (up to 19 dB) and contrast ratio (CR) in closed-chest acquisition (3 dB).@en

Purpose: Intraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice. Methods: In this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed. Results: As a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction. Conclusions: This work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis.@en

Purpose: To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE). Methods: Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume. Results: In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were ≤5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 ± 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow. Conclusions: Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (≤10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers.@en

Suppressing tissue clutter is an essential step in blood flow estimation and visualization, even when using ultrasound contrast agents. Blind source separation (BSS)-based clutter filter for high-framerate ultrasound imaging has been reported to perform better in tissue clutter suppression than the conventional frequency-based wall filter and nonlinear contrast pulsing schemes. The most notable BSS technique, singular value decomposition (SVD) has shown compelling results in cases of slow tissue motion. However, its performance degrades when the tissue motion is faster than the blood flow speed, conditions that are likely to occur when imaging the small vessels, such as in the myocardium. Independent component analysis (ICA) is another BSS technique that has been implemented as a clutter filter in the spatiotemporal domain. Instead, we propose to implement ICA in the spatial domain where motion should have less impact. In this work, we propose a clutter filter with the combination of SVD and ICA to improve the contrast-to-background ratio (CBR) in cases where tissue velocity is significantly faster than the flow speed. In an in vitro study, the range of fast tissue motion velocity was 5-25 mm/s and the range of flow speed was 1-12 mm/s. Our results show that the combination of ICA and SVD yields 7-10 dB higher CBR than SVD alone, especially in the tissue high-velocity range. The improvement is crucial for cardiac imaging where relatively fast myocardial motions are expected.@en

Left ventricular (LV) blood flow is an inherently complex time-varying 3-D phenomenon, where 2-D quantification often ignores the effect of out-of-plane motion. In this study, we describe high frame rate 4-D echocardiographic particle image velocimetry (echo-PIV) using a prototype matrix transesophageal transducer and a dynamic LV phantom for testing the accuracy of echo-PIV in the presence of complex flow patterns. Optical time-resolved tomographic PIV (tomo-PIV) was used as a reference standard for comparison. Echo-PIV and tomo-PIV agreed on the general profile of the LV flow patterns, but echo-PIV smoothed out the smaller flow structures. Echo-PIV also underestimated the flow rates at greater imaging depths, where the PIV kernel size and transducer point spread function were large relative to the velocity gradients. We demonstrate that 4-D echo-PIV could be performed in just four heart cycles, which would require only a short breath-hold, providing promising results. However, methods for resolving high velocity gradients in regions of poor spatial resolution are required before clinical translation.@en

Treatment of abdominal aortic (AA) aneurysms and stenotic lesions may be improved by analyzing their associated blood flow patterns. Angle-independent blood flow patterns in the AA can be obtained by combining echo-particle image velocimetry (ePIV) with high frame rate contrast-enhanced ultrasonography. However, ePIV performance is affected by ultrasound contrast agent (UCA) concentration, microbubble stability and tissue clutter. In this study we assessed the influence of acoustic pressure and UCA concentration on image quality for ePIV analysis. We also compared amplitude modulation (AM) and singular value decomposition (SVD) as tissue suppression strategies for ePIV. Fourteen healthy volunteers were imaged in the region of the distal AA. We tested four different UCA bolus volumes (0.25, 0.5, 0.75 and 1.5 ml) and four different acoustic output pressures (mechanical indices: 0.01, 0.03, 0.06 and 0.09). As image quality metrics, we measured contrast-to-background ratio, bubble disruption ratio and maximum normalized cross-correlation value during ePIV. At mechanical indices e 0.06, we detected severe bubble destruction, suggesting that very low acoustic pressures should be used for ePIV. SVD was able to suppress tissue clutter better than AM. The maximum tracking correlation was affected by both UCA concentration and flow rate, where at high flow rates, lower UCA concentrations resulted in slightly higher correlation values but more signal drop-outs during late diastole. High frame rate ePIV was successfully performed in the AA of healthy volunteers and shows promise for future studies in patients.@en

Cardiac function and vascular function are closely related to the flow of blood within. The flow velocities in these larger cavities easily reach 1 m/s, and generally complex spatiotemporal flow patterns are involved, especially in a non-physiologic state. Visualization of such flow patterns using ultrasound can be greatly enhanced by administration of contrast agents. Tracking the high-velocity complex flows is challenging with current clinical echographic tools, mostly because of limitations in signal-to-noise ratio; estimation of lateral velocities; and/or frame rate of the contrast-enhanced imaging mode. This review addresses the state of the art in 2-D high-frame-rate contrast-enhanced echography of ventricular and deep-vessel flow, from both technological and clinical perspectives. It concludes that current advanced ultrasound equipment is technologically ready for use in human contrast-enhanced studies, thus potentially leading to identification of the most clinically relevant flow parameters for quantifying cardiac and vascular function.@en

Phospholipid-coated microbubbles with a uniform acoustic response are a promising avenue for functional ultrasound sensing. A uniform acoustic response requires both a monodisperse size distribution and uniform viscoelastic shell properties. Monodisperse microbubbles can be produced in a microfluidic flow focusing device. Here, we investigate whether such monodisperse microbubbles have uniform viscoelastic shell properties and thereby a uniform “mono-acoustic” response. To this end, we visualized phase separation of the DSPC and DPPE-PEG5000 lipid shell components and measured the resonance curves of nearly 2000 single and freely floating microbubbles using a high-frequency acoustic scattering technique. The results demonstrate inhomogeneous phase-separated shell microdomains across the monodisperse bubble population, which may explain the measured inhomogeneous viscoelastic shell properties. The shell viscosity varied over an order of magnitude and the resonance frequency by a factor of two indicating both a variation in shell elasticity and in initial surface tension despite the relatively narrow size distribution.@en

Introduction: To improve carotid artery stenting (CAS), more information about the functioning of the stent is needed. Therefore, a method that can image the flow near and around a stent is required. The aim of this study was to evaluate the performance of high-frame-rate contrast-enhanced ultrasound (HFR CEUS) in the presence of a stent. Methodology: HFR CEUS acquisitions of a carotid artery phantom, a silicone tube with diameter 8 mm, with and without a stent were acquired at transmit voltages of 2V, 4V and 10V using a Verasonics ultrasound system and C5-2 probe. Different concentrations of ultrasound contrast agent (UCA) were tested in a blood mimicking fluid (BMF). Particle image velocimetry (PIV) analysis was performed on Singular Value Decomposition (SVD) filtered images. Mean and peak velocities, and correlation coefficients were compared between stented and non-stented regions. Also, experimental results were compared with theoretical and numerical models. Results: The averaged experimental mean velocity (0.113 m/s) was significant lower than the theoretical and numerical mean velocity (0.129 m/s). The averaged experimental peak velocity (0.152 m/s) was significant lower than the theoretical and numerical peak velocity (0.259 m/s). Correlation coefficients and averaged mean velocity values were lower (difference of 0.022 m/s) in stented regions compared to non-stented regions. Conclusion: In vitro experiments showed an underestimation of mean and peak velocities in stented regions compared to non-stented regions. However, the microbubbles can be tracked efficiently and the expected laminar flow profile can be quantified using HFR CEUS near and around a stent.@en

Blood flow patterns in the human left ventricle (LV) have shown relation to cardiac health. However, most studies in the literature are limited to a few patients and results are hard to generalize. This study aims to provide a new framework to generate more generalized insights into LV blood flow as a function of changes in anatomy and wall motion. In this framework, we studied the four-dimensional blood flow in LV via computational fluid dynamics (CFD) in conjunction with a statistical shape model (SSM), built from segmented LV shapes of 150 subjects. We validated results in an in-vitro dynamic phantom via time-resolved optical particle image velocimetry (PIV) measurements. This combination of CFD and the SSM may be useful for systematically assessing blood flow patterns in the LV as a function of varying anatomy and has the potential to provide valuable data for diagnosis of LV functionality.@en

Ultrafast 3D transesophageal echocardiographic (TEE) imaging, combined with 3D echo particle image velocimetry (ePIV), would be ideal for tracking the complex blood flow patterns in the heart. We are developing a miniature pediatric matrix TEE transducer that employs micro-beamforming (μBF) and allows high framerate in 3D. In this paper, we assess the feasibility of 3D ePIV with a high frame rate, small aperture transducer and the influence of the micro-beamforming technique. We compare the results of 3D ePIV on simulated images using the μBF transducer and an idealized, fully sampled (FS) matrix transducer. For the two transducers, we have simulated high-framerate imaging of an 8.4mm diameter artery having a known 4D velocity field. The simulations were performed in FieldII. 1000 3D volumes, at a rate of 1000 volumes/sec, were created using a single diverging transmission per volume. The error in the 3D velocity estimation was measured by comparing the ePIV results of both transducers to the ground truth. The results on the simulated volumes show that ePIV can estimate the 4D velocity field of the arterial phantom using these small-aperture transducers suitable for pediatric 3D TEE. The μBF transducer (RMSE 44.0%) achieved comparable ePIV accuracy to that of the FS transducer (RMSE 42.6%).@en

Ultrasound (US) contrast agents consist of microbubbles ranging from 1 to 10 μm in size. The acoustical response of individual microbubbles can be studied with high-frame-rate optics or an "acoustical camera"(AC). The AC measures the relative microbubble oscillation while the optical camera measures the absolute oscillation. In this article, the capabilities of the AC are extended to measure the absolute oscillations. In the AC setup, microbubbles are insonified with a high- (25 MHz) and low-frequency US wave (1-2.5 MHz). Other than the amplitude modulation (AM) from the relative size change of the microbubble (employed in Renaud, Bosch, van der Steen, and de Jong (2012a). "An 'acoustical camera' for in vitro characterization of contrast agent microbubble vibrations,"Appl. Phys. Lett. 100(10), 101911, the high-frequency response from individual vibrating microbubbles contains a phase modulation (PM) from the microbubble wall displacement, which is the extension described here. The ratio of PM and AM is used to determine the absolute radius, R0. To test this sizing, the size distributions of two monodisperse microbubble populations (R 0 = 2.1 and 3.5 μm) acquired with the AC were matched to the distribution acquired with a Coulter counter. As a result of measuring the absolute size of the microbubbles, this "extended AC"can capture the full radial dynamics of single freely floating microbubbles with a throughput of hundreds of microbubbles per hour. @en

Natural and active shear wave elastography (SWE) are potential ultrasound-based techniques to non-invasively assess myocardial stiffness, which could improve current diagnosis of heart failure. This study aims to bridge the knowledge gap between both techniques and discuss their respective impacts on cardiac stiffness evaluation. We recorded the mechanical waves occurring after aortic and mitral valve closure (AVC, MVC) and those induced by acoustic radiation force throughout the cardiac cycle in four pigs after sternotomy. Natural SWE showed a higher feasibility than active SWE, which is an advantage for clinical application. Median propagation speeds of 2.5–4.0 m/s and 1.6–4.0 m/s were obtained after AVC and MVC, whereas ARF-based median speeds of 0.9–1.2 m/s and 2.1–3.8 m/s were reported for diastole and systole, respectively. The different wave characteristics in both methods, such as the frequency content, complicate the direct comparison of waves. Nevertheless, a good match was found in propagation speeds between natural and active SWE at the moment of valve closure, and the natural waves showed higher propagation speeds than in diastole. Furthermore, the results demonstrated that the natural waves occur in between diastole and systole identified with active SWE, and thus represent a myocardial stiffness in between relaxation and contraction.@en