Left ventricular high frame rate echo-particle image velocimetry: clinical application and comparison with conventional imaging.

BACKGROUND: Echo-Particle Image Velocimetry (echoPIV) tracks speckle patterns from ultrasound contrast agent(UCA), being less angle-sensitive than colour Doppler. High frame rate (HFR) echoPIV enables tracking of high velocity flow in the left ventricle (LV). We aimed to demonstrate the potential clinical use of HFR echoPIV and investigate the feasibility and accuracy in patients. METHODS: Nineteen patients admitted for heart failure were included. HFR contrast images were acquired from an apical long axis view (ALAX), using a fully-programmable ultrasound system. A clinical UCA was continuously infused with a dedicated pump. Additionally, echocardiographic images were obtained using a clinical system, including LV contrast-enhanced images and pulsed-wave (PW) Doppler of the LV inflow and outflow in ALAX. 11 patients underwent CMR and 4 cardiac CT as clinically indicated. These CMR and CT images were used as reference. In 10 patients with good echoPIV tracking and reference imaging, the intracavitary flow was compared between echoPIV, conventional and UCA echocardiography. RESULTS: EchoPIV tracking quality was good in 12/19 (63%), moderate in 2/19 (10%) and poor in 5/19 (26%) subjects. EchoPIV could determine inflow velocity in 17/19 (89%), and outflow in 14/19 (74%) patients. The correlation of echoPIV and PW Doppler was good for the inflow (R2 = 0.77 to PW peak; R2 = 0.80 PW mean velocity) and moderate for the outflow (R2 = 0.54 to PW peak; R2 = 0.44 to PW mean velocity), with a tendency for echoPIV to underestimate PW velocities. In selected patients, echoPIV was able in a single acquisition to demonstrate flow patterns which required multiple interrogations with classical echocardiography. Those flow patterns could also be linked to anatomical abnormalities as seen in CMR or CT. CONCLUSION: HFR echoPIV tracks multidirectional and complex flow patterns which are unapparent with conventional echocardiography, while having comparable feasibility. EchoPIV tends to underestimate flow velocities as compared to PW Doppler. It has the potential to provide in one acquisition all the functional information obtained by conventional imaging, overcoming the angle dependency of Doppler and low frame rate of classical contrast imaging.

A Tiled Ultrasound Matrix Transducer for Volumetric Imaging of the Carotid Artery.

High frame rate three-dimensional (3D) ultrasound imaging would offer excellent possibilities for the accurate assessment of carotid artery diseases. This calls for a matrix transducer with a large aperture and a vast number of elements. Such a matrix transducer should be interfaced with an application-specific integrated circuit (ASIC) for channel reduction. However, the fabrication of such a transducer integrated with one very large ASIC is very challenging and expensive. In this study, we develop a prototype matrix transducer mounted on top of multiple identical ASICs in a tiled configuration. The matrix was designed to have 7680 piezoelectric elements with a pitch of 300 µm × 150 µm integrated with an array of 8 × 1 tiled ASICs. The performance of the prototype is characterized by a series of measurements. The transducer exhibits a uniform behavior with the majority of the elements working within the -6 dB sensitivity range. In transmit, the individual elements show a center frequency of 7.5 MHz, a -6 dB bandwidth of 45%, and a transmit efficiency of 30 Pa/V at 200 mm. In receive, the dynamic range is 81 dB, and the minimum detectable pressure is 60 Pa per element. To demonstrate the imaging capabilities, we acquired 3D images using a commercial wire phantom.

Local myocardial stiffness variations identified by high frame rate shear wave echocardiography.

BACKGROUND: Shear waves are generated by the closure of the heart valves. Significant differences in shear wave velocity have been found recently between normal myocardium and disease models of diffusely increased muscle stiffness. In this study we correlate in vivo myocardial shear wave imaging (SWI) with presence of scarred tissue, as model for local increase of stiffness. Stiffness variation is hypothesized to appear as velocity variation. METHODS: Ten healthy volunteers (group 1), 10 hypertrophic cardiomyopathy (HCM) patients without any cardiac intervention (group 2), and 10 HCM patients with prior septal reduction therapy (group 3) underwent high frame rate tissue Doppler echocardiography. The SW in the interventricular septum after aortic valve closure was mapped along two M-mode lines, in the inner and outer layer. RESULTS: We compared SWI to 3D echocardiography and strain imaging. In groups 1 and 2, no change in velocity was detected. In group 3, 8/10 patients showed a variation in SW velocity. All three patients having transmural scar showed a simultaneous velocity variation in both layers. Out of six patients with endocardial scar, five showed variations in the inner layer. CONCLUSION: Local variations in stiffness, with myocardial remodeling post septal reduction therapy as model, can be detected by a local variation in the propagation velocity of naturally occurring shear waves.

The effect of size range on ultrasound-induced translations in microbubble populations.

Microbubble translations driven by ultrasound-induced radiation forces can be beneficial for applications in ultrasound molecular imaging and drug delivery. Here, the effect of size range in microbubble populations on their translations is investigated experimentally and theoretically. The displacements within five distinct size-isolated microbubble populations are driven by a standard ultrasound-imaging probe at frequencies ranging from 3 to 7 MHz, and measured using the multi-gate spectral Doppler approach. Peak microbubble displacements, reaching up to 10 µm per pulse, are found to describe transient phenomena from the resonant proportion of each bubble population. The overall trend of the statistical behavior of the bubble displacements, quantified by the total number of identified displacements, reveals significant differences between the bubble populations as a function of the transmission frequency. A good agreement is found between the experiments and theory that includes a model parameter fit, which is further supported by separate measurements of individual microbubbles to characterize the viscoelasticity of their stabilizing lipid shell. These findings may help to tune the microbubble size distribution and ultrasound transmission parameters to optimize the radiation-force translations. They also demonstrate a simple technique to characterize the microbubble shell viscosity, the fitted model parameter, from freely floating microbubble populations using a standard ultrasound-imaging probe.

Design of an Ultrasound Transceiver ASIC with a Switching-Artifact Reduction Technique for 3D Carotid Artery Imaging.

This paper presents an ultrasound transceiver application-specific integrated circuit (ASIC) directly integrated with an array of 12 × 80 piezoelectric transducer elements to enable next-generation ultrasound probes for 3D carotid artery imaging. The ASIC, implemented in a 0.18 µm high-voltage Bipolar-CMOS-DMOS (HV BCD) process, adopted a programmable switch matrix that allowed selected transducer elements in each row to be connected to a transmit and receive channel of an imaging system. This made the probe operate like an electronically translatable linear array, allowing large-aperture matrix arrays to be interfaced with a manageable number of system channels. This paper presents a second-generation ASIC that employed an improved switch design to minimize clock feedthrough and charge-injection effects of high-voltage metal-oxide-semiconductor field-effect transistors (HV MOSFETs), which in the first-generation ASIC caused parasitic transmissions and associated imaging artifacts. The proposed switch controller, implemented with cascaded non-overlapping clock generators, generated control signals with improved timing to mitigate the effects of these non-idealities. Both simulation results and electrical measurements showed a 20 dB reduction of the switching artifacts. In addition, an acoustic pulse-echo measurement successfully demonstrated a 20 dB reduction of imaging artifacts.

High-Frame-Rate Contrast-enhanced US Particle Image Velocimetry in the Abdominal Aorta: First Human Results.

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 flow 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. © RSNA, 2018 Online supplemental material is available for this article.

Photoacoustic imaging of sub-diffraction objects with spectral contrast.

Photoacoustic imaging couples the chemical specificity of optical absorption with the viewing depth of ultrasound. Systems based on linear array transducers have the versatility to be applied in various (pre-) clinical scenarios but face a trade-off between viewing depth and image resolution depending on transducer frequency and aperture. We propose here a method to disentangle, with precision, small, closely spaced targets with optical spectral contrast, without impairing the imaging depth. Photoacoustic data sets were recorded at two different optical wavelengths. We accurately recovered object separation distances (mean error=2.3%±6%) from the phase difference between signals across the array, down to a spacing of 1/20th of the system's beam-formed lateral resolution. The proposed method may enable the translation of super-resolution microscopy to deep tissue imaging.

Acoustic droplet vaporization is initiated by superharmonic focusing.

Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon have the potential to be a highly efficient system for local drug delivery, embolotherapy, or for tumor imaging. The physical mechanisms underlying the acoustic activation of these phase-change emulsions into a bubbly dispersion, termed acoustic droplet vaporization, have not been well understood. The droplets have a very high activation threshold; its frequency dependence does not comply with homogeneous nucleation theory and localized nucleation spots have been observed. Here we show that acoustic droplet vaporization is initiated by a combination of two phenomena: highly nonlinear distortion of the acoustic wave before it hits the droplet and focusing of the distorted wave by the droplet itself. At high excitation pressures, nonlinear distortion causes significant superharmonics with wavelengths of the order of the droplet size. These superharmonics strongly contribute to the focusing effect; therefore, the proposed mechanism also explains the observed pressure thresholding effect. Our interpretation is validated with experimental data captured with an ultrahigh-speed camera on the positions of the nucleation spots, where we find excellent agreement with the theoretical prediction. Moreover, the presented mechanism explains the hitherto counterintuitive dependence of the nucleation threshold on the ultrasound frequency. The physical insight allows for the optimization of acoustic droplet vaporization for therapeutic applications, in particular with respect to the acoustic pressures required for activation, thereby minimizing the negative bioeffects associated with the use of high-intensity ultrasound.

Effect of interstitial fluid pressure on shear wave elastography: an experimental and computational study.

Objective. An elevated interstitial fluid pressure (IFP) can lead to strain-induced stiffening of poroelastic biological tissues. As shear wave elastography (SWE) measures functional tissue stiffness based on the propagation speed of acoustically induced shear waves, the shear wave velocity (SWV) can be used as an indirect measurement of the IFP. The underlying biomechanical principle for this stiffening behavior with pressurization is however not well understood, and we therefore studied how IFP affects SWV through SWE experiments and numerical modeling.Approach. For model set-up and verification, SWE experiments were performed while dynamically modulating IFP in a chicken breast. To identify the confounding factors of the SWV-IFP relationship, we manipulated the material model (linear poroelastic versus porohyperelastic), deformation assumptions (geometric linearity versus nonlinearity), and boundary conditions (constrained versus unconstrained) in a finite element model mimicking the SWE experiments.Main results. The experiments demonstrated a statistically significant positive correlation between the SWV and IFP. The model was able to reproduce a similar SWV-IFP relationship by considering an unconstrained porohyperelastic tissue. Material nonlinearity was identified as the primary factor contributing to this relationship, whereas geometric nonlinearity played a smaller role. The experiments also highlighted the importance of the dynamic nature of the pressurization procedure, as indicated by a different observed SWV-IFP for pressure buildup and relaxation, but its clinical relevance needs to be further investigated.Significance. The developed model provides an adaptable framework for SWE of poroelastic tissues and paves the way towards non-invasive measurements of IFP.

A comparison of ultrafast and conventional spectral Doppler ultrasound to measure cerebral blood flow velocity during inguinal hernia repair in infants.

BACKGROUND: Ultrafast cerebral Doppler ultrasound enables simultaneous quantification and visualization of cerebral blood flow velocity. The aim of this study is to compare the use of conventional and ultrafast spectral Doppler during anesthesia and their potential to show the effect of anesthesiologic procedures on cerebral blood flow velocities, in relation to blood pressure and cerebral oxygenation in infants undergoing inguinal hernia repair. METHODS: A single-center prospective observational cohort study in infants up to six months of age. We evaluated conventional and ultrafast spectral Doppler cerebral ultrasound measurements in terms of number of successful measurements during the induction of anesthesia, after sevoflurane induction, administration of caudal analgesia, a fluid bolus and emergence of anesthesia. Cerebral blood flow velocity was quantified in pial arteries using conventional spectral Doppler and in the cerebral cortex using ultrafast Doppler by peak systolic velocity, end diastolic velocity and resistivity index. RESULTS: Twenty infants were included with useable conventional spectral Doppler images in 72/100 measurements and ultrafast Doppler images in 51/100 measurements. Intraoperatively, the success rates were 53/60 (88.3%) and 41/60 (68.3%), respectively. Cerebral blood flow velocity increased after emergence for both conventional (end diastolic velocity, from 2.01 to 2.75 cm/s, p < 0.001) and ultrafast spectral Doppler (end diastolic velocity, from 0.59 to 0.94 cm/s), whereas cerebral oxygenation showed a reverse pattern with a decrease after the emergence of the infant (85% to 68%, p < 0.001). CONCLUSION: It is possible to quantify cortical blood flow velocity during general anesthesia using conventional and ultrafast spectral Doppler cerebral ultrasound. Cerebral blood flow velocity and blood pressure decreased, while regional cerebral oxygenation increased during general anesthesia. Ultrafast spectral Doppler ultrasound offers novel insights into perfusion within the cerebral cortex, unattainable through conventional spectral ultrasound. Yet, ultrafast Doppler is curtailed by a lower success rate and a more rigorous learning curve compared to conventional method.

Automatic Max-Likelihood Envelope Detection Algorithm for Quantitative High-Frame-Rate Ultrasound for Neonatal Brain Monitoring.

OBJECTIVE: Post-operative brain injury in neonates may result from disturbed cerebral perfusion, but accurate peri-operative monitoring is lacking. High-frame-rate (HFR) cerebral ultrasound could visualize and quantify flow in all detectable vessels using spectral Doppler; however, automated quantification in small vessels is challenging because of low signal amplitude. We have developed an automatic envelope detection algorithm for HFR pulsed wave spectral Doppler signals, enabling neonatal brain quantitative parameter maps during and after surgery. METHODS: HFR ultrasound data from high-risk neonatal surgeries were recorded with a custom HFR mode (frame rate = 1000 Hz) on a Zonare ZS3 system. A pulsed wave Doppler spectrogram was calculated for each pixel containing blood flow in the image, and spectral peak velocity was tracked using a max-likelihood estimation algorithm of signal and noise regions in the spectrogram, where the most likely cross-over point marks the blood flow velocity. The resulting peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) were compared with other detection schemes, manual tracking and RIs from regular pulsed wave Doppler measurements in 10 neonates. RESULTS: Envelope detection was successful in both high- and low-quality arterial and venous flow spectrograms. Our technique had the lowest root mean square error for EDV, PSV and RI (0.46 cm/s, 0.53 cm/s and 0.15, respectively) when compared with manual tracking. There was good agreement between the clinical pulsed wave Doppler RI and HFR measurement with a mean difference of 0.07. CONCLUSION: The max-likelihood algorithm is a promising approach to accurate, automated cerebral blood flow monitoring with HFR imaging in neonates.

Ultrasound Shear Wave Elastography in Cardiology.

The advent of high-frame rate imaging in ultrasound allowed the development of shear wave elastography as a noninvasive alternative for myocardial stiffness assessment. It measures mechanical waves propagating along the cardiac wall with speeds that are related to stiffness. The use of cardiac shear wave elastography in clinical studies is increasing, but a proper understanding of the different factors that affect wave propagation is required to correctly interpret results because of the heart's thin-walled geometry and intricate material properties. The aims of this review are to give an overview of the general concepts in cardiac shear wave elastography and to discuss in depth the effects of age, hemodynamic loading, cardiac morphology, fiber architecture, contractility, viscoelasticity, and system-dependent factors on the measurements, with a focus on clinical application. It also describes how these factors should be considered during acquisition, analysis, and reporting to ensure an accurate, robust, and reproducible measurement of the shear wave.

An Ultrasound Matrix Transducer for High-Frame-Rate 3-D Intra-cardiac Echocardiography.

OBJECTIVE: Described here is the development of an ultrasound matrix transducer prototype for high-frame-rate 3-D intra-cardiac echocardiography. METHODS: The matrix array consists of 16 × 18 lead zirconate titanate elements with a pitch of 160 µm × 160 µm built on top of an application-specific integrated circuit that generates transmission signals and digitizes the received signals. To reduce the number of cables in the catheter to a feasible number, we implement subarray beamforming and digitization in receive and use a combination of time-division multiplexing and pulse amplitude modulation data transmission, achieving an 18-fold reduction. The proposed imaging scheme employs seven fan-shaped diverging transmit beams operating at a pulse repetition frequency of 7.7 kHz to obtain a high frame rate. The performance of the prototype is characterized, and its functionality is fully verified. RESULTS: The transducer exhibits a transmit efficiency of 28 Pa/V at 5 cm per element and a bandwidth of 60% in transmission. In receive, a dynamic range of 80 dB is measured with a minimum detectable pressure of 10 Pa per element. The element yield of the prototype is 98%, indicating the efficacy of the manufacturing process. The transducer is capable of imaging at a frame rate of up to 1000 volumes/s and is intended to cover a volume of 70° × 70° × 10 cm. CONCLUSION: These advanced imaging capabilities have the potential to support complex interventional procedures and enable full-volumetric flow, tissue, and electromechanical wave tracking in the heart.

Analytic prediction of droplet vaporization events to estimate the precision of ultrasound-based proton range verification.

BACKGROUND: The safety and efficacy of proton therapy is currently hampered by range uncertainties. The combination of ultrasound imaging with injectable radiation-sensitive superheated nanodroplets was recently proposed for in vivo range verification. The proton range can be estimated from the distribution of nanodroplet vaporization events, which is stochastically related to the stopping distribution of protons, as nanodroplets are vaporized by protons reaching their maximal LET at the end of their range. PURPOSE: Here, we aim to estimate the range estimation precision of this technique. As for any stochastic measurement, the precision will increase with the sample size, that is, the number of detected vaporizations. Thus, we first develop and validate a model to predict the number of vaporizations, which is then applied to estimate the range verification precision for a set of conditions (droplet size, droplet concentration, and proton beam parameters). METHODS: Starting from the thermal spike theory, we derived a model that predicts the expected number of droplet vaporizations in an irradiated sample as a function of the droplet size, concentration, and number of protons. The model was validated by irradiating phantoms consisting of size-sorted perfluorobutane droplets dispersed in an aqueous matrix. The number of protons was counted with an ionization chamber, and the droplet vaporizations were recorded and counted individually using high frame rate ultrasound imaging. After validation, the range estimate precision was determined for different conditions using a Monte Carlo algorithm. RESULTS: A good agreement between theory and experiments was observed for the number of vaporizations, especially for large (5.8 ± 2.2 µm) and medium (3.5 ± 1.1 µm) sized droplets. The number of events was lower than expected in phantoms with small droplets (2.0 ± 0.7 µm), but still within the same order of magnitude. The inter-phantom variability was considerably larger (up to 30x) than predicted by the model. The validated model was then combined with Monte Carlo simulations, which predicted a theoretical range retrieval precision improving with the square-root of the number of vaporizations, and degrading at high beam energies due to range straggling. For single pencil beams with energies between 70 and 240 MeV, a range verification precision below 1% of the range required perfluorocarbon concentrations in the order of 0.3-2.4 µM. CONCLUSION: We proposed and experimentally validated a model to provide a quick estimate of the number of vaporizations for a given set of conditions (droplet size, droplet concentration, and proton beam parameters). From this model, promising range verification performances were predicted for realistic perfluorocarbon concentrations. These findings are an incentive to move towards preclinical studies, which are critical to assess the achievable droplet distribution in and around the tumor, and hence the in vivo range verification precision.

High-Frame-Rate Volumetric Porcine Renal Vasculature Imaging.

OBJECTIVE: The aim of this study was to assess the feasibility and imaging options of contrast-enhanced volumetric ultrasound kidney vasculature imaging in a porcine model using a prototype sparse spiral array. METHODS: Transcutaneous freehand in vivo imaging of two healthy porcine kidneys was performed according to three protocols with different microbubble concentrations and transmission sequences. Combining high-frame-rate transmission sequences with our previously described spatial coherence beamformer, we determined the ability to produce detailed volumetric images of the vasculature. We also determined power, color and spectral Doppler, as well as super-resolved microvasculature in a volume. The results were compared against a clinical 2-D ultrasound machine. RESULTS: Three-dimensional visualization of the kidney vasculature structure and blood flow was possible with our method. Good structural agreement was found between the visualized vasculature structure and the 2-D reference. Microvasculature patterns in the kidney cortex were visible with super-resolution processing. Blood flow velocity estimations were within a physiological range and pattern, also in agreement with the 2-D reference results. CONCLUSION: Volumetric imaging of the kidney vasculature was possible using a prototype sparse spiral array. Reliable structural and temporal information could be extracted from these imaging results.

Continuous shear wave measurements for dynamic cardiac stiffness evaluation in pigs.

Ultrasound-based shear wave elastography is a promising technique to non-invasively assess the dynamic stiffness variations of the heart. The technique is based on tracking the propagation of acoustically induced shear waves in the myocardium of which the propagation speed is linked to tissue stiffness. This measurement is repeated multiple times across the cardiac cycle to assess the natural variations in wave propagation speed. The interpretation of these measurements remains however complex, as factors such as loading and contractility affect wave propagation. We therefore applied transthoracic shear wave elastography in 13 pigs to investigate the dependencies of wave speed on pressure-volume derived indices of loading, myocardial stiffness, and contractility, while altering loading and inducing myocardial ischemia/reperfusion injury. Our results show that diastolic wave speed correlates to a pressure-volume derived index of operational myocardial stiffness (R = 0.75, p < 0.001), suggesting that both loading and intrinsic properties can affect diastolic wave speed. Additionally, the wave speed ratio, i.e. the ratio of systolic and diastolic speed, correlates to a pressure-volume derived index of contractility, i.e. preload-recruitable stroke work (R = 0.67, p < 0.001). Measuring wave speed ratio might thus provide a non-invasive index of contractility during ischemia/reperfusion injury.

Higher Order Singular Value Decomposition Filter for Contrast Echocardiography.

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).

Independent Component Analysis Filter for Small Vessel Contrast Imaging During Fast Tissue Motion.

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.

Imaging Scheme for 3-D High-Frame-Rate Intracardiac Echography: A Simulation Study.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is normally treated by RF ablation. Intracardiac echography (ICE) is widely employed during RF ablation procedures to guide the electrophysiologist in navigating the ablation catheter, although only 2-D probes are currently clinically used. A 3-D ICE catheter would not only improve visualization of the atrium and ablation catheter, but it might also provide the 3-D mapping of the electromechanical wave (EW) propagation pattern, which represents the mechanical response of cardiac tissue to electrical activity. The detection of this EW needs 3-D high-frame-rate imaging, which is generally only realizable in tradeoff with channel count and image quality. In this simulation-based study, we propose a high volume rate imaging scheme for a 3-D ICE probe design that employs 1-D micro-beamforming in the elevation direction. Such a probe can achieve a high frame rate while reducing the channel count sufficiently for realization in a 10-Fr catheter. To suppress the grating-lobe (GL) artifacts associated with micro-beamforming in the elevation direction, a limited number of fan-shaped beams with a wide azimuthal and narrow elevational opening angle are sequentially steered to insonify slices of the region of interest. An angular weighted averaging of reconstructed subvolumes further reduces the GL artifacts. We optimize the transmit beam divergence and central frequency based on the required image quality for EW imaging (EWI). Numerical simulation results show that a set of seven fan-shaped transmission beams can provide a frame rate of 1000 Hz and a sufficient spatial resolution to visualize the EW propagation on a large 3-D surface.

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature.

Superheated nanodroplet (ND) vaporization by proton radiation was recently demonstrated, opening the door to ultrasound-based in vivo proton range verification. However, at body temperature and physiological pressures, perfluorobutane nanodroplets (PFB-NDs), which offer a good compromise between stability and radiation sensitivity, are not directly sensitive to primary protons. Instead, they are vaporized by infrequent secondary particles, which limits the precision for range verification. The radiation-induced vaporization threshold (i.e., sensitization threshold) can be reduced by lowering the pressure in the droplet such that ND vaporization by primary protons can occur. Here, we propose to use an acoustic field to modulate the pressure, intermittently lowering the proton sensitization threshold of PFB-NDs during the rarefactional phase of the ultrasound wave. Simultaneous proton irradiation and sonication with a 1.1 MHz focused transducer, using increasing peak negative pressures (PNPs), were applied on a dilution of PFB-NDs flowing in a tube, while vaporization was acoustically monitored with a linear array. Sensitization to primary protons was achieved at temperatures between [Formula: see text] and 40 °C using acoustic PNPs of relatively low amplitude (from 800 to 200 kPa, respectively), while sonication alone did not lead to ND vaporization at those PNPs. Sensitization was also measured at the clinically relevant body temperature (i.e., 37 °C) using a PNP of 400 kPa. These findings confirm that acoustic modulation lowers the sensitization threshold of superheated NDs, enabling a direct proton response at body temperature.