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Background: High‐intensity focused ultrasound (HIFU) and radiofrequency (RF) are non‐invasive modalities for skin rejuvenation, but their combined effects have not been evaluated. Objective: We evaluated and compared the efficacy of HIFU alone and combined HIFU and bipolar RF using a newly designed probe. Methods: Twenty‐two Korean adults with facial wrinkles and aging underwent treatment on both sides of their face: HIFU‐only on the left and HIFU combined with RF on the right. Skin parameters were measured at different time points to evaluate the improvement in skin rejuvenation. Results: HIFU treatment significantly improved skin parameters, including pore volume and number, skin elasticity, depth of eye wrinkles, degree of sagging in the eye area, nasolabial folds and cheeks, volume of the jawline, skin density, and permittivity. Furthermore, combining bipolar RF with HIFU treatment enhanced efficacy in reducing pore number, improving skin elasticity, diminishing eye wrinkle depth, and increasing skin moisturization. These findings indicate that bipolar RF can synergically improve skin rejuvenation by providing a thermal effect to the upper papillary dermis, which is more superficial than the target area of HIFU. Conclusion: Combining HIFU with bipolar RF synergistically improves skin rejuvenation, including pore reduction, periorbital wrinkle improvement, skin elasticity, and skin moisturization. [ABSTRACT FROM AUTHOR]

Objectives: This study intended to compare the safety and clinical efficacy between two treatments of uterine fibroids: laparoscopic myomectomy (LM) and high intensity focused ultrasound (HIFU). Material and methods: Clinical data were collected from 587 uterine fibroid patients who were treated in The People's Hospital of Nanchuan, Chongqing from January 1, 2018 to December 31, 2019. Among the patients, 287 cases were treated with HIFU (observation group), and 300 cases were treated with LM (control group). The progression-free survival (PFS) was taken as the primary endpoint. The secondary endpoints included operation results (including operative time, intraoperative blood loss, and intraoperative fluid replacement), complications, hemoglobin level one month after surgery and clinical efficacy. In addition, the fibroid volume of the observation group before treatment and 3, 6, and 12 months after treatment were also analyzed. Results: The operative time of observation group was evidently shortened compared to the control group, and the intraoperative blood loss and intraoperative fluid replacement of observation group were also considerably reduced (all p < 0.05), but there was no significant difference in the hemoglobin level between the two groups one month after surgery (p > 0.05). In terms of curative effect, the total effective rate of HIFU group and LM group was 98.6% (283/287) and 95.3% (286/300) respectively, with statistically significant difference (p < 0.05). In terms of complications, the incidence of bleeding and infection in HIFU group was obviously lower than that in LM group (both p < 0.05), while no significant differences were observed in the remaining complications (all p > 0.05). Fibroid volume comparisons before treatment and 3, 6 and 12 months after operation in observation group showed that fibroid volume decreased significantly (all p < 0.05). The median follow-up time was 30.6 months. The mean PFS of patients in the observation group and control group was 29.71 months (95% CI 28.24-29.75) and 26.74 months (95% CI 26.49-28.33), respectively (HR 0.47; 95% CI, 0.29 to 0.76; Log-rank p = 0.0019). Conclusions: HIFU could improve the intraoperative efficacy and reduce the complications of patients with uterine fibroids and has excellent performance in improving clinical efficacy and prolonging PFS. HIFU can be used as an alternative to surgical treatment. [ABSTRACT FROM AUTHOR]

Objectives: Microfocused ultrasound (MFU) and hyaluronic acid (HA) filler injection are increasingly popular aesthetic procedures. HA filler injection is generally recommended after MFU if combined treatment is required in a single visit. However, data regarding the safe and optimal time of MFU treatment after HA injection is still limited. The purpose of this study was to evaluate the degree of HA loss when performing MFU treatment after dermal filler injection. Methods: Fourteen subjects were recruited in this pilot study. HA was injected intradermally on four 2 × 2 cm areas at the abdomen (0.25 ml/site). Site A was served as control whereas site B, C, D were treated with MFU using 1.5 mm transducer at 60 min, Day 14, and Day 28 after the injection, respectively. All experimental sites were biopsied using a 3‐mm punch biopsy to evaluate the histopathological profile at baseline and Day 56. Grading of the quantity of retained HA was evaluated by a blinded experienced dermatopathologist. Results: All 14 subjects completed the study. One subject has been excluded due to the poor quality of histopathologic slides. Seven subjects (53.9%) at site B and 6 subjects (46.2%) at site C had HA loss at Day 56 compared with baseline. The mean HA grading at baseline and Day 56 was 3.7 vs. 2.8 (p < 0.001) at site B and 3.7 vs. 3.0 (p = 0.001) at site C, respectively. There was no statistical difference between the mean HA grading at baseline and Day 56 at site D (3.7 vs. 3.3, p = 0.073). No inflammation or granuloma was observed on Day 56 of the study. Conclusions: MFU treatment after HA injection appears to be safe. However, some degree of HA loss was observed if MFU treatment was done within 2 weeks after HA injection. [ABSTRACT FROM AUTHOR]

This review article reviews the published results of the clinical use of intravaginal non-invasive HIFU therapy for the treatment of urogenital atrophy, stress urinary incontinence, and wide vagina syndrome. Vaginal distension and genitourinary syndromes of menopause create physical, psychological, and functional problems for women and their partners. Existing invasive treatments can lead to certain complications, so safer and more effective minimally invasive medicine is desirable. Our goal was to evaluate the efficacy and safety of microfocus ultrasound therapy as a form of non-invasive HIFU therapy administered in the vaginal canal in female patients. This review uses the results of a number of recent studies from Argentina, Poland, Japan and other countries using medical devices: Feminine HIFU, manufactured by Sveltia, Argentina, and Ultra Vera, manufactured by Hironic, Republic of Korea. The purpose of the study is to study the results of the clinical application of high-intensity focused ultrasound as a new treatment method in the field of gynecology. High Intensity Focused Ultrasound (HIFU) is a new technology in gynecology that involves regenerative thermal effects on deeper layers of vaginal tissues that cannot be achieved with laser and radio frequency equipment. The results of studies with a total number of participants in more than 100 patients from several groups who underwent clinical examination support suggestions for a potential therapeutic effect as a preferred method of therapy or an addition to laser and other methods of treatment, supported by an evidence base. The value of the study is to provide effective treatment of pathologies due to the formation of new collagen fibers that create a structural framework in the fascial plate of the vagina and adjacent fascia, and the muscles of the small pelvis due to a certain mode of HIFU exposure. The results are promising and motivate further research. [ABSTRACT FROM AUTHOR]

Background: The treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility. Case presentation: A 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up. Conclusion: Ultrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding. [ABSTRACT FROM AUTHOR]

In the medical field, ultrasound is commonly used for diagnostic imaging due to its ability to provide real-time images. However, High-Intensity Focused Ultrasound (HIFU) is also used for other clinical purposes, such as thermal tissue ablation. In the case of varicose veins, the potential role and benefits of HIFU have been known for a long time despite in-vivo results have mostly been preliminary and experimental, particularly regarding its effect on venous wall. The aim of this brief report is to describe how HIFU acts on venous wall in human incompetent great saphenous veins. [ABSTRACT FROM AUTHOR]

Epilepsy affects about 1% of the population. Approximately one third of patients with epilepsy are drug-resistant (DRE). Resective surgery is an effective treatment for DRE, yet invasive, and not all DRE patients are suitable resective surgery candidates. Focused ultrasound, a novel non-invasive neurointerventional method is currently under investigation as a treatment alternative for DRE. By emitting one or more ultrasound waves, FUS can target structures in the brain at millimeter resolution. High intensity focused ultrasound (HIFU) leads to ablation of tissue and could therefore serve as a non-invasive alternative for resective surgery. It is currently under investigation in clinical trials following the approval of HIFU for essential tremor and Parkinson's disease. Low intensity focused ultrasound (LIFU) can modulate neuronal activity and could be used to lower cortical neuronal hyper-excitability in epilepsy patients in a non-invasive manner. The seizure-suppressive effect of LIFU has been studied in several preclinical trials, showing promising results. Further investigations are required to demonstrate translation of preclinical results to human subjects. [ABSTRACT FROM AUTHOR]

Introduction: As a non-invasive method of tumor hyperthermia, high intensity focused ultrasound (HIFU) has been widely used in the treatment of various solid tumors in recent years. The purpose of this study was to investigate the effect of HIFU combined with ethanol on biological tissue lesions. Material and Methods: Firstly, 0.5ml 95% ethanol was injected into the porcine liver tissue in vitro, then HIFU was used to irradiate the porcine liver. The B-mode ultrasound and needle hydrophone were used to monitor the cavitation. A thermocouple was also used to measure the real-time focal temperature. The ultrasonic signal scattered at the focal point of HIFU irradiation was collected by the fiber hydrophone, and the attenuation coefficient was calculated. Finally, the attenuation coefficient was input into the Khokhlov-Zabolotskaya-Kuznetov (KZK) equation and combined with the Pennes equation. The thermal lesion of the porcine liver was simulated by MATLAB software. Results: The length of the long axis of the lesion area simulated by the attenuation coefficient of cavitation was closer to the length of the long axis of the actual measured lesion area with ethanol injection, but the length of the short axis of the simulated lesion area was smaller than that of the measured lesion area. However, the length of the long axis of the lesion area simulated by the attenuation coefficient of cavitation was larger than the length of the long axis of the lesion area simulated by the attenuation coefficient of liver at room temperature. The same results were obtained for the length of short axis. Conclusion: HIFU combined with ethanol can produce larger lesions to biological tissues and improve the therapeutic effect. [ABSTRACT FROM AUTHOR]

The acoustic propagation characteristic of ultrasound determines that the energy of ultrasound beam will decrease with the increase of its propagation depth in the body. Similarly, the energy of High Intensity Focused Ultrasound (HIFU) will be attenuated with the increase of HIFU propagation depth in the body. Ensuring sufficient ultrasound energy deposition in the HIFU ablation region for tumor ablation is usually achieved by increasing the ultrasound irradiation power or prolonging the ultrasound ablation time. However, these two methods may damage the normal tissue adjacent to the HIFU ablation region. Herein, we constructed the nanoparticles conjugated with tumor-homing bacteria as the biological tumor-homing synergist to facilitate HIFU-mediated tumor ablation avoiding the potential safety risk. In our strategy, Bifidobacterium bifidum (B. bifidum) was selectively colonized in the hypoxic region of solid tumors after been injected into 4T1 breast cancer bearing-BALB/c mice via the tail vein due to its anaerobic growth characteristic. The amount of B. bifidum with negative surface potential in the hypoxic region of solid tumors was increased by its anaerobic proliferation. Polyethylenimine (PEI) -modified Poly (lactic- co -glycolic) acid nanoparticles loaded sodium bicarbonate (PEI-PLGA-NaHCO 3 -NPs) with positive surface potential injected into 4T1 breast cancer bearing-BALB/c mice via the tail vein displayed the tumor-homing ability by the electrostatic adsorption with B. bifidum colonized solid tumors. PEI-PLGA-NaHCO 3 -NPs could release NaHCO 3 to produce carbon dioxide (CO 2) as cavitation nuclei inside the acidic microenvironment of solid tumors. When HIFU irradiated solid tumors contained with more cavitation nuclei, the ultrasound energy deposition at the tumor region was increased to destroy the tumors more effectively. Meanwhile, the improved efficiency of HIFU-mediated tumor ablation reduced the dependence of the tumor ablation on the ultrasound energy dose, which improved the safety of HIFU-mediated tumor ablation to the non-targeted ablation tissue. This tumor-homing synergist shows the potential application value on the HIFU-mediated tumor ablation in the clinical. • There is a strong electrostatic adsorption between PEI-PLGA-NaHCO 3 -NPs and tumor-homing B. bifidum. • PEI-PLGA-NaHCO 3 -NPs enter tumors more quickly with a larger quantity and remain longer by the electrostatic adsorption. • PEI-PLGA-NaHCO 3 -NPs produce CO 2 inside tumor acidic microenvironment to facilitate HIFU-mediated tumor ablation. • Good biocompatibility and biosafety guarantee the further applications of this synergist in HIFU-mediated tumor ablation. [ABSTRACT FROM AUTHOR]

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect. Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (<1–2 h) treatment effects. Temperature was measured in vivo via MR thermometry. Histological data was collected for lesion assessment. Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters. Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment. [ABSTRACT FROM AUTHOR]

Findings from numerical investigation of thermal aspects of tissue phantoms subjected to high intensity focused ultrasound (HIFU) during the process of multiple sonications have been presented. Various scanning pathways are chosen to deliver the acoustic energy and to place multiple lesions at the desired locations within the tissue. A new scanning method based on the calculation of the largest distance between any two consecutive lesions is proposed and developed, which can possibly reduce the total treatment time by eliminating the cooling period. This new approach is compared with conventional scanning methods, namely, raster scan, spiral scan from the center outwards and spiral scan from the outside to the center. Various parameters that affect the thermal response of the tissue due to the generation of multiple lesions are defined and studied so that the energy that is given to each spot can be modulated. It is found that modulation of thermal energy provides better control over HIFU exposure and heating time modulation results into a reduced treatment time. The study highlighted the potential advantages of the proposed scanning method vis-à-vis the other conventional approaches. In particular, compared to the other methods, the proposed approach resulted in the realization of almost uniform distribution of thermal energy over the entire ROI leading to almost simultaneous destruction of the affected lesions. The present study can provide the requisite guidance for HIFU-based treatment planning and also highlights the need for optimizing the scanning pathway on the basis of total number of lesions and time parameters. [ABSTRACT FROM AUTHOR]

• The first demonstration of the generation of cavitation clouds within an intravascular scale hollow cylindrical transducer. • Peak internal pressures are dependant on element length and resonant mode. • Highest pressures are achieved in thickness mode and are impacted by internal reflections and the eventual development of a standing wave pattern. • Cavitation investigated as a function of pulsing scheme using a combination of hydrophone and imaging based methods. • This approach has potential use for enhancing aspiration based mechanical thrombectomy. Thrombotic occlusions of large blood vessels are increasingly treated with catheter based mechanical approaches, one of the most prominent being to employ aspiration to extract clots through a hollow catheter lumen. A central technical challenge for aspiration catheters is to achieve sufficient suction force to overcome the resistance of clot material entering into the distal tip. In this study, we examine the feasibility of inducing cavitation within hollow cylindrical transducers with a view to ultimately using them to degrade the mechanical integrity of thrombus within the tip of an aspiration catheter. Hollow cylindrical radially polarized PZT transducers with 3.3/2.5 mm outer/inner diameters were assessed. Finite element simulations and hydrophone experiments were used to investigate the pressure field distribution as a function of element length and resonant mode (thickness, length). Operating in thickness mode (∼5 MHz) was found to be associated with the highest internal pressures, estimated to exceed 23 MPa. Cavitation was demonstrated to be achievable within the transducer under degassed water (10 %) conditions using hydrophone detection and high-frequency ultrasound imaging (40 MHz). Cavitation clouds occupied a substantial portion of the transducer lumen, in a manner that was dependent on the pulsing scheme employed (10 and 100 μs pulse lengths; 1.1, 11, and 110 ms pulse intervals). Collectively the results support the feasibility of achieving cavitation within a transducer compatible with mounting in the tip of an aspiration format catheter. [ABSTRACT FROM AUTHOR]

mSOUND is an open-source toolbox written in MATLAB. This toolbox is intended for modeling linear/ nonlinear acoustic wave propagation in media (primarily biological tissues) with arbitrary heterogeneities, in which, the speed of sound, density, attenuation coefficient, power-law exponent, and nonlinear coefficient are all spatially varying functions. The computational model is an iterative one-way model based on a mixed domain method. In this article, a general guideline is given along with three representative examples to illustrate how to set up simulations using mSOUND. The first example uses the transient mixed-domain method (TMDM) forward projection to compute the transient acoustic field for a given source defined on a plane. The second example uses the frequency-specific mixed-domain method (FSMDM) forward projection to rapidly obtain the pressure distribution directly at the frequencies of interest, assuming linear or weakly nonlinear wave propagation. The third example demonstrates how to use TMDM backward projection to reconstruct the initial acoustic pressure field to facilitate photoacoustic tomography (PAT). mSOUND (https://m-sound.github.io/mSOUND/home) is designed to be complementary to existing ultrasound modeling toolboxes and is expected to be useful for a wide range of applications in medical ultrasound including treatment planning, PAT, transducer design, and characterization. [ABSTRACT FROM AUTHOR]

High intensity focused ultrasound (HIFU) treatments typically involve the ablation of tissue volumes comprising multiple focal sites. One aspect of treatment planning involves the definition of a sequence of ultrasound pulses and corresponding focal sites as the sonication trajectory. Here, numerical simulations of the thermal effects of different trajectories are performed for HIFU exposures delivered to an ex vivo bovine liver sample by a clinical array (Sonalleve V2 3.0T system, Profound Medical Corp., Canada). Simulations consider boiling histotripsy regime with millisecond-long pulses that include shocks. Focusing of the ultrasound beam in tissue was modeled by the Westervelt equation, and the temperature field was modeled by the bioheat equation. To explore different treatment strategies, trajectories were considered with discrete foci located along two or four concentric circles with radii from 2 to 8 mm. Two approaches for traversing these focal sites were compared: In the first approach each discrete focus was sonicated by a sequence of 15 pulses before moving to the next site in the trajectory. In the second approach, each focus was sonicated once before moving to the next site, with sonications over the whole trajectory repeated 15 times. The influence of the trajectory's size and the pulsing strategy on the temperature field was analyzed. It is shown that the structure of the temperature field is more uniform with a longer time interval between repeated irradiation of each focus, and the optimal time interval ranges from three to six pulse repetition periods. [ABSTRACT FROM AUTHOR]

Focused ultrasound (FUS) has been utilized for the treatment of localized prostate cancer. Initially, FUS was performed as a whole-gland treatment comparable to radical prostatectomy or radiation therapy. However, after overall downward stage migration due to health screening programs involving prostate-specific antigen testing, as well as advances in conservative or observative strategies such as active surveillance, FUS has evolved from a whole-gland treatment to a focal treatment. This new treatment technique aims to ablate tumors while preserving the normal prostate tissue, thereby ensuring better preservation of urinary and erectile function. In this article, we review the mechanism and clinical outcomes of the FUS procedure. [ABSTRACT FROM AUTHOR]

High intensity focused ultrasound (HIFU) has been widely used in clinical treatment of cervical cancer for its non-invasiveness and sharp treatment margins with very low complication rates. However, how to intensify the therapeutic efficacy of HIFU by specifically focusing the ultrasound energy on targeting pathological tissues is still a bottleneck for it to realize successful cancer ablation. Herein, a multifunctional organic-inorganic hybrid nanovesicles, by coating ultrathin silica shell on the surface of poly (lactic- co -glycolic acid) (PLGA) loaded with perfluorocarbon (PFOB), hydrophobic antitumor ruthenium complex (RuPOP) and superparamagnetic Fe 3 O 4 , has been designed to achieve synchronous ultrasound (US)/magnetic resonance imaging (MR) dual mode imaging-guided HIFU-triggered chemotherapy. The introduction of PFOB in this nanosystem could cause phase transition and make it gasification to cause collapse of the outer ultrathin silicon shell under HIFU irradiation, which results in enhanced intensive mechanical stress during blasting and enhanced therapeutic effect. The blasting behavior of this nanosystem triggered by HIFU also induced the on-demand RuPOP burst release in tumor site, thus maximizing the inhibition on residual tumor induced by inhomogeneous HIFU ablation. Taken together, this treatment strategy could overcome the inevitable tumor recurrence and significantly reduces systemic side effects of HIFU, thus could be further developed for noninvasive cancer therapy. Herein an intelligent nano-bomb has been designed to achieve synchronous ultrasound/magnetic resonance dual-modality imaging-guided HIFU-triggered on-demand site-specific drug release and successful cancer ablation. Unlabelled Image • An intelligent nano-bomb with on-demand drug burst release property is designed. • The nano-bomb synergizes with HIFU to realize successful cancer ablation. • The nano-bomb achieves synchronous ultrasound/MRI dual mode imaging-guided therapy. [ABSTRACT FROM AUTHOR]

Objective: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. Methods: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). Results: Successful technical treatments were achieved in 80 $\%$ of the patients. All patients underwent the treatment with no sedation and 60 $\%$ of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 $\pm$ 1.8 mm while 6.2 $\pm$ 1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 $\%$ and 70 $\%$ of patients, respectively. Conclusion: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts. [ABSTRACT FROM AUTHOR]

The growth of bubble nuclei in high intensity focused ultrasound (HIFU) is investigated. The imposed pressure on the nuclei is given by the experiments for the backscattering of HIFU from a laser-induced bubble interface. The lower limit of initial radius, Romin over which the bubble grows explosively, is calculated using the dynamical equation of motion for a spherical bubble in which the liquid compressibility and the thermal diffusion through the bubble interface are taken into consideration. The relationship between Romin and the absolute value of the minimum of imposed pressure |Pmin| is obtained for various temperature ranges. It is shown that temperature dependency of |Pmin| is in good agreement with that obtained directly from the corresponding experiments. It is also shown that appropriate choice of physical properties makes it possible to predict the relationship between Romin and |Pmin| in a temperature range from that in different temperature ranges even though the imposed pressure on the nuclei is different with each other. The results also show that temperature dependency of surface tension is a key factor to determine Romin. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) treatment is a promising non-invasive method for killing or destroying the diseased tissues by locally delivering thermal and mechanical energy without damaging surrounding normal tissues. In HIFU, measuring the temperature at the site of delivery is important for improving therapeutic efficacy, controlling safety, and appropriately planning a treatment. Several researchers have proposed photoacoustic thermometry for monitoring HIFU treatment, but they had many limitations, including the inability to image while the HIFU is on, inability to provide two-dimensional monitoring, and the inability to be used clinically. In this paper, we propose a novel integrated real-time photoacoustic thermometry system for HIFU treatment monitoring. The system provides ultrasound B-mode imaging, photoacoustic structural imaging, and photoacoustic thermometry during HIFU treatment in real-time for both in vitro and in vivo environments, without any interference from the strong therapeutic HIFU waves. We have successfully tested the real-time photoacoustic thermometry by investigating the relationship between the photoacoustic amplitude and the measured temperature with in vitro phantoms and in vivo tumor-bearing mice. The results show the feasibility of a real-time photoacoustic thermometry system for safe and effective monitoring of HIFU treatment. [ABSTRACT FROM AUTHOR]

High intensity focused ultrasound (HIFU) has gained increasing attention as a noninvasive therapeutic method for wide range of biomedical applications from drug delivery to cancer treatment. However, high level of ultrasonic power required for efficient HIFU treatment can cause adverse effects such as damage to surrounding healthy tissues and skin burns. One of the strategies to improve the therapeutic mechanism of HIFU is to use ultrasound absorption agents during the treatment. The objectives of current study are to investigate the feasibility of adopting gold nanoparticles (AuNPs) as ultrasound absorption agents to enhance the HIFU thermal ablation when the NPs were injected locally to the focal region; and to examine the dose effects of AuNPs on both heating and cooling mechanisms of HIFU. To this end, we conducted an experimental study on tissue-mimicking phantoms where AuNPs were injected to the focal region under the guidance of ultrasound imaging. A set of thermal parameters including temperature, specific absorption rate of acoustic energy, and cooling rate were measured to monitor the mechanism of AuNPs-mediated HIFU. The results suggest that both heating and cooling rates of HIFU procedure could be greatly improved by injecting AuNPs, which demonstrates the feasibility of using AuNPs to reduce the level of ultrasonic power from extracorporeal source for HIFU treatment. [ABSTRACT FROM AUTHOR]

Placenta accreta is an abnormal invasion of the placenta within the myometrium, which has increasing rate and could result in maternal mortality or morbidity. The objective of this study was to evaluate the feasibility of treating placenta accreta with high-intensity focused ultrasound (HIFU) using an ex vivo model. A toroidal HIFU transducer working at 2.5 MHz with an integrated ultrasound-imaging probe was used. Ex vivo experiments were performed in eight human placentae (from 39 to 40 weeks) within a configuration that mimicked clinical conditions as closely as possible. The fetal side of the placenta was placed in contact with the sterile envelope that covered the HIFU device to simulate the uterine serosa. HIFU lesions were studied on sonograms and macroscopically. In total, 19 single HIFU lesions were created with the same exposure parameters for all of the lesions. The exposure time was 75 s. The acoustic power was 90 W. HIFU lesions were created at different distances (2, 6, 7 and 8 mm) from the uterine serosa by adjusting the thickness of the coupling water and thus, the distance between the HIFU emitters and placental tissues. All of the lesions were homogeneous and approximately spherical in shape. The two diameters of the HIFU lesions were on average 14.6 ± 2.1 mm and 14.1 ± 2.3 mm. Lesions were immediately visible on sonograms after each HIFU exposure as a hyperechoic region. The distance between the surface of the placenta and HIFU lesion as measured on ultrasound images was closely correlated with the same distance that was measured on gross pathology (r = 0.89 , p < 0.05). This study demonstrates that HIFU may be an interesting option for adjuvant treatment during a cesarean of placenta accreta. These results must be validated under real clinical conditions. • A toroidal HIFU transducer can create large lesions in the placenta in short time. • All of the lesions were homogeneous and approximately spherical in shape. • HIFU may be an interesting option for adjuvant treatment of placenta accreta. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to evaluate the efficacy of high intensity focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas (FA) after 6 and 12 months. Materials and methods: Between December 2013 and November 2014, 27 patients with histologically confirmed FA received one application of HIFU under local anesthesia (NCT02011919). Follow-up visits occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A volume reduction of more than 65% was defined as success. Core needle biopsy (CNB) was offered after 12 months if indistinct residuals were visible on ultrasound (US). Results: A successful reduction in FA volume after 12 months was achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which was resolved in 63% (10/16). All patients were satisfied with the cosmetic related outcome. Twenty-four patients (89%) would repeat the procedure. After 12 months 21 patients with sonographically indistinct residuals underwent a CNB. There were no vital cells in 86%. Three cases showed vital cells of FA. Retrospectively possible reasons in these three cases were an insufficient treatment due to bad visibility and insufficient fixation of the FA during HIFU and/or a too short follow-up time. Conclusion: US-guided HIFU is an effective procedure and a minimally invasive alternative for the treatment of breast FA. [ABSTRACT FROM AUTHOR]

Highlights • Sumatriptan increased mechanical thresholds in the periorbital region for four days. • Pulsed FUS increased mechanical thresholds post therapy in the periorbital region. • Ablative HIFU did not increase mechanical thresholds post therapy. • FUS may provide a therapeutic option for patients suffering from chronic migraines. Abstract Chronic migraines (CM) are the third most common disease and are refractory to medical treatment in 15% of patients. Currently, temporary relief is achieved with steroid blocks or pulsed radiofrequency ablation, which have short-term benefits. Our project aims to develop a non-invasive treatment for medically refractory chronic migraine, which does not require a permanent implant. This project investigates the safety and effectiveness of pulsed focused ultrasound (FUS) in a validated rodent headache model of cutaneous allodynia associated with chronic migraine (CM) as compared to sumatriptan and ablative lesioning. We demonstrate a significant reduction in mechanical thresholds as measured through Von Frey filaments in CM in the forepaw and periorbital region (p < 0.001). Sumatriptan and pulsed FUS both significantly improve thresholds at day 3 after treatment in the periorbital region. Ablative lesioning has no effect. This study provides initial evidence that FUS may provide an important therapeutic option for patients suffering from CM. [ABSTRACT FROM AUTHOR]

Objectives: This study compares volume reduction of benign thyroid nodules three months after Radiofrequency Ablation (RFA), Microwave Ablation (MWA) or High Intensity Focused Ultrasound (HIFU) to evaluate which of these methods is the most effective and safe alternative to thyroidectomy or radioiodine therapy.Material and Methods: Ninety-four patients (39 male, 55 female) with a total of 118 benign, symptomatic thyroid nodules were divided into three subgroups. HIFU was applied to 14 patients with small nodules. The other 80 patients were divided up into two groups of 40 patients each for RFA and MWA in the assumption that both methods are comparable effective. The pre-ablative and post-ablative volume was measured by ultrasound.Results: RFA showed a significant volume reduction of nodules of 50 % (p<0.05), MWA of 44 % (p<0.05) and HIFU of 48 % (p<0.05) three months after ablation. None of the examined ablation techniques caused serious or permanent complications.Conclusion: RFA, MWA and HIFU showed comparable results considering volume reduction. All methods are safe and effective treatments of benign thyroid nodules.Key Points: • Thermal Ablation can be used to treat benign thyroid nodules • Thermal Ablation can be an alternative to thyroidectomy or radioiodine therapy • Radiofrequency Ablation, Microwave Ablation, High Intensity Focused Ultrasound are safe and effective. [ABSTRACT FROM AUTHOR]

Focused ultrasound (FUS/HIFU) relies on ablation of pathological tissues by delivering a sufficiently high level of acoustic energyin situof the human body. Magnetic Resonance guided FUS (MRgFUS/HIFU) and Ultrasound guided (USgFUS/HIFU) are image guided techniques combined with therapeutic FUS for monitoring purposes. The principles and technologies of FUS/HiFU are described in this paper including the basics of MR guidance techniques and MR temperature mapping. Clinical applications of FUS/HIFU gained CE and FDA approvals for the treatment of various benign and few malignant lesions in the last two decades. Current technical limitations of ultrasound guided and MRI guided Focused Ultrasound, as well as adverse effects for the application of this technique are outlined including challenges of ablating moving organs (liver and kidney). An outlook to possible applications is provided; exampling clinical trials discussing future options. [ABSTRACT FROM PUBLISHER]

High intensity focused ultrasound surgery still requires relatively a long surgical time due to small size of coagulative necrosis per each sonication. In order to increase a region of coagulative necrosis, dual-frequency ultrasound scheme has been proposed and showed notable results. In this paper, a novel dual-frequency ultrasound transducer based on the inversion layer technique is presented. Finite element analysis simulation was conducted, and the prototype transducer was fabricated to demonstrate the performance of the proposed method. The optimized thickness ratio between the inverted and non-inverted piezoelectric layers was chosen as 0.3:0.7. The proposed transducer with the chosen ratio generated the fundamental (at 1.2 MHz) frequency and the second harmonic frequency (at 2.4 MHz) ultrasound at the same time. The performance of the proposed transducer was numerically and experimentally verified through electrical impedance, pulse-echo response, and beam profile tests. [ABSTRACT FROM PUBLISHER]

Purpose: To evaluate the effect of differences in sonication duration and power on the size of postcontrast ablation zone following magnetic resonance-guided focused ultrasound (MRgFUS) of bone in a swine femoral bone model.Materials and Methods: Experimental procedures received approval from the Institutional Committee on Animal Research. MRgFUS was used to create two thermal lesions in the left femur of six pigs. Each target was subjected to six sonications. 400J of energy was used for each sonication. However, the distal target received the standard sonication duration of 20 seconds (20W), while the proximal target received a longer sonication duration of 40 seconds (10W). MRgFUS lesions were imaged with fat-saturated spoiled gradient echo sequence at 3.0T MRI 10 minutes following the administration of contrast. Maximum three-plane dimensions of the hypoenhanced ablation area were measured.Results: Postcontrast MR images demonstrated ovoid regions of hypoenhancement at each target. The average depth of ablation was significantly greater for the shorter high-power sonications (7.3 mm), compared to the longer lower-power sonications (4.5 mm), P = 0.026. The craniocaudal dimension was also greater for the shorter ablations 26.7 mm compared to the longer sonications 21.0 mm, P = 0.006.Conclusion: Contrary to anecdotal clinical experience, this preclinical model suggests that during MRgFUS of bone, standard duration, higher-power sonications resulted in deeper ablation volumes compared to long duration, lower-power sonications. These results suggest that to achieve deeper ablations, if longer sonications are used, then the power should be relatively maintained, for a net energy increase.Level Of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1418-1422. [ABSTRACT FROM AUTHOR]

Background: During lengthy magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU) thermal ablations in abdominal organs, the therapeutic work-flow is frequently hampered by various types of physiological motion occurring at different time-scales. If left un-addressed this can lead to an incomplete therapy and/or to tissue damage of organs-at-risk. While previous studies focus on correction schemes for displacements occurring at a particular time-scale within the work-flow of an MRg-HIFU therapy, in the current work we propose a motion correction strategy encompassing the entire work-flow. Methods: The proposed motion compensation framework consists of several linked components, each being adapted to motion occurring at a particular time-scale. While respiration was addressed through a fast correction scheme, long term organ drifts were compensated using a strategy operating on time-scales of several minutes. The framework relies on a periodic examination of the treated area via MR scans which are then registered to a reference scan acquired at the beginning of the therapy. The resulting displacements were used for both on-the-fly re-optimization of the interventional plan and to ensure the spatial fidelity between the different steps of the therapeutic work-flow. The approach was validated in three complementary studies: an experiment conducted on a phantom undergoing a known motion pattern, a study performed on the abdomen of 10 healthy volunteers and during 3 in-vivo MRg-HIFU ablations on porcine liver. Results: Results have shown that, during lengthy MRg-HIFU thermal therapies, the human liver and kidney can manifest displacements that exceed acceptable therapeutic margins. Also, it was demonstrated that the proposed framework is capable of providing motion estimates with sub-voxel precision and accuracy. Finally, the 3 successful animal studies demonstrate the compatibility of the proposed approach with the work-flow of an MRg-HIFU intervention under clinical conditions. Conclusions: In the current study we proposed an image-based motion compensation framework dedicated to MRg-HIFU thermal ablations in the abdomen, providing the possibility to re-optimize the therapy plan on-the-fly with the patient on the interventional table. Moreover, we have demonstrated that even under clinical conditions, the proposed approach is fully capable of continuously ensuring the spatial fidelity between the different phases of the therapeutic work-flow. [ABSTRACT FROM AUTHOR]

High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, 111 In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of 111 In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24 h after systematic delivery of 111 In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors. [ABSTRACT FROM AUTHOR]

Adenomyosis is a disorder of uterus in which endometrial glands and stroma are present within the uterine musculature. The main clinical manifestations are dysmenorrhea and menorrhagia. Adenomyosis has a great impact on both the quality of life and fertility of women. The treatment of adenomyosis remains an immense challenge. Relevant articles were searched through MEDLINE and PubMed between 2000 and March 2017. The search terms of adenomyosis, magnetic resonance imaging (MRI) features of adenomyosis, high intensity focused ultrasound (HIFU), ultrasound-guided HIFU and MRgFUS were used. There were no language restrictions. HIFU is a non-invasive local thermal ablation technique which has been used in the treatment of both focal and diffuse adenomyosis. Several case studies have demonstrated that HIFU presents low rate of minor and/or major complications and, at the same time, a long symptom-relief period. Multiple factors such as the enhancement type of the adenomyotic lesion, volume of the adenomyotic lesions, number of hyperintense foci on T2WI, location of the uterus, location of adenomyotic lesions, thickness of the abdominal wall and distance from the skin to the adenomyotic lesions contribute to the efficacy of HIFU. Consequently, based on these contributing factors, specific and strict selection criteria have been used to achieve higher efficacy. Thus, patients with pelvic endometriosis, adhesions between the bowel and the uterus, or an abdominal surgical scar wider than 10 mm, are not suitable for HIFU treatment. Moreover, HIFU-treated patients with adenomyosis, who wished to conceive, showed high conception and live birth rates. HIFU is a new and promising treatment option for patients with adenomyosis, but its efficacy, safety, cost-effectiveness and fertility outcome must be evaluated by randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: With an increasing number of imaging studies being done nowadays, the number of incidentally discovered thyroid nodules is expected to rise. Although many of these nodules are small and benign in nature, some do grow and may cause pressure and/or thyrotoxic symptoms. Surgical resection has traditionally been recommended for symptomatic nodules but is associated with risk of hypothyroidism, bleeding, infection, and nerve damage. High intensity focused ultrasound (HIFU) is one of the non-surgical thermal ablation techniques that may serve as an alternative in the treatment of benign thyroid nodules. The present review is to systematically evaluate the efficacy and safety of HIFU ablation. Methods: We comprehensively searched all studies that evaluated the use of HIFU ablation as a treatment of benign thyroid nodules from Medline (PubMed) and Cochrane Library electronic databases using specific keywords. All titles identified by the search strategy were independently screened by two authors. Case reports, animal studies, editorials, expert opinions, reviews without original data and studies on pediatric population were excluded. Multiple reports of the same dataset were assessed and the most representative and updated report of a study was included. Results: Five original studies were found. All treated thyroid nodules were confirmed to be benign cytologically and either appeared solid or predominantly (>70%) solid on ultrasonography. Only one type of commercially available US-guided device with an extracorporeal probe (3 MHz) was used in all the reported treatments. No major complications including recurrent laryngeal nerve injury, skin burn or haematoma were reported in all of the studies. The overall nodule volume reduction after single session of HIFU ablation ranged between 45 and 68%, depending on nodule size and length of follow-up. Conclusions: Despite the few number of studies, our review appeared to suggest that HIFU is a safe and efficacious method of treating symptomatic benign thyroid nodules. However, larger-scale, prospective trials with longer follow-up period are indeed required to confirm this. In terms of the ablation itself, relative to other ablation techniques, there are still much room for improvements in shortening treatment duration and expanding the range of treatable nodules. [ABSTRACT FROM AUTHOR]

Combination of polymer therapeutics and hyperthermia has been shown to enhance accumulation in selectively heated tumor tissue. The additional use of heat shock (HS)-targeting towards tumor tissues can further enhance accumulation and retention, and improve therapeutic outcomes. In this work, high intensity focused ultrasound (HIFU) was used to generate hyperthermia in prostate tumor tissue. Upregulation of the cell surface HS receptor glucose regulated protein 78 kDa (GRP78) was observed after treatment with HIFU hyperthermia which was then targeted by specific HS-targeting peptides. We used the peptide sequence WDLAWMFRLPVG attached to the side chains of water-soluble N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing docetaxel (DOC) conjugated via a lysosomally degradable linker. It was shown that HIFU-mediated HS-targeted copolymer–DOC conjugates improved treatment efficacy in a murine prostate tumor xenograft model. These results show that the use of HIFU hyperthermia in combination with HS-targeted polymer–drug conjugates has potential to improve therapeutic outcomes in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

An important limitation to successful cancer treatment with chemotherapeutics is the inability to achieve therapeutically effective drug concentrations while avoiding healthy tissue damage. In this work, a new tumor-targeting peptide iRGD (CCRGDKGPDC) was used to modify drug-loaded low temperature-sensitive liposomes (iRGD-LTSL-DOX) to explore the anti-tumor effects in combination with high intensity focused ultrasound (HIFU) in vitro and in vivo. iRGD-LTSL-DOX can specifically target to ανβ3-positive cells and locally release the encapsulated doxorubicin (DOX) in a hyperthermia-triggered manner. In vivo results showed that DOX from iRGD-LTSL-DOX was intravascularly released and rapidly penetrated into tumor interstitial space after HIFU-triggered heat treatment, thereby overcoming the limited tumor penetration of anticancer drugs. Significantly stronger anti-tumor efficacy further supported the effective combination of iRGD-LTSL-DOX with HIFU-induced hyperthermia. Our study provided a novel tumor-targeting LTSL-DOX and demonstrated its usefulness in HIFU-induced hyperthermia-triggered drug delivery. [ABSTRACT FROM AUTHOR]

• The novelty of using short HIFU pulses to compensate for the continuous sonication drawbacks. • The novelty of considering different fractions of hypoxic region as real tumor microenvironment. • The novelty of noticing the thermal inertia and microstructural interaction in the TSL-HIFU system. • By the expansion of hypoxic fraction to 70%, the therapeutic efficacy of conventional drug delivery is reduced up to 2 times. • High acoustic powers induce coagulation necrosis in the hypoxic region and mild hyperthermia in richly vascularized regions. Poor half-life, short circulation, systemic toxicity, insufficient accumulation, and ultimately weak therapeutic response are the most important obstacles in the conventional chemotherapy. Thermosensitive liposomes (TSLs) with encapsulated anti-cancer drug doxorubicin combined with high intensity focused ultrasound (HIFU) has the potential to overcome the shortcomings of conventional chemotherapy through targeted drug delivery. In the HIFU-TSL drug delivery system, complex physicochemical and biological processes are involved; however, many works in this field suffer from a comprehensive analysis. Regarding this, the present study has the novelty of developing an advanced multi-physical and multi-compartment model to simulate the complex processes in conventional and TSL-mediated chemotherapy paired with HIFU-induced hyperthermia. Elaborating the determinant role of tumor microenvironment is another novelty, which was underrepresented in earlier investigations and is noticed in our study through the modeling of hypoxic region. Additionally, unlike previous studies that used the classical bio-heat transfer model, this study has innovation in considering the thermal inertia as well as microstructural interactions in the bio-heat transfer equation. Last by not the least, many researchers evaded the harms of continuous irradiation, which in the present work is replaced by pulsed ultrasound as an emerging method for thermal necrosis and mild hyperthermia. The results reveal that the hypoxic region prevents efficient drug delivery due to the disruption of microvascular network and reduces chemotherapy-induced cell death. A comparison between targeted drug delivery and conventional chemotherapy suggests that TSL-mediated drug delivery leads to increased cell death by more than 100% by providing high circulation time and improved bioavailability. Besides this, increasing the acoustic power (from 3 to 8.7 W) leads to a desirable achievement, which is thermal necrosis of central tumor region and high fraction of killed cells (FKCs). The FKCs in the proposed HIFU-TSL system reaches about 58% (3 W), 60% (4.1 W), 70% (7 W), and 78% (8.7 W) at 24 h after TSL-doxorubicin administration, while this value is about 30% in the conventional chemotherapy. In conclusion, this study confirms the benefits of HIFU-TSL drug delivery system. This method has the potential to be used as a targeted drug delivery system to improve anti-cancer drug efficacy, while considerably prevents the normal tissue damage. [Display omitted]. [ABSTRACT FROM AUTHOR]

Liver transplantation is the mainstay of treatment for end stage liver diseases, including metabolic and congenital liver diseases. The number of suitable donor organs is, however, limited, and a whole-liver transplant requires complex surgery. Cell therapy, such as intra-portal hepatocytes transplantation, has been considered as a bridging therapy to liver transplantation but has shown a mixed clinical outcome with limited success, including low level of engraftment of transplanted hepatocytes. Here, we report a novel cell delivery technique in a rat model by creating a cavity inside the liver parenchyma by non-invasive high intensity focused ultrasound histotripsy. Our in vivo experimental results together with histologic observations show that direct injection of cells inside the cavity can facilitate successful uptake, proliferation and integration of the transplanted hepatocytes in the recipient liver. We were able to restore the plasma albumin level to 50% of the normal level in Nagase analbuminemic rats (serum albumin level of the Nagase rats was initially nil) by cell therapy after high intensity focused ultrasound-mediated histotripsy. We believe that this novel technique would enable the delivery of a large number of cells into the liver to restore liver function, particularly as a treatment for metabolic liver diseases. This novel method of intra-hepatic hepatocyte transplantation might be an invaluable tool for cell therapy in the future. [ABSTRACT FROM AUTHOR]

As the use of HIFU in the clinic becomes more widespread there is an ever increasing need to standardise quality assurance protocols, an important step in facilitating the wider acceptance of HIFU as a therapeutic modality. This article reviews pertinent aspects of HIFU treatment delivery, encompassing the closely related aspects of quality assurance and calibration. Particular attention is given to the description and characterisation of relevant acoustic field parameters and the measurement of acoustic power. Where appropriate, recommendations are made. [ABSTRACT FROM AUTHOR]

In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumours, kidney stone fragmentation, enhancing anti-tumour immune response, and tissue decellularisation for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilise different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of non-invasive surgery. [ABSTRACT FROM AUTHOR]

A recipe was created to improve the tissue-mimicking (TM) bovine serum albumin (BSA) polyacrylamide hydrogel (PAG) reported in our previous study (Choi MJ, Guntur SR, Lee KI, Paeng DG, Coleman AJ. Ultrasound Med Biol 2013; 29:439–448). In that work, the concentration of acrylamide in TM BSA PAG was increased to make its attenuation coefficient the same as that of a tissue. However, this increase made the PAG stiffer and less homogeneous. In addition, the increase in acrylamide caused a significant increase in temperature over the denaturation threshold of BSA during polymerization, which required forced cooling so that the PAG did not become opaque at room temperature after polymerization. To eliminate those shortcomings, we substituted the increased acrylamide with a viscous polysaccharide liquid (corn syrup). The concentration of corn syrup was optimized to 20% (w/v, tested in the volume of 50 mL), so that the acoustic properties of the PAG would be close to those of human liver. The improved TM (iTM) BSA PAG constructed in this study had a speed of sound of 1588 ± 9 m/s, an attenuation coefficient of 0.51 ± 0.06 dB cm −1 at 1 MHz and a backscattering coefficient of 0.22 ± 0.09 × 10 −3 sr −1 cm −1 MHz −1 . The density and acoustic impedance were 1057 kg/m 3 and 1.68 MRayl, respectively, and the non-linear parameter ( B / A ) was 5.9 ± 0.3. The thermal, optical and mechanical properties were almost the same as those of the BSA PAG ( Lafon et al.2005 ). Experimental verification indicated that the thermal lesions visualized in the proposed iTM BSA PAG by high-intensity focused ultrasound were highly reproducible. In conclusion, iTM BSA PAG was proven to eliminate TM BSA PAG shortcomings effectively and is expected to be a promising test phantom for clinical high-intensity focused ultrasound device. [ABSTRACT FROM AUTHOR]

A bstract Stem cells are promising therapeutics for cardiovascular diseases, and i.v. injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemoattractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (pFUS), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemoattractant expression in pFUS-treated tissue prior to cell infusions. We demonstrate that pFUS is nondestructive to murine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate that local upregulation of chemoattractants in pFUS-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when pFUS treatments and cell infusions were repeated daily. This study demonstrates that pFUS defines transient 'molecular zip codes' of elevated chemoattractants in targeted muscle tissue, which effectively provides spatiotemporal control and tunability of the homing process for multiple stem cell types. pFUS is a clinically translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. S tem C ells 2013;31:2551-2560 [ABSTRACT FROM AUTHOR]

A shape memory biodegradable polyurethane composite is prepared and shape recovery and simultaneous release of embedded copper sulfate are realized by high intensity focused ultrasound (HIFU). The composite shows an excellent HIFU-controlled shape recovery performance, wherein temporal and spatial control can be realized by switching the HIFU on/off or selecting the place where the ultrasound is focused. The composite shows an excellent HIFU switchable drug release function. The release process of a model payload can be tuned by adjusting the HIFU intensity and time. The shape memory polyurethane shows a rapid enzymatic biodegradation rate. This polyurethane composite has potential applications in minimally invasive interventional therapy devices. [ABSTRACT FROM AUTHOR]

Abstract: Au nanoparticles-coated, perfluorohexane-encapsulated and PEGylated mesoporous silica nanocapsule-based enhancement agents (MSNC@Au-PFH-PEG, abb. as MAPP) have been synthesized, for the ultrasound-induced cytoclasis, contrast-intensified ultrasound (US) imaging and US-guided high intensity focused ultrasound (HIFU) surgical therapy. Both the US-induced thermal effect and US triggered release of loaded model drug with MAPP under US exposure indicated the excellent US sensitivity of MAPP and its applicability for the combined chemo-/thermal therapy and future potential for HIFU ablation; US imaging under different modes verify the attractive US contrast intensification by using MAPP; US-guided HIFU therapy ex vivo and in vivo with MAPP is found to be highly efficient on rabbit VX2 xenograft tumor ablation due to the high thermal energy accumulation and increased mechanical/thermal effects from US-induced PFH bubble cavitations. MAPP can be promisingly used as an inorganic theranostic platform for contrast-intensified US imaging, combined chemotherapy and efficient HIFU tumor ablation under the guidance by the intensified US. [Copyright &y& Elsevier]

Objective: To analyse the clinical dosimetry of high intensity focused ultrasound (HIFU) for the treatment of inoperable pancreatic cancer in humans. Methods: 136 patients with advanced pancreatic cancer were treated with HIFU, including 89 male and 47 female patients. The median targeted volume (Vt) was 31.1 cm3 (range: 9.8-102.1). The median of the average ultrasound power (Pavg) was 225 W (range: 117-399), and the median energy of the ultrasound (Etotal) was 278.3 kJ (range: 70.5-1195.2). Spearman rank correlation analysis for HIFU dosimetric analysis was conducted. Results: There was a significant correlation between greyscale changes after HIFU ablation and HIFU dose intensity (DI), Pavg, and unit time (Tu). However, no correlation was found between greyscale changes after HIFU ablation and gender, age, pancreatic cancer position, or depth of tumour. Conclusions: We preliminarily deem that dose intensity and sound power can act as good reference points for HIFU dosimetry in the treatment of pancreatic tumours using the Chongqing system. If there was no obvious change in the ultrasound-monitored image following HIFU treatment for pancreatic cancer, the Pavg and DI should be no less than 260 W and 11 kJ/cm3, respectively. [ABSTRACT FROM AUTHOR]

Discrepancies between hyperecho-predicted necrosed volume in ultrasound (US) images and the actual size of a thermal lesion might cause incomplete ablation or damage normal structures during high intensity focused US (HIFU) ablations. A novel dual-frequency sonication procedure is proposed to reduce this discrepancy. HIFU transducers of either 1 or 3.5 MHz were applied to transparent tissue-mimicking phantoms and ex vivo bovine liver samples. A diagnostic probe and a charge-coupled device (CCD) camera were used to record lesion formation in real time, allowing for comparison of the sizes of the hyperechoes in US images and the protein denaturing area on optical images. Bovine liver specimens were segmented to reveal the lesion's terminal sizes. Differences between actual lesion volume and hyperechoes in US images were demonstrated to be dependent on acoustic frequency and intensity. At a low frequency (1 MHz), the hyperechoes appeared to be larger than the actual volume, but the difference decreased with the duration of ablation. In contrast, at a high frequency (3.5 MHz), the hyperechoes were smaller for ablations lasting longer than 10 s. Moreover, given certain low-intensity conditions, lesions were formed without detectable hyperechoes (3.5 MHz), or hyperechoes appeared before a visible lesion was formed (1 MHz). Dual frequency sonications (low frequency followed by high frequency) produce more stable and larger lesions, and with less position shift, which might be useful for designing future ablation strategies. [ABSTRACT FROM AUTHOR]

Hig hintensity focused ultrasound (HIFU) has been applied for drug delivery in various disease conditions. Delivery of antibacterial-nanoparticles into dental hard tissues may open up new avenues in the treatment of dental infections. However, the basic mechanism of bubble dynamics, its characterization, and working parameters for effective delivery of nanoparticles, warrants further understanding. This study was conducted to highlight the basic concept of HIFU and the associated bubble dynamics for the delivery of nanoparticles. Characterization experiments to deliver micro-scale particles into simulated tubular channels, activity of ultrasonic bubbles, and pressure measurement inside the HIFU system were conducted. Subsequently, experiments were carried out to test the ability of HIFU to deliver nanoparticles into human dentine using field emission scanning electron micrographs (FESEM) and elemental dispersive X-ray analysis (EDX). The characterization experiments showed that the bubbles collapsing at the opening of tubular channels were able to propel particles along their whole length. The pressure measured showed sufficient negative and positive pressure suggesting that the bubble grew to a certain size before collapsing, thus enabling the particles to be pushed. The FESEM and EDX analysis highlighted the ability of HIFU to deliver nanoparticles deep within the dentinal tubules. This study highlighted the characteristics and the mechanism involved of the bubbles generated by the HIFU and their capability to deliver nanoparticles. [ABSTRACT FROM AUTHOR]