Peak Negative Pressure Research Articles

Correlation Between Brain Tissue Damage and Inertial Cavitation Dose Quantified Using Passive Cavitation Imaging

Focused ultrasound (FUS)-induced cavitation-mediated brain therapies have become emerging therapeutic modalities for neurologic diseases. Cavitation monitoring is essential to ensure the safety of all cavitation-mediated therapeutic techniques as inertial cavitation can be associated with tissue damage. The objective of this study was to reveal the correlation between the inertial cavitation dose, quantified by passive cavitation imaging (PCI), and brain tissue histologic-level damage induced by FUS in combination with microbubbles. An ultrasound image-guided FUS system consisting of a single-element FUS transducer (1.5 MHz) and a co-axially aligned 128-element linear ultrasound imaging array was used to perform FUS treatment of mice. Mice were sonicated by FUS with different peak negative pressures (0.5 MPa, 1.1 MPa, 4.0 MPa and 6.5 MPa) in the presence of systemically injected microbubbles. The acoustic emissions from the FUS-activated microbubbles were passively detected by the imaging array. The pre-beamformed channel data were acquired and processed offline using the frequency-domain delay, sum and integration algorithm to generate inertial cavitation maps. All the mice were sacrificed after the FUS treatment, and their brains were harvested and processed for hematoxylin and eosin staining. The obtained inertial cavitation maps revealed the dynamic changes of microbubble behaviors during FUS treatment at different pressure levels. It was found that the inertial cavitation dose quantified based on PCI had a linear correlation with the scale of histologic-level tissue damage. Findings from this study suggested that PCI can be used to predict histologic-level tissue damage associated with the FUS-induced cavitation.

In vivo imaging of sterile microglial activation in rat brain after disrupting the blood-brain barrier with pulsed focused ultrasound: [18F]DPA-714 PET study

BackgroundMagnetic resonance imaging (MRI)-guided pulsed focused ultrasound combined with the infusion of microbubbles (pFUS+MB) induces transient blood-brain barrier opening (BBBO) in targeted regions. pFUS+MB, through the facilitation of neurotherapeutics’ delivery, has been advocated as an adjuvant treatment for neurodegenerative diseases and malignancies. Sterile neuroinflammation has been recently described following pFUS+MB BBBO. In this study, we used PET imaging with [18F]-DPA714, a biomarker of translocator protein (TSPO), to assess for neuroinflammatory changes following single and multiple pFUS+MB sessions.MethodsThree groups of Sprague-Dawley female rats received MRI-guided pFUS+MB (Optison™; 5–8 × 107 MB/rat) treatments to the left frontal cortex and right hippocampus. Group A rats were sonicated once. Group B rats were sonicated twice and group C rats were sonicated six times on weekly basis. Passive cavitation detection feedback (PCD) controlled the peak negative pressure during sonication. We performed T1-weighted scans immediately after sonication to assess efficiency of BBBO and T2*-weighted scans to evaluate for hypointense voxels. [18F]DPA-714 PET/CT scans were acquired after the BBB had closed, 24 h after sonication in group A and within an average of 10 days from the last sonication in groups B and C. Ratios of T1 enhancement, T2* values, and [18F]DPA-714 percent injected dose/cc (%ID/cc) values in the targeted areas to the contralateral brain were calculated. Histological assessment for microglial activation/astrocytosis was performed.ResultsIn all groups, [18F]DPA-714 binding was increased at the sonicated compared to non-sonicated brain (%ID/cc ratios > 1). Immunohistopathology showed increased staining for microglial and astrocytic markers in the sonicated frontal cortex compared to contralateral brain and to a lesser extent in the sonicated hippocampus. Using MRI, we documented BBB disruption immediately after sonication with resolution of BBBO 24 h later. We found more T2* hypointense voxels with increasing number of sonications. In a longitudinal group of animals imaged after two and after six sonications, there was no cumulative increase of neuroinflammation on PET.ConclusionUsing [18F]DPA-714 PET, we documented in vivo neuroinflammatory changes in association with pFUS+MB. Our protocol (utilizing PCD feedback to minimize damage) resulted in neuroinflammation visualized 24 h post one sonication. Our findings were supported by immunohistochemistry showing microglial activation and astrocytosis. Experimental sonication parameters intended for BBB disruption should be evaluated for neuroinflammatory sequelae prior to implementation in clinical trials.

Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs

In this study, we designed and validated a platform for ultrasound and microbubble-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have been shown to reprogram tumor cells and sensitize them to clinically used chemotherapy. To overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into nanocarriers. Focused ultrasound combined with gas-filled microbubbles provides a noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded particles. A single handheld, curvilinear ultrasound array was used in this study for image-guided therapy with clinical-grade SonoVue contrast agent. First, we validated the platform on phantoms to optimize the microbubble cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA nanoparticles co-loaded with antisense-miRNA-21 and antisense-miRNA-10b to pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the ultrasound treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles to visually assess nanoparticle extravasation. Fluorescent microscopy suggested the presence of nanoparticles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that the proposed platform may be used to safely and noninvasively enhance the delivery of miRNA-loaded nanoparticles to target regions in deep organs in large animal models.

The CMST Airgun Array Model—A Simple Approach to Modeling the Underwater Sound Output From Seismic Airgun Arrays

This paper describes the theoretical and numerical basis for the Centre for Marine Science and Technology airgun array model (Cagam), a relatively simple airgun array model that has been used by the center for a number of years. Comparisons with the measured data from the International Association of Oil and Gas Producers Exploration and Production Sound and Marine Life, Joint Industry Programme Svein Vaage Broadband Airgun Study data set, were carried out for a single airgun of a range of sizes and types and several two-gun clusters. When calibrated for the time integrated squared pressure, the model predicted positive peak levels to an accuracy of ±0.6 dB and successfully predicted the overall spectral shape, including its high-frequency roll-off. There were larger errors in prediction of negative peak pressures, with Cagam underpredicting the negative peak pressure by up to 2.3 dB. For a single airgun, Cagam tended to slightly overestimate the bubble pulse frequency and to underestimate the bubble damping, with both these discrepancies increasing for two-gun clusters. A comparison with the Agora2 model, used for several studies by participants in the 2016 International Airgun Modelling Workshop, is also included.

Acoustic radiation force imaging using a single-shot spiral readout

The purpose of this study is to develop and validate rapid magnetic resonance acoustic radiation force imaging (MR-ARFI) using a single shot spiral readout for focused ultrasound (FUS) guidance and for local tissue displacement measurements. A magnetic resonance guided FUS system was used to focus a 3 MHz ultrasound beam to a predetermined position. MR-ARFI was performed with a Bruker 7 T MRI using a modified single-shot spiral readout, with additional motion encoding gradients that convert local displacement into the phase image. Post processing was then used to analyze the resulting displacement and to evaluate the method’s performance for the detection of tissue changes resulting from thermal ablation. The single-shot spiral readout acquires a single MR-ARFI image in one second, which is up to two orders of magnitude faster than conventional 2D spin-warp spin echo that acquires the k-space data line by line. The ARFI displacement in tissue mimicking phantoms was detected and localized with less than 5% geometric distortion. The ARFI displacement was also measured pre and post thermal ablation in an ex vivo chicken breast. For transmitted peak negative pressure of 8.6 MPa, the maximum displacement of the tissue that was ablated to 70 °C was 78% lower than the pre-ablated tissue. Since spiral readout is not prone to geometrical distortion, it is well-suited for FUS guidance, without generating undesired temperature elevation. Additionally, local displacement measurements of tissues can be performed rapidly during thermal ablation procedures and may help to assess the success of the treatment.

Pressure wave propagation effects in the eye after photoablation

A transient pressure wave created in photoablation-based laser corneal refractive surgery propagates along the optical axis of the eye from the cornea toward the fundus. Along its path, it is attenuated, reflected several times at tissue interfaces, focused due to the spherical shape of the cornea, and partially phase-converted to a tensile wave after passing the acoustic focus. Employing the numerical acoustic eye model, the dynamics of the acoustic focusing is described in detail. The simulated pressure waveforms are first validated against the existing measurements. Then, the calculated full pressure fields are used to obtain the extreme values of the pressure amplitude at every point within the eye over the whole timespan of interest. Over these pressure maps, various threshold contours obtained from the existing literature are superimposed to help ophthalmologists investigate the consequences of acoustic focusing within the human eye during laser keratorefractive surgery. The comparison indicates that the simulated negative peak pressure values used in the contemporary broad beam and flying spot laser-assisted in situ keratomileusis/photorefractive keratectomy treatments exceed some of the reported threshold values. The critical volume where the thresholds are surpassed is located near the lens-vitreous boundary and extends to the retina for wide beams. The photoablation-induced pressure wave focusing is, therefore, a mechanism that needs to be researched carefully and included in the list of potential risks accompanying refractive laser surgery.

Enhanced Shock Scattering Histotripsy With Pseudomonopolar Ultrasound Pulses.

Shock scattering histotripsy involves a complex interaction between positive and negative phases of an acoustic burst to initiate a robust cavitation bubble cloud. To more precisely study these effects and optimize shock scattering histotripsy therapy, we constructed a frequency compounding transducer to generate pseudomonopolar ultrasound pulses. The transducer consisted of 113 individual piezoelectric elements with various resonant frequencies (250 kHz, 500 kHz, 750 kHz, 1 MHz, 1.5 MHz, 2 MHz, and 3 MHz). For each resonant frequency, an extremely short pulse could be generated. Pseudomonopolar peak positive pulses were generated by aligning the principal peak positive pressures of individual frequency components temporally, so that they added constructively, and destructive interference occurred outside the peak-positive-overlapped temporal window. After inverting the polarity of the excitation signals, pseudomonopolar peak negative pulses were generated similarly by aligning principal peak negative pressures. Decoupling the positive and negative acoustic phases could have significant advantages for therapeutic applications enhancing precision and avoiding cavitation at tissue interfaces by using mostly positive pressure pulses. For example, we show that 16 shock scattering bubble clouds can be generated using only peak positive pulses following a single peak negative pulse that initiates a pressure release "seed cloud" from which the first shock front is "scattered." Subsequent positive only pulses result in a precise elongated lesion within red blood cell phantoms.

Acoustic droplet vaporization-mediated dissolved oxygen scavenging in blood-mimicking fluids, plasma, and blood

Acoustic droplet vaporization (ADV) has been shown to reduce the partial pressure of oxygen (PO2) in a fluid. The goals of this study were three-fold: 1) to determine the ADV pressure amplitude threshold in fluids that had physiologically relevant values for surface tension, protein concentration, and viscosity; 2) to assess whether these parameters and fluid mixing affect ADV-mediated PO2 reduction; and 3) to assess the feasibility of ADV-mediated PO2 reduction in plasma and whole blood. In vitro ADV experiments were conducted using perfluoropentane droplets (number density: 5 × 106 ± 0.2 × 106/mL) dispersed in fluids (saline, polyvinylpyrrolidone solutions, porcine plasma, or porcine whole blood) that had a physiological range of surface tensions (62–68 mN/m), protein concentrations (0 and 68.7 mg/mL), and viscosities (0.7–4 cP). Droplets were exposed to pulsed ultrasound (5 MHz, 4.25 MPa peak negative pressure) while passing through a 37 °C flow system with inline PO2 sensors. In select experiments, the fluid also passed through mixing channels after ultrasound exposure. Our results revealed that the ADV pressure thresholds were the same for all fluids. Surface tension and protein concentration had no effect on PO2 reduction. Increasing viscosity attenuated PO2 reduction. However, the attenuated effect was absent after fluid mixing. Furthermore, ADV-mediated PO2 reduction in whole blood (30.8 ± 3.2 mmHg) was less than that in a polyvinylpyrrolidone solution (40.2 ± 2.1 mmHg) with equal viscosity. These findings should be considered when planning clinical studies of ADV-mediated PO2 reduction and other biomedical applications of ADV.

Characteristics of wind pressures on retractable dome roofs and external peak pressure coefficients for cladding design

This study investigates the characteristics of wind pressures on retractable dome roofs. Wind tunnel tests were conducted on spherical dome roofs with various wall height-span ratios (0.1–0.5) and opening ratios (0%, 10%, 30% and 50%). After the characteristics of mean and peak pressure coefficients were examined, the peak pressure coefficients on closed dome roofs were compared with those of the current Japanese wind load code (AIJ-RLB (2015)), and peak pressure coefficients on dome roofs with openings for cladding design were proposed. The analysis results can be summarized as follows. As wall height-span ratio increases, the absolute values of mean and minimum pressure coefficients increase, and the absolute values of minimum pressure coefficients on the outermost interior of open dome roofs increase with opening ratio. For cladding design of dome roofs with openings, dome roofs were divided into two zones, and negative and positive peak pressure coefficients were proposed based on experimental results.

Transcranial Low-Intensity Pulsed Ultrasound Modulates Structural and Functional Synaptic Plasticity in Rat Hippocampus.

Plasticity of synaptic structure and function play an essential role in neuronal development, cognitive functions, and degenerative diseases. Recently, low-intensity pulsed ultrasound (LIPUS) stimulation has been reported as a promising technology for neuromodulation. However, the effect of LIPUS stimulation on the structural and functional synaptic plasticity in rat hippocampus has not yet been addressed. The aim of this study was to investigate whether LIPUS stimulation could affect the dendritic structure, electrophysiological properties, and expression level of glutamate receptors GluN2A, GluN2B, and GluR1 subunits in rat hippocampus. Transcranial LIPUS was delivered to CA1 of the intact hippocampus of rats ( n = 40 ) for 10 days (10 min/day) with the following parameters: fundamental frequency of 0.5 MHz, pulse repetition frequency (PRF) of 500 Hz, peak negative pressure of 0.42 MPa, and Ispta of 360 mW/cm2. The effect of LIPUS on dendritic structure, electrophysiological properties, and the expression of neurotransmitter receptors was measured using Golgi staining, electrophysiological recording, and western blotting, respectively. Golgi staining and electrophysiological recordings showed that LIPUS stimulation significantly increased the density of dendritic spines (0.72 ± 0.17 versus 0.94 ± 0.19 spines/ [Formula: see text], ) and the frequency of spontaneous excitatory postsynaptic current (0.37 ± 0.14 versus 1.77 ± 0.37 Hz, ) of CA1 hippocampal neurons. Furthermore, the western blotting analysis demonstrated a significant increase in the expression level of GluN2A ( ). The results illustrated the effect of LIPUS on the dendritic structure, function, and neurotransmitter receptors, which may provide a powerful tool for treating neurodegenerative diseases.

Intrinsic threshold versus shock scattering histotripsy treatment of clots in vitro

Catheter-directed thrombolytics are the frontline therapy for iliofemoral deep vein thrombosis. We have demonstrated that histotripsy can enhance the efficacy of the thrombolytic recombinant tissue plasminogen activator (rt-PA) through the mechanical activity of bubble clouds. Depending on the histotripsy pulse duration, bubble activity can be initiated via shock wave scattering or exceeding the peak negative pressure of the intrinsic cavitation threshold. In this study, the thrombolytic efficacy and bubble activity of shock scattering and intrinsic threshold histotripsy were compared. The mass loss was assessed of retracted human whole blood clots exposed to rt-PA (0 or 2.68 μg/mL) and histotripsy pulses of 1 (intrinsic threshold) or 5 (shock scattering) cycles duration. During the histotripsy exposure, bubble cloud emissions were captured on a linear array and processed to form passive acoustic images. The combination of rt-PA and histotripsy was more efficacious than rt-PA alone at 25 MPa peak negative pressure for single-cycle pulses, and 20 MPa peak negative pressure for five-cycle pulses. The degree of thrombolytic efficacy correlated with bubble cloud emissions within the clot. Overall, these results indicate that rt-PA and shock scattering or intrinsic threshold histotripsy is a promising combination thrombolytic therapy.

In vitro assessment of the relationship between medium stiffness and bubble activity for histotripsy-induced liquefaction

Histotripsy is a focused ultrasound therapy that ablates tissue via the mechanical activity of bubble clouds. While effective for healthy tissues, histotripsy-induced bubble expansion will be mitigated in stiff chronic pathologies. In this study, the bubble cloud activity necessary for liquefaction of agarose phantoms with elastic moduli ranging from 12.3 ± 3.67 to 142 ± 44.9 kPa was investigated. Bubble clouds were initiated with 1-MHz pulses of 5-μs duration and peak negative pressures of 12 to 24 MPa. Bubble cloud emissions were mapped via passive cavitation imaging, and correlated with liquefaction using receiver operating characteristic analysis. The maximum power of emissions, and azimuthal location of the maximum power, were recorded for each experimental condition. For phantoms with elastic moduli between 12.3 and 85.8 kPa, no change was indicated in the bubble activity necessary for liquefaction. A larger acoustic power was associated with liquefaction of phantoms with elastic moduli of 142 kPa compared to 22.1 kPa. For a given peak negative pressure of the histotripsy pulse, no change in the peak power or azimuthal location of peak emissions was observed. These results indicate that a fixed bubble activity dose predicts histotripsy liquefaction over a wide range of medium stiffness.

Microbubble translation in plane-wave ultrasound transmission

Primary radiation force is capable of translating microbubbles in the focal region of single-element and array ultrasound probes. This effect can be harnessed to enhance the contact between ligand-bearing microbubbles and targeted endothelium for applications in targeted drug delivery and ultrasound molecular imaging. In this study, displacements of lipid-coated microbubbles associated with plane-wave transmission are investigated using the multi-gate Doppler approach, and compared with focused-wave transmission at equivalent peak negative pressures. In plane wave transmission, the radiation force is nearly uniform over the field of view and therefore allows for a more uniform translation of microbubbles compared to focused wave. Statistically determined median displacements are in good agreement with the axial and lateral ultrasound beamplots both in plane-wave and focused-wave transmissions, while peak microbubble displacements reveal a number of discrepancies. Distinct size-isolated microbubble populations (diameters 1–2 μm, 3–4 μm, 4–5 μm, 5–8 μm, and polydisperse) were tested, showing important differences in their displacements and a strong driving frequency dependence thereof. These findings help tune the ultrasound transmission parameters for uniform and size-selective microbubble translations.

Detection of nucleic acid-loaded microbubbles in mouse hearts during ultrasound-mediated delivery

Heart disease is a leading cause of death worldwide. Recently, there has been a growing interest in nucleic acid-based therapeutics, such as microRNAs (miRs) or microRNA inhibitors (antimiRs), for cardiac repair. Previous studies have shown that regulating microRNA levels in the heart can promote proliferation of cardiac cells, decrease fibrosis, and improve cardiac function. Ultrasound targeted microbubble destruction (UTMD) is in development to focus the delivery of therapeutic nucleic acids to the heart and reduce adverse systemic effects. Microbubbles can be loaded with nucleic acids and exposed to ultrasound in order to induce cavitation and enhance delivery at the target site. In this study phospholipid-coated microbubbles were loaded with therapeutic miR mimics or antimiRs and injected intravenously in mice. Ultrasound pulses (2.5 MHz, 0.9 MPa peak negative pressure) were applied to the heart using a P4-1 array on a Verasonics Vantage ultrasound system. The ultrasound images were analyzed to detect microbubbles in the heart during treatment. Increased mean intensity during infusion was associated with increased delivery of nucleic acids to the heart as assessed with qPCR. The results suggest that quantitative analysis of ultrasound images to detect microbubbles in vivo may aid in monitoring UTMD treatment for improved cardiac health.

Ascertaining the relationship between acoustic droplet vaporization, inertial cavitation, and hemolysis

Mechanical stress associated with inertial cavitation (IC) can cause hemolysis. The goal of this study was to determine whether hemolysis occurs during acoustic droplet vaporization (ADV) and subsequent microbubble activity. Perfluoropentane droplets were manufactured using an amalgamation protocol, diluted 30-fold in porcine whole blood, and pumped through a flow phantom maintained at 37 °C. Droplets were insonified with a 5 MHz focused transducer (peak negative pressures of 0.25 MPa to 4.25 MPa, pulse length of 40 cycles, and a pulse repetition frequency of 500 Hz). A 128-element array was used to monitor the nucleation of ADV and to record cavitation emissions. Free hemoglobin in the effluents was assayed to detect hemolytic activity. Hemolysis, IC, and ADV were detected at pressures of 2.25 MPa and higher. At 4.25 MPa, 0.38 ± 0.08% hemoglobin was released post-hemolysis. A positive linear relationship was observed between the percent hemoglobin released and IC dose. Due to the concurrence of ADV and IC, it was not possible to determine whether ADV causes hemolysis independent of IC. These findings should be considered when planning studies of biomedical application of ADV. [Work supported in part by an Acoustic Society of America Robert W. Young Award.]

Focused ultrasound-mediated microbubble destruction for glioblastoma treatment

Glioblastoma is the most common primary brain tumor with a poor prognosis despite advances in various treatment modalities, such as radiation therapy (RT). This study compared the tumor growth inhibition effects of focused ultrasound-targeted microbubble destruction (UTMD) therapy with the RT using an orthotopic mouse glioma model. Mice were implanted with GL261 glioblastoma cells and divided into three groups: control group (no treatment); RT group (2 Gy/day, 5 days/week, 3 consecutive weeks); and UTMD group (FUS sonication in the presence of systemically injected microbubbles at the peak negative pressure of 1.5 MPa, frequency of 1.44 MHz, and 2 treatments/week for 3 consecutive weeks). Contrast-enhanced magnetic resonance imaging (MRI) was performed once every four days for measuring the tumor volume. Both UTMD and RT caused significant growth inhibition compared to the control group; however, there was no significant difference between the UTMD and RT groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that the number of apoptotic tumor cells in both RT and UTMD groups were significantly higher than the control group without the difference between these two groups. This study suggests that UTMD suppressed glioblastoma tumor growth and this effect was comparable with that achieved by RT.

Mapping Microbubble and Ultrasound Spatio-temporal Interaction by M-mode Imaging: The Study of Feasibility

Ultrasound (US) and microbubble (MB) interaction is an important factor in the research of bioacoustics, as well as targeted drug and gene delivery. In this study, we demonstrate the feasibility of pulse−echo M-mode imaging system to be used for the visualization and quantification of US–MB interaction in both spatial and temporal dimensions. The system incorporates an exposure chamber with the cell–MB suspension, a 2.7 MHz focused US transducer, a US pulser–receiver and the customized LabView software. The results of cell and MB interaction obtained after M-mode image analysis have showed the US–MB interaction to be non-uniform in space and non-stationary in time. In order to quantify the spatio-temporal US–MB interaction, we have introduced the time function of spatial homogeneity dynamics. We have observed that the effective duration of interaction can be characterized at the predefined threshold of spatial homogeneity. For example, at the US excitation of 360 kPa peak negative pressure (15 bursts transmitted at 80 Hz pulse repetition frequency), the US–MB interaction persists for more than 5 seconds in the range at 4 mm depth of the exposure chamber with more than 50% of homogeneity. The system proposed in this assay is feasible for the characterization of US–MB interaction and can be exploited to optimize the MB concentration and/or the US excitation parameters.

Controlled Ultrasound Erosion for Transdermal Delivery and Hepatitis B Immunization

Although ultrasound is effective for transdermal delivery, it remains difficult to control the position, shape and size of localized skin transport regions. We developed an ultrasound erosion protocol to generate a single-site, circular delivery region with controlled size at the center of patched skin. We found that (i) shorter ultrasound pulses (25 cycles) with higher pulse repetition frequency (4 kHz) and higher peak negative pressure (17.0 MPa) resulted in larger (0.995 mm2) and deeper (∼300 µm) skin delivery regions with a higher success rate (94.44%); and (ii) temperature elevation of the skin increased with ultrasound exposure time, with a 30-s safety threshold. Furthermore, we found that hair follicles decreased the delivery controllability of ultrasound erosion. Therefore, we selected the skin of the hind legs of mice without dense hair follicles to deliver more than 1 μL of vaccine solution and successfully elicit immune responses against hepatitis B surface antigen.

Acoustic Field of Phased-Array Ultrasound Transducer with the Focus/Foci Shifting

High-intensity focused ultrasound (HIFU) is becoming popular in the treatment of solid tumors because of its non-invasiveness with few complications. The acoustic field is of importance in evaluating the safe focus shifting distance and determining the treatment plan. The propagation of finite-amplitude acoustic wave from a 331-element HIFU phased-array with focus steering along and transverse to the transducer axis and 4-foci shifting on the focal plane was simulated using the angular spectrum approach (ASA) with a marching second-order operator-splitting scheme. In addition, the acoustic field produced by a truncated asymmetric transesophageal HIFU annular array was also simulated, and the effects of driving frequency and the number of concentric rings were investigated. Because of the nonlinear effects, the peak negative pressure is lower than that of peak positive pressure at the main lobe but has a larger beam size. However, the peak positive and negative pressures at the grating lobe are quite similar. The effects of the focus shifting distances on the main and grating lobe (both acoustic pressure and − 6 dB beam size) were evaluated. With the focus shifting axially away from the transducer surface, the main lobe has decreased acoustic pressure by ~ 1.9 fold and increased beam size by ~ 4.5 fold while the grating lobe has the increased acoustic pressure by ~ 1.8 fold. The focus shifting laterally leads to the reduced pressure at the main lobe by ~ 1.4 fold but the slight decrease at the grating lobe by ~ 1.1 fold. In comparison, the shifting of multi-foci has similar influences on the main lobe but increases the pressure at the grating lobe. Driving frequency of annular array is found to have greater influences on the peak pressure and beam size. Our algorithm can simulate the acoustic field of phased-array in arbitrary shape and optimize the transducer design, and the focus shifting distance and strategy should be selected appropriately for the safe HIFU exposure.

Wave effects in a realistic tunnel induced by the passage of high-speed trains

As a high-speed train passes through a tunnel, aerodynamic pressure waves propagate backwards and forward in the tunnel, and they persist for a long time after the train is gone. Understanding the aerodynamic characteristics influenced by various factors on a tunnel is essential for ensuring the safety of tunnel structures. Field measurements were conducted in a 2812 m-long tunnel to systematically investigate the pressure characteristics during the passage of CRH2-150C and CRH380AL high-speed trains through the tunnel, both in single-train and intersecting cases. The results reveal that as the train speed increases, the location of the maximum peak-to-peak pressure variation shifts toward the tunnel entrance, mainly driven by the change in the negative pressure peak. The train length induces significant differences in peak pressures on the tunnel wall in the middle of the tunnel, and a long train brings more massive subsequent pressure waves than a short train in the post-train stage, but they decay faster. The intersection of two trains in the tunnel not only causes a significant change in the peak pressure and its location, but also has a significant effect on damage factor (the damage level on a structure subjected to a specific load) after train leaving the tunnel, with a 65.3% of this factor during trains operating in the tunnel.