Hypoxia-Specific Metal-Organic Frameworks Augment Cancer Immunotherapy of High-Intensity Focused Ultrasound.

As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play a vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, a hypoxia-specific metal-organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances the photoacoustic imaging effects to achieve accurate intraoperative navigation. Within the HIFU-established severe hypoxic environment, AQ4N is activated sequentially, following which it cooperates with Fe3+ to effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses IDO-1 activity and degrades the immunosuppressive tumor microenvironment aggravated by postoperative hypoxia. In vivo studies demonstrate that the MOF-mediated immunotherapy greatly inhibits the growth of primary/distant tumors and eliminates lung metastasis. This work establishes a robust delivery platform to improve immunotherapy and the overall prognosis of HIFU surgery with high specificity and potency.

Focal Therapy in Grade Group 3 Prostate Cancer.

PURPOSE OF THIS REVIEW: Treatment of intermediate risk prostate cancer remains controversial. Clearly some patients with low volume favorable intermediate risk can be followed with active surveillance. Those with high volume bilateral disease need more radical whole gland therapy. The question remains on how to best treat low volume localized unfavorable intermediate risk prostate cancer (GG3) while maintaining quality of life. Focal therapy has been becoming a popular option for many patients with localized prostate cancer. Most studies looking at focal therapy for prostate cancer have been limited to GG1 and GG2, many of whom may not need treatment. We set out to review the literature evaluating the safety and efficacy of focal therapy for GG3 prostate cancer. RECENT FINDINGS: We reviewed multiple peer review articles obtained from a PubMed search. While in field biopsy recurrence rates approach 20%, failure free survival and overall survival exceeds 90%. While focal therapy for unfavorable GG3 intermediate risk prostate cancer may have higher rates of local recurrence with appropriate post procedure follow up, patients who need salvage therapy are easily identified and survival rates are very high. Focal therapy is a good option for patients with localized low volume GG3 prostate cancer without compromising cancer survival and preserving quality of life.

Suppressing the HIFU interference in ultrasound guiding images with a diffusion-based deep learning model.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pilot Study on High-Intensity Focused Ultrasound (HIFU) for Basal Cell Carcinoma: Effectiveness and Safety.

Background: The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally invasive treatment alternatives. Traditional surgical approaches, while effective, often result in notable cosmetic and functional limitations, particularly for lesions located on the face. This study explores High-Intensity Focused Ultrasound (HIFU) as a promising, non-invasive treatment option that aims to overcome these challenges, potentially revolutionizing BCC treatment by offering a balance between efficacy and cosmetic outcomes. Methods: Our investigation enrolled 8 patients, presenting a total of 15 BCC lesions, treated with a 20 MHz HIFU device. The selection of treatment parameters was precise, utilizing probe depths from 0.8 mm to 2.3 mm and energy settings ranging from 0.7 to 1.3 Joules (J) per pulse, determined by the lesion's infiltration depth as assessed via pre-procedure ultrasonography. A key component of our methodology included dermatoscopic monitoring, which allowed for detailed observation of the lesions' response to treatment over time. Patient-reported outcomes and satisfaction levels were systematically recorded, providing insights into the comparative advantages of HIFU. Results: Initial responses after HIFU treatment included whitening and edema, indicative of successful lesion ablation. Early post-treatment observations revealed minimal discomfort and quick recovery, with crust formation resolving within two weeks for most lesions. Over a period of three to six months, patients reported significant improvement, with lesions becoming lighter and blending into the surrounding skin, demonstrating effective and aesthetically pleasing outcomes. Patient satisfaction surveys conducted six months post-treatment revealed high levels of satisfaction, with 75% of participants reporting very high satisfaction due to minimal scarring and the non-invasive nature of the procedure. No recurrences of BCC were noted, attesting to the efficacy of HIFU as a treatment option. Conclusions: The findings from this study confirm that based on dermoscopy analysis, HIFU is a highly effective and patient-preferred non-invasive treatment modality for Basal Cell Carcinoma. HIFU offers a promising alternative to traditional surgical and non-surgical treatments, reducing the cosmetic and functional repercussions associated with BCC management. Given its efficacy, safety, and favorable patient satisfaction scores, HIFU warrants further investigation and consideration for broader clinical application in the treatment of BCC, potentially setting a new standard in dermatologic oncology care. This work represents a pilot study that is the first to describe the use of HIFU in the treatment of BCC.

Optimized Schlieren imaging for real-time visualization of high-intensity focused ultrasound waves.

OBJECTIVES: This article presents an low-cost experimental setup for visualizing refraction anomalies caused by high-intensity focused ultrasound (HIFU). The technique is based on Schlieren imaging, commonly used to visualize temperature and pressure differences in a medium. With this setup, double images of the Schlieren or their shadows to be investigated occur, so that the experimental setup is modified to avoid these double image artifacts. METHODS: The optical setup mainly consists of a point light source, a parabolic mirror, and a camera. Birefringence artifacts are avoided by placing the point light source at a certain vertical distance to the camera, so that the light beam passes through the medium only once. The soundfield is generated by a HIFU transducer in a water tank placed in the beam path of the optical setup. RESULTS: The experimental setup is capable of capturing Schlieren or shadow images. These images show the soundfield without disturbing double images and enable further analysis and qualitative assessment of the soundfield. CONCLUSIONS: The presented setup provides a reliable and efficient method for visualizing refraction anomalies caused by the sonic field of a HIFU transducer and allows for accurate depiction of the refraction anomalies. The double images that usually occur are avoided.

2D ultrasound thermometry during thermal ablation with high-intensity focused ultrasound.

The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has recently gained momentum. Guidance is provided by either magnetic resonance imaging (MRI) or conventional B-mode ultrasound imaging, each with its own advantages and disadvantages. The main limitation of ultrasound imaging is its inability to provide temperature measurements over the ranges corresponding to the target temperatures during ablative thermal therapies (between 55 °C and 70 °C). Here, variations in ultrasound backscattered energy (ΔBSE) were used to monitor temperature increases in liver tissue up to an absolute value of 90 °C during and after HIFU treatment. In vitro experimental measurements were performed in 47 bovine liver samples using a toroidal HIFU transducer operating at 2.5 MHz to increase the temperature of tissues. An ultrasound imaging probe working at 7.5 MHz was placed in the center of the HIFU transducer to monitor the backscattered signals. The free-field acoustic power was set to 9 W, 12 W or 16 W in the different experiments. HIFU sonications were performed for 240 s using a duty cycle of 83 % to allow ultrasound imaging and raw radiofrequency data acquisition during exposures. Measurements showed a linear relationship between ΔBSE (in dB) and temperature (r = 0.94, p < 0.001) over a temperature range from 37 °C to 90 °C, with a high reliability of temperature measurements below 75 °C. Monitoring can be performed at the frame rate of ultrasound imaging scanners with an accuracy within an acceptable threshold of 5 °C, given the temperatures targeted during thermal ablations. If the maximum temperature reached is below 70 °C, ΔBSE is also a reliable approach for estimating the temperature during cooling. Histological analysis shown the impact of the treatment on the spatial arrangement of cells that can explain the observed variation of ΔBSE. These results demonstrate the ability of ΔBSE measurements to estimate temperature in ultrasound images within an effective therapeutic range. This method can be implemented clinically and potentially applied to other thermal-based therapies.

Numerical studies on shortening the duration of HIFU ablation therapy and their experimental validation.

High Intensity Focused Ultrasound (HIFU) is used in clinical practice for thermal ablation of malignant and benign solid tumors located in various organs. One of the reason limiting the wider use of this technology is the long treatment time resulting from i.a. the large difference between the size of the focal volume of the heating beam and the size of the tumor. Therefore, the treatment of large tumors requires scanning their volume with a sequence of single heating beams, the focus of which is moved in the focal plane along a specific trajectory with specific time and distance interval between sonications. To avoid an undesirable increase in the temperature of healthy tissues surrounding the tumor during scanning, the acoustic power and exposure time of each HIFU beam as well as the time intervals between sonications should be selected in such a way as to cover the entire volume of the tumor with necrosis as quickly as possible. This would reduce the costs of treatment. The aim of this study was to quantitatively evaluate the hypothesis that selecting the average acoustic power and exposure time for each individual heating beam, as well as the temporal intervals between sonications, can significantly shorten treatment time. Using 3D numerical simulations, the dependence of the duration of treatment of a tumor with a diameter of 5 mm or 9 mm (requiring multiple exposure to the HIFU beam) on the sonication parameters (acoustic power, exposure time) of each single beam capable of delivering the threshold thermal dose (CEM43 = 240 min) to the treated tissue volume was examined. The treatment duration was determined as the sum of exposure times to individual beams and time intervals between sonications. The tumor was located inside the ex vivo tissue sample at a depth of 12.6 mm. The thickness of the water layer between the HIFU transducer and the tissue was 50 mm. The sonication and scanning parameters selected using the developed algorithm shortened the duration of the ablation procedure by almost 14 times for a 5-mm tumor and 20 times for a 9-mm tumor compared to the duration of the same ablation plan when a HIFU beam was used of a constant acoustic power, constant exposure time (3 s) and constant long time intervals (120 s) between sonications. Results of calculations of the location and size of the necrotic lesion formed were experimentally verified on ex vivo pork loin samples, showing good agreement between them. In this way, it was proven that the proper selection of sonication and scanning parameters for each HIFU beam allows to significantly shorten the time of HIFU therapy.

Prediction of high-intensity focused ultrasound (HIFU)-induced lesion size using the echo amplitude from the focus in tissue.

In the realm of high-intensity focused ultrasound (HIFU) therapy, the precise prediction of lesion size during treatment planning remains a challenge, primarily due to the difficulty in quantitatively assessing energy deposition at the target site and the acoustic properties of the tissue through which the ultrasound wave propagates. This study investigates the hypothesis that the echo amplitude originating from the focus is indicative of acoustic attenuation and is directly related to the resultant lesion size. Echoes from multi-layered tissues, specifically porcine tenderloin and bovine livers, with varying fat thickness from 0 mm to 35 mm were collected using a focused ultrasound (FUS) transducer operated at a low power output and short duration. Subsequent to HIFU treatment under clinical conditions, the resulting lesion areas in the ex vivo tissues were meticulously quantified. A novel treatment strategy that prioritizes treatment spots based on descending echo amplitudes was proposed and compared with the conventional raster scan approach. Our findings reveal a consistent trend of decreasing echo amplitudes and HIFU-induced lesion areas with the increasing fat thickness. For porcine tenderloin, the values decreased from 2541.7 ± 641.9 mV and 94.4 ± 17.9 mm2 to 385(342.5) mV and 24.9 ± 18.7 mm2, and for bovine liver, from 1406(1202.5) mV and 94.4 ± 17.9 mm2 to 502.1 ± 225.7 mV and 9.4 ± 6.3 mm2, respectively, as the fat thickness increases from 0 mm to 35 mm. Significant correlations were identified between preoperative echo amplitudes and the HIFU-induced lesion areas (R = 0.833 and 0.784 for the porcine tenderloin and bovine liver, respectively). These correlations underscore the potential for an accurate and dependable prediction of treatment outcomes. Employing the proposed treatment strategy, the ex vivo experiment yielded larger lesion areas in bovine liver at a penetration depth of 8 cm compared to the conventional approach (58.84 ± 17.16 mm2 vs. 44.28 ± 15.37 mm2, p < 0.05). The preoperative echo amplitude from the FUS transducer is shown to be a reflective measure of acoustic attenuation within the wave propagation window and is closely correlated with the induced lesion areas. The proposed treatment strategy demonstrated enhanced efficiency in ex vivo settings, affirming the feasibility and accuracy of predicting HIFU-induced lesion size based on echo amplitude.

Is high-intensity focused ultrasound a magical solution to endometriosis? A systematic review.

Background: Endometriosis presents a significant challenge in gynecological endocrinology, affecting approximately 1 in 10 women of reproductive age. Abdominal wall endometriosis (AWE) and rectosigmoid deep infiltrating endometriosis (DIE) pose unique clinical complexities. High-intensity focused ultrasound (HIFU) has emerged as a novel alternative for treating these conditions, offering a noninvasive option with potential therapeutic benefits. Methods: A systematic review was conducted following PRISMA guidelines to investigate the safety and efficacy of HIFU therapy for AWE and rectosigmoid DIE. The literature search encompassed databases from inception to January 20, 2024. Eligible studies included observational studies, case reports, and clinical trials evaluating HIFU treatment for endometriosis. Data extraction and risk of bias assessment were performed following established protocols. Results: Fourteen studies were included, comprising 330 patients with AWE and 28 patients with rectosigmoid DIE. HIFU treatment demonstrated significant efficacy, with many patients experiencing complete remission, and clinical effectiveness. Reductions in lesion volume posttreatment were consistent across studies. However, safety concerns were noted, including pain at the treatment site, hematuria, and skin burns. Adverse effects underscored the importance of careful patient selection and monitoring during HIFU therapy. Conclusion: HIFU therapy shows promise as a noninvasive approach for managing AWE and rectosigmoid DIE. While efficacy outcomes are encouraging, safety considerations warrant attention. Further research, particularly randomized controlled trials with larger sample sizes, is needed to validate findings and optimize treatment protocols.

The safety and efficacy of myomectomy in the treatment of recurrent uterine fibroids after HIFU.

OBJECTIVE: To evaluate the safety and efficacy of myomectomy for recurrent uterine fibroids (UFs) after high-intensity focused ultrasound (HIFU) ablation. METHODS: This was a retrospective study. Patients who underwent abdominal myomectomy (AM) and laparoscopic myomectomy (LM) from January 2018 to December 2021 at the Three Gorges Hospital of Chongqing University were included. Among them, 73 had undergone prior HIFU ablation (Group 1), while 120 had not undergone HIFU (Group 2). Outcome measures included operating time, estimated blood loss (EBL), blood transfusion, postoperative activity times (PAT), duration of hospital stay (DOHS), and complications. RESULTS: The operating time was 90.0 min (70.5, 115.0) for Group 1 and 110.0 min (81.5, 130.0) for Group 2 (P < 0.05). During all AM pathways, there were no significant differences observed between the two groups in EBL, blood transfusion, PAT, DOHS, and complications; however, operating time was shorter in Group 1. The operating time, EBL, blood transfusion, PAT, DOHS, and complications were similar in both groups during LM pathway. During the follow-up 40 (range: 24-53) months, the rate of relief, recurrence, and reintervention in Groups 1 and 2 was 78.1% versus 74.1%, 14.6% versus 16.4%, and 3.7% versus 2.6%, respectively (P > 0.05). CONCLUSION: Myomectomy is a safe and effective surgical method for treating recurrent UFs after HIFU. Myomectomy for treating recurrent UFs resulted in a shorter operative and hospital stay, reduced blood loss, faster postoperative recovery, and fewer complications, better symptom relief rates, and lower risk of recurrence or reintervention. These findings indicate that previous HIFU ablation does not worsen the outcomes of the subsequent myomectomy.

A Fast and Interactive Augmented Reality System for PET/CT-guided Intervention of Neuroblastoma.

Neuroblastoma is the most common type of extracranial solid tumor in children and can often result in death if not treated. High-intensity focused ultrasound (HIFU) is a non-invasive technique for treating tissue that is deep within the body. It avoids the use of ionizing radiation, avoiding long-term side-effects of these treatments. The goal of this project was to develop the rendering component of an augmented reality (AR) system with potential applications for image-guided HIFU treatment of neuroblastoma. Our project focuses on taking 3D models of neuroblastoma lesions obtained from PET/CT and displaying them in our AR system in near real-time for use by physicians. We used volume ray casting with raster graphics as our preferred rendering method, as it allows for the real-time editing of our 3D radiologic data. Some unique features of our AR system include intuitive hand gestures and virtual user interfaces that allow the user to interact with the rendered data and process PET/CT images for optimal visualization. We implemented the feature to set a custom transfer function, set custom intensity cutoff points, and region-of-interest extraction via cutting planes. In the future, we hope to incorporate this work as part of a complete system for focused ultrasound treatment by adding ultrasound simulation, visualization, and deformable registration.

High Intensity Focused Ultrasound (20 MHz) and Cryotherapy as Therapeutic Options for Granuloma Annulare and Other Inflammatory Skin Conditions.

INTRODUCTION: In dermatology, inflammatory skin conditions impose a substantial burden worldwide, with existing therapies showing limited efficacy and side effects. This report aims to compare a novel immunological activation induced by hyperthermic 20 MHz high intensity focused ultrasound (HIFU) with conventional cryotherapy. The bioeffects from the two methods are initially investigated by numerical models, and subsequently compared to clinical observations after treatment of a patient with the inflammatory disease granuloma annulare (GA). METHODS: Clinical responses to moderate energy HIFU and cryotherapy were analysed using numerical models. HIFU-induced pressure and heat transfer were calculated, and a three-layer finite element model simulated temperature distribution and necrotic volume in the skin. Model output was compared to 22 lesions treated with HIFU and 10 with cryotherapy in a patient with GA. RESULTS: Cryotherapy produced a necrotic volume of 138.5 mm3 at - 92.7 °C. HIFU at 0.3-0.6 J/exposure and focal depths of 0.8 or 1.3 mm generated necrotic volumes up to only 15.99 mm3 at temperatures of 68.3-81.2 °C. HIFU achieved full or partial resolution in all treated areas, confirming its hyperthermic immunological activation effect, while cryotherapy also resolved lesions but led to scarring and dyspigmentation. CONCLUSION: Hyperthermic immunological activation of 20 MHz HIFU shows promise for treating inflammatory skin conditions as exemplified by GA. Numerical models demonstrate minimal skin necrosis compared to cryotherapy. Suggested optimal HIFU parameters are 1.3 mm focal depth, 0.4-0.5 J/exposure, 1 mm spacing, and 1 mm margin. Further studies on GA and other inflammatory diseases are recommended.

Achieving NPVR ≥ 80% as technical success of high-intensity focused ultrasound ablation for uterine fibroids: a cohort study.

OBJECTIVE: To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group. MATERIALS AND METHODS: Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan-Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group. MAIN RESULTS: A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR < 70% group, 31.0% in the NPVR 70-79% group, 18.2% in the NPVR 80-89% group and 17.8% in the NPVR ≥ 90% group (P < 0.05). However, no difference was found between the group of NPVR 80-89% and the group of NPVR ≥ 90% (P = 0.499). Age of patients and signal intensity on T2-weighted imaging (T2WI) of tumours were found to be independent risk factors for long-term re-intervention in the NPVR ≥ 80% group. A younger age and greater signal intensity on T2W images corresponded to a greater risk of re-intervention. CONCLUSION: USgHIFU, an alternative treatment for uterine fibroids, has reliable long-term efficacy. NPVR ≥ 80% can be used as a sign of technical success, which can reduce re-intervention rates. However, an important step is to communicate with patients in combination with the age of patients and the signal intensity on T2WI of fibroids. TRIAL REGISTRATION: This retrospective study was approved by the ethics committee at our institution (Registration No. HF2023001; Date: 06/04/2023). The Chinese Clinical Trial Registry provided full approval for the study protocol (Registration No. CHiCTR2300074797; Date: 16/08/2023).

The Effectiveness of High-Intensity Focused Ultrasound in Treating Nasal Obstruction Caused by Inferior Turbinate Hypertrophy: A Clinical Study.

Background Nasal obstruction due to inferior turbinate hypertrophy is a common medical complaint among ENT clinic patients, which can significantly affect the patient's quality of life, and some are compelled to use topical intranasal decongestants. Conservative management is the first line of treatment; however, surgical reduction of the inferior turbinate becomes necessary if the symptoms persist after three months of treatment. The optimal surgical technique is controversial. High-intensity focused ultrasound (HIFU) is a minimally invasive surgical option that targets tissue volume precisely and minimally impacts surrounding tissue. This study aimed to assess the effectiveness and safety of HIFU in treating patients suffering from nasal obstruction due to inferior turbinate hypertrophy. Methods This prospective study was conducted from February to December 2016. The study lasted over six months. Patients with a history of allergic and non-allergic rhinitis participated in this study. It included 43 patients who had been experiencing chronic nasal obstruction due to bilateral inferior turbinate hypertrophy and had not shown improvement after three months of medical treatment. The patients underwent Ultrasound Volumetric Tissue Reduction (UVTR) surgery using the D & A Ultrasurg device (Diamant Medical Equipment Ltd., Amman, Jordan) under local anesthesia. The effectiveness, safety, and tolerance of HIFU were assessed subjectively for six months using a well-designed questionnaire utilizing a visual analog scale (VAS) and nasal endoscopy after the surgery. Results The study included 43 patients, 22 male and 21 female, aged 13 to 65 years. The study found that 40 (93%) patients showed significant improvement in nasal obstruction within a month of the surgery. However, three (7%) patients continued to experience persistent nasal obstruction even after six months of follow-up. The procedure was well-tolerated, with low rates of complications after surgery and reasonable pain control. During the surgery, 20 (46.5%) patients reported mild pain described as a pressure-like sensation, and 10 out of 43 patients (23%) required paracetamol after the procedure. Four patients (9.3%) had mild bleeding, which was treated with an ultrasound nasal probe without nasal packing. All patients experienced crusting of the nasal cavity during the first week, but no crustation was observed after the first month. There were no reported cases of synechia among the patients. Conclusion This study confirms that HIFU treatment is a reliable and effective treatment for improving short-term nasal obstruction caused by inferior turbinate hypertrophy. The procedure is easily applied and well-tolerated in outpatient clinics.

Experimental and Computational Analysis of High-Intensity Focused Ultrasound Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids.

High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality that uses precise acoustic energy to ablate cancerous tissues through coagulative necrosis. In this context, we investigate the efficacy of HIFU ablation in two distinct cellular configurations, namely 2D monolayers and 3D spheroids of epithelial breast cancer cell lines (MDA-MB 231 and MCF7). The primary objective is to compare the response of these two in vitro models to HIFU while measuring their ablation percentages and temperature elevation levels. HIFU was systematically applied to the cell cultures, varying ultrasound intensity and duty cycle during different sonication sessions. The results indicate that the degree of ablation is highly influenced by the duty cycle, with higher duty cycles resulting in greater ablation percentages, while sonication duration has a minimal impact. Numerical simulations validate experimental observations, highlighting a significant disparity in the response of 2D monolayers and 3D spheroids to HIFU treatment. Specifically, tumor spheroids require lower temperature elevations for effective ablation, and their ablation percentage significantly increases with elevated duty cycles. This study contributes to a comprehensive understanding of acoustic energy conversion within the biological system during HIFU treatment for 2D versus 3D ablation targets, holding potential implications for refining and personalizing breast cancer therapeutic strategies.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

MRI-based monitoring of prostate cancer after HIFU: Inter-reader agreement and diagnostic performance of the PI-FAB score.

PURPOSE: To investigate inter-reader agreement, and diagnostic performance of the Prostate Imaging after Focal Ablation (PI-FAB) score applied to multiparametric MRI (mpMRI) in patients who underwent focal high-intensity focused ultrasound (HIFU) therapy for localized prostate cancer. METHODS: In this retrospective, IRB-approved, single-center study, 73 men, who underwent focal HIFU treatment and received follow-up mpMRIs with subsequent prostate biopsies, were included. The PI-FAB score was applied to follow-up MRIs at 6, 12, and 36 months post-HIFU by two radiologists with different experience levels. Inter-reader agreement was assessed using Gwet's AC1, and the diagnostic performance of the PI-FAB score was assessed in relation to histopathologic results of subsequent prostate biopsies for each reader. RESULTS: PI-FAB scores showed substantial to almost perfect inter-reader agreement (AC1: 0.80-0.95) and demonstrated high specificity (Reader 1: 90-98 %, Reader 2: 87-98 %) and NPVs (Reader 1: 91-100 %, Reader 2: 88-97 %) in ruling out residual or recurrent in-field prostate cancer post-HIFU. Sensitivity (Reader 1: ≥43 %, Reader 2: ≥14 %) and PPVs (Reader 1: ≥33 %, Reader 2: ≥14 %) were mostly relatively lower, with notable disparities between the two readers, indicating the potential influence of radiologist experience. CONCLUSIONS: The PI-FAB score provides a consistent and reliable tool for post-HIFU monitoring of prostate cancer using mpMRI. It demonstrates substantial to almost perfect inter-reader agreement and is particularly effective in excluding in-field residual or recurrent prostate cancer post-HIFU treatment. Its application can potentially enhance post-treatment patient care, emphasizing its value as a non-invasive MRI-based monitoring approach after focal ablative therapy of the prostate.

Advances in Tumor Management: Harnessing the Potential of Histotripsy.

Tissue ablation techniques have long been used in clinical settings to treat various oncologic diseases. However, many of these techniques are invasive and can cause substantial adverse effects. Histotripsy is a noninvasive, nonionizing, nonthermal tissue ablation technique that has the potential to replace surgical interventions in various clinical settings. Histotripsy works by delivering high-intensity focused ultrasound waves to target tissue. These waves create cavitation bubbles within tissues that rapidly expand and collapse, thereby mechanically fractionating the tissue into acellular debris that is subsequently absorbed by the body's immune system. Preclinical and clinical studies have demonstrated the efficacy of histotripsy in treating a range of diseases, including liver, pancreatic, renal, and prostate tumors. Safety outcomes of histotripsy have been generally favorable, with minimal adverse effects reported. However, further studies are needed to optimize the technique and understand its long-term effects. This review aims to discuss the importance of histotripsy as a noninvasive tissue ablation technique, the preclinical and clinical literature on histotripsy and its safety, and the potential applications of histotripsy in clinical practice. Keywords: Tumor Microenvironment, Ultrasound-High-Intensity Focused (HIFU), Ablation Techniques, Abdomen/GI, Genital/Reproductive, Nonthermal Tissue Ablation, Histotripsy, Clinical Trials, Preclinical Applications, Focused Ultrasound © RSNA, 2024.

High-Intensity Focused Ultrasound in Dentistry: A Literature Review.

Although high-intensity focused ultrasound (HIFU) has been applied widely in medicine, utilising its non-invasive dual ablation and thermal coagulation properties, its application in dentistry has primarily remained in the research phase, predominantly in in vitro studies. Nonetheless, there has been a consistent increase in the number of publications on this subject in recent decades, focusing on areas such as remineralisation of dentine surfaces, removal of smear layers, drug delivery, and microbial elimination. The number of advantages HIFU can offer, such as its non-surgical nature, absence of ionising radiation, lack of residue, and absence of aerosols, is driving this upward trend, indicating the potential for HIFU in clinical dentistry and ongoing efforts towards developing HIFU-based devices for routine dental use. This succinct review aims to outline the historical context, operational mechanisms of HIFU, summarise recent dental research, and provide a forward-looking perspective on the role of HIFU in modern clinical dentistry.

Safety and Efficacy of High-Intensity Focused Ultrasound and Monopolar Radiofrequency Combination Therapy for Skin Tightening: A Retrospective Study in Malaysia.

Background: High-intensity focused ultrasound (HIFU) and monopolar radiofrequency (MRF) are common treatment modalities that have shown significant results in skin tightening. Nevertheless, the novel combination of these two treatments is new to the Malaysian landscape. Thus, this study aims to investigate the safety and efficacy of this novel combination treatment for the Malaysian population. Methods: This retrospective study included data on HIFU and MRF combination therapy for skin tightening collected from an aesthetic clinic in Johor Bahru, Malaysia from June 2018 to May 2021. Efficacy was assessed using the Global Aesthetic Improvement Scale (GAIS) and Glogau classification, while the safety of the treatment was analysed using pain scores and adverse events (AEs). Results: A total of 56 patients with a mean age of 47.7 years old (SD 10.00) were included in this study. The majority of the patients had Fitzpatrick skin types III and IV. Most of the patients were Chinese, followed by Malay, Indian and others. Most patients (96.4%) showed clinically significant improvement in skin tightening after treatment, with 15 patients scoring 1 (very much improved) and 39 scoring 2 (improved). All patients reported transient mild erythema, with no serious AEs, such as burn, swelling, numbness or muscle weakness. Among the patients, 80% reported a pain score of 5, while 10% reported pain scores of 4 and 6. Conclusion: Combining HIFU with MRF therapy improved GAIS scores by 96.4%, indicating a secure and efficient skin-tightening method. Transient erythema was shown to be the most common side effect of this combination.