Deep Bera

Viability of endothelial cells after ultrasound-mediated sonoporation: Influence of targeting, oscillation, and displacement of microbubbles

Microbubbles (MBs) have been shown to create transient or lethal pores in cell membranes under the influence of ultrasound, known as ultrasound-mediated sonoporation. Several studies have reported enhanced drug delivery or local cell death induced by MBs that are either targeted to a specific biomarker (targeted microbubbles, tMBs) or that are not targeted (non-targeted microbubbles, ntMBs). However, both the exact mechanism and the optimal acoustic settings for sonoporation are still unknown. In this study we used real-time uptake patterns of propidium iodide, a fluorescent cell impermeable model drug, as a measure for sonoporation. Combined with high-speed optical recordings of MB displacement and ultra-high-speed recordings of MB oscillation, we aimed to identify differences in MB behavior responsible for either viable sonoporation or cell death. We compared ntMBs and tMBs with identical shell compositions exposed to long acoustic pulses (500-50,000cycles) at various pressures (150-500kPa). Propidium iodide uptake highly correlated with cell viability; when the fluorescence intensity still increased 120s after opening of the pore, this resulted in cell death. Higher acoustic pressures and longer cycles resulted in more displacing MBs and enhanced sonoporation. Non-displacing MBs were found to be the main contributor to cell death, while displacement of tMBs enhanced reversible sonoporation and preserved cell viability. Consequently, each therapeutic application requires different settings: non-displacing ntMBs or tMBs are advantageous for therapies requiring cell death, especially at 500kPa and 50,000cycles, whereas short acoustic pulses causing limited displacement should be used for drug delivery.

Design of a miniature ultrasound probe for 3D transesophageal echocardiography

The relatively large size of most of the current 3D Transesophageal Echocardiography probes (TEE) enables their usage in adults for short procedures only. In this paper, we propose a new miniature 3D TEE probe with a head volume of 1 cm3, that would be suitable for use in neonates or for prolonged transnasal use in adults. We focus on partitioned designs, in which a minority of transmit elements is directly wired out and the majority of receive elements connect to a limited number of receive cables via an ASIC that performs a nine-fold data reduction in receive mode. The designs are motivated based on the pressure and beam width of the transmitted field, and the resolution, grating lobes and side lobes in the received field.

A front-end ASIC with receive sub-array beamforming integrated with a 32 × 32 PZT matrix transducer for 3-D transesophageal echocardiography

This paper presents a power- and area-efficient front-end ASIC that is directly integrated with an array of 32 × 32 piezoelectric transducer elements to enable the 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 cables required in the probes narrow shaft by means of 96 sub-array beamformers, which have a compact element-matched layout and employ mismatch-scrambling to enhance the dynamic range. The ASIC consumes less than 230 mW while receiving and its functionality has been successfully demonstrated in a 3-D imaging experiment.

Three-dimensional beamforming combining micro-beamformed RF datasets

A general challenge in 3D volumetric imaging is the large channel count. One solution uses integrated microbeamformers. The reconstruction of the entire volume from these micro-beamformed datasets can be performed in many ways. In this paper we propose two 3D multiline beamforming techniques, suitable for producing volumes at high frame rate and compare the image qualities to a fully-sampled matrix. The performance of the proposed beamforming techniques was evaluated with simulations in FieldII. Results show that the proposed simple volume reconstruction technique (using 25 transmissions) produces volumes at very high frame rate, but with sharp intensity changes within the volume. The proposed advanced technique (using 169 transmissions) produces volumes very similar to a fully-sampled matrix transducer despite the micro-beamforming.

Synthetic Aperture Sequential Beamforming for phased array imaging

Synthetic Aperture Sequential Beamforming (SASB) is adapted for phased array ultrasound imaging. The primary advantage of using SASB is an improved lateral resolution without storing the raw channel data which can be realized on ultrasound systems with a relatively simple frontend. The performance of the beamforming technique is evaluated with simulations in Field II and by off-line processing of phantom data using a commercial ultrasound scanner. Results show that the lateral resolution improved by 20% in comparison to conventional dynamic receive beamforming.

Multiline 3D beamforming using micro-beamformed datasets for pediatric transesophageal echocardiography

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.

Fast Volumetric Imaging Using a Matrix Transesophageal Echocardiography Probe with Partitioned Transmit–Receive Array

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 59 Hz 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.

Acoustic characterization of a miniature matrix transducer for pediatric 3D transesophageal echocardiography

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.

Volumetric imaging using adult matrix TEE with separated transmit and receive array

The design of 3D TEE transducers poses severe technical challenges: channel count, electronics integration with high and low voltages, heat dissipation, etc. We present an adult matrix TEE probe with separate transmit (Tx) and receive (Rx) arrays allowing optimization in both Tx and Rx [1]. Tx elements are directly wired out, Rx employs integrated micro-beamformers in low-voltage (1.8/5.0V) chip technology. The prototype is fully integrated into a gastroscopic tube.

Particle image velocimetry on simulated 3D ultrafast ultrasound from pediatric matrix TEE transducers

Ultrafast 3D transesophageal echocardiographic (TEE) imaging, combined with 3D echo particle image velocimetry (ePIV), would be ideal for tracking the complex blood flow patterns in the heart. We are developing a miniature pediatric matrix TEE transducer that employs micro-beamforming (μBF) and allows high framerate in 3D. In this paper, we assess the feasibility of 3D ePIV with a high frame rate, small aperture transducer and the influence of the micro-beamforming technique. We compare the results of 3D ePIV on simulated images using the μBF transducer and an idealized, fully sampled (FS) matrix transducer. For the two transducers, we have simulated high-framerate imaging of an 8.4mm diameter artery having a known 4D velocity field. The simulations were performed in FieldII. 1000 3D volumes, at a rate of 1000 volumes/sec, were created using a single diverging transmission per volume. The error in the 3D velocity estimation was measured by comparing the ePIV results of both transducers to the ground truth. The results on the simulated volumes show that ePIV can estimate the 4D velocity field of the arterial phantom using these small-aperture transducers suitable for pediatric 3D TEE. The μBF transducer (RMSE 44.0%) achieved comparable ePIV accuracy to that of the FS transducer (RMSE 42.6%).