High-intensity Focused Ultrasound Treatment Research Articles

Motion Accuracy of Pneumatic Stepper Motor-Driven Robotic System Developed for MRI-Guided High-Intensity Focused Ultrasound Treatment of Prostate Disease

The latest advancement in high-intensity focused ultrasound (HIFU) treatment technology integrates magnetic resonance imaging (MRI) guidance for precise treatment of prostate disease. As conventional electromagnetic motors are not applicable for utilization within MRI scanners, we have developed a prototype robotic system driven by pneumatic stepper motors to control the movement of the HIFU transducer within an intrarectal probe during MRI-guided HIFU treatment procedures. These pneumatic stepper motors were constructed entirely from MRI-compatible plastic materials. Assessment of the robotic system’s MRI compatibility was conducted utilizing a 3.0T MRI scanner, revealing no discernible MRI image distortion with a minor decrease in the signal-to-noise ratio (2.8%) during the motor operation. The robotic system enabled the transducer to move inside the probe with two degrees of freedom, allowing both linear and rotational motion. The positional accuracy of the transducer movement was assessed, yielding ±0.20 and ±0.22 mm accuracies in the forward and backward linear movements, respectively, and ±0.79° and ±0.74° accuracies in the clockwise and counterclockwise rotational motions, respectively. Emulation of authentic HIFU procedures involved creating a two-dimensional array of thermal lesions in a tissue-mimicking phantom, achieving positional accuracy within ±1 mm for the generated HIFU focal spots. The prototype robotic system incorporating pneumatic stepper motors fabricated entirely from MRI-compatible plastic materials has demonstrated the requisite positional accuracy necessary for effective HIFU treatment of prostate disease, indicating substantial promise for future clinical application.

The Predictive Effect of Quantitative Analysis of Signal Intensity Heterogeneity on T2-Weighted MR Images for High-intensity Focused Ultrasound Treatment of Uterine Fibroids

Rationale and ObjectiveTo investigate whether the quantitative index of signal intensity (SI) heterogeneity on T2-weighted (T2W) magnetic resonance images can predict the difficulty and efficacy of high-intensity focused ultrasound (HIFU) ablation for uterine fibroids. Materials and MethodsThe standard deviation (SD) of T2W image (T2WI) SI was used to quantify SI heterogeneity. The correlation between SD and the non-perfused volume ratio (NPVR) in 575 patients undergoing HIFU treatment was retrospectively analyzed, and the efficacy of SD in predicting NPVR was discussed. Three classifications were made based on the SD, and the ablation difficulty and ablation effect of different grades were compared. A total of 65 cases from another center were used as an external validation set to verify the classification performance of SD. ResultsThe SD of SI was negatively correlated with NPVR (r=-0.460, p<0.001). The predictive efficiency of SD for the ablation effect was higher than that of the scaled signal intensity (0.767 vs. 0.701, p=0.006). Univariate and multivariate logistic regression analyses showed that SD was an independent predictor of ablation effect. Based on SD, the three classifications were divided into SD I: SD<101.0, SD II: 101.0≤SD<138.7, and SD III: SD≥138.7. The treatment time, sonication time, treatment intensity, and total energy of SD I were lower than those of SD II and III (p<0.05). ConclusionThe heterogeneity of T2WI SI of uterine fibroids is negatively correlated with NPVR. The SD of SI can be used to predict the ablation difficulty and ablation effect of HIFU.

MR Diffusion-Weighted Imaging in Evaluating Immediate HIFU Treatment Response of Uterine Fibroids.

Nowadays, High Intensity Focused Ultrasound (HIFU) is a common surgery option for the treatment of uterine fibroids in China, the immediate response of which is clinically evaluated using Contrast Enhanced (CE) imaging. However, the injection of gadolinium with its potential adverse effect is of concern in CE and therefore, it deserves efforts to find a better imaging method without the need for contrast agent injection for this task. To assess the role of diffusion-weighted imaging (DWI) in evaluating the immediate therapeutic response of HIFU treatment for uterine fibroids in comparison with CE. 68 patients with 74 uterine fibroids receiving HIFU treatment were enrolled, and immediate treatment response was assessed using post-surgical DWI images. Semi-quantitative ordinal ablation quality grading and quantitative nonperfusion volume (NPV) measurement based on DWI and CE imaging were determined by two experienced radiologists. Agreement of ablation quality grading between DWI and CE was assessed using the weighted kappa coefficient, while intraobserver, interobserver and interprotocol agreements of NPV measurements within and between DWI and CE were evaluated using the intraclass correlation (ICC) and Bland-Altman analysis. Grading of immediate HIFU treatment response showed a moderate agreement between DWI and CE (weighted kappa = 0.446, p < 0.001). NPV measured in 65 fibroids with DWI of Grade 3~5 showed very high ICCs for the intraobserver and interobserver agreement within DWI and CE (all ICC > 0.980, p < 0.001) and also for the interprotocol agreement between DWI and CE (ICC = 0.976, p < 0.001). DWI could provide satisfactory ablation quality grading, and reliable NPV quantification results to assess immediate therapeutic responses of HIFU treatment for uterine fibroids in most cases, which suggests that non-contrast enhanced DWI might be potentially used as a more costeffective and convenient method in a large proportion of patients for this task replacing CE imaging.

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

PurposeTo 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. MethodsIn 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. ResultsPI-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. ConclusionsThe 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.

Passive Elastography for Clinical HIFU Lesion Detection.

High-intensity Focused Ultrasound (HIFU) is a promising treatment modality for a wide range of pathologies including prostate cancer. However, the lack of a reliable ultrasound-based monitoring technique limits its clinical use. Ultrasound currently provides real-time HIFU planning, but its use for monitoring is usually limited to detecting the backscatter increase resulting from chaotic bubble appearance. HIFU has been shown to generate stiffening in various tissues, so elastography is an interesting lead for ablation monitoring. However, the standard techniques usually require the generation of a controlled push which can be problematic in deeper organs. Passive elastography offers a potential alternative as it uses the physiological wave field to estimate the elasticity in tissues and not an external perturbation. This technique was adapted to process B-mode images acquired with a clinical system. It was first shown to faithfully assess elasticity in calibrated phantoms. The technique was then implemented on the Focal One® clinical system to evaluate its capacity to detect HIFU lesions in vitro (CNR = 9.2 dB) showing its independence regarding the bubbles resulting from HIFU and in vivo where the physiological wave field was successfully used to detect and delineate lesions of different sizes in porcine liver. Finally, the technique was performed for the very first time in four prostate cancer patients showing strong variation in elasticity before and after HIFU treatment (average variation of 33.0 ± 16.0 % ). Passive elastography has shown evidence of its potential to monitor HIFU treatment and thus help spread its use.

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.

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.

Abstract 3845: High-intensity focused ultrasound ablation increases tumor specific lymphocytes in prostate cancer

Abstract The treatment of localized prostate cancer has been revolutionized by High-Intensity Focused Ultrasound (HIFU), an FDA-approved procedure. Thermal HIFU achieves the destruction of tumor tissue through the noninvasive delivery of ultrasonic energy, causing rapid heating of the targeted area. Given that prostate cancer typically exhibits a low presence of tumor-infiltrating lymphocytes crucial for antitumor immunity, this study aimed to investigate whether HIFU has the potential to activate antitumor immunity and enhance lymphocyte infiltration within the tumor. RM1 tumors were implanted on the flanks of syngeneic C57BL/6J mice, with one tumor subjected to HIFU treatment. The growth of the contralateral tumor was monitored, and at the end of the study, tumors were collected to evaluate immune cell infiltration. Blood samples were obtained from patients both before and after prostatectomy or HIFU treatment. Peripheral blood mononuclear cells (PBMCs) were then isolated to analyze the immune cell population. In murine experiments, the application of HIFU to one tumor resulted in a reduction in the growth of the contralateral (untreated) tumor, specifically when the contralateral tumor was of the same type, but not when it was a different tumor type. Notably, HIFU led to an augmented infiltration of CD4+ and CD8+ lymphocytes into the contralateral (untreated) tumor. Depletion studies further affirmed that the antitumor immune response triggered by HIFU relies on CD4+ and CD8+ lymphocytes. In human subjects, HIFU was observed to elevate the CD4+ and CD8+ lymphocyte populations in PBMCs. HIFU induces a potent antitumor immune response that effectively inhibits the progression of murine prostate tumors. This immune response is contingent upon CD4+ and CD8+ lymphocytes. HIFU demonstrates significant promise in activating antitumor immune responses in patients diagnosed with prostate cancer. Subsequent research endeavors should delve into models of metastatic prostate cancer, exploring the potential synergy of cytoreductive prostate tumor ablation with systemic immunotherapies to elicit a robust and comprehensive antitumor immune response. Citation Format: Shengchen Su, Yanping Wang, Eric M. Lo, Hyung L. Kim. High-intensity focused ultrasound ablation increases tumor specific lymphocytes in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3845.

Repeated high‑intensity focused ultrasound combined with iodine‑125 seed interstitial brachytherapy offers improved quality of life and pain control for patients with advanced pancreatic cancer: A 52‑patient retrospective study.

Patients diagnosed with pancreatic cancer who have 5-year survival rates of ~5% are typically in the advanced stage. Pancreatic cancer has become the third leading cause of cancer-related death in the United States and there is still a lack of effective treatments to improve patient survival rate. Hence, the purpose of the present retrospective study was to assess the potential clinical impact of repeated high-intensity focused ultrasound (HIFU) combined with iodine-125 (125I) interstitial brachytherapy for the treatment of patients with advanced pancreatic cancer who were ineligible for or declined surgery and chemotherapy. A total of 52 patients diagnosed with advanced pancreatic cancer were included in the study. At least one course of HIFU therapy combined with percutaneous ultrasound-guided 125I seed implantation was administered to each patient. The clinical assessment included an evaluation of Karnofsky Performance Scale (KPS) score at baseline, and at 1 and 2 months after combined therapy. Pain intensity was additionally evaluated with the numerical rating score (NRS). Overall survival (OS) times and survival rates at 3, 6, 9 and 12 months after combined treatment were evaluated. Adverse events commonly associated with HIFU and 125I seed implantation were recorded, and the severity of adverse events was graded according to the Common Terminology Criteria for Adverse Events, version 4. All 52 patients received successful repeated HIFU treatment combined with 125I seed implantation and were included in the analysis of efficacy and safety. The median OS time of patients was estimated to be 13.1 months (95% CI, 11.3-14.8). The survival rates at 3, 6, 9 and 12 months were 100.0, 86.5, 61.5 and 53.8%, respectively. The mean KPS score was 62.7±6.3 at baseline, 73.7±7.9 at 1 month and 68.8±6.5 at 2 months after combined treatment. KPS score increased significantly after combined therapy. The mean NRS score was 6.7±1.6 at baseline, and 4.7±1.7 and 5.4±1.5 at 1 and 2 months after combined treatment, respectively. The number of patients with severe pain and the NRS score were both significantly lower at 1 and 2 months after 125I seed implantation compared with those at baseline. No serious complications were detected during the follow-up period. In conclusion, the present study demonstrated the survival benefit and improvement in quality of life of patients with advanced pancreatic cancer receiving repeated HIFU treatment combined with 125I interstitial brachytherapy, which may provide new ideas and methods for the treatment of pancreatic cancer.

Evaluating the Effects of Water Balloons on High-Intensity Focused Ultrasound for Treating Uterine Fibroids

ObjectiveIn the treatment of uterine fibroids with ultrasound guided high intensity focused ultrasound (HIFU), water balloons are considered to be a valuable aid for improving safety and efficiency. However, the water balloons worsen the pathway for acoustic transmission, causing degraded performance both in ultrasound therapy and in ultrasound imaging. This study aims at establishing a protocol to evaluate the effects of the water balloon. MethodsSimulations and experiments were carefully conducted to quantitatively investigate the effects of water ballons on the efficiency of HIFU energy delivery and on the quality of ultrasound guiding images. More specifically, HIFU-induced temperature increases in the focal region, together with spatial resolution, contrast and signal-to-noise ratio in the ultrasound guiding images were compared under the conditions with and without the water balloon. ResultsExperiment results showed that the use of water balloons led to the dropping of temperature up to 10 degrees Celsius within the focal region in some specific situations, but quality of the guiding images was relatively less affected. ConclusionThe study provided the knowledge on what influences the water balloon could have in the ultrasound guided HIFU treatment; it also established a practical and standardized evaluation scheme for further optimizing the water balloon, such as its material and internal liquid compositions. This study can potentially help improve the efficiency and safety of treating uterine fibroids with ultrasound guided HIFU systems.

Healing Process after High-Intensity Focused Ultrasound Treatment of Benign Skin Lesions: Dermoscopic Analysis and Treatment Guidelines.

Background: High-Intensity Focused Ultrasound (HIFU) has emerged as a precise and non-invasive modality for tissue ablation and healing. This study presents a detailed dermoscopic analysis of skin healing post-High-Intensity Focused Ultrasound (HIFU) treatment, focusing on common benign skin lesions, such as seborrheic keratosis, sebaceous hyperplasia, vascular lesions, and sebaceous nevi. Methods: Prior to HIFU treatment, a comprehensive assessment was conducted, integrating ultrasound scanning and clinical evaluations. The TOOsonix System ONE-M was employed for HIFU treatments, with parameters tailored to each lesion type. Results: A common pattern observed across all lesions includes initial whitening post treatment, followed by scab formation and the development of a pink area with reparative vessels. This study, however, highlights distinct differences in fibrosis patterns and healing timelines across different lesion types. Each lesion type exhibited unique fibrosis patterns post treatment. Flatter variants of seborrheic keratosis healed within a month, displaying hypopigmentation and reparative vessels, alongside a distinct lattice fibrosis pattern in more verrucous forms, which took about two months to heal. Sebaceous hyperplasia, characterized by rapid healing within three weeks, demonstrated fibrosis with pink areas and perpendicular white lines, concluding with a slight depression. Vascular lesions varied in healing time based on depth, with superficial ones showing whitening and crust formation, while deeper lesions had vessel occlusion and size reduction accompanied by concentric fibrotic bands. Sebaceous nevi presented the longest healing duration of three months, characterized by amorphous white-gray structures, scab formation, and the emergence of pink areas with branching vessels, leading to clear skin with reduced white lines. Conclusions: in conclusion, this meticulous clinical evaluation highlights the unique healing characteristics and timelines for each skin lesion type treated with HIFU. These insights are invaluable for optimizing follow-up assessments, identifying potential complications, and refining treatment protocols. By providing detailed insights into the healing timelines and patterns for different types of lesions, patients can be better informed about their post-treatment journey.

Evaluation of functional and oncological outcomes of localized prostate cancer after different minimally invasive therapeutic methods: A single center experience.

To study the functional and oncological results of minimally invasive treatment methods: cryoablation, brachytherapy, and high-intensity focused ultrasound (HIFU) therapy of localized prostate cancer in a single hospital. One hundred sixty patients with localized prostate cancer were treated with minimally invasive methods (53, 52, 55 patients with cryoablation, brachytherapy and HIFU therapy, respectively). Prostate-specific antigen and evaluation of post-procedure biopsies were used as an assessment. The review of functional indicators and quality of life was made with International Index of Erectile Function (IIEF-5), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), quality of life (QoL) questionnaires. Patients after cryoablation showed worse results of oncological control according to positive repeat biopsies, best indicators were observed after brachytherapy. When considering the IPSS results, there were statistically significantly worse scores in the brachytherapy group in the early postoperative period, these differences do not reach statistical significance in the late period in the brachytherapy and cryoablation groups. Patients in the cryoablation group showed worse indicators of IIEF-5; in the early postoperative period; in the late follow-up period, the indicators of erectile function in patients in the cryoablation group did not statistically significantly differ from those in patients after brachytherapy. Patients after HIFU therapy showed fewer cases of de novo erectile dysfunction during the follow-up period of 3 years, higher average IIEF-5 scores, lower IPSS scores and better QoL results. The recurrence of prostate cancer was statistically significantly higher in the International Society of Urological Pathology (ISUP) 3 grade group. HIFU therapy had better urination indicators compared to other groups, that can be associated with the laser enucleation of prostatic hyperplasia. The advantage was noted in patients after HIFU therapy when comparing the parameters to the IIEF-5 thus, HIFU treatment had a better impact on patients' QoL with localized prostate cancer.

FOLFIRINOX plus high intensity focused ultrasound for locally advanced/borderline resectable pancreatic ductal adenocarcinoma: A prospective single arm phase II trial.

670 Background: FOLFIRINOX has been the standard regimen for locally advanced pancreatic cancer (LAPC) for palliation and borderline resectable pancreatic cancer (BRPC) for neoadjuvant treatment. According to the results of animal studies, concurrent use of high intensity focused ultrasound (HIFU) and chemotherapy can enhance the drug delivery to the target tissue. In this phase II trial, we aimed to evaluate the safety and therapeutic efficacy of FOLFIRINOX plus HIFU for patients with LAPC or BRPC. Methods: This study was designed as a prospective single center phase II trial (Study identifier: NCT05262452). We prospectively enrolled 60 patients (M:F=35:25; median age, 67.0 years old) with LAPC (n=23) or BRPC (n=37). The median tumor size was 4.0 cm (Interquartile range, 2.7-4.6). All patients were treated by FOLFIRINOX (oxaliplatin, 85mg/m2 of body-surface area; irinotecan, 180mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion) every 2 weeks until disease progression. HIFU was combined in the first 4 cycles of chemotherapy with following parameters: intensity of 2.0 kw/cm2, duty cycle of 1%, exposure time of 3 seconds and PRF of 10Hz. Follow-up contrast enhanced CT was taken every 4 cycles for the response evaluation using response evaluation criteria for solid tumor 1.1. Overall survival (OS) and progression-free survival were estimated using Kaplan-Meier method. All analyses were intention-to-treat. Results: Two patients withdrew the consent, and two patients could not complete planned 4 cycles of FOLFIRINOX plus HIFU treatment owing to sepsis from severe neutropenia related to chemotherapy. Among 56 patients who completed the 4 cycle of FOLFIRINOX plus HIFU and continued chemotherapy, partial response was achieved in 36 patients (60.0%, 36/60), and stable disease in 20 patients. Regarding the adverse effect (AE), 32 of 60 patients experienced grade 3 (n=22) or grade 4 (n=10) AE, all of them were related to FOLFIRINOX chemotherapy. No AE related to HIFU was observed. The estimated OS was 94.8%, 75.9% and 67.6% at 6-, 12- and 18 months, respectively. Regarding the PFS, the 6-, 12- and 18-month PFS was 91.9%, 70.3% and 56.2%, respectively. Conclusions: FOLFIRINOX plus HIFU was safe and effective treatment for LAPC/BRPC, providing 60.0% of partial response rate without any additional AE to chemotherapy. Clinical trial information: NCT05262452 .

Non-contrast enhanced MRI for efficiency evaluation of high-intensity focused ultrasound in adenomyosis ablation

Objective To investigate the value of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) in evaluating the therapeutic effect of high-intensity focused ultrasound (HIFU) in adenomyosis ablation. Material and methods One hundred eighty-nine patients with adenomyosis were treated with HIFU. The ablation areas on T2WI and DWI sequences were classified into different types: type I, relatively ill-defined rim or unrecognizable; subtype IIa, well-defined rim with hyperintensity; subtype IIb, well-defined rim with hypointensity. The volume of ablation areas on T2WI (VT2WI) and DWI (VDWI) was measured and compared with the non-perfused volume (NPV), and linear regression was conducted to analyze their correlation with NPV. Results The VT2WI of type I and type II (subtype IIa and subtype IIb) were statistically different from the corresponding NPV (p = 0.004 and 0.024, respectively), while no significant difference was found between the VDWI of type I and type II with NPV (p = 0.478 and 0.561, respectively). In the linear regression analysis, both VT2WI and VDWI were positively correlated with NPV, with R 2 reaching 0.96 and 0.97, respectively. Conclusions Both T2WI and DWI have the potential for efficient evaluation of HIFU treatment in adenomyosis, and DWI can be a replacement for CE-T1WI to some extent.

Real-Time Reconstruction of HIFU Focal Temperature Field Based on Deep Learning.

Objective and Impact Statement: High-intensity focused ultrasound (HIFU) therapy is a promising noninvasive method that induces coagulative necrosis in diseased tissues through thermal and cavitation effects, while avoiding surrounding damage to surrounding normal tissues. Introduction: Accurate and real-time acquisition of the focal region temperature field during HIFU treatment marked enhances therapeutic efficacy, holding paramount scientific and practical value in clinical cancer therapy. Methods: In this paper, we initially designed and assembled an integrated HIFU system incorporating diagnostic, therapeutic, and temperature measurement functionalities to collect ultrasound echo signals and temperature variations during HIFU therapy. Furthermore, we introduced a novel multimodal teacher-student model approach, which utilizes the shared self-expressive coefficients and the deep canonical correlation analysis layer to aggregate each modality data, then through knowledge distillation strategies, transfers the knowledge from the teacher model to the student model. Results: By investigating the relationship between the phantoms, invitro, and invivo ultrasound echo signals and temperatures, we successfully achieved real-time reconstruction of the HIFU focal 2D temperature field region with a maximum temperature error of less than 2.5 °C. Conclusion: Our method effectively monitored the distribution of the HIFU temperature field in real time, providing scientifically precise predictive schemes for HIFU therapy, laying a theoretical foundation for subsequent personalized treatment dose planning, and providing efficient guidance for noninvasive, nonionizing cancer treatment.

Ultrasound Monitoring of Simultaneous high-intensity focused ultrasound (HIFU) therapy using minimum-peak-sidelobe coded excitation

Bipolar sequences can be readily transmitted by ultrasound (US) pulser hardware with the full driving voltage to boost the echo magnitude in B-mode monitoring of HIFU treatment. In this study, a novel single-transmit bipolar sequence with minimum-peak-sidelobe (MPS) level is developed not only to restore the image quality of US monitoring but also remove acoustic interference from simultaneous HIFU transmission. The proposed MPS code is designed with an equal number of positive and negative bits and the bit duration should be an integer multiple of the period of the HIFU waveform. In addition, different permutations of code sequence are searched in order to obtain the optimal encoding. The received imaging echo is firstly decoded by matched filtering to cancel HIFU interference and to enhance the echo magnitude of US monitoring. Then, Wiener filtering is applied as the second-stage pulse compression to improve the final image quality. Simulations and phantom experiments are performed to compare the single-transmit MPS decoding with conventional two-transmit methods such as pulse-inversion subtraction (PIS) and Golay decoding for their performance in simultaneous US monitoring of HIFU treatment. Results show that the MPS decoding effectively removes HIFU interference even in the presence of tissue motion. The image quality of PIS and Golay decoding, on the other hand, is compromised by the uncancelled HIFU components due to tissue motion. Simultaneous US monitoring of tissue ablation using the proposed MPS decoding has also demonstrated to be feasible in ex-vivo experiments. Compared to the notch filtering that also allows single-transmit HIFU elimination, the MPS decoding is preferrable because it does not suffer from the tradeoff between residual HIFU and speckle deterioration in US monitoring images.

Study of rib protection devices based on resistant muffler theory for transcostal focused ultrasound therapy

High-intensity focused ultrasound (HIFU) is one of the effective means of treating cancer. One of the current challenges in HIFU treatment is how to minimize thermal damage to the rib during transcostal HIFU treatment and ensure that sufficient energy is delivered to the target area. In this paper, a sound insulation device mounted in front of the rib is proposed to address this challenge. The device is designed based on resistant anechoic theory, combining both reflective and resonant sound energy-blocking mechanisms to enhance the transmission loss and filter bandwidth. The structural parameters of the device are optimized using an orthogonal test method. A finite element method was used to simulate the sound and temperature fields of the sound insulation device with and without different rib spacings. The simulation results demonstrate a significant decrease in sound pressure at the ribs under the protection of the sound insulation device, with no significant difference in sound pressure at the target area. Consequently, the temperature at the ribs decreases, while the temperature at the target area tissue is guaranteed. Furthermore, transcostal HIFU experiments are conducted using real pig ribs and the experimental results validate the accuracy of the simulation results.

Long-term Efficacy of Fibroid Devascularization with Ultrasound-Guided High-Intensity Focused Ultrasound

High-intensity focused ultrasound (HIFU) has been increasingly used for treatment of uterine leiomyoma. The superiority of HIFU therapy targeting uterine leiomyoma blood vessels, however, still needs to be further explored. This study aims to evaluate the long-term efficacy of fibroid devascularization with ultrasound-guided HIFU (USgHIFU) and the effects of treatment on the ovarian reserve and endometrial injury. Fibroid devascularization was assessed with the Adler grade obtained by color Doppler flow imagingand power Doppler imaging (PDI). The targeted vessels were covered and then sonicated by HIFU focal spots. The patients were followed up at 1 month, 3 months, 6 months, 1 year, 2 years and 3 years after treatment. Adverse effects and complications were recorded. The non-perfusion volume rate (NPVR), fibroid volume shrinkage rate (FVSR), Adler Grade, symptom severity score (SSS) and uterine fibroid symptom and quality of life (UFS-QOL) were evaluated. Adverse events (AEs)were recorded. In Center 1, the enrolled patients completed the anti-Müllerian hormone (AMH) test before and at 6 months after treatment. A total of 117 eligible patients were consecutively enrolled to receive interventions and follow-up evaluations of the three centers from January 2019 to May 2023. The 1-month and 6-monthNPVRs were 66.60%±33.14% and 51.12%±39.84%, respectively. The mean FVSRs at 1 month and 6 months after treatment were 38.20% and 43.89%, respectively. No significant difference was observed in AMH levels before and after treatment (p>0.05). No irreversible endometrial injury was observed in MR images after HIFU treatment. No significant difference was observed in both 1-month and 6-monthFVSRs among Center 1, 2 and 3 (p>0.05). No severe AEs occurred. For long-term outcomes, significant differences were observed in Adler grade, FV, FVSR, SSS, reduction in SSSand UFS-QOL before and after treatment (p<0.001) whereas no significant difference was observed in Adler grade among 3 months, 1 year, 2 years and 3 years after treatment (p>0.05). The SSSs were reduced by 33.42% at 1 year, 42.32% at 2 years and 52.46% at 3 years after treatment. For patients with uterine fibroids, USgHIFU-induced devascularization is a safe and effective treatment option. It has little effect on ovarian function and the endometrial injury is reversible, which could be attractive for patients who plan to become pregnant.

Follow-Up of Men Who Have Undergone Focal Therapy for Prostate Cancer with HIFU-A Real-World Experience.

To determine oncological and functional outcomes and side effects after focal therapy of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU). This retrospective single-center study included 57 consecutive patients with localised PCa. Aged 18-80 with ≤2 suspicious lesions on mpMRI (PIRADS ≥ 3), PSA of ≤15 ng/mL, and an ISUP GG of ≤2. HIFU was performed between November 2014 and September 2018. All men had an MRI/US fusion-guided targeted biopsy (TB) combined with a TRUS-guided 10-core systematic biopsy (SB) prior to focal therapy. HIFU treatment was performed as focal, partial, or hemiablative, depending on the prior histopathology. Follow-up included Questionnaires (IIEF-5, ICIQ, and IPSS), prostate-specific antigen (PSA) measurement, follow-up mpMRI, and follow-up biopsies. The median age of the cohort was 72 years (IQR 64-76), and the median PSA value before HIFU was 7.3 ng/mL (IQR 5.75-10.39 ng/mL). The median follow-up was 27.5 (IQR 23-41) months. At the time of the follow-up, the median PSA value was 2.5 ng/mL (IQR 0.94-4.96 ng/mL), which shows a significant decrease (p < 0.001). In 17 (29.8%) men, mpMRI revealed a suspicious lesion, and 19 (33.3%) men had a positive biopsy result. Only IIEF values significantly decreased from 16 (IQR 10.75-20.25) to 11.5 (IQR 4.5-17) (p < 0.001). The rate of post-HIFU complications was low, at 19.3% (11 patients). The limitation of this study is the lack of long-term follow-up. HIFU as a therapy option for nonmetastatic, significant prostate cancer is effective in the short term for carefully selected patients and shows a low risk of adverse events and side effects.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.