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Objective: Tissue susceptibility to histotripsy disintegration has been reported to depend on its elastic properties. This work was aimed at investigation of histotripsy efficiency for liquefaction of human hematomas, depending on their stiffness and degree of retraction over time (0-10 d)., Methods: As an in vitro hematoma model, anticoagulated human blood samples (200 mL) were recalcified at different temperatures. In one set of samples, the shear modulus was measured by shear wave elastography during blood clotting at 10℃, 22℃ and 37℃, and then daily during further aging. The ultrastructure of the samples was analyzed daily with scanning electron microscopy (SEM). Another set of blood samples (50-200 mL) were recalcified at 37℃ for density and retraction measurements over aging and exposed to histotripsy at varying time points. Boiling histotripsy (2.5 ms pulses) and hybrid histotripsy (0.2 ms pulses) exposures (2 MHz, 1% dc, P+/P-/A s = 182/-27/207 MPa in situ) were used to produce either individual cigar-shaped or volumetric (0.8-3 mL) lesions in samples incubated for 3 h, 5 d and 10 d. The obtained lesions were sized, then the lysate aspirated under B-mode guidance was analyzed ultrastructurally and diluted in distilled water for sizing of residual fragments., Results: It was found that clotting time decreased from 113 to 25 min with the increase in blood temperature from 10℃ to 37℃. The shear modulus increased to 0.53 ± 0.17 kPa during clotting and remained constant within 8 d of incubation at 2℃. Sample volumes decreased by 57% because of retraction within 10 d. SEM revealed significant echinocytosis but unchanged ultrastructure of the fibrin meshwork. Liquefaction rate and lesion dimensions produced with the same histotripsy protocols correlated with the increase in the degree of retraction and were lower in retracted samples versus freshly clotted samples. More than 80% of residual fibrin fragments after histotripsy treatment were shorter than 150 µm; the maximum length was 208 µm, allowing for unobstructed aspiration of the lysate with most clinically used needles., Conclusion: The results indicate that hematoma susceptibility to histotripsy liquefaction is not entirely determined by its stiffness, and correlates with the retraction degree., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pulsed high-intensity focused ultrasound (pHIFU) uses nonlinearly distorted millisecond-long ultrasound pulses of moderate intensity to induce inertial cavitation in tissue without administration of contrast agents. The resulting mechanical disruption permeabilizes the tissue and enhances the diffusion of systemically administered drugs. This is especially beneficial for tissues with poor perfusion such as pancreatic tumors. Here, we characterize the performance of a dual-mode ultrasound array designed for image-guided pHIFU therapies in producing inertial cavitation and ultrasound imaging. The 64-element linear array (1.071 MHz, an aperture of 14.8×51.2 mm, and a pitch of 0.8 mm) with an elevational focal length of 50 mm was driven by the Verasonics V-1 ultrasound system with extended burst option. The attainable focal pressures and electronic steering range in linear and nonlinear operating regimes (relevant to pHIFU treatments) were characterized through hydrophone measurements, acoustic holography, and numerical simulations. The steering range at ±10% from the nominal focal pressure was found to be ±6 mm axially and ±11 mm azimuthally. Focal waveforms with shock fronts of up to 45 MPa and peak negative pressures up to 9 MPa were achieved at focusing distances of 38-75 mm from the array. Cavitation behaviors induced by isolated 1-ms pHIFU pulses in optically transparent agarose gel phantoms were observed by high-speed photography across a range of excitation amplitudes and focal distances. For all focusing configurations, the appearance of sparse, stationary cavitation bubbles occurred at the same P - threshold of 2 MPa. As the output level increased, a qualitative change in cavitation behavior occurred, to pairs and sets of proliferating bubbles. The pressure P - at which this transition was observed corresponded to substantial nonlinear distortion and shock formation in the focal region and was thus dependent on the focal distance of the beam ranging within 3-4 MPa for azimuthal F -numbers of 0.74-1.5. The array was capable of B-mode imaging at 1.5 MHz of centimeter-sized targets in phantoms and in vivo pig tissues at depths of 3-7 cm, relevant to pHIFU applications in abdominal targets.

A Sonalleve magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) clinical system (Profound Medical, Mississauga, ON, Canada) has been shown to generate nonlinear ultrasound fields with shocks up to 100 MPa at the focus as required for HIFU applications such as boiling histotripsy of hepatic and renal tumors. The Sonalleve system has two versions V1 and V2 of the therapeutic array, with differences in focusing angle, focus depth, arrangement of elements, and the size of a central opening that is twice larger in the V2 system compared to the V1. The goal of this study was to compare the performance of the V1 and V2 transducers for generating high-amplitude shock-wave fields and to reveal the impact of different array geometries on shock amplitudes at the focus. Nonlinear modeling of the field in water using boundary conditions reconstructed from holography measurements shows that at the same power output, the V2 array generates 10-15-MPa lower shock amplitudes at the focus. Consequently, substantially higher power levels are required for the V2 system to reach the same shock-wave exposure conditions in histotripsy-type treatments. Although this difference is mainly caused by the smaller focusing angle of the V2 array, the larger central opening of the V2 array has a nontrivial impact. By excluding coherently interacting weakly focused waves coming from the central part of the source, the presence of the central opening results in a somewhat higher effective focusing angle and thus higher shock amplitudes at the focus. Axisymmetric equivalent source models were constructed for both arrays, and the importance of including the central opening was demonstrated. These models can be used in the "HIFU beam" software for simulating nonlinear fields of the Sonalleve V1 and V2 systems in water and flat-layered biological tissues.

Boiling histotripsy (BH) is a focused ultrasound technology that uses millisecond-long pulses with shock fronts to induce mechanical tissue ablation. The pulsing scheme and mechanisms of BH differ from those of cavitation cloud histotripsy, which was previously developed for benign prostatic hyperplasia. The goal of the work described here was to evaluate the feasibility of using BH to ablate fresh ex vivo human prostate tissue as a proof of principle for developing BH for prostate applications. Fresh human prostate samples (N = 24) were obtained via rapid autopsy (<24 h after death, institutional review board exempt). Samples were analyzed using shear wave elastography to ensure that mechanical properties of autopsy tissue were clinically representative. Samples were exposed to BH using 10- or 1-ms pulses with 1% duty cycle under real-time B-mode and Doppler imaging. Volumetric lesions were created by sonicating 1-4 rectangular planes spaced 1 mm apart, containing a grid of foci spaced 1-2 mm apart. Tissue then was evaluated grossly and histologically, and the lesion content was analyzed using transmission electron microscopy and scanning electron microscopy. Observed shear wave elastography characterization of ex vivo prostate tissue (37.9 ± 22.2 kPa) was within the typical range observed clinically. During BH, hyperechoic regions were visualized at the focus on B-mode, and BH-induced bubbles were also detected using power Doppler. As treatment progressed, hypoechoic regions of tissue appeared, suggesting successful tissue fractionation. BH treatment was twofold faster using shorter pulses (1 ms vs. 10 ms). Histological analysis revealed lesions containing completely homogenized cell debris, consistent with histotripsy-induced mechanical ablation. It was therefore determined that BH is feasible in fresh ex vivo human prostate tissue producing desired mechanical ablation. The study supports further work aimed at translating BH technology as a clinical option for prostate ablation., Competing Interests: Conflict of interest disclosure The authors declare no conflicts of interest., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

"HIFU beam" is a freely available software tool that comprises a MATLAB toolbox combined with a user-friendly interface and binary executable compiled from FORTRAN source code (HIFU beam. (2021). Available: http://limu.msu.ru/node/3555?language=en). It is designed for simulating high-intensity focused ultrasound (HIFU) fields generated by single-element transducers and annular arrays with propagation in flat-layered media that mimic biological tissues. Numerical models incorporated in the simulator include evolution-type equations, either the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation or one-way Westervelt equation, for radially symmetric ultrasound beams in homogeneous and layered media with thermoviscous or power-law acoustic absorption. The software uses shock-capturing methods that allow for simulating strongly nonlinear acoustic fields with high-amplitude shocks. In this article, a general description of the software is given along with three representative simulation cases of ultrasound transducers and focusing conditions typical for therapeutic applications. The examples illustrate major nonlinear wave effects in HIFU fields including shock formation. Two examples simulate propagation in water, involving a single-element source (1-MHz frequency, 100-mm diameter, 90-mm radius of curvature) and a 16-element annular array (3-MHz frequency, 48-mm diameter, and 35-mm radius of curvature). The third example mimics the scenario of a HIFU treatment in a "water-muscle-kidney" layered medium using a source typical for abdominal HIFU applications (1.2-MHz frequency, 120-mm diameter, and radius of curvature). Linear, quasi-linear, and shock-wave exposure protocols are considered. It is intended that "HIFU beam" can be useful in teaching nonlinear acoustics; designing and characterizing high-power transducers; and developing exposure protocols for a wide range of therapeutic applications such as shock-based HIFU, boiling histotripsy, drug delivery, immunotherapy, and others.

Large-volume soft tissue hematomas are a serious clinical problem, which, if untreated, can have severe consequences. Current treatments are associated with significant pain and discomfort. It has been reported that in an in vitro bovine hematoma model, pulsed high-intensity focused ultrasound (HIFU) ablation, termed histotripsy, can be used to rapidly and non-invasively liquefy the hematoma through localized bubble activity, enabling fine-needle aspiration. The goals of this study were to evaluate the efficiency and speed of volumetric histotripsy liquefaction using a large in vitro human hematoma model. Large human hematoma phantoms (85 cc) were formed by recalcifying blood anticoagulated with citrate phosphate dextrose/saline-adenine-glucose-mannitol solution. Typical boiling histotripsy pulses (10 or 2 ms) or hybrid histotripsy pulses using higher-amplitude and shorter pulses (0.4 ms) were delivered at 1% duty cycle while continuously translating the HIFU focus location. Histotripsy exposures were performed under ultrasound guidance with a 1.5-MHz transducer (8-cm aperture, F# = 0.75). The volume of liquefied lesions was determined by ultrasound imaging and gross inspection. Untreated hematoma samples and samples of the liquefied lesions aspirated using a fine needle were analyzed cytologically and ultrastructurally with scanning electron microscopy. All exposures resulted in uniform liquid-filled voids with sharp edges; liquefaction speed was higher for exposures with shorter pulses and higher shock amplitudes at the focus (up to 0.32, 0.68 and 2.62 mL/min for 10-, 2- and 0.4-ms pulses, respectively). Cytological and ultrastructural observations revealed completely homogenized blood cells and fibrin fragments in the lysate. Most of the fibrin fragments were less than 20 μm in length, but a number of fragments were up to 150 μm. The lysate with residual debris of that size would potentially be amenable to fine-needle aspiration without risk for needle clogging in clinical implementation., Competing Interests: Conflict of interest disclosure The authors declare no conflicts of interest., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. All rights reserved.)

Pulsed focused ultrasound (pFUS) uses short acoustic pulses delivered at low duty cycle and moderate intensity to noninvasively apply mechanical stress or introduce disruption to tissue. Ultrasound-guided pFUS has primarily been used for inducing cavitation at the focus, with or without contrast agents, to promote drug delivery to tumors. When applied in tandem with contrast agents, pFUS is often administered using an ultrasound imaging probe, which has a small footprint and does not require a large acoustic window. The use of nonlinear pFUS without contrast agents was recently shown to be beneficial for localized tissue disruption, but required higher ultrasound pressure levels than a conventional ultrasound imaging probe could produce. In this work, we present the design of a compact dual-use 1-MHz transducer for ultrasound-guided pFUS without contrast agents. Nonlinear pressure fields that could be generated by the probe, under realistic power input, were simulated using the Westervelt equation. In water, fully developed shocks of 42-MPa amplitude and peak negative pressure of 8 MPa were predicted to form at the focus at 458-W acoustic power or 35% of the maximum reachable power of the transducer. In absorptive soft tissue, fully developed shocks formed at higher power (760 W or 58% of the maximum reachable power) with the shock amplitude of 33 MPa and peak negative pressure of 7.5 MPa. The electronic focus-steering capabilities of the array were evaluated and found to be sufficient to cover a target with dimensions of 19 mm in axial direction and 44 mm in transversal direction.

Aim: of the study: demonstrate the feasibility of non-invasive mechanical disintegration of human prostate tissue using pulsed high-intensity focused ultrasound (pHIFU), a method termed boiling histotripsy., Materials and Methods: An ultrasound experimental system was developed for producing localized mechanical lesions in ex vivo biological tissue samples under ultrasound guidance. A series of experiments was carried out to create small single-focus lesions (volume < 2 mm3) and one large lesion (volume > 50 mm3) in ex vivo prostate tissue samples. After irradiation, two samples were bisected to visualize the region of destruction; the other tissue samples were examined histologically., Results: During pHIFU irradiation under B-mode ultrasound guidance, a region of increased echogenicity caused by formation of vapor-gas bubbles was visualized in the target region. After exposure, small and large lesions filled with a suspension of liquefied tissue were observed. Histological examination confirmed that the prostate tissue in the focal region was disintegrated into subcellular fragments., Conclusion: A pilot study showed the feasibility of using boiling histotripsy as a non-invasive method for treating prostate diseases.

The authors have recently shown that irregular reflections of spark-generated pressure weak shocks from a smooth rigid surface can be studied using an optical interferometer [Karzova, Lechat, Ollivier, Dragna, Yuldashev, Khokhlova, and Blanc-Benon, J. Acoust. Soc. Am. 145(1), 26-35 (2019)]. The current study extends these results to the reflection from rough surfaces. A Mach-Zehnder interferometer is used to measure pressure waveforms. Simulations are based on the solution of axisymmetric Euler equations. It is shown that roughness causes a decrease of the Mach stem height and the appearance of oscillations in the pressure waveforms. Close to rough surfaces, the pressure was higher compared to the smooth surface.

The irregular reflection of weak acoustic shock waves, known as the von Neumann reflection, has been observed experimentally and numerically for spherically diverging waves generated by an electric spark source. Two optical measurement methods are used: a Mach-Zehnder interferometer for measuring pressure waveforms and a Schlieren system for visualizing shock fronts. Pressure waveforms are reconstructed from the light phase difference measured by the interferometer using the inverse Abel transform. In numerical simulations, the axisymmetric Euler equations are solved using finite-difference time-domain methods and the spark source is modeled as an instantaneous energy injection with a Gaussian shape. Waveforms and reflection patterns obtained from the simulations are in good agreement with those measured by the interferometer and the Schlieren methods. The Mach stem formation is observed close to the surface for incident pressures within the range of 800 to 4000 Pa. Similarly, as for strong shocks generated by blasts, it is found that for spherical weak shocks the Mach stem length increases with distance following a parabolic law. This study confirms the occurrence of irregular reflections at acoustic pressure levels and demonstrates the benefits of the Mach-Zehnder interferometer method when microphone measurements cannot be applied.

Linear and nonlinear propagation of high amplitude acoustic pulses through a turbulent layer in air is investigated using a two-dimensional KZK-type (Khokhlov-Zabolotskaya-Kuznetsov) equation. Initial waves are symmetrical N-waves with shock fronts of finite width. A modified von Kármán spectrum model is used to generate random wind velocity fluctuations associated with the turbulence. Physical parameters in simulations correspond to previous laboratory scale experiments where N-waves with 1.4 cm wavelength propagated through a turbulence layer with the outer scale of about 16 cm. Mean value and standard deviation of peak overpressure and shock steepness, as well as cumulative probabilities to observe amplified peak overpressure and shock steepness, are analyzed. Nonlinear propagation effects are shown to enhance pressure level in random foci for moderate initial amplitudes of N-waves thus increasing the probability to observe highly peaked waveforms. Saturation of the pressure level is observed for stronger nonlinear effects. It is shown that in the linear propagation regime, the turbulence mainly leads to the smearing of shock fronts, thus decreasing the probability to observe high values of steepness, whereas nonlinear effects dramatically increase the probability to observe steep shocks.

Newer imaging and therapeutic ultrasound technologies may benefit from in situ pressure levels higher than conventional diagnostic ultrasound. One example is the recently developed use of ultrasonic radiation force to move kidney stones and residual fragments out of the urinary collecting system. A commercial diagnostic 2.3 MHz C5-2 array probe has been used to deliver the acoustic pushing pulses. The probe is a curvilinear array comprising 128 elements equally spaced along a convex cylindrical surface. The effectiveness of the treatment can be increased by using higher transducer output to provide a stronger pushing force; however nonlinear acoustic saturation can be a limiting factor. In this work nonlinear propagation effects were analyzed for the C5-2 transducer using a combined measurement and modeling approach. Simulations were based on the three-dimensional Westervelt equation with the boundary condition set to match low power measurements of the acoustic pressure field. Nonlinear focal waveforms simulated for different numbers of operating elements of the array at several output power levels were compared to fiber-optic hydrophone measurements and were found to be in good agreement. It was shown that saturation effects do limit the acoustic pressure in the focal region of a diagnostic imaging probe.

We present the results of a pilot study demonstrating the feasibility of non-invasive non-thermal disintegration of human mucinous carcinoma of the breast ex vivo using sequences of high-intensity focused ultrasound pulses in boiling histotripsy regimen. The target volume was sonicated by focusing ultrasound pulses (n=20) of 1.5 MHz frequency, 10-msec duration and 1-sec pulse repetition period, 517 W acoustic power within the pulse, and 103 MPa shock front amplitude at the focus into each node of a volumetric grid 4×4×1 mm. Sonication was visualized and controlled using B-mode ultrasound imaging, total time of the treatment was 21 min. Histological hematoxylin and eosin and Masson's trichrome staining revealed the absence of tumor elements in the treated region confirming destruction of cancer cells and their nuclei after boiling histotripsy procedure., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Accurate measurement of high-amplitude, broadband shock pulses in air is an important part of laboratory-scale experiments in atmospheric acoustics. Although various methods have been developed, specific drawbacks still exist and need to be addressed. Here, a schlieren optical method was used to reconstruct the pressure signatures of nonlinear spherically diverging short acoustic pulses generated using an electric spark source (2.5 kPa, 33 μs at 10 cm from the source) in homogeneous air. A high-speed camera was used to capture light rays deflected by refractive index inhomogeneities, caused by the acoustic wave. Pressure waveforms were reconstructed from the light intensity patterns in the recorded images using an Abel-type inversion method. Absolute pressure levels were determined by analyzing at different propagation distances the duration of the compression phase of pulses, which changed due to nonlinear propagation effects. Numerical modeling base on the generalized Burgers equation was used to evaluate the smearing of the waveform caused by finite exposure time of the high-speed camera and corresponding limitations in resolution of the schlieren technique. The proposed method allows the study of the evolution of spark-generated shock waves in air starting from the very short distances from the spark, 30 mm, up to 600 mm.

The aim of this study is to show the evidence of Mach stem formation for very weak shock waves with acoustic Mach numbers on the order of 10(-3) to 10(-2). Two representative cases are considered: reflection of shock pulses from a rigid surface and focusing of nonlinear acoustic beams. Reflection experiments are performed in air using spark-generated shock pulses. Shock fronts are visualized using a schlieren system. Both regular and irregular types of reflection are observed. Numerical simulations are performed to demonstrate the Mach stem formation in the focal region of periodic and pulsed nonlinear beams in water.

Background: There is increasing interest in using ultrasound for thermal ablation, histotripsy, and thermal or cavitational enhancement of drug delivery for the treatment of pancreatic cancer. Ultrasonic and thermal modelling conducted as part of the treatment planning process requires acoustic property values for all constituent tissues, but the literature contains no data for the human pancreas., Purpose: This study presents the first acoustic property measurements of human pancreatic samples and provides examples of how these properties impact a broad range of ultrasound therapies., Methods: Data were collected on human pancreatic tissue samples at physiological temperature from 23 consented patients in cooperation with a hospital pathology laboratory. Propagation of ultrasound over the 2.1-4.5 MHz frequency range through samples of various thicknesses and pathologies was measured using a set of custom-built ultrasonic calipers, with the data processed to estimate sound speed and attenuation. The results were used in acoustic and thermal simulations to illustrate the impacts on extracorporeal ultrasound therapies for mild hyperthermia, thermal ablation, and histotripsy implemented with a CE-marked clinical system operating at 0.96 MHz., Results: The mean sound speed and attenuation coefficient values for human samples were well below the range of values in the literature for non-human pancreata, while the human attenuation power law exponents were substantially higher. The simulated impacts on ultrasound mediated therapies for the pancreas indicated that when using the human data instead of the literature average, there was a 30% reduction in median temperature elevation in the treatment volume for mild hyperthermia and 43% smaller volume within a 60°C contour for thermal ablation, all driven by attenuation. By comparison, impacts on boiling and intrinsic threshold histotripsy were minor, with peak pressures changing by less than 15% (positive) and 1% (negative) as a consequence of the counteracting effects of attenuation and sound speed., Conclusion: This study provides the most complete set of speed of sound and attenuation data available for the human pancreas, and it reiterates the importance of acoustic material properties in the planning and conduct of ultrasound-mediated procedures, particularly thermal therapies., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Histotripsy is a relatively new therapeutic ultrasound technology to mechanically liquefy tissue into subcellular debris using high-amplitude focused ultrasound pulses. In contrast to conventional high-intensity focused ultrasound thermal therapy, histotripsy has specific clinical advantages: the capacity for real-time monitoring using ultrasound imaging, diminished heat sink effects resulting in lesions with sharp margins, effective removal of the treated tissue, a tissue-selective feature to preserve crucial structures, and immunostimulation. The technology is being evaluated in small and large animal models for treating cancer, thrombosis, hematomas, abscesses, and biofilms; enhancing tumor-specific immune response; and neurological applications. Histotripsy has been recently approved by the US Food and Drug Administration to treat liver tumors, with clinical trials undertaken for benign prostatic hyperplasia and renal tumors. This review outlines the physical principles of various types of histotripsy; presents major parameters of the technology and corresponding hardware and software, imaging methods, and bioeffects; and discusses the most promising preclinical and clinical applications. [ABSTRACT FROM AUTHOR]

Extracorporeal shock wave therapy (ESWT) achieves its therapeutic purpose mainly through the biological effects produced by the interaction of shock waves with tissues, and the accurate measurement and calculation of the mechanical parameters of shock waves in tissues are of great significance in formulating the therapeutic strategy and evaluating the therapeutic effect. This study utilizes the approach of implanting flexible polyvinylidene fluoride (PVDF) vibration sensors inside the tissue-mimicking phantom of various thicknesses to capture waveforms at different depths during the impact process in real time. Parameters including positive and negative pressure changes (P + , P - ), pulse wave rise time ([Formula: see text]), and energy flux density (EFD) are calculated, and frequency spectrum analysis of the waveforms is conducted. The dynamic response, propagation process, and attenuation law of the shock wave in the phantom under different impact intensities were analyzed. Results showed that flexible PVDF sensors could precisely acquire the characteristics of pulse waveform propagating within the phantom. At the same depth, as the driving pressure increases, P + and P - increase linearly, and [Formula: see text] remains constant. At the same driving pressure, P + , P - , and EFD decay exponentially with increasing propagation depth. At the same depth, the spectra of pulse waveforms are similar, and the increasing driving pressure does not cause significant changes in carrier frequency and modulation frequency. The research findings could provide a reference for developing ESWT devices, improving treatment strategies, and enhancing the safety of clinical applications., Competing Interests: Declarations. Ethical approval: This is an observational study. The Beihang University Research Ethics Committee has confirmed that no ethical approval is required. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2025. Australasian College of Physical Scientists and Engineers in Medicine.)

The exponential growth of therapeutic ultrasound applications demonstrates the power of the technology to leverage the combinations of transducer technology and treatment monitoring techniques to effectively control the preferred bioeffect to elicit the desired clinical effect.Objective: This review provides an overview of the most commonly used bioeffects in therapeutic ultrasound and describes existing transducer technologies and monitoring techniques to ensure treatment safety and efficacy.Methods and materials: Literature reviews were conducted to identify key choices that essential in terms of transducer design, treatment parameters and procedure monitoring for therapeutic ultrasound applications. Effective combinations of these options are illustrated through descriptions of several clinical indications, including uterine fibroids, prostate disease, liver cancer, and brain cancer, that have been successful in leveraging therapeutic ultrasound to provide effective patient treatments.Results: Despite technological constraints, there are multiple ways to achieve a desired bioeffect with therapeutic ultrasound in a target tissue. Visualizations of the interplay of monitoring modality, bioeffect, and applied acoustic parameters are presented that demonstrate the interconnectedness of the field of therapeutic ultrasound. While the clinical indications explored in this review are at different points in the clinical evaluation path, based on the ever expanding research being conducted in preclinical realms, it is clear that additional clinical applications of therapeutic ultrasound that utilize a myriad of bioeffects will continue to grow and improve in the coming years.Conclusions: Therapeutic ultrasound will continue to improve in the next decades as the combination of transducer technology and treatment monitoring techniques will continue to evolve and be translated in clinical settings, leading to more personalized and efficient therapeutic ultrasound mediated therapies. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the feasibility of using a ring array ultrasound (US) transducer, guided by ultrasound tomography (UST), for generating and monitoring mild hyperthermia (MHTh). Methods: In silico and in vitro experiments were designed to evaluate the efficacy of a ring array US transducer for generating MHTh and monitoring changes in temperature. In a series of in silico studies, we compared the acoustic focal profiles produced by a ring array US transducer transmitting at different frequencies and further investigated the effectiveness of UST-guidance in implementing aberration correction to enhance the focal profile. In vitro experiments evaluated the capability of using a ring array US transducer to generate and maintain MHTh and the accuracy of using UST to monitor temperature changes. Results: The simulations demonstrated that a ring array US transducer achieves symmetrical and localized acoustic focusing. In a heterogenous tissue model, a ring array US transducer achieved a superior acoustic focus by implementing aberration correction with guidance from UST. In vitro experiments demonstrated the capability of a ring array US transducer to generate MHTh in a tissue-mimicking phantom in an average of 117 ± 18 s and subsequently maintain MHTh. Lastly, a ring array US transducer utilized UST to track temperature changes in a preheated water-filled inclusion while it passively cooled from 45 °C to 25 °C, with a maximum error of 0.58 °C. Conclusion: A ring array US transducer can noninvasively generate and monitor MHTh, overcoming many limitations of current clinical systems. The closed geometry of the transducer is optimal for acoustic focusing and UST-guidance allows for improved aberration correction in a heterogenous medium. Utilizing UST thermometry with the same ring array US transducer will allow for implementing an image-guided, temperature-controlled, all-acoustic MHTh system. [ABSTRACT FROM AUTHOR]

Introduction: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation. Methods: In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups. Results: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability. Conclusion: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon. [ABSTRACT FROM AUTHOR]

Partial differential equations (PDEs) can be solved numerically by finite element method (FEM). θ -difference FEM scheme carries out spatial discretization with FEM and temporal discretization with θ -difference scheme which is the generalization of forward Euler scheme, backward Euler scheme and Crank–Nicolson (CN) scheme. In this paper, C-Bézier basis is used to construct finite dimensional subspace of FEM and full-discrete scheme of parabolic equations is developed with θ -difference FEM scheme. In addition, the stability and error estimation of θ -difference FEM scheme are analyzed. While 0 < θ < 1 2 , θ -difference FEM scheme is conditionally stable, and 1 2 ≤ θ ≤ 1 , this scheme is unconditionally stable. Furthermore, some numerical examples are given to verify the effectiveness of θ -difference FEM scheme. It's worth noting that the numerical precision of C-Bézier basis is improved 3–5 orders of magnitude comparing with classical Lagrange basis and it also has higher numerical accuracy than CN finite difference method(FDM) and backward FDM. [ABSTRACT FROM AUTHOR]

Background: Focused ultrasound therapy has been widely used for the treatment of various diseases, employing different types of transducers. The focused ultrasound pressure fields inevitably exhibit nonlinear effects, which can influence the ablation region. However, the nonlinear effects exhibit noticeable variations across different applications. The characterization of the nonlinear pressure fields of ultrasound is important for the effective implementation of focused ultrasound therapy., Purpose: The traditional angular spectrum method (ASM) was extended to accurately and efficiently simulate the propagation of weakly nonlinear ultrasound in heterogeneous mediums of clinical model. The nonlinear effects were further analyzed in relationship to the transducer parameters that are different in various applications., Methods: The pressure fields were simulated using the extended ASM, incorporating calculations for phase aberration in the frequency domain and magnitude compensation in the spatial domain to account for heterogeneous acoustic impedance mismatch. Validation was performed by comparison to k-Wave simulation results using two simplified clinical models, an abdominal soft tissue and a transcranial skull model. The nonlinear effects were then analyzed in relation to the transducer parameters of f-number and effective source area based on the same acoustic output power. The analysis of nonlinear effects was conducted under both homogeneous medium and the clinical models., Results: The simulation results demonstrated a maximum error of 3.93% in the calculated harmonic pressure of the abdominal model, and a maximum error of 4.89% within the transcranial model when comparing the extended ASM simulation results to those obtained from k-Wave simulations. The characterization of the nonlinear effects reveals a strong correlation with the transducer parameters. Specifically, the results indicate that the nonlinear effects intensify with an increase in the effective source area and f-number, under the same acoustic output power of the transducer. However, the clinical model also showed an influence on the nonlinear effects in relation to the f-number., Conclusion: The extended ASM was demonstrated as an accurate and efficient simulation tool, and the simulation results provide a reference for evaluating the intensity of nonlinear effects in various transducer designs., (© 2024 American Association of Physicists in Medicine.)

Renal anisotropy is a complex property of the kidney and often poses a challenge in obtaining consistent measurements when using shear wave elastography to detect chronic kidney disease. To circumvent the challenge posed by renal anisotropy in clinical settings, a dimensionless biomarker termed the 'anisotropic ratio' was introduced to establish a correlation between changes in degree of renal anisotropy and progression of chronic kidney disease through an in silico perspective. To achieve this, an efficient model reduction approach was developed to model the anisotropic property of kidneys. Good agreement between the numerical and experimental data were obtained, as percentage errors of less than 5.5% were reported when compared against experimental phantom measurement from the literature. To demonstrate the applicability of the model to clinical measurements, the anisotropic ratio of sheep kidneys was quantified, with both numerical and derived experimental results reporting a value of .667. Analysis of the anisotropic ratio with progression of chronic kidney disease demonstrated that patients with normal kidneys would have a lower anisotropic ratio of .872 as opposed to patients suffering from renal impairment, in which the anisotropic ratio may increase to .904, as determined from this study. The findings demonstrate the potential of the anisotropic ratio in improving the detection of chronic kidney disease using shear wave elastography., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Introduction: Accurate temperature and thermal lesion prediction is very important for high-intensity focused ultrasound (HIFU) in the treatment of tumors. The traditional focal temperature and thermal lesion prediction methods usually use constant acoustic and thermal parameters. However, HIFU irradiation of biological tissue will cause its temperature rise and change the tissue characteristic parameters, which will affect the sound field and temperature field. Material and Methods: The constant acoustic and thermal parameters, dynamic acoustic and thermal parameters, constant acoustic and dynamic thermal parameters, dynamic acoustic and constant thermal parameters were used for simulation by Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation and Pennes biological heat transfer equation (PBHTE), and their effects and differences on the focal temperature and thermal lesion of biological tissue were compared and analyzed. Results: The focal temperature predicted by constant acoustic parameters was less than that predicted by dynamic acoustic parameters, and the thermal lesion area predicted by constant acoustic parameters was also smaller than that predicted by dynamic acoustic parameters. On the premise of using dynamic acoustic parameters, the focal temperature predicted by dynamic thermal parameters was higher than that predicted by constant thermal parameters. When the acoustic parameters remained constant, the focal temperature predicted by dynamic thermal parameters was lower than that predicted by constant thermal parameters, but their predicted thermal lesion areas were almost the same. Conclusion: The temperature-dependent acoustic and thermal parameters should be considered when predicting focal temperature and thermal lesion of biological tissue, so that doctors can use the appropriate thermal dose in the surgical treatment of HIFU. [ABSTRACT FROM AUTHOR]

Introduction: The large aperture concave spherical focused ultrasonic transducer has stronger acoustic focusing effect and can obtain good temperature rise effect. The purpose of this study was to explore the effect of different frequency, duty cycle and inner radius parameters on temperature rise of multi-layer biological tissue. Material and Methods: The simulation model of high-intensity focused ultrasound (HIFU) irradiated multilayer biological tissue was constructed. By changing the irradiation frequency, duty cycle and inner radius of large aperture concave spherical focused ultrasonic transducer, the sound field and temperature field of multilayer biological tissue were simulated and calculated by using Westervelt nonlinear acoustic wave equation and Pennes biological heat conduction equation, respectively. Results: The intensity of sound field increased with the increase of frequency, while it decreased with the increase of inner radius, but the duty cycle almost had no effect on the intensity of sound field. The focal temperature increased with the increase of frequency and duty cycle, but decreased with the increase of inner radius. Conclusion: By selecting appropriate parameters of transducer, the optimum temperature rise in the target area of biological tissue can be obtained by using a large aperture concave spherical focused ultrasonic transducer. [ABSTRACT FROM AUTHOR]

Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons. In vivo Achilles tendons (n = 28) from 15–20kg Yorkshire pigs (n = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed. Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16° to 27°. There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm2, 53.2mm2, 77.8mm2 and 91.6mm2. The average areas of skin necrosis were 5.4mm2, 21.8mm2, 37.2mm2, and 91.4mm2. Histologic analysis confirmed tissue ablation and structural collagen fiber disruption. This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions. [ABSTRACT FROM AUTHOR]

Since its inception about two decades ago, histotripsy – a non-thermal mechanical tissue ablation technique – has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity. In addition, most types of histotripsy rely on the presence of high-amplitude shocks that develop in the pressure profile at the focus due to nonlinear propagation effects. Those requirements, in turn, dictate aspects of the instrument design, both in terms of driving electronics, transducer dimensions and intensity limitations at surface, shape (primarily, the F-number) and frequency. The combination of the optimized instrumentation and the bio-effects from bubble activity and streaming on different tissues, lead to target clinical applications for each histotripsy method. Here, the differences and similarities in the physical mechanisms and resulting bioeffects of each method are reviewed and tied to optimal instrumentation and clinical applications. [ABSTRACT FROM AUTHOR]

Spherical weak blast propagation above a rough periodic surface is investigated by performing numerical simulations of the Euler equations. The study of the reflection pattern shows that waves diffracted by the surface asperities merge to form an effective reflected shock. It is initially detached from the incident shock but gradually catches up with it. If the source energy is sufficient, the reflected shock interacts with the incident one and Mach reflection occurs. Thus, the triple point has a similar trajectory to that over a smooth surface. In addition, the maximal overpressure is shown to be greater for small roughness scales in a layer near the surface. Far from the surface, it is close to that of a smooth surface for small roughness scales and to the free field for the highest ones. The increase in the maximal overpressure is related to oscillations on the waveforms that appear behind the shock. These properties are associated with the existence of a surface wave that propagates along the surface. Comparison of results in the linear regime with an analytic solution confirms this explanation. [ABSTRACT FROM AUTHOR]

Casualty analysis of major terrorist attacks in recent decades shows an enormous increase in fatalities and economic losses. Due to frequent terrorist attacks and failure of engineering structures under blast load, this issue has gained the attention of scientists and structural engineers. Recently, threat due to explosions is considerably raised owing to the availability of small size explosive devices with powerful and high range explosive materials. Thus, there is an immediate need for the structures, vulnerable to such tragic events, to be analysed and designed to resist these extreme loading conditions. To predict the behavior of structure under explosion loads, blast load analysis needs to be done. The effective blast parameters such as standoff distance, angle of incidence, explosive type and charge weight with its damaging effects discussed by various researchers have been overviewed in the present work. Further, it is uneconomical to harden the structure to resist the blast load. Therefore, certain strategies which can be adapted to mitigate the effect of blast pressure have also been analysed, and discussed different analytical models for prediction of blast loads. The paper present basics of blast for beginner researchers and structural engineers to understand such complex loading scenario. [ABSTRACT FROM AUTHOR]

Purpose: In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments repositioned with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments are compared between the C5-2 and a custom (SC-50) probe that produces a longer focal beam and burst duration. Materials and Methods: Effectiveness was quantified by the number of stones expelled from a calyx phantom consisting of a 30-mm deep, water-filled well in a block of tissue mimicking material. Each probe was positioned below the phantom to move stones against gravity. Single propulsion bursts of 50 ms or 3 s duration were applied to three separate targets: 10 fragments of 2 different sizes (1-2 and 2-3 mm) and a single 4 × 7 mm human stone. Safety studies consisted of porcine kidneys exposed to an extreme dose of 10-minute burst duration, including a 7-day survival study and acute studies with surgically implanted stones. Results: Although successful in the clinical trial, the shorter focal beam and maximum 50 ms burst duration of the C5-2 probe moved stones, but did not expel any stones from the phantom's 30-mm deep calyx. The results were similar with the SC-50 probe under the same 50 ms burst duration. Longer (3 s) bursts available with the SC-50 probe expelled all stones at both 4.5 and 9.5 cm 'skin-to-stone' depths with lower probe heating compared to the C5-2. No abnormal behavior, urine chemistry, serum chemistry, or histological findings were observed within the kidney or surrounding tissues for the 10 min burst duration used in the animal studies. Conclusions: A longer focal beam and burst duration improved expulsion of a stone and multiple stone fragments from a phantom over a broad range of clinically relevant penetration depths and did not cause kidney injury in animal studies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to simulate the effect of high intensity focused ultrasound (HIFU) in non-homogenous medium for targeting atherosclerotic plaques in vivo. Materials and methods: A finite-difference time-domain heterogeneous model for acoustic and thermal tissue response in the treatment region was derived from ultrasound images of the treatment region. A 3.5 MHz dual mode ultrasound array suitable for targeting peripheral vessels was used. The array has a lateral and elevation focus at 40 mm with fenestration in its centre through which a 7.5 MHz diagnostic transducer can be placed. Two cases were simulated where seven adjacent HIFU shots (∼5000 W/cm2, 2-s exposure time) were targeted on the plaque tissue within the femoral artery. The transient bioheat equation with a convective term to account for blood flow was used to predict the thermal dose. The results of the simulation model were then validated against the histology data. Results: The simulation model predicted the HIFU-induced damage for both cases, and correlated well with the histology data. For the first case thermal damage was detected within the targeted plaque, while for the second case thermal damage was detected in the pre-focal region. Conclusion: The results suggest that a realistic, image-based acoustic and thermal model of the treatment region is capable of predicting the extent of thermal damage to target plaque tissue. The model considered the effect of the wall thickness of large arteries and the heat-sink effect of flowing blood. The model is used for predicting the size and pattern of HIFU damage in vivo. [ABSTRACT FROM AUTHOR]

The efficiency of shock wave lithotripsy (SWL), a noninvasive firstline therapy for millions of nephrolithiasis patients, has not improved substantially in the past two decades, especially in regard to stone clearance. Here, we report a new acoustic lens design for a contemporary electromagnetic (EM) shock wave lithotripter, based on recently acquired knowledge of the key lithotripter field characteristics that correlate with efficient and safe SWL. The new lens design addresses concomitantly three fundamental drawbacks in EM lithotripters, namely, narrow focal width, nonidealized pulse profile, and significant misalignment in acoustic focus and cavitation activities with the target stone at high output settings. Key design features and performance of the new lens were evaluated using model calculations and experimental measurements against the original lens under comparable acoustic pulse energy (E+) of 40 mJ. The -6-dB focal width of the new lens was enhanced from 7.4 to 11 mm at this energy level, and peak pressure (41 MPa) and maximum cavitation activity were both realigned to be within 5 mm of the lithotripter focus. Stone comminution produced by the new lens was either statistically improved or similar to that of the original lens under various in vitro test conditions andwas significantly improved in vivo in a swine model (89% vs. 54%, P = 0.01), and tissue injury was minimal using a clinical treatment protocol. The general principle and associated techniques described in this work can be applied to design improvement of all EM lithotripters. [ABSTRACT FROM AUTHOR]

There is a dearth of information on the reflection of very weak shock waves on curved surfaces; and particularly a distinct lack of experimental data at Mach numbers below 1.03. A previous study at Mach numbers between 1.03 and 1.05 showed that there are variations in the accepted reflection evolution on curved surfaces. That work indicated the existence of an apparent regular refection pattern in the curved shock wave reflection evolution which is also predicted for very much weaker waves in acoustic studies. To improve spatial resolution, the current study is performed in a large shock tube with a test section height of 450 mm using a 520 mm radius curved test piece with zero initial ramp angle. Imaging is primarily using shadowgraphy and high-speed photography. Experiments concentrated on tests in a range of 1.007 ≤ M ≤ 1.09 with some tests at higher values. No shear layer is evident at the lower Mach numbers as for von Neumann and weak Mach reflection patterns. Transitioned regular reflection appears to cease at incident Mach numbers below 1.07. A reflection pattern resembling a regular reflection exists in the transition between the three-shock patterns and transitioned regular reflection. [ABSTRACT FROM AUTHOR]