Epinephrine-induced Effects on Cerebral Microcirculation and Oxygenation Dynamics Using Multimodal Monitoring and Functional Photoacoustic Microscopy.

BACKGROUND: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia. METHODS: The authors investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow-up histologic assessment. RESULTS: The authors report three main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 min, P < 0.0001, n = 6) that outlasted the concurrent increase in arterial blood pressure, while larger vessels demonstrated an initial increase in flow (108 ± 6% of baseline at 6 min, P = 0.02, n = 6). Second, oxyhemoglobin decreased significantly within cerebral vessels with a more pronounced effect in smaller vessels (microvessels to 69 ± 8% of baseline at 6 min, P < 0.0001, n = 6). Third, oxyhemoglobin desaturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (from 31 ± 11 mmHg at baseline to 56 ± 12 mmHg, 80% increase, P = 0.01, n = 12). In the aged brains, microvascular constriction was less prominent yet slower to recover compared to young brains, but tissue oxygenation was increased, confirming relative hyperoxia. CONCLUSIONS: Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.

Stretchable Nanolayered Thermoelectric Energy Harvester on Complex and Dynamic Surfaces.

Thermoelectric generators (TEGs) provide a unique solution for energy harvesting from waste heat, presenting a potential solution for green energy. However, traditional rigid and flexible TEGs cannot work on complex and dynamic surfaces. Here, we report a stretchable TEG (S-TEG) (over 50% stretchability of the entire device) that is geometrically suitable for various complex and dynamic surfaces of heat sources. The S-TEG consists of hot-pressed nanolayered p-(Sb2Te3) and n-(Bi2Te3)-type thermoelectric couple arrays and exploits the wavy serpentine interconnects to integrate all units. The internal resistance of a 10 × 10 array is 22 ohm, and the output power is ∼0.15 mW/cm2 at ΔT = 19 K on both developable and nondevelopable surfaces, which are much improved compared with those of existing S-TEGs. The energy harvesting of S-TEG from the dynamic surfaces of the human skin offers a potential energy solution for the wearable devices for health monitoring.

Rietveld Analysis and Electrical Properties of BiInO3 Doped KNN-Based Ceramics.

Rietveld refinement is used to investigate the crystal structure of prepared (0.965 - x)(K0.48Na0.52)NbO3- xBiInO3-0.035(Bi0.5Na0.5)ZrO3 (KNN- xBI-BNZ) ceramics. From refined results, the distortion degree of crystal structures in KNN- xBI-BNZ ceramics presents a rising trend with BiInO3 modification, which is in keeping with the results of diffuseness. The spontaneous polarization ( Ps) is also calculated using refined structural parameters. The submicron domains are observed when x = 0.004, which presents good electrical properties ( d33 = 317 pC/N, Tc = 336 °C) simultaneously. Excellent thermal stability of ceramics modified with BiInO3 is observed in a broad temperature range.

Flexible, Wearable Wireless-Charging Power System Incorporating Piezo-Ultrasonic Arrays and MXene-Based Solid-State Supercapacitors.

With the continuous development of wearable electronics, higher requirements are put forward for flexible, detachable, stable output, and long service life power modules. Given the limited capacity of energy storage devices, the integration of energy capture and storage is a viable approach. Here, we present a flexible, wearable, wireless-charging power system that integrates a piezoelectric ultrasonic array harvester (PUAH) with MXene-based solid-state supercapacitors (MSSSs) in a soft wristband format for sustainable applications. The MSSS as the energy storage module is developed by using Ti3C2Tx nanosheet-loaded inserted finger-like carbon cloth skeletons as electrodes and poly(vinyl alcohol)/H3PO4 gel as electrolytes, with high energy density (58.74 Wh kg-1) and long cycle life (99.37%, 10,000 cycles). A two-dimensional stretchable piezoelectric array as a wireless-charging module hybridizes high-performance 1-3 composite units with serpentine electrodes, which allows wireless power via ultrasonic waves, with a maximum power density of 1.56 W cm-2 and an output voltage of 20.75 V. The overall PUAH-MSSS wireless energy supply system is 2 mm thick and offers excellent energy conversion/storage performance, cyclic stability, and mechanical flexibility. The results of this project will lay the foundation for the development of next-generation wearable electronics.

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. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future.

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. The first-principles calculations reveal that the negative piezoelectric effect of γ-glycine originates from the stretching and compression of glycine molecules induced by hydrogen bonding interactions. The synthetic γ-glycine/PVA films exhibit a piezoelectricity of 10.4 picocoulombs per newton and an ultrahigh piezoelectric voltage coefficient of 324 × 10-3 volt meters per newton. The biofilms are further developed into flexible, bioresorbable, wireless piezo-ultrasound electrotherapy devices, which are demonstrated to shorten wound healing by ~40% and self-degrade in preclinical wound models. These encouraging results offer reliable approaches for engineering piezoelectric biofilms and developing transient bioelectronics.

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. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Longitudinal intravital imaging of mouse placenta.

Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.

Dense Crystalline/Amorphous Phosphides/Oxides Interfacial Sites for Enhanced Industrial-Level Large Current Density Seawater Oxidation.

Designing high-efficiency and low-cost catalysts with high current densities for the oxygen evolution reaction (OER) is critical for commercial seawater electrolysis. Here, we present a heterophase synthetic strategy for constructing an electrocatalyst with dense heterogeneous interfacial sites among crystalline Ni2P, Fe2P, CeO2, and amorphous NiFeCe oxides on nickel foam (NF). The synergistic effect of high-density crystalline and amorphous heterogeneous interfaces effectively promotes the redistribution of the charge density and optimizes the adsorbed oxygen intermediates, lowering the energy barrier and promoting the O2 desorption, thus enhancing the OER performance. The obtained NiFeO-CeO2/NF catalyst exhibited outstanding OER catalytic activity, with low overpotentials of 338 and 408 mV required to attain high current densities of 500 and 1000 mA cm-2, respectively, in alkaline natural seawater electrolytes. The solar-driven seawater electrolysis system presents a record-setting and stable solar-to-hydrogen conversion efficiency of 20.10%. This work provides directives for developing highly effective and stable catalysts for large-scale clean energy production.

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. However, existing photoacoustic tomography methods collect signals either sequentially or through numerous detector elements, leading to either low imaging speed or high system complexity and cost. To address these issues, here we introduce a method to capture a 3D photoacoustic image of vasculature using a single laser pulse and a single-element detector that functions as 6,400 virtual ones. Our method enables ultrafast volumetric imaging of hemodynamics in the human body at up to 1 kHz and requires only a single calibration for different objects and for long-term operations. We demonstrate 3D imaging of hemodynamics at depth in humans and small animals, capturing the variability in blood flow speeds. This concept can inspire other imaging technologies and find applications such as home-care monitoring, biometrics, point-of-care testing, and wearable monitoring.

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. We demonstrate this technique in vessels in the feet of healthy human volunteers by capturing haemodynamic changes in response to vascular occlusion. Single-shot volumetric photoacoustic imaging using a single-element detector may facilitate the early detection and monitoring of peripheral vascular diseases and may be advantageous for use in biometrics and point-of-care testing.

Multiscale photoacoustic tomography using reversibly switchable thermochromics.

Significance: Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep tissues, mainly due to wavelength-dependent optical attenuation and inaccurate acoustic inversion. Aim: Previous work has demonstrated that reversible color-shifting can drastically improve the detection sensitivity of PAT by suppressing nonswitching background signals. We aim to develop a new color switching-based PAT method using reversibly switchable thermochromics (ReST). Approach: We developed a family of ReST with excellent water dispersion, biostability, and temperature-controlled color changes by surface modification of commercial thermochromic microcapsules with the hydrophilic polysaccharide alginate. Results: The optical absorbance of the ReST was switched on and off repeatedly by modulating the surrounding temperature, allowing differential photoacoustic detection that effectively suppressed the nonswitching background signal and substantially improved image contrast and detection sensitivity. We demonstrate reversible thermal-switching imaging of ReST in vitro and in vivo using three PAT modes at different length scales. Conclusions: ReST-enabled PAT is a promising technology for high-sensitivity deep tissue imaging of molecular activity in temperature-related biomedical applications, such as cancer thermotherapy.

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. In addition to its remarkable mechanical and piezoelectric performance, the growth mechanisms, the recyclability, the sensitivity, and repairability of the 3D-printed Rochelle salt cuttlebone composite were studied. Furthermore, the versatility of composite has been explored and applied as smart sensor armor for football players and fall alarm knee pads, focusing on incorporated mechanical reinforcement and electrical self-sensing capabilities with data collection of the magnitude and distribution of impact forces, which offers new ideas for the design of next-generation smart monitoring electronics in sports, military, aerospace, and biomedical engineering.

Optical-resolution photoacoustic microscopy with a needle-shaped beam.

Optical-resolution photoacoustic microscopy (OR-PAM) can visualize wavelength-dependent optical absorption at the cellular level. However, OR-PAM suffers from a limited depth of field (DOF) due to the tight focus of the optical excitation beam, making it challenging to acquire high-resolution images of samples with uneven surfaces or high-quality volumetric images without z-scanning. To overcome this limitation, we propose needle-shaped beam photoacoustic microscopy (NB-PAM), which can extend the DOF to up to ~28-fold Rayleigh lengths via customized diffractive optical elements (DOEs). The DOE generate a needle beam with a well-maintained beam diameter, a uniform axial intensity distribution, and negligible sidelobes. The advantage of using NB-PAM is demonstrated by both histology-like imaging of fresh slide-free organs using a 266 nm laser and in vivo mouse brain vasculature imaging using a 532 nm laser. The approach provides new perspectives for slide-free intraoperative pathological imaging and in-vivo organ-level imaging.

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. We introduce optimized piezoceramic printing and processing strategies to produce highly responsive piezoelectric microtransducers that operate at ultrasonic frequencies. The 3D printed dense piezoelectric elements achieve high piezoelectric coefficients and complex architectures. The resulting piezoelectric charge constant, d33, and coupling factor, kt, of the 3D printed piezoceramic reach 583 pC/N and 0.57, approaching the properties of pristine ceramics. The integrated printing of transducer packaging materials and 3D printed piezoceramics with microarchitectures create opportunities for miniaturized piezoelectric ultrasound transducers capable of acoustic focusing and localized cavitation within millimeter-sized channels, leading to miniaturized ultrasonic devices that enable a wide range of biomedical applications.

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)NbO3, KNN]-based lead-free ceramics with composition-driven multiphase coexistence and their application on high-frequency ultrasonic transducers for multifunctional acoustic tweezers. A high piezoelectric constant d33 value of 332 pC/N, a good Curie temperature TC value of 348 °C, and improved in situ temperature stability were obtained in the piezoceramics via the construction multiple phases near room temperature and domain engineering. One to three piezocomposites were further fabricated based on the synthesized ceramics for higher electromechanical coupling properties. Lead-free high-frequency transducers as multifunctional acoustic tweezers for precise and selective manipulation of microparticles were designed and manufactured with a high center frequency of 23.4 MHz and a broad -6 dB bandwidth of 75.4%. Additionally, a stable transducer performance was obtained over a test temperature range of 23-60 °C, indicating good thermal stability in environments with fluctuating temperatures. Research on lead-free high-frequency transducers for ultrasound imaging and precise and selective manipulation of microparticles demonstrates their broad potential in fields such as medical therapy and diagnosis.

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. Nevertheless, conventional UETC systems are rigid, bulky, and based on toxic lead-based piezoelectric materials, raising efficiency and safety concerns. Here, we present a novel transcutaneous UETC system based on a two-dimensional flexible lead-free piezoelectric array (f-LFPA) that hybridizes high-performance (piezoelectric coefficient d33 ≈ 503 pC N-1) (K,Na)NbO3-based eco-friendly piezo-units with soft structural components. The newly developed lead-free piezo-unit exhibits submicron ferroelectric domains and superior energy harvesting figures of merit (d33g33 ≈ 20 000 × 10-15 m2 N-1), resulting in the prepared f-LFPA demonstrating a high output voltage of 22.4 V, a power density of 0.145 W cm-2, and a signal-to-noise ratio of more than 30 dB within the FDA safety limits, while maintaining the flexibility for wide-angle receiving. Further ex vivo experiment demonstrates the adequate power supply capabilities of the f-LFPA and its possible application in future implantable eco-friendly bioelectronics for diagnostics, therapy, and real-time monitoring.

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. The device integrates a two-dimensional piezo-array with 32-pixel stimulating electrodes in a flexible printed circuit board. Each piezo-element can be ultrasonically and individually activated, thus, spatially reconfigurable electronic patterns can be dynamically applied via programmable ultrasound beamlines. As a proof of concept, we demonstrate the ultrasound-induced pattern reconstruction in ex vivo murine retinal tissue, showing the potential of this approach to restore functional, life-enhancing vision in people living with blindness.

Design and Fabrication of 15-MHz Ultrasonic Transducers Based on a Textured Pb(Mg1/3Nb2/3)O3-Pb(Zr, Ti)O3 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. Recently, textured ceramic materials can be produced at low cost and exhibit high piezoelectric strain constants and large electromechanical coupling coefficients. In this work, 15-MHz ultrasonic transducers with an effective aperture of 2.5 mm in diameter based on these highly 〈001〉 textured ceramics have been successfully fabricated. The fabricated transducers achieved a central frequency of 15 MHz, a fractional bandwidth of 67% (at -6 dB), a high effective electromechanical coupling coefficient [Formula: see text] of 0.55, and a low insertion loss (IL) of 21 dB. Ex vivo ultrasonic imaging of a porcine eyeball was used to assess the tomography quality of the transducer. The results show that utilized textured ceramic has a great potential in developing ultrasonic devices for biomedical imaging purposes.

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). The CFT-UT is made of transparent lithium niobate coated with indium-tin-oxide as electrodes. A transparent cylindrical lens is attached to the transducer surface to provide an acoustic focal line with a length of 9 mm. The excitation light can pass directly through the CFT-UT from the above and thus enables a reflection imaging mode. High-speed imaging is achieved by fast optical scanning of the focused excitation light along the CFT-UT focal line. With the confocal alignment of the optical excitation and acoustic detection, a relatively high detection sensitivity is maintained over the entire scanning range. The CFT-UT-based OR-PAM system has achieved a cross-sectional frame rate of 500 Hz over the scanning range of 9 mm. We have characterized the system's performance on phantoms and demonstrated its application on small animal models in vivo. We expect the new CFT-UT-based OR-PAM will find matched biomedical applications that need high imaging speed over a large field of view.