Search

Transcranial MR-guided focused ultrasound (MRgFUS) is a rapidly developing technology in neuroscience for manipulating brain structure and function without open surgery. The effectiveness of transcranial MRgFUS for thermoablation is well established, and the technique is actively employed worldwide for movement disorders including essential tremor. A growing number of centers are also investigating the potential of microbubble-mediated focused ultrasound-induced opening of the blood-brain barrier (BBB) for targeted drug delivery to the brain. Here, we provide a technical overview of the principles, clinical workflow, and operator considerations of transcranial MRgFUS procedures for both thermoablation and BBB opening., (© 2020 The Author(s)Published by S. Karger AG, Basel.)

Background: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) systems currently employ computed tomography (CT)-based aberration corrections, which may provide suboptimal trans-skull focusing., Objectives: The objective of this study was to evaluate a contrast agent microbubble imaging-based transcranial focusing method, echo-focusing (EF), during TcMRgFUS for essential tremor., Methods: A clinical trial of TcMRgFUS thalamotomy using EF for the treatment of essential tremor was conducted (NCT03935581; funded by InSightec [Tirat Carmel, Israel]). Patients (n = 12) were injected with Definity (Lantheus Medical Imaging, North Billerica, MA) microbubbles, and EF was performed using a research feature add-on to a commercial TcMRgFUS system (ExAblate Neuro, InSightec). Subablative thermal sonications carried out using (1) EF and (2) CT-based aberration corrections were compared via magnetic resonance thermometry, and the optimal focusing method for each patient was employed for TcMRgFUS thalamotomy., Results: EF aberration corrections provided increased sonication efficiency, decreased focal size, and equivalent targeting accuracy relative to CT-based focusing. EF aberration corrections were employed successfully for lesion formation in all 12 patients, 3 of whom had previously undergone unsuccessful TcMRgFUS thalamotomy via CT-based focusing. There were no adverse events related directly to the EF procedure., Conclusions: EF is feasible and appears safe during TcMRgFUS thalamotomy for essential tremor and improves on the trans-skull focal quality provided by existing CT-based focusing methods. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Purpose: To correlate the accumulated thermal dose (ATD) with lesion size in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy to help guide future clinical treatments., Materials and Methods: Thirty-six patients with medication-refractory essential tremor were treated using a commercial MRgFUS brain system (ExAblate 4000, InSightec) in a 3T MR scanner (MR750, GE Healthcare). Intraoperative MR-thermometry was performed to measure the induced temperature and thermal dose distributions (thermal coefficient = -0.00909 ppm/°C). The ATD was calculated over multiple sonications with appropriate corrections for spatial-shifting artifacts. The ATD profile sizes obtained for dose values of 17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C (CEM) were correlated with the corresponding lesion sizes measured via axial T1- and T2-weighted MR images acquired 1 day post-treatment., Results: Of a total of 232 included sonications, 83 required corrections for off-resonance-induced spatial-shifting artifacts (correction range = [1.1,2.2] mm). The mean lesion sizes measured on T2-weighted MR images (6.2 ± 1.3 mm, mean ± SD) were 15% larger than those measured on corresponding T1-weighted MR images (5.3 ± 1.2 mm, mean ± SD). The ATD values that provided the best correlations with the measured lesion sizes on T2- and T1-weighted MR images were 100 and 200 CEM, respectively., Conclusion: The ATD was correlated with lesion size measured 1 day following MRgFUS thalamotomy for essential tremor. These data provide useful information for predicting brain lesion size and determining treatment endpoints in future clinical MRgFUS procedures., (© 2018 American Association of Physicists in Medicine.)

Background: Magnetic resonance-guided focused ultrasound is an emerging, minimally invasive thermoablation technique for medically refractory essential tremor. Beyond the initial year, data regarding efficacy and potential predictors of efficacy are still preliminary., Objectives: The objective of this study was to assess the outcome at 2 years and the association between lesion volume and outcome 1 year after treatment., Methods: We reviewed data from 37 patients who underwent unilateral magnetic resonance-guided focused ultrasound thalamotomy, with primary outcome being dominant tremor subscore of the Clinical Rating Scale for Tremor. We used multivariable linear regression to model initial lesion volume with 1-year outcome, adjusting for other clinically relevant variables., Results: Although we detected a trend in loss of clinical benefit within the first year, the dominant tremor score at 2 years continued to be significantly improved (43.4%, 95% confidence interval 27.8%-59.0%) from baseline. Secondarily, initial lesion volume is significantly associated with 1-year outcome., Conclusion: Our findings show that magnetic resonance-guided focused ultrasound thalamotomy results in sustained tremor reduction for medically refractory essential tremor even in the long term, and we highlight areas for improvement., (© 2018 International Parkinson and Movement Disorder Society.)

Purpose: To analyze clinical data indicating a reduction in the induced energy-temperature efficiency relationship during transcranial focused ultrasound (FUS) Essential Tremor (ET) thalamotomy treatments at higher acoustic powers, establish its relationship with the spatial distribution of the focal temperature elevation, and explore its cause., Methods: A retrospective observational study of patients (n = 19) treated between July 2015 and August 2016 for (ET) by FUS thalamotomy was performed. These data were analyzed to compare the relationships between the applied power, the applied energy, the resultant peak temperature achieved in the brain, and the dispersion of the focal volume. Full ethics approval was received and all patients provided signed informed consent forms before the initiation of the study. Computer simulations, animal experiments, and clinical system tests were performed to determine the effects of skull heating, changes in brain properties and transducer acoustic output, respectively. All animal procedures were approved by the Animal Care and Use Committee and conformed to the guidelines set out by the Canadian Council on Animal Care. MATLAB was used to perform statistical analysis., Results: The reduction in the energy efficiency relationship during treatment correlates with the increase in size of the focal volume at higher sonication powers. A linear relationship exists showing that a decrease in treatment efficiency correlates positively with an increase in the focal size over the course of treatment (P < 0.01), supporting the hypothesis of transient skull and tissue heating causing acoustic aberrations leading to a decrease in efficiency. Changes in thermal conductivity, perfusion, absorption rates in the brain, as well as ultrasound transducer acoustic output levels were found to have minimal effects on the observed reduction in efficiency., Conclusions: The reduction in energy-temperature efficiency during high-power FUS treatments correlated with observed increases in the size of the focal volume and is likely caused by transient changes in the tissue and skull during heating., (© 2018 American Association of Physicists in Medicine.)

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

Background: Transcranial magnetic resonance guided focused ultrasound is an emerging technology under evaluation for treatment of essential tremor, a prevalent movement disorder. A qualitative evaluation is performed by a clinician periodically during the procedure to maximize treatment effects and minimize adverse effects. The present work demonstrates a magnetic resonance-compatible method to enable more precise, quantitative measurement of tremor severity., Methods: Tremor severity was measured in 12 patients pre-, post-, and intra-operatively, using a magnetic resonance-compatible tablet and a computerized adaptation of drawing tasks from the widely-used Fahn-Tolosa-Marin Tremor Rating Scale. Tremor metrics based on spectral analysis were calculated for each drawing and compared using Wilcoxon signed rank tests., Results: Tremor metrics in the dominant (treated) hand were significantly and consistently lower post-operatively compared to pre-operatively, but there was no significant difference in the non-dominant (untreated) hand, as expected. Intra-operative metrics were intermediate between pre- and post-operative metrics., Conclusions: Use of the tablet for quantitative tremor measurement was demonstrated pre-, post-, and intra-operatively during treatment of essential tremor, complementing standard qualitative assessment. With additional work, the system has potential to add objectivity to clinical trials and to aid treatment decision-making by providing a metric for optimization during the procedure, which may eventually lead to more optimal treatment. Enhancements and further studies are suggested, and extensions to fMRI studies of essential tremor and Parkinson's disease are also likely.

Recent clinical data showing thermal lesions from treatments of essential tremor using MR-guided transcranial focused ultrasound shows that in many cases the focus is oblique to the main axis of the phased array. The potential for this obliquity to extend the focus into lateral regions of the brain has led to speculation as to the cause of the oblique focus, and whether it is possible to realign the focus. Numerical simulations were performed on clinical export data to analyze the causes of the oblique focus and determine methods for its correction. It was found that the focal obliquity could be replicated with the numerical simulations to within [Formula: see text] of the clinical cases. It was then found that a major cause of the focal obliquity was the presence of sidelobes, caused by an unequal deposition of power from the different transducer elements in the array at the focus. In addition, it was found that a 65% reduction in focal obliquity was possible using phase and amplitude corrections. Potential drawbacks include the higher levels of skull heating required when modifying the distribution of power among the transducer elements, and the difficulty at present in obtaining ideal phase corrections from CT information alone. These techniques for the reduction of focal obliquity can be applied to other applications of transcranial focused ultrasound involving lower total energy deposition, such as blood-brain barrier opening, where the issue of skull heating is minimal.

Background: Essential tremor is the most common movement disorder and is often refractory to medical treatment. Surgical therapies, using lesioning and deep brain stimulation in the thalamus, have been used to treat essential tremor that is disabling and resistant to medication. Although often effective, these treatments have risks associated with an open neurosurgical procedure. MR-guided focused ultrasound has been developed as a non-invasive means of generating precisely placed focal lesions. We examined its application to the management of essential tremor., Methods: Our study was done in Toronto, Canada, between May, 2012, and January, 2013. Four patients with chronic and medication-resistant essential tremor were treated with MR-guided focused ultrasound to ablate tremor-mediating areas of the thalamus. Patients underwent tremor evaluation and neuroimaging at baseline and 1 month and 3 months after surgery. Outcome measures included tremor severity in the treated arm, as measured by the clinical rating scale for tremor, and treatment-related adverse events., Findings: Patients showed immediate and sustained improvements in tremor in the dominant hand. Mean reduction in tremor score of the treated hand was 89·4% at 1 month and 81·3% at 3 months. This reduction was accompanied by functional benefits and improvements in writing and motor tasks. One patient had postoperative paraesthesias which persisted at 3 months. Another patient developed a deep vein thrombosis, potentially related to the length of the procedure., Interpretation: MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor. If larger trials validate the safety and ascertain the efficacy and durability of this new approach, it might change the way that patients with essential tremor and potentially other disorders are treated., Funding: Focused Ultrasound Foundation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This prospective, open-label trial (NCT04720469) screened 16 consecutive mrET patients who had undergone MRgFUS thalamotomy at least 1 year prior (MRgFUS SB 1 sb ). Herein, staged, bilateral MRgFUS thalamotomy was safe in a small sample of patients with mrET. Keywords: essential tremor; bilateral; thalamotomy; focused ultrasound; safety EN essential tremor bilateral thalamotomy focused ultrasound safety 1559 1561 3 10/24/23 20231001 NES 231001 Staged, open-surgical lesioning of the thalamic ventral intermediate nucleus to abate medication-refractory essential tremor (mrET) has been historically associated with a high frequency of adverse events (AEs), including speech and balance impairments.[1] More recently, the real-time imaging and thermometry guidance offered by magnetic resonance-guided focused ultrasound (MRgFUS) have allowed for minimally-invasive thalamotomies with increased focal accuracy to address upper limb tremor in ET patients.[2] Qualitative and semi-quantitative trials evaluating the safety of staged, bilateral MRgFUS thalamotomy have reported AEs that were mostly transient with mild to moderate severity based on patients' and physicians' perceived deficits.[[3], [5]] However, a comprehensive quantitative analysis of the potential post-thalamotomy changes in stance and gait balance (ie, equilibrium), and oro-motor function is lacking. We comprehensively evaluated the incidence and severity of AEs, including changes in equilibrium, speech, and cognition, following staged, bilateral MRgFUS thalamotomy for patients with mrET. [Extracted from the article]

Background: The ventral intermediate nucleus of the thalamus is not readily visible on structural magnetic resonance imaging. Therefore, a method for its visualization for stereotactic targeting is desirable.Objective: The objective of this study was to define a tractography-based methodology for the stereotactic targeting of the ventral intermediate nucleus.Methods: The lateral and posterior borders of the ventral intermediate nucleus were defined by tracking the pyramidal tract and medial lemniscus, respectively. A thalamic seed was then created 3 mm medial and anterior to these borders, and its structural connections were analyzed. The application of this method was assessed in an imaging cohort of 14 tremor patients and 15 healthy controls, in which we compared the tractography-based targeting to conventional targeting. In a separate surgical cohort (3 tremor and 3 tremor-dominant Parkinson's disease patients), we analyzed the accuracy of this method by correlating it with intraoperative neurophysiology.Results: Tractography of the thalamic seed revealed the tracts corresponding to cerebellar input and motor cortical output fibers. The tractography-based target was more lateral (12.5 [1.2] mm vs 11.5 mm for conventional targeting) and anterior (8.5 [1.1] mm vs 6.7 [0.3] mm, anterior to the posterior commissure). In the surgical cohort, the Euclidian distance between the ventral intermediate nucleus identified by tractography and the surgical target was 1.6 [1.1] mm. The locations of the sensory thalamus, lemniscus, and pyramidal tracts were concordant within <1 mm between tractography and neurophysiology.Interpretation: The tractography-based methodology for identification of the ventral intermediate nucleus is accurate and useful. This method may be used to improve stereotactic targeting in functional neurosurgery procedures. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]