Objective: Assessing myocardial perfusion in acute myocardial infarction is important for guiding clinicians in choosing appropriate treatment strategies. Echocardiography can be used due to its direct feedback and bedside nature, but it currently faces image quality issues and an inability to differentiate coronary macro- from micro-circulation. We previously developed an imaging scheme using high frame-rate contrast-enhanced ultrasound (HFR CEUS) with higher order singular value decomposition (HOSVD) that provides dynamic perfusion and vascular flow visualization. In this study, we aim to show the ability of this technique to image perfusion deficits and investigate the potential occurrence of false-positive contrast detection. Methods: We used a porcine model comprising occlusion and release of the left anterior descending coronary artery. During slow contrast agent infusion, the afore-mentioned imaging scheme was used to capture and process the data offline using HOSVD. Results: Fast and slow coronary flow was successfully differentiated, presumably representing the different compartments of the micro-circulation. Low perfusion was seen in the area that was affected, as expected by vascular occlusion. Furthermore, we also imaged coronary flow dynamics before, during and after release of the occlusion, the latter showing hyperemia as expected. A contrast agent destruction test showed that the processed images contained actual contrast signal in the cardiac phases with minimal motion. With larger tissue motion, tissue signal leaked into the contrast-enhanced images. Conclusion: Our results demonstrate the feasibility of HFR CEUS with HOSVD as a viable option for assessing myocardial perfusion. Flow dynamics were resolved, which potentially helped to directly evaluate coronary flow deficits.

Emerging handheld and wearable ultrasound devices enable diagnosis and long-term monitoring outside clinical settings. They require a low-power, highly complex, locally integrated system to process the RF data. The analog-to-digital converter (ADC) is a critical building block in the receive chain of these systems as it enables digital beamforming and image reconstruction. However, the ADCs currently used in cart-based imaging systems are bulky and consume too much power to be integrated into battery-powered devices. This article investigates how the area and power consumption of the commonly used successive approximation register (SAR) ADC can be reduced without negatively affecting B-mode and color-Doppler image quality. A Monte Carlo (MC) simulation study was performed in which RF data acquired with a phased-array transducer in Field II were digitized using a model of a nonideal ADC. Five different nonidealities were applied to four commonly used SAR-ADC architectures. B-mode and color-Doppler images were reconstructed from the digitized RF data. The impact of the nonidealities on the image quality was evaluated by means of three image quality metrics (IQM): peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and contrast-to-noise ratio (CNR). The effectiveness of error correction and ways of calibration are also discussed. The results show that both B-mode imaging and color-Doppler imaging are inherently resilient to nonidealities, particularly capacitor mismatch, leading to relaxed ADC requirements and paving the way for more practical in-probe digitization.

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.

Objective: The assessment of blood-flow volume (BFV) is clinically relevant for the diagnosis and monitoring of cardiovascular dysfunctions and the prevention of subsequent secondary diseases. Non-invasive BFV measurement based on ultrasound methods are appealing for lower cost, real-time operation, and equipment portability. Recently, complex ultrasound research scanners with 1024 channels controlling the elements of a 2-D matrix array probe, have been demonstrated suitable for off-line accurate BFV estimates. In this work, a streamlined approach, using a 256-channel research scanner paired with a 256-element 2-D sparse spiral array, is proposed and validated. Methods: This setup allows for simultaneous scanning of the vessel's longitudinal and transverse sections through an interleaved transmission sequence. In real-time, the longitudinal scan is used to determine the flow direction, while the transverse scan captures both the dynamic cross-sectional area and the local velocities by high frame rate color flow mapping. Results: Flow phantom experiments under steady and pulsatile flow conditions were conducted to assess the performance by comparing the measurements with the outputs of a reference flow sensor. The proposed method provided accurate and precise BFV values for both flow conditions, with mean percentage error and standard deviation always lower than 9.4% and 2.8%, respectively. Furthermore, preliminary in vivo experiments have produced results consistent with those reported in the literature. Conclusion: The proposed method based on the use of a sparse array has permitted accurate and precise phantom BFV measurements and has been shown suitable for real-time arterial BFV measurements.

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.

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: 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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

This work describes an ASIC design for high-frame-rate 3D intracardiac echocardiography probes. The chip is the first to combine element-level high-voltage pulsers and time-gain-compensation analog frontends as well as subarray beamformers and in-probe digitization in a pitch-matched fashion. The integration challenge is met by a shared hybrid beamforming ADC with the highest reported area and power efficiency. The achieved beamformer size of three elements enables acquisition at 1000 volumes/s while, in combination with a custom datalink, still providing sufficient channel-count reduction for catheter integration.

An in vivo range verification technology for proton beam cancer therapy, preferably in real-time and with submillimeter resolution, is desired to reduce the present uncertainty in dose localization. Acoustical imaging technologies exploiting possible local interactions between protons and microbubbles or nanodroplets might be an interesting option. Unfortunately, a theoretical model capable of characterising the acoustical field generated by an individual proton on nanometer and micrometer scales is still missing. In this work, such a model is presented. The proton acoustic field is generated by the adiabatic expansion of a region that is locally heated by a passing proton. To model the proton heat deposition, secondary electron production due to protons has been quantified using a semi-empirical model based on Rutherford's scattering theory, which reproduces experimentally obtained electronic stopping power values for protons in water within 10% over the full energy range. The electrons transfer energy into heat via electron-phonon coupling to atoms along the proton track. The resulting temperature increase is calculated using an inelastic thermal spike model. Heat deposition can be regarded as instantaneous, thus, stress confinement is ensured and acoustical initial conditions are set. The resulting thermoacoustic field in the nanometer and micrometer range from the single proton track is computed by solving the thermoacoustic wave equation using k-space Green's functions, yielding the characteristic amplitudes and frequencies present in the acoustic signal generated by a single proton in an aqueous medium. Wavefield expansion and asymptotic approximations are used to extend the spatial and temporal ranges of the proton acoustic field.

Intra-cardiac echography (ICE) probes (Fig. 32.2.1) are widely used in electrophysiology for their good procedure guidance and relatively safe application. ASICs are increasingly employed in these miniature probes to enhance signal quality and reduce the number of connections needed in mm-diameter catheters [1]-[5]. 3D visualization in real-time is additionally enabled by 2D transducer arrays with, for each transducer element, a high-voltage (HV) transmit (TX) part, to generate acoustic pulses of sufficient pressure, and a receive (RX) path, to process the resulting echoes. To achieve the required reduction in RX channels, micro-beamforming (BF), which merges the signals from a subarray using a delay-and-sum operation, has been shown to be an effective solution [3], [4]. However, due to the frame-rate reduction that is associated with BF, these designs cannot serve emerging high-frame-rate imaging modes (1000 volumes/s) like 3D blood-flow and elastography imaging. In-probe digitization has recently been investigated to provide further channel-count reduction, make data transmission more robust, and enable pre-processing in the probe [1]-[3]. However, these earlier designs have either no TX functionality [2], [3] or only low-voltage (LV) TX [1] integrated. Combining BF and digitization with area-hungry HV transmitters in a pitch-matched scalable fashion while supporting high-frame-rate imaging remains an unmet challenge. The work presented in this paper meets this target, enabled by a hybrid ADC, the small die size of which allows for co-integration with 65V element-level pulsers.

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 29 °C 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.