Magnetic Resonance-guided High-intensity Focused Ultrasound Research Articles

Intravoxel incoherent motion (IVIM)-derived perfusion fraction mapping for the visual evaluation of MR-guided high intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids

Background A method for periprocedural contrast agent-free visualization of uterine fibroid perfusion could potentially shorten magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment times and improve outcomes. Our goal was to test feasibility of perfusion fraction mapping by intravoxel incoherent motion (IVIM) modeling using diffusion-weighted MRI as method for visual evaluation of MR-HIFU treatment progression. Methods Conventional and T2-corrected IVIM-derived perfusion fraction maps were retrospectively calculated by applying two fitting methods to diffusion-weighted MRI data (b = 0, 50, 100, 200, 400, 600 and 800 s/mm2 at 1.5 T) from forty-four premenopausal women who underwent MR-HIFU ablation treatment of uterine fibroids. Contrast in perfusion fraction maps between areas with low perfusion fraction and surrounding tissue in the target uterine fibroid immediately following MR-HIFU treatment was evaluated. Additionally, the Dice similarity coefficient (DSC) was calculated between delineated areas with low IVIM-derived perfusion fraction and hypoperfusion based on CE-T1w. Results Average perfusion fraction ranged between 0.068 and 0.083 in areas with low perfusion fraction based on visual assessment, and between 0.256 and 0.335 in surrounding tissues (all p < 0.001). DSCs ranged from 0.714 to 0.734 between areas with low perfusion fraction and the CE-T1w derived non-perfused areas, with excellent intraobserver reliability of the delineated areas (ICC 0.97). Conclusion The MR-HIFU treatment effect in uterine fibroids can be visualized using IVIM perfusion fraction mapping, in moderate concordance with contrast enhanced MRI. IVIM perfusion fraction mapping has therefore the potential to serve as a contrast agent-free imaging method to visualize the MR-HIFU treatment progression in uterine fibroids.

Preliminary insights into high-intensity focused ultrasound ablation for symptomatic uterine fibroids: a first look in Egypt

BackgroundUterine fibroids are common gynecological conditions that affect a significant number of women of reproductive age and may necessitate surgical intervention for their removal. However, there is a rising trend toward minimally invasive procedures, such as magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) ablation. This report provides the first experience in Egypt and North Africa on the use of MRgHIFU ablation as a therapeutic option for uterine fibroids.ResultsThis study demonstrates a correlation between post-operative NPV% and symptom improvement. Following a three-month follow-up period, a significant reduction in pain scores and excessive bleeding was observed. Importantly, there was no significant elevation in hemoglobin levels (11.23 ± 2.23 to 11.25 ± 1.71 g/dL) after treatment. Furthermore, the mean non-perfused volume ratio in the treated fibroids was 46 ± 27.3% (SD) among the 20 participants. These findings suggest a favorable therapeutic outcome of MRgHIFU, with no serious adverse effects reported.ConclusionMRgHIFU is a noninvasive therapeutic approach for the treatment of uterine myomas, offering significant benefits in terms of pain reduction and improved quality of life. This particular study represents the pioneering clinical experience of this innovative therapy in Egypt.

Occurrence and Risk Factors for Perioperative Treatment Discontinuation during Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) Therapy in Symptomatic Uterine Fibroids-A Retrospective Case-Control Study.

The main aim of our study involves the analysis of reasons and risk factors for perioperative treatment discontinuation in patients with symptomatic uterine fibroids (UFs) who were qualified for magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) and in whom the procedure was discontinued. The presented research included 372 women who were primarily eligible for MR-HIFU, but the procedure was interrupted. The reasons and risk factors for treatment discontinuation were analyzed. A statistical comparison of two cohorts (patients in whom the treatment was discontinued and completed) was conducted based on epidemiological factors, UF characteristics and the implementation of uterotonics. The mean discontinuation rate was 18.28% (n = 68). The main reason was the malposition of the intestines (52.94% of all cases). The thermoablation of subserosal UFs was a statistically significant risk factor of perioperative treatment discontinuation (OR 4.62, CI 95% 2.04-10.56), while the therapy of intramural UFs considerably decreased the risk (OR 0.21, CI 95% 0.08-0.51). The volume of the targeted UF was negatively correlated with the risk of discontinuation (OR 0.991, CI 95% 0.986-0.996). Augmentation with oxytocin, but not misoprostol, during the procedure significantly decreased the risk of potential discontinuation (OR 0.15, CI 95% 0.045-0.387, p < 0.001). Although the discontinuation rate seems to be relatively low, further prospective randomized trials are needed to confirm our results. The establishment of particular eligibility criteria for the treatment is a crucial issue in this area. Resigning from the procedure in cases at a high risk of discontinuation might increase patient safety and shorten the time to introduce the most appropriate therapy.

SURG-02. MAGNETIC RESONANCE-GUIDED HIGH-INTENSITY FOCUSED ULTRASOUND (MRGHIFU) FOR TREATMENT OF LOW GRADE GLIOMA IN A PEDIATRIC PATIENT

Abstract INTRODUCTION Transcranial magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has demonstrated efficacy in the treatment of adult essential tremor through targeted thermoablation visualized in real-time with MR thermography. The minimally invasive nature of MRgHIFU and lack of ionizing radiation makes it an appealing treatment modality for pediatric patients. There is limited data describing MRgHIFU for pediatric brain tumors. This case report describes the use of MRgHIFU to treat a low grade glioma in a pediatric patient. METHODS A prospective, non-randomized, single-arm study enrolled patients 8-22 years old with benign intracranial tumors requiring intervention to be treated with the ExAblate 4000 System. Clinical and radiographic examinations were performed at the following intervals after treatment: 1 day, 14 days, 3 months, 6 months, and 1 year. RESULTS One patient was treated with MRgHIFU in 2022. A 12 year-old female with headaches and Neurofibromatosis Type 1 (NF1) without prior medical or surgical treatment presented with a progressive enhancing lesion in the right parieto-occipital region. Stereotactic biopsy confirmed pathological diagnosis of a low-grade glioma. MRgHIFU was used to treat the lesion with 5 sonications ranging 600-800 watts resulting in immediate T2 and FLAIR changes. There were no complications or adverse events. MRI demonstrated slight volume reduction after one year. The patient scored herself a 7 on the Patient Global Impression of Change scale for considerable improvement. Her headaches improved and she participates actively in school and sports. CONCLUSION MRgHIFU is an attractive alternative to open craniotomy and/or radiation for pediatric patients with benign brain tumors. In our experience with one patient, the use of MRgHIFU for treatment of a low-grade glioma demonstrated safety in addition to radiographic disease control at 1 year with favorable patient impression scores. Additional patient enrollment and extended follow-up time will be necessary to determine generalizability and therapeutic longevity.

Occurrence of adverse events after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) therapy in symptomatic uterine fibroids—a retrospective case-control study

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

Comparative Characterization of Nonlinear Ultrasound Fields Generated by Sonalleve V1 and V2 MR-HIFU Systems.

A Sonalleve magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) clinical system (Profound Medical, Mississauga, ON, Canada) has been shown to generate nonlinear ultrasound fields with shocks up to 100 MPa at the focus as required for HIFU applications such as boiling histotripsy of hepatic and renal tumors. The Sonalleve system has two versions V1 and V2 of the therapeutic array, with differences in focusing angle, focus depth, arrangement of elements, and the size of a central opening that is twice larger in the V2 system compared to the V1. The goal of this study was to compare the performance of the V1 and V2 transducers for generating high-amplitude shock-wave fields and to reveal the impact of different array geometries on shock amplitudes at the focus. Nonlinear modeling of the field in water using boundary conditions reconstructed from holography measurements shows that at the same power output, the V2 array generates 10-15-MPa lower shock amplitudes at the focus. Consequently, substantially higher power levels are required for the V2 system to reach the same shock-wave exposure conditions in histotripsy-type treatments. Although this difference is mainly caused by the smaller focusing angle of the V2 array, the larger central opening of the V2 array has a nontrivial impact. By excluding coherently interacting weakly focused waves coming from the central part of the source, the presence of the central opening results in a somewhat higher effective focusing angle and thus higher shock amplitudes at the focus. Axisymmetric equivalent source models were constructed for both arrays, and the importance of including the central opening was demonstrated. These models can be used in the "HIFU beam" software for simulating nonlinear fields of the Sonalleve V1 and V2 systems in water and flat-layered biological tissues.

An adaptive targeting algorithm for magnetic resonance-guided high-intensity focused ultrasound controlled hyperthermia.

Mild hyperthermia has been demonstrated to improve the efficacy of chemotherapy, radiation, and immunotherapy in various cancer types. One localized, non-invasive method of administering mild hyperthermia is magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU). However, challenges for ultrasound such as beam deflection, refraction and coupling issues may result in a misalignment of the HIFU focus and the tumor during hyperthermia. Currently, the best option is to stop the treatment, wait for the tissue to cool, and redo the treatment planning before restarting the hyperthermia. This current workflow is both time-consuming and unreliable. An adaptive targeting algorithm was developed for MRgHIFU controlled hyperthermia treatments for cancer therapeutics. This algorithm executes in real time while hyperthermia is being administered to ensure that the focus is within our target region. If a mistarget is detected, the HIFU system will electronically steer the focus of the HIFU beam to the correct target. The goal of this study was to quantify the accuracy and precision of the adaptive targeting algorithm's ability to correct a purposely misplanned hyperthermia treatment in real-time using a clinical MRgHIFU system. A gelatin phantom with acoustic properties matched to the average speed of sound in human tissue was used to test the adaptive targeting algorithm's accuracy and precision. The target was purposely offset 10mm away from the focus at the origin, in four orthogonal directions, allowing the algorithm to correct for this mistarget. In each direction, 10 data sets were collected for a total sample size of 40. Hyperthermia was administered with a target temperature set at 42°C. The adaptive targeting algorithm was run during the hyperthermia treatment and 20 thermometry images were collected after the beam steering occurred. The location of the focus was quantified by calculating the center of heating on the MR thermometry data. The average calculated trajectory passed to the HIFU system was 9.7mm±0.4mm where the target trajectory was 10mm. The accuracy of the adaptive targeting algorithm after the beam steering correction was 0.9mm and the precision was 1.6mm. The adaptive targeting algorithm was implemented successfully and was able to correct the 10mm mistargets with high accuracy and precision in gelatin phantoms. The results demonstrate the capability to correct the MRgHIFU focus location during controlled hyperthermia.

Protocolo de tratamiento del temblor esencial

Essential tremor (ET) is the most prevalent movement disorder in adults and on occasion, it can be highly debilitating. First-line treatment is pharmacological (mainly propranolol and primidone) and tends to be effective in most patients. With time, up to 50% of patients are either not going to tolerate the medication or are going to be refractory to said therapies. In the case of intolerance and/or debilitating and drugresistant tremor, botulinum toxin injections or neurosurgical procedures such as deep brain stimulation of the ventral intermediate nucleus of the thalamus or ablative procedures such as radiofrequency thalamotomy, Gamma Knife® or magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) radiosurgery may be indicated. This protocol summarizes therapeutic recommendations based on scientific evidence for the management of patients with ET.

MR-guided ultrasound-stimulated microbubble therapy enhances radiation-induced tumor response

High intensity focused ultrasound (HIFU) systems have been approved for therapeutic ultrasound delivery to cause tissue ablation or induced hyperthermia. Microbubble agents have also been used in combination with sonication exposures. These require temperature feedback and monitoring to prevent unstable cavitation and prevent excess tissue heating. Previous work has utilized lower power and pressure to oscillate microbubbles and transfer energy to endothelial cells in the absence of thermally induced damage that can radiosensitize tumors. This work investigated whether reduced acoustic power and pressure on a commercial available MR-integrated HIFU system could result in enhanced radiation-induced tumor response after exposure to ultrasound-stimulated microbubbles (USMB) therapy. A commercially available MR-integrated HIFU system was used with a hyperthermia system calibration provided by the manufacturer. The ultrasound transducer was calibrated to reach a peak negative pressure of − 750 kPa. Thirty male New Zealand white rabbits bearing human derived PC3 tumors were grouped to receive no treatment, 14 min of USMB, 8 Gy of radiation in a separate irradiation cabinet, or combined treatments. In vivo temperature changes were collected using MR thermometry at the tumor center and far-field muscle region. Tissues specimens were collected 24 h post radiation therapy. Tumor cell death was measured and compared to untreated controls through hematoxylin and eosin staining and immunohistochemical analysis. The desired peak negative pressure of − 750 kPa used for previous USMB occurred at approximately an input power of 5 W. Temperature changes were limited to under 4 °C in ten of twelve rabbits monitored. The median temperature in the far-field muscle region of the leg was 2.50 °C for groups receiving USMB alone or in combination with radiation. Finally, statistically significant tumor cell death was demonstrated using immunohistochemical analysis in the combined therapy group compared to untreated controls. A commercial MR-guided therapy HIFU system was able to effectively treat PC3 tumors in a rabbit model using USMB therapy in combination with radiation exposures. Future work could find the use of reduced power and pressure levels in a commercial MR-guided therapy system to mechanically stimulate microbubbles and damage endothelial cells without requiring high thermal doses to elicit an antitumor response.

Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model.

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time imaging and acoustic energy modulation, this modality enables precise temperature control within a defined area. Many thermal applications are being explored with this noninvasive, nonionizing technology, such as hyperthermia generation, to release drugs from thermosensitive liposomal carriers. These drugs can include chemotherapies such as doxorubicin, for which targeted release is desired due to the dose-limiting systemic side effects, namely cardiotoxicity. Doxorubicin is a mainstay for treating a variety of malignant tumors and is commonly used in relapsed or recurrent rhabdomyosarcoma (RMS). RMS is the most common solid soft tissue extracranial tumor in children and young adults. Despite aggressive, multimodal therapy, RMS survival rates have remained the same for the past 30 years. To explore a solution for addressing this unmet need, an experimental protocol was developed to evaluate the release of thermosensitive liposomal doxorubicin (TLD) in an immunocompetent, syngeneic RMS mouse model using MRgHIFU as the source of hyperthermia for drug release.

Magnetic resonance guided high intensity focused ultrasound for uterine fibroids and adenomyosis has no effect on ovarian reserve

Introduction Uterine fibroids are the most common benign tumors in healthy women. High Intensity Focused Ultrasound (HIFU) is a modern, noninvasive thermal ablation method for treating uterine fibroids. There is increasing evidence that ultrasound guided HIFU (US-HIFU) has no adverse impact on ovarian reserve but little data exists on magnetic resonance guided HIFU (MR-HIFU). There are different options to estimate ovarian reserve, perhaps the most reliable being the measurement of serum Anti-Müllerian hormone (AMH). Material and methods Seventy-four (74) premenopausal women with serum AMH 0.1 ug/L or over, aged 24–48 and with fibroids or adenomyosis treated with MR-HIFU were enrolled in our study. AMH levels were analyzed before and 3 months after the MR-HIFU treatment. Correlations between AMH level changes and position of fibroids, fibroid volume, non-perfused volume ratio, and treatment energies were studied. Results The median AMH level before the HIFU treatment was 1.20 (range: 0.1–7.75 ug/L) and after the treatment 1.23 (range: 0.1–8.51 ug/L). No significant change was detected (p = .90). The patients were divided in three subgroups depending on the baseline AMH levels. The changes were not significant in any of the subgroups. Neither did the location of the treated fibroid affect the change of AMH levels nor the total energy used during treatment. Conclusions MR-HIFU does not compromise the ovarian reserve. Neither the location of the treated fibroid nor the total energy used during MR-HIFU had any effect on the change of AMH levels.

A feasibility study of wireless inductively coupled surface coil for MR-guided high-intensity focused ultrasound ablation of rodents on clinical MRI systems

Recently, to conduct preclinical imaging research on clinical MRI systems has become an attractive alternative to researchers due to its wide availability, cost, and translational application to clinical human studies when compared to dedicated small animal, high-field preclinical MRI. However, insufficient signal-to-noise ratio (SNR) significantly degrades the applicability of those applications which require high SNR, e.g. magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) treatment. This study introduces a wireless inductively coupled surface (WICS) coil design used on a clinical 3 T MRI system for MRgHIFU ablation. To evaluate the SNR improvement and temperature accuracy of WICS coil, the ex vivo experiments were performed on the pork tenderloins (n = 7) and the hind legs of deceased Sprague–Dawley rats (n = 5). To demonstrate the feasibility, the in vivo experiments were performed on the hind leg of Sprague–Dawley rat (n = 1). For all experiments, temperature measurements were performed before and during HIFU ablation. Temperature curves with and without WICS coil were compared to evaluate the temperature precision in ex vivo experiments. The use of WICS coil improves the temperature accuracy from 0.85 to 0.14 °C, demonstrating the feasibility of performing small animal MRgHIFU experiments using clinical 3 T MRI system with WICS coil.

Diffusion-weighted MRI with deep learning for visualizing treatment results of MR-guided HIFU ablation of uterine fibroids.

No method is available to determine the non-perfused volume (NPV) repeatedly during magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablations of uterine fibroids, as repeated acquisition of contrast-enhanced T1-weighted (CE-T1w) scans is inhibited by safety concerns. The objective of this study was to develop and test a deep learning-based method for translation of diffusion-weighted imaging (DWI) into synthetic CE-T1w scans, for monitoring MR-HIFU treatment progression. The algorithm was retrospectively trained and validated on data from 33 and 20 patients respectively who underwent an MR-HIFU treatment of uterine fibroids between June 2017 and January 2019. Postablation synthetic CE-T1w images were generated by a deep learning network trained on paired DWI and reference CE-T1w scans acquired during the treatment procedure. Quantitative analysis included calculation of the Dice coefficient of NPVs delineated on synthetic and reference CE-T1w scans. Four MR-HIFU radiologists assessed the outcome of MR-HIFU treatments and NPV ratio based on the synthetic and reference CE-T1w scans. Dice coefficient of NPVs was 71% (± 22%). The mean difference in NPV ratio was 1.4% (± 22%) and not statistically significant (p = 0.79). Absolute agreement of the radiologists on technical treatment success on synthetic and reference CE-T1w scans was 83%. NPV ratio estimations on synthetic and reference CE-T1w scans were not significantly different (p = 0.27). Deep learning-based synthetic CE-T1w scans derived from intraprocedural DWI allow gadolinium-free visualization of the predicted NPV, and can potentially be used for repeated gadolinium-free monitoring of treatment progression during MR-HIFU therapy for uterine fibroids. • Synthetic CE-T1w scans can be derived from diffusion-weighted imaging using deep learning. • Synthetic CE-T1w scans may be used for visualization of the NPV without using a contrast agent directly after MR-HIFU ablations of uterine fibroids.

A robotic MR-guided high-intensity focused ultrasound platform for intraventricular hemorrhage: assessment of clot lysis efficacy in a brain phantom.

Intraventricular hemorrhage (IVH) is a neurovascular complication due to premature birth that results in blood clots forming within the ventricles. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has been investigated as a noninvasive treatment to lyse clots. The authors designed and constructed a robotic MRgHIFU platform to treat the neonatal brain that facilitates ergonomic patient positioning. The clot lysis efficacy of the platform is quantified using a brain phantom and clinical MRI system. A thermosensitive brain-mimicking phantom with ventricular cavities was developed to test the clot lysis efficacy of the robotic MRgHIFU platform. Whole porcine blood was clotted within the phantom's cavities. Using the MRgHIFU platform and a boiling histotripsy treatment procedure (500 W, 10-msec pulse duration, 1.0% duty cycle, and 40-second duration), the clots were lysed inside the phantom. The contents of the cavities were vacuum filtered, and the remaining mass of the solid clot particles was used to quantify the percentage of clot lysis. The interior of the phantom's cavities was inspected for any collateral damage during treatment. A total of 9 phantoms were sonicated, yielding an average (± SD) clot lysis of 97.0% ± 2.57%. Treatment resulted in substantial clot lysis within the brain-mimicking phantoms that were apparent on postsonication T2-weighted MR images. No apparent collateral damage was observed within the phantom after treatment. The results from the study showed the MRgHIFU platform was successful at lysing more than 90% of a blood clot at a statistically significant level. The robotic MRgHIFU platform was shown to lyse a large percentage of a blood clot with no observable collateral damage. These results demonstrate the platform's ability to induce clot lysis when targeting through simulated brain matter and show promise toward the final application in neonatal patients.

Therapeutic Outcome of MR-Guided High-Intensity Focused Ultrasound (MR-HIFU) in Solitary versus Multiple Uterine Fibroids.

MR-guided high-intensity focused ultrasound (MR-HIFU) is an effective method for treating symptomatic uterine fibroids, especially solitary lesions. The aim of our study was to compare the clinical and morphological outcomes of patients who underwent MR-HIFU due to solitary fibroid (SF) or multiple fibroids (MFs) in a prospective clinical trial. We prospectively included 21 consecutive patients with SF (10) and MF (11) eligible for MR-guided HIFU. The morphological data were assessed using mint Lesion™ for MRI. The clinical data were determined using the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire before and 6 months after treatment. Unpaired and paired Wilcoxon-test and t-tests were applied, and Pearson’s coefficient was used for correlation analysis. A p-value of 0.05 was considered statistically significant. The volume of treated fibroids significantly decreased in both the SF (mean baseline: 118.6 cm3; mean 6-month follow-up: 64.6 cm3) and MF (107.2 cm3; 55.1 cm3) groups. The UFS-QOL showed clinical symptoms significantly improved for patients in both the SF and MF groups regarding concern, activities, energy/mood, and control. The short-term outcome for the treatment of symptomatic fibroids in myomatous uterus by MR-guided HIFU is clinically similar to that of solitary fibroids.

Bilateral Focused Ultrasound Pallidotomy for Parkinson-Related Facial Dyskinesia-A Case Report.

BackgroundFor safety reasons, both magnetic resonance‐guided high‐intensity focused ultrasound (MRgHiFUS) thalamotomy and pallidotomy are currently approved exclusively for unilateral treatment, but axial symptoms like levodopa‐induced orofacial dyskinesia require a bilateral approach.ObjectivesWe report the first case of successful bilateral MRgHiFUS pallidotomy for peak‐dose dyskinesia in a patient with Parkinson's disease (PD).MethodsThe treatment decision was based on the patient's reluctance toward brain implants and pump therapies and the fact that he had limited access to a deep brain stimulation center in his home country. The treatment was planned as staged procedure with an interval of 18 months because of travel restrictions because of the coronavirus disease (COVID)‐19 pandemic.ResultsAfter the second treatment, levodopa‐induced orofacial dyskinesia remitted and improved bradykinesia and rigidity with stable gait and good postural reflexes.ConclusionsThis promising result suggests that in selected PD patients with dyskinesia, staged bilateral MRgHiFUS pallidotomy might be considered.

Innovative and conventional \u201cconservative\u201d technologies for the treatment of uterine fibroids in Italy: a multidimensional assessment

BackgroundTo evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard “conservative” procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE).MethodsA Health Technology Assessment was conducted, assuming the payer’s perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients’ clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids’ experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy).ResultsLiterature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients’ perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients’ productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of − 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs.ConclusionsResults suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits.

Comparison of two invasive non-surgical treatment options for uterine myomas: uterine artery embolization and magnetic resonance guided high intensity focused ultrasound\u2014systematic review

BackgroundUterine Artery Embolization (UAE) and Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) are two noninvasive treatments for uterine leiomyoma.MethodsThis systematic review, following PRISMA guidelines, analyzed the effectiveness of two treatments by comparing percent fibroid volume shrinkage immediately after the procedure and after 3, 6, 12 and 24 months of follow-up and also assessed and compared common complications following treatment. The search utilized Science Direct, PubMed, MEDLINE, Google Scholar and BioMed Central databases, selecting manuscripts published during the period 2000 and 2020. Studies with premenopausal patients with previous treatments for uterine leiomyoma and/or with other pelvic diseases were excluded.ResultsTwenty-nine papers satisfied inclusion and exclusion criteria. Results were pooled and stratified by treatment and follow-up time. Weighted fibroid volume percent shrinkage after UAE was statistically significantly greater than MRgHIFU at 6, 12, and 24 months follow-up times. However, UAE had statistically significantly more complications, such as pain, nausea and vomiting. However, this study cannot conclude that UAE is more effective than MRgHIFU due to confounding factors.

A robotic magnetic resonance-guided high-intensity focused ultrasound platform for neonatal neurosurgery: Assessment of targeting accuracy and precision in a brain phantom.

Intraventricular hemorrhage (IVH) is one of the most serious neurovascular complications resulting from premature birth. It can result in clotting of blood within the ventricles, which causes a buildup of cerebrospinal fluid that can lead to posthemorrhagic ventricular dilation and posthemorrhagic hydrocephalus. Currently, there are no direct treatments for these blood clots as the standard of care is invasive surgery to insert a shunt. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has been investigated as a noninvasive treatment to lyse blood clots. However, current MRgHIFU systems are not suitable in the context of treating IVH in neonates. We have developed a robotic MRgHIFU neurosurgical platform designed to treat the neonatal brain. This platform facilitates ergonomic patient positioning and directs treatment through their open anterior fontanelle while providing a larger treatment volume. The platform is based on an MR-compatible robot developed by our group. Further development of the platform has warranted investigation of its targeting ability to assess its feasibility in the neonatal brain. This study aimed to quantify the platform's targeting accuracy, precision, and repeatability using a brain phantom and clinical MRI system. A thermosensitive brain-mimicking phantom was developed to test the platform's targeting accuracy. Rectangular grid patterns were created with HIFU thermal energy "lesions" in the phantoms by targeting specific coordinate points. The intended target locations were demarcated by inserting carbon fiber rods through a targeting assessment template. Coordinates for the intended and actual targets were derived from T2-weighted MRI scans, and the centroid distance between them was measured. Subsequently, the platform's targeting accuracy was quantified according to equations derived from ISO Standard 9283:1998. HIFU ablation resulted in distinct thermal lesions within the thermosensitive phantoms, which appeared as discrete hypointense regions in T2-weighted MR scans. A total of 127 target points were included in the data analysis, which yielded a targeting accuracy of 0.6mm and targeting precision of 1.2mm. The robotic MRgHIFU platform was shown to have a high degree of accuracy, precision, and repeatability. The results demonstrate the platform's functionality when targeting through simulated brain matter. These results serve as an initial verification of the platform targeting ability and showed promise toward the final application in a neonatal brain.

Combination of MRI‐Guided High‐Intensity Focused Ultrasound and Bioluminescent Biological Systems to Assess Thermal Therapies for Tumor and Tumor Microenvironment

AbstractThis work presents an integrated technology for assessing in vivo anticancer treatments in mice, based on various heating conditions. Bioluminescence imaging (BLI) is used to assess the physiological response of tumor and tumor microenvironment (TME) to heat treatment induced by magnetic resonance‐guided high‐intensity focused ultrasound (MRgHIFU). Transgenic tumor cells and mouse models with either constitutive or thermo‐induced luciferase expressions are combined to monitor cell viability and heat‐induced processes in the tumor and TME. BLI performed after MRgHIFU heating shows that a moderate increase in temperature (45 °C) over 5 min can be exploited to promote heat‐activable treatments in the tumor and its TME, without inducing direct cell death. A higher temperature rise over a shorter exposure time can induce cell death in the tumor, as revealed by a reduction in the BLI signal after treatment. Under these conditions, BLI also reveals that the TME can be stimulated by heat without inducing necrosis. These integrated technologies and models are useful to assess, in vivo in mice, the efficacy of various anticancer strategies exploiting local heat deposition by noninvasive MRgHIFU, including those combining tumor ablation with local drug administration using thermosensitive nanovehicles.