Robust acoustic directional sensing enabled by synergy between resonator-based sensor and deep learning.

We demonstrate enhanced acoustic sensing arising from the synergy between resonator-based acoustic sensor and deep learning. We numerically verify that both vibration amplitude and phase are enhanced and preserved at and off the resonance in our compact acoustic sensor housing three cavities. In addition, we experimentally measure the response of our sensor to single-frequency and siren signals, based on which we train convolutional neural networks (CNNs). We observe that the CNN trained by using both amplitude and phase features achieve the best accuracy on predicting the incident direction of both types of signals. This is even though the signals are broadband and affected by noise thought to be difficult for resonators. We attribute the improvement to a complementary effect between the two features enabled by the combination of resonant effect and deep learning. This observation is further supported by comparing to the CNNs trained by the features extracted from signals measured on reference sensor without resonators, whose performances fall far behind. Our results suggest the advantage of this synergetic approach to enhance the sensing performance of compact acoustic sensors on both narrow- and broad-band signals, which paves the way for the development of advanced sensing technology that has potential applications in autonomous driving systems to detect emergency vehicles.

Near-field radiative heat transfer in three-body Weyl semimetals.

We investigate the near-field radiative heat transfer in a three-body system made of Weyl semimetals. At infinitesimal temperature gradient, the rotation of the middle and the right bodies leads to heat transfer suppression, enabling thermal switching with considerably enhanced heat flux but slightly smaller ratio than two-body system without the middle body, due to stronger cavity surface plasmon polariton modes and their mismatch caused by relative rotation. By further moving the middle body to induce asymmetric cavity sizes, the three-body system can achieve a switching ratio exceeding the two-body counterpart due to asymmetric cavity modes coupling. As the temperature gradient increases to 200 K, the highest switching ratio by optimally tuning the rotation and cavity size asymmetry decreases slightly yet still outperforms the two-body system. Our results provide important understanding of the near-field radiative heat transfer in many-body systems consisting of Weyl semimetals.

Near-field radiative heat transfer in three-body Weyl semimetals: erratum.

This erratum corrects a typographical error in Eq. (4) of our published paper [Opt. Express30(18), 31584 (2022).10.1364/OE.465017]. This misprint does not influence the results and conclusions presented in the original Article.

Passive Cavitation Mapping by Cavitation Source Localization From Aperture-Domain Signals-Part I: Theory and Validation Through Simulations.

Passive cavitation mapping (PCM) algorithms for diagnostic ultrasound arrays based on time exposure acoustics (TEA) exhibit poor axial resolution, which is in part due to the diffraction-limited point spread function of the imaging system and poor rejection by the delay-and-sum beamformer. In this article, we adapt a method for speed of sound estimation to be utilized as a cavitation source localization (CSL) approach. This method utilizes a hyperbolic fit to the arrival times of the cavitation signals in the aperture domain, and the coefficients of the fit are related to the position of the cavitation source. Wavefronts exhibiting poor fit to the hyperbolic function are corrected to yield improved source localization. We demonstrate through simulations that this method is capable of accurate estimation of the origin of coherent spherical waves radiating from cavitation/point sources. The average localization error from simulated microbubble sources was 0.12 ± 0.12mm ( 0.15 ± 0.14λ0 for a 1.78-MHz transmit frequency). In simulations of two simultaneous cavitation sources, the proposed technique had an average localization error of 0.2mm ( 0.23λ0 ), whereas conventional TEA had an average localization error of 0.81mm ( 0.97λ0 ). The reconstructed PCM-CSL image showed a significant improvement in resolution compared with the PCM-TEA approach.

Passive Cavitation Mapping by Cavitation Source Localization From Aperture-Domain Signals-Part II: Phantom and In Vivo Experiments.

Passive cavitation mapping (PCM) techniques typically utilize a time-exposure acoustic (TEA) approach, where the received radio frequency data are beamformed, squared, and integrated over time. Such PCM-TEA cavitation maps typically suffer from long-tail artifacts and poor axial resolution with pulse-echo diagnostic arrays. Here, we utilize a recently developed PCM technique based on cavitation source localization (CSL), which fits a hyperbolic function to the received cavitation wavefront. A filtering method based on the root-mean-square error (rmse) of the hyperbolic fit is utilized to filter out spurious signals. We apply a wavefront correction technique to the signals with poor fit quality to recover additional cavitation signals and improve cavitation localization. Validation of the PCM-CSL technique with rmse filtering and wavefront correction was conducted in experiments with a tissue-mimicking flow phantom and an in vivo mouse model of cancer. It is shown that the quality of the hyperbolic fit, necessary for the PCM-CSL, requires an rmse < 0.05 mm2 in order to accurately localize the cavitation sources. A detailed study of the wavefront correction technique was carried out, and it was shown that, when applied to experiments with high noise and interference from multiple cavitating microbubbles, it was capable of effectively correcting noisy wavefronts without introducing spurious cavitation sources, thereby improving the quality of the PCM-CSL images. In phantom experiments, the PCM-CSL was capable of precisely localizing sources on the therapy beam axis and off-axis sources. In vivo cavitation experiments showed that PMC-CSL showed a significant improvement over PCM-TEA and yielded acceptable localization of cavitation signals in mice.

Current Trends in Nursing Research Across Five Locations: The United States, South Korea, Taiwan, Japan, and Hong Kong.

PURPOSE: Despite the importance of research in the discipline of nursing, current trends in nursing research have rarely been discussed across countries. The purpose of this article was to identify current trends in nursing research across five countries, including the United States, South Korea, Taiwan, Japan, and Hong Kong, in order to provide directions for future global nursing research. ORGANIZING CONSTRUCT: A discussion article. METHODS: To identify the current trends, seven leaders from the five countries had discussions through a series of workshops and conference presentations. After the most recent conference, all the leaders reflected for a month on their presentations and compiled the exemplars and cases from their experience and the existing literature in individual countries into a table. The tables and supporting references were collected at the completion of the reflection period. Then, the PowerPoint (Microsoft Corporation, Redmond, WA, USA) slideshows of the conference presentations by the leaders and the collected tables were analyzed using a content analysis. FINDINGS: Six themes reflecting the current trends in nursing research were extracted: (a) demographic alterations; (b) increasing diversities and globalization; (c) technology innovation; (d) individualized or personal care and population health initiatives; (e) health policies and regulations; and (f) nursing workforce changes. CONCLUSIONS: Future directions for nursing research across the countries were proposed: (a) cost-effectiveness research; (b) implementation science; (c) data science; (d) training of the future generation of nurse researchers; (e) population health; and (f) team science. CLINICAL RELEVANCE: This topic could be applied to any clinical settings.

Ultrasound and microbubble mediated therapeutic delivery: Underlying mechanisms and future outlook.

Beyond the emerging field of oncological ultrasound molecular imaging, the recent significant advancements in ultrasound and contrast agent technology have paved the way for therapeutic ultrasound mediated microbubble oscillation and has shown that this approach is capable of increasing the permeability of microvessel walls while also initiating enhanced extravasation and drug delivery into target tissues. In addition, a large number of preclinical studies have demonstrated that ultrasound alone or combined with microbubbles can efficiently increase cell membrane permeability resulting in enhanced tissue distribution and intracellular drug delivery of molecules, nanoparticles, and other therapeutic agents. The mechanism behind the enhanced permeability is the temporary creation of pores in cell membranes through a phenomenon called sonoporation by high-intensity ultrasound and microbubbles or cavitation agents. At low ultrasound intensities (0.3-3 W/cm2), sonoporation may be caused by microbubbles oscillating in a stable motion, also known as stable cavitation. In contrast, at higher ultrasound intensities (greater than 3 W/cm2), sonoporation usually occurs through inertial cavitation that accompanies explosive growth and collapse of the microbubbles. Sonoporation has been shown to be a highly effective method to improve drug uptake through microbubble potentiated enhancement of microvascular permeability. In this review, the therapeutic strategy of using ultrasound for improved drug delivery are summarized with the special focus on cancer therapy. Additionally, we discuss the progress, challenges, and future of ultrasound-mediated drug delivery towards clinical translation.

Fano-Like Acoustic Resonance for Subwavelength Directional Sensing: 0-360 Degree Measurement.

Directional sound sensing plays a critical role in many applications involving the localization of a sound source. However, the sensing range limit and fabrication difficulties of current acoustic sensing technologies pose challenges in realizing compact subwavelength direction sensors. Here, a subwavelength directional sensor is demonstrated, which can detect the angle of an incident wave in a full angle range (0°âˆ¼360°). The directional sensing is realized with acoustic coupling of Helmholtz resonators each supporting a monopolar resonance, which are monitored by conventional microphones. When these resonators scatter sound into free-space acoustic modes, the scattered waves from each resonator interfere, resulting in a Fano-like resonance where the spectral responses of the constituent resonators are drastically different from each other. This work provides a critical understanding of resonant coupling as well as a viable solution for directional sensing.

Ultrasound-mediated delivery of miRNA-122 and anti-miRNA-21 therapeutically immunomodulates murine hepatocellular carcinoma in vivo.

Hepatocellular carcinoma (HCC) is the most common cause of cancer-related mortality, and patients with HCC show poor response to currently available treatments, which demands new therapies. We recently developed a synthetic microRNA-based molecularly targeted therapy for improving HCC response to chemotherapy by eliminating drug resistance. We used ultrasound-targeted microbubble destruction (UTMD) to locally deliver microRNA-loaded nanoparticles to HCC. Since the immune microenvironment plays a crucial role in HCC disease development and response to treatment, and UTMD and microRNAs have the potential to interfere with the immune system, in this study we analyzed the immunomodulatory effects of UTMD and miRNAs in HCC. We used an immunocompetent syngeneic HCC mouse model for the study. We conducted cytokine profiling in tumor, lymph nodes, and serum of animals within the first 24 h of treatment to analyze changes in the level of pro- and antitumoral cytokines. The results showed: (1) Hepa1-6 syngeneic tumors expressed HCC-related cytokines, (2) UTMD-microRNA combination therapy triggered transient cytokine storms, and (3) delivery of microRNA-122 and anti-microRNA-21 affected the immune microenvironment by decreasing the level of GM-CSF in tumors while modulating protumoral IL-1α, IL-1ß, IL-5, IL-6 and IL-17 and antitumoral IL-2 and IL-12 in tumor-proximal lymph nodes, and increasing IL-2 in the serum of tumor-bearing mice. Local delivery of targeted therapy by UTMD significantly reduced the concentration of IL-12 and IL-17 in lymph nodes of treated and contralateral tumors suggesting a systemic response. CONCLUSION: UTMD-mediated delivery of microRNA-122 and anti-microRNA-21 modulated the immune microenvironment of Hepa1-6 tumors at the level of cytokine expressions. Exploiting antitumoral immune effects could enhance the therapeutic efficacy of the proposed combination therapy for HCC.

Damped resonance for broadband acoustic absorption in one-port and two-port systems.

We demonstrate broadband perfect acoustic absorption by damped resonances through inclusion of lossy porous media. By minimally placing the lossy materials around the necks of single-resonance Helmholtz resonators, where acoustic energy is concentrated, we show an increase in absorption bandwidths (>100% of the resonance frequency). Using the damped resonance, we demonstrate three types of broadband acoustic absorbers in one-port and two-port systems: broadband absorbers (one-port), broadband sparse absorbers (two-port), and broadband duct absorbers (two-port). Our approach for broadband absorption allows to minimize the number of resonances for compact absorbers, while it is beneficial for practical applications owing to the minimum use of porous materials.

Ultrasound-guided delivery of thymidine kinase-nitroreductase dual therapeutic genes by PEGylated-PLGA/PIE nanoparticles for enhanced triple negative breast cancer therapy.

AIM: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Since no targeted therapy is available, gene-directed enzyme prodrug therapy (GDEPT) could be an attractive strategy for treating TNBC. MATERIALS & METHODS: Polyethylene glycol (PEG)ylated-poly(lactic-co-glycolic acid)/polyethyleneimine nanoparticles (PLGA/PEI NPs) were synthesized and complexed with TK-NTR fusion gene. Ultrasound (US) and microbubble (MB) mediated sonoporation was used for efficient delivery of the TK-NTR-DNA-NP complex to TNBC tumor in vivo for cancer therapy. Therapeutic effect was evaluated by treating TNBC cells in vitro and tumor xenograft in vivo by using prodrugs ganciclovir (GCV) and CB1954. RESULTS: TNBC cells treated with GCV/CB1954 prodrugs after transfection of TK-NTR-DNA by PEGylated-PLGA/PEI NP resulted in high apoptotic-index. US-MB image-guided delivery of TK-NTR-DNA-NP complex displayed significant expression level of TK-NTR protein and showed tumor reduction when treated with GCV/CB1954 prodrugs in TNBC xenograft in vivo. CONCLUSION: US-MB image-guided delivery of TK-NTR gene by PEGylated-PLGA/PEI NPs could be a potential prodrug therapy for TNBC in the clinic.

Longitudinal assessment of ultrasound-guided complementary microRNA therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer related deaths worldwide and new strategies to efficiently treat HCC are critically needed. The aim of this study was to assess the longitudinal treatment effects of two complementary miRNAs (miRNA-122 and antimiR-21) encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA) - poly ethylene glycol (PEG) nanoparticles (PLGA-PEG-NPs), administered by an ultrasound-guided and microbubble-mediated delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance. Optimized US parameters resulted in a 9-16 fold increase (p = 0.03) in miRNA delivery in vivo in HCC tumors after two US treatments compared to tumors without US treatment. Furthermore, when combined with doxorubicin (10 mg/kg), longitudinal miRNA delivery showed a significant inhibition of tumor growth in both resistant and non-resistant tumors compared to non-treated, and doxorubicin treated controls. We also found that ultrasound-guided miRNA therapy was not only effective in inhibiting HCC tumor growth but also allowed lowering the dose of doxorubicin needed to induce apoptosis. In conclusion, the results of this study suggest that ultrasound-guided and MB-mediated delivery of miRNA-122 and antimiR-21, when combined with doxorubicin, is a highly effective approach to treat resistant HCC while reducing doxorubicin doses needed for treating non-resistant HCC in longitudinal treatment experiments. Further refinement of this strategy could potentially lead to better treatment outcomes for patients with HCC.

Laser-Induced Focused Ultrasound for Cavitation Treatment: Toward High-Precision Invisible Sonic Scalpel.

Beyond the implementation of the photoacoustic effect to photoacoustic imaging and laser ultrasonics, this study demonstrates a novel application of the photoacoustic effect for high-precision cavitation treatment of tissue using laser-induced focused ultrasound. The focused ultrasound is generated by pulsed optical excitation of an efficient photoacoustic film coated on a concave surface, and its amplitude is high enough to produce controllable microcavitation within the focal region (lateral focus <100 µm). Such microcavitation is used to cut or ablate soft tissue in a highly precise manner. This work demonstrates precise cutting of tissue-mimicking gels as well as accurate ablation of gels and animal eye tissues.

Ultrasound-guided drug delivery in cancer.

Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

Out-coupling of Longitudinal Photoacoustic Pulses by Mitigating the Phase Cancellation.

Waves of any kinds, including sound waves and light waves, can interfere constructively or destructively when they are overlapped, allowing for myriad applications. However, unlike continuous waves of a single frequency, interference of photoacoustic pulses is often overlooked because of their broadband characteristics and short pulse durations. Here, we study cancellation of two symmetric photoacoustic pulses radiated in the opposite direction from the same photoacoustic sources near a free surface. The cancellation occurs when one of the two pulses is reflected with polarity reversal from the free surface and catches up with the other. The cancellation effect, responsible for reduced signal amplitudes, is systematically examined by implementing a thin transparent matching medium of the same acoustic impedance. By changing the thickness of the transparent layer, the overlap of the two symmetric pulses is controlled. For optimized matching layers, the cancellation effect can be significantly reduced, while the resulting output waveform remains unchanged. Similar to the planar absorber, different dimensional absorbers including cylinders and spheres also exhibit the cancellation between the outward and inward waves. This work could provide further understanding of photoacoustic generation and a simple strategy for increasing photoacoustic signal amplitudes.

Nano-structural characteristics of carbon nanotube-polymer composite films for high-amplitude optoacoustic generation.

We demonstrate nano-structural characteristics of carbon nanotube (CNT)-polydimethylsiloxane (PDMS) composite films that can be used as highly efficient and robust ultrasound transmitters for diagnostic and therapeutic applications. An inherent architecture of the nano-composite provides unique thermal, optical, and mechanical properties that are accommodated not just for efficient energy conversion but also for extraordinary robustness against pulsed laser ablation. First, we explain a thermoacoustic transfer mechanism within the nano-composite. CNT morphologies are examined to determine a suitable arrangement for heat transfer to the surrounding PDMS. Next, we introduce an approach to enhance optical extinction of the composite films, which uses shadowed deposition of a thin Au layer through an as-grown CNT network. Finally, the transmitter robustness is quantified in terms of laser-induced damage threshold. This reveals that the CNT-PDMS films can withstand an order-of-magnitude higher optical fluence (and extinction) than a Cr film used as a reference. Such robustness is crucial to increase the maximum-available optical energy for optoacoustic excitation and pressure generation. All of these structure-originated characteristics manifest the CNT-PDMS composite films as excellent optoacoustic transmitters for high-amplitude and high-frequency ultrasound generation.

Continuous fabrication of scalable 2-dimensional (2D) micro- and nanostructures by sequential 1D mechanical patterning processes.

We present a versatile and simple methodology for continuous and scalable 2D micro/nano-structure fabrication via sequential 1D patterning strokes enabled by dynamic nano-inscribing (DNI) and vibrational indentation patterning (VIP) as well as a 'single-stroke' 2D patterning using a DNI tool in VIP.

Phenethyl isothiocyanate sensitizes glioma cells to TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a promising antitumor therapy. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL, highlighting the need for strategies to overcome TRAIL resistance. Here we show that in combination with phenethyl isothiocyanate (PEITC), exposure to TRAIL induced apoptosis in TRAIL-resistant glioma cells. Subtoxic concentrations of PEITC significantly potentiated TRAIL-induced cytotoxicity and apoptosis in glioma cells. PEITC dramatically upregulated DR5 receptor expression but had no effects on DR4 receptor. PEITC enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-induced-p53.

Digitoxin sensitizes glioma cells to TRAIL-mediated apoptosis by upregulation of death receptor 5 and downregulation of survivin.

Glioblastoma multiforme is the most lethal and aggressive astrocytoma among primary brain tumors in adults. However, most glioblastoma cells have been reported to be resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Here, we have shown that digitoxin (DT), a clinically approved cardiac glycoside for heart failure, can induce TRAIL-mediated apoptosis of glioblastoma cells. DT in noncytotoxic doses (20 nmol/l) can increase TRAIL-induced apoptosis in TRAIL-resistant U87MG glioblastoma cells. Treatment with DT led to apoptosis and a robust reduction in the levels of the antiapoptotic protein survivin by inducing its proteasomal degradation; however, it did not affect the levels of many other apoptosis regulators. Moreover, silencing survivin with small interfering RNAs sensitized glioma cells to TRAIL-induced apoptosis, underscoring the functional role of survivin depletion in the TRAIL-sensitizing actions of DT. We demonstrate that inactivation of survivin and death receptor 5 expression by DT is sufficient to restore TRAIL sensitivity in resistant glioma cells. Our results suggest that combining DT with TRAIL treatments may be useful in the treatment of TRAIL-resistant glioma cells.

Micro-ultrasonic cleaving of cell clusters by laser-generated focused ultrasound and its mechanisms.

Laser-generated focused ultrasound (LGFU) is a unique modality that can produce single-pulsed cavitation and strong local disturbances on a tight focal spot (<100 µm). We utilize LGFU as a non-contact, non-thermal, high-precision tool to fractionate and cleave cell clusters cultured on glass substrates. Fractionation processes are investigated in detail, which confirms distinct cell behaviors in the focal center and the periphery of LGFU spot. For better understanding of local disturbances under LGFU, we use a high-speed laser-flash shadowgraphy technique and then fully visualize instantaneous microscopic processes from the ultrasound wave focusing to the micro-bubble collapse. Based on these visual evidences, we discuss possible mechanisms responsible for the focal and peripheral disruptions, such as a liquid jet-induced wall shear stress and shock emissions due to bubble collapse. The ultrasonic micro-fractionation is readily available for in vitro cell patterning and harvesting. Moreover, it is significant as a preliminary step towards high-precision surgery applications in future.