Single-element Transducer Research Articles

High-frequency quantitative ultrasound for characterizing collagen fiber alignment in murine tendon using angular dependence of integrated backscatter

Two major complications following tendon surgery are adhesion formation and re-rupture. There is a need to develop an ultrasound imaging system for non-invasive, non-destructive, longitudinal monitoring of tendon structure throughout a rehabilitation protocol to optimize restoration of range of motion and mechanical properties. Type I collagen is the primary extracellular matrix protein in tendon, and its organization impacts tendon function. The objective of the present study is to develop a high-frequency quantitative ultrasound spectral analysis technique to characterize collagen fiber alignment in murine tendon. This work tests the hypothesis that the integrated backscatter coefficient (IBC) will exhibit anisotropy in murine tendon with aligned structure, and isotropy in murine liver with inhomogeneous structure. Backscattered echoes from murine tail tendon and liver were acquired at varying insonification angles using 38-MHz and 55-MHz single-element transducers. B-mode and IBC parametric images were computed, and the average IBC value in a region of interest was determined at each insonification angle. The IBC was angular-dependent in tendon and isotropic in liver. These data suggest that the IBC can be used to detect collagen fiber alignment in murine tendon, and contribute to establishing the foundation for a dedicated device to non-invasively monitor collagen remodeling during tendon healing.

Focused ultrasound phantom model for blood brain barrier disruption

In this paper a high intensity focused ultrasound (FUS) phantom model was developed, in order to be used in experiments for Blood Brain Barrier (BBB) disruption. The target was to create a phantom model that represents the disruption of the BBB during ultrasound application. An appropriate experimental setup was created bearing a single element transducer with diameter 50 mm and geometric focus 100 mm operating at 0.5 MHz. It included a set of tubes and a connector with multiple 0.4 mm openings, through which a suitable liquid is being circulated with a pump. The lesions were sealed with a thin homogenous layer of wax, preventing a liquid leakage. The system was tested successfully with FUS and a liquid leakage was achieved after FUS application. This set up is the first phantom model that has the potential to be utilized as a cost-effective solution for performing experiments for BBB disruption, without the need of using animal models.

Steering single-element lead zirconate titanate ultrasound transducers using biaxial driving

Previous work has shown that biaxial driving using two phase-offset orthogonal electric fields (propagation and lateral) improves the efficiency of ferroelectric materials by reducing coercivity and, hence, energy dissipation. In the current investigation, we demonstrated the capability of the biaxial method to steer ultrasound waves in single-element piezoceramic transducers made of prismatic lead zirconate titanate (PZT). We conducted finite element analysis simulations for 133 kHz (model 1) and 470 kHz biaxial (model 2) transducers models. We performed experimental validation with biaxially driven single-element transducers (n = 3) operating at an average frequency of 131 kHz with the same characteristics as model 1. For both models, we found non-symmetric steering that was a function of both the phase and power of the second electric field. At a constant electrical power (1 W) on the propagation electrodes, simulations for the 133 kHz model predicted maximal steering of 10.3°, 22.6°, and 30.9° for lateral electrode powers of 0.1 W, 0.5 W, and 1.0 W, respectively. Experimentally, for model 1, the maximal steering was 11.7° ± 1.9°, 23.5° ± 3.5°, and 30.2° ± 4.4° for the lateral electrode powers of 0.1 W, 0.5 W, and 1.0 W, respectively. Simulations for the 470 kHz model predicted maximal steering of 8.8°, 16.1°, and 27° for lateral electrode powers of 0.1 W, 0.5 W, and 1.0 W, respectively. Simulations showed that the cause of the steering asymmetry was a non-uniform shear deformation associated with the slightly off-resonance lateral electric field driving frequency. This is the first demonstration of ultrasound steering using a single-element transducer, which can have important applications for ultrasound focusing with phased arrays.

An ionizing radiation acoustic imaging (iRAI) technique for real-time dosimetric measurements for FLASH radiotherapy.

FLASH radiotherapy (FLASH-RT) is a novel irradiation modality with ultra-high dose rates (>40Gy/s) that have shown tremendous promise for its ability to enhance normal tissue sparing while maintaining comparable tumor cell eradication toconventional radiotherapy (CONV-RT). Due to its extremely high dose rates, clinical translation of FLASH-RT is hampered by risky delivery and current limitations in dosimetric devices, which cannot accurately measure, in real time, dose at deeper tissue. This work aims to investigate ionizing radiation acoustic imaging (iRAI) as a promising image-guidance modality for real-time deep tissue dose measurements during FLASH-RT. The underlying hypothesis is that iRAI can enable mapping of dose deposition with respect to surrounding tissue with a single linear accelerator (linac) pulse precision in real time. In this work, the relationship between iRAI signal response and deposited dose was investigated as well as the feasibility of using a proof-of-concept dual-modality imaging system of ultrasound and iRAI for treatment beam co-localization with respect to underlying anatomy. Two experimental setups were used to study the feasibility of iRAI for FLASH-RT using 6MeV electrons from a modified Varian Clinac. First, experiments were conducted using a single element focused transducer to take a series of point measurements in a gelatin phantom, which was compared with independent dose measurements using GAFchromic film. Secondly, an ultrasound and iRAI dual-modality imaging system utilizing a phased array transducer was used to take coregistered two-dimensional (2D) iRAI signal amplitude images as well as ultrasound B-mode images, to map the dose deposition with respect to surrounding anatomy in an ex vivo rabbit liver model with a single linac pulse precision. Using a single element transducer, iRAI measurements showed a highly linear relationship between the iRAI signal amplitude and the linac dose per pulse (r2 =0.9998) with a repeatability precision of 1% and a dose resolution error <2.5% in a homogenous phantom when compared to GAFchromic film dose measurements. These phantom results were used to develop a calibration curve between the iRAI signal response and the delivered dose per pulse. Subsequently, a normalized depth dose curve was generated that agreed with film measurements with an RMSE of 0.0243, using correction factors to account for deviations in measurement conditions with respect to calibration. Experiments on the ex-vivo rabbit liver model demonstrated that a 2D iRAI image could be generated successfully from a single linac pulse, which was fused with the B-mode ultrasound image to provide information about the beam position with respect to surrounding anatomy in real time. This work demonstrates the potential of using iRAI for real-time deep tissue dosimetry in FLASH-RT. Our results show that iRAI signals are linear with dose and can accurately map the delivered radiation dose with respect to soft tissue anatomy. With its ability to measure dose for individual linac pulses at any location within surrounding soft tissue while identifying where that dose is being delivered anatomically in real time, iRAI can be an indispensable tool to enable safe and efficient clinical translation of FLASH-RT.

Highly sensitive lipid detection and localization in atherosclerotic plaque with a dual-frequency intravascular photoacoustic/ultrasound catheter.

Intravascular photoacoustic/ultrasound (IVPA/US) is an emerging hybrid imaging modality that provides specific lipid detection and localization, while maintaining co-registered artery morphology, for diagnosis of vulnerable plaque in cardiovascular disease. However, current IVPA/US approaches based on a single-element transducer exhibit compromised performance for lipid detection due to the relatively low contrast of lipid absorption and conflicting detection bands for photoacoustic and ultrasound signals. Here, we present a dual-frequency IVPA/US catheter for highly sensitive detection and precision localization of lipids. The low frequency transducer provides enhanced photoacoustic sensitivity, while the high frequency transducer maintains state-of-the-art spatial resolution for ultrasound imaging. The boosted capability of IVPA/US imaging enables a multi-scale analysis of lipid distribution in swine with coronary atherosclerosis. The dual-frequency IVPA/US catheter has a diameter of 1 mm and flexibility to easily adapt to current catheterization procedures and is a significant step toward clinical diagnosis of vulnerable plaque.

Improved evaluation of backscatter characteristics of soft tissue using high-frequency annular array

Clinical ultrasound is widely used for quantitative diagnosis. To clarify the relationship between anatomical and acoustic properties, high resolution imaging using high-frequency ultrasound (HFU) is required. However, when tissue properties are evaluated using HFU, the depth of field (DOF) is limited. To overcome this problem, an annular array transducer, which has a simple structure and produces high-quality images, is applied to HFU measurement. In previous phantom experiments, we demonstrated that the HFU annular array extends the DOF compared to that of a single-element transducer for quantitative ultrasound (QUS) analysis. Here, we extend that work by applying QUS methods to an ex vivo rat liver. The present study demonstrates that an annular array extends the region and improves the resolution for tissue characterization for an excised healthy rat liver. Amplitude envelope statistics and spectral-based analysis are used as QUS methods.

MEASUREMENT THICKNESS OF PROTECTIVE-DECORATIVE COATINGS ON CONCRETE BASES

The factors affecting to the ultrasonic testing of the coating thickness on concrete are considered. The structure and design of the transducer used to solve this problem. Features of the organization of the measurement process are described. Options for creating reference samples for tuning and testing ultrasonic thickness gauges used to solve this problem. The results of measuring the thickness of the polyurethane coating on concrete obtained on the Bulat 3 device using a specialized transducer are presented. The characteristics of concrete, which necessitate the use of special protective and decorative materials (surface abrasion, insufficient density, low hydrophobicity, etc.), and the characteristics of organic polymer coatings (adhesion, elasticity, wear resistance, chemical resistance, and hardness), which depend significantly on dry film thickness (protective layer). It is indicated that in order for the coating to ensure the fulfillment of the declared parameters taking into account economic feasibility, it is necessary to fulfill the requirements for a given minimum coating thickness, and that the use of the ultrasonic testing method seems to be the optimal method for measuring the coating thickness. Factors affecting the measurement process (the ratio of acoustic impedances, reflection coefficient and its variation range for various types of concrete and the most common coatings) are also considered. It is indicated that, based on a number of experiments with different types of transducers (dual element, single element and single element with the delay line), the maximum sensitivity and measurement range are ensured by using a direct single element transducer with a delay line. The data on the choice of the operating frequency of the transducer is given, depending on the range of measured coating thicknesses. The design and construction of the transducer, the features of the construction of its elements and their influence on the transducer characteristics, the principle of measuring the coating thickness and its implementation on the Bulat 3 ultrasonic thickness gauge are described. The char-acteristics of the device that allowed it to be used for such measurements are indicated. Information is provided on various options for the implementation of reference samples of the coating, on the methodology for their testing and the measurement results.

Versatile Single-Element Ultrasound Imaging Platform using a Water-Proofed MEMS Scanner for Animals and Humans

Single-element transducer based ultrasound (US) imaging offers a compact and affordable solution for high-frequency preclinical and clinical imaging because of its low cost, low complexity, and high spatial resolution compared to array-based US imaging. To achieve B-mode imaging, conventional approaches adapt mechanical linear or sector scanning methods. However, due to its low scanning speed, mechanical linear scanning cannot achieve acceptable temporal resolution for real-time imaging, and the sector scanning method requires specialized low-load transducers that are small and lightweight. Here, we present a novel single-element US imaging system based on an acoustic mirror scanning method. Instead of physically moving the US transducer, the acoustic path is quickly steered by a water-proofed microelectromechanical (MEMS) scanner, achieving real-time imaging. Taking advantage of the low-cost and compact MEMS scanner, we implemented both a tabletop system for in vivo small animal imaging and a handheld system for in vivo human imaging. Notably, in combination with mechanical raster scanning, we could acquire the volumetric US images in live animals. This versatile US imaging system can be potentially used for various preclinical and clinical applications, including echocardiography, ophthalmic imaging, and ultrasound-guided catheterization.

Single-Element Ultrasonic Transducer for Non-Invasive Measurements

A simple, passive, single-element ultrasonic transducer is proposed for non-invasive measurements. Operating the transducer at different resonant modes allows the adaptation of the emitted sound pattern to various requirements. The emitted sound field is simulated and experimentally characterized. We demonstrate the suitability of the transducer prototype for non-invasive continuous level measurement in laboratory as well as field environment over an extended level- and temperature range. The measured performance fulfils typical requirements for invasive level sensors. The versatility of the transducer enables its application in a wide range of non-invasive measurements.

Suppression of Lamb wave excitation via aperture control of a transducer array for ultrasonic clamp-on flow metering.

During ultrasonic clamp-on flow metering, Lamb waves propagating in the pipe wall may limit the measurement accuracy by introducing absolute errors in the flow estimates. Upon reception, these waves can interfere with the up and downstream waves refracting from the liquid, and disturb the measurement of the transit time difference that is used to obtain the flow speed. Thus, suppression of the generation of Lamb waves might directly increase the accuracy of a clamp-on flow meter. Existing techniques apply to flow meters with single element transducers. This paper considers the application of transducer arrays and presents a method to achieve a predefined amount of suppression of these spurious Lamb waves based on appropriate amplitude weightings of the transducer elements. Finite element simulations of an ultrasonic clamp-on flow measurement setting will be presented to show the effect of array aperture control on the suppression of the Lamb waves in a 1-mm-thick stainless steel pipe wall. Furthermore, a proof-of-principle experiment will be shown that demonstrates a good agreement with the simulations.

ARTSENS® Pen—portable easy-to-use device for carotid stiffness measurement: technology validation and clinical-utility assessment

Objective: The conventional medical imaging modalities used for arterial stiffness measurement are non-scalable and unviable for field-level vascular screening. The need for an affordable, easy-to-operate automated non-invasive technologies remains unmet. To address this need, we present a portable image-free ultrasound device—ARTSENS® Pen, that uses a single-element ultrasound transducer for carotid stiffness evaluation. Approach: The performance of the device was clinically validated on a cohort of 523 subjects. A clinical-grade B-mode ultrasound imaging system (ALOKA eTracking) was used as the reference. Carotid stiffness measurements were taken using the ARTSENS® Pen in sitting posture emulating field scenarios. Main results: A statistically significant correlation (r > 0.80, p < 0.0001) with a non-significant bias was observed between the measurements obtained from the two devices. The ARTSENS® Pen device could perform highly repeatable measurements (with variation smaller than 10%) on a relatively larger percentage of the population when compared to the ALOKA system. The study results also revealed the sensitivity of ARTSENS® Pen to detect changes in arterial stiffness with age. Significance: The easy-to-use technology and the automated algorithms of the ARTSENS® Pen make it suitable for cardiovascular risk assessment in resource-constrained settings.

Autoregressive Model-Based Reconstruction of Quantitative Acoustic Maps From RF Signals Sampled at Innovation Rate

The principle of quantitative acoustic microscopy (QAM) is to form two-dimensional (2D) acoustic parameter maps from a collection of radiofrequency (RF) signals acquired by raster scanning a biological sample. Despite their relatively simple structure consisting of two main reflections, RF signals are currently sampled at very high frequencies, e.g. , at 2.5 GHz for QAM system employing a single-element transducer with a center frequency of 250-MHz. The use of such high sampling frequencies is challenging because of the potentially large amount of acquired data and the cost of the necessary analog to digital converters. Based on a parametric model characterizing QAM RF signals, the objective of this article is to use the finite rate of innovation (FRI) framework in order to significantly reduce the number of acquired samples. These are then used to compute Fourier coefficients that are directly fed into a state-of-the-art autoregressive (AR)-based method to estimate the model parameters, which finally leads to the reconstruction of accurate 2D maps. The combination of FRI and AR model for sampling and parametric map recovery allows decreasing the required number of samples per RF signal up to a factor of 18 compared to a conventional approach, with a minimal accuracy loss of quantitative acoustic maps, as proven by visual evaluations and numerical results, i.e. PSNR of 24.50 dB and 24.51 dB for the reconstructed speed of sound map and acoustic impedance map respectively.

Validation of differences in backscatter coefficients among four ultrasound scanners with different beamforming methods.

The backscatter coefficient (BSC) indicates the absolute scatterer property of a material, independently of clinicians and system settings. Our study verified that the BSC differed among the scanners, transducers, and beamforming methods used for quantitative ultrasound analyses of biological tissues. Measurements were performed on four tissue-mimicking homogeneous phantoms containing spherical scatterers with mean diameters of 20 and 30µm prepared at concentrations of 0.5 and 2.0 wt%, respectively. The BSCs in the different systems were compared using ultrasound scanners with two single-element transducers and five linear high- or low-frequency probes. The beamforming methods were line-by-line formation using focused imaging (FI) and parallel beam formation using plane wave imaging (PWI). The BSC of each system was calculated by the reference phantom method. The mean deviation from the theoretical BSC computed by the Faran model was analyzed as the benchmark validation of the calculated BSC. The BSCs calculated in systems with different properties and beamforming methods well concurred with the theoretical BSC. The mean deviation was below ± 2.8dB on average, and within the approximate standard deviation (± 2.2dB at most) in all cases. These variations agreed with a previous study in which the largest error among four different scanners with FI beamforming was 3.5dB. The BSC in PWI was equivalent to those in the other systems and to those of FI beamforming. This result indicates the possibility of ultra-high frame-rate BSC analysis using PWI.

Development of a Stationary 3D Photoacoustic Imaging System Using Sparse Single-Element Transducers: Phantom Study

Photoacoustic imaging (PAI) is an emerging label-free and non-invasive modality for imaging biological tissues. PAI has been implemented in different configurations, one of which is photoacoustic computed tomography (PACT) with a potential wide range of applications, including brain and breast imaging. Hemispherical Array PACT (HA-PACT) is a variation of PACT that has solved the limited detection-view problem. Here, we designed an HA-PACT system consisting of 50 single element transducers. For implementation, we initially performed a simulation study, with parameters close to those in practice, to determine the relationship between the number of transducers and the quality of the reconstructed image. We then used the greatest number of transducers possible on the hemisphere and imaged copper wire phantoms coated with a light absorbing material to evaluate the performance of the system. Several practical issues such as light illumination, arrangement of the transducers, and an image reconstruction algorithm have been comprehensively studied.

Oscillating endoskeletal antibubbles

An antibubble is a gas bubble with a liquid droplet inside. Antibubbles have a potential role in ultrasonic imaging, ultrasound-guided drug delivery, and hydrocarbon leakage detection. The liquid core droplets inside antibubbles can be stabilised with a process called Pickering stability. Other systems proposed include spoke crystals to suspend the droplet or endoskeletal structures. In this study, the oscillatory response of microscopic endoskeletal antibubbles to ultrasound has been investigated, primarily to determine whether the presence of an endoskeleton attenuates the oscillation amplitude of the antibubble. Three emulsions containing (anti)bubbles were prepared for evaluation. Each emulsion was pipetted into the observation chamber of a high-speed microscopic observation system. A high-speed camera, operating at 10 million frames per second, was couples to the microscope. During camera recording, the materials were subjected to ultrasound pulses from a laboratory-assembled single-element transducer. The presence of an endoskeleton with droplets hampers the oscillation of antibubbles as compared to identical bubbles without endoskeleton and droplet content.

MRI monitoring of temperature and displacement for transcranial focus ultrasound applications

BackgroundTranscranial focus ultrasound applications applied under MRI-guidance benefit from unrivaled monitoring capabilities, allowing the recording of real-time anatomical information and biomarkers like the temperature rise and/or displacement induced by the acoustic radiation force. Having both of these measurements could allow for better targeting of brain structures, with improved therapy monitoring and safety. MethodWe investigated the use of a novel MRI-pulse sequence described previously in Bour et al., (2017) to quantify both the displacement and temperature changes under various ultrasound sonication conditions and in different regions of the brain. The method was evaluated in vivo in a non-human primate under anesthesia using a single-element transducer (f = 850 kHz) in a setting that could mimic clinical applications. Acquisition was performed at 3 T on a clinical imaging system using a modified single-shot gradient echo EPI sequence integrating a bipolar motion-sensitive encoding gradient. Four slices were acquired sequentially perpendicularly or axially to the direction of the ultrasound beam with a 1-Hz update frequency and an isotropic spatial resolution of 2-mm. A total of twenty-four acquisitions were performed in three different sets of experiments. Measurement uncertainty of the sequence was investigated under different acoustic power deposition and in different regions of the brain. Acoustic simulation and thermal modeling were performed and compared to experimental data. ResultsThe sequence simultaneously provides relevant information about the focal spot location and visualization of heating of brain structures: 1) The sequence localized the acoustic focus both along as well as perpendicular to the ultrasound direction. Tissue displacements ranged from 1 to 2 μm. 2) Thermal rise was only observed at the vicinity of the skull. Temperature increase ranged between 1 and 2 °C and was observed delayed relative the sonication due to thermal diffusion. 3) The fast frame rate imaging was able to highlight magnetic susceptibility artifacts related to breathing, for the most caudal slices. We demonstrated that respiratory triggering successfully restored the sensitivity of the method (from 0.7 μm to 0.2 μm). 4) These results were corroborated by acoustic simulations. ConclusionsThe current rapid, multi-slice acquisition and real-time implementation of temperature and displacement visualization may be useful in clinical practices. It may help defining operational safety margins, improving therapy precision and efficacy. Simulations were in good agreement with experimental data and may thus be used prior treatment for procedure planning.

Phospholipid conjugated prodrugs for targeted delivery using ultrasound with microbubbles and nanodroplets

Therapeutic payloads remain a challenge for phospholipid-stabilized microbubbles that are currently used as contrast agents in diagnostic ultrasound imaging. High loading is difficult to achieve due to the metastable phospholipid monolayer that lacks cargo volume, requiring lengthy drug-loaded particle tethering strategies or other sophisticated methods. The purpose of this work is to demonstrate that phospholipid conjugation can anchor chemotherapeutics to the microbubble shell with minimal disruption to phospholipid packing, resulting in an ultrasound theranostic agent that requires minimal preparation prior to administration. Using a Steglich esterification reaction, several potent chemotherapeutics were conjugated to phospholipids and were subsequently incorporated into liposomes, microbubbles, and nanodroplets for biological and particle characterization. Prodrug structures were confirmed with 1H and 13C NMR. Retention of biological activity for each phospholipid prodrug was demonstrated with an MTT cell proliferation assay using liposomes. Loading and stability of nanodroplets and microbubbles were measured with UV-Vis spectroscopy. To demonstrate site-specific delivery potential, these solutions were suspended in a submersible cell culture chamber with adhered HeLa cells. A single element transducer was used to apply a radiation force and fragmentation pulse sequence. Ultrasound-exposed and non-exposed areas treated with prodrug-containing microbubbles and nanodroplets were compared, demonstrating local efficacy.

Real-time imaging of brain displacement during FUS neuromodulation in rodents in vivo

Focused ultrasound (FUS) is capable of modulating the central and peripheral nervous system. Temperature increase, cavitation, and acoustic radiation force have been proposed as potential mechanisms. Thus, tissue displacement imaging during FUS modulation is critical to understanding its physical mechanism. A cranial window was formed to perform imaging during FUS neuromodulation in C57BL/6 mice. FUS sonications were performed with a 4 MHz single-element transducer with a focal volume 0.2 × 0.9 mm (Sonic Concepts, WA), an applied tone burst of 0.5 ms and peak positive pressures varying from 1.9 to 6.7 MPa. Real-time channel data using plane wave sequences were acquired with an 18 MHz linear array (Vermon, France) and axial displacements throughout the entire brain were estimated using 1D cross-correlation (9λ window, 99% overlap) at 1 kHz frame rate. Downward displacements were only detected during FUS within the focal region. During modulation, the cumulative displacement ranged from 0.021 ± 0.017 μm (n = 3) at 3.1 MPa to 0.24 ± 0.004 μm at 6.7 MPa (n = 3). Displacement decreased post-FUS and returned to null within 1–2 ms. Unlike in a preliminary phantom study, no shear waves were detected. Real-time displacement imaging could thus provide effective targeting and monitoring as well as unveil the mechanism during FUS modulation.Focused ultrasound (FUS) is capable of modulating the central and peripheral nervous system. Temperature increase, cavitation, and acoustic radiation force have been proposed as potential mechanisms. Thus, tissue displacement imaging during FUS modulation is critical to understanding its physical mechanism. A cranial window was formed to perform imaging during FUS neuromodulation in C57BL/6 mice. FUS sonications were performed with a 4 MHz single-element transducer with a focal volume 0.2 × 0.9 mm (Sonic Concepts, WA), an applied tone burst of 0.5 ms and peak positive pressures varying from 1.9 to 6.7 MPa. Real-time channel data using plane wave sequences were acquired with an 18 MHz linear array (Vermon, France) and axial displacements throughout the entire brain were estimated using 1D cross-correlation (9λ window, 99% overlap) at 1 kHz frame rate. Downward displacements were only detected during FUS within the focal region. During modulation, the cumulative displacement ranged from 0.021 ± 0.017 μm (n ...

Estimation of Backscatter Coefficients Using an In Situ Calibration Source.

The objective of this article is to demonstrate the feasibility of estimating the backscatter coefficient (BSC) using an in situ calibration source. Traditional methods of estimating the BSC in vivo using a reference phantom technique do not account for transmission losses due to intervening layers between the ultrasonic source and the tissue region to be interrogated, leading to increases in bias and variance of BSC-based estimates. To account for transmission losses, an in situ calibration approach is proposed. The in situ calibration technique employs a titanium sphere that is well-characterized ultrasonically, biocompatible, and embedded inside the sample. A set of experiments was conducted to evaluate the embedded titanium spheres as in situ calibration targets for BSC estimation. The first experiment quantified the backscattered signal strength from titanium spheres of three sizes: 0.5, 1, and 2 mm in diameter. The second set of experiments assessed the repeatability of BSC estimates from the titanium spheres and compared these BSCs to theory. The third set of experiments quantified the ability of the titanium bead to provide an in situ reference spectrum in the presence of a lossy layer on top of the sample. The final set of experiments quantified the ability of the bead to provide a calibration spectrum over multiple depths in the sample. All experiments were conducted using an L9-4/38 linear array connected to a SonixOne system. The strongest signal was observed from the 2-mm titanium bead with the signal-to-noise ratio (SNR) of 11.6 dB with respect to the background speckle. Using an analysis bandwidth of 2.5-5.5 MHz, the mean differences between the experimentally derived BSCs and BSCs derived from the Faran theory were 0.54 and 0.76 dB using the array and a single-element transducer, respectively. The BSCs estimated using the in situ calibration approach without the layer and with the layer and using the reference phantom approach with the layer were compared to the reference phantom approach without the layer present. The mean differences in BSCs were 0.15, 0.73, and -9.69 dB, respectively. The mean differences of the BSCs calculated from data blocks located at depths that were either 30 pulse lengths above or below the actual bead depth compared to the BSC calculated at bead depth were -1.55 and -1.48 dB, respectively. The results indicate that an in situ calibration target can account for overlaying tissue losses, thereby improving the robustness of BSC-based estimates.

A One-Sided Acoustic Trap for Cell Immobilization Using 30-MHz Array Transducer.

Biological studies often involve the investigation of immobilized (or trapped) particles and cells. Various trapping methods without touching, such as optical, magnetic, and acoustic tweezers, have been developed to trap small particles. Here, we present the manipulation of a single cell or multiple cells using ultrasound-array-based single-beam acoustic tweezers (UA-SBATs). In SBATs, only a one-sided tightly focused acoustic beam produces a high acoustic gradient force-a mechanism that mirrors that of optical tweezers. As a result, targeted cells can be attracted to the beam center and immobilized within its trapping zone. Since an array transducer allows acoustic beam steering and scanning electronically instead of mechanical translation, it can manipulate cells more simply and quickly compared with single-element transducers, especially in biocompatible setup. In this experiment, a customized 30-MHz array transducer with an interdigitally bonded (IB) 2-2 piezocomposite was employed to immobilize MCF-12F cells. Cells were attracted to the center of the beam and laterally displaced with the array transducer without any damages to the cells. These findings suggest that UA-SBAT can be a promising tool for cell manipulation and may pave the way for exploring new biological applications.