Fast acoustic droplet ejection based on annular array transducer.

Acoustic droplet ejection (ADE) has become the preferred method for liquid transfer in a variety of applications including synthetic biology, genotyping and drug discovery. Comparing with traditional pipetting techniques, the accuracy and data reproducibility of ADE based liquid transfer are improved, waste and cost are reduced, and cross-contamination is eliminated. The key component in the ADE system is the ultrasound transducer, which is responsible for generating focused ultrasound beam for droplet ejection. However, current ADE systems commonly utilize a single-element focused transducer with a fixed focal length that require mechanical movement to focus on the liquid surface, resulting in reduced liquid transfer efficiency. In this study, we first present a high-frequency annular array transducer for the ADE technology, which enables rapid and dynamic axial focusing to the liquid surface without mechanically moving the transducer, thereby accelerating liquid transfer. Experimental results show that the proposed 10 MHz, 5-element annular array transducer has good dynamic axial focusing ability, and can achieve accurate and stable droplet ejection of nanoliter volume at the designed focal length of 26-32 mm. Our results highlight the potential of the annular array transducer in advancing ADE system for rapid liquid transfer. This technology is expected to be useful in a variety of applications where precise and high-throughput liquid transfer is crucial.

An adaptive spatiotemporal filter for ultrasound localization microscopy based on density canopy clustering.

Ultrasound Localization Microscopy (ULM) facilitates structural and hemodynamic imaging of microvessels with a resolution of tens of micrometers. In ULM, the extraction of effective microbubble signals is crucial for image quality. Singular Value Decomposition (SVD) is currently the most prevalent method for microbubble signal extraction in ULM. Most existing ULM studies employ a fixed SVD filter threshold using empirical values which will lead to imaging quality degradation due to the insufficient separation of blood signals. In this study, we propose an adaptive and non-threshold SVD filter based on canopy-density clustering, termed DCC-SVD. This filter automatically classifies the components of the SVD based on the density of their spatiotemporal features, eliminating the need for parameter selection. In in vitro tube phantom, DCC-SVD demonstrated its ability to adaptive separation of blood and bubble signal at varying microbubble concentrations and flow rates. We compared the proposed DCC-SVD method with the Block-match 3D (BM3D) filter and a classical adaptive method called spatial similarity matrix (SSM), using concentration-variable in vivo rat brain data, as well as open-source rat kidney and mouse tumor datasets. The proposed DCC-SVD improved the global spatial resolution by approximately 4 µm from 30.39 µm to 26.02 µm. It also captured vessel structure absent in images obtained by other methods and yielded a smoother vessel intensity profile, making it a promising spatiotemporal filter for ULM imaging.

A transcranial multiple waves suppression method for plane wave imaging based on Radon transform.

Transcranial ultrasound imaging presents a significant challenge due to the intricate interplay between ultrasound waves and the heterogeneous human skull. The skull's presence induces distortion, refraction, multiple scattering, and reflection of ultrasound signals, thereby complicating the acquisition of high-quality images. Extracting reflections from the entire waveform is crucial yet exceedingly challenging, as intracranial reflections are often obscured by strong amplitude direct waves and multiple scattering. In this paper, a multiple wave suppression method for ultrasound plane wave imaging is proposed to mitigate the impact of skull interference. Drawing upon prior research, we developed an enhanced high-resolution linear Radon transform using the maximum entropy principle and Bayesian method, facilitating wavefield separation. We detailed the process of wave field separation in the Radon domain through simulation of a model with a high velocity layer. When plane waves emitted at any steering angles, both multiple waves and first arrival waves manifested as distinct energy points. In the brain simulation, we contrasted the characteristic differences between skull reflection and brain-internal signal in Radon domain, and demonstrated that multiples suppression method reduces side and grating lobe levels by approximately 30 dB. Finally, we executed in vitro experiments using a monkey skull to separate weak intracranial reflection signals from strong skull reflections, enhancing the contrast-to-noise ratio by 85 % compared to conventional method using full waveform. This study deeply explores the effect of multiples on effective signal separation, addresses the complexity of wavefield separation, and verifies its efficacy through imaging, thereby significantly advancing ultrasound transcranial imaging techniques.

Low-intensity focused ultrasound stimulation promotes stroke recovery via astrocytic HMGB1 and CAMK2N1 in mice.

BACKGROUND: Low-intensity focused ultrasound stimulation (LIFUS) has been developed to enhance neurological repair and remodelling during the late acute stage of ischaemic stroke in rodents. However, the cellular and molecular mechanisms of neurological repair and remodelling after LIFUS in ischaemic stroke are unclear. METHODS: Ultrasound stimulation was treated in adult male mice 7 days after transient middle cerebral artery occlusion. Angiogenesis was measured by laser speckle imaging and histological analyses. Electromyography and fibre photometry records were used for synaptogenesis. Brain atrophy volume and neurobehaviour were assessed 0-14 days after ischaemia. iTRAQ proteomic analysis was performed to explore the differentially expressed protein. scRNA-seq was used for subcluster analysis of astrocytes. Fluorescence in situ hybridisation and Western blot detected the expression of HMGB1 and CAMK2N1. RESULTS: Optimal ultrasound stimulation increased cerebral blood flow, and improved neurobehavioural outcomes in ischaemic mice (p<0.05). iTRAQ proteomic analysis revealed that the expression of HMGB1 increased and CAMK2N1 decreased in the ipsilateral hemisphere of the brain at 14 days after focal cerebral ischaemia with ultrasound treatment (p<0.05). scRNA-seq revealed that this expression pattern belonged to a subcluster of astrocytes after LIFUS in the ischaemic brain. LIFUS upregulated HMGB1 expression, accompanied by VEGFA elevation compared with the control group (p<0.05). Inhibition of HMGB1 expression in astrocytes decreased microvessels counts and cerebral blood flow (p<0.05). LIFUS reduced CAMK2N1 expression level, accompanied by increased extracellular calcium ions and glutamatergic synapses (p<0.05). CAMK2N1 overexpression in astrocytes decreased dendritic spines, and aggravated neurobehavioural outcomes (p<0.05). CONCLUSION: Our results demonstrated that LIFUS promoted angiogenesis and synaptogenesis after focal cerebral ischaemia by upregulating HMGB1 and downregulating CAMK2N1 in a subcluster of astrocytes, suggesting that LIFUS activated specific astrocyte subcluster could be a key target for ischaemic brain therapy.

A Multiplexed 32 × 32 2D Matrix Array Transducer for Flexible Sub-Aperture Volumetric Ultrasound Imaging.

A fully-sampled two-dimensional (2D) matrix array ultrasonic transducer is essential for fast and accurate three-dimensional (3D) volumetric ultrasound imaging. However, these arrays, usually consisting of thousands of elements, not only face challenges of poor performance and complex wiring due to high-density elements and small element sizes but also put high requirements for electronic systems. Current commercially available fully-sampled matrix arrays, dividing the aperture into four fixed sub-apertures to reduce system channels through multiplexing are widely used. However, the fixed sub-aperture configuration limits imaging flexibility and the gaps between sub-apertures lead to reduced imaging quality. In this study, we propose a high-performance multiplexed matrix array by the design of 1-3 piezocomposite and gapless sub-aperture configuration, as well as optimized matching layer materials. Furthermore, we introduce a sub-aperture volumetric imaging method based on the designed matrix array, enabling high-quality and flexible 3D ultrasound imaging with a low-cost 256-channel system. The influence of imaging parameters, including the number of sub-apertures and steering angle on imaging quality was investigated by simulation, in vitro and in vivo imaging experiments. The fabricated matrix array has a center frequency of 3.4 MHz and a -6 dB bandwidth of above 70%. The proposed sub-aperture volumetric imaging method demonstrated a 10% improvement in spatial resolution, a 19% increase in signal-to-noise ratio, and a 57.7% increase in contrast-to-noise ratio compared with the fixed sub-aperture array imaging method. This study provides a new strategy for high-quality volumetric ultrasound imaging with a low-cost system.

Portal Vein Pressure Estimation and Portal Hypertension Discrimination Based on Subharmonic Scattering of Ultrasound Contrast Agent Microbubbles.

OBJECTIVE: The acquisition of real-time portal vein pressure (PVP) is important for portal hypertension (PH) discrimination to monitor disease progress and select treatment options. To date, the PVP evaluation approaches are either invasive or noninvasive but with less stability and sensitivity. METHODS: We customized an open ultrasound scanner to explore in vitro and in vivo the ultrasound contrast agent SonoVue microbubbles' subharmonic characteristics with acoustic pressure and local ambient pressure, and obtained promising results of PVP measurements in canine models with induced PH by ligation or embolization of portal vein. RESULTS: In in vitro experiments, the highest correlations between the subharmonic amplitude of SonoVue microbubbles and ambient pressure were observed at acoustic pressures of 523 kPa and 563 kPa (r = -0.993, -0.993, P<0.05, respectively). The correlation coefficients between absolute subharmonic amplitudes and PVP (10.7-35.4 mmHg) were the highest among existing studies using microbubbles as pressure sensors (r values ranged from -0.819 to -0.918). The PH (>16 mmHg) diagnostic capacity also achieved a high level (563 kPa, sensitivity = 93.3%, specificity = 91.7%, accuracy = 92.6%). CONCLUSION: This study proposes a promising measurement for PVP with the highest accuracy, sensitivity, and specificity in an in vivo model compared to existing studies. Future investigations are planned to assess the feasibility of this technique in clinical practice. SIGNIFICANCE: This is the first study that comprehensively investigates the role of the subharmonic scattering signals from SonoVue microbubbles in evaluating PVP in vivo. It represents a promising alternative to invasive measurements for portal pressure.

A New Method of Plane-Wave Ultrasound Imaging Based on Reverse Time Migration.

Coherent plane-wave compounding technique enables rapid ultrasound imaging with comparable image quality to traditional B-mode imaging that relies on focused beam transmission. However, existing methods assume homogeneity in the imaged medium, neglecting the heterogeneity in sound velocities and densities present in real tissues, resulting in noise reverberation. This study introduces the Reverse Time Migration (RTM) method for ultrasound plane-wave imaging to overcome this limitation, which is combined with a method for estimating the speed of sound in layered media. Simulation results in a homogeneous background demonstrate that RTM reduces side lobes and grating lobes by approximately 30 dB, enhancing the contrast-to-noise ratio by 20% compared to conventional delay and sum (DAS) beamforming. Moreover, RTM achieves superior imaging outcomes with fewer compounding angles. The lateral resolution of the RTM with 5-9 angle compounding is able to achieve the effectiveness of the DAS method with 15-19 angle compounding, and the CNR of the RTM with 11-angle compounding is almost the same as that of the DAS with 21-angle compounding. In a heterogeneous background, experimental simulations and in vitro wire phantom experiments confirm RTM's capability to correct depth imaging, focusing reflected waves on point targets. In vitro porcine tissue experiments enable accurate imaging of layer interfaces by estimating the velocities of multiple layers containing muscle and fat. The proposed imaging procedure optimizes velocity estimation in complex media, compensates for the impact of velocity differences, provides more reliable imaging results.

Recent Advances in LDH/g-C3N4 Heterojunction Photocatalysts for Organic Pollutant Removal.

Environmental pollution has been decreased by using photocatalytic technology in conjunction with solar energy. An efficient method to obtain highly efficient photocatalysts is to build heterojunction photocatalysts by combining graphitic carbon nitride (g-C3N4) with layered double hydroxides (LDHs). In this review, recent developments in LDH/g-C3N4 heterojunctions and their applications for organic pollutant removal are systematically exhibited. The advantages of LDH/g-C3N4 heterojunction are first summarized to provide some overall understanding of them. Then, a variety of approaches to successfully assembling LDH and g-C3N4 are simply illustrated. Last but not least, certain unmet research needs for the LDH/g-C3N4 heterojunction are suggested. This review can provide some new insights for the development of high-performance LDH/g-C3N4 heterojunction photocatalysts. It is indisputable that the LDH/g-C3N4 heterojunctions can serve as high-performance photocatalysts to make new progress in organic pollutant removal.

The Emergence of Functional Ultrasound for Noninvasive Brain-Computer Interface.

A noninvasive brain-computer interface is a central task in the comprehensive analysis and understanding of the brain and is an important challenge in international brain-science research. Current implanted brain-computer interfaces are cranial and invasive, which considerably limits their applications. The development of new noninvasive reading and writing technologies will advance substantial innovations and breakthroughs in the field of brain-computer interfaces. Here, we review the theory and development of the ultrasound brain functional imaging and its applications. Furthermore, we introduce latest advancements in ultrasound brain modulation and its applications in rodents, primates, and human; its mechanism and closed-loop ultrasound neuromodulation based on electroencephalograph are also presented. Finally, high-frequency acoustic noninvasive brain-computer interface is prospected based on ultrasound super-resolution imaging and acoustic tweezers.

Modulation of deep neural circuits with sonogenetics.

Noninvasive control of neuronal activity in the deep brain can be illuminating for probing brain function and treating dysfunctions. Here, we present a sonogenetic approach for controlling distinct mouse behavior with circuit specificity and subsecond temporal resolution. Targeted neurons in subcortical regions were made to express a mutant large conductance mechanosensitive ion channel (MscL-G22S), enabling ultrasound to trigger activity in MscL-expressing neurons in the dorsal striatum and increase locomotion in freely moving mice. Ultrasound stimulation of MscL-expressing neurons in the ventral tegmental area could activate the mesolimbic pathway to trigger dopamine release in the nucleus accumbens and modulate appetitive conditioning. Moreover, sonogenetic stimulation of the subthalamic nuclei of Parkinson's disease model mice improved their motor coordination and mobile time. Neuronal responses to ultrasound pulse trains were rapid, reversible, and repeatable. We also confirmed that the MscL-G22S mutant is more effective to sensitize neurons to ultrasound compared to the wild-type MscL. Altogether, we lay out a sonogenetic approach which can selectively manipulate targeted cells to activate defined neural pathways, affect specific behaviors, and relieve symptoms of neurodegenerative disease.

Mechanism of low-frequency, low-intensity ultrasound modulation of the mouse retina.

Objective.Ultrasound has been shown to modulate the activity of retinal ganglion cells (RGCs) in mice, but the mechanism remains poorly understood. This study aims to address this question.Approach.Multi-electrode recordings together with pharmacological methods were used to investigate the possible cellular/circuitry mechanism(s) underlying the neuronal modulation induced by low-frequency (1 MHz), low-intensity (ISPTA0.5 W cm-2) ultrasound stimulation.Main results.We found that ultrasound activated mechanosensitive channels (transient receptor potential vanilloid 4 (TRPV4) channels are involved) in Müller cells, causing the release of glutamate, which acts on the extrasynapticN-methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity.Significance.Our results reveal a novel mechanism of low-frequency, low-intensity ultrasound modulation, involving TRPV4 as a mechanosensitive target for ultrasound and glutamate as an essential mediator of neuron-glia communication. These findings also demonstrate that the mechanical-force-mediated pathway is important for retinal signal modulation during visual processes, such as visual accommodation.

Noninvasive Estimation of Tumor Interstitial Fluid Pressure from Subharmonic Scattering of Ultrasound Contrast Microbubbles.

The noninvasive estimation of interstitial fluid pressure (IFP) using ultrasound contrast agent (UCA) microbubbles as pressure sensors will provide tumor treatments and efficacy assessments with a promising tool. This study aimed to verify the efficacy of the optimal acoustic pressure in vitro in the prediction of tumor IFPs based on UCA microbubbles' subharmonic scattering. A customized ultrasound scanner was used to generate subharmonic signals from microbubbles' nonlinear oscillations, and the optimal acoustic pressure was determined in vitro when the subharmonic amplitude reached the most sensitive to hydrostatic pressure changes. This optimal acoustic pressure was then applied to predict IFPs in tumor-bearing mouse models, which were further compared with the reference IFPs measured using a standard tissue fluid pressure monitor. An inverse linear relationship and good correlation (r = -0.853, p < 0.001) existed between the subharmonic amplitude and tumor IFPs at the optimal acoustic pressure of 555 kPa, and pressure sensitivity was 1.019 dB/mmHg. No statistical differences were found between the pressures measured by the standard device and those estimated via the subharmonic amplitude, as confirmed by cross-validation (mean absolute errors from 2.00 to 3.09 mmHg, p > 0.05). Our findings demonstrated that in vitro optimized acoustic parameters for UCA microbubbles' subharmonic scattering can be applied for the noninvasive estimation of tumor IFPs.

A Novel Dual-Element Catheter for Improving Non-Uniform Rotational Distortion in Intravascular Ultrasound.

For the early diagnosis of atherosclerosis and interventions, intravascular ultrasound (IVUS) is a valuable tool for intravascular luminal imaging. Compared with the array-based method, mechanically rotating IVUS catheters dominate the clinical applications because of their less complexity and better suitability for high-frequency ultrasound imaging. However, mechanically rotating catheters are suffering from non-uniform rotational distortion (NURD) which hinders accurate image acquisition. In this study, a dual-element imaging catheter is proposed, in which two elements with the same frequency and similar performance are assembled in a back-to-back arrangement. When the catheter encounters a NURD due to acute bending, the abnormal image of one element can be replaced by the normal image of the opposite element, thus eliminating the NURD in the reconstructed image. Moreover, two images can be obtained in one rotation and the imaging frame rate is doubled in the absence of NURD. The performance of the two elements was quantitatively assessed by a wire phantom. And the complementary imaging protocols were evaluated by a tissue phantom and ex vivo porcine vessel. The results show that the proposed strategy can be promising in clinical studies.

Mechanosensitive channel MscL induces non-apoptotic cell death and its suppression of tumor growth by ultrasound.

Mechanosensitive channel of large conductance (MscL) is the most thoroughly studied mechanosensitive channel in prokaryotes. Owing to its small molecular weight, clear mechanical gating mechanism, and nanopore forming ability upon opening, accumulating studies are implemented in regulating cell function by activating mechanosensitive channel of large conductance in mammalian cells. This study aimed to investigate the potentials of mechanosensitive channel of large conductance as a nanomedicine and a mechano-inducer in non-small cell lung cancer (NSCLC) A549 cells from the view of molecular pathways and acoustics. The stable cytoplasmic vacuolization model about NSCLC A549 cells was established via the targeted expression of modified mechanosensitive channel of large conductance channels in different subcellular organelles. Subsequent morphological changes in cellular component and expression levels of cell death markers are analyzed by confocal imaging and western blots. The permeability of mitochondrial inner membrane (MIM) exhibited a vital role in cytoplasmic vacuolization formation. Furthermore, mechanosensitive channel of large conductance channel can be activated by low intensity focused ultrasound (LIFU) in A549 cells, and the suppression of A549 tumors in vivo was achieved by LIFU with sound pressure as low as 0.053 MPa. These findings provide insights into the mechanisms underlying non-apoptotic cell death, and validate the nanochannel-based non-invasive ultrasonic strategy for cancer therapy.

Low-Intensity Focused Ultrasound Ameliorates Ischemic Heart Failure Related to the Cholinergic Anti-Inflammatory Pathway.

OBJECTIVES: This study aims to determine the effect of low-intensity focused ultrasound (LIFU) in ischemic heart failure (IHF) and explore the potential neuroimmune mechanism. METHODS: Sprague-Dawley rats were subjected to ultrasound (US) with specific parameters, and electrocardiograms were recorded to analyze the effect of LIFU and/or vagal denervation on heart rate. Thereafter, myocardial infarction (MI) was induced by left anterior artery ligation, and LIFU was performed three times a day for 25 days after MI. Echocardiography, Masson staining, and ELISA were used to evaluate the effect of LIFU on the structure and function of the heart. Finally, ELISA, flow cytometry, qRT-PCR, and Western blot analysis were performed to determine the effect of LIFU on the inflammation and the expression of the cholinergic anti-inflammatory pathway (CAP)-related mediators. RESULTS: LIFU reduced heart rate in rats (control vs LIFU, P < .01), and vagotomy (VT) eliminated this effect of LIFU on heart rate (VT vs LIFU + VT, P > .01). LIFU-ameliorated IHF in terms of cardiac structure and function (MI vs MI + LIFU, P < .01), but VT abrogated the beneficial effect of LIFU (MI + VT vs MI + LIFU + VT, P > .01). After the treatment of LIFU, decreased levels of inflammatory cytokines, increased proportion of anti-inflammatory macrophages, and increased expression of CAP-related mediators (MI vs MI + LIFU, P < .01). CONCLUSIONS: LIFU ameliorates IHF whereas the CAP plays a promising role. LIFU has the potential to be a novel nonpharmacological and noninvasive therapy for the treatment of coronary artery disease and other cardiovascular diseases.

Correlation Between Portal Vein Pressure and Subharmonic Scattering Signals From SonoVue Microbubbles in Canines.

The current gold standard for the clinical diagnosis of portal hypertension (PH) is an invasive and indirect estimation of portal vein pressure (PVP). Therefore, the need for a non-invasive PVP measurement method is urgent. Subharmonic scattering of ultrasound contrast agent (UCA) microbubbles is under investigation in clinical research as a pressure indicator. However, the driving acoustic pressure must be optimized to improve the ambient pressure sensitivity of the subharmonic amplitude for different UCAs. In this study, for the first time, we obtained the relationship between the PVP and the amplitude of the subharmonic signal scattered from SonoVue microbubbles by using two canines to build the PH model. The results revealed a desirable linear correlation between the subharmonic amplitude and PVP (<20 mmHg) at the incident acoustic pressure of 453 kPa (r = -0.910, p < 0.005; sensitivity: -2.003 dB/mmHg); this was one order of magnitude higher in sensitivity than that of the in vitro case with a detectable pressure variation of approximately 1 mmHg. This indicates the feasibility of using UCA microbubbles to accurately measure low ambient pressures in vivo and further exhibits the potential of the method for non-invasive pressure estimation in clinical applications.

Deep learning for the diagnosis of suspicious thyroid nodules based on multimodal ultrasound images.

Objectives: This study aimed to differentially diagnose thyroid nodules (TNs) of Thyroid Imaging Reporting and Data System (TI-RADS) 3-5 categories using a deep learning (DL) model based on multimodal ultrasound (US) images and explore its auxiliary role for radiologists with varying degrees of experience. Methods: Preoperative multimodal US images of 1,138 TNs of TI-RADS 3-5 categories were randomly divided into a training set (n = 728), a validation set (n = 182), and a test set (n = 228) in a 4:1:1.25 ratio. Grayscale US (GSU), color Doppler flow imaging (CDFI), strain elastography (SE), and region of interest mask (Mask) images were acquired in both transverse and longitudinal sections, all of which were confirmed by pathology. In this study, fivefold cross-validation was used to evaluate the performance of the proposed DL model. The diagnostic performance of the mature DL model and radiologists in the test set was compared, and whether DL could assist radiologists in improving diagnostic performance was verified. Specificity, sensitivity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristics curves (AUC) were obtained. Results: The AUCs of DL in the differentiation of TNs were 0.858 based on (GSU + SE), 0.909 based on (GSU + CDFI), 0.906 based on (GSU + CDFI + SE), and 0.881 based (GSU + Mask), which were superior to that of 0.825-based single GSU (p = 0.014, p< 0.001, p< 0.001, and p = 0.002, respectively). The highest AUC of 0.928 was achieved by DL based on (G + C + E + M)US, the highest specificity of 89.5% was achieved by (G + C + E)US, and the highest accuracy of 86.2% and sensitivity of 86.9% were achieved by DL based on (G + C + M)US. With DL assistance, the AUC of junior radiologists increased from 0.720 to 0.796 (p< 0.001), which was slightly higher than that of senior radiologists without DL assistance (0.796 vs. 0.794, p > 0.05). Senior radiologists with DL assistance exhibited higher accuracy and comparable AUC than that of DL based on GSU (83.4% vs. 78.9%, p = 0.041; 0.822 vs. 0.825, p = 0.512). However, the AUC of DL based on multimodal US images was significantly higher than that based on visual diagnosis by radiologists (p< 0.05). Conclusion: The DL models based on multimodal US images showed exceptional performance in the differential diagnosis of suspicious TNs, effectively increased the diagnostic efficacy of TN evaluations by junior radiologists, and provided an objective assessment for the clinical and surgical management phases that follow.

[FPGA Implementation of Digital Coordinate Conversion of Intravascular Ultrasound Imaging System Based on CORDIC Algorithm].

In order to facilitate doctors to better obtain cardiovascular images by using intravascular ultrasound imaging system and make a more accurate diagnosis, a digital coordinate conversion method of intravascular ultrasound imaging system based on CORDIC algorithm is proposed, it converts polar coordinates into rectangular coordinates through angular rotation and orientation calculation. The experimental simulation test is carried out on the platform of intravascular ultrasound imaging system by FPGA. Experimental simulation shows that, CORDIC algorithm can effectively output sine and cosine values, compared with the traditional table finding method, this algorithm has faster speed, stronger real-time performance and needs less hardware resources. It is more suitable for intravascular ultrasound imaging system.

Low-frequency, low-intensity ultrasound modulates light responsiveness of mouse retinal ganglion cells.

Objective. Ultrasound modulates the firing activity of retinal ganglion cells (RGCs), but the effects of lower-frequency, lower-intensity ultrasound on RGCs and underlying mechanism(s) remain poorly understood. This study aims to address these questions.Approach. Multi-electrode recordings were used in this study to record the firing sequences of RGCs in isolated mouse retinas. RGCs' background firing activities as well as their light responses were recorded with or without ultrasound stimulation. Cross-correlation analyses were performed to investigate the possible cellular/circuitry mechanism(s) underlying ultrasound modulation.Main results. It was found that ultrasound stimulation of isolated mouse retina enhanced the background activity of ON-RGCs and OFF-RGCs. In addition, background ultrasound stimulation shortened the light response latency of both ON-RGCs and OFF-RGCs, while enhancing part of the RGCs' (both ON- and OFF-subtypes) light response and decreasing that of the others. In some ON-OFF RGCs, the ON- and OFF-responses of an individual cell were oppositely modulated by the ultrasound stimulation, which suggests that ultrasound stimulation does not necessarily exert its effect directly on RGCs, but rather via its influence on other type(s) of cells. By analyzing the cross-correlation between the firing sequences of RGC pairs, it was found that concerted activity occurred during ultrasound stimulation differed from that occurred during light stimulation, in both spatial and temporal aspects. These results suggest that the cellular circuits involved in ultrasound- and light-induced concerted activities are different and glial cells may be involved in the circuit in response to ultrasound.Significance. These findings demonstrate that ultrasound affects neuronal background activity and light responsiveness, which are critical for visual information processing. These results may also imply a hitherto unrecognized role of glial cell activation in the bidirectional modulation effects of RGCs and may be critical for the nervous system.

Biomimetic nanoparticles directly remodel immunosuppressive microenvironment for boosting glioblastoma immunotherapy.

Glioblastoma (GBM), as a very aggressive cancer of central nervous system, is very challenging to completely cure by the conventional combination of surgical resection with radiotherapy and chemotherapy. The success of emerging immunotherapy in hot tumors has attracted considerable interest for the treatment of GBM, but the unique tumor immunosuppressive microenvironment (TIME) of GBM leads to the failure of immunotherapy. Here, we show the significant improvement of the immunotherapy efficacy of GBM by modulating the TIME through novel all-in-one biomimetic nanoparticles (i.e. CS-I/J@CM NPs). The nanoparticles consist of utrasmall Cu2-x Se nanoparticles (NPs) with outstanding intrinsic properties (e.g., photo-responsive Fenton-like catalytic property for inducing immunogenic cell death (ICD) and alleviating the hypoxia of tumor), indoximod (IND, an inhibitor of indoleamine-2,3-dioxygenease in tumor), JQ1 (an inhibitor for reducing the expression of PD-L1 by tumor cells), and tumor cell membrane for improving the targeting capability and accumulation of nanoparticles in tumor. We reveal that these smart CS-I/J@CM NPs could drastically activate the immune responses through remodeling TIME of GBM by multiple functions. They could (1) increase M1-phenotype macrophages at tumor site by promoting the polarization of tumor-associated macrophages through the reactive oxygen species (ROS) and oxygen generated from the Fenton-like reaction between nanoparticles and H2O2 within tumor under NIR II irradiation; (2) decrease the infiltration of Tregs cells at tumor site through the release of IND; (3) decrease the expression of PD-L1 on tumor cells through JQ1. The notable increments of anti-tumor CD8+T cells in the tumor and memory T cells (TEM) in the spleen show excellent therapy efficacy and effectively prevent the recurrence of GBM after modulation of the TIME. This work demonstrates the modulation of TIME could be a significant strategy to improve the immunotherapy of GBM and other cold tumors.