scholarly journals Accumulated thermal dose in MRI-guided focused ultrasound for essential tremor: repeated sonications with low focal temperatures

2020 ◽  
Vol 132 (6) ◽  
pp. 1802-1809 ◽  
Author(s):  
Ryan M. Jones ◽  
Shona Kamps ◽  
Yuexi Huang ◽  
Nadia Scantlebury ◽  
Nir Lipsman ◽  
...  
Keyword(s):  
Essential Tremor ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Lesion Size ◽  
Thermal Dose ◽  
Mr Thermometry ◽  
Dose Accumulation ◽  
Regression Slope ◽  
Tremor Suppression ◽  
Mri Guided

OBJECTIVEThe object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C–54°C.METHODSSeventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors’ institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = −0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance–induced spatial-shifting artifacts.RESULTSMean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C–54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor.CONCLUSIONSIn transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.

Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome

2020 ◽  
Vol 91 (9) ◽  
pp. 921-927
Author(s):  
Anish N Kapadia ◽  
Gavin J B Elias ◽  
Alexandre Boutet ◽  
Jürgen Germann ◽  
Aditiya Pancholi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Clinical Outcome ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Lesion Size ◽  
Post Treatment ◽  
Medial Lemniscus ◽  
Invasive Treatment ◽  
Tremor Suppression ◽  
Registration Number

BackgroundMRI-guided focused ultrasound (MRgFUS) thalamotomy is a promising non-invasive treatment option for medication-resistant essential tremor. However, it has been associated with variable efficacy and a relatively high incidence of adverse effects.ObjectivesTo assess the evolution of radiological findings after MRgFUS thalamotomy and to evaluate their significance for clinical outcomes.MethodsNinety-four patients who underwent MRgFUS between 2012 and 2017 were retrospectively evaluated. Lesion characteristics were assessed on routine MRI sequences, as well as with tractography. Relationships between imaging appearance, extent of white matter tract lesioning (59/94, on a 4-point scale) and clinical outcome were investigated. Recurrence was defined as >33% loss of tremor suppression at 3 months relative to day 7.ResultsAcute lesions demonstrated blood products, surrounding oedema and peripheral diffusion restriction. The extent of dentatorubrothalamic tract (DRTT) lesioning was significantly associated with clinical improvement at 1 year (t=4.32, p=0.001). Lesion size decreased over time (180.8±91.5 mm3 at day 1 vs 19.5±19.3 mm3 at 1-year post-treatment). Higher post-treatment oedema (t=3.59, p<0.001) was associated with larger lesions at 3 months. Patients with larger lesions at day 1 demonstrated reduced rates of tremor recurrence (t=2.67, p=0.019); however, lesions over 170 mm3 trended towards greater incidence of adverse effects (sensitivity=0.60, specificity=0.63). Lesion encroachment on the medial lemniscus (Sn=1.00, Sp=0.32) and pyramidal tract (Sn=1.00, Sp=0.12) were also associated with increased adverse effects incidence.ConclusionLesion size at day 1 predicts symptom recurrence, with fewer recurrences seen with larger lesions. Greater DRTT lesioning is associated with treatment efficacy. These findings may have implications for lesion targeting and extent.Trial registration numberNCT02252380.

MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes

Neurology ◽  
2017 ◽  
Vol 89 (8) ◽  
pp. 771-775 ◽  
Author(s):  
Alfonso Fasano ◽  
Maheleth Llinas ◽  
Renato P. Munhoz ◽  
Eugen Hlasny ◽  
Walter Kucharczyk ◽  
...  
Keyword(s):  
Side Effects ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Invasive Technique ◽  
Sustained Improvement ◽  
Future Studies ◽  
Mri Guided

Objective:To report the 6-month single-blinded results of unilateral thalamotomy with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than essential tremor.Methods:Three patients with tremor due to Parkinson disease, 2 with dystonic tremor in the context of cervicobrachial dystonia and writer's cramp, and 1 with dystonia gene–associated tremor underwent MRgFUS targeting the ventro-intermedius nucleus (Vim) of the dominant hemisphere. The primary endpoint was the reduction of lateralized items of the Tremor Rating Scale of contralateral hemibody assessed by a blinded rater.Results:All patients achieved a statistically significant, immediate, and sustained improvement of the contralateral tremor score by 42.2%, 52.0%, 55.9%, and 52.9% at 1 week and 1, 3, and 6 months after the procedure, respectively. All patients experienced transient side effects and 2 patients experienced persistent side effects at the time of last evaluation: hemitongue numbness and hemiparesis with hemihypoesthesia.Conclusions:Vim MRgFUS is a promising, incision-free, but nevertheless invasive technique to effectively treat tremors other than essential tremor. Future studies on larger samples and longer follow-up will further define its effectiveness and safety.Clinicaltrials.gov identifier:NCT02252380.Classification of evidence:This study provides Class IV evidence that for patients with tremor not caused by essential tremor, MRgFUS of the Vim improves the tremor of the contralateral hemibody at 6 months.

scholarly journals Predicting lesion size by accumulated thermal dose in MR-guided focused ultrasound for essential tremor

2018 ◽  
Vol 45 (10) ◽  
pp. 4704-4710 ◽  
Author(s):  
Yuexi Huang ◽  
Nir Lipsman ◽  
Michael L. Schwartz ◽  
Vibhor Krishna ◽  
Francesco Sammartino ◽  
...  
Keyword(s):  
Essential Tremor ◽  
Focused Ultrasound ◽  
Lesion Size ◽  
Thermal Dose

scholarly journals Outcome and Complications of MR Guided Focused Ultrasound for Essential Tremor: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohit Agrawal ◽  
Kanwaljeet Garg ◽  
Raghu Samala ◽  
Roopa Rajan ◽  
Vikas Naik ◽  
...  
Keyword(s):  
Essential Tremor ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Meta Analysis ◽  
Post Procedure ◽  
Standard Mean Difference ◽  
Significant Difference ◽  
Long Term Follow Up

Background: Magnetic resonance guided focused ultrasound (MRgFUS) is a relatively novel technique to treat essential tremor (ET). The objective of this review was to analyze the efficacy and the safety profile of MRgFUS for ET.Methods: A systematic literature review was done. The post procedure changes in the Clinical Rating Scale for Tremor (CRST) score, hand score, disability and quality of life scores were analyzed.Results: We found 29 studies evaluating 617 patients. DTI based targeting was utilized in six cohorts. A significant difference was observed in the pooled standard mean difference between the pre and postoperative total CRST score (p-value &lt; 0.001 and 0.0002), hand score (p-value 0.03 and 0.02); and the disability at 12 months (p-value 0.01). Head pain and dizziness were the most in procedure complications. The immediate pooled proportion of ataxia was 50%, while it was 20% for sensory complications, which, respectively, declined to 31 and 13% on long term follow up. A significant reduction (p = 0.03) in immediate ataxia related complications was seen with DTI targeting.Conclusion: MRgFUS for ET seems to be an effective procedure for relieving unilateral tremor. Use of DTI based targeting revealed a significant reduction in post procedure ataxia related complications as compared to traditional targeting techniques. Analysis of other complications further revealed a decreasing trend on follow up.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor

Neurology ◽  
2019 ◽  
Vol 93 (24) ◽  
pp. e2284-e2293 ◽  
Author(s):  
Casey H. Halpern ◽  
Veronica Santini ◽  
Nir Lipsman ◽  
Andres M. Lozano ◽  
Michael L. Schwartz ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Adverse Events ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Prospective Trial ◽  
Postural Tremor ◽  
Hand Tremor

ObjectiveTo test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.MethodsOutcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.ResultsMeasured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2, p = 0.0098) and disability (95% CI 1–4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.ConclusionsResults at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Magnetic resonance–guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson's disease and essential tremor cases

2018 ◽  
Vol 128 (1) ◽  
pp. 202-210 ◽  
Author(s):  
Menashe Zaaroor ◽  
Alon Sinai ◽  
Dorith Goldsher ◽  
Ayelet Eran ◽  
Maria Nassar ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Innovative Technology ◽  
The Mean

OBJECTIVEThalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation.METHODSPatients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39).RESULTSThirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46–87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2–30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6–24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14–45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13–24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850–23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°–60°C).CONCLUSIONSMRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse events profile of MRgFUS over other surgical approaches for treating tremor with similar efficacy. Large randomized studies are needed to assess prolonged efficacy and safety.

scholarly journals Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound

Neurology ◽  
2017 ◽  
Vol 88 (14) ◽  
pp. 1329-1333 ◽  
Author(s):  
Sebastian R. Schreglmann ◽  
Ronald Bauer ◽  
Stefan Hägele-Link ◽  
Kailash P. Bhatia ◽  
Parashkev Natchev ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Essential Tremor ◽  
Repeated Measures ◽  
Focused Ultrasound ◽  
Prospective Trial ◽  
Manual Dexterity ◽  
Fine Motor ◽  
Hand Tremor ◽  
Mri Guided

Objective:To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET).Methods:This was a prospective, uncontrolled, single-center interventional study. Patients with ET fulfilling criteria for interventional therapy received unilateral ablation of the cerebellothalamic tract (CTT) by MRIgFUS. Motor symptoms, manual dexterity, cognition, and quality of life were assessed before intervention and at 48 hours and 1, 3, and 6 months after intervention. Rating of standardized video recordings was blinded for evaluation time points. Primary outcome was the change in unilateral hand tremor score of the treated hand.Results:Six patients received MRIgFUS ablation of the CTT contralateral to the treated hand. Repeated-measures comparison determined a statistically significant 83% reduction (before vs 6 months after intervention mean ± SD; absolute reduction; 95% confidence interval) in the unilateral treated hand subscore (14.3 ± 4.9 vs 2.5 ± 2.6; 11.8; 8.4–15.2; p < 0.001), while quality of life improved by 52% (50.5 ± 19.4 vs 24.8 ± 11.4; 25.7; 3.5–47.28; p = 0.046). Measures for manual dexterity, attention and coordination, and overall cognition were unchanged. Transient side effects (n = 3) were ipsilateral hand clumsiness and mild gait instability for up to 3 months.Conclusions:Unilateral MRIgFUS lesioning of the CTT was highly efficacious in reducing contralateral hand tremor in ET without affecting fine motor function and dexterity over 6 months of follow-up. Adverse effects were mild and transient.Classification of evidence:This study provides Class IV evidence that for patients with ET, transcranial MRIgFUS ablation of the cerebellothalamic tract improves tremor.

scholarly journals Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson’s disease

2020 ◽  
pp. 1-8 ◽  
Author(s):  
Timothy R. Miller ◽  
Sijia Guo ◽  
Elias R. Melhem ◽  
Howard M. Eisenberg ◽  
Jiachen Zhuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Temperature Rise ◽  
Focused Ultrasound ◽  
Threshold Model ◽  
Average Energy ◽  
Lesion Size ◽  
Temperature Threshold ◽  
Treatment Efficiency ◽  
Mr Thermometry

OBJECTIVEMagnetic resonance–guided focused ultrasound (MRgFUS) ablation of the globus pallidus interna (GPi) is being investigated for the treatment of advanced Parkinson’s disease symptoms. However, GPi lesioning presents unique challenges due to the off-midline location of the target. Furthermore, it remains uncertain whether intraprocedural MR thermometry data can predict final lesion characteristics.METHODSThe authors first performed temperature simulations of GPi pallidotomy and compared the results with those of actual cases and the results of ventral intermediate nucleus (VIM) thalamotomy performed for essential tremor treatment. Next, thermometry data from 13 MRgFUS pallidotomy procedures performed at their institution were analyzed using 46°C, 48°C, 50°C, and 52°C temperature thresholds. The resulting thermal models were compared with resulting GPi lesions noted on postprocedure days 1 and 30. Finally, the treatment efficiency (energy per temperature rise) of pallidotomy was evaluated.RESULTSThe authors’ modeled acoustic intensity maps correctly demonstrate the elongated, ellipsoid lesions noted during GPi pallidotomy. In treated patients, the 48°C temperature threshold maps most accurately predicted postprocedure day 1 lesion size, while no correlation was found for day 30 lesions. The average energy/temperature rise of pallidotomy was higher (612 J/°C) than what had been noted for VIM thalamotomy and varied with the patients’ skull density ratios (SDRs).CONCLUSIONSThe authors’ acoustic simulations accurately depicted the characteristics of thermal lesions encountered following MRgFUS pallidotomy. MR thermometry data can predict postprocedure day 1 GPi lesion characteristics using a 48°C threshold model. Finally, the lower treatment efficiency of pallidotomy may make GPi lesioning challenging in patients with a low SDR.

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