Search

This paper presents an ultrasound transceiver application-specific integrated circuit (ASIC) designed for 3-D ultrasonic imaging of the carotid artery. This application calls for an array of thousands of ultrasonic transducer elements, far exceeding the number of channels of conventional imaging systems. The 3.6 x 6.8 mm² ASIC interfaces a piezo-electric transducer (PZT) array of 24 x 40 elements, directly integrated on top of the ASIC, to an imaging system using only 24 transmit and receive channels. Multiple ASICs can be tiled together to form an even bigger array. The ASIC, implemented in a 0.18 μm high-voltage (HV) BCD process, consists of a reconfigurable switch matrix and row-level receive circuits. Each element is associated with a compact bootstrapped HV transmit switch, an isolation switch for the receive circuits and programmable logic that enables a variety of imaging modes. Electrical and acoustic experiments successfully demonstrate the functionality of the ASIC. In addition, the ASIC has been successfully used in a 3-D imaging experiment., Accepted author manuscript, Electronic Instrumentation, ImPhys/Acoustical Wavefield Imaging

This paper presents an area- and power-efficient application-specified integrated circuit (ASIC) for 3-D forward-looking intravascular ultrasound imaging. The ASIC is intended to be mounted at the tip of a catheter, and has a circular active area with a diameter of 1.5 mm on the top of which a 2-D array of piezoelectric transducer elements is integrated. It requires only four micro-coaxial cables to interface 64 receive (RX) elements and 16 transmit (TX) elements with an imaging system. To do so, it routes high-voltage (HV) pulses generated by the system to selected TX elements using compact HV switch circuits, digitizes the resulting echo signal received by a selected RX element locally, and employs an energy-efficient load-modulation datalink to return the digitized echo signal to the system in a robust manner. A multi-functional command line provides the required sampling clock, configuration data, and supply voltage for the HV switches. The ASIC has been realized in a 0.18-μm HV CMOS technology and consumes only 9.1 mW. Electrical measurements show 28-V HV switching and RX digitization with a 16-MHz bandwidth and 53-dB dynamic range. Acoustical measurements demonstrate successful pulse transmission and reception. Finally, a 3-D ultrasound image of a three-needle phantom is generated to demonstrate the imaging capability., Accepted author manuscript, Electronic Instrumentation, ImPhys/Acoustical Wavefield Imaging

Intravascular ultrasound is an imaging modality used to visualize atherosclerosis from within the inner lumen of human arteries. Complex lesions like chronic total occlusions require forward-looking intravascular ultrasound (FL-IVUS), instead of the conventional side-looking geometry. Volumetric imaging can be achieved with 2D array transducers, which present major challenges in reducing cable count and device integration. In this work we present an 80-element lead zirconium titanate (PZT) matrix ultrasound transducer for FL-IVUS imaging with a front-end application-specific integrated circuit (ASIC) requiring only 4 cables. After investigating optimal transducer designs we fabricated the matrix transducer consisting of 16 transmit (TX) and 64 receive (RX) elements arranged on top of an ASIC having an outer diameter of 1.5 mm and a central hole of 0.5 mm for a guidewire. We modeled the transducer using finite element analysis and compared the simulation results to the values obtained through acoustic measurements. The TX elements showed uniform behavior with a center frequency of 14 MHz, a -3 dB bandwidth of 44 % and a transmit sensitivity of 0.4 kPa/V at 6 mm. The RX elements showed center frequency and bandwidth similar to the TX elements, with an estimated receive sensitivity of 3.7 μV/Pa. We successfully acquired a 3D FL image of three spherical reflectors in water using delay-and-sum beamforming and the coherence factor method. Full synthetic aperture acquisition can be achieved with frame rates on the order of 100 Hz. The acoustic characterization and the initial imaging results show the potential of the proposed transducer to achieve 3D FL-IVUS imaging., Electronic Instrumentation, ImPhys/Acoustical Wavefield Imaging

Until now, no matrix transducer has been realized for 3D transesophageal echocardiography (TEE) in pediatric patients. In 3D TEE with a matrix transducer, the biggest challenges are to connect a large number of elements to a standard ultrasound system, and to achieve a high volume rate (>200 Hz). To address these issues, we have recently developed a prototype miniaturized matrix transducer for pediatric patients with micro-beamforming and a small central transmitter. In this paper we propose two multiline parallel 3D beamforming techniques (μBF25 and μBF169) using the micro-beamformed datasets from 25 and 169 transmit events to achieve volume rates of 300 Hz and 44 Hz, respectively. Both the realizations use angle-weighted combination of the neighboring overlapping sub-volumes to avoid artifacts due to sharp intensity changes introduced by parallel beamforming. In simulation, the image quality in terms of the width of the point spread function (PSF), lateral shift invariance and mean clutter level for volumes produced by μBF25 and μBF169 are similar to the idealized beamforming using a conventional single-line acquisition with a fully-sampled matrix transducer (FS4k, 4225 transmit events). For completeness, we also investigated a 9 transmit-scheme (3 × 3) that allows even higher frame rates but found worse B-mode image quality with our probe. The simulations were experimentally verified by acquiring the μBF datasets from the prototype using a Verasonics V1 research ultrasound system. For both μBF169 and μBF25, the experimental PSFs were similar to the simulated PSFs, but in the experimental PSFs, the clutter level was ∼10 dB higher. Results indicate that the proposed multiline 3D beamforming techniques with the prototype matrix transducer are promising candidates for real-time pediatric 3D TEE., Accepted author manuscript, ImPhys/Acoustical Wavefield Imaging, Electronic Instrumentation

We describe a 3-D multiline parallel beamforming scheme for real-time volumetric ultrasound imaging using a prototype matrix transesophageal echocardiography probe with diagonally diced elements and separated transmit and receive arrays. The elements in the smaller rectangular transmit array are directly wired to the ultrasound system. The elements of the larger square receive aperture are grouped in 4 × 4-element sub-arrays by micro-beamforming in an application-specific integrated circuit. We propose a beamforming sequence with 85 transmit–receive events that exhibits good performance for a volume sector of 60° × 60°. The beamforming is validated using Field II simulations, phantom measurements and in vivo imaging. The proposed parallel beamforming achieves volume rates up to 59Hz and produces good-quality images by angle-weighted combination of overlapping sub-volumes. Point spread function, contrast ratio and contrast-to-noise ratio in the phantom experiment closely match those of the simulation. In vivo 3-D imaging at 22-Hz volume rate in a healthy adult pig clearly visualized the cardiac structures, including valve motion., Accepted Author Manuscript, Electronic Instrumentation, ImPhys/Acoustical Wavefield Imaging

The huge amount of data that needs to be transferred between probe and imaging system becomes a major issue when the data transfer capacity is limited, e.g. in handheld systems, wireless probes and miniaturized probes. The amount of data can be significantly reduced by using two-stage beamforming. The first stage consists of a fixed focus algorithm that compresses channel data to scanline data. This can be done by integrated electronics in the handle. In the second stage the scanline data is further beamformed in the imaging system to obtain images that are synthetically focused at all depths. Here we present a wave equation two-stage beamforming method for phased array imaging that is computationally efficient and outperforms PSASB, a time-of-flight alternative, in terms of lateral resolution and contrast-to-noise ratio., Accepted Author Manuscript, ImPhys/Acoustical Wavefield Imaging, ImPhys/Quantitative Imaging

This paper presents a front-end application-specified integrated circuit (ASIC) integrated with a 2-D PZT matrix transducer that enables in-probe digitization with acceptable power dissipation for the next-generation endoscopic and catheter-based 3-D ultrasound imaging systems. To achieve power-efficient massively parallel analog-to-digital conversion (ADC) in a 2-D array, a 10-bit 30 MS/s beamforming ADC that merges the subarray beamforming and digitization functions in the charge domain is proposed. It eliminates the need for costly intermediate buffers, thus significantly reducing both power consumption and silicon area. Self-calibrated charge references are implemented in each subarray to further optimize the system-level power efficiency. High-speed datalinks are employed in combination with the subarray beamforming scheme to realize a 36-fold channel-count reduction and an aggregate output data rate of 6 Gb/s for a prototype receive array of 24 x 6 elements. The ASIC achieves a record power efficiency of 0.91 mW/element during receive. Its functionality has been demonstrated in both electrical and acoustic imaging experiments., Accepted Author Manuscript, Electronic Instrumentation, ImPhys/Acoustical Wavefield Imaging

In vivo cell tracking of therapeutic, tumor, and endothelial cells is an emerging field and a promising technique for imaging cardiovascular disease and cancer development. Site-specific labeling of endothelial cells with the MRI contrast agent superparamagnetic iron oxide (SPIO) in the absence of toxic agents is challenging. Therefore, the aim of this in vitro study was to find optimal parameters for efficient and safe SPIO-labeling of endothelial cells using ultrasound-activated CD31-targeted microbubbles for future MRI tracking. Ultrasound at a frequency of 1 MHz (10,000 cycles, repetition rate of 20 Hz) was used for varying applied peak negative pressures (10–160 kPa, i.e. low mechanical index (MI) of 0.01–0.16), treatment durations (0–30 s), time of SPIO addition (-5 min– 15 min with respect to the start of the ultrasound), and incubation time after SPIO addition (5 min– 3 h). Iron specific Prussian Blue staining in combination with calcein-AM based cell viability assays were applied to define the most efficient and safe conditions for SPIO-labeling. Optimal SPIO labeling was observed when the ultrasound parameters were 40 kPa peak negative pressure (MI 0.04), applied for 30 s just before SPIO addition (0 min). Compared to the control, this resulted in an approximate 12 times increase of SPIO uptake in endothelial cells in vitro with 85% cell viability. Therefore, ultrasound-activated targeted ultrasound contrast agents show great potential for effective and safe labeling of endothelial cells with SPIO., ImPhys/Acoustical Wavefield Imaging

Ultrasound contrast agents consist of gas-filled coated microbubbles that oscillate upon ultrasound insonification. Their characteristic oscillatory response provides contrast enhancement for imaging and has the potential to locally enhance drug delivery. Since microbubble response depends on the local acoustic pressure, an ultrasound compatible chamber is needed to study their behavior and the underlying drug delivery pathways. In this study, we determined the amplitude of the acoustic pressure in the CLINIcell, an optically transparent chamber suitable for cell culture. The pressure field was characterized based on microbubble response recorded using the Brandaris 128 ultra-high speed camera and an iterative processing method. The results were compared to a control experiment performed in an OptiCell, which is conventionally used in microbubble studies. Microbubbles in the CLINIcell responded in a controlled manner, comparable to those in the OptiCell. For frequencies from 1 to 4 MHz, the mean pressure amplitude was -5.4 dB with respect to the externally applied field. The predictable ultrasound pressure demonstrates the potential of the CLINIcell as an optical, ultrasound, and cell culture compatible device to study microbubble oscillation behavior and ultrasound-mediated drug delivery., ImPhys/Acoustical Wavefield Imaging

Typically, ultrasonic flow meters assume linear wave propagation. Nevertheless, if the transducers of an ultrasonic flow sensor excite a pressure wave with a high amplitude, nonlinear wave propagation effects become significant. The appearance of higher harmonics increases the bandwidth of the received signal, which may potentially lead to a more precise flow measurement. However, the question arises whether the increased bandwidth can be used in practice, since the intensity of the 2nd harmonic can be 25 dB below the fundamental. One exploit of the increased bandwidth is to filter the received signals and to obtain two components: the fundamental and the 2nd harmonic. Differences between the upstream and downstream transit times are directly related to the flow speed, and these can be computed for each component of the received signals. This paper shows that averaging the transit time differences of the fundamental signals and the 2nd harmonic signals results in a lower standard deviation compared to the standard deviation of the transit time differences of the fundamental or the 2nd harmonic signal alone. This demonstrates the feasibility of using non-linear wave propagation to improve the precision of flow measurements using ultrasound., Accepted Author Manuscript, ImPhys/Acoustical Wavefield Imaging, Electronic Instrumentation

ImPhys/Acoustical Wavefield Imaging

Treatment of abdominal aortic (AA) aneurysms and stenotic lesions may be improved by analyzing their associated blood flow patterns. Angle-independent blood flow patterns in the AA can be obtained by combining echo-particle image velocimetry (ePIV) with high frame rate contrast-enhanced ultrasonography. However, ePIV performance is affected by ultrasound contrast agent (UCA) concentration, microbubble stability and tissue clutter. In this study we assessed the influence of acoustic pressure and UCA concentration on image quality for ePIV analysis. We also compared amplitude modulation (AM) and singular value decomposition (SVD) as tissue suppression strategies for ePIV. Fourteen healthy volunteers were imaged in the region of the distal AA. We tested four different UCA bolus volumes (0.25, 0.5, 0.75 and 1.5 ml) and four different acoustic output pressures (mechanical indices: 0.01, 0.03, 0.06 and 0.09). As image quality metrics, we measured contrast-to-background ratio, bubble disruption ratio and maximum normalized cross-correlation value during ePIV. At mechanical indices ≥ 0.06, we detected severe bubble destruction, suggesting that very low acoustic pressures should be used for ePIV. SVD was able to suppress tissue clutter better than AM. The maximum tracking correlation was affected by both UCA concentration and flow rate, where at high flow rates, lower UCA concentrations resulted in slightly higher correlation values but more signal drop-outs during late diastole. High frame rate ePIV was successfully performed in the AA of healthy volunteers and shows promise for future studies in patients., Accepted Author manuscript, ImPhys/Acoustical Wavefield Imaging

This paper presents the design, fabrication and characterization of a miniature PZT-on-CMOS matrix transducer for real-time pediatric 3-dimensional (3D) transesophageal echocardiography (TEE). This 3D TEE probe consists of a 32 × 32 array of PZT elements integrated on top of an Application Specific Integrated Circuit (ASIC). We propose a partitioned transmit/receive array architecture wherein the 8 × 8 transmitter elements, located at the centre of the array, are directly wired out and the remaining receive elements are grouped into 96 sub-arrays of 3 × 3 elements. The echoes received by these sub-groups are locally processed by micro-beamformer circuits in the ASIC that allow pre-steering up to ±37°. The PZT-on-CMOS matrix transducer has been characterized acoustically and has a centre frequency of 5.8 MHz, -6 dB bandwidth of 67%, a transmit efficiency of 6 kPa/V at 30 mm, and a receive dynamic range of 85 dB with minimum and maximum detectable pressures of 5 Pa and 84 kPa respectively. The properties are very suitable for a miniature pediatric real-time 3D TEE probe., Accepted author manuscript, ImPhys/Acoustical Wavefield Imaging, Electronic Instrumentation

Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available UCAs for high-frequency CEUS (hfCEUS) is largely unknown, while shell properties have been shown to be an important factor for their performance. The aim of our study was to produce UCAs in-house for hfCEUS. Twelve different UCA formulations A-L were made by either sonication or mechanical agitation. The gas core consisted of C4F10 and the main coating lipid was either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC; A-F formulation) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC; G-L formulation). Mechanical agitation resulted in UCAs with smaller microbubbles (number weighted mean diameter ∼1 μm) than sonication (number weighted mean diameter ∼2 μm} ). UCA formulations with similar size distributions but different main lipid components showed that the DPPC-based UCA formulations had higher nonlinear responses at both the fundamental and subharmonic frequencies in vitro for hfCEUS using the Vevo2100 high-frequency preclinical scanner (FUJIFILM VisualSonics, Inc.). In addition, UCA formulations F (DSPC-based) and L (DPPC-based) that were made by mechanical agitation performed similar in vitro to the commercially available Target-Ready MicroMarker (FUJIFILM VisualSonics, Inc.). UCA formulation F also performed similar to Target-Ready MicroMarker in vivo in pigs with similar mean contrast intensity within the kidney ( n = 7 ), but formulation L did not. This is likely due to the lower stability of formulation L in vivo. Our study shows that DSPC-based microbubbles produced by mechanical agitation resulted in small microbubbles with high nonlinear responses suitable for hfCEUS imaging., ImPhys/Acoustical Wavefield Imaging

One of the main challenges for ultrasound molecular imaging is acoustically distinguishing nonbound microbubbles from those bound to their molecular target. In this in vitro study, we compared two types of in-house produced targeted lipid-coated microbubbles, either consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, C16:0 (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine, C18:0 (DSPC) as the main lipid, using the Brandaris 128 ultrahigh-speed camera to determine vibrational response differences between bound and nonbound biotinylated microbubbles. In contrast to previous studies that studied vibrational differences upon binding, we used a covalently bound model biomarker (i.e., streptavidin) rather than physisorption, to ensure binding of the biomarker to the membrane. The microbubbles were insonified at frequencies between 1 and 4 MHz at pressures of 50 and 150 kPa. This paper shows lower acoustic stability of bound microbubbles, of which DPPC-based microbubbles deflated most. For DPPC microbubbles with diameters between 2 and 4μm driven at 50 kPa, resonance frequencies of bound microbubbles were all higher than 1.8 MHz, whereas those of nonbound microbubbles were significantly lower. In addition, the relative radial excursions at resonance were also higher for bound DPPC microbubbles. These differences did not persist when the pressure was increased to 150 kPa, except for the acoustic stability which further decreased. No differences in resonance frequencies were observed between bound and nonbound DSPC microbubbles. Nonlinear responses in terms of emissions at the subharmonic and second harmonic frequencies were similar for bound and nonbound microbubbles at both pressures. In conclusion, we identified differences in vibrational responses of bound DPPC microbubbles with diameters between 2 and 4μm that distinguish them from nonbound ones., ImPhys/Acoustical Wavefield Imaging

Acoustic behavior of lipid-coated microbubbles has been widely studied, which has led to several numerical microbubble dynamics models that incorporate lipid coating behavior, such as buckling and rupture. In this study we investigated the relationship between micro-bubble acoustic and lipid coating behavior on a nanosecond scale by using fluorescently labeled lipids. It is hypothesized that a local increased concentration of lipids, appearing as a focal area of increased fluorescence intensity (hot spot) in the fluorescence image, is related to buckling and folding of the lipid layer thereby highly influencing the microbubble acoustic behavior. To test this hypothesis, the lipid microbubble coating was fluorescently labeled. The vibration of the microbubble (n= 177; 2.3-10.3 μm in diameter) upon insonification at an ultrasound frequency of 0.5 or 1 MHz at 25 or 50 kPa acoustic pressure was recorded with the UPMC Cam, an ultra-high-speed fluorescence camera, operated at ∼4-5 million frames per second. During short tone-burst excitation, hot spots on the microbubble coating occurred at relative vibration amplitudes > 0.3 irrespective of frequency and acoustic pressure. Around resonance, the majority of the microbubbles formed hot spots. When the microbubble also deflated acoustically, hot spot formation was likely irreversible. Although compression-only behavior (defined as substantially more microbubble compression than expansion) and subharmonic responses were observed in those microbubbles that formed hot spots, both phenomena were also found in microbubbles that did not form hot spots during insonification. In conclusion, this study reveals hot spot formation of the lipid monolayer in the microbubble's compression phase. However, our experimental results show that there is no direct relationship between hot spot formation of the lipid coating and microbubble acoustic behaviors such as compression-only and the generation of a subharmonic response. Hence, our, ImPhys/Acoustical Wavefield Imaging

This paper presents a power-and area-efficient front-end application-specific integrated circuit (ASIC) that is directly integrated with an array of 32 × 32 piezoelectric transducer elements to enable next-generation miniature ultrasound probes for real-time 3-D transesophageal echocardiography. The 6.1 × 6.1 mm2 ASIC, implemented in a low-voltage 0.18-μm CMOS process, effectively reduces the number of receive (RX) cables required in the probe's narrow shaft by ninefold with the aid of 96 delay-and-sum beamformers, each of which locally combines the signals received by a sub-array of 3 × 3 elements. These beamformers are based on pipeline-operated analog sample-and-hold stages and employ a mismatch-scrambling technique to prevent the ripple signal associated with the mismatch between these stages from limiting the dynamic range. In addition, an ultralow-power low-noise amplifier architecture is proposed to increase the power efficiency of the RX circuitry. The ASIC has a compact element matched layout and consumes only 0.27 mW/channel while receiving, which is lower than the state-of-the-art circuit. Its functionality has been successfully demonstrated in 3-D imaging experiments., Electronic Instrumentation, ImPhys/Acoustical Wavefield Imaging

Echocardiography is a portable, safe, and low-cost imaging technique for accurate assessment of the heart. In transesophageal echocardiography (TEE) the esophagus is utilized as the imaging window to examine the cardiac anatomy and function. In conventional TEE probes, a one-dimensional (1D) ultrasound array is employed to obtain two-dimensional (2D) cross-sectional images of the heart. Since cardiac morphology, leakage of valves and function of the outflow tracts are all three-dimensional (3D) phenomena, it is beneficial to interpret them from 3D images. Therefore, there is high clinical demand for matrix TEE probes that are capable of providing real-time volumetric images [1]. Several matrix arrays (Philips X7-2t, Siemens V5M TEE, General Electric 6VTD) have been developed for this purpose, however all of them are large in size (~10 cm3) and uncomfortable to use on non-anesthetized patients [2]. We aim to develop a matrix TEE probe with a small head volume (<1 cm3), which is suitable for long term monitoring of cardiac system on adults and in babies. We have developed a prototype of a small matrix TEE probe, which consists of a piezoelectric matrix transducer directly mounted on an Application Specific Integrated Circuit (ASIC). The ASIC performs the task of micro-beamforming, signal amplification and efficient data reduction. The piezoelectric matrix array consist of a 32×32 PZT elements with a pitch of 150 μm × 150 μm. The transmit aperture consists of 8×8 elements at the centre of the array, which are directly wired out to the ultrasound system. The remaining 864 elements are used in receive and are organized in 96 sub-arrays of 3×3 elements to reduce the cable count with a factor of 9. The signals from the individual elements in a sub-array are combined to a single output signal using a micro-beamformer on the ASIC. The micro-beamformer allows pre-steering of 0◦, ±17◦, and ±37◦ angles in both lateral and elevation directions. By recording datasets for diffe, Op lijst van EWI - EI, ImPhys/Acoustical Wavefield Imaging, ImPhys/Medical Imaging, Electronic Instrumentation