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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]

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. [ABSTRACT FROM AUTHOR]

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]

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]