Objective
Contrast-enhanced ultrasound (CEUS) presents distinct advantages in diagnostic echography. Utilizing microbubbles (MBs) as conventional contrast agents enhances vascular visualization and organ perfusion, facilitating real-time, non-invasive procedures. There is a current tendency to replace traditional polydisperse MBs with novel monodisperse formulations in an attempt to optimize contrast enhancement and guarantee consistent behavior and reliable imaging outcomes. This study investigates the contrast enhancement achieved using various-sized monodisperse MBs and their influence on non-linear imaging artifacts observed in traditional CEUS.

Methods
To explore the differences between monodisperse and polydisperse populations without excessive experimentation, numerical simulations are employed for delivering precise, objective and expeditious results. The iterative non-linear contrast source (INCS) method has previously demonstrated efficacy when simulating ultrasound propagation in large populations in which each bubble has individual properties and several orders of multiple scattering are significant. Therefore, this method is employed to realistically simulate both monodisperse and polydisperse MBs.

Results
Our findings in CEUS imaging indicate that scattering from resonant monodisperse MBs is 11.8 dB stronger than scattering from polydisperse MBs. Furthermore, the amplitude of non-linear imaging artifacts downstream of the monodisperse population is 19.4 dB stronger compared with polydisperse suspension.

Conclusion
Investigating the impact of multiple scattering on polydisperse populations compared with various monodisperse suspensions has revealed that monodisperse MBs are more effective contrast agents, especially when at resonance. Despite the strong signal-to-noise ratio of monodisperse populations, imaging artifacts caused by non-linear wave propagation are also enhanced, resulting in further mis-classification of MBs as tissue.

This article presents a 4096-element ultrasound probe for high volume-rate (HVR) cardiovascular imaging. The probe consists of two application-specific integrated circuits (ASICs), each of which interfaces with a 2048-element monolithically-integrated capacitive micro-machined ultrasound transducer (CMUT) array. The probe can image a 60° × 60° × 10-cm volume at 2000 volumes/s, the highest volume-rate with in-probe channel-count reduction reported to date. It uses 2 × 2 delay-and-sum micro-beamforming (μBF) and 2× time-division multiplexing (TDM) to achieve an 8× receive (RX) channel-count reduction. Equalization, trained using a pseudorandom bit-sequence generated on the chip, reduces TDM-induced crosstalk by 10 dB, enabling power-efficient scaling of the cable drivers. The ASICs also implement a novel transmit (TX) beamformer (BF) that operates as a programmable digital pipeline, which enables steering of arbitrary pulse-density modulated (PDM) waveforms. The TX BF drives element-level 65 V unipolar pulsers, which in turn drive the CMUT array. Both the TX BF and RX μBF are programmed with shift-registers (SRs) that can either be programmed in a row-column fashion for fast upload times, or daisy-chain fashion for a higher flexibility. The layout of the ASICs is matched to the 365-μm-pitch monolithically-integrated CMUT array. While operating, the RX and logic power consumption per element is 0.85 and 0.10 mW, respectively. TX power consumption is highly waveform dependent, but is nominally 0.34 mW. Compared to the prior art, the probe has the highest volume rate, and features among the largest imaging arrays (both in terms of element-count and aperture) with a high flexibility in defining the TX waveform. These properties make it a suitable option for applications requiring HVR imaging of a large region of interest.

The field of contrast-enhanced ultrasound (CEUS) combines nonlinearly oscillating microbubbles (MBs) with dedicated pulse sequences to reveal the vascular function of organs. Clinical ultrasound contrast agents consist of polydisperse MB suspensions with diameters ranging from 0.5 to 10 μ⁢m and resonance frequencies ranging from 1 to 15 MHz. As a result, just a small fraction of MBs resonates at a given ultrasound frequency. MB suspensions with narrow size distributions can be tuned for a specific imaging frequency, boost CEUS sensitivity, and enable deeper vascular imaging. However, their enhanced nonlinear behavior makes imaging susceptible to nonlinear-wave-propagation artifacts. Here we numerically investigate the impact of the acoustic wavefront shape on the imaging of nonlinearly oscillating, monodisperse MBs. Specifically, our approach relies on an extension of the iterative nonlinear-contrast-source method that accounts for all nonlinear effects in CEUS. We demonstrate that supersonic X-shaped wavefronts referred to as “X waves” can be used to generate ultrasound images of monodisperse MBs without nonlinear-wave-propagation artifacts. In contrast, imaging based on focused, planar, and diverging wavefronts leads to significant nonlinear artifacts. Taken together, our results show that X waves can harness the full potential of monodisperse MBs by enabling their sensitive and specific detection in a tissue context.

Mapping corrosion depths along pipeline sections using guided-wave-based tomographic methods is a challenging task. Accurate defect sizing depends heavily on the precision of the forward model in guided wave tomography. This model is fitted to measured data using inversion techniques. This study evaluates the effectiveness of a recursive extrapolation scheme for tomography applications and full waveform inversion. It employs a table-driven approach, with precomputed extrapolation operators stored across a spectrum of wavenumbers. This enables fast modelling for extensive pipe sections, approaching the speed of ray tracing while accurately handling complex velocity models within the full frequency band. This ensures an accurate representation of diffraction phenomena. The study examines the assumptions underlying the extrapolation approach, namely, the negligible reflection and conversion of modes at defects. In our tomography approach, we intend to use multiple wave modes— (Formula presented.), (Formula presented.), and (Formula presented.) —and helical paths. The acoustic extrapolation method is validated through numerical studies for different wave modes, solving the 3D elastodynamic wave equation. Comparison with an experimentally measured single-mode wavefield from an aluminium plate with an artificial defect reveals good agreement.

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.

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.

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.

Echography is an important medical diagnostic technique. Historically, the key improvement driver was the hypothesis that higher image quality leads to better diagnoses and increased patient health. Here, a major parameter is the signal to noise ratio (SNR). Diffraction and attenuation reduce pressure levels during propagation. Thus, an SNR increase yields detection at larger depths benefitting traditionally difficult to image patients (eg large/obese patients). Peak pressures are limited by safety standards (mechanical/thermal index). Thus, to increase SNR more sensitive transducers are required. The state of the art Noise Equivalent Pressure (NEP) for piezotransducers / cMUTs / pMUTs is ~0.5 Pa at 1 MHz [1],[2],[3]. A recent innovation is the Integrated Photonic Ultrasound Transducer (IPUT), which combines a membrane and a photonic waveguide to measure ultrasound waves. Literature [5] reported such a device producing a 0.38 Pa NEP at 0.47 MHz and 21% -6 dB bandwidth with a 169x smaller spatial footprint compared to 0.5 x 0.5 wavelength2. Here, we cascade IPUTs into array elements and transform IPUT sensitivity per area into high absolute sensitivity. Several transducer elements were created by cascading up to 16 IPUTs. After designing these devices, their performance was predicted, and subsequently they were fabricated via VTT’s 3 µm thick silicon-on-insulator (SOI) waveguide platform. IPUT performance was measured in a water tank using a custom calibrated source transducer. The transfer functions and noise of each signal chain component was measured and analyzed. The results showed for a 5 cascaded IPUT element a measured NEP of 4 mPa at 0.54 MHz with a 13% -6 dB bandwidth. This improves on the state-of-the-art by a factor of 90-116x.

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.

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.

Volumetric echocardiography can potentially give a more complete picture of cardiac dynamics than its two-dimensional (2D) counterpart. Current clinical volumetric imaging probes have relatively low frame rates, and often require ECG gating to stitch together an entire volume. This makes measuring fast dynamics of the heart as well as imaging patients with irregular heartbeats difficult. We have previously designed and manufactured 2D sparse arrays with elements seeded in a density-tapered spiral pattern for cardiac imaging. Using these prototypes, we demonstrate in this paper the first high-frame-rate volumetric closed-chest porcine cardiac as well as open-chest myocardial blood flow results. These preliminary results suggest the potential of performing high-frame-rate volumetric cardiac imaging using the sparse spiral arrays.

This paper presents a pitch-matched transceiver ASIC integrated with a 2-D transducer array for a wearable ultrasound device for transfontanelle ultrasonography. The ASIC combines 8-fold multiplexing, 4-channel micro-beamforming (μ BF) and sub-array-level digitization to achieve a 128-fold channel-count reduction. The μ BF is based on passive boxcar integration and interfaces with a 10-bit 40 MS/s SAR ADC in the charge domain, thus obviating the need for explicit anti-alias filtering 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 concatenates outputs of four ADCs, leading to an aggregate 3.84 Gb/s data rate. Per channel, the RX circuit consumes 2.06 mW and occupies 0.05 mm2.

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.

High frame rate 3D intracardiac echography (3D-ICE) might enable full-volumetric flow, tissue, and electro-mechanical wave tracking in the heart, thus supporting complex interventional procedures. Designing ICE transducers is very challenging due to the constraints imposed by the catheter's diameter on the transducer aperture and cable accommodation within the shaft. Current ICE probes only offer a 2D or limited 3D field of view at low frame rates. This work presents the design, fabrication, and characterization of an ICE prototype transducer aiming at high frame rate 3D imaging with a large field of view.

Ultrasound imaging is an attractive imaging modality due to its low-cost and real-time feedback, although it often falls short in image quality compared to MRI and CT imaging. Conventional ultrasound image reconstruction, such as Delay-and-Sum beamforming, is derived from maximum-likelihood estimation. As such, no prior information is exploited in the image formation process, which limits potential image quality. Maximum-a-posteriori (MAP) beamforming aims to overcome this issue, but often relies on rough approximations of the underlying signal statistics. Deep learning based reconstruction methods have demonstrated impressive results over the past years, but often lack interpretability and require vast amounts of data.In this work we present a neural MAP beamforming technique, which efficiently combines deep learning in the MAP beamforming framework. We show that this model-based deep learning approach can achieve high-quality imaging, improving over the state-of-the-art, without compromising the real-time abilities of ultrasound imaging.

In contrast-enhanced echography, the simulation of nonlinear propagation of ultrasound through a population of oscillating microbubbles imposes a computational challenge. Also, the numerical complexity increases because each scatterer has individual properties. To address these problems, the Iterative Nonlinear Contrast Source (INCS) method has been extended to include a large population of nonlinearly responding microbubbles. The original INCS method solves the Westervelt equation in a four-dimensional spatiotemporal domain by generating increasingly accurate field corrections to iteratively update the acoustic pressure. The field corrections are computed by the convolution of a nonlinear contrast source with the Green's function of the linear background medium. Because the convolution integral allows a coarse discretization, INCS can efficiently deal with large-scale problems. To include a population of microbubbles, these are considered as individual contrast point sources with their own nonlinear response. The field corrections are computed as before, but now, in each iteration, the temporal signature of each contrast point source is computed by solving the bubble's Marmottant equation. Physically, each iteration adds an order of multiple scattering. Here, the performance of the extended INCS method and the significance of multiple scattering is demonstrated through various results from different configurations.

Ultrasound insonification of microbubbles can locally enhance drug delivery by increasing the cell membrane permeability. To aid development of a safe and effective therapeutic microbubble, more insight into the microbubble-cell interaction is needed. In this in vitro study we aimed to investigate the initial 3D morphology of the endothelial cell membrane adjacent to individual microbubbles (n = 301), determine whether this morphology was affected upon binding and by the type of ligand on the microbubble, and study its influence on microbubble oscillation and the drug delivery outcome. High-resolution 3D confocal microscopy revealed that targeted microbubbles were internalized by endothelial cells, while this was not the case for non-targeted or IgG1-κ control microbubbles. The extent of internalization was ligand-dependent, since α_vβ₃-targeted microbubbles were significantly more internalized than CD31-targeted microbubbles. Ultra-high-speed imaging (~17 Mfps) in combination with high-resolution confocal microscopy (n = 246) showed that microbubble internalization resulted in a damped microbubble oscillation upon ultrasound insonification (2 MHz, 200 kPa peak negative pressure, 10 cycles). Despite damped oscillation, the cell's susceptibility to sonoporation (as indicated by PI uptake) was increased for internalized microbubbles. Monitoring cell membrane integrity (n = 230) showed the formation of either a pore, for intracellular delivery, or a tunnel (i.e. transcellular perforation), for transcellular delivery. Internalized microbubbles caused fewer transcellular perforations and smaller pore areas than non-internalized microbubbles. In conclusion, studying microbubble-mediated drug delivery using a state-of-the-art imaging system revealed receptor-mediated microbubble internalization and its effect on microbubble oscillation and resulting membrane perforation by pores and tunnels.

Over the last 15 years, literature on nondestructive testing has shown that the generation of higher harmonics and nonlinear mixing of waves could be used to obtain the nonlinearity parameters of an elastic medium and thereby gather information about its state, e.g., aging and fatigue. To design ultrasound measurement setups based on these phenomena, efficient numerical modeling tools are needed. In this paper, the iterative nonlinear contrast source method for numerical modeling of nonlinear acoustic waves is extended to the one-dimensional elastic case. In particular, nonlinear mixing of two collinear bulk waves (one compressional, one shear) in a homogeneous, isotropic medium is considered, taking into account its third-order elastic constants ( A,  B,  and  C). The obtained results for nonlinear propagation are in good agreement with a benchmark solution based on the modified Burgers equation. The results for the resonant waves that are caused by the one-way and two-way mixing of primary waves are in quantitative agreement with the results in the literature [Chen, Tang, Zhao, Jacobs, and Qu, J. Acoust. Soc. Am. 136(5), 2389-2404 (2014)]. The contrast source approach allows the identification of the propagating and evanescent components of the scattered wavefield in the wavenumber-frequency domain, which provides physical insight into the mixing process and explains the propagation direction of the resonant wave.

In this article, an application-specific integrated circuit (ASIC) for 3-D, high-frame-rate ultrasound imaging probes is presented. The design is the first to combine element-level, high-voltage (HV) transmitters and analog front-ends, subarray beamforming, and in-probe digitization in a scalable fashion for catheter-based probes. The integration challenge is met by a hybrid analog-to-digital converter (ADC), combining an efficient charge-sharing successive approximation register (SAR) first stage and a compact single-slope (SS) second stage. Application in large ultrasound imaging arrays is facilitated by directly interfacing the ADC with a charge-domain subarray beamformer, locally calibrating interstage gain errors and generating the SAR reference using a power-efficient local reference generator. Additional hardware-sharing between neighboring channels ultimately leads to the lowest reported area and power consumption across miniature ultrasound probe ADCs. A pitch-matched design is further enabled by an efficient split between the core circuitry and a periphery block, the latter including a datalink performing clock data recovery (CDR) and time-division multiplexing (TDM), which leads to a 12-fold total channel count reduction. A prototype of $8{\times }9$ elements was fabricated in a TSMC 0.18- $\mu \text{m}$ HV BCD technology and a 2-D PZT transducer matrix with a pitch of $160 \mu \text{m}$ , and a center frequency of 6 MHz was manufactured on the chip. The imaging device operates at up to 1000 volumes/s, generates 65-V transmit pulses, and has a receive power consumption of only 1.23 mW/element. The functionality has been demonstrated electrically as well as in acoustic and imaging experiments.

Over the past decades, ultrasound imaging has made considerable progress based on the advancement of imaging systems as well as transducer technology. With the need for advanced transducer arrays with complex designs and technical requirements, there is also a need for suitable tools to characterize such transducers. However, despite the importance of acoustic characterization to assess the performance of novel transducer arrays, the characterization process of highly complex transducers might involve various manual steps, which are laborious, time-consuming, and subject to errors. These factors can hinder the full characterization of a prototype transducer, leading to an under-representation or inadequate evaluation. To come to an extensive, high-quality evaluation of a prototype transducer, the acoustic characterization of each transducer element is indispensable in both transmit and receive operations. In this paper, we propose a pipeline to automatically perform the acoustic characterization of a matrix transducer using a research imaging system. The performance of the pipeline is tested on a prototype matrix transducer consisting of 960 elements. The results show that the proposed pipeline is capable of performing the complete acoustic characterization of a high-element count transducer in a fast and convenient way.