Search

Purpose The ExAblate body MRgFUS system requires advanced beamforming strategies for volumetric hyperthermia. This study aims to develop and evaluate electronic beam steering, multi-focal patterns, and sector vortex beamforming approaches in conjunction with partial array activation using an acoustic and biothermal simulation framework along with phantom experiments. Methods The simulation framework was developed to calculate the 3D acoustic intensity and temperature distribution resulting from various beamforming and scanning strategies. A treatment cell electronically sweeping a single focus was implemented and evaluated in phantom experiments. The acoustic and thermal focal size of vortex beam propagation was quantified according to the vortex modes, number of active array elements, and focal depth. Results Turning off a percentage of the outer array to increase the f-number increased the focal size with a decrease in focal gain. 60% active elements allowed generating a sonication cell with an off-axis of 10 mm. The vortex mode number 4 with 60% active elements resulted in a larger heating volume than using the full array. Volumetric hyperthermia in the phantom was evaluated with the vortex mode 4 and respectively performed with 100% and 80% active elements. MR thermometry demonstrated that the volumes were found to be 18.8 and 29.7 cm3, respectively, with 80% array activation producing 1.58 times larger volume than the full array. Conclusions This study demonstrated that both electronic beam steering and sector vortex beamforming approaches in conjunction with partial array activation could generate large volume heating for HT delivery using the ExAblate body array.

Background Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) therapy of pelvic tumors is currently assessed by visual estimation of the proportion of tumor that can be reached by the device’s focus (coverage). Since it is important to assess whether enough energy reaches the tumor to achieve ablation, a methodology for estimating the proportion of the tumor that can be ablated (treatability) was developed. Predicted treatability was compared against clinically achieved thermal ablation. Methods MR Dixon sequence images of five patients with recurrent gynecological tumors were acquired during their treatment. Acousto-thermal simulations were performed using k-Wave for three exposure points (the deepest and shallowest reachable focal points within the tumor, identified from tumor coverage analysis, and a point halfway in-between) per patient. Interpolation between the resulting simulated ablated tissue volumes was used to estimate the maximum treatable depth and hence, tumor treatability. Predicted treatability was compared both to predicted tumor coverage and to the clinically treated tumor volume. The intended and simulated volumes and positions of ablated tissues were compared. Results Predicted treatability was less than coverage by 52% (range: 31–78%) of the tumor volume. Predicted and clinical treatability differed by 9% (range: 1–25%) of tumor volume. Ablated tissue volume and position varied with beam path length through tissue. Conclusion Tumor coverage overestimated patient suitability for MRgHIFU therapy. Employing patient-specific simulations improved treatability assessment. Patient treatability assessment using simulations is feasible.

Objectives Fiducial markers improve accuracy in external beam radiation therapy (EBRT) for treatment of prostate cancer (PCa). However, many patients recur after EBRT necessitating additional treatment, such as MR-guided transurethral ultrasound ablation (TULSA). Residual markers may compromise TULSA through ultrasound field distortions and generation of local susceptibility artifacts. The objective was to investigate how markers affect the ablation outcome during clinical TULSA treatments. Subjects and methods A retrospective analysis was performed on nine patients with radiorecurrent PCa and residual markers who received TULSA. The MR susceptibility artifact was quantified as a function of marker type, size and orientation, in particular for thermometry. The spatial distribution of markers inside the prostate was recorded, and the resulting impact on the thermal dose was measured. The thermal dose measurements were directly compared to the residual enhancing prostatic tissue observed on the immediate and control post-TULSA contrast enhanced (CE) image. Results Successful thermal dose accumulation to the target boundary occurred for 14/20 (70%) of markers, confirmed with CE imaging. Gold markers situated simultaneously close to the urethra (≤12 mm) and far from the target boundary (≥13 mm) reduced the ultrasound depth of heating. Nitinol markers produced large, hypointense artifacts that disrupted thermometry and compromised treatment. Artifacts from gold markers were less pronounced, but when located near the target boundary, also affected treatment. Conclusion Marker composition, orientation and location inside the prostate can all potentially impact treatment outcome. Proper patient selection through detailed MRI screening is critical to ensure successful radiorecurrent PCa treatment outcomes with TULSA.

Purpose To investigate the feasibility of using an apparent diffusion coefficient (ADC) classification in predicting the technical outcome of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it to the Funaki classification. Materials and methods Forty-two patients with forty-eight uterine fibroids underwent diffusion-weighted imaging (DWI) before MRgHIFU treatment. The DW images were acquired with five different b-values. Correlations between ADC values and treatment parameters were assessed. Optimal ADC cutoff values were determined to predict technical outcomes, that is, nonperfused volume ratios (NPVr) such that three classification groups were created (NPVr of 80%). Results were compared to the Funaki classification using receiver-operating-characteristic (ROC) curve analysis, with statistical significance being tested with the Chi-square test. Results A statistically significant negative correlation (Spearman’s ρ = –0.31, p-value < 0.05) was detected between ADC values and NPV ratios. ROC curve analysis indicated that optimal ADC cutoff values of 980 × 10−6mm2/s (NPVr > 80%) and 1800 × 10−6mm2/s (NPVr < 30%) made it possible to classify fibroids into three groups: ADC I (NPVr > 80%), ADC II (NPVr 30–80%) and ADC III (NPVr < 30%). Analysis of the whole model area under the curve resulted in values of 0.79 for the ADC classification (p-value = 0.0007) and 0.62 for the Funaki classification (p-value = 0.0527). Conclusions Lower ADC values prior to treatment correlate with higher NPV ratios. The ADC classification seems to be able to predict the NPV ratio and may even outperform the Funaki classification. Based on these results DWI and ADC maps should be included in the MRI screening protocol.

Purpose This article will report results from the in-vivo application of a previously published model-predictive control algorithm for MR-HIFU hyperthermia. The purpose of the investigation was to test the controller’s in-vivo performance and behavior in the presence of heterogeneous perfusion. Materials and methods Hyperthermia at 42°C was induced and maintained for up to 30 min in a circular section of a thermometry slice in the biceps femoris of German landrace pigs (n=5) using a commercial MR-HIFU system and a recently developed MPC algorithm. The heating power allocation was correlated with heat sink maps and contrast-enhanced MRI images. The temporal change in perfusion was estimated based on the power required to maintain hyperthermia. Results The controller performed well throughout the treatments with an absolute average tracking error of 0.27 ± 0.15 °C and an average difference of 1.25 ± 0.22 °C between and The MPC algorithm allocates additional heating power to sub-volumes with elevated heat sink effects, which are colocalized with blood vessels visible on contrast-enhanced MRI. The perfusion appeared to have increased by at least a factor of ∼1.86 on average. Conclusions The MPC controller generates temperature distributions with a narrow spectrum of voxel temperatures inside the target ROI despite the presence of spatiotemporally heterogeneous perfusion due to the rapid thermometry feedback available with MR-HIFU and the flexible allocation of heating power. The visualization of spatiotemporally heterogeneous perfusion presents new research opportunities for the investigation of stimulated perfusion in hypoxic tumor regions.

Purpose: Oral cancers are one of the commonly diagnosed tumors worldwide in human and veterinary patients. Most oral cancers are surgically resected; however, obtaining an adequate margin of safety in patients without compromising their quality of life is often challenging. Herein, we investigated the ability of non-invasive focused ultrasound (FUS) to thermally ablate a biopsy confirmed canine oral cancer. Materials and Methods: A male canine patient with a large neurilemmoma (schwannoma) mass on the left maxilla, with evidence of thinning and loss of alveolar bone and pressure necrosis, was treated with FUS ablation instead of the traditional maxillectomy procedure. FUS ablations were performed in three sessions over three weeks. Tumor remission was determined with computed tomography and histopathological examination of the treated site. Additionally, the anti-tumor immune effects of FUS were assessed by flow cytometry analysis of blood and tumor samples. Results: Complete tumor remission was noted at the treated site. Treatment related adverse events were primarily thermal burns of the buccal mucosa, which were managed with periodic hyperbaric oxygen therapy and surgical coverage of the underlying exposed bones with gingival flaps. Enhanced proliferation of adaptive immunity cells (e.g., T-cells) was observed in tumor and blood samples. Conclusion: Our limited investigation in a canine oral cancer patient suggests that FUS may avoid the need for large-scale resection of bony tissues, thus potentially improving quality of life.

This article promotes the use of High Intensity Focused Ultrasound (HIFU) as a tool for affecting the local properties of tissue engineered constructs in vitro. HIFU is a low cost, non-invasive technique used for eliciting focal thermal elevations at variable depths within tissues. HIFU can be used to denature proteins within constructs, leading to decreased permeability and potentially increased local stiffness. Adverse cell viability effects remain restricted to the affected area. The methods described in this article are explored through the scope of articular cartilage tissue engineering and the fabrication of osteochondral constructs, but may be applied to the engineering of a variety of different tissues.

AimTo use magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU), magnetic resonance imaging (MRI) and histopathology for noninvasively ablating, quantifying and characterizing ablated renal tissue.MethodsSix anesthetized/mechanically-ventilated pigs underwent single/double renal sonication (n = 24) using a 3T-MRg-HIFU (1.1 MHz frequency and 3000J-4400J energies). T2-weighted fast spin echo (T2-W), perfusion saturation recovery gradient echo and contrast enhanced (CE) T1-weighted (T1-W) sequences were used for treatment planning, temperature monitoring, lesion visualization, characterization and quantification, respectively. Histopathology was conducted in excised kidneys to quantify and characterize cellular and vascular changes. Paired Student's t-test was used and a P-value < 0.05 was considered statistically significant.ResultsAblated renal parenchyma could not be differentiated from normal parenchyma on T2-W or non-CE T1-W sequences. Ablated renal lesions were visible as hypoenhanced regions on perfusion and CE T1-W MRI sequences, suggesting perfusion deficits and necrosis. Volumes of ablated parenchyma on CE T1-W images in vivo (0.12-0.36 cm(3) for single sonication 3000J, 0.50-0.84 cm(3), for double 3000J, 0.75-0.78 cm(3) for single 4400J and 0.12-2.65 cm(3) for double 4400J) and at postmortem (0.23-0.52 cm(3), 0.25-0.82 cm(3), 0.45-0.68 cm(3) and 0.29-1.80 cm(3), respectively) were comparable. The ablated volumes on 3000J and 4400J double sonication were significantly larger than single (P < 0.01), thus, the volume and depth of ablated tissue depends on the applied energy and number of sonication. Macroscopic and microscopic examinations confirmed the locations and presence of coagulation necrosis, vascular damage and interstitial hemorrhage, respectively.ConclusionContrast enhanced MRI provides assessment of MRg-HIFU renal ablation. Histopathology demonstrated coagulation necrosis, vascular damage and confirmed the volume of damage seen on MRI.

Aim: To investigate the ovarian function and pregnancy outcome of patients with uterine fibroids and the influencing factors after high intensity focused ultrasound (HIFU) ablation treatment. Methods: A total of 80 patients were recruited. All patients were divided into the pregnancy group (64 cases) and the non‐pregnancy group (16 cases). The pregnancy group was categorized into the good pregnancy outcome (GOP) group (46 cases) and adverse pregnancy outcome (APO) group (18 cases). The general data of all study subjects were collected. The changes of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), inhibin B (INHB), and antral follicle count (AFC) before HIFU and 3, 6, and 12 months after HIFU were compared. The related factors affecting pregnancy and pregnancy outcomes were analyzed. Results: There were no significant differences in AMH, FSH, INHB levels, and AFC at 6 and 12 months after HIFU compared with those before HIFU in pregnancy and non‐pregnancy groups (p > 0.05). This study demonstrated that patients with prior history of pregnancy, younger age, lower body mass index (BMI), and smaller fibroids volume had a higher pregnancy rate (p < 0.05). Besides, younger age and smaller fibroids volume were associated with better pregnancy outcomes (p < 0.05). Conclusions: HIFU in the treatment of uterine fibroids has little effect on ovarian function and does not increase the risk of infertility and adverse pregnancy. The prior history of pregnancy, age, BMI, and fibroids volume are essential factors affecting the postoperative pregnancy. [ABSTRACT FROM AUTHOR]

This study deals with numerical simulations of the growth of bubble nuclei and the corresponding bubble cloud formation in a pressure field given by high intensity focused ultrasound (HIFU) backscattered from a laser-induced bubble interface. The imposed pressure on the nuclei is calculated with the Ghost Fluid Method (GFM). The growth of nuclei in a microscopic field that cannot be resolved under Eulerian grids in the GFM is evaluated by using the Keller equation for bubble dynamics. Once the nuclei grow so lager that they can be captured with the level-set function, the GFM with the level-set method takes over the computation in the macroscopic field. The validity of present method is confirmed by the growth of a single bubble nucleus placed on the HIFU propagation axis near the laser-induced bubble. The first growth and the following collapse of the bubble captured with the level-set function in the macroscopic field are in fairly good agreement with those predicted by the Keller equation with keeping acceptable mass conservation, although the accuracy depends on the grid resolution. It is also shown that there exists a bubble configuration where multiple bubbles grow more stably than those when each bubble grows solely: the stable multiple bubbles become a new reflector of HIFU leading to a high negative pressure field where next cavitation inception can occur. Finally, we demonstrate the cone-like bubble cloud formation observed in experiments (Ogasawara et al. (2018); Horiba et al. (2020)) using the present method. The simulated cloud formation process supports the experiments. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the efficacy and safety of ultrasound cycloplasty(UCP)in the treatment of neovascular glaucoma(NVG).METHODS: Thirty patients(30 eyes)with NVG who were treated with UCP at our hospital from January 2018 to December 2018 were collected. All patients received comprehensive ophthalmic examination. Visual acuity, best corrected visual acuity(BCVA), intraocular pressure(IOP), pain grade score, ocular surface, number of glaucoma drugs and complications were recorded before and 1, 3d, 1wk and 1, 2, 3, 6mo after operation, and the efficacy and safety were evaluated.RESULTS: The postoperative visual acuity was improved, the pain score was decreased, and the use of intraocular pressure-lowering drugs was decreased and the IOP decreased significantly(PThe preoperation visual acuity, pain score, use of intraocular pressure-lowering drugs and IOP was \〖1.63±0.59(LogMAR)\〗, \〖2(1,4)\〗, \〖4(4,4)\〗 and(44.19±13.72)mmHg. The postoperative IOP were decreased at different observation time within 6mo, and the differences with preoperative IOP were statistically significant(all Pr=0.928, P. The number of glaucoma drugs and pain scores were decreased, and the differences with that of preoperation were statistically significant(PPCONCLUSION: UCP is high safety and few complications for NVG treatment. It has significant effect on reducing IOP, relieving ocular pain. The higher the preoperation IOP, the greater the IOP reduction after surgery. It was a promising anti-glaucoma method.

Yaotai Wang,1 Chun Chen,1 Yong Luo,1 Jie Xiong,1 Yu Tang,1 Haiyan Yang,1 Lu Wang,1 Fujie Jiang,1 Xuan Gao,2 Die Xu,2 Huanan Li,1 Qi Wang,1 Jianzhong Zou1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods: Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results: Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting ability of synergistic agent. Multimodal imaging chose the best treatment time according to the distribution of nanoparticles in the body to guide the efficient and effective treatment of HIFU. CL-ICG-PFH-NPs could serve as a phase change agent and form microbubbles that can facilitate HIFU ablation by mechanical effects, acoustic streaming and shear stress. This lays a foundation for the imaging and treatment of tumors.Conclusion: In this work, a biological targeting synergistic agent was successfully constructed with good stability and physicochemical properties. This biological targeting synergistic agent can not only provide information for early diagnosis of tumors but also realize multimodal imaging monitoring during HIFU ablation simultaneously with HIFU treatment, which improves the shortcomings of HIFU treatment and has broad application prospects.Keywords: high-intensity focused ultrasound, nanoparticles, photoacoustic imaging, fluorescence imaging, ultrasound imaging, image-guided therapy

The introduction of thermal relaxation makes non-Fourier heat transfer more effective than Pennes equation to reflect rapid bio-heat transferring during HIFU, however, the contribution of thermal relaxation in specific tissues needs to be further clarified. In this study, we first measured the thermal relaxation times of porcine muscle and porcine fat. Combining with experimental measurements, the effects of thermal relaxation on temperature elevation in the tissues were investigated by using Pennes equation, thermal wave model of bio-heat transfer (TWMBT) and dual phase-lag (DPL) bio-heat transfer. Results showed that: a) The thermal relaxation times of porcine muscle and porcine fat are experimentally determined as 5.71± 0.11 s and 5.02± 0.06 s, respectively. b) In the absence of cavitation, DPL bio-heat transfer is more accurate to predict the temperature elevation at the focus and 2 mm from the focus than Pennes equation and TWMBT. Particularly, comparing with the reported of bologna (16 s) used in most of the theoretical analysis, the utilization of the measured thermal relaxation time for a specific tissue in DPL bio-heat transfer is more effective in predicting the temperature elevation during HIFU. c) Acoustic cavitation and nonlinear propagation is easier to happen in fat, under which all bio-heat transfer models are failed to forecast the temperature elevation induced by HIFU. The results demonstrate that different tissues have different thermal relaxation, DPL bio-heat transfer with the measured thermal relaxation times of specific tissues can accurately predict the temperature elevation during HIFU without cavitation.

Objective To investigate the prevalence of pelvic adhesions in patients with uterine fibroids after high-intensity focused ultrasound (HIFU) treatment, then analyze the influencing factors of pelvic adhesions. Materials and methods From October 2010 to March 2020, a total of 2619 patients with uterine fibroids underwent either hysterectomy, myomectomy, or cesarean section in Suining Central Hospital of Sichuan province. Of the 2619 patients, 810 were excluded because of a documented history of either pelvic infections, endometriosis, prior abdominopelvic surgery, or gynecological malignancies; 1809 patients were enrolled and the data were retrospectively assessed for the prevalence and patterns of pelvic adhesions. Among them, 96 patients with uterine fibroids had had prior HIFU treatment (HIFU group), 1713 patients had not had HIFU or surgical treatments (control group). Results Among the 96 patients in the HIFU group, adhesions were detected in 42 patients, the incidence of pelvic adhesion being 43.75%; the 1713 patients in the control group, adhesions were detected in 619 patients, the prevalence of pelvic adhesion being 36.14%. No statistically significant difference in the incidence of adhesion between the two groups was observed (p = .132), no significant difference in location of pelvic adhesions between the two groups and no significant difference in the severity of adhesions between the two groups was observed (p > .05). Conclusions Based on our results with limited numbers, we concluded that HIFU treatment did not significantly increase the risk of pelvic adhesions.

Background Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) ablation of pelvic tumors is initially evaluated clinically for treatment feasibility using referral images, acquired using standard supine diagnostic imaging, followed by MR screening of potential patients lying on the MRgHIFU couch in a ‘best-guess’ treatment position. Existing evaluation methods result in ≥40% of referred patients being screened out because of tumor non-targetability. We hypothesize that this process could be improved by development of a novel algorithm for predicting tumor coverage from referral imaging. Methods The algorithm was developed from volunteer images and tested with patient data. MR images were acquired for five healthy volunteers and five patients with recurrent gynaecological cancer. Subjects were MR imaged supine and in oblique-supine-decubitus MRgHIFU treatment positions. Body outline and bones were segmented for all subjects, with organs-at-risk and tumors also segmented for patients. Supine images were aligned with treatment images to simulate a treatment dataset. Target coverage (of patient tumors and volunteer intra-pelvic soft tissue), i.e. the volume reachable by the MRgHIFU focus, was quantified. Target coverage predicted from supine imaging was compared to that from treatment imaging. Results Mean (±standard deviation) absolute difference between supine-predicted and treatment-predicted coverage for 5 volunteers was 9 ± 6% (range: 2–22%) and for 4 patients, was 12 ± 7% (range: 4–21%), excluding a patient with poor acoustic coupling (coverage difference was 53%). Conclusion Prediction of MRgHIFU target coverage from referral imaging appears feasible, facilitating further development of automated evaluation of patient suitability for MRgHIFU.

Introduction: Prostate cancer is the third leading cause of death from cancer among Canadian men. High intensity focused ultrasound (HIFU) is a novel approach for primary treatment of localized prostate cancer. Little is known, however, about its costs. We aimed to collect the direct costs and health-related quality of life (HRQoL) data of HIFU in primary treatment of localized low and intermediate risk prostate cancer in Ontario., Materials and Methods: We collected direct costs and HRQoL data of 20 patients with localized low or intermediate risk prostate cancer who received whole-gland HIFU at a privately owned clinic in Ontario. We compared the direct costs of HIFU, open radical prostatectomy (ORP), robot assisted radical prostatectomy (RARP), and external beam radiation therapy (RT) in primary treatment of localized low and intermediate risk prostate cancer., Results: The average direct costs of HIFU, ORP, RARP, and RT per case in 2023 are $14,886.78, $14,192.26, $21,794.55, and $17,377.51, respectively. The median and interquartile range (IQR) of the study participants' age and HRQoL data prior to the HIFU procedure were 64.5 (11.25) years, 94.5 (8.65), 38.5 (4), 6.0 (4.46), and 22.5 (8.32), respectively., Conclusion: Our healthcare payer's perspective costing study revealed median direct costs per case of HIFU and favorable HRQoL outcomes compared to other treatment options for primary treatment of localized low and intermediate risk prostate cancer in Ontario. A health economic model is warranted to analyze the cost-effectiveness of HIFU compared to other treatment options in primary treatment of localized low and intermediate risk prostate cancer.

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., Competing Interests: Conflicts of interest Dr Marini reports that in the past, he has received honoraria for speaking engagements from Fotona Laser and honoraria for participation in investigational studies with Lumenis. These potential conflicts of interest are disclosed in the interest of transparency and full disclosure. All other authors of this work have declared that they have no conflicts of interest to disclose., (Copyright © 2024 American Academy of Dermatology, Inc. All rights reserved.)

In the last decades there has been progress in the treatment of essential tremor (TE) especially in the surgical field and to a lesser extent in the pharmacological field. We carry out a review of the currently available treatments. The first intervention is the use of non-pharmacological and non-surgical strategies (general advice, occupational therapy, speech therapy, psychotherapy). With discrete advances, the pharmacological treatment is not very satisfactory. Only 30-60% of patients have a positive response, and in these the anti-tremor effectiveness is 40-60%. The first-line drugs are still propranolol and primidone. In cases with severe tremor we will consider a surgical option, the method of choice being thalamotomy using high-intensity focused ultrasound. In the future we must continue to study the pathophysiology of TE, develop drugs specifically designed for TE and improve the technology of available invasive techniques., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

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

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

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

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

The blood-brain barrier (BBB), comprised of brain endothelial cells with tight junctions (TJ) between them, regulates the extravasation of molecules and cells into and out of the central nervous system (CNS). Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of a broad range of brain disorders. Current strategies for BBB opening are invasive, not specific, and lack precise control over the site and timing of BBB opening, which may limit their clinical translation. In the present report, we describe a novel approach based on a combination of stem cell delivery, heat-inducible gene expression and mild heating with high-intensity focused ultrasound (HIFU) under MRI guidance to remotely permeabilize BBB. The permeabilization of the BBB will be controlled with, and limited to where selected pro-inflammatory factors will be secreted secondary to HIFU activation, which is in the vicinity of the engineered stem cells and consequently both the primary and secondary disease foci. This therapeutic platform thus represents a non-invasive way for BBB opening with unprecedented spatiotemporal precision, and if properly and specifically modified, can be clinically translated to facilitate delivery of different diagnostic and therapeutic agents which can have great impact in treatment of various disease processes in the central nervous system.

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p < 0.001).Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200–250 W is effective and safe in normal-sized canines.

Boiling histotripsy is a promising High-Intensity Focused Ultrasound (HIFU) technique that can be used to induce mechanical tissue fractionation at the HIFU focus via cavitation. Two different types of cavitation produced during boiling histotripsy exposure can contribute towards mechanical tissue destruction: (1) a boiling vapour bubble at the HIFU focus and (2) cavitation clouds in between the boiling bubble and the HIFU source. Control of the extent and degree of mechanical damage produced by boiling histotripsy is necessary when treating a solid tumour adjacent to normal tissue or major blood vessels. This is, however, difficult to achieve with boiling histotripsy due to the stochastic formation of the shock scattering-induced inertial cavitation clouds. In the present study, a new histotripsy method termed pressure-modulated shockwave histotripsy is proposed as an alternative to or in addition to boiling histotripsy without inducing the shock scattering effect. The proposed concept is (a) to generate a boiling vapour bubble via localised shockwave heating and (b) subsequently control its extent and lifetime through manipulating peak pressure magnitudes and a HIFU pulse length. To demonstrate the feasibility of the proposed method, bubble dynamics induced at the HIFU focus in an optically transparent liver tissue phantom were investigated using a high speed camera and a passive cavitation detection systems under a single 10, 50 or 100 ms-long 2, 3.5 or 5 MHz pressure-modulated HIFU pulse with varying peak positive and negative pressure amplitudes from 5 to 89 MPa and −3.7 to −14.6 MPa at the focus. Furthermore, a numerical simulation of 2D nonlinear wave propagation with the presence of a boiling bubble at the focus of a HIFU field was conducted by numerically solving the generalised Westervelt equation. The high speed camera experimental results showed that, with the proposed pressure-modulated shockwave histotripsy, boiling bubbles generated by shockwave heating merged together, forming a larger bubble (of the order of a few hundred micron) at the HIFU focus. This coalesced boiling bubble then persisted and maintained within the HIFU focal zone until the end of the exposure (10, 50, or 100 ms). Furthermore, and most importantly, no violent cavitation clouds which typically appear in boiling histotripsy occurred during the proposed histotripsy excitation (i.e. no shock scattering effect). This was likely because that the peak negative pressure magnitude of the backscattered acoustic field by the boiling bubble was below the cavitation cloud intrinsic threshold. The size of the coalesced boiling bubble gradually increased with the peak pressure magnitudes. In addition, with the proposed method, an oval shaped lesion with a length of 0.6 mm and a width of 0.1 mm appeared at the HIFU focus in the tissue phantom, whereas a larger lesion in the form of a tadpole (length: 2.7 mm, width: 0.3 mm) was produced by boiling histotripsy. Taken together, these results suggest that the proposed pressure-modulated shockwave histotripsy could potentially be used to induce a more spatially localised tissue destruction with a desired degree of mechanical damage through controlling the size and lifetime of a boiling bubble without the shock scattering effect.

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect.Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (

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

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

• BH ablation rate in liver tissue was insensitive to the changes in pulsing protocol. • BH ablation rate in bovine myocardium increased with pulse length and number. • A universal BH dose sufficient for any tissue type is unlikely to be established. • Product of pulse duration and their number per point is a more relevant dose metric for planning BH of collagenous tissues. • Number of pulses per point is a more suitable dose metric for treatment planning of primarily cellular targets. This work was focused on the newly developed ultrasonic approach for non-invasive surgery – boiling histotripsy (BH) – recently proposed for mechanical ablation of tissues using pulsed high intensity focused ultrasound (HIFU). The BH lesion is known to depend in size and shape on exposure parameters and mechanical properties, structure and composition of tissue being treated. The aim of this work was to advance the concept of BH dose by investigating quantitative relationships between the parameters of the lesion, pulsing protocols, and targeted tissue properties. A HIFU focus of a 1.5 MHz 256-element array driven by power-enhanced Verasonics system was electronically steered along the grid within 12 × 4 × 12 mm volume to produce volumetric lesions in porcine liver (soft, with abundant collagenous structures) and bovine myocardium (stiff, homogenous cellular) ex vivo tissues with various pulsing protocols (1–10 ms pulses, 1–15 pulses per point). Quantification of the lesion size and completeness was performed through serial histological sectioning, and a computer vision approach using a combination of manual and automated detection of fully fractionated and residual tissue based on neural network ResNet-18 was developed. Histological sample fixation led to underestimation of BH ablation rate compared to the ultrasound-based estimations, and provided similar qualitative feedback as did gross inspection. This suggests that gross observation may be sufficient for qualitatively evaluating the BH treatment completeness. BH efficiency in liver tissue was shown to be insensitive to the changes in pulsing protocol within the tested parameter range, whereas in bovine myocardium the efficiency increased with either increasing pulse length or number of pulses per point or both. The results imply that one universal mechanical dose metric applicable to an arbitrary tissue type is unlikely to be established. The dose metric as a product of the BH pulse duration and the number of pulses per sonication point (BHD1) was shown to be more relevant for initial planning of fractionation of collagenous tissues. The dose metric as a number of pulses per point (BHD2) is more suitable for the treatment planning of softer targets primarily containing cellular tissue, allowing for significant acceleration of treatment using shorter pulses. [ABSTRACT FROM AUTHOR]

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

A new reconstruction approach that combines Reverse Time Migration (RTM) and Genetic Algorithms (GAs) is proposed for solving the inverse problem associated with transluminal shear wave elastography. The transurethral identification of the first thermal lesion generated by transrectal High Intensity Focused Ultrasound (HIFU) for the treatment of prostate cancer, was used to preliminarily test in silico the combined reconstruction method. The RTM method was optimised by comparing reconstruction images from several cross-correlation techniques, including a new proposed one, and different device configurations in terms of the number and arrangement of emitters and receivers of the conceptual transurethral probe. The best results were obtained for the new proposed cross-correlation method and a device configuration with 3 emitters and 32 receivers. The RTM reconstructions did not completely contour the shape of the HIFU lesion, however, as planned for the combined approach, the areas in the RTM images with high level of correlation were used to narrow down the search space in the GA-based technique. The GA-based technique was set to find the location of the HIFU lesion and the increment in stiffness and viscosity due to thermal damage. Overall, the combined approach achieves lower level of error in the reconstructed values, and in a shorter computational time, compared to the GA-based technique alone. The lowest errors were accomplished for the location of HIFU lesion, followed by the contrast ratio of stiffness between thermally treated tissue and non-treated normal tissue. The homologous ratio of viscosity obtained higher level of error. Further investigation considering diverse scenarios to be reconstructed and with experimental data is required to fully evaluate the feasibility of the combined approach. • Reverse Time Migration and Genetic Algorithm are combined for elastography. • Monitoring a HIFU lesion is used to in silico test the combined inversion approach. • The change in viscoelastic properties serves to identify the HIFU lesion location. • A new correlation method yields improved results for the Reverse Time Migration. • The combined approach speeds up the inversion and yields lower reconstruction errors. [ABSTRACT FROM AUTHOR]

PurposeTo investigate criteria that can identify dominant treatable prostate cancer foci with high certainty at endorectal magnetic resonance imaging (MRI) and MR spectroscopic (MRS) imaging, and thus facilitate selection of patients who are radiological candidates for MR-guided focal therapy.Materials and methodsWe retrospectively identified 88 patients with biopsy-proven prostate cancer who underwent endorectal MRI and MRS imaging prior to radical prostatectomy with creation of histopathological tumor maps. Two independent readers noted the largest tumor foci at MRI, if visible, and the volume of concordant abnormal tissue at MRS imaging, if present. A logistic random intercept model was used to determine the association between clinical and MR findings and correct identification of treatable (over 0.5 cm3) dominant intraprostatic tumor foci.ResultsReaders 1 and 2 identified dominant tumor foci in 50 (57%) and 58 (65%) of 88 patients; 42 (84%) and 48 (83%) of these were dominant treatable lesions at histopathology, respectively. Within the statistical model, the volume of concordant spectroscopic abnormality was the only factor that predicted correct identification of a dominant treatable lesion on T2-weighted images (odds ratio=1.75; 95% confidence interval=1.08 to 2.82; P value=0.02). In particular, all visible lesions on T2-weighted imaging associated with at least 0.54 cm3 of concordant spectroscopic abnormality were correctly identified dominant treatable tumor foci.ConclusionPatients with dominant intraprostatic tumor foci seen on T2-weighted MRI and associated with at least 0.54 cm3 of concordant MRS imaging abnormality may be radiological candidates for MR-guided focal therapy.

Acoustic cavitation which occurs at high intensities of ultrasound waves can be fatal for tumor cells. The existence of dissolved gases and also the presence of nanoparticles (NPs) in a liquid, irradiated by ultrasound, decrease the acoustic cavitation onset threshold and the resulting bubbles collapse. On the other hand, due to unique capabilities and optical properties of gold nanoparticles (GNPs), they have been emphasized as effective NPs in the field of tumor therapy. Absorption of the laser light by GNPs causes the water molecules around the NPs to evaporate and produces vapor cavities. In this paper, we have reviewed published studies in the fields of ultrasound therapy, sonodynamic therapy (SDT) and synergism of low-level ultrasound and also laser radiation in the presence of GNPs.

Purpose: In local hyperthermia, precise temperature control throughout the entire target region is key for swift, safe, and effective treatment. In this article, we present a model predictive control (MPC) algorithm providing voxel-level temperature control in magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) and assess the improvement in performance it provides over the current state of the art. Materials and methods: The influence of model detail on the prediction quality and runtime of the controller is evaluated and a tissue mimicking phantom is characterized using the resulting model. Next, potential problems arising from modeling errors are evaluated in silico and in the characterized phantom. Finally, the controller’s performance is compared to the current state-of-the-art hyperthermia controller in side-by-side experiments. Results: Modeling diffusion by heat exchange between four neighboring voxels achieves high predictive performance and results in runtimes suited for real-time control. Erroneous model parameters deteriorate the MPC’s performance. Using models derived from thermometry data acquired during low powered test sonications, however, high control performance is achieved. In a direct comparison with the state-of-the-art hyperthermia controller, the MPC produces smaller tracking errors and tighter temperature distributions, both in a homogeneous target and near a localized heat sink. Conclusion: Using thermal models deduced from low-powered test sonications, the proposed MPC algorithm provides good performance in phantoms. In direct comparison to the current state-of-the-art hyperthermia controller, MPC performs better due to the more finely tuned heating patterns and therefore constitutes an important step toward stable, uniform hyperthermia.

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis. Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses. Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033–1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029–1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF

Objective: To develop and evaluate a combined motion-assisted/gated MRHIFU heating strategy designed to accelerate the treatment procedure by reducing the required number of sonications to ablate a target volume in the pancreas. Methods: A planning method for combined motion-assisted/gated MRHIFU using 4D-MRI and motion characterization is introduced. Six healthy volunteers underwent 4D-MRI for target motion characterization on a 3.0-T clinical scanner. Using displacement patterns, simulations were performed for all volunteers for three sonication approaches: gated, combined motion-assisted/gated, and static. The number of sonications needed to ablate the pancreas head was compared. The influence of displacement amplitude and target volume size was investigated. Spherical target volumes (8, 15, 20 and 34 mL) and displacement amplitudes ranging from 5 to 25 mm were evaluated. For this case, the number of sonications required to ablate the whole target was determined. Results: The number of required sonications was lowest for a static target, 62 on average (range 49–78). The gated approach required most sonications, 126 (range 97–159). The combined approach was almost as efficient as the hypothetical static case, with an average of 78 (range 53–123). Simulations showed that with a 5-mm displacement amplitude, the target could be treated by making use of motion-assisted MRHIFU sonications only. In that case, this approach allowed the lowest number of sonication, while for 10 mm and above, the number of required sonications increased. Conclusion: The use of a combined motion-assisted/gated MRHIFU strategy may accelerate tumor ablation in the pancreas when respiratory-induced displacement amplitudes are between 5 and 10 mm.

Purpose: The objective of this study was to investigate the bactericidal effects of high intensity focused ultrasound (HIFU) on Bacillus Calmette–Guerin (BCG, a substitute for Mycobacterium tuberculosis) in vitro and in vivo, and to explore the underlying mechanisms. Materials and methods: HIFU, at a fixed frequency of 1 MHz, was applied to both BCG culture suspensions and subcutaneous BCG abscesses in rats. Results: HIFU irradiation significantly reduced the bacterial survival rate and caused temperature elevations both in vitro and in vivo. Furthermore, BCG suspensions irradiated for 15 s at 3185 and 6369 W/cm2 had increased cell wall damage, which resulted in morphological changes compared to the untreated control group. Additionally, we observed histological changes in the rat subcutaneous abscesses after HIFU ablation at 6369 W/cm2. H&E staining of infected lesions showed coagulative necrosis with central nucleus dissolution and increased infiltration of inflammatory cells, as well as nuclear pyknosis and nuclear fragmentation in the periphery. The volumes of the subcutaneous abscesses in the HIFU-treated group were significantly lower than those in the sham-treated group. Conclusion: HIFU has the therapeutic potential to treat BCG-infected tissues in rats. We theorize that a combination of mechanical, cavitation, and thermal effects most efficiently inactivate BCG bacteria via HIFU. This study is expected to provide a bio-plausible basis for a noninvasive and effective treatment for tuberculosis.

Objective: To evaluate the outcomes of subsequent pregnancies in patients with a history of cesarean scar pregnancy (CSP) treated with high intensity focused ultrasound (HIFU) followed by ultrasound-guided dilation and curettage (USg-D&C). Methods: A retrospective analysis was performed on data collected from 154 patients with CSP who were treated by HIFU followed by USg-D&C in Suining Central Hospital between January 2015 and January 2018. Among them, 28 patients wanted to conceive following treatment. Baseline characteristics, treatment results, intraoperative hemorrhages during USg-D&C, post-curettage serum beta human chorionic gonadotropin (β-hCG) levels and vaginal bleeding were investigated. Subsequent pregnancy outcomes, including intervals between pregnancy and treatment of CSP, complications during pregnancy, and outcomes of newborns were evaluated. Results: All patients with CSP were successfully treated by HIFU combined with USg-D&C. Of the 28 CSP patients who intended to conceive after the treatment, 23 patients (82.14%) successfully conceived. The average interval between conception and HIFU treatment was 18.38 ± 10.04 months. Eighteen patients (78.26%) had an intrauterine pregnancy, in which 12 had delivery by cesarean section, 1 had an ongoing pregnancy, and 5 had an abortion in the first trimester. Among the other 5 women, 3 had tubal ectopic pregnancy and 2 had recurrent CSP. These five patients underwent laparoscopy within the first trimester. Conclusion: HIFU followed by USg-D&C is an effective and safe treatment for patients with CSP who wish to conceive. Prospective multi-center studies with larger sample sizes and longer follow-up periods are needed to compare this treatment with others.

Objective: To evaluate the safety and feasibility of combined procedures: HIFU combined with systemic MTX followed by ultrasound-guided curettage or hysteroscopic resection while treating placenta accreta (PA). Method: This study included 21 patients diagnosed with retained PA with marked vascularity after abortion or delivery from July 2015 to December 2017. Patients with high serum β-hCG level (≥100 mIU/mL) received systemic MTX + HIFU treatment for 3 days and the ones with low β-hCG level (

Purpose: Osteomyelitis is one of the most serious complications linked to diabetes and increases the possibility of limb amputation considerably. There exists an important clinical need to improve management of osteomyelitis, especially for diabetic patients who are more susceptible to failures, relapses and chronicity of multiple bone infections. Magnetic resonance-guided focused ultrasound (MRgFUS) can offer a clinical management option for patients with osteomyelitis by providing a non-surgical and potentially rapid-recovery treatment option. Material and Methods: A retrospective study with patients with confirmed osteomyelitis (n = 75) was performed at evaluating the feasibility to target bone infection sites with a clinically approved MRgFUS device (Sonalleve, Profound Medical, Mississauga, ON, Canada). The developed methodology allows using preexisting diagnostic magnetic resonance imaging (MRI) or computed tomography (CT) scans to evaluate the treatment feasibility directly using a MRgFUS treatment planning software. Results: 74.7% of the cases included in our study passed the targetability criteria. Cases were deemed non-targetable if the target was less than 1 cm from the skin or close to a neuro-vascular bundle, metallic implants, or in the way of a defect in the overlying skin. For cases that passed the targetability criteria, an average among patients of 92.7 ± 5.2% of the gross treatment volume could be reached using treatment cells available at the Sonalleve system. Conclusion: The retrospective study presented here is the first step to demonstrate the feasibility of utilizing MRgFUS for the thermal treatment of osteomyelitis.

Background: The use of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) to deliver mild hyperthermia requires stable temperature mapping for long durations. This study evaluates the effects of respiratory motion on MR thermometry precision in pediatric subjects and determines the in vivo feasibility of circumventing breathing-related motion artifacts by delivering MR thermometry-controlled HIFU mild hyperthermia during repeated forced breath holds. Materials and methods: Clinical and preclinical studies were conducted. Clinical studies were conducted without breath-holds. In phantoms, breathing motion was simulated by moving an aluminum block towards the phantom along a sinusoidal trajectory using an MR-compatible motion platform. In vivo experiments were performed in ventilated pigs. MR thermometry accuracy and stability were evaluated. Results: Clinical data confirmed acceptable MR thermometry accuracy (0.12–0.44 °C) in extremity tumors, but not in the tumors in the chest/spine and pelvis. In phantom studies, MR thermometry accuracy and stability improved to 0.37 ± 0.08 and 0.55 ± 0.18 °C during simulated breath-holds. In vivo MR thermometry accuracy and stability in porcine back muscle improved to 0.64 ± 0.22 and 0.71 ± 0.25 °C during breath-holds. MR-HIFU hyperthermia delivered during intermittent forced breath holds over 10 min duration heated an 18-mm diameter target region above 41 °C for 10.0 ± 1.0 min, without significant overheating. For a 10-min mild hyperthermia treatment, an optimal treatment effect (TIR > 9 min) could be achieved when combining 36–60 s periods of forced apnea with 60–155.5 s free-breathing. Conclusion: MR-HIFU delivery during forced breath holds enables stable control of mild hyperthermia in targets adjacent to moving anatomical structures.

Background: The goal of this study is to evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) for patients with colorectal liver metastases (CRLM) but were contraindicated for resection and radiofrequency ablation. Methods: Patients between 20 and 80 years of age with 1–3 liver metastases from colorectal cancer were selected. Included patients have had their primary lesions removed with no evidence of extrahepatic metastasis prior to the study. Ultrasound-guided HIFU was employed and target regions' ablation was achieved with repeated sonications from the deep to shallow regions of the tumors section by section. Results: Thirteen patients were enrolled. The most common adverse events (AEs) were pain (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase (ALT) (n = 5), and skin edema (n = 4). No grade ≥ 3 AEs occurred and while most patients (76.9%) achieved a complete response, three patients achieved a partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but the tumors were mostly isolated to the liver (8/9). The median follow-up period was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and the median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and the median OS was 25 months. Conclusion: This study indicates that the HIFU treatment is safe, is able to achieve a good tumor response rate and long-term prognosis even when the foci were in high-risk locations, and should be considered for patients who were considered unsuitable for other local treatments. [ABSTRACT FROM AUTHOR]

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

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

With the widespread use of serum PSA level screening and multi-parameter magnetic resonance imaging, the number of diagnoses of prostate cancer has increased. Traditionally. prostate cancer is mainly treated through active monitoring. radical prostatectomy or radiotherapy. Local treatment is a relatively new method the main feature is the local ablation of prostate cancer lesions and the preservation of surrounding healthy tissues. Compared with total gland therapy. local therapy has relatively satisfactory mid-term efficacy and a lower incidence of complications. At present the most discussed local treatment methods mainly include cryotherapy, high-intensity focused ultrasound. laser ablation. photodynamic therapy, and irreversible electroporation. This article combines the existing literature reports at home and abroad to review the local treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. Materials and methods: In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007–November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6–12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. Results: 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). Conclusion: Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours. [ABSTRACT FROM AUTHOR]

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

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