Optical-resolution parallel ultraviolet photoacoustic microscopy for slide-free histology.

Intraoperative imaging of slide-free specimens is crucial for oncology surgeries, allowing surgeons to quickly identify tumor margins for precise surgical guidance. While high-resolution ultraviolet photoacoustic microscopy has been demonstrated for slide-free histology, the imaging speed is insufficient, due to the low laser repetition rate and the limited depth of field. To address these challenges, we present parallel ultraviolet photoacoustic microscopy (PUV-PAM) with simultaneous scanning of eight optical foci to acquire histology-like images of slide-free fresh specimens, improving the ultraviolet PAM imaging speed limited by low laser repetition rates.

Ultrasound Control of Genomic Regulatory Toolboxes for Cancer Immunotherapy.

There remains a critical need for the precise control of CRISPR (clustered regularly interspaced short palindromic repeats)-based technologies. Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation. We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome.

A Novel Approach to Harnessing Acoustic A-Lines to Detect Circulating Tumor Cells in Flowing Blood.

Circulating tumor cells (CTCs) are associated with tumor burden and treatment response and, as hallmarks of the initiation of tumor dissemination, can predict the likelihood of metastatic progression before widespread tumors can be detected by standard anatomic imaging. However, early diagnosis of recurrence through the detection of CTCs is limited by their low prevalence in blood and the limited sensitivity of existing technologies. To address these challenges, we investigated the use of ultrasound and targeted microbubbles (MBs) for early CTC detection.

High-frequency wearable ultrasound array belt for small animal echocardiography.

Wearable ultrasound has been widely developed for long-term, continuous imaging without the need for bulky system manipulation and repeated manual locating. To potentially lead to more accurate and reliable imaging monitoring, this work presents the design, fabrication, and evaluation of a novel high-frequency wearable ultrasound array belt (WUAB) for small animal echocardiography. The fabrication process involved precise dicing technology for a λ-pitch design.

Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon.

Current malaria diagnostics are invasive, lack sensitivity, and rapid tests are plagued by deletions in target antigens. Here we introduce the Cytophone, an innovative photoacoustic flow cytometer platform with high-pulse-rate lasers and a focused ultrasound transducer array to noninvasively detect and identify malaria-infected red blood cells (iRBCs) using specific wave shapes, widths, and time delays generated from the absorbance of laser energy by hemozoin, a universal biomarker of malaria infection. In a population of Cameroonian adults with uncomplicated malaria, we assess our device for safety in a cross-sectional cohort (n = 10) and conduct a performance assessment in a longitudinal cohort (n = 20) followed for 30 ± 7 days after clearance of parasitemia.

Four-dimensional (4D) Ultrasound Shear Wave Elastography Using Sequential Excitation.

Objective: Current shear wave elastography methods primarily focus on 2D imaging. To explore mechanical properties of biological tissues in 3D, a four-dimensional (4D, x, y, z, t) ultrasound shear wave elastography is required. However, 4D ultrasound shear wave elastography is still challenging due to the limitation of the hardware of standard ultrasound acquisition systems.

Flexible, biodegradable ultrasonic wireless electrotherapy device based on highly self-aligned piezoelectric biofilms.

Biodegradable piezoelectric devices hold great promise in on-demand transient bioelectronics. Existing piezoelectric biomaterials, however, remain obstacles to the development of such devices due to difficulties in large-scale crystal orientation alignment and weak piezoelectricity. Here, we present a strategy for the synthesis of optimally orientated, self-aligned piezoelectric γ-glycine/polyvinyl alcohol (γ-glycine/PVA) films via an ultrasound-assisted process, guided by density functional theory.

Noninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation.

Lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation.

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies.

Integrating a Fundus Camera with High-Frequency Ultrasound for Precise Ocular Lesion Assessment.

Ultrasound A-scan is an important tool for quantitative assessment of ocular lesions. However, its usability is limited by the difficulty of accurately localizing the ultrasound probe to a lesion of interest. In this study, a transparent LiNbO single crystal ultrasound transducer was fabricated, and integrated with a widefield fundus camera to guide the ultrasound local position.

Ultrasound Flow Imaging Study on Rat Brain with Ultrasound and Light Stimulations.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain's response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging.

Wearable bioadhesive ultrasound shear wave elastography.

Acute liver failure (ALF) is a critical medical condition defined as the rapid development of hepatic dysfunction. Conventional ultrasound elastography cannot continuously monitor liver stiffness over the course of rapidly changing diseases for early detection due to the requirement of a handheld probe. In this study, we introduce wearable bioadhesive ultrasound elastography (BAUS-E), which can generate acoustic radiation force impulse (ARFI) to induce shear waves for the continuous monitoring of modulus changes.

Ultrafast longitudinal imaging of haemodynamics via single-shot volumetric photoacoustic tomography with a single-element detector.

Techniques for imaging haemodynamics use ionizing radiation or contrast agents or are limited by imaging depth (within approximately 1 mm), complex and expensive data-acquisition systems, or low imaging speeds, system complexity or cost. Here we show that ultrafast volumetric photoacoustic imaging of haemodynamics in the human body at up to 1 kHz can be achieved using a single laser pulse and a single element functioning as 6,400 virtual detectors. The technique, which does not require recalibration for different objects or during long-term operation, enables the longitudinal volumetric imaging of haemodynamics in vasculature a few millimetres below the skin's surface.

Growing recyclable and healable piezoelectric composites in 3D printed bioinspired structure for protective wearable sensor.

Bionic multifunctional structural materials that are lightweight, strong, and perceptible have shown great promise in sports, medicine, and aerospace applications. However, smart monitoring devices with integrated mechanical protection and piezoelectric induction are limited. Herein, we report a strategy to grow the recyclable and healable piezoelectric Rochelle salt crystals in 3D-printed cuttlebone-inspired structures to form a new composite for reinforcement smart monitoring devices.

Non-Invasive Hybrid Ultrasound Stimulation of Visual Cortex In Vivo.

The optic nerve is the second cranial nerve (CN II) that connects and transmits visual information between the retina and the brain. Severe damage to the optic nerve often leads to distorted vision, vision loss, and even blindness. Such damage can be caused by various types of degenerative diseases, such as glaucoma and traumatic optic neuropathy, and result in an impaired visual pathway.

3D Printing and processing of miniaturized transducers with near-pristine piezoelectric ceramics for localized cavitation.

The performance of ultrasonic transducers is largely determined by the piezoelectric properties and geometries of their active elements. Due to the brittle nature of piezoceramics, existing processing tools for piezoelectric elements only achieve simple geometries, including flat disks, cylinders, cubes and rings. While advances in additive manufacturing give rise to free-form fabrication of piezoceramics, the resultant transducers suffer from high porosity, weak piezoelectric responses, and limited geometrical flexibility.

Single-shot 3D photoacoustic tomography using a single-element detector for ultrafast imaging of hemodynamics.

Imaging hemodynamics is crucial for the diagnosis, treatment, and prevention of vascular diseases. However, current imaging techniques are limited due to the use of ionizing radiation or contrast agents, short penetration depth, or complex and expensive data acquisition systems. Photoacoustic tomography shows promise as a solution to these issues.

2-D Array Design and Fabrication With Pitch-Shifting Interposer at Frequencies From 4 MHz up to 10 MHz.

High element density and strict constraints of the element's size have significantly limited the design and fabrication of 2-D ultrasonic arrays, especially fully sampled 2-D arrays. Recently, 3-D printing technology has been one of the most rapidly developing fields. Along with the great progress of 3-D printing technology, complex and detailed 3-D structures have become readily available with a short iteration cycle, which allows us to reduce the complexity of routing and helps to ameliorate assembly problems in 2-D ultrasound array fabrication.

High-speed wide-field photoacoustic microscopy using a cylindrically focused transparent high-frequency ultrasound transducer.

Combining focused optical excitation and high-frequency ultrasound detection, optical-resolution photoacoustic microscopy (OR-PAM) can provide micrometer-level spatial resolution with millimeter-level penetration depth and has been employed in a variety of biomedical applications. However, it remains a challenge for OR-PAM to achieve a high imaging speed and a large field of view at the same time. In this work, we report a new approach to implement high-speed wide-field OR-PAM, using a cylindrically-focused transparent ultrasound transducer (CFT-UT).

Flexible ultrasound-induced retinal stimulating piezo-arrays for biomimetic visual prostheses.

Electronic visual prostheses, or biomimetic eyes, have shown the feasibility of restoring functional vision in the blind through electrical pulses to initiate neural responses artificially. However, existing visual prostheses predominantly use wired connections or electromagnetic waves for powering and data telemetry, which raises safety concerns or couples inefficiently to miniaturized implant units. Here, we present a flexible ultrasound-induced retinal stimulating piezo-array that can offer an alternative wireless artificial retinal prosthesis approach for evoking visual percepts in blind individuals.

Potassium Sodium Niobate-Based Lead-Free High-Frequency Ultrasonic Transducers for Multifunctional Acoustic Tweezers.

Ultrasonic transducers may need to operate in direct contact with the human body, especially with the skin or closer to blood vessels. Eco-friendly lead-free materials and devices are therefore being vigorously developed for biosafety considerations. This work presents high-performance potassium sodium niobate [(K,Na)NbO, KNN]-based lead-free ceramics with composition-driven multiphase coexistence and their application on high-frequency ultrasonic transducers for multifunctional acoustic tweezers.

Flexible lead-free piezoelectric arrays for high-efficiency wireless ultrasonic energy transfer and communication.

Implantable medical electronics (IMEs) are now becoming increasingly prevalent for diagnostic and therapeutic purposes. Despite extensive efforts, a primary challenge for IMEs is reliable wireless power and communication to provide well-controlled, therapeutically relevant effects. Ultrasonic energy transfer and communication (UETC) employing traveling ultrasound waves to transmit energy has emerged as a promising wireless strategy for IMEs.

Manipulation and Mechanical Deformation of Leukemia Cells by High-Frequency Ultrasound Single Beam.

Ultrasound single-beam acoustic tweezer system has attracted increasing attention in the field of biomechanics. Cell biomechanics play a pivotal role in leukemia cell functions. To better understand and compare the cell mechanics of the leukemia cells, herein, we fabricated an acoustic tweezer system in-house connected with a 50-MHz high-frequency cylinder ultrasound transducer.

3D Printing of Nacre-Inspired Structures with Exceptional Mechanical and Flame-Retardant Properties.

Flame-retardant and thermal management structures have attracted great attention due to the requirement of high-temperature exposure in industrial, aerospace, and thermal power fields, but the development of protective fire-retardant structures with complex shapes to fit arbitrary surfaces is still challenging. Herein, we reported a rotation-blade casting-assisted 3D printing process to fabricate nacre-inspired structures with exceptional mechanical and flame-retardant properties, and the related fundamental mechanisms are studied. 3-(Trimethoxysilyl)propyl methacrylate (TMSPMA) modified boron nitride nanoplatelets (BNs) were aligned by rotation-blade casting during the 3D printing process to build the "brick and mortar" architecture.

Design and Fabrication of 15-MHz Ultrasonic Transducers Based on a Textured Pb(MgNb)O-Pb(Zr, Ti)O Ceramic.

Ultrasound medical imaging is an entrenched and powerful tool for medical diagnosis. Image quality in ultrasound is mainly dependent on performance of piezoelectric transducer elements, which is further related to the electromechanical performance of the constituent piezoelectric materials. With rising need for piezoelectric materials with better performance and low cost, a highly 〈001〉 textured piezo ceramic, Pb(Mg1/3Nb2/3)O3-Pb(Zr, Ti)O3, has been developed.