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      MR-guided high-focused ultrasound for renal sympathetic denervation—a feasibility study in pigs

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          Abstract

          Background

          Renal sympathetic denervation has recently gained clinical relevance for the treatment of therapy-resistant hypertension. Denervation is currently mainly performed using catheter-based transarterial radiofrequency ablation of periarterial sympathetic nerve fibers. Since this approach has numerous limitations, we conducted a study to evaluate the feasibility, safety, and efficacy of magnetic resonance-guided high-focused ultrasound (MRgHiFUS) for renal sympathetic denervation in pigs as an alternative to catheter-based ablation.

          Methods

          Renal periarterial MRgHiFUS was performed under general anesthesia in ten pigs. Blood pressure measurements and magnetic resonance imaging (MRI) of the kidneys, renal arteries, and surrounding structures were obtained immediately before and after the interventions and after 4 weeks. Histological examinations of periarterial tissues and determination of renal norepinephrine (NE) concentration were performed to assess treatment efficacy.

          Results and discussion

          In each pig, 9.8 ± 2.6 sonications with a mean energy deposition of 2,670 ± 486 J were performed. The procedure was well tolerated by all pigs. No major complications occurred. MRgHiFUS induced periarterial edema in three pigs, but only one pig showed corresponding histological changes. The NE level of the treated kidney was lower in five pigs (-8% to -38%) compared to the untreated side. Overall, there was no significant difference between the NE values of both kidneys in any of the treated pigs. Postinterventional MRI indicated absorption of ultrasound energy at the transverse process and fascia.

          Conclusion

          MRgHiFUS had some thermal periarterial effects but failed to induce renal denervation. Insufficient energy deposition is most likely attributable to a small acoustic window with beam path impediment in the porcine model. Since HiFUS treatment in humans is expected to be easier to perform due to better access to renal sympathetic nerves, further studies of this method are desirable to investigate the potential of MRgHiFUS as an alternative for patients not suitable for catheter-based renal sympathicolysis.

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          Most cited references27

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          Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.

          Renal sympathetic hyperactivity is associated with hypertension and its progression, chronic kidney disease, and heart failure. We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension (ie, systolic blood pressure >/=160 mm Hg on three or more antihypertensive medications, including a diuretic) to assess safety and blood-pressure reduction effectiveness. We enrolled 50 patients at five Australian and European centres; 5 patients were excluded for anatomical reasons (mainly on the basis of dual renal artery systems). Patients received percutaneous radiofrequency catheter-based treatment between June, 2007, and November, 2008, with subsequent follow-up to 1 year. We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients. Primary endpoints were office blood pressure and safety data before and at 1, 3, 6, 9, and 12 months after procedure. Renal angiography was done before, immediately after, and 14-30 days after procedure, and magnetic resonance angiogram 6 months after procedure. We assessed blood-pressure lowering effectiveness by repeated measures ANOVA. This study is registered in Australia and Europe with ClinicalTrials.gov, numbers NCT 00483808 and NCT 00664638. In treated patients, baseline mean office blood pressure was 177/101 mm Hg (SD 20/15), (mean 4.7 antihypertensive medications); estimated glomerular filtration rate was 81 mL/min/1.73m(2) (SD 23); and mean reduction in renal noradrenaline spillover was 47% (95% CI 28-65%). Office blood pressures after procedure were reduced by -14/-10, -21/-10, -22/-11, -24/-11, and -27/-17 mm Hg at 1, 3, 6, 9, and 12 months, respectively. In the five non-treated patients, mean rise in office blood pressure was +3/-2, +2/+3, +14/+9, and +26/+17 mm Hg at 1, 3, 6, and 9 months, respectively. One intraprocedural renal artery dissection occurred before radiofrequency energy delivery, without further sequelae. There were no other renovascular complications. Catheter-based renal denervation causes substantial and sustained blood-pressure reduction, without serious adverse events, in patients with resistant hypertension. Prospective randomised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition.
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            MR imaging-guided focused ultrasound surgery of uterine leiomyomas: a feasibility study.

            The feasibility and safety of magnetic resonance (MR) imaging-guided focused ultrasound surgery for uterine leiomyomas is reported. Sequential sonications were delivered to nine targets. Temperature-sensitive phase-difference MR imaging monitored the location of the focus and measured tissue temperature elevations, ensuring therapeutic dose. MR images and hysterectomy specimens were evaluated. Six leiomyomas received full therapeutic doses, and 98.5% of the sonications were visualized. MR thermometry was successful in all sonications and cases. Focal necrotic lesions were seen in all cases at MR, and five were pathologically confirmed. MR imaging-guided focused ultrasound causes thermocoagulation and necrosis in uterine leiomyomas and is feasible and safe, without serious consequences.
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              Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study.

              Noninvasive thermal ablation using magnetic resonance (MR)-guided focused ultrasound (MRgFUS) has been shown to be clinically effective in uterine fibroids, and is being evaluated for ablation of breast, liver, and brain lesions. Recently MRgFUS has been evaluated for palliation of pain caused by bone metastases. We present the clinical results of a multicenter study using MRgFUS for palliation of bone metastases pain. A multicenter study to evaluate the safety and efficacy of MRgFUS palliative treatment of bone metastases was conducted in patients suffering from painful metastatic bone lesions for which other treatments were either ineffective or not feasible. Thirty-one patients with painful bone metastases underwent the MRgFUS procedure in three medical centers. Treatment safety was evaluated by assessing the device-related complications. Effectiveness of pain palliation was evaluated using the visual analog pain score (VAS), and measurable changes in the intake of opioid analgesics. Thirty-six procedures were performed on 31 patients. Mean follow-up time was 4 months. 25 patients underwent the planned treatment and were available for 3 months post-treatment follow-up. 72% of the patients (18/25) reported significant pain improvement. Average VAS score was reduced from 5.9 prior to treatment to 1.8 at 3 months post treatment. 67% of patients with recorded medication data reported a reduction in their opioid usage. No device-related severe adverse events were recorded. The results suggest that MRgFUS has the ability to provide an accurate, effective, and safe noninvasive palliative treatment for patients with bone metastases.
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                Author and article information

                Contributors
                Journal
                J Ther Ultrasound
                J Ther Ultrasound
                Journal of Therapeutic Ultrasound
                BioMed Central
                2050-5736
                2014
                4 August 2014
                : 2
                : 12
                Affiliations
                [1 ]Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany
                [2 ]Department of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin 13353, Germany
                Article
                2050-5736-2-12
                10.1186/2050-5736-2-12
                4160576
                25232481
                50dc3524-e27b-4504-a1d8-f9ca5f9e4a04
                Copyright © 2014 Freyhardt et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 March 2014
                : 9 June 2014
                Categories
                Research

                hypertension,renal sympathetic denervation,mrghifus sympathicolysis

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