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Background: Several options exist for surgical management of essential tremor (ET), including radiofrequency lesioning, deep brain stimulation and γ knife radiosurgery of the ventralis intermedius nucleus of the thalamus. Recently, magnetic resonance-guided focused ultrasound (MRgFUS) has been developed as a less-invasive surgical tool aimed to precisely generate focal thermal lesions in the brain., Methods: Patients underwent tremor evaluation and neuroimaging study at baseline and up to 6 months after MRgFUS. Tremor severity and functional impairment were assessed at baseline and then at 1 week, 1 month, 3 months and 6 months after treatment. Adverse effects were also sought and ascertained by directed questions, neuroimaging results and neurological examination., Results: The current feasibility study attempted MRgFUS thalamotomy in 11 patients with medication-resistant ET. Among them, eight patients completed treatment with MRgFUS, whereas three patients could not complete the treatment because of insufficient temperature. All patients who completed treatment with MRgFUS showed immediate and sustained improvements in tremors lasting for the 6-month follow-up period. Skull volume and maximum temperature rise were linearly correlated (linear regression, p=0.003). Other than one patient who had mild and delayed postoperative balance, no patient developed significant postsurgical complications; about half of the patients had bouts of dizziness during the MRgFUS., Conclusions: Our results demonstrate that MRgFUS thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory ET. However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor., Methods: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability)., Results: Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001)., Conclusions: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

Object: Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube., Methods and Results: In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance., Conclusions: The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

The use of image guidance in medical applications is constantly growing because of its tremendous impact on the future of health care. Although image-based tissue tracking has been thoroughly explored in the academic literature for years, it has not yet matured to become widely accepted by clinicians. Undetected tissue movements in image-based clinical procedures may cause safety and efficacy difficulties. We introduce an image-based approach for detecting tissue movements during clinical procedures. Our method has been validated in more than 600 true clinical cases. The results show that our algorithm agrees with an expert analysis in 98% of the cases, showing zero events of false alarms and zero events of undetected motion. The results show that the approach provides a clinically ready motion detection algorithm. These robust results are achieved by introducing the concept of weighted directional descriptors (WDDs). The technique analyzes the directivity and confidence level of each anatomical feature and uses it to weight local inputs resulting in a robust motion vector. The robustness is further increased by a novel preprocess that screens out features that may be misleading or are repeated in the adjacent search zone. The technique meets the requirements, as defined by our clinicians, and is now integrated in true medical systems. In particular, our approach has been uniquely developed and integrated into a clinical product. ExAblate is the first Food and Drug Administration (FDA)-approved magnetic resonance (MR)-guided noninvasive surgical device using focused ultrasound therapy. It is used in commercial clinics and in leading medical academic research institutions, attesting to the success of our method and its practical clinical value.

Transcranial magnetic resonance (MR)-guided high-intensity focused ultrasound (tcMRgHIFU) implies a novel, noninvasive treatment strategy for various brain diseases. Nine patients with chronic neuropathic pain were treated with selective medial thalamotomies. Precisely located thermal ablations of 4mm in diameter were produced at peak temperatures of 51 degrees C to 60 degrees C under continuous visual MR guidance and MR thermometry. The resulting lesions are clearly visible on follow-up MR imaging. All treatments were well tolerated, without side effects or neurological deficits. This is the first report on successful clinical application of tcMRgHIFU in functional brain disorders, portraying it as safe and reliable for noninvasive neurosurgical interventions.

Introduction: Magnetic resonance imaging (MRI)-guided focused ultrasound is a novel technique that was developed to enable precise, image-guided targeting and destruction of tumors by thermocoagulation. The system, ExAblate2000, is a focused ultrasound delivery system embedded within the MRI bed of a conventional diagnostic MRI scanner. The device delivers small volumetric sonications from an ultrasound phased array transmitter that converge energy to selectively destroy the target. Temperature maps generated by the MRI scanner verify the location and thermal rise as feedback, as well as thermal destruction. To assess the safety, feasibility, and precision of this technology in the brain, we have used the ExAblate system to create predefined thermal lesions in the brains of pigs., Methods: Ten pigs underwent bilateral craniectomy to provide a bone window for the ultrasound beams. Seven to 10 days later, the animals were anesthetized and positioned in the ExAblate system. A predefined, 1-cm frontal para ventricular region was delineated as the target and treated with multiple sonications. MRI was performed immediately and 1 week after treatment. The animals were then sacrificed and the brains removed for pathological study. The size of individual sonication points and the location of the lesion were compared between the planned dose maps, posttreatment MRI scans, and pathological specimen., Results: High-energy sonications led to precise coagulation necrosis of the specified targets as shown by subsequent MRI, macroscopic, and histological analysis. The thermal lesions were sharply demarcated from the surrounding brain with no anatomic or histological abnormalities outside the target., Conclusion: MRI-guided focused ultrasound proved a precise and an effective means to destroy anatomically predefined brain targets by thermocoagulation with minimal associated edema or damage to adjacent structures. Contrast-enhanced T1-, T2-, and diffusion-weighted MRI scans may be used for real-time assessment of tissue destruction.

MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used.