Search

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.

Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the present study, a new sonothrombolysis method is proposed for treating embolus without the use of thrombolytic drugs. Our proposed method involves (a) generating a spatially localised acoustic radiation force in a blood vessel against the blood flow to trap moving blood clots (i.e., generation of an acoustic net), (b) producing acoustic cavitation to mechanically destroy the trapped embolus, and (c) acoustically monitoring the trapping and mechanical fractionation processes. Three different ultrasound transducers with different purposes were employed in the proposed method: (1) 1-MHz dual focused ultrasound (dFUS) transducers for capturing moving blood clots, (2) a 2-MHz High Intensity Focused Ultrasound (HIFU) source for fractionating blood clots and (3) a passive acoustic emission detector with broad bandwidth (10 kHz to 20 MHz) for receiving and analysing acoustic waves scattered from a trapped embolus and acoustic cavitation. To demonstrate the feasibility of the proposed method, in vitro experiments with an optically transparent blood vessel-mimicking phantom filled with a blood mimicking fluid and a blood clot (1.2 to 5 mm in diameter) were performed with varying the dFUS and HIFU exposure conditions under various flow conditions (from 1.77 to 6.19 cm/s). A high-speed camera was used to observe the production of acoustic fields, acoustic cavitation formation and blood clot fragmentation within a blood vessel by the proposed method. Numerical simulations of acoustic and temperature fields generated under a given exposure condition were also conducted to further interpret experimental results on the proposed sonothrombolysis. Our results clearly showed that fringe pattern-like acoustic pressure fields (fringe width of 1 mm) produced in a blood vessel by the dFUS captured an embolus (1.2 to 5 mm in diameter) at the flow velocity up to 6.19 cm/s. This was likely to be due to the greater magnitude of the dFUS-induced acoustic radiation force exerted on an embolus in the opposite direction to the flow in a blood vessel than that of the drag force produced by the flow. The acoustically trapped embolus was then mechanically destructed into small pieces of debris (18 to 60 μm sized residual fragments) by the HIFU-induced strong cavitation without damaging the blood vessel walls. We also observed that acoustic emissions emitted from a blood clot captured by the dFUS and cavitation produced by the HIFU were clearly distinguished in the frequency domain. Taken together, these results can suggest that our proposed sonothrombolysis method could be used as a promising tool for treating thrombosis and embolism through capturing and destroying blood clots effectively.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel non-invasive ablation technique that uses focused sound energy to destroy focal tumors, primarily via heat deposition. It is widely used for palliation of pain from bone metastases and has also recently gained popularity as a technique for ablation of benign bone tumors and facet degenerative joint disease (rhizotomy). Clinically, in a subset of patients who have undergone MRgFUS of bone, a variety of treatment responses have been noted on follow-up imaging, including focal sclerosis within the target lesion or more exuberant proliferative changes associated with the periosteum. In this study, high resolution peripheral quantitative CT (HR-pQCT) was used to evaluate remodeling of bone following ablation in a swine model of MRgFUS and compared to samples from a control, non-treated femur. Within each treated femur, two lesions were created: a higher energy focused ultrasound dose was used for one lesion compared to a lower energy dose for the second lesion. Exuberant, extra-cortical bone formation was detected at the higher energy ablation zones, with volumes ranging from 340 mm3 to 1040 mm3. More subtle endosteal and cortical changes were detected in the lower energy ablation zones, however cortical thickness was significantly increased at these sites compared to control bone. For both high and low energy lesions, lower bone mineral density and tissue mineral density was noted in treated regions compared to control regions, consistent with the formation of newly mineralized tissue. Following HR-pQCT analysis, Fourier transform infrared (FTIR) spectroscopy was subsequently used to detect biochemical changes associated with remodeling of bone following MRgFUS, and compared to samples from the control, non-treated femur. Findings were compared with histopathologic examination following hematoxylin-eosin staining. FTIR analysis demonstrated lower mineral/phosphate ratio and increased crystallinity compared to the control samples (p = 0.013). Histopathologic review demonstrated associated areas of endosteal inflammation, scarring, fat necrosis, and new extra-cortical bone formation associated with the ablations. Overall, these findings provide novel characterization of new bone formation following MRgFUS ablation.

Abstract Objective To investigate the safety and feasibility of high intensity focused ultrasound (HIFU) ablation followed by ultrasound-guided dilation and curettage (USg-D&C) for two types patients with cesarean scar pregnancy (CSP-I and CSP-II). Materials and methods This study was a retrospective analysis of 101 CSP-I patients and 52 CSP-II patients who received HIFU ablation followed by USg-D&C from Jun 2014 to Oct 2020. The diameter of gestational sac/mass, thickness of the intervening myometrium, intraoperative blood loss, operation time, length of hospital stays, adverse effects and β-HCG level in the two groups were compared. Results All patients successfully received HIFU ablation under conscious sedation. The median total treatment time of HIFU ablation and median USg-D&C time in the CSP-I group were statistically longer than those in the CSP-II group (P 0.05). The average time needed for β-HCG return to normal levels was 26.08 ± 5.02. and 28.15 ± 4.99 days for CSP-I and CSP-II, respectively (P > 0.05). The percentage of adverse effects and complications was not significantly different between the two groups (P > 0.05). Conclusions HIFU ablation followed by USg-D&C was safe and effective in treating the CSP-I patients and CSP-II patients, which may be a potential noninvasive therapeutic option for patients with CSP.

Simple Summary: Liver malignancy affects thousands of people, and its treatment is constantly evolving. Ablative therapies are a series of minimally invasive modalities that treat these tumors in combination with other established forms of treatment such as chemotherapy and surgery. Ablative therapy is well-studied in the case of the most common type of liver malignancy, hepatocellular carcinoma. There is much less information on ablative therapy in non-hepatocellular carcinoma liver malignancy treatment. Therefore, we have described the available literature, focusing on ablative therapy's promising results, shortcomings, and detail areas for future research on the topic of non-hepatocellular carcinoma of the liver. Surgical extirpation of liver tumors remains a proven approach in the management of metastatic tumors to the liver, particularly those of colorectal origin. Ablative, non-resective therapies are an increasingly attractive primary therapy for liver tumors as they are generally better tolerated and result in far less morbidity and mortality. Ablative therapies preserve greater normal liver parenchyma allowing better post-treatment liver function and are particularly appropriate for treating subsequent liver-specific tumor recurrence. This article reviews the current status of ablative therapies for non-hepatocellular liver tumors with a discussion of many of the clinically available approaches. [ABSTRACT FROM AUTHOR]

The non-perfused volume (NPV) is an important indicator of treatment success immediately after prostate ablation. However, visualization of the NPV first requires an injection of MRI contrast agents into the bloodstream, which has many downsides. Purpose of this study was to develop a deep learning model capable of predicting the NPV immediately after prostate ablation therapy without the need for MRI contrast agents. A modified 2D deep learning UNet model was developed to predict the post-treatment NPV. MRI imaging data from 95 patients who had previously undergone prostate ablation therapy for treatment of localized prostate cancer were used to train, validate, and test the model. Model inputs were T1/T2-weighted and thermometry MRI images, which were always acquired without any MRI contrast agents and prior to the final NPV image on treatment-day. Model output was the predicted NPV. Model accuracy was assessed using the Dice-Similarity Coefficient (DSC) by comparing the predicted to ground truth NPV. A radiologist also performed a qualitative assessment of NPV. Mean (std) DSC score for predicted NPV was 85% ± 8.1% compared to ground truth. Model performance was significantly better for slices with larger prostate radii (> 24 mm) and for whole-gland rather than partial ablation slices. The predicted NPV was indistinguishable from ground truth for 31% of images. Feasibility of predicting NPV using a UNet model without MRI contrast agents was clearly established. If developed further, this could improve patient treatment outcomes and could obviate the need for contrast agents altogether. Trial Registration Numbers Three studies were used to populate the data: NCT02766543, NCT03814252 and NCT03350529. [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]

In transabdominal histotripsy, ultrasound pulses are focused into the body to noninvasively destroy soft tissues via cavitation. However, the ability to focus is limited by phase aberration, or decorrelation of the ultrasound pulses due to spatial variation in the speed of sound throughout heterogeneous tissue. Phase aberration shifts, broadens, and weakens the focus, thereby reducing the safety and efficacy of histotripsy therapy. This paper reviews and discusses aberration effects in histotripsy and in related therapeutic ultrasound techniques (e.g., high intensity focused ultrasound), with an emphasis on aberration by soft tissues. Methods for aberration correction are reviewed and can be classified into two groups: model-based methods, which use segmented images of the tissue as input to an acoustic propagation model to predict and compensate phase differences, and signal-based methods, which use a receive-capable therapy array to detect phase differences by sensing acoustic signals backpropagating from the focus. The relative advantages and disadvantages of both groups of methods are discussed. Importantly, model-based methods can correct focal shift, while signal-based methods can restore substantial focal pressure, suggesting that both methods should be combined in a 2-step approach. Aberration correction will be critical to improving histotripsy treatments and expanding the histotripsy treatment envelope to enable non-invasive, non-thermal histotripsy therapy for more patients. [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]

Due to resistance and intolerance to chemotherapy, localized lesion resection may be required in some patients with Gestational trophoblastic neoplasia (GTN), which may lead to massive bleeding. In this case report, we describe the successful use of high-intensity focused ultrasound (HIFU) as an effective pretreatment method for surgical procedure in a patient with GTN to reduce the perioperative risk and the impact on fertility. A 26-year-old woman was diagnosed with high-risk GTN (FIGO Stage III: 12 prognostic scores) after a hydatidiform mole. The fifth chemotherapy cycle was interrupted due to severe chemotherapy toxicity. However, the uterine lesion was still present and the beta-human chorionic gonadotropin (β-hCG) level was not restored to normal. Therefore, ultrasound-guided HIFU was performed as a pretreatment method to shrink the lesion and prevent massive bleeding during localized lesion resection. The effectiveness of ablation was evaluated immediately using contrast-enhanced ultrasound and Color Flow Doppler ultrasonography. One month after HIFU treatment, the uterine lesion was completely resected under hysteroscopic surgery. During the surgery, HIFU was found to have shrunk the lesion and there was minimal bleeding (5 mL). The uterine cavity morphology and menstruation returned to normal after surgery. The patient has showed no signs of recurrence as of one-year follow-up. Ultrasound-guided HIFU ablation may be a new choice for high-risk GTN patients with chemoresistance or chemo-intolerance. As a noninvasive pretreatment method, HIFU can shrink the uterine lesion, and reduce the risk of bleeding with no obvious effect on fertility. [ABSTRACT FROM AUTHOR]

Our study aims at the comprehensive analysis of adverse events (AEs) in patients with symptomatic uterine fibroids (UFs) who underwent magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) in the last 6 years in one of the major Polish centers performing this type of therapy. The presented retrospective case-control study was conducted in the Department of Obstetrics and Gynecology, Pro-Familia Hospital, Rzeszów in cooperation with the Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, Warsaw. The study enrolled 372 women with symptomatic UFs who underwent MR-HIFU and reported AEs during or after the procedure. The occurrence of particular AEs was analyzed. Statistical comparison of two cohorts (patients with and without AEs) was conducted based on epidemiological factors, UF characteristics, fat layer thickness, the presence of abdominal scars and technical parameters of the procedure. The overall mean occurrence rate of AEs was 8.9% (n = 33). No major AEs were reported. The only statistically significant risk factor of AEs was the treatment of type II UFs according to Funaki (OR 2.12, CI 95%, p = 0.043). Other investigated factors did not have a statistically significant influence on AE occurrence. Abdominal pain was the most common AE. Our data showed that MR-HIFU seemed to be a safe procedure. The AE rate after the treatment is relatively low. According to the obtained data it seems that the occurrence of AEs does not depend on the technical parameters of the procedure and the volume, position and location of UFs. Further prospective, randomized studies and with long follow-up are necessary to confirm the final conclusions. [ABSTRACT FROM AUTHOR]

This study deals with a numerical simulation of the growth of bubble nuclei and the corresponding bubble cloud formation in a pressure field given by high intensity focused ultrasound (HIFU) backscattered from a laser-induced bubble interface. In the present paper, using a multiscale numerical method (Tamura et al., Japanese J. Multiphase Flow, 2022) in which the ghost fluid method is coupled with bubble dynamics, the growth of the bubble cloud which consists of multiple bubble layers is simulated continuously as observed in the experiments. It is shown that the distance between the first cavitation inception point and a laser-induced bubble interface is about 0.27λ, where λ, is the wavelength of HIFU; the distance between bubble layers in the cloud is also about 0.35λ: these distances in the simulation are in good agreement with the experiments. The influence of the configuration of bubble nuclei on the final form of a cone-shaped bubble cloud is investigated. It is also shown that the shape of each bubble layer, which depends on the initial configuration of bubble nuclei, affects the final formation of bubble clouds. This is because that the negative pressure due to the backscattering of HIFU is dependent on the shape of each bubble layer. The results also show that the averaged final shape of bubble clouds quantitively matches the results as observed in the experiment by Horiba et al. (J. Acoust. Soc. Am., 2020). [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]

Uterine fibroids are the most common benign uterine tumours in women of reproductive age. They can present with different symptoms, including menorrhagia, cramping lower abdominal pain, bloating, urinary/bowel symptoms, spotting, and infertility. Management could be medical and surgical. Other options include uterine artery embolization and non-invasive treatment with high-intensity focused ultrasound (HIFU). We present a case of a 32-year-old woman with menorrhagia and severe pelvic pain. Ultrasound examination revealed an intramural myoma measuring 93x98x87 mm. The patient signed informed consent for HIFU ablation of the fibroid. Three months after the procedure, an MRI scan showed the fibroid had shrunk to 75% of its original size with dimensions 32x35x29. After six months, she became pregnant and gave birth to a healthy infant at 38-weeks gestation with caesarean section, at which point the fibroid measured 2 cm. HIFU is an alternative to surgical therapies and is highly beneficial in women wishing for future pregnancies. Preserving the option for future pregnancies in patients with uterine fibroids is only one of its benefits and might be the key solution for these women. HIFU treatment of uterine fibroids is an innovative approach. It should be encouraged: it is widely adopted in similar cases where it has positively impacted the treatment of uterine fibroids. [ABSTRACT FROM AUTHOR]

• A novel passive cavitation imaging (PCI) scheme was proposed to tackle two practical problems in monitoring high intensity focused ultrasound (HIFU) treatment. • Firstly, a cavitation detection network (CD-NET) model was introduced for the first time to detect the occurrence of cavitation to avoid false positive visualizations in the PCI procedure. • Secondly, cavitation intensity baseline was derived from experiment data, which can help display the dynamic cavitation activities in a more reliable manner. • The enhanced PCI scheme offer an effective method for monitoring HIFU therapies involving cavitation. Passive cavitation imaging (PCI) is an effective technique for monitoring high intensity focused ultrasound (HIFU) procedure due to the correlation between cavitation activities and the therapeutic effects. Nevertheless, current PCI techniques are unable to recognize noise signals from non-cavitation situations, and they fail to accurately visualize the highly dynamic cavitation activities due to the lack of a stable baseline reference. In this study, a deep learning-based cavitation detection network (CD-NET) was proposed to determine whether passively received channel signals originated from cavitation activities or were merely noises. Additionally, a cavitation intensity baseline was derived to better display the drastically time-varying cavitation activities. The CD-NET model was trained and validated with data collected from in-vitro and ex-vivo HIFU sonication experiments, and then tested by in-vivo rabbit experiments. Both CD-NET models, trained with data from the in-vitro agar phantoms and ex-vivo bovine liver tissues, successfully distinguished between cavitation and non-cavitation activities from the same study object, achieving accuracies as high as 99.7% and 99.5%, respectively. In addition, the models trained on in-vitro and ex-vivo datasets achieved accuracies of 88.1% and 91.4%, respectively, when detecting cavitation events from unseen in-vivo data. The results demonstrate that the improved PCI scheme, utilizing the CD-NET model and a data-derived cavitation baseline, is resistant to noise from non-cavitation situations and can depict the dynamic characteristics of cavitation more reliably. In conclusion, this study addressed two practical challenges in PCI techniques, allowing for better monitoring of cavitation-related HIFU sonication in clinical applications. [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]

• In this study, we proposed a novel diffusion-based deep learning (DL) model (HIFU-Diff) for suppressing the HIFU interference in the ultrasound guiding images. • The HIFU-Diff network can achieve superior performance in preserving fine details of the original ultrasound image even under strong acoustic interference from the HIFU sonication, especially in the complex in-vivo situations. • The proposed HIFU-Diff network has high potential to realize truly real-time monitoring of HIFU treatment in ultrasound guided HIFU systems. In ultrasound guided high-intensity focused ultrasound (HIFU) surgery, it is necessary to transmit sound waves at different frequencies simultaneously using two transducers: one for the HIFU therapy and another for the ultrasound imaging guidance. In this specific setting, real-time monitoring of non-invasive surgery is challenging due to severe contamination of the ultrasound guiding images by strong acoustic interference from the HIFU sonication. This paper proposed the use of a deep learning (DL) solution, specifically a diffusion implicit model, to suppress the HIFU interference. We considered the images contaminated with HIFU interference as low-resolution images, and those free from interference as high-resolution. While suppressing HIFU interference using the diffusion implicit (HIFU-Diff) model, the task was transformed into generating a high-resolution image through a series of forward diffusion steps and reverse sampling. A series of ex-vivo and in-vivo experiments, conducted under various parameters, were designed to validate the performance of the proposed network. Quantitative evaluation and statistical analysis demonstrated that the HIFU-Diff network achieved superior performance in reconstructing interference-free images under a variety of ex-vivo and in-vivo conditions, compared to the most commonly used notch filtering and the recent 1D FUS-Net deep learning network. The HIFU-Diff maintains high performance with 'unseen' datasets from separate experiments, and its superiority is more pronounced under strong HIFU interferences and in complex in-vivo situations. Furthermore, the reconstructed interference-free images can also be used for quantitative attenuation imaging, indicating that the network preserves acoustic characteristics of the ultrasound images. With the proposed technique, HIFU therapy and the ultrasound imaging can be conducted simultaneously, allowing for real-time monitoring of the treatment process. This capability could significantly enhance the safety and efficacy of the non-invasive treatment across various clinical applications. To the best of our knowledge, this is the first diffusion-based model developed for HIFU interference suppression. [ABSTRACT FROM AUTHOR]

BackgroundNo reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication.MethodsWe collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated.ResultsA total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm3, p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time (p = 0.001), treatment duration (p = 0.002), and ablated energy (p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm3/min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency (p = 0.067), treatment speed (p = 0.007), treatment efficiency (p = 0.001), NPV per energy (p = 0.005), and NPV per sonication (p = 0.004) than other 2 groups.ConclusionLetrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results.

High-intensity focused ultrasound (HIFU), with inherent advantages of improved ultrasonic depth and low off-target damage, holds the promising capability for glioma treatment, but the relatively long therapeutic time and potential physical complications may hamper its clinical application. Herein, a bovine serum albumin (BSA)-based nanoplatform with in situ growth of MnO2 was synthesized, and Protoporphyrin IX (PpIX) was further anchored to obtain a versatile PpIX@MnO2@BSA nanoplatform (denoted as BMP). By employing HIFU as the exogenous irradiation source, a high-efficacy sonodynamic therapy (SDT) is developed, in which the excited BMP enables the production of tumoricidal reactive oxygen species (ROS). The inherent tumor microenvironment (TME)-responsive property of MnO2 endows BMP with specific T1-weighted magnetic resonance imaging (MRI) by releasing Mn2+, and the simultaneously generated O2 facilitates hypoxia alleviation as well as 1O2 generation. Compared with HIFU therapy alone, suppression of glioma growth and improved survival benefits are achieved through the designed TME-responsive nanocomposite under HIFU exposure. The high-efficacy SDT strategy combining BMP and HIFU demonstrated favorable TME-responsive T1-weighted MRI, hypoxic environment alleviation, and anti-tumor capability, providing a perspective paradigm for MRI-guided glioma treatment. [ABSTRACT FROM AUTHOR]

Aims: This study was conducted to explore the high-intensity focused ultrasound (HIFU) prepared antigen-sensitized dendritic cells (DC) and the induction of cytotoxic T lymphocyte (CTL) killing effects by DC and to observe their anti-tumor immunity effects on BALB/c mice.Methods and Material: GM-CSF and IL-4 were used to culture the mouse bone marrow-derived DC. HIFU was used to prepare CT-26 tumor cell antigen-sensitive DC vaccines. The capability of T cell proliferation was detected by 3H-TdR, and the CTL cytotoxicity was detected using standard 4h51Cr release assay. The DC-based tumor vaccine prepared using HIFU irradiation was given to normal BALB/c mice. The mice were injected with CT-26 cancer cells subcutaneously seven days later. Further, the occurrence time of the tumor, its weight and volume on the 20th day was observed, and the allergic DC group challenged using repeated-freezing-thawing method alone with the normal saline control group (negative control group) were used to compare group differences.Results: DC in the HIFU group, tumor cell freeze-thawing group, tumor supernatant group, and phosphate buffer solution (PBS) group could induce T cell proliferation in vitro. However, the ability to induce T cell proliferation of DC in the HIFU group and tumor cell freeze-thawing group was significantly higher than those in the tumor supernatant and PBS groups (P < 0. 05). CTL induced in vitro by DC in the HIFU group, and the tumor cell freeze-thawing group had significant cytotoxicity to colon cancer, being significantly different from those in the tumor supernatant and PBS groups (P < 0.05). There was no significant difference between the cytotoxicity of CTL induced in vitro in the HIFU group and the tumor cell freeze-thawing group (P > 0.05). Additionally, significant differences in the occurrence time of the tumor, its weight and volume on the 20th day, and the median survival time of mice among the HIFU group, the repeated-freezing-thawing group, and the negative control group were observed (P < 0.01 or P < 0.05). There was a significant difference between the HIFU and the repeated-freezing-thawing group (P < 0.05).Conclusions: HIFU prepared antigen-sensitized DC could cause substantial proliferation of T cells and CTL with strong anti-tumor effects. The DC-based tumor vaccine prepared using HIFU irradiation affected active immunization on the tumor occurrence in vitro and was better than the DC-based tumor vaccine prepared using the repeated-freezing-thawing method. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of high-intensity focused ultrasound (HIFU) combined with suction curettage in the treatment of exogenous cesarean scar pregnancy (CSP). Methods: A retrospective single-center observational study was conducted. A total of 41 patients diagnosed with exogenous CSP were enrolled in this study. All patients received HIFU combined with suction curettage. Results: Twenty-nine patients were administered one session of HIFU ablation. In addition, the other 12 patients received 2 HIFU sessions. Suction curettage was performed in all patients after HIFU, and no patient was converted to laparoscopy or hysterectomy. The mean blood loss during suction curettage was 99 ml. Three patients received two sessions of suction curettage. The success rate of our study was 92.68%. The mean time for serum β-HCG normalization was 23.18 ± 3.13 days. The average menstruation recovery time was 29.38 ± 3.34 days. Based on the blood loss during suction curettage, 41 patients were divided into a bleeding group and a control group. The size of the gestational sac in the bleeding group (3.80 ± 0.87 cm) was larger than that in the control group (3.39 ± 0.77 cm) (P < 0.05). The thickness of the myometrium between the bladder and gestational sac in the bleeding group (2.37 ± 0.89 mm) was less than that in the control group (2.75 ± 0.75 mm) (P < 0.05). Conclusion: The results suggested that HIFU combined with suction curettage could be considered an effective treatment for exogenous CSP of < 9 weeks. The size of the gestational sac and the thickness of the myometrium between the bladder and gestational sac might be high-risk factors for blood loss during this treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the proposed study was to conduct a feasibility study using a flat rectangular (2 × 10 mm2) transducer operating at 4.0 MHz for creating thermal lesions in an arterial atherosclerotic plaque phantom. The proposed method can be used in the future for treating atherosclerotic plaques in human arteries. Materials and methods: The flat rectangular transducer was firstly assessed in agar/silica evaporated milk phantom, polyacrylamide phantom and freshly excised turkeytissue phantom. Then, the same transducer was assessed in an arterial atherosclerotic plaque phantom which was created in the laboratory with a very low cost. The recipe of the atherosclerotic plaque phantom was 4% w/v agar, 1% w/v gypsum, 2% w/v butter and 93% water. The amount of plaque removal was evaluated visually and using an X-Ray system. Results: It was shown that the flat rectangular transducer can create thermal lesions on the agar/silica evaporated milk phantom, polyacrylamide phantom and in excised tissue. The size of the lesions matches the geometry of the transducer. Moreover, this transducer destroyed 27.1% of the atherosclerotic plaque phantom with 8 W acoustical power and 30 s duration. Conclusions: This feasibility study demonstrated that atherosclerotic plaque can be destroyed using a very small flat rectangular (2 × 10 mm2) transducer in a very small time interval of 30 s. In future clinical trials the transducer will be incorporated in a catheter which will be inserted intravascular (1–3 mm) wide and can be used to treat atherosclerotic plaques in the coronary arteries. [ABSTRACT FROM AUTHOR]

Objective To investigate the MRI features and clinical outcomes of unexpected uterine sarcomas in patients after high-intensity focused ultrasound (HIFU) ablation for presumed uterine fibroids. Materials and methods 15,759 consecutive patients who came for HIFU treatment, from November 2008 to September 2019, for presumed uterine fibroids were retrospectively reviewed. All the patients had completed a pre-HIFU MRI. All MRI images were independently analyzed and interpreted by two radiologists in every center. Results According to the T2WI MRI features of hyperintensity, accompanied by irregular margins, necrosis or cystic degeneration, multi-lobulated lesion with internal septation, 46 patients were suspected to be uterine sarcomas before HIFU. Eleven patients were histologically diagnosed as uterine sarcomas after laparotomy. Among the 15713 patients who received HIFU treatment for presumed uterine fibroids, 8 patients were found to have occult recurrence during the follow-up period, and 6 were confirmed histologically as uterine sarcomas after laparotomy. The incidence rate of uterine sarcomas was 0.108% (17/15759). Among them, 12 cases were low-grade endometrial stromal sarcoma (LG-ESS) and 5 cases were uterine leiomyosarcoma (LMS). No histological dissemination of the sarcoma was detected in patients with unexpected uterine sarcomas. Conclusion Although some MRI features of uterine sarcomas and uterine fibroids overlapped, MRI is valuable in distinguishing between uterine fibroids and uterine sarcomas. HIFU does not seem to cause histological dissemination of the sarcoma, but follow-up visits should be strictly adhered to in order to detect unexpected uterine sarcomas at an early stage and to treat them in a timely manner.

High-intensity focused ultrasound (HIFU) has been shown to be a valuable tool in the management of small liver tumors such as hepatocellular carcinoma (HCC). It has been shown to be a safe and effective means to ablate small HCC even in the presence of advanced cirrhosis. This review examines the challenges faced during HIFU ablation when the target tumors are located in difficult locations such as the liver dome, close to the rib cage, near large blood vessels or the heart, or adjacent to hollow viscera; and the special maneuvers employed to tackle such lesions.

High Intensity Focused Ultrasound (HIFU) capably bridges the disciplines of surgery, oncology and biomedical engineering science. It provides the precision associated with a surgical tool whilst remaining a truly non-invasive technique. Oxford has been a centre for both clinical and preclinical research in HIFU over the last twenty years. Research into this technology in the UK has a longer history, with much of the early research being carried out by Professor Gail ter Haar and her team at the Institute of Cancer Research at Sutton in Surrey. A broad range of potential applications have been explored extending from tissue ablation to novel drug delivery. This review presents Oxford’s clinical studies and applications for the development of this non-invasive therapy. This includes treatment of solid abdominal tumours comprising those of the liver, kidney, uterus, pancreas, pelvis and prostate. It also briefly introduces preclinical and translational works that are currently being undertaken at the Institute of Biomedical Engineering, University of Oxford. The safety, wide tolerability and effectiveness of this technology is comprehensively demonstrated across these studies. These results can facilitate the incorporation of HIFU as a key clinical management strategy.

Simple Summary: Desmoid tumors are benign neoplasms that invade locally, causing significant disability and morbidity. Historically, patients with desmoid tumors have been treated with surgery despite the significant morbidity associated with this modality. Less invasive treatments have emerged, including active surveillance, systemic therapy, radiotherapy, and local ablation. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed 262 patients with desmoid tumors treated at our institution over a period of 30 years. Our results suggest that initial active surveillance is a good option for patients with small and minimally symptomatic desmoid tumors, while tyrosine kinase inhibitors, local ablation, and surgery seem to be equally effective in those with more aggressive disease. The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0–87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and feasibility of high intensity focused ultrasound (HIFU) ablation followed by ultrasound-guided dilation and curettage (USg-D&C) for two types patients with cesarean scar pregnancy (CSP-I and CSP-II).Materials and Methods: This study was a retrospective analysis of 101 CSP-I patients and 52 CSP-II patients who received HIFU ablation followed by USg-D&C from Jun 2014 to Oct 2020. The diameter of gestational sac/mass, thickness of the intervening myometrium, intraoperative blood loss, operation time, length of hospital stays, adverse effects and β-HCG level in the two groups were compared.Results: All patients successfully received HIFU ablation under conscious sedation. The median total treatment time of HIFU ablation and median USg-D&C time in the CSP-I group were statistically longer than those in the CSP-II group (P < 0.05). The average intraoperative median blood loss was 39 ml in the CSP-I group and 65 ml in the CSP-II group (P < 0.05). The duration of hospitalization was 7.07 ± 1.83 days in the CSP-I group and 7.18 ± 1.72 days in the CSP-II group (P > 0.05). The average time needed for β-HCG return to normal levels was 26.08 ± 5.02. and 28.15 ± 4.99 days for CSP-I and CSP-II, respectively (P > 0.05). The percentage of adverse effects and complications was not significantly different between the two groups (P > 0.05).Conclusions: HIFU ablation followed by USg-D&C was safe and effective in treating the CSP-I patients and CSP-II patients, which may be a potential noninvasive therapeutic option for patients with CSP. [ABSTRACT FROM AUTHOR]

One of the problems with ultrasound imaging during high-intensity focused ultrasound (HIFU) treatment is that the therapeutic ultrasound components interfere with the diagnostic ultrasound components, making it impossible to monitor the tissue changes during HIFU exposure. In this study, a convolutional neural network (CNN) framework was applied to the reconstructed ultrasound images with HIFU noise to remove the therapeutic ultrasound components while the diagnostic ultrasound components remain intact. In the experiments, the chicken breast was used as a tissue sample and exposed to HIFU in the water tank. The ultrasound images with and without noise were acquired during an intermission period of HIFU exposure and the noise-reduced images was predicted using the proposed multi-layer regression CNN model through the training process. As a result, ultrasound images with sufficient spatial resolution to detect the thermal lesion were acquired. [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]

Purpose: The study evaluated high-intensity-focused ultrasound (HIFU) for benign thyroid nodules in terms of efficiency, complication rate, influence of preablative nodule size, parameters influencing the therapeutic success and hormonal-thyroid-function. Methods: Seventy-two patients with 75 nodules were treated with HIFU at 2 centers from 2014–2019. Median nodule volume was 4.4 ml (range 0.33–53). The therapeutic ultrasound probe (EchoPulse THC900888-H) generated 80–90 °C in the target tissue with 87.6–320.3 J per sonication. Nodal volume was measured at baseline and over 12 months after therapy in a retrospective bicentric-study with long-term follow-up. Hormonal-thyroid function (TSH, T3, T4) was measured before and after ablation. Complications were assessed. Results: Significant volume reduction (p < 0.05 Wilcoxon-signed-rank test) of thyroid nodules was 38.98% at 3 months, 37.32% at 6 months, 61.54% at 9 months and 60.66% at 12 months. Volume reduction of nodules <3 ml did not differ significantly from nodules >3 ml (p > 0.05 Mann–Whitney test). At 3 months solid nodules had a significant volume reduction of 52.08%, complex nodules of 32.57%, nodules treated under regional anesthesia of 33.07% and under general anesthesia of 49.47%. Hormonal-thyroid function was not influenced significantly by HIFU therapy (p > 0.05 Wilcoxon-signed-rank test). Complication rate was 3.8%. No long-term complications occurred. Conclusion: Significant volume reduction of thyroid nodules up to 12 months after HIFU was shown. All complications were reversible. Therapy was more efficient in solid than complex nodules and in nodules treated under general anesthesia than with regional anesthesia. Hormonal-thyroid-function was not affected. Trial registraftion number: 2020-1728-evBO. Date of registration: 16.06.2020. Agency: Ethik-Kommission bei der Landesäztekammer Hessen [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

Yu Tang, Chun Chen, Binglei Jiang, Lu Wang, Fujie Jiang, Disen Wang, Yaotai Wang, Haiyan Yang, Xia Ou, Yan Du, Qi Wang, Jianzhong Zou State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.Conclusion: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.Keywords: high intensity focused ultrasound, aptamers, nanoparticles, Bifidobacterium bifidum, tumor treatment

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, 111In-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 111In-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 24h after systematic delivery of 111In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors.

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.

Cancer immunotherapy, which enhances the body's immune response and inhibits immune escape to eliminate or combat tumors, holds great promise for cancer treatment. However, it still faces many challenges, such as low response rate and immune-related adverse events, which limit its clinical applications. Ultrasound, as a safe, effective and non-invasive technique, has been widely used in diagnostics and therapeutics of tumors. In recent years, many studies have confirmed that ultrasound can also mediate tumor immunotherapy. High intensity focused ultrasound can destroy tumor tissue and lead to the in situ production of tumor fragments at the same time, which can be used as antigens of the immune system to form in situ vaccines to induce a systemic immune response. The ultrasound-targeted microbubble destruction technique with microbubbles as the carrier mediates the targeted delivery of immunomodulatory adjuvants to tumor cells or immune cells. It can not only enhance the host immune response and improve immunotherapy efficacy, but also reduce the dosage of immunoregulatory adjuvants and side effects. Sonodynamic therapy can induce immunogenic cell death to elicit an immune response and the combination with immunotherapy can achieve higher therapeutic efficacy. In this review, research advances in ultrasound-mediated tumor immunotherapy are summarized, and the potential and challenges of its application are discussed.

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.

According to the traditional method of high intensity focused ultrasound (HIFU) treatment, the acoustic and thermal characteristic parameters of constant temperature (room temperature or body temperature) are used to predict thermal lesion. Based on the nonlinear spherical beam equation (SBE) and Pennes bio-heat transfer equation, and a new acoustic-thermal coupled model is proposed. The constant and temperature-dependent acoustic and thermal characteristic parameters are used to predict thermal lesion, and the predicted lesion area are compared with each other. Moreover, the relationship between harmonic amplitude ratio (P2/P1) and thermal lesion is studied. Combined with the known experimental data of acoustic and thermal characteristic parameters of biological tissue and data fitting method, the relationship between acoustic and thermal characteristic parameters and temperature is obtained; and the thermal lesion simulation calculation is carried out by using the acoustic and thermal characteristic parameters under constant temperature and temperature- dependent acoustic and thermal characteristic parameters, respectively. The simulation results show that under the same irradiation condition, the thermal lesion predicted by temperature-dependent acoustic and thermal characteristic parameters is larger than that predicted by traditional method, and the thermal lesion increases with the decrease of harmonic amplitude ratio.

The biological focal region (BFR) induced by a single high-intensity focused ultrasound (HIFU) exposure is considered to be the foundation of the ultrasound ablation of tumor lesions. The purpose of this study was to explore the relationship between the acoustic focal region (AFR) and the BFRs with different combinations of power and time in low-power cumulative HIFU treatment. The finite-difference time-domain (FDTD) method was used to simulate AFR and BFR during HIFU ablation. The acoustic fields, the temperature profiles, and the shapes of BFRs were calculated by the Westervelt equation, Pennes’ equation, and the equivalent thermal dose model. In order to verify the simulation rules, phantom and ex vivo bovine livers were exposed by HIFU with a different power and time. The results demonstrated that in the low-power cumulative HIFU treatment, when the lengths of BFRs and the length of AFR were approximately equal, the shape of the BFR induced by ‘high power × short time’ exposure was closer to that of AFR than the shape of the BFR induced by ‘low power × long time’ exposure, and the exposure energy required was significantly reduced. The analysis revealed the relationship between the BFR and the AFR with different acoustic power. This study provides a reference for doctors to determine power, time, and movement distance in clinical treatment.

Drug-loaded nanoparticles have been widely used as synergists in high-intensity focused ultrasound (HIFU) tumor ablation therapy. However, these synergists have certain limitations, such as poor tumor targeting and low accumulation at the tumor site, that restrict the therapeutic efficacy of HIFU. In this study, we utilized drug-loaded nanoparticles conjugated with genetically engineered bacteria which can selectively colonize the hypoxic areas of tumor to facilitate HIFU ablation. Genetically modified Escherichia coli carrying gas vesicles (GVs- E. coli), which were gas-filled protein nanostructures, had a negatively charged surface and could specifically target into the tumor. In contrast, paclitaxel (PTX) and perfluorohexane (PFH) co-loaded cationic lipid nanoparticles (PTX-CLs) had a positively charged surface, hence, GVs- E. coli was used as a vehicle by conjugating with PTX-CLs via electrostatic adsorption and subsequently attracting more PTX-CLs to the tumor site. To improve the therapeutic efficiency of HIFU, the GVs in GVs- E. coli and PFH encapsulated in PTX-CLs could act as cavitation nuclei to enhance the HIFU cavitation effect, while PTX entrapped in PTX-CLs was released at the tumor site under HIFU irradiation, enhancing the therapeutic efficacy of HIFU and chemo-synergistic therapy. This novel combination strategy has great potential for cancer treatment. • Drug-loaded nanoparticles were electrostatically adsorbed on engineered GVs- E. coli. • GVs- E. coli can selectively colonize tumor site and generate gas vesicles to enhance the HIFU cavitation effect. • These attract more drug-loaded NPs to the tumor site to promote apoptosis. • The novel strategy actualize synergies of HIFU/chemotherapy in tumor treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Computer-Aided Design & Computer Graphics / Jisuanji Fuzhu Sheji Yu Tuxingxue Xuebao is the property of Gai Kan Bian Wei Hui and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Encapsulation of cytotoxic drugs for a localized release is an effective way to increase the therapeutic window of such agents. In this article we present the localized release of doxorubicin (DOX) from phosphatidyldiglycerol (DPPG 2) based thermosensitive liposomes using MR-HIFU mediated hyperthermia in a swine model. German landrace pigs of weights between 37.5 and 53.5 kg received a 30-min infusion of DOX containing thermosensitive liposomes (50 mg DOX/m2). The pigs' biceps femoris was treated locally in two separate target areas with mild hyperthermia using magnetic resonance guided high intensity focused ultrasound, starting 10 min and 60 min after initiation of the infusion, respectively. The pharmacokinetics and biodistribution of DOX were determined and an analysis of the treatment parameters' influence was performed. Compared to untreated tissue, we found a 15-fold and a 7-fold increase in DOX concentration in the muscle volumes that had undergone hyperthermia starting 10 min and 60 min after the beginning of the infusion, respectively. The pharmacokinetic analysis showed a prolonged circulation time of DOX and a correlation between the AUC of extra-liposomal DOX in the bloodstream and the amount of DOX accumulated in the target tissue. We have demonstrated a workflow for MR-HIFU hyperthermia drug delivery that can be adapted to a clinical setting, showing that HIFU-hyperthermia is a suitable method for local drug release of DOX using DPPG 2 based thermosensitive liposomes in stationary targets. Using the developed pharmacokinetic model, an optimization of the drug quantity deposited in the target via the timing of infusion and hyperthermia should be possible. [Display omitted] • MR-HIFU Hyperthermia-mediated release of doxorubicin from thermosensitive liposomes • A human-like large animal model was used to facilitate clinical translation. • Local enhancement of drug concentration by factor 15 compared to control tissue. • The leakage half-life of DPPG 2 -TSL-DOX was calculated via pharmacokinetic modelling. • Local drug delivery is maximized by maximized blood doxorubicin during hyperthermia. [ABSTRACT FROM AUTHOR]

Introduction: Endovenous techniques such as ultrasound guided foam sclerotherapy, thermal methods, or glues are generally recommended to occlude incompetent veins. However, these methods can be technically challenging and risky for patients with severe atrophic skin disorders like lipodermatosclerosis or atrophie blanche. High intensity focused ultrasound (HIFU), which has been shown to coagulate and occlude veins successfully, may offer an alternative method. This case report details ultrasound guided HIFU to occlude non-invasively a refluxing perforator vein causing active ulcers. Report: A 95 year old man presented to the Institute for Functional Phlebology (Melk, Austria) with painful recurrent ulcers in his left medial calf. His limb was scored C2,3,4a, b,6, Ep, Ap, Pr,18 according to the Clinical, Etiology, Anatomic, Pathophysiology (CEAP) classification. Lower limb ultrasound revealed a refluxing posterior tibial perforating vein, measuring 2.7 mm in diameter at the level of the fascia. Extracorporeal HIFU pulses were delivered to this vein with the Sonovein device (Theraclion, Malakoff, France). Sonication was applied for eight seconds at a mean acoustic power of 80 W. The patient was followed up for three months post-treatment and occlusion was evaluated by duplex ultrasound. There were no complications during treatment or follow up. Three months after the treatment, reflux was abolished and the two initially active ulcers had healed. Discussion: Although this is an early report, this study shows that HIFU can be successful in ablation of incompetent perforator veins in the treatment of venous leg ulcers.