Objective: High-frame-rate (HFR) ultrasonic imaging combined with an ultrasound contrast agent (UCA) can be used to study blood flow patterns using echo-particle image velocimetry (echoPIV). Pulse inversion is a common contrast-specific multipulsing scheme for suppressing tissue clutter in ultrasound images while selectively enhancing nonlinear signals from the UCA. However, in fast flow, the displacement of UCA between pulses leads to phase shifts in the echoes that may result in loss of UCA signal, hindering blood flow tracking with echoPIV. Methods: In the present work, a phase-compensation algorithm is proposed to reduce motion-induced signal loss in HFR contrast-enhanced ultrasound imaging using pulse-inversion Doppler (PID). Results: The PID-based phase-compensation algorithm increased image intensity in the high-velocity regions by up to 6 dB in both in vitro and patient data. Also, after PID-based phase compensation, echoPIV was able to measure 27% higher vector velocities in the patient data. Conclusion: The results reveal the feasibility of PID-based phase compensation for reducing signal loss in fast-flow HFR contrast-enhanced ultrasound and its potential for improving blood flow estimation.

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.

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.

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.

Three-dimensional ultrasound has initially been used to address volumetric imaging for diagnostic purposes and represents the leading-edge technological orientation in both transducer and IC (integrated circuit) architecture and design. However, new applications are coming up like biomarker measurements, preoperative navigation, real time surgery guidance or therapeutic procedures where 3D ultrasound modalities are key but their design objectives may need to be thought outside 3D echocardiography and radiology technological trade-offs. For those new applications, system architectures would need less complexity and imaging performances enabling easier hardware reconfigurability tailored to application-oriented imaging. This paper presents an ongoing development where a large matrix transducer has been assembled with multiple ASIC dies in a reconfigurable way. The transducer has a central frequency of 8MHz, a square pitch of 150μm× 150μm capable to fully image the upper carotid window thanks to a large aperture of 80×240 elements, resulting in a transducer active footprint of 12×36 square millimeters.

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.

In this letter, a compact high-voltage (HV) transmit circuit for dense 2-D transducer arrays used in 3-D ultrasonic imaging systems is presented. Stringent area requirements are addressed by a unipolar pulser with embedded transmit/receive switch. Combined with a capacitive HV level shifter, it forms the ultrasonic HV transmit circuit with the lowest reported HV transistor count and area without any static power consumption. The balanced latched-based level shifter implementation makes the design insensitive to transients on the HV supply caused by pulsing, facilitating application in probes with limited local supply decoupling, such as imaging catheters. Favorable scaling through resource sharing benefits massively arrayed architectures while preserving full individual functionality. A prototype of 8 × 9 elements was fabricated in the TSMC 0.18 μm HV BCD technology and a 160μm×160μm PZT transducer matrix is manufactured on the chip. The system is designed to drive 65-V peak-to-peak pulses on 2-pF transducer capacitance and hardware sharing of six elements allows for an area of only 0.008 mm2 per element. Electrical characterization as well as acoustic results obtained with the 6-MHz central frequency transducer are demonstrated.

The integration of 2D ultrasonic transducer arrays and pitch-matched ASICs has enabled the realization of various 3D ultrasound imaging devices in recent years [1]-[3]. As applications such as 3D intravascular ultrasonography, intra-cardiac echocardiography, and trans-fontanelle ultrasonography call for miniaturization and improved spatial resolution, higher-frequency transducers (>5MHz) with a correspondingly smaller array pitch (<150m) are needed. Such devices generally employ a large number of transducer elements, calling for channel-count reduction in the ASIC while meeting stringent restrictions on per-element power consumption and die area. Micro-beamforming (BF) is an effective way of reducing channel count by performing a delay-and-sum operation on the echo signals received within a sub-array [1]. However, prior BF implementations employ per-element capacitive memory to realize the delay [1], [2], making it increasingly difficult to apply BF in smaller-pitch arrays.

This article presents a compact analog front-end (AFE) circuit for ultrasound receivers with linear-in-dB continuous gain control for time-gain compensation (TGC). The AFE consists of two variable-gain stages, both of which employ a novel complementary current-steering network (CCSN) as the interpolator to realize continuously variable gain. The first stage is a trans-impedance amplifier (TIA) with a hardware-sharing inverter-based input stage to save power and area. The TIA's output couples capacitively to the second stage, which is a class-AB current amplifier (CA). The AFE is integrated into an application-specific integrated circuit (ASIC) in a 180-nm high-voltage BCD technology and assembled with a 100 μm-pitch PZT transducer array of 8 × 8 elements. Both electrical and acoustic measurements show that the AFE achieves a linear-in-dB gain error below ±0.4 dB within a 36-dB gain range, which is > 2 × better than the prior art. Per channel, the AFE occupies 0.025 mm2 area, consumes 0.8 mW power, and achieves an input-referred noise density of 1.31 pA/√Hz.

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.

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.

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.

In the above article [1], the authors regret that there was a mistake in calculating the mol% of the microbubble coating composition used. For all experiments, the unit in mg/mL was utilized and the conversion mistake only came when converting to mol% in order to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol [2], [3], not 328.53 g/mol. On page 556, Table I should read as shown here.

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

Intravascular ultrasound (IVUS) is a well-established diagnostic method that provides images of the vessel wall and atherosclerotic plaques. We investigate the potential for phased-array IVUS utilizing coded excitation (CE) for improving the penetration depth and image signal-to-noise ratio (SNR). It is realized on a new experimental broadband capacitive micromachined ultrasound transducer (CMUT) array, operated in collapse mode, with 96 elements placed at the circumference of a catheter tip with a 1.2- {mm} diameter. We characterized the array performance for CE imaging and showed that the -6-dB device bandwidth at a 30-V dc biasing is 25 MHz with a 20-MHz center frequency, with a transmit sensitivity of 37 kPa/V at that frequency. We designed a linear frequency modulation code to improve penetration depth by compensating for high-frequency attenuation while preserving resolution by a mismatched filter reconstruction. We imaged a wire phantom and a human coronary artery plaque. By assessing the image quality of the reconstructed wire phantom image, we achieved 60- and 70- mu{mathrm {m}} axial resolutions using the short pulse and coded signal, respectively, and gained 8 dB in SNR for CE. Our developed system shows 20-frames/s, pixel-based beam-formed, real-time IVUS images.

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

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

Recently, we realized a prototype matrix transducer consisting of 48 rows of 80 elements on top of a tiled set of Application Specific Integrated Circuits (ASICs) implementing a row-level control connecting one transmit/receive channel to an arbitrary subset of elements per row. A fully sampled array data acquisition is implemented by a column-by-column (CBC) imaging scheme (80 transmit-receive shots) which achieves 250 volumes/second (V/s) at a pulse repetition frequency of 20 kHz. However, for several clinical applications such as carotid pulse wave imaging (CPWI), a volume rate of 1000 per second is needed. This allows only 20 transmit-receive shots per 3D image. In this study, we propose a shifting aperture scheme and investigate the effects of receive/transmit aperture size and aperture shifting step in the elevation direction. The row-level circuit is used to interconnect elements of a receive aperture in the elevation (row) direction. An angular weighting method is used to suppress the grating lobes caused by the enlargement of the effective elevation pitch of the array, as a result of element interconnection in the elevation direction. The effective aperture size, level of grating lobes, and resolution/sidelobes are used to select suitable reception/transmission parameters. Based on our assessment, the proposed imaging sequence is a full transmission (all 80 elements excited at the same time), a receive aperture size of 5 and an aperture shifting step of 3. Numerical results obtained at depths of 10, 15, and 20 mm show that, compared to the fully sampled array, the 1000 V/s is achieved at the expense of, on average, about two times wider point spread function and 4 dB higher clutter level. The resulting grating lobes were at -27 dB. The proposed imaging sequence can be used for carotid pulse wave imaging to generate an informative 3D arterial stiffness map, for cardiovascular disease assessment.