IN [1], there is a mistake in the timing diagram shown in Fig. 6. Switches S 1-S 4 are skipping some of the samples and the rate at which they are operating implies a TDM rate of 10 MHz, whereas (as described in [1]) this should be 20 MHz. In the updated Fig. 6, S 1-S 4 have been updated and a minor change has been made to the timing shown for switches Q₁ and Q₂, such that the correct TDM rate is indicated and no sample provided to the S/H stage via N1-N4 is skipped in the diagram. (Figure presented).

Ultrasound contrast agents, comprised of phospholipid-coated microbubbles, can be produced as monodisperse populations using a microfluidic flow-focusing device. However, microbubble coalescence remains a significant challenge. High production temperatures (e.g., 55 °C) can be used to suppress coalescence, but it complicates the microfluidic device design and is incompatible with targeting agents and drug conjugates. This study investigates the production of monodisperse microbubbles at room temperature with the addition of the amphiphilic surfactant Pluronic F68. Two 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based phospholipid formulations were investigated: F1, containing 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[carbonyl-methoxypolyethylene glycol] (DPPE-PEG5000), and F2, which included both DPPE-PEG5000 and polyoxyethylene(40) stearate (PEG40-stearate). We characterized the size stability and acoustic behavior of monodisperse microbubbles produced with various Pluronic F68 concentrations. Adding 5-10 mol % Pluronic F68 was found to effectively suppress coalescence and facilitated the production of monodisperse microbubbles that remained shelf stable for at least 7 days. Acoustic attenuation measurements revealed a shell stiffness ranging from 0.78 to 0.93 N/m for these microbubbles. The 10 mol % Pluronic F68 addition (10PF) demonstrated superior monodispersity and was selected for further experiments. Upon dilution, the size and resonance frequencies of both F1-10PF and F2-10PF decreased over time, though F2-10PF showed better stability compared to F1-10PF for both metrics. Both F1-10PF and F2-10PF exhibited a stronger subharmonic scattering intensity than SonoVue (clinical approved microbubbles), which offers potential for blood pressure sensing. Our study shows that incorporating Pluronic F68 facilitates the production of monodisperse microbubbles at room temperature that are stable long-term and have excellent acoustical properties, with the F2-10PF formulation demonstrating better stability than the F1-10PF.

Here we propose an ultrasound contrast-based imaging method that enables non-invasive quantitative assessment of ambient pressure changes inside the body (such as blood pressure). We subject the microbubbles in the contrast agent to two frequencies: A low-frequency (57 kHz) signal that dynamically manipulates the ambient pressure, and a series of high-frequency (4 MHz) pulses for exciting and imaging the bubble response. The imaging pulses exploit the ambient pressure sensitivity of the subharmonic microbubble response, while the low-frequency signal provided an intrinsic calibration for measurement of ambient pressure changes. We tested this approach in an in vitro setup and show that it can visualize and quantify ambient pressure differences with a sensitivity of 0.5 dB/kPa.

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.

The accurate determination of the transfer function of ultrasound transducers is important for their design and operational performance. However, conventional methods for quantifying the transfer function, such as hydrophone measurements, radiation force balance, and pulse-echo measurements, are costly and complex due to specialized equipment required. In this study, we introduce a novel approach to estimate the transfer function of ultrasound transducers by measuring the acoustic streaming velocity generated by the transducer. We utilize an experimental setup consisting of a water tank with a millimeter scale, an ink-filled syringe, and a camera for recording the streaming phenomenon. Through streaming velocity measurements in the frequency range from 2 to 8 MHz, we determined the transfer function of an unfocused circular transducer with a center frequency of 5 MHz and a radius of 5.6 mm. We compared the performance of our method with hydrophone and pulse-echo measurements. At the center frequency, we measured a transmit efficiency of 1.9 kPa/V using the streaming approach, while hydrophone and pulse-echo measurements yielded transmit efficiencies of 2.1 kPa/V and 1.8 kPa/V, respectively. These findings demonstrate that the proposed method for estimating the transfer function of ultrasound transducers achieves a sufficient level of accuracy comparable to pulse-echo and hydrophone measurements.

This article presents an application-specific integrated circuit (ASIC) for catheter-based 3-D ultrasound imaging probes. The pitch-matched design implements a comprehensive architecture with high-voltage (HV) transmitters, analog front ends, hybrid beamforming analog-To-digital converters (ADCs), and data transmission to the imaging system. To reduce the number of cables in the catheter while maintaining a small footprint per element, transmission (TX) beamforming is realized on the chip with a combination of a shift register (SR) and a row/column (R/C) approach. To explore an additional cable-count reduction in the receiver part of the design, a channel with a combination of time-division multiplexing (TDM), subarray beamforming, and multi-level pulse amplitude modulation (PAM) data transmission is also included. This achieves an 18-fold cable-count reduction and minimizes the power consumption in the catheter by a load modulation (LM) cable driver. It is further explored how common-mode interference can limit beamforming gain and a strategy to reduce its impact with local regulators is discussed. The chip was fabricated in TSMC 0.18-m HV BCD technology and a 2-D PZT transducer matrix of 16 × 18 elements with a pitch of 160 m and a center frequency of 6 MHz was manufactured on the chip. The system can generate all required TX patterns at up to 30 V, provides quick settling after the TX phase, and has an reception (RX) power consumption of only 1.12 mW/element. The functionality and operation of up to 1000 volumes/s have been demonstrated in electrical and acoustic imaging experiments.

This article presents a pitch-matched transceiver application-specific integrated circuit (ASIC) for a wearable ultrasound device intended for transfontanelle ultrasonography, which includes element-level 20-V unipolar pulsers with transmit (TX) beamforming, and receive (RX) circuitry that combines eightfold multiplexing, four-channel micro-beamforming (?BF), and subgroup-level digitization to achieve an initial 32-fold channel-count reduction. The ?BF is based on passive boxcar integration, merged with a 10-bit 40 MS/s SAR ADC in the charge domain, thus obviating the need for explicit anti-alias filtering (AAF) and power-hungry ADC drivers. A compact and low-power reference generator employs an area-efficient MOS capacitor as a reservoir to quickly set a reference for the ADC in the charge domain. A low-power multi-level data link, based on 16-level pulse-amplitude modulation, concatenates the outputs of four ADCs, providing an overall 128-fold channel-count reduction. A prototype transceiver ASIC was fabricated in a 180-nm BCD technology, and interfaces with a 2-D PZT transducer array of 16 × 16 elements with a pitch of 125 ?m and a center frequency of 9 MHz. The ASIC consumes 1.83 mW/element. The data link achieves an aggregate 3.84 Gb/s data rate with 3.3 pJ/bit energy efficiency. The ASIC's functionality has been demonstrated through electrical, acoustic, and imaging experiments.

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.

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.

Understanding and controlling the ultrasound contrast agent (UCA)'s response to an applied ultrasound pressure field are crucial when investigating ultrasound imaging sequences and therapeutic applications. The magnitude and frequency of the applied ultrasonic pressure waves affect the oscillatory response of the UCA. Therefore, it is important to have an ultrasound compatible and optically transparent chamber in which the acoustic response of the UCA can be studied. The aim of our study was to determine the in situ ultrasound pressure amplitude in the ibidi μ -slide I Luer channel, an optically transparent chamber suitable for cell culture, including culture under flow, for all microchannel heights (200, 400, 600, and 800 μm). First, the in situ pressure field in the 800- μm high channel was experimentally characterized using Brandaris 128 ultrahigh-speed camera recordings of microbubbles (MBs) and a subsequent iterative processing method, upon insonification at 2 MHz, 45° incident angle, and 50-kPa peak negative pressure (PNP). Control studies in another cell culture chamber, the CLINIcell, were compared with the obtained results. The pressure amplitude was -3.7 dB with respect to the pressure field without the ibidi μ -slide. Second, using finite-element analysis, we determined the in situ pressure amplitude in the ibidi with the 800- μm channel (33.1 kPa), which was comparable to the experimental value (34 kPa). The simulations were extended to the other ibidi channel heights (200, 400, and 600 μm) with either 35° or 45° incident angle, and at 1 and 2 MHz. The predicted in situ ultrasound pressure fields were between -8.7 and -1.1 dB of the incident pressure field depending on the listed configurations of ibidi slides with different channel heights, applied ultrasound frequencies, and incident angles. In conclusion, the determined ultrasound in situ pressures demonstrate the acoustic compatibility of the ibidi μ -slide I Luer for different channel heights, thereby showing its potential for studying the acoustic behavior of UCAs for imaging and therapy.

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).

There is an increased desire for miniature ultrasound probes with small apertures to provide volumetric images at high frame rates for in-body applications. Satisfying these increased requirements makes simultaneous achievement of a good lateral resolution a challenge. As micro-beamforming is often employed to reduce data rate and cable count to acceptable levels, receive processing methods that try to improve spatial resolution will have to compensate the introduced reduction in focusing. Existing beamformers do not realize sufficient improvement and/or have a computational cost that prohibits their use. Here we propose the use of adaptive beamforming by deep learning (ABLE) in combination with training targets generated by a large aperture array, which inherently has better lateral resolution. In addition, we modify ABLE to extend its receptive field across multiple voxels. We illustrate that this method improves lateral resolution both quantitatively and qualitatively, such that image quality is improved compared with that achieved by existing delay-and-sum, coherence factor, filtered-delay-multiplication-and-sum and Eigen-based minimum variance beamformers. We found that only in silica data are required to train the network, making the method easily implementable in practice.

This article presents a low-power and small-area transceiver application-specific integrated circuit (ASIC) for 3-D trans-fontanelle ultrasonography. A novel micro-beamforming receiver architecture that employs current-mode summation and boxcar integration is used to realize delay-and-sum on an N -element sub-array using N× fewer capacitive memory elements than conventional micro-beamforming implementations, thus reducing the hardware overhead associated with the memory elements. The boxcar integration also obviates the need for explicit anti-aliasing filtering in the analog front end, thus further reducing die area. These features facilitate the use of micro-beamforming in smaller pitch applications, as demonstrated by a prototype transceiver ASIC employing micro-beamforming on sub-arrays of N=4 elements, targeting a wearable ultrasound device that monitors brain perfusion in preterm infants via the fontanel. To meet its strict spatial resolution requirements, a 10-MHz 100- μ m-pitch piezoelectric transducer array is employed, leading to a per-element die area > 2 × smaller than prior designs employing micro-beamforming.

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.