An augmented hybrid multibaseline and referenceless MR thermometry motion compensation algorithm for MRgHIFU hyperthermia.

PURPOSE: A hybrid principal component analysis and projection onto dipole fields (PCA-PDF) MR thermometry motion compensation algorithm was optimized with atlas image augmentation and validated. METHODS: Experiments were conducted on a 3T Philips MRI and Profound V1 Sonalleve high intensity focused ultrasound (high intensity focused ultrasound system. An MR-compatible robot was configured to induce motion on custom gelatin phantoms. Trials with periodic and sporadic motion were introduced on phantoms while hyperthermia was administered. The PCA-PDF algorithm was augmented with a predictive atlas to better compensate for larger sporadic motion. RESULTS: During periodic motion, the temperature SD in the thermometry was improved from 1 . 1 ± 0 . 1 $$ 1.1\pm 0.1 $$ to 0 . 5 ± 0 . 1 ∘ $$ 0.5\pm 0.{1}^{\circ } $$ C with both the original and augmented PCA-PDF application. For large sporadic motion, the augmented atlas improved the motion compensation from the original PCA-PDF correction from 8 . 8 ± 0 . 5 $$ 8.8\pm 0.5 $$ to 0 . 7 ± 0 . 1 ∘ $$ 0.7\pm 0.{1}^{\circ } $$ C. CONCLUSION: The PCA-PDF algorithm improved temperature accuracy to <1°C during periodic motion, but was not able to adequately address sporadic motion. By augmenting the PCA-PDF algorithm, temperature SD during large sporadic motion was also reduced to <1°C, greatly improving the original PCA-PDF algorithm.

MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients.

OBJECTIVE: To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids. METHODS: A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded. RESULTS: The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns. CONCLUSION: MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis. CLINICAL RELEVANCE STATEMENT: Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely. KEY POINTS: • Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

US-guided high-intensity focused ultrasound in pancreatic cancer treatment: a consensus initiative between Chinese and European HIFU centers.

Purpose: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) represents a safe and effective non-invasive thermoablative technique for managing inoperable pancreatic cancer. This treatment method significantly alleviates disease-related symptoms and reduces pancreatic tumor volume. However, the current body of evidence is constrained by a lack of randomized controlled trials. The utilization of USgHIFU is primarily indicated for patients with unresectable, locally advanced, or metastatic pancreatic cancer, particularly those experiencing symptoms due to a locally advanced primary tumor.Methods: This collaborative consensus paper, involving European and Chinese HIFU centers treating pancreatic cancer, delineates criteria for patient selection, focusing on those most likely to benefit from USgHIFU treatment. Consideration is given to endpoints encompassing symptom alleviation, local response rates, other oncological outcomes, as well as overall and progression-free survival. Additionally, this paper defines relevant contraindications, side effects, and complications associated with USgHIFU. The publication also explores the feasibility and role of USgHIFU within the context of palliative care, including standard systemic chemotherapy.Results: The non-invasive local treatment of advanced pancreatic cancer using HIFU should be regarded as an adjunctive option alongside systemic chemotherapy or best supportive care for managing this aggressive disease. Based on the ability of USgHIFU therapy to mitigate pain and reduce primary tumor volume, it should be considered as a complementary therapy for symptomatic patients with inoperable pancreatic cancer and as a potential means of tumor debulking. The underutilized yet promising USgHIFU exhibits the potential to enhance patients' quality of life by alleviating cancer-related pain. Experts in the field should evaluate this treatment option be evaluated by experts in this field, with this consensus paper potentially serving as a guiding resource for the medical community.Conclusions: US-guided HIFU for advanced pancreatic cancer addresses treatment goals, available options, success rates, and limitations. As a non-invasive, effective local therapy, complementary to chemotherapy and best supportive care, it plays a pivotal role in pain relief, reducing of tumor volume, and potentially improving survival rates.

Controlled Hyperthermia With High-Intensity Focused Ultrasound and Ultrasound Contrast Agent Microbubbles in Porcine Liver.

OBJECTIVE: The objective of this work was to study microbubble-enhanced temperature elevation with high-intensity focused ultrasound (HIFU) at different acoustic pressures and under image guidance. The microbubbles were administered with either local or vascular injections (that mimic systemic injections) in perfused and non-perfused ex vivo porcine liver under ultrasound image guidance. METHODS: Porcine liver was insonified for 30 s with a single-element HIFU transducer (0.9 MHz, 0.413 ms, 82% duty cycle, focal pressures of 0.6-3.5 MPa). Contrast microbubbles were injected either locally or through the vasculature. A needle thermocouple at the focus measured temperature elevation. Diagnostic ultrasound (Philips iU22, C5-1 probe) guided placement of the thermocouple and delivery of microbubbles and monitored the procedure in real time. RESULTS: At lower acoustic pressures (0.6 and 1.2 MPa) in non-perfused liver, inertial cavitation of the injected microbubbles led to greater temperatures at the focus compared with HIFU-only treatments. At higher pressures (2.4 and 3.5 MPa) native inertial cavitation in the tissue (without injecting microbubbles) resulted in temperature elevations similar to those after injecting microbubbles. The heated area was larger when using microbubbles at all pressures. In the presence of perfusion, only local injections provided a sufficiently high concentration of microbubbles necessary for significant temperature enhancement. CONCLUSION: Local injections of microbubbles provide a higher concentration of microbubbles in a smaller area, avoiding acoustic shadowing, and can lead to higher temperature elevation at lower pressures and increase the size of the heated area at all pressures.

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

BACKGROUND: 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. PURPOSE: 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. METHODS: 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 10 mm 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. RESULTS: The average calculated trajectory passed to the HIFU system was 9.7 mm ± 0.4 mm where the target trajectory was 10 mm. The accuracy of the adaptive targeting algorithm after the beam steering correction was 0.9 mm and the precision was 1.6 mm. CONCLUSION: The adaptive targeting algorithm was implemented successfully and was able to correct the 10 mm mistargets with high accuracy and precision in gelatin phantoms. The results demonstrate the capability to correct the MRgHIFU focus location during controlled hyperthermia.

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.

Alternative- and focal therapy trends for prostate cancer: a total population analysis of in-patient treatments in Germany from 2006 to 2019.

PURPOSE: Focal therapy (FT) offers an alternative approach for prostate cancer (PCa) treatment in selected patients. However, little is known on its actual establishment in health care reality. PATIENTS AND METHODS: We defined FT as high-intensity focused ultrasound (HIFU), hyperthermia ablation, cryotherapy, transurethral ultrasound ablation (TULSA) or vascular-targeted photodynamic therapy (VTP) TOOKAD®. We analyzed the nationwide German hospital billing database for a PCa diagnosis in combination with FT. For analyses on the hospital level, we used the reimbursement.INFO tool based on hospitals' quality reports. The study period was 2006 to 2019. RESULTS: We identified 23,677 cases of FT from 2006 to 2019. Considering all PCa cases with surgery, radiotherapy or FT, the share of FT was stable at 4%. The annual caseload of FT increased to a maximum of 2653 cases in 2008 (p < 0.001) and then decreased to 1182 cases in 2014 (p < 0.001). Since 2015, the cases of FT remained on a plateau around 1400 cases per year. The share of HIFU was stable at 92-96% from 2006 to 2017 and decreased thereafter to 75% in 2019 (p = 0.015). In 2019, VTP-TOOKAD® increased to 11.5% and TULSA to 6%. In 2006, 21% (62/299) of urological departments performed FT and 20 departments reached > 20 FT procedures. In 2019, 16% (58/368) of urological departments performed FT and 7 departments reached > 20 FT. In 2019, 25 urological departments offered FT other than HIFU: 5 centers hyperthermia ablation, 11 centers VTP TOOKAD®, 3 centers cryotherapy, 6 centers TULSA. CONCLUSION: The FT development in Germany followed the Gartner hype cycle. While HIFU treatment is the most commonly performed FT, the share of newer FT modalities such as VTP-TOOKAD® and TULSA is remarkably increasing.

Parameter estimation in high-intensity focused ultrasound therapy.

Hyperthermia using High-Intensity Focused Ultrasound (HIFU) is an acoustic therapy for cancer treatment. This technique consists of an increase in the temperature field of the tumor to achieve coagulative necrosis and immediate cell death. Therefore, for having a successful treatment, the physical problem requires to know several properties due to the high variability from individual to individual, or even for the same individual under different physiological conditions. This article presents a numerical simulation of hyperthermia therapy for cancer treatment using HIFU, as well as the estimation of parameters that influence the physical problem. Two mathematical models were considered to solve the forward problem. The acoustic model based on acoustic pressure performs a frequency-domain study, and the bioheat transfer model a time-dependent study. These models were solved using Comsol Multiphysics® software in a 2D-axisymmetric rectangular domain to determine the temperature field. Parameter estimation was coded in Matlab Mathworks® environment using a Bayesian approach. The Markov Chain Monte Carlo method by the Metropolis-Hastings algorithm was implemented, and the simulated temperature measurements were considered. Results suggest that specific HIFU therapy can be performed for each patient by estimating appropriate parameters for cancer treatment and provides the possibility to define procedures before and during the treatment.

Hyperthermia-induced doxorubicin delivery from thermosensitive liposomes via MR-HIFU in a pig model.

PURPOSE: Encapsulation of cytotoxic drugs for a localized release is an effective way to increase the therapeutic window of such agents. In this article we present the localized release of doxorubicin (DOX) from phosphatidyldiglycerol (DPPG2) based thermosensitive liposomes using MR-HIFU mediated hyperthermia in a swine model. MATERIALS AND METHODS: German landrace pigs of weights between 37.5 and 53.5 kg received a 30-min infusion of DOX containing thermosensitive liposomes (50 mg DOX/m2). The pigs' biceps femoris was treated locally in two separate target areas with mild hyperthermia using magnetic resonance guided high intensity focused ultrasound, starting 10 min and 60 min after initiation of the infusion, respectively. The pharmacokinetics and biodistribution of DOX were determined and an analysis of the treatment parameters' influence was performed. RESULTS: Compared to untreated tissue, we found a 15-fold and a 7-fold increase in DOX concentration in the muscle volumes that had undergone hyperthermia starting 10 min and 60 min after the beginning of the infusion, respectively. The pharmacokinetic analysis showed a prolonged circulation time of DOX and a correlation between the AUC of extra-liposomal DOX in the bloodstream and the amount of DOX accumulated in the target tissue. CONCLUSIONS: We have demonstrated a workflow for MR-HIFU hyperthermia drug delivery that can be adapted to a clinical setting, showing that HIFU-hyperthermia is a suitable method for local drug release of DOX using DPPG2 based thermosensitive liposomes in stationary targets. Using the developed pharmacokinetic model, an optimization of the drug quantity deposited in the target via the timing of infusion and hyperthermia should be possible.

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer: A Systematic Review.

Purpose: MRI-guided transurethral ultrasound ablation (TULSA) uses real-time MR thermometry feedback to target prostate disease. We systematically review the literature to synthesize efficacy, functional, and safety outcomes and assess the influence of planned ablation fraction on outcome. Materials and Methods: PubMed, Embase, and the Cochrane Library were searched from inception to June 2021 following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies reporting at least one efficacy, functional, or safety outcome after a single TULSA treatment were included. The relationship of freedom from salvage treatment and potency preservation with planned ablation volume was modeled. Results: Two hundred twenty-four patients were treated in 10 studies with up to a 5-year follow-up, mainly for primary localized prostate cancer (PCa) plus smaller cohorts with recurrent PCa, and locally advanced PCa (LAPC). The prostate-specific antigen decline from baseline up to 2 years, including focal to whole-gland ablation plans, was 54% to 97%. The rate of salvage treatment after one TULSA treatment for primary PCa was 7% to 17%. Continence and potency preservation were from 92% to 100% and from 75% to 98%. Urinary symptoms were stable in men with good voiding function at baseline, and 85% of men with concurrent PCa and lower urinary tract symptoms met the criteria for improvement. Symptom relief in a small cohort of men with LAPC was observed. Grade III adverse events were incurred by 13/224 men (6%), with no rectal injury/fistula or Grade IV complication. The planned ablation fraction was linearly related to salvage-free survival. The relationship between potency preservation and planned ablation fraction followed a sigmoid curve. Conclusions: As an alternative to conventional treatments, TULSA is safe and effective for prostate tissue ablation in men with primary PCa. There is also evidence that TULSA delivers effective relief of urinary symptoms while treating PCa in a single, low-morbidity procedure. The likelihood of freedom from additional treatment or potency preservation is associated with the planned ablation fraction.

Computational modeling of thermal combination therapies by magneto-ultrasonic heating to enhance drug delivery to solid tumors.

For the first time, inspired by magnetic resonance imaging-guidance high intensity focused ultrasound (MR-HIFU) technology, i.e., medication therapy and thermal ablation in one session, in a preclinical setting based on a developed mathematical model, the performance of doxorubicin (Dox) and its encapsulation have been investigated in this study. Five different treatment methods, that combine medication therapy with mild hyperthermia by MRI contrast ([Formula: see text]) and thermal ablation via HIFU, are investigated in detail. A comparison between classical chemotherapy and thermochemistry shows that temperature can improve the therapeutic outcome by stimulating biological properties. On the other hand, the intravascular release of ThermoDox increases the concentration of free drug by 2.6 times compared to classical chemotherapy. The transport of drug in interstitium relies mainly on the diffusion mechanism to be able to penetrate deeper and reach the cancer cells in the inner regions of the tumor. Due to the low drug penetration into the tumor center, thermal ablation has been used for necrosis of the central areas before thermochemotherapy and ThermoDox therapy. Perfusion of the region around the necrotic zone is found to be damaged, while cells in the region are alive and not affected by medication therapy; so, there is a risk of tumor recurrence. Therefore, it is recommended that ablation be performed after the medication therapy. Our model describes a comprehensive assessment of MR-HIFU technology, taking into account many effective details, which can be a reliable guide towards the optimal use of drug delivery systems.

The What, the Why, and the How of Liver Ablations: A Practical Guide for the Medical Oncologist.

Interventional oncology plays a major role within modern oncological patient management. Image-guided thermal ablation has been recognized as a successful local therapeutic option in patients with primary and secondary malignant liver diseases, as also recalled by the recent European Society of Medical Oncology (ESMO) guidelines on colorectal metastases. As image-guided treatments may be as effective as surgery in selected patients with liver lesions, the clinical oncologist should be familiar with the indications, risks, and technical aspects of liver ablation in order to provide their patients with the best outcomes. This article provides a broad overview of the most commonly used ablation techniques and highlights the most relevant technical aspects such as the ideal setting in the operating theatre; which image-guided methods are available, including the growing application of fusion imaging; or contrast-enhanced ultrasound for guiding/monitoring the procedure. A further aim is to expand the knowledge among medical oncologists about liver ablation procedures and to provide insights into the future perspectives of percutaneous minimally invasive procedures in the liver.

Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study.

BACKGROUND: Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE: To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS: A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS: The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION: Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness.

MR-Guided High-Intensity Directional Ultrasound Ablation of Prostate Cancer.

PURPOSE OF REVIEW: The goal of this paper was to review the novel treatment modality of high-intensity transurethral directional ultrasound for prostate cancer. RECENT FINDINGS: Prostate cancer is a heterogeneous disease with some patients electing for active surveillance and focal therapies instead of definitive treatment with radical prostatectomy or radiation therapy. Prostate MRI has become a cornerstone of prostate cancer diagnosis, targeted biopsy, and treatment planning. Transurethral high-intensity directional ultrasound allows for MRI-guided ablation of the prostate gland with the ability to contour boundaries and spare critical structures, such as the neurovascular bundle and urinary sphincter. Although results are still emerging, this may offer patients a new option for focal therapy with a favorable side-effect profile. High-intensity transurethral directional ultrasound is an emerging treatment modality for both whole-gland and focal ablation with promising early results. Further research is needed to establish safety, tolerability, and long-term oncologic outcomes.

500 Cases of High-intensity Focused Ultrasound (HIFU) Ablated Uterine Fibroids and Adenomyosis.

OBJECTIVE: Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. MATERIALS AND METHODS: This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16  cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. RESULTS: Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. CONCLUSION: HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.

Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes.

The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.

Focused Ultrasound Hyperthermia Augments Release of Glioma-derived Extracellular Vesicles with Differential Immunomodulatory Capacity.

Background: Increasing evidence points to the critical role of extracellular vesicles (EVs) as molecular parcels that carry a diverse array of bioactive payloads for coordination of complex intracellular signaling. Focused ultrasound (FUS) hyperthermia is a technique for non-invasive, non-ionizing sublethal heating of cells in a near-instantaneous manner; while it has been shown to improve drug delivery and immunological recognition of tumors, its impact on EVs has not been explored to date. The goal of this study was to determine whether FUS impacts the release, proteomic profile, and immune-activating properties of tumor-derived EVs. Methods: Monolayered murine glioma cells were seeded within acoustically transparent cell culture chambers, and FUS hyperthermia was applied to achieve complete coverage of the chamber. Glioma-derived EVs (GEVs) were isolated for characterization by Nanoparticle Tracking Analysis, cryo-electron microscopy and mass spectrometry. An in vitro experimental setup was designed to further dissect the impact of GEVs on innate inflammation; immortalized murine dendritic cells (DCs) were pulsed with GEVs (either naïve or FUS hyperthermia-exposed) and assayed for production of IL-12p70, an important regulator of DC maturation and T helper cell polarization toward the interferon-γ-producing type 1 phenotype. Results: We confirmed that FUS hyperthermia significantly augments GEV release (by ~46%) as well as shifts the proteomic profile of these GEVs. Such shifts included enrichment of common EV-associated markers, downregulation of markers associated with cancer progression and resistance and modulation of inflammation-associated markers. When DCs were pulsed with GEVs, we noted that naïve GEVs suppressed IL-12p70 production by DCs in a GEV dose-dependent manner. In contrast, GEVs from cells exposed to FUS hyperthermia promoted a significant upregulation in IL-12p70 production by DCs, consistent with a pro-inflammatory stimulus. Conclusion: FUS hyperthermia triggers release of proteomically distinct GEVs that are capable of facilitating an important component of innate immune activation, lending both to a potential mechanism by which FUS interfaces with the tumor-immune landscape and to a role for GEV-associated biomarkers in monitoring response to FUS.

Temperature elevation in tissue detected in vivo based on statistical analysis of ultrasonic scattered echoes.

It is demanded to monitor temperature in tissue during oncological hyperthermia therapy. In the present study, we non-invasively measured the temperature elevation inside the abdominal cavity and tumour tissue of a living rat induced by capacitive-coupled radiofrequency heating. In the analysis of ultrasound scattered echoes, the Nakagami shape parameter m in each region of interest was estimated at each temperature. The Nakagami shape parameter m has temperature dependence; hence, the temperature increase inside tissue specimens can be detected with the m values. By carrying out in vivo experiments, we visualized the temperature increase inside the abdominal cavity and tumour tissue of living rats using two-dimensional hot-scale images indicating the absolute values of the ratio changes of the m values. In both the abdominal cavity and tumour tissue, the brightness in the hot-scale images clearly increased with increasing temperature. The increases in brightness in the hot-scale images imply the temperature elevations inside the abdominal cavity and tumour tissue of the living rats. The study results prove that the acoustic method we proposed is a promising method for monitoring changes in the internal temperature of the human body under hyperthermia treatment.

Intraoperative imaging findings in transcranial MR imaging-guided focused ultrasound treatment at 1.5T may accurately detect typical lesional findings correlated with sonication parameters.

OBJECTIVES: To assess the intraoperative neuroimaging findings in patients treated with transcranial MR-guided focused ultrasound (tcMRgFUS) thalamotomy using 1.5T equipment in comparison with the 48-h follow-up. METHODS: Fifty prospectively enrolled patients undergoing unilateral tcMRgFUS thalamotomy for either medication-refractory essential tremor (n = 39) or Parkinson tremor (n = 11) were included. Two radiologists evaluated the presence and size of concentric lesional zones (zone I, zone II, and zone III) on 2D T2-weighted sequences acquired intraoperatively after the last high-energy sonication and at 48 h. Sonication parameters including number of sonications, delivered energy, and treatment temperatures were also recorded. Differences in lesion pattern and size were assessed using the McNemar test and paired t test, respectively. RESULTS: Zones I, II, and III were visualized in 34 (68%), 50 (100%), and 44 (88%) patients, and 31 (62%), 50 (100%), and 45 (90%) patients after the last high-energy sonication for R1 and R2, respectively. All three concentric zones were visualized intraoperatively in 56-58% of cases. Zone I was significantly more commonly visualized at 48 h (p < 0.001). Diameter of zones I and II and the thickness of zone III significantly increased at 48 h (p < 0.001). Diameters of zones I and II measured intraoperatively demonstrated significant correlation with thermal map temperatures (p ≤ 0.001). Maximum temperature significantly correlated with zone III thickness at 48 h. A threshold of 60.5° had a sensitivity of 56.5-66.7% and a specificity of 70.5-75.5% for thickness > 6 mm at 48 h. CONCLUSIONS: Intraoperative imaging may accurately detect typical lesional findings, before completing the treatment. These imaging characteristics significantly correlate with sonication parameters and 48-h follow-up. KEY POINTS: • Intraoperative T2-weighted images allow the visualization of the zone I (coagulation necrosis) in most of the treated patients, while zone II (cytotoxic edema) is always detected. • Lesion size depicted with intraoperative transcranial MRgFUS imaging correlates well with procedure parameters. • Intraoperative transcranial MRgFUS imaging may have a significant added value for treating physicians.

An experience-based review of HIFU in functional interventional neuroradiology: transcranial MRgFUS thalamotomy for treatment of tremor.

Tremor is a common and very disabling symptom in patients with essential tremor and Parkinson's disease. In the recent years, transcranial ablation of thalamic nuclei using magnetic resonance guided high-intensity focused ultrasound has emerged as a minimally invasive treatment for tremor. The aim of this review is to discuss, in the light of our single-center experience, the technique, current applications, results, and future perspectives of this novel technology.