Single-element Transducer Research Articles

Biaxial ultrasound driving technique for small animal blood–brain barrier opening

Biaxial driving can more efficiently convert electrical power to forward acoustic power in piezoelectric materials, and the interaction between the orthogonal electric fields can produce a combination of extensional and shear deformations as a function of the phase difference between them to allow dynamic steering of the beam with a single-element. In this study, we demonstrate for the first time the application of a single-element biaxially driven ring transducer in vivo for blood–brain barrier opening in mice, and compare it to that achieved with a conventional single-element highly focused (F# = 0.7) spherical transducer operating at a similar frequency. Transcranial focused ultrasound (0.45 MPa, 10 ms pulse length, 1 Hz repetition frequency, 30 s duration) was applied bilaterally to mice with a 40 μl/kg bolus of DefinityTM microbubbles, employing either a single-element biaxial ring (1.482 MHz, 10 mm inner diameter, 13.75 mm outer diameter) or spherical (1.5 MHz, 35 mm diameter, F# = 0.7; RK50, FUS Instruments) transducer on each side. Follow-up MRI scans (T1 pre- and post- 0.2 mmol/kg Gd injection, T2) were acquired to assess blood–brain barrier opening volume and potential damage. Compared to blood–brain barrier opening achieved with a conventional single-element spherical focused transducer, the opening volume achieved with a single-element biaxial ring transducer was 35% smaller (p = 0.002) with a device of a ring diameter of 40% the aperture size. Axial refocusing was further demonstrated with the single-element biaxial ring transducer, yielding a 1.63 mm deeper, five-fold larger opening volume (p = 0.048) relative to its small-focus mode. The biaxial ring transducer achieved a more localized opening compared to the spherical focused transducer under the same parameters, and further enabled dynamic axial refocusing with a single-element transducer with a smaller fabrication footprint.

Generation of Induced Wavefront Focalization in the Human Temporal Bone Using a Standard Focused Ultrasound Single-Element Transducer

Generation of Induced Wavefront Focalization in the Human Temporal Bone Using a Standard Focused Ultrasound Single-Element Transducer

Electrowetting-driven liquid lens for ultrasound: Enabling controllable focal length and flexible beam steering

Focused ultrasound is an increasingly popular non-invasive treatment modality. Still, its fixed focal point requires an array ultrasound transducer or scanning system to cover different therapeutic scenarios. To address this limitation, we developed an electrically-controlled liquid lens that enables dynamic beam focusing and steering of the incident plane ultrasound beam. The lens was carefully optimized for low-energy attenuation and low-voltage driving. We evaluated the performance of the lens using a homemade 5.5-MHz planar transducer with a 7.5-mm aperture. Our results demonstrate that the planar ultrasound beam can be adjusted to a focused beam with a focal length from 27 mm to 32 mm within 1 s by increasing the electric input (0–60 V) to the lens. Additionally, the beam angle of the ultrasound is tunable from −5 to 5° by adjusting the charge distribution on the lens. Our design enables real-time, fast-response, on-demand changing of focal length and beam angle for a single-element planar transducer. Our study presents a promising technology for altering the ultrasound beam of a planar single-element transducer for different ultrasound applications. The development of this electrically-controlled liquid lens has the potential to enhance the efficacy of focused ultrasound treatment and improve patient outcomes.

Feasibility of Ultrasonic Heating through Skull Phantom Using Single-element Transducer.

Noninvasive neurosurgery has become possible through the use of transcranial focused ultrasound (FUS). This study assessed the heating ability of single element spherically focused transducers operating at 0.4 and 1.1 MHz through three-dimensional (3D) printed thermoplastic skull phantoms. Phantoms with precise skull bone geometry of a male patient were 3D printed using common thermoplastic materials following segmentation on a computed tomography head scan image. The brain tissue was mimicked by an agar-based gel phantom developed in-house. The selection of phantom materials was mainly based on transmission-through attenuation measurements. Phantom sonications were performed through water, and then, with the skull phantoms intervening the beam path. In each case, thermometry was performed at the focal spot using thermocouples. The focal temperature change in the presence of the skull phantoms was reduced to less than 20 % of that recorded in free field when using the 0.4 MHz transducer, whereas the 1.1 MHz trans-skull sonication produced minimal or no change in focal temperature. The 0.4 MHz transducer showed better performance in trans-skull transmission but still not efficient. The inability of both tested single element transducers to steer the beam through the high attenuating skull phantoms and raise the temperature at the focus was confirmed, underlying the necessity to use a correction technique to compensate for energy losses, such those provided by phased arrays. The proposed phantom could be used as a cost-effective and ergonomic tool for trans-skull FUS preclinical studies.

Initial Study of A-mode Ultrasound Spectroscopy Through Mechanical Wave Scattering Phenomenon for Measuring 3D-printed Bone Model Density

In Indonesia, the prevalence of osteoporosis is high. Given the economic burden it may impose on the population, this condition must be taken seriously. Dual-energy X-ray absorptiometry is the gold standard for diagnosing osteoporosis (DEXA). However, due to its high cost, non-portability, and radiation risk, DEXA cannot be applied to large populations. An alternative method for evaluating bone quality is ultrasound. It is more affordable, portable, and has no radiation risk. In this preliminary study, an A-mode ultrasound spectroscopy prototype for assessing the density of a 3D-printed bone model is designed. A single-element transducer (Transmit-Tx/Receive-Rx), a reconfigurable and modular FPGA-based ultrasound beamformer system, and a Raspberry Pi 3 are the system's control units. The raw radio frequency (RF) signal is acquired from three variations of density of the 3D-printed bone model, i.e., 100%, 60%, and 40%, to represent normal bone, osteopenia, and osteoporosis. The designed prototype can adequately characterize the mechanical wave scattering pattern of the 3D-printed bone model indicated by the increased tendency in the maximum amplitude when the density of the bone model is increasing. The tendency is the opposite for delay time and Power Spectral Density (PSD). These three signal parameters are potential candidate parameters to represent bone density. For future work, the selected candidate parameters can later be used as reference values while adding a significant data so that a machine learning method can be employed to extract representative features of bone density level, i.e., normal bone, osteopenia, and osteoporosis.

A phased array ultrasound system with a robotic arm for neuromodulation.

Ultrasonic neuromodulation (UNMOD) provides a non-invasive brain stimulation. However, the high-resolution region-specificity of UNMOD with a single element transducer combined with a mechanical positioning system could have limits due to the intrinsic positioning error from mechanical systems. A phased array system could lead to highly selective neuromodulation with electronic control. A specialized phased-array system with a robotic arm is implemented for a rhesus monkey model. Various primary motor cortex areas related to tail, hand, and mouth were stimulated with a 200μm step size. The ultrasonic parameters were ISPTA of 840mW/cm2, pulse repetition frequency of 100Hz, and a 5% duty factor at 600kHz. The induced movement were recorded and analyzed. Separate digits, mouth, and tongue motions were successfully induced by electronically controlling the focus. The identical body part movement could be induced when the focus was moved back to the identical primary motor cortex with electronic control. Accordingly, the reproducibility of UNMOD could be partially validated with rhesus monkey model. A phased-array system appears to have a potential for the non-invasive and region-selective neuromodulation method.

Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer

PurposeThe study aims to provide insights on the practicality of using single-element transducers for transcranial Focused Ultrasound (tFUS) thermal applications.MethodsFUS sonications were performed through skull phantoms embedding agar-based tissue mimicking gels using a 1 MHz single-element spherically focused transducer. The skull phantoms were 3D printed with Acrylonitrile Butadiene Styrene (ABS) and Resin thermoplastics having the exact skull bone geometry of a healthy volunteer. The temperature field distribution during and after heating was monitored in a 3 T Magnetic Resonance Imaging (MRI) scanner using MR thermometry. The effect of the skull’s thickness on intracranial heating was investigated.ResultsA single FUS sonication at focal acoustic intensities close to 1580 W/cm2 for 60 s in free field heated up the agar phantom to ablative temperatures reaching about 90 °C (baseline of 37 °C). The ABS skull strongly blocked the ultrasonic waves, resulting in zero temperature increase within the phantom. Considerable heating was achieved through the Resin skull, but it remained at hyperthermia levels. Conversely, tFUS through a 1 mm Resin skull showed enhanced ultrasonic penetration and heating, with the focal temperature reaching 70 °C.ConclusionsThe ABS skull demonstrated poorer performance in terms of tFUS compared to the Resin skull owing to its higher ultrasonic attenuation and porosity. The thin Resin phantom of 1 mm thickness provided an efficient acoustic window for delivering tFUS and heating up deep phantom areas. The results of such studies could be particularly useful for accelerating the establishment of a wider range of tFUS applications.

Piezoelectric bimorph-driven ultrasound scanner for high frequency ultrasound imaging

Ultrasound imaging commonly uses mechanical or electronic scanning methods. However, the mechanical scanning systems are bulky and susceptible to electromagnetic interference, while electronic scanning systems are complex and expensive. A more affordable and compact solution for high frequency preclinical and clinical imaging is single-element transducer based ultrasound imaging. This method offers high spatial resolution with low cost and low complexity. In this study, a novel single-element high frequency ultrasound imaging scanner was introduced. The scanner is based on piezoelectric bimorph drive and designed to be low-cost, compact, and handheld. Tungsten wire phantom imaging was performed on a dedicated ultrasound imaging system, and the obtained results were analyzed and compared. The results demonstrate that piezoelectric bimorph drive allows for high frequency imaging with a scanning speed of up to 208 frames per second. The image quality was higher than that of electromagnetic motor drive. The versatility of the ultrasound imaging system makes it suitable for preclinical and clinical applications, including small animal imaging, ophthalmic imaging, skin imaging, and intraoperative ultrasound imaging.

Higher harmonics dynamic focalization in single-element ring transducers using biaxial driving

Biaxial driving is a new driving technique that allows the steering of the ultrasound field generated by a single-element piezoceramic transducer. Because of their natural axisymmetric geometry, ultrasound generation with ring transducers can take advantage of the biaxial driving to change the focus of the beam generated by this type of transducer using only two driving signals. In this study, we applied the biaxial driving technique into a single-element PZT ring transducer operating at 500 kHz to produce a change in size and position of the focal spot while using the 1st (482 kHz), 3rd (1.362 MHz) and 5th (2.62 MHz) harmonic excitation. The transducer had a thickness of 2.85 mm, an inner diameter of 9.75 mm and a ring width of 2.0 mm, and two pairs of electrodes as required for biaxial driving. Simulation and experimental results showed that both the focal area and the distance at which the focal area centre was located changed as a function of the phase and power difference between the two driving signals. Experimental results showed that the focal area could be reduced from 31.6 mm2 (conventional driving) to 3.4 mm2 (89 % reduction) when using the first harmonic excitation. For the third harmonic, the focal area could be reduced from 4.0 mm2 (conventional driving) to 3.3 mm2 (17.5 % reduction). For the fifth harmonic, the focal area could be reduced from 1.7 mm2 (conventional driving) to 1 mm2 (41.7 % reduction). Results also demonstrated the centre of the focus could be displaced between 3.0 mm and 9.3 mm from the surface of the transducer when using the first harmonic, between 7.3 mm and 8.4 mm at the third harmonic, and between 4.9 mm and 8.2 mm at the fifth harmonic. The reduction in the focus area, as well as the possibility to displace the focus dynamically will be advantageous for preclinical applications of focused ultrasound, especially on drug delivery and neuromodulation studies in small rodents.

Assessing sensing techniques for detecting markers of approaching ecdysis in juvenile tropical rock lobsters, Panulirus ornatus

The development of hatchery technology for spiny lobsters has promoted interest in the establishment of a commercial on shore lobster aquaculture industry in Australia. Cannibalism in culture is extensive with cannibalistic interactions occurring during a relatively brief vulnerability while moulting. Therefore, pre-ecdysis characterisation would create an opportunity to intervene and disrupt cannibalism. Detecting pre-ecdysis with a sensor would open the scope of research into cannibalism reducing culture environments. During this study, three markers that have the potential to indicate ecdysis are assessed: growth of the new integument, formation of suture lines, and pigment changes. These markers were assessed using high frequency imaging ultrasound, computer vision, and digital image analysis in the HSV colour space, respectively.For individual animals, carotenoid pigment shift is an early and clear marker of pre-ecdysis, however variability between individuals excludes pigmentation being useful in characterising pre-ecdysis. Suture line definition was problematic under visible light because its definition was reduced by similarly coloured pigments, therefore using suture lines as a pre-ecdysis characteriser requires better definition. A logical research approach to enhance suture line clarity in images is to image them with light outside the visible spectrum. Growth of the new integument was visible on sonographs beneath the branchiostegites indicating that ultrasound may be a useful tool for sensing pre-ecdysis in lobsters. Ultrasonic investigation using a single element transducer may be a lower cost and robust sensing solution to detect new integument growth and is a high priority future research pathway.

THE USE OF ULTRASOUND TOMOGRAPHY TO IMPROVE ULTRASOUND CONTROL EFFICIENCY

To ensure safe and reliable operation of pipeline systems, it is necessary to regularly carry out work on technical diagnostics. Ultrasonic inspection is one of the most common methods for pipeline technical condition determining. It has many advantages over other control methods among which there can be distinguished accessibility, the absence of additional requirements for equipping the object under examination, the absence of an impact on the object of control itself, and safety. But ultrasonic inspection also has disadvantages some of which can be eliminated by using an individual piezo elements of multi-element transducer instead of simple single-element transducers.
 The method of pipeline wall thickness determining using piezo elements of a multi-element transducer, as well as searching for and identifying the type and size of the defect, is known as ultrasonic tomography.
 This paper presents the main features of the transducers used in ultrasonic tomography, possibilities of ultrasonic tomography when it is used in field pipeline diagnostics. The advantages of using the method of ultrasonic tomography in comparison with conventional ultrasonic control are considered.

Single-shot photoacoustic imaging with single-element transducer through a spatiotemporal encoder.

Current photoacoustic (PA) imaging modalities typically require either serial detection with a single-element transducer or parallel detections with an ultrasonic array, indicating a dilemma between system cost and imaging throughput. PA topography through ergodic relay (PATER) was recently developed to address this bottleneck. However, PATER requires object-specific calibration due to varied boundary condition and must be recalibrated through pointwise scanning for each object before measurements, which is time-consuming and severely limits practical application. We aim to develop a new single-shot PA imaging technique that only requires a one-time calibration for imaging different objects using a single-element transducer. We develop an imaging method, PA imaging through a spatiotemporal encoder (PAISE), to address the above issue. The spatial information is effectively coded into unique temporal features by the spatiotemporal encoder, which allows for compressive image reconstruction. An ultrasonic waveguide is proposed as a critical element to guide the PA waves from the object into the prism, which effectively accounts for the varied boundary condition of different objects. We further add irregular-shaped edges on the prism to introduce randomized internal reflections and further facilitate the scrambling of acoustic waves. The proposed technique is validated through comprehensive numerical simulations and experiments, and it is demonstrated that PAISE can successfully overcome the changed boundary condition and can image different samples given a single calibration. The proposed PAISE technique is capable of single-shot widefield PA imaging with a single-element transducer and does not require sample-specific calibration, which successfully overcomes the major limitation of previous PATER technology.

Binary Volume Acoustic Holograms

In recent years, high-resolution additive manufacturing has enabled a diverse range of low-cost methods for ultrasonic wave-front shaping. Acoustic holograms, in particular, allow for the generation of arbitrary diffraction-limited acoustic fields at megahertz frequencies from single-element transducers. These are phase plates that function as direct acoustic analogs to thin optical holograms. In this work, it is shown that, by using multiple polymer three-dimensional (3D) printing, two-material (binary) acoustic analogs to ``thick'' or volume optical holograms can also be generated. First, an analytic approach for designing a volume hologram that diffracts a set of input fields onto a desired set of output fields is briefly summarized. Next, a greedy-optimization approach based on random downhill binary search able to account for the constraints imposed by the chosen fabrication method is introduced. Finally, an experimental test case designed to diffract the field generated by a 2.54-cm planar lead zirconate titanate (PZT) transducer onto eight distinct patterns dependent on the direction of the incident field is used to validate the approach and the design method. Field scans of the eight target fields demonstrate that acoustic analogs of optical volume holograms can be generated using multipolymer printing and that these allow the multiplexing of distinct fields onto different incident field directions.

Inkjet-printed P(VDF-TrFE) film for high-frequency annular array.

An innovative processing to deposit P(VDF-TrFE) film on silicon wafers by an inkjet printing method was used to fabricate high-frequency annular array prototype. This prototype has a total aperture of 7.3 mm and 8 active elements. A polymer-based lens with low acoustic attenuation was added to the flat deposition on the wafer, setting the geometric focus to 13.8 mm. With a thickness of around 11 μm, the electromechanical performance of P(VDF-TrFE) films was evaluated with an effective thickness coupling factor of 22%. Electronics allowing all elements to simultaneously emit as a single element transducer was developed. In reception, a dynamic focusing, based on eight independent amplifying channels, was preferred. The center frequency of the prototype was 21.3 MHz, the insertion loss was 48.5 dB and the -6 dB fractional bandwidth was 143%. The trade-off sensitivity/bandwidth has rather favored the large bandwidth. Dynamic focusing on reception was applied and allowed to improvements in the lateral-full width at half maximum as shown on images obtained with a wire phantom at several depths. The next step, for a fully operational multi-element transducer, will be to achieve a significant increase of the acoustic attenuation in the silicon wafer.

Development of Single-Channel Dual-Element Custom-Made Ultrasound Scanner with Miniature Optical Position Tracker for Freehand Imaging.

Handheld ultrasound has great potential in resource-limited areas, and can improve healthcare for rural populations. Single-channel ultrasound has been widely used in many clinical ultrasound applications, and optical tracking is considered accurate and reliable. In this study, we developed a 10 MHz lead magnesium niobate-lead titanate (PMN-PT) dual-element ultrasound transducer combined with a miniature optical position tracker, and then measured the rectus femoris of the thigh, upper arm, and cheek muscles. Compared to single-element transducers, dual-element transducers improve the contrast of near-field signals, effectively reduce noise, and are suitable for measuring curved surfaces. The purpose of position tracking is to calculate the location of the ultrasound transducer during the measurement process. By utilizing positioning information, 2D ultrasound imaging can be achieved while maintaining structural integrity. The dual-element ultrasound scanner presented in this study can enable continuous scanning over a large area without a scanning width limitation. The custom-made dual-element ultrasound scanner has the advantage of being a portable, reliable, and low-cost ultrasound device, and is helpful in popularizing medical care for remote villages.

Transcranial 3D ultrasound localization microscopy using a large element matrix array with a multi-lens diffracting layer: an in vitro study

Objective. Early diagnosis and acute knowledge of cerebral disease require to map the microflows of the whole brain. Recently, ultrasound localization microscopy (ULM) was applied to map and quantify blood microflows in 2D in the brain of adult patients down to the micron scale. Whole brain 3D clinical ULM remains challenging due to the transcranial energy loss which reduces significantly the imaging sensitivity. Approach. Large aperture probes with a large surface can increase both the field of view and sensitivity. However, a large active surface implies thousands of acoustic elements, which limits clinical translation. In a previous simulation study, we developed a new probe concept combining a limited number of elements and a large aperture. It is based on large elements, to increase sensitivity, and a multi-lens diffracting layer to improve the focusing quality. In this study, a 16 elements prototype, driven at 1 MHz frequency, was made and in vitro experiments were performed to validate the imaging capabilities of this new probe concept. Main results. First, pressure fields emitted from a large single transducer element without and with diverging lens were compared. Low directivity was measured for the large element with the diverging lens while maintaining high transmit pressure. The focusing quality of 4 × 3cm matrix arrays of 16 elements without/with lenses were compared. In vitro experiments in a water tank and through a human skull were achieved to localize and track microbubbles in tubes. Significance. ULM was achieved demonstrating the strong potential of multi-lens diffracting layer to enable microcirculation assessment over a large field of view through the bones.

Super-resolution cellular ultrasound imaging via localization of nanodroplets

Ultrasound localization microscopy (ULM) had made it possible to differentiate microbubble contrast agents that are separated only by a few micrometers and, thus, opening the path for super-resolution imaging. However, due to the innate limits of acoustic waves and microbubble imaging, similar levels of resolution to optical imaging (i.e., submicron resolution) are still very challenging. In this paper, we utilize ULM to achieve cellular imaging by using phase-change perfluorocarbon nanodroplets (PFCnDs) as a contrast agent that were fabricated with spontaneous nucleation method. To identify the point spread function (PSF) of a single nanodroplet, gaussian fit function was applied for reconstruction. Nanodroplets were injected into cells through patch clamping and later captured with two transducers: a single element transducer for focused ultrasound and linear array transducer for imaging. Nonlinear imaging (NLO) was used to maximize the sound to noise ratio (SNR), which enables optimal amplitude. With the PSF of a phase-transitioned nanodroplet known, stochastic activation of multiple nanodroplets within a cell was accumulated to image a full cell morphology. These findings can lead researchers to develop effective ultrasound imaging paradigms that can visualize intracellular level of organs in deep tissue invivo.

Assessing machine independence of quantitative ultrasonography to evaluate vision degrading myodesopsia

Vision degrading myodesopsia (VDM) results from clinically significant vitreous opacities that reduce contrast sensitivity (CS) and visual quality of life (VQOL). Previous studies with a single clinical system for quantitative ultrasonography (QUS) found correlations with CS and VQOL as measured by the N.E.I. Visual Function Questionnaire (VFQ). Here, we evaluated a cohort of patients to determine if VDM as evaluated by QUS is machine independent. 28 eyes from 14 patients (age 56 ± 14 years) experiencing VDM were scanned with two different clinical ophthalmic ultrasound systems in succession: one with a 15-MHz single element transducer (23mm focal length, 7 mm aperture) and one with a 20 MHz annular array (five elements, 22 mm focal length, 9 mm total aperture). Images were acquired as a longitudinal plane through premacular vitreous in temporal gaze. Three QUS parameters and a composite score were computed from the vitreous region within each set of log-compressed envelope data and averaged over artifact-free frames. A linear regression comparing QUS parameters computed fromeach system showed statistically significant correlations (R ≥ 0.86, p < 0.001). Moreover, QUS parameters from both systems were correlated with CS and VFQ scores. The results from this study suggest the QUS parameters are independent of scanner and could be universally applied to assess VDM.

Heterogenous angular spectrum approach based holograms for trans-skull focused ultrasound therapy

Focused Ultrasound (FUS) therapy in the brain entails accounting for strong distortions in the transmitted wavefields introduced by the skull. While these aberrations are compensated by MR-guided FUS (MRgFUS) phased array-based systems by adjusting the phase and amplitude of individual transducer elements, their cost and reliance on MRI may limit their widespread adoption. This work presents phase-only acoustic holograms coupled to a single transducer element as a safe, effective, and affordable alternative. We used the Heterogenous Angular Spectrum Approach (HASA) to propagate between the transducer and target plane(s) and applied automated differentiation for gradient computation to iteratively optimize the phase of the holographic lens. To test our design approach, we employed experimentally validated k-wave simulation. Our results show a 9 dB increase in the peak signal-to-noise ratio (PSNR) of the target acoustic field at 1 MHz as compared to the case where aberrations are uncorrected. Furthermore, we addressed the effect of frequency and aperture on the quality of hologram construction. We showed the feasibility of implementing it in a clinical-scale FUS system targeting deep (>6 cm) brain structures. In summary, the combination of HASA with automated differentiation is an efficient and accurate tool for hologram design through heterogeneous media.

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

Objective. Ultrasound neuromodulation has become an emerging method for the therapy of neurodegenerative and psychiatric diseases. The phased array ultrasonic transducer enables multi-target ultrasound neuromodulation in small animals, but the relatively large size and mass and the thick cables of the array limit the free movement of small animals. Furthermore, spatial interference may occur during multi-target ultrasound brain stimulation with multiple micro transducers. Approach. In this study, we developed a miniature power ultrasound transducer and used the virtual source time inversion method and 3D printing technology to design, optimize, and manufacture the acoustic holographic lens to construct a multi-target ultrasound neuromodulation system for free-moving mice. The feasibility of the system was verified by in vitro transcranial ultrasound field measurements, in vivo dual-target blood-brain barrier (BBB) opening experiments, and in vivo dual-target ultrasound neuromodulation experiments. Main results. The developed miniature transducer had a diameter of 4.0 mm, a center frequency of 1.1 MHz, and a weight of 1.25 g. The developed miniature acoustic holographic lens had a weight of 0.019 g to generate dual-focus transcranial ultrasound. The ultrasonic field measurements’ results showed that the bifocal’s horizontal distance was 3.0 mm, the −6 dB focal spot width in the x-direction was 2.5 and 2.25 mm, and 2.12 and 2.24 mm in the y-direction. Finally, the in vivo experimental results showed that the system could achieve dual-target BBB opening and ultrasound neuromodulation in freely-moving mice. Significance. The ultrasonic neuromodulation system based on a miniature single-element transducer and the miniature acoustic holographic lens could achieve dual-target neuromodulation in awake small animals, which is expected to be applied to the research of non-invasive dual-target ultrasonic treatment of brain diseases in awake small animals.