Effectiveness of high-intensity focused ultrasound combined with gonadotropin-releasing hormone agonist or combined with levonorgestrel-releasing intrauterine system for adenomyosis: A systematic review and meta-analysis.

Gonadotropin-Releasing Hormone Agonist (GnRH-a) and levonorgestrel releasing intrauterine system (LNG-IUS) are conventional conservative treatments for adenomyosis, and high-intensity focused ultrasound (HIFU) is a novel ablation technique. This study aimed to investigate the effectiveness of HIFU combined with GnRH-a or LNG-IUS for adenomyosis patients. In this systematic review and meta-analysis, Pubmed, Embase, Cochrane Library and Scopus databases were searched up to December 2021. Published studies comparing HIFU plus GnRH-a with HIFU plus LNG-IUS in adenomyosis patients were assessed for eligibility by two independent authors. Risk of bias tool was utilized for risk evaluation. We selected treatment effective rate of dysmenorrhea (pain during menstruation) as the primary outcome; effective rate of menorrhagia severity and reduction rate of adenomyotic lesion as the secondary outcomes. Adverse effects were assessed. Four studies with a total 729 patients were enrolled in the meta-analysis. HIFU plus LNG-IUS showed lower dysmenorrhea [within 6 months: risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83-0.93, p < 0.00001; over 1 year: RR 0.73, 95% CI 0.65-0.82, p < 0.00001] and less menorrhagia severity (RR 0.63, 95% CI 0.60-0.66, p < 0.00001) than HIFU plus GnRH-a. Both groups demonstrated equal efficacy in adenomyotic lesion reduction rate (RR 1.03, 95% CI 0.97-1.09, p = 0.30). Adverse effects happened equally in both groups. Combination therapy of HIFU and LNG-IUS revealed better effectiveness in treating dysmenorrhea and menorrhagia than that of HIFU and GnRH-a. However, interpreting the conclusion should be approached with caution as a result of significant heterogeneity.

Laser tattoo removal strategies: Part II: A review of the methods, techniques, and complications involved in tattoo removal.

The rising global popularity of cosmetic and corrective tattoos has concurrently led to an increased demand for their removal. While in the past, methods like surgical excision, chemical destruction, and dermabrasion were employed, lasers have emerged as a reliable and effective tool for tattoo removal. Increasing technological options and combination treatment strategies have raised the importance of understanding the various approaches to laser tattoo removal along with their respective clinical impact. This CME aims to describe the multifaceted aspects of laser tattoo removal, including the method selection, application principles, and safety considerations. Furthermore, it addresses the factors considered when selecting the most suitable laser to achieve optimal treatment outcomes.

Development and validation of a deep learning-based method for automatic measurement of uterus, fibroid, and ablated volume in MRI after MR-HIFU treatment of uterine fibroids.

INTRODUCTION: The non-perfused volume divided by total fibroid load (NPV/TFL) is a predictive outcome parameter for MRI-guided high-intensity focused ultrasound (MR-HIFU) treatments of uterine fibroids, which is related to long-term symptom relief. In current clinical practice, the MR-HIFU outcome parameters are typically determined by visual inspection, so an automated computer-aided method could facilitate objective outcome quantification. The objective of this study was to develop and evaluate a deep learning-based segmentation algorithm for volume measurements of the uterus, uterine fibroids, and NPVs in MRI in order to automatically quantify the NPV/TFL. MATERIALS AND METHODS: A segmentation pipeline was developed and evaluated using expert manual segmentations of MRI scans of 115 uterine fibroid patients, screened for and/or undergoing MR-HIFU treatment. The pipeline contained three separate neural networks, one per target structure. The first step in the pipeline was uterus segmentation from contrast-enhanced (CE)-T1w scans. This segmentation was subsequently used to remove non-uterus background tissue for NPV and fibroid segmentation. In the following step, NPVs were segmented from uterus-only CE-T1w scans. Finally, fibroids were segmented from uterus-only T2w scans. The segmentations were used to calculate the volume for each structure. Reliability and agreement between manual and automatic segmentations, volumes, and NPV/TFLs were assessed. RESULTS: For treatment scans, the Dice similarity coefficients (DSC) between the manually and automatically obtained segmentations were 0.90 (uterus), 0.84 (NPV) and 0.74 (fibroid). Intraclass correlation coefficients (ICC) were 1.00 [0.99, 1.00] (uterus), 0.99 [0.98, 1.00] (NPV) and 0.98 [0.95, 0.99] (fibroid) between manually and automatically derived volumes. For manually and automatically derived NPV/TFLs, the mean difference was 5% [-41%, 51%] (ICC: 0.66 [0.32, 0.85]). CONCLUSION: The algorithm presented in this study automatically calculates uterus volume, fibroid load, and NPVs, which could lead to more objective outcome quantification after MR-HIFU treatments of uterine fibroids in comparison to visual inspection. When robustness has been ascertained in a future study, this tool may eventually be employed in clinical practice to automatically measure the NPV/TFL after MR-HIFU procedures of uterine fibroids.

Noninvasive Monitoring of Tissue Temperature Changes Induced by Focused Ultrasound Exposure using Sparse Expression of Ultrasonic Radio Frequency Echo Signals.

Background: Noninvasive therapies such as focused ultrasound were developed to be used for cancer therapies, vessel bleeding, and drug delivery. The main purpose of focused ultrasound therapy is to affect regions of interest (ROI) of tissues without any injuries to surrounding tissues. In this regard, an appropriate monitoring method is required to control the treatment. Methods: This study is aimed to develop a noninvasive monitoring technique of focused ultrasound (US) treatment using sparse representation of US radio frequency (RF) echo signals. To this end, reasonable results in temperature change estimation in the tissue under focused US radiation were obtained by utilizing algorithms related to sparse optimization as orthogonal matching pursuit (OMP) and accompanying Shannon's entropy. Consequently, ex vivo tissue experimental tests yielded two datasets, including low-intensity focused US (LIFU) and high-intensity focused US (HIFU) data. The proposed processing method analyzed the ultrasonic RF echo signal and expressed it as a sparse signal and calculated the entropy of each frame. Results: The results indicated that the suggested approach could noninvasively estimate temperature changes between 37°C and 47°C during LIFU therapy. In addition, it represented temperature changes during HIFU ablation at various powers, ranging from 10 to 130 W. The normalized mean square error of the proposed method is 0.28, approximately 2.15 on previous related methods. Conclusion: These results demonstrated that this novel proposed approach, including the combination of sparsity and Shanoon's entropy, is more feasible and effective in temperature change estimation than its predecessors.

Boiling histotripsy exhibits anti-fibrotic effects in animal models of liver fibrosis.

Liver fibrosis is a hallmark of chronic liver disease which could lead to liver cirrhosis or liver cancer. However, there is currently lack of a direct treatment for liver fibrosis. Boiling histotripsy (BH) is an emerging non-invasive high-intensity focused ultrasound technique that can be employed to mechanically destruct solid tumour at the focus via acoustic cavitation without significant adverse effect on surrounding tissue. Here, we investigated whether BH can mechanically fractionate liver fibrotic tissue thereby exhibiting an anti-fibrotic effect in an animal model of liver fibrosis. BH-treated penumbra and its identical lobe showed reduced liver fibrosis, accompanied by increased hepatocyte specific marker expression, compared to the BH-untreated lobe. Furthermore, BH treatment improved serological liver function markers without notable adverse effects. The ability of BH to reduce fibrosis and promote liver regeneration in liver fibrotic tissue suggests that BH could potentially be an effective and reliable therapeutic approach against liver fibrosis.

Study Protocol of a Randomized, Two-Arm, Phase I/II Trial Investigating the Feasibility, Safety, and Efficacy of Local Treatment with US-Guided High-Intensity Focused Ultrasound in Combination with Palliative Chemotherapy in Inoperable Pancreatic Cancer.

BACKGROUND: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects. STUDY DESIGN: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

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.

High-intensity Focused Ultrasound-A New Choice to Conduct Pulmonary Artery Denervation.

This research aimed to explore whether high-intensity focused ultrasound (HIFU) could conduct pulmonary artery denervation (PADN). HIFU was performed in pulmonary arteries of 6 normotensive rabbits at dose of 250W, 6 times for each rabbit, and an additional 6 rabbits served as controls. Then ATEPH was induced in both groups by intravenous infusion of autogeneic thrombus. Hemodynamics and ultrasonography parameters were measured by right heart catheter and echocardiography pre- and post-establishment of ATEPH models in both groups. Histological analysis and immunohistochemistry of tyrosine hydroxylase (TH) were also performed. After PADN procedures, 5 rabbits were successfully conducted PADN, of which ablation zone was also observed in right auricle or right lung in 4 rabbits. Ablation zone was detected only in right lung in 1 rabbit. Compared with control group, milder right heart hemodynamic changes were found in PADN group, accompanied by improved ultrasound parameters in PADN group. HIFU can acutly damage SNs around pulmonary artery successfully, which may be a new choice to conduct PADN. However, the accuracy of HIFU with PADN needs to be improved.

Predicting the Prognosis of HIFU Ablation of Uterine Fibroids Using a Deep Learning-Based 3D Super-Resolution DWI Radiomics Model: A Multicenter Study.

RATIONALE AND OBJECTIVES: To assess the feasibility and efficacy of a deep learning-based three-dimensional (3D) super-resolution diffusion-weighted imaging (DWI) radiomics model in predicting the prognosis of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: This retrospective study included 360 patients with uterine fibroids who received HIFU treatment, including Center A (training set: N = 240; internal testing set: N = 60) and Center B (external testing set: N = 60) and were classified as having a favorable or unfavorable prognosis based on the postoperative non-perfusion volume ratio. A deep transfer learning approach was used to construct super-resolution DWI (SR-DWI) based on conventional high-resolution DWI (HR-DWI), and 1198 radiomics features were extracted from manually segmented regions of interest in both image types. Following data preprocessing and feature selection, radiomics models were constructed for HR-DWI and SR-DWI using Support Vector Machine (SVM), Random Forest (RF), and Light Gradient Boosting Machine (LightGBM) algorithms, with performance evaluated using area under the curve (AUC) and decision curves. RESULT: All DWI radiomics models demonstrated superior AUC in predicting HIFU ablated uterine fibroids prognosis compared to expert radiologists (AUC: 0.706, 95% CI: 0.647-0.748). When utilizing different machine learning algorithms, the HR-DWI model achieved AUC values of 0.805 (95% CI: 0.679-0.931) with SVM, 0.797 (95% CI: 0.672-0.921) with RF, and 0.770 (95% CI: 0.631-0.908) with LightGBM. Meanwhile, the SR-DWI model outperformed the HR-DWI model (P < 0.05) across all algorithms, with AUC values of 0.868 (95% CI: 0.775-0.960) with SVM, 0.824 (95% CI: 0.715-0.934) with RF, and 0.821 (95% CI: 0.709-0.933) with LightGBM. And decision curve analysis further confirmed the good clinical value of the models. CONCLUSION: Deep learning-based 3D SR-DWI radiomics model demonstrated favorable feasibility and effectiveness in predicting the prognosis of HIFU ablated uterine fibroids, which was superior to HR-DWI model and assessment by expert radiologists.

Mild hyperthermia with magnetic resonance- guided high intensity focused ultrasound combined with salvage chemoradiation for recurrent rectal cancer.

INTRODUCTION: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU). METHODS: All patients were deemed ineligible for salvage surgery and were evaluated in a multidisciplinary fashion with a surgical oncologist, radiation oncologist and medical oncologist. Radiation was delivered to a dose of 30.6 Gy in 1.8 Gy per fraction with concurrent capecitabine. MR-HIFU was delivered on days 1, 8 and 15 of concurrent chemoradiation. Our primary objective was feasibility and toxicity. RESULTS: Six patients (total 11 screened) were treated with concurrent chemoradiation and mild hyperthermia with MR-HIFU. Tumor size varied between 3.1-16.6 cm. Patients spent an average of 228 min in the MRI suite and sonication with the external transducer lasted an average of 35 min. There were no complications on the day of the MR-HIFU procedure and all acute toxicities (no grade >/=3 toxicities) resolved after completion of treatment. There were no late grade >/=3 toxicities. CONCLUSION: Mild hyperthermia with MR-HIFU, in combination with concurrent chemoradiation for appropriately selected patients, is safe for localized pelvic recurrences from rectal cancer. The potential for MR-HIFU to be applied in the recurrent setting in rectal cancer treatment requires further technical development and prospective evaluation.

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.

Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

Feasibility, safety and efficacy of high intensity focused ultrasound ablation as a preoperative treatment for challenging hysteroscopic myomectomy.

PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.

Risk factors affecting long-term efficacy of ultrasound-guided high-intensity focused ultrasound treatment for multiple uterine fibroids.

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

The Synergistic Effect of High Intensity Focused Ultrasound on In-vitro Remineralization of Tooth Enamel by Calcium Phosphate Ion Clusters.

Background: Remineralization of dental enamel is an important intervention strategy for the treatment of demineralized lesions. Existing approaches have limitations such as failure to adequately reproduce both the ideal structural and mechanical properties of the native tooth. The ability of ultrasound to control and accelerate the crystallization processes has been widely reported. Therefore, a new approach was explored for in-vitro enamel remineralization involving the synergistic effect of high-intensity focused ultrasound (HIFU) coupled with calcium phosphate ion clusters (CPICs). Methods: The demineralized enamel was treated with CPICs, with or without subsequent HIFU exposure for different periods (2.5, 5, and 10 min). The specimens were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. The surface hardness and crystallographic properties of the treated specimens were evaluated using Vickers microhardness testing and X-ray diffraction (XRD), respectively. Results: SEM revealed distinct, organized, and well-defined prismatic structures, showing clear evidence of remineralization in the combined CPIC/HIFU treatment groups. AFM further revealed a decrease in the surface roughness values with increasing HIFU exposure time up to 5 min, reflecting the obliteration of interprismatic spaces created during demineralization. The characteristic Raman band at 960 cm-1 associated with the inorganic phase of enamel dominated well in the HIFU-treated specimens. Importantly, microhardness testing further demonstrated that new mineral growth also recovered the mechanical properties of the enamel in the HIFU-exposed groups. Critical to our aspirations for developing this into a clinical process, these results were achieved in only 5 min. Conclusion: HIFU exposure can synergise and significantly accelerate in-vitro enamel remineralization process via calcium phosphate ion clusters. Therefore, this synergistic approach has the potential for use in future clinical interventions.

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.

The Impact of High Intensity Focused Ultrasound (HIFU) on Tumor-Specific Immune Responses of Prostate Cancer.

High intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS), has garnered recent attention as a non-invasive therapeutic strategy for prostate cancer. It utilizes focused acoustic energy to achieve localized thermal ablation, while also potentially exerting immunomodulatory effects. This review aims to elucidate the mechanisms underlying how HIFU influences tumor-specific immune responses in prostate cancer. These mechanisms include the release of tumor-associated antigens and damage-associated molecular patterns, the activation of innate immune cells, the facilitation of antigen presentation to adaptive immune cells, the enhancement of activation and proliferation of tumor-specific cytotoxic T lymphocytes, and the attenuation of the immunosuppressive tumor microenvironment by reducing the activity of regulatory T cells and myeloid-derived suppressor cells. Both preclinical investigations and emerging clinical data in prostate cancer models highlight HIFU's potential to modulate the immune system, as evidenced by increased infiltration of effector immune cells, elevated levels of pro-inflammatory cytokines, and improved responsiveness to immune checkpoint inhibitors. HIFU induces immunogenic cell death, leading to the release of tumor antigens and danger signals that activate dendritic cells and facilitate cross-presentation to cytotoxic T cells. Additionally, FUS ablation reduces immunosuppressive cells and increases infiltration of CD8+ T cells into the tumor, reshaping the tumor microenvironment. By priming the immune system while overcoming immunosuppression, combining FUS with other immunotherapies like checkpoint inhibitors and cancer vaccines holds promise for synergistic anti-tumor effects. Despite challenges in optimizing parameters and identifying suitable patients, FUS represents a novel frontier by modulating the tumor microenvironment and enhancing anti-tumor immunity through a non-invasive approach.

Hand Dystonia after Focused Ultrasound Thalamotomy in Essential Tremor.

INTRODUCTION: Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im). CASE PRESENTATION: MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia. CONCLUSION: This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.

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.