A tip-coupled, two-cantilever, non-resonant microsystem for direct measurement of liquid viscosity.

We report a non-resonant piezoelectric microelectromechanical cantilever system for the measurement of liquid viscosity. The system consists of two PiezoMEMS cantilevers in-line, with their free ends facing each other. The system is immersed in the fluid under test for viscosity measurement. One of the cantilevers is actuated using the embedded piezoelectric thin film to oscillate at a pre-selected non-resonant frequency. The second cantilever, the passive one, starts to oscillate due to the fluid-mediated energy transfer. The relative response of the passive cantilever is used as the metric for the fluid's kinematic viscosity. The fabricated cantilevers are tested as viscosity sensors by carrying out experiments in fluids with different viscosities. The viscometer can measure viscosity at a single frequency of choice, and hence some important considerations for frequency selection are discussed. A discussion on the energy coupling between the active and the passive cantilevers is presented. The novel PiezoMEMS viscometer architecture proposed in this work will overcome several challenges faced by state-of-the-art resonance MEMS viscometers, by enabling faster and direct measurement, straightforward calibration, and the possibility of shear rate-dependent viscosity measurement.

Improving PMUT Receive Sensitivity via DC Bias and Piezoelectric Composition.

The receive sensitivity of lead zirconate titanate (PZT) piezoelectric micromachined ultrasound transducers (PMUTs) was improved by applying a DC bias during operation. The PMUT receive sensitivity is governed by the voltage piezoelectric coefficient, h31,f. With applied DC biases (up to 15 V) on a 2 µm PbZr0.52Ti0.48O3 film, e31,f increased 1.6 times, permittivity decreased by a factor of 0.6, and the voltage coefficient increased by ~2.5 times. For released PMUT devices, the ultrasound receive sensitivity improved by 2.5 times and the photoacoustic signal improved 1.9 times with 15 V applied DC bias. B-mode photoacoustic imaging experiments showed that with DC bias, the PMUT received clearer photoacoustic signals from pencil leads at 4.3 cm, compared to 3.7 cm without DC bias.

A Transparent Ultrasound Array for Real-Time Optical, Ultrasound, and Photoacoustic Imaging.

Objective and Impact Statement. Simultaneous imaging of ultrasound and optical contrasts can help map structural, functional, and molecular biomarkers inside living subjects with high spatial resolution. There is a need to develop a platform to facilitate this multimodal imaging capability to improve diagnostic sensitivity and specificity. Introduction. Currently, combining ultrasound, photoacoustic, and optical imaging modalities is challenging because conventional ultrasound transducer arrays are optically opaque. As a result, complex geometries are used to coalign both optical and ultrasound waves in the same field of view. Methods. One elegant solution is to make the ultrasound transducer transparent to light. Here, we demonstrate a novel transparent ultrasound transducer (TUT) linear array fabricated using a transparent lithium niobate piezoelectric material for real-time multimodal imaging. Results. The TUT-array consists of 64 elements and centered at ~6 MHz frequency. We demonstrate a quad-mode ultrasound, Doppler ultrasound, photoacoustic, and fluorescence imaging in real-time using the TUT-array directly coupled to the tissue mimicking phantoms. Conclusion. The TUT-array successfully showed a multimodal imaging capability and has potential applications in diagnosing cancer, neurological, and vascular diseases, including image-guided endoscopy and wearable imaging.

Modeling combined ultrasound and photoacoustic imaging: Simulations aiding device development and artificial intelligence.

Combined ultrasound and photoacoustic (USPA) imaging has attracted several pre-clinical and clinical applications due to its ability to simultaneously display structural, functional, and molecular information of deep biological tissue in real time. However, the depth and wavelength dependent optical attenuation and the unknown optical and acoustic heterogeneities limit the USPA imaging performance in deep tissue regions. Novel instrumentation, image reconstruction, and artificial intelligence (AI) methods are currently being investigated to overcome these limitations and improve the USPA image quality. Effective implementation of these approaches requires a reliable USPA simulation tool capable of generating US based anatomical and PA based molecular contrasts of deep biological tissue. Here, we developed a hybrid USPA simulation platform by integrating finite element models of light (NIRFast) and ultrasound (k-Wave) propagations for co-simulation of B-mode US and PA images. The platform allows optimization of different design parameters for USPA devices, such as the aperture size and frequency of both light and ultrasound detector arrays. For designing tissue-realistic digital phantoms, a dictionary-based function has been added to k-Wave to generate various levels of ultrasound speckle contrast. The feasibility of modeling US imaging combined with optical fluence dependent multispectral PA imaging is demonstrated using homogeneous as well as heterogeneous tissue phantoms mimicking human organs (e.g., prostate and finger). In addition, we also demonstrate the potential of the simulation platform to generate large scale application-specific training and test datasets for AI enhanced USPA imaging. The complete USPA simulation codes together with the supplementary user guides have been posted to an open-source repository (https://github.com/KothapalliLabPSU/US-PA_simulation_codes).

Flexible Thin-Film PZT Ultrasonic Transducers on Polyimide Substrates.

We report flexible thin-film lead zirconate titanate (PZT)-based ultrasonic transducers on polyimide substrates. The transducers are bar resonators designed to operate in the width extension mode. The active elements are 1 µm thick PZT films that were crystallized on Si substrates at 700 °C and transferred to 5 µm thick solution-cast polyimide via dissolution of an underlying release layer. Underwater pitch-catch testing between two neighboring 100 µm × 1000 µm elements showed a 0.2 mV signal at a 1.5 cm distance for a driving voltage of 5 V peak at 9.5 MHz. With the same excitation, a 33 kPa sound pressure output at a 6 mm distance and a 32% bandwidth at -6 dB were measured by hydrophone.

Towards a Low-Cost and Portable Photoacoustic Microscope for Point-of-Care and Wearable Applications.

Several breakthrough applications in biomedical imaging have been reported in the recent years using advanced photoacoustic microscopy imaging systems. While two photon and other optical microscopy systems have recently emerged in portable and wearable form, there is much less work reported on the portable and wearable photoacoustic microscopy (PAM) systems. Working towards this goal, we report our studies on a low-cost and portable photoacoustic microscopy system that uses a custom fabricated 2.5 mm diameter ring ultrasound transducer integrated with a fiber-coupled laser diode. The ultrasound transducer is centered at 17.25 MHz, and shows ~ 45% and ~ 100% fractional bandwidths for ultrasound pulse-echo and photoacoustic A-line signals respectively. To achieve overall system portability, besides the imaging head, other backend imaging system components need to be readily portable as well. In this direction, we have studied the potential use of compact pre-amplifiers, scanning stages and microcontroller based data acquisition and reconstruction for photoacoustic imaging. The portable PAM system is validated by imaging phantoms embedded with light absorbing targets. Future directions that will likely help achieve a completely portable and wearable photoacoustic microscopy system are discussed.

A Deep Learning Approach to Photoacoustic Wavefront Localization in Deep-Tissue Medium.

Optical photons undergo strong scattering when propagating beyond 1-mm deep inside biological tissue. Finding the origin of these diffused optical wavefronts is a challenging task. Breaking through the optical diffusion limit, photoacoustic (PA) imaging (PAI) provides high-resolution and label-free images of human vasculature with high contrast due to the optical absorption of hemoglobin. In real-time PAI, an ultrasound transducer array detects PA signals, and B-mode images are formed by delay-and-sum or frequency-domain beamforming. Fundamentally, the strength of a PA signal is proportional to the local optical fluence, which decreases with the increasing depth due to depth-dependent optical attenuation. This limits the visibility of deep-tissue vasculature or other light-absorbing PA targets. To address this practical challenge, an encoder-decoder convolutional neural network architecture was constructed with custom modules and trained to identify the origin of the PA wavefronts inside an optically scattering deep-tissue medium. A comprehensive ablation study provides strong evidence that each module improves the localization accuracy. The network was trained on model-based simulated PA signals produced by 16 240 blood-vessel targets subjected to both optical scattering and Gaussian noise. Test results on 4600 simulated and five experimental PA signals collected under various scattering conditions show that the network can localize the targets with a mean error less than 30 microns (standard deviation 20.9 microns) for targets below 40-mm imaging depth and 1.06 mm (standard deviation 2.68 mm) for targets at a depth between 40 and 60 mm. The proposed work has broad applications such as diffused optical wavefront shaping, circulating melanoma cell detection, and real-time vascular surgeries (e.g., deep-vein thrombosis).

A Photoacoustic Imaging Device Using Piezoelectric Micromachined Ultrasound Transducers (PMUTs).

A linear piezoelectric micromachined ultrasound transducer (PMUT) array was fabricated and integrated into a device for photoacoustic imaging (PAI) of tissue phantoms. The PMUT contained 65 array elements, with each element having 60 diaphragms of [Formula: see text] diameter and [Formula: see text] pitch. A lead zirconate titanate (PZT) thin film was used as the piezoelectric layer. The in-air vibration response of the PMUT array elements showed a first mode resonance between 6 and 8 MHz. Hydrophone measurements showed 16.2 kPa average peak ultrasound pressure output at 7.5 mm from one element excited with 5 Vpp input. A receive sensitivity of ~0.48 mV/kPa was observed for a PMUT array element with 0 dB gain. The PMUT array was bonded to a custom-printed circuit board to enable compact integration with an optical fiber bundle for PAI. A broad photoacoustic bandwidth of ~89% was observed for the photoacoustic response captured from absorbing pencil lead targets. Linear scanning of a single element of a PMUT array was performed on different tissue phantoms embedded with light-absorbing targets to successfully demonstrate B-mode PAI using PMUTs.

Optical-Resolution Photoacoustic Microscopy Using Transparent Ultrasound Transducer.

The opacity of conventional ultrasound transducers can impede the miniaturization and workflow of current photoacoustic systems. In particular, optical-resolution photoacoustic microscopy (OR-PAM) requires the coaxial alignment of optical illumination and acoustic-detection paths through complex beam combiners and a thick coupling medium. To overcome these hurdles, we developed a novel OR-PAM method on the basis of our recently reported transparent lithium niobate (LiNbO3) ultrasound transducer (Dangi et al., Optics Letters, 2019), which was centered at 13 MHz ultrasound frequency with 60% photoacoustic bandwidth. To test the feasibility of wearable OR-PAM, optical-only raster scanning of focused light through a transducer was performed while the transducer was fixed above the imaging subject. Imaging experiments on resolution targets and carbon fibers demonstrated a lateral resolution of 8.5 µm. Further, we demonstrated vasculature mapping using chicken embryos and melanoma depth profiling using tissue phantoms. In conclusion, the proposed OR-PAM system using a low-cost transparent LiNbO3 window transducer has a promising future in wearable and high-throughput imaging applications, e.g., integration with conventional optical microscopy to enable a multimodal microscopy platform capable of ultrasound stimulation.

Lithium niobate-based transparent ultrasound transducers for photoacoustic imaging.

This Letter demonstrates lithium niobate (LiNbO3)-based transparent ultrasound transducers (TUTs) for photoacoustic imaging applications. The TUTs were fabricated by coating the top and bottom surfaces of a 0.25 mm thick LiNbO3wafer with transparent indium-tin-oxide (ITO) electrodes. The resulting transducers showed ∼80% optical transparency in the wavelength range of 690-970 nm. The TUTs had a resonant frequency of 14.5 MHz and ∼70% photoacoustic bandwidth. The versatility of the TUT approach is demonstrated by introducing two different transparent photoacoustic imaging (PAI) geometries. In one method, which suits endoscopy applications, an optical fiber of a laser diode is directly fixed on the backside of a 2.5 mm diameter TUT, and the fiber-TUT device is raster scanned to form 3D photoacoustic images. In the second method, which suits high-throughput applications, a free-space optical-only raster scanning of the laser fiber across a 1 cm×1 cm planar TUT yielded 3D photoacoustic images. The proposed TUT approach is low in cost, easy to manufacture, compatible with conventional clinical ultrasound electronics, and scalable for different configurations, including 2D TUT arrays to achieve real-time 3D high-throughput PAI.

Light-Emitting-Diode-Based Multispectral Photoacoustic Computed Tomography System.

Photoacoustic computed tomography (PACT) has been widely explored for non-ionizing functional and molecular imaging of humans and small animals. In order for light to penetrate deep inside tissue, a bulky and high-cost tunable laser is typically used. Light-emitting diodes (LEDs) have recently emerged as cost-effective and portable alternative illumination sources for photoacoustic imaging. In this study, we have developed a portable, low-cost, five-dimensional (x, y, z, t, λ ) PACT system using multi-wavelength LED excitation to enable similar functional and molecular imaging capabilities as standard tunable lasers. Four LED arrays and a linear ultrasound transducer detector array are housed in a hollow cylindrical geometry that rotates 360 degrees to allow multiple projections through the subject of interest placed inside the cylinder. The structural, functional, and molecular imaging capabilities of the LED-PACT system are validated using various tissue-mimicking phantom studies. The axial, lateral, and elevational resolutions of the system at 2.3 cm depth are estimated as 0.12 mm, 0.3 mm, and 2.1 mm, respectively. Spectrally unmixed photoacoustic contrasts from tubes filled with oxy- and deoxy-hemoglobin, indocyanine green, methylene blue, and melanin molecules demonstrate the multispectral molecular imaging capabilities of the system. Human-finger-mimicking phantoms made of a bone and blood tubes show structural and functional oxygen saturation imaging capabilities. Together, these results demonstrate the potential of the proposed LED-based, low-cost, portable PACT system for pre-clinical and clinical applications.

Thin Film PZT-Based PMUT Arrays for Deterministic Particle Manipulation.

Lead zirconate titanate (PZT)-based piezoelectric micromachined ultrasonic transducers (PMUTs) for particle manipulation applications were designed, fabricated, characterized, and tested. The PMUTs had a diaphragm diameter of 60 [Formula: see text], a resonant frequency of ~8 MHz, and an operational bandwidth (BW) of 62.5%. Acoustic pressure output in water was 9.5 kPa at 7.5 mm distance from a PMUT element excited with a unipolar waveform at 5 Vpp . The element consisted of 20 diaphragms connected electrically in parallel. Particle trapping of 4 [Formula: see text] silica beads was shown to be possible with 5 Vpp unipolar excitation. Trapping of multiple beads by a single element and deterministic control of particles via acoustophoresis without the assistance of microfluidic flow were demonstrated. It was found that the particles move toward diaphragm areas of highest pressure, in agreement with literature and simulations. Unique bead patterns were generated at different driving frequencies and were formed at frequencies up to 60 MHz, much higher than the operational BW. Levitation planes were generated above the 30 MHz driving frequency.

A Comprehensive Study of Ultrasound Transducer Characteristics in Microscopic Ultrasound Neuromodulation.

In order to improve the spatial resolution of transcranial focused ultrasound stimulation (tFUS), we have recently proposed microscopic ultrasound stimulation (µUS). In µUS, either an electronically phased array of ultrasound transducers or several millimeter-sized focused transducers are placed on the brain surface or sub-millimeter-sized transducers are implanted inside the brain tissue to steer and deliver a focused ultrasound pressure directly to the neural target. A key element in both tFUS and µUS is the ultrasound transducer that converts electrical power to acoustic pressure. The literature lacks a comprehensive study (in a quantitative manner) of the transducer characteristics, such as dimension, focusing, acoustic matching, backing material, and sonication frequency (fp), in the µUS. This paper studies the impact of these design parameters on the acoustic beam profile of millimeter-sized transducers with the emphasis on the stimulation spatial resolution and energy efficiency, which is defined as the µUS figure-of-merit (FoM). For this purpose, disc-shaped focused and unfocused piezoelectric (PZT-5A) transducers with different dimension (diameter, thickness), backing material (PCB, air) and acoustic matching in the frequency range of 2.2-9.56 MHz were fabricated. Our experimental studies with both water and sheep brain phantom medium demonstrate that acoustically matched focused transducers with high quality factor are desirable for µUS, as they provide fine spatial resolution and high acoustic intensities with low input electrical power levels (i.e., high FoM).

Evaluation of High Frequency Piezoelectric Micromachined Ultrasound Transducers for Photoacoustic Imaging.

In this work, the design, fabrication, and characterization of piezoelectric micromachined ultrasound transducer (PMUT) arrays for photoacoustic imaging applications are reported. An 80-element linear PMUT array with each element having 53 PMUT cells of 125 µm cell diameter were fabricated using 650 nm thick lead zirconate titanate (PZT) as the active piezoelectric layer. The PMUTs are designed to operate at ~10 MHz resonant frequency. The PMUT elements are validated for photoacoustic imaging using an agar gel phantom with embedded pencil leads as the imaging target. Photoacoustic A-line response of the targets captured by single PMUT element shows ~7 MHz center frequency with ~4.8 MHz bandwidth. B-mode images reconstructed from A-lines recorded during the linear scanning of a single element clearly imaged all the targets, thus validating the potential of the fabricated PMUTs for photoacoustic imaging.

Ring ultrasound transducer based miniaturized photoacoustic imaging system.

In recent years photoacoustic microscopy systems have attracted significant attention from biomedical researchers due to its ability to provide label-free imaging of hemoglobin (vasculature), lipids, and melanin with high spatial and temporal resolutions even from deeper (> 1 mm) depths inside biological tissue. This work reports the development of a low-cost and miniaturized photoacoustic (PA) imaging device for microscopy applications. A ring ultrasound transducer with 2.5 mm outer diameter and 0.5 mm inner diameter is fabricated using a 150 µm thick PZT element as the piezoelectric layer. The ring ultrasound transducer is integrated with a pulsed laser diode with integrated optical fiber which is coaxially fed through the transducer. Raster scanning of the integrated device is used to obtain 3 dimensional images of a tissue-mimicking phantom.