Carbon nanofibers/liquid metal composites for high temperature laser ultrasound.

As the demand for clean energy becomes greater worldwide, there will also be an increasing demand for next generation nuclear power plants that incorporate advanced sensors and monitoring equipment. A major challenge posed by nuclear power plants is that, during normal operation, the reactor compartment is subjected to high operating temperatures and radiation flux. Diagnostic sensors monitoring such structures are also subject to temperatures reaching hundreds of degrees Celsius, which puts them at risk for heat degradation. In this work, the ability of carbon nanofibers to work in conjunction with a liquid metal as a photoacoustic transmitter was demonstrated at high temperatures. Fields metal, a Bi-In-Sn eutectic, and gallium are compared as acoustic mediums. Fields metal was shown experimentally to have superior performance over gallium and other reference cases. Under stimulation from a low fluence 6 ns pulse laser at 6 mJ/cm2 with 532 nm green light, the Fields metal transducer transmitted a 200 kHz longitudinal wave with amplitude >5.5 times that generated by a gallium transducer at 300 °C. Each high temperature test was conducted from a hot to cold progression, beginning as high as 300 °C, and then cooling down to 100 °C. Each test shows increasing signal amplitude of the liquid metal transducers as temperature decreases. Carbon nanofibers show a strong improvement over previously used candle-soot nanoparticles in both their ability to produce strong acoustic signals and absorb higher laser fluences up to 12 mJ/cm2.

The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy.

Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, histotripsy is distinct from the conventional HIFU techniques resulting in hyperthermia and thermal injury. Phase I human trials have shown the initial safety and efficacy of histotripsy in treating patients with malignant liver tumors. In addition to tissue ablation, a promising benefit of M-HIFU has been stimulating a local and systemic antitumor immune response in preclinical models and potentially in the Phase I trial. Preclinical studies combining systemic immune therapies appear promising, but clinical studies of combinations have been complicated by systemic toxicities. Consequently, combining M-HIFU with systemic immunotherapy has been demonstrated in preclinical models and may be testing in future clinical studies. An additional alternative is to combine intratumoral M-HIFU and immunotherapy using microcatheter-placed devices to deliver both M-HIFU and immunotherapy intratumorally. The promise of M-HIFU as a component of anti-cancer therapy is promising, but as forms of HIFU are tested in preclinical and clinical studies, investigators should report not only the parameters of the energy delivered but also details of the preclinical models to enable analysis of the immune responses. Ultimately, as clinical trials continue, clinical responses and immune analysis of patients undergoing M-HIFU including forms of histotripsy will provide opportunities to optimize clinical responses and to optimize application and scheduling of M-HIFU in the context of the multi-modality care of the cancer patient.

Vortex-ultrasound for microbubble-mediated thrombolysis of retracted clots.

Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots.

A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis.

This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.

Intravascular Sono-Ablation for In-Stent Restenosis Relief: Transducer Development and the In-Vitro Demonstration.

OBJECTIVE: This study aimed to propose a new clinical modality for the relief of in-stent restenosis (ISR) using focused ultrasound (FUS) ablation. In the first research stage, a miniaturized FUS device was developed for the sonification of the remaining plaque after stenting, known as one of the causes of ISR. METHODS: This study presents a miniaturized (<2.8 mm) intravascular FUS transducer for ISR treatment. The performance of the transducer was predicted through a structural-acoustic simulation, followed by fabrication of the prototype device. Using the prototype FUS transducer, we demonstrated tissue ablation with bio-tissues over metallic stents, mimicking in-stent tissue ablation. Next, we conducted a safety test by detecting the existence of thermal damage to the arterial tissue upon sonication with a controlled dose. RESULTS: The prototype device successfully delivered sufficient acoustic intensity (>30 W/cm2) to a bio tissue (chicken breast) through a metallic stent. The ablation volume was approximately 3.9 × 7.8 × 2.6 mm3. Furthermore, 1.5 min sonication was sufficient to obtain an ablating depth of approximately 1.0 mm, not thermally damaging the underlying artery vessel. CONCLUSION: We demonstrated in-stent tissue sonoablation, suggesting it could be as a future ISR treatment modality. SIGNIFICANCE: Comprehensive test results provide a key understanding of FUS applications using metallic stents. Furthermore, the developed device can be used for sonoablation of the remaining plaque, providing a novel approach to the treatment of ISR.

Noninvasive liquid level sensing with laser generated ultrasonic waves.

This article proposes a noninvasive liquid level sensing technique using laser-generated ultrasound waves for nuclear power plant applications. Liquid level sensors play an important role of managing the coolant system safely and stably in the plant structure. Current sensing techniques are mostly intrusive, performing inside the fluidic structure, which is disadvantageous in terms of the regular maintenance of the plant system. Furthermore, typical intrusive sensors do not perform stably under varying environmental conditions such as temperature and radiation. In this study, sensing units are attached to the outer surface of a liquid vessel to capture guided ultrasound waves in a nonintrusive manner. The signal intensity of the guided wave dissipates when the signal interacts with the internal liquid media. The sensing mechanism is mathematically expressed as an index value to correlate the liquid level with the sensor signal. For the acoustic wave generation, laser-generated ultrasound was adopted instead of using typical contact type transducers. Following the simulation validation of the proposed concept, the performance of the developed sensor was confirmed through experimental results under elevated liquid temperature conditions. The nonlinear multivariable regression exhibited the best-fit to the datasets measured under the variable liquid level and temperature conditions.

Dual-Frequency Intravascular Sonothrombolysis: An In Vitro Study.

Thrombo-occlusive disease is one of the leading causes of death worldwide. There has been active research on safe and effective thrombolysis in preclinical and clinical studies. Recently, the dual-frequency transcutaneous sonothrombolysis with contrast agents [microbubbles (MBs)] has been reported to be more efficient in trigging the acoustic cavitation, which leads to a higher lysis rate. Therefore, there is increasing interest in applying dual-frequency technique for more significant efficacy improvement in intravascular sonothrombolysis since a miniaturized intravascular ultrasound transducer typically has a limited power output to fully harness cavitation effects. In this work, we demonstrated this efficacy enhancement by developing a new broadband intravascular transducer and testing dual-frequency sonothromblysis in vitro. A broadband intravascular transducer with a center frequency of 750 kHz and a footprint size of 1.4 mm was designed, fabricated, and characterized. The measured -6-dB fractional bandwidth is 68.1%, and the peak negative pressure is 1.5 MPa under the driving voltage of 80 Vpp. By keeping one frequency component at 750 kHz, the second frequency component was selected from 450 to 650 kHz with an interval of 50 kHz. The in vitro sonothrombolysis tests were conducted with a flow model and the results indicated that the MB-mediated, dual-frequency (750+500 kHz) sonothrombolysis yields an 85% higher lysis rate compared with the single-frequency treatment, and the lysis rate of dual-frequency sonothrombolysis increases with the difference between the two frequency components. These findings suggest a dual-frequency excitation technique for more efficient intravascular sonothrombolysis than conventional single-frequency excitation.

A multi-pillar piezoelectric stack transducer for nanodroplet mediated intravascular sonothrombolysis.

We aim to develop a nanodroplet (ND)-mediated intravascular ultrasound (US) transducer for deep vein thrombosis treatments. The US device, having an efficient forward directivity of the acoustic beam, is capable of expediting the clot dissolution rate by activating cavitation of NDs injected onto a thrombus. We designed and prototyped a multi-pillar piezoelectric stack (MPPS) transducer composed of four piezoelectric stacks. Each stack was made of five layers of PZT-4 plates, having a dimension of 0.85 × 0.85 × 0.2 mm3. The transducer was characterized by measuring the electrical impedance and acoustic pressure, compared to simulation results. Next, in-vitro tests were conducted in a blood flow mimicking system using the transducer equipped with an ND injecting tube. The miniaturized transducer, having an aperture size of 2.8 mm, provided a high mechanical index of 1.52 and a relatively wide focal zone of 3.4 mm at 80 Vpp, 0.96 MHz electric input. The mass-reduction rate of the proposed method (NDs + US) was assessed to be 4.1 and 4.6 mg/min with and without the flow model, respectively. The rate was higher than that (1.3-2.7 mg/min) of other intravascular ultrasound modalities using micron-sized bubble agents. The ND-mediated intravascular sonothrombolysis using MPPS transducers was demonstrated with an unprecedented lysis rate, which may offer a new clinical option for DVT treatments. The MPPS transducer generated a high acoustic pressure (~3.1 MPa) at a distance of approximately 2.2 wavelengths from the small aperture, providing synergistic efficacy with nanodroplets for thrombolysis without thrombolytic agents.

Magneto-sonothrombolysis with combination of magnetic microbubbles and nanodroplets.

This paper reports a novel technique using the rotational magnetic field oscillation and low-intensity sub-megahertz ultrasound stimulation of magnetic microbubbles (MMBs) to promote the nanodroplets (NDs) phase transition and improve the permeation of NDs into the blood clot fibrin network to enhance the sonothrombolysis efficiency. In this study, the influence of different treatment methods with a combination of MMBs and NDs on the thrombolysis rate of both unretracted and retracted clots were investigated, including the stable and inertial cavitation, tPA effects, MMBs/NDs concentration ratio, sonication factors (input voltage, duty cycle) and rotational magnetic field factors (flux density, frequency). We demonstrated that tPA-mediated magneto-sonothrombolysis in combining NDs with MMBs could significantly enhance in vitro lysis of both unretracted clots (85 ± 8.3%) and retracted clots (57 ± 6.5%) in a flow model with 30 min treatment. The results showed that the combination of MMBs and NDs substantially improves in vitro lysis of blood clots with an unprecedented lysis rate.

A 1.5-D Array for Acoustic Radiation Force (ARF)-Induced Peak Displacement-Based Tissue Anisotropy Assessment With a Row-Column Excitation Method.

Many biological tissues, including muscle or kidney, are mechanically anisotropic, and the degree of anisotropy (DoA) in mechanical properties is diagnostically relevant. DoA can be assessed either using the ratio of shear wave velocities (SWVs) or acoustic radio forced impulse (ARFI)-induced peak displacements (PD) measured longitudinal over transverse orientations. Whether using SWV or PD as a basis, DoA expressed as the ratio of values requires 90° transducer rotation when a linear array is employed. This large rotation angle is prone to misalignment errors. One solution is the use of a fully sampled matrix array for electronic rotation of point spread function (PSF). However, the challenges of matrix array are its high fabrication cost and complicated fabrication procedures. The cheaper and simpler alternative of matrix array is the use of a row-column array. A 3×64 elements 1.5-D array with a row-column excitation mode is proposed to assess DoA in mechanical properties using the PD ratio. Different numbers of elements in elevational and lateral directions were selected to have orthogonal ARFI excitation beams without rotating the transducer. A custom-designed flex circuit was used to fabricate the array with a simpler electrode connection than a fully sampled matrix array. The performance of the array was evaluated in Field II simulation and experiment. The output pressure was 0.57-MPa output under a 40- [Formula: see text] excitation with a -6-dB point spread dimension of 14×4 mm2 in orthogonal directions. The PD was measured to be [Formula: see text] in an isotropic elastic phantom with Young's modulus of 5.4 kPa. These results suggest that the array is capable of assessing DoA using PD ratio without physical rotation of the transducer. The array has the potential to reduce the misalignment errors for DoA assessment.

Direct Acoustic Imaging Using a Piezoelectric Organic Light-Emitting Diode.

Conventional ultrasonic imaging requires acoustic scanning over a target object using a piezoelectric transducer array, followed by signal processing to reconstruct the image. Here, we report a novel ultrasonic imaging device that can optically display an acoustic signal on the surface of a piezoelectric transducer. By fabricating an organic light-emitting diode (OLED) on top of a piezoelectric crystal, lead zirconate titanate (PZT), an acousto-optical piezoelectric OLED (p-OLED) transducer is realized, converting an acoustic wave profile directly to an optical image. Because of the integrated device architecture, the resulting p-OLED features a high acousto-optic conversion efficiency at the resonance frequency, providing a piezoelectric field to drive the OLED. By incorporating an electrode array in the p-OLED, we demonstrate a novel tomographic ultrasound imaging device that is operated without a need for conventional signal processing.

Examining the Influence of Low-Dose Tissue Plasminogen Activator on Microbubble-Mediated Forward-Viewing Intravascular Sonothrombolysis.

Previous work revealed that a forward-viewing intravascular (FVI) transducer can be used for microbubble (MB)-mediated sonothrombolysis and that the clot lysis was dependent on MB concentration. This study examined the effects of combining tissue plasminogen activator (tPA) with MB-mediated FVI sonothrombolysis. In vitro clot lysis and passive cavitation experiments were conducted to study the effect of low-dose tPA in FVI sonothrombolysis with varying MB concentrations. Enhanced FVI sonothrombolysis was observed in cases in which ultrasound (US) was combined with tPA or MBs compared with control, tPA alone or US alone. The lysis rate of US + tPA + MBs was improved by up to 130%, 31% and 8% for MB concentrations of 106, 107 and 108 MBs/mL, respectively, compared with MBs + US alone. Changes in stable and inertial cavitation doses were observed, corresponding to changes in clot lysis in MB-mediated FVI sonothrombolysis with and without tPA.

Stress-Sensing Method via Laser-Generated Ultrasound Wave Using Candle Soot Nanoparticle Composite.

This article aims to develop a semi-noncontact stress-sensing system using a laser-generated ultrasound (LGU) wave assisted by candle soot nanoparticle (CSNP) composite. While the acoustoelastic effect is commonly targeted to measure the stress level, efforts to combine it with the LGU wave signal have been lacking due to weak signal intensity. In this study, the CSNP-based transducer is designed to potentiate the photoacoustic energy conversion. To demonstrate the wave propagation with the designed parameters, a numerical simulation was first conducted. The experimental results showed that a laser intensity of 6.5 mJ/cm2 was enough to generate the subsurface longitudinal (SSL) wave from the CSNP composite transducer. The normal beam projection is the most effective wave-generation method, exhibiting the highest signal magnitude compared with inclined projection cases. Finally, the laser-assisted stress-sensing system was assessed by increasing the internal pressure of an air tank. The sensitivity of the developed sensor system was estimated to be 0.296 ns/MPa, showing a correlation of 0.983 with the theoretical prediction. The proposed sensing system can be used to monitor the structural integrity of nuclear power plants.

Adaptive signal decomposition and dispersion removal based on the matching pursuit algorithm using dispersion-based dictionary for enhancing damage imaging.

This paper aims to develop a method for high-resolution damage imaging for a sparsely distributed sensor network on a plate-like structure. Techniques for dispersion removal and signal decomposition are indispensable to accurate damage localization. By combining the dispersion-removed wave packets with the damage-imaging algorithm, a point-like damage can be precisely localized. In this article, a matching pursuit algorithm was utilized to decompose overlapping wave packets and then recompress the dispersion. The matching pursuit dictionary was constructed based on an asymptotic solution of the dispersion relation for Lamb waves in toneburst wave packets. The dispersion-based Hanning-window dictionary provided the parametric information for the extracted wave packets, such as propagation time-delay, dispersion extent, and phase. The parameters were leveraged for the dispersion-removal algorithm. Results of the simulation indicate that the proposed algorithm is capable of recompressing multiple dispersive wave packets with the different modes. Finally, the proposed approach was validated by the results of the experiment using a sparse array of piezoelectric wafers on an aluminum plate. Extracting the parameters of individual wave packets and removing the dispersion through matching pursuit, the algorithm for minimum-variance imaging produced a high-quality image with a fine spatial resolution. The image artifacts were significantly suppressed, and the accuracy was improved by 62.1% compared to conventional minimum-variance imaging.

Stress Measurement of a Pressurized Vessel Using Ultrasonic Subsurface Longitudinal Wave With 1-3 Composite Transducers.

This article aims to develop a stress-sensing method for a pressurized vessel based on subsurface longitudinal (SSL) waves confined in a specific waveform by using 1-3 composite transducers. Although ultrasonic SSL waves have been commonly utilized for stress sensing, wave excitation under the predefined function using the composite-type transmitter is not well studied. In this article, composite-type transducers having a wide frequency bandwidth (> 60%) and a predominant thickness mode are utilized to enhance the signal intensity of the SSL wave and the accuracy of the sensor by incorporating a specific toneburst waveform. Finite element analysis demonstrates that the signal intensity of the composite-type transducer is up to 45.3% higher than that of a single-phase transducer. Pulse-echo tests reveal that the frequency bandwidth of the developed transducer reaches up to 60.7% and is, therefore, sufficient (> 57.0%) to transmit and receive Hanning-windowed toneburst signals. Results of stress sensing affirm a linear relationship between the time delay of SSL wave and the mechanical stress of a pressurized vessel (0.335 ns/MPa). Accordingly, the regression model is constructed via principal component regression (PCR) under temperature-varying condition. PCR has a less significant degree of error (0.62 MPa) compared to that of a typical least square regression (9.49 MPa).

Miniaturized Intracavitary Forward-Looking Ultrasound Transducer for Tissue Ablation.

OBJECTIVE: This paper aims to develop a miniaturized forward-looking ultrasound transducer for intracavitary tissue ablation, which can be used through an endoscopic device. The internal ultrasound (US) delivery is capable of directly interacting with the target tumor, resolving adverse issues of currently available US devices, such as unintended tissue damage and insufficient delivery of acoustic power. METHODS: To transmit a high acoustic pressure from a small aperture (<3 mm), a double layer transducer (1.3 MHz) was designed and fabricated based on numerical simulations. The electric impedance and the acoustic pressure of the actual device was characterized with an impedance analyzer and a hydrophone. Ex vivo tissue ablation tests and temperature monitoring were then conducted with porcine livers. RESULTS: The acoustic intensity of the transducer was 37.1 W/cm2 under 250 Vpp and 20% duty cycle. The tissue temperature was elevated to 51.8 °C with a 67 Hz pulse-repetition frequency. The temperature profile in the tissue indicated that ultrasound energy was effectively absorbed inside the tissue. During a 5-min sonification, an approximate tissue volume of 2.5 × 2.5 × 1.0 mm3 was ablated, resulting in an irreversible lesion. CONCLUSION: This miniaturized US transducer is a promising medical option for the precise tissue ablation, which can reduce the risk of unintended tissue damage found in noninvasive US treatments. SIGNIFICANCE: Having a small aperture (2 mm), the intracavitary device is capable of ablating a bio tissue in 5 min with a relatively low electric power (<17 W).

Sonothrombolysis with magnetic microbubbles under a rotational magnetic field.

Thrombosis is an extremely critical clinical condition where a clot forms inside a blood vessel which blocks the blood flow through the cardiovascular system. Previous sonothrombolysis methods using ultrasound and microbubbles (MBs) often have a relatively low lysis rate due to the low microbubbles concentration at clot region caused by blood flow in the vessel. To solve this problem, the magnetic microbubbles (MMBs) that can be retained by an outer magnetic field against blood flow are used in this study. Here we report the development of a new method using the rotational magnetic field to trap and vibrate magnetic microbubbles at target clot region and then using an intravascular forward-looking ultrasound transducer to activate them acoustically. In this study, we investigated the influence of different blood flow conditions, vessel occlusion conditions (partial and fully occluded), clot ages (fresh, retracted), ultrasound parameters (input voltage, duty cycle) and rotational magnetic field parameters (amplitude, frequency) on the thrombolysis rate. The results showed that the additional use of magnetic microbubbles significantly enhances in vitro lysis of blood clot.

Candle Soot Carbon Nanoparticles in Photoacoustics: Advantages and Challenges for Laser Ultrasound Transmitters.

This manuscript provides a review of candle-soot nanoparticle (CSNP) composite laser ultrasound transmitters (LUT), and compares and contrasts this technology to other carboncomposite designs. Among many carbon-based composite LUTs, a CSNP composite has shown its advantages of maximum energy conversion and fabrication simplicity for developing highly efficient ultrasound transmitters. This review focuses on the advantages and challenges of the CSNP-composite transmitter in the aspects of nanostructure design, fabrication procedure, and promising applications. Included are a brief description of the basic principles of the laser ultrasound transmitter, a review of general properties of CSNPs, as well as details on the fabrication method, photoacoustic performance, and design factors. A comparison of the CSNP-nanocomposite to other carbon-nanocomposites is provided. Lastly, representative applications of carbon-nanocomposite transmitters and future perspectives on CSNP-composite transmitters are presented.

Enhanced damage imaging of a metallic plate using matching pursuit algorithm with multiple wavepaths.

Waveforms received by sensors resulting from multiple wavepaths overlap and are hard to interpret. Because of this difficulty, they are usually intentionally ignored, thereby only the first arrival of wave mode being used for damage localization. This article proposes an imaging algorithm for damage localization by incorporating multiple wavepaths using piezoelectric wafers affixed on a metallic plate. Matching pursuit (MP) algorithm to enhance image quality is adopted for separating each wave packet individually. MP algorithm is an adaptive time-frequency signal decomposition technique that matches the best-fit elementary atom functions from an overcomplete dictionary. This study proposes a new dictionary composed of atom functions that constitute possible wave packets propagated by an excitation of Hann-windowed toneburst. The proposed dictionary converges faster and separates individual wave packets more accurately than typical Gaussian based dictionaries. Simulated studies first confirm the performance of MP algorithm with the proposed dictionary in comparison with those using conventional non-adaptive time-frequency analysis as well as MP with heuristic Gaussian-based dictionaries. The results of this study validate the proposed algorithm that multiple wavepaths can localize the damage with three to four piezoelectric wafers versus typical approaches employing only primary scattered waves.