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

Authors: Jones RM, Kamps S, Huang Y, Scantlebury N, Lipsman N, Schwartz ML, Hynynen K

The 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. Seventy-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. Mean 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. In 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.

Introduction

Purpose Thermal ablation
Study Objective To correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound thalamotomy for essential tremor when focal temperatures are limited to 50–54°C.
Animal model / Human subject Homo sapiens (human patients with essential tremor); strain: N/A; age: not reported; sex: not reported
Disease model essential tremor
MRI or image guidance method MRI-guided focused ultrasound (MRgFUS) with intraoperative MR thermometry (proton resonance frequency shift) and axial T1- and T2-weighted MRI for targeting/verification
Targeted brain region(s) Thalamus

Outcomes and Safety

Summary of Outcomes Repeated low‑temperature (50–54°C) MRgFUS sonications produced ablation lesions that yielded clinically significant tremor suppression up to 1 year (dominant CRST scores improved at 3 months and 1 year, with no significant difference versus ≥55°C treatments). Successful parameters: repeated sonications at 50–54°C (and comparable outcomes with ≥55°C), with accumulated thermal dose thresholds correlating with lesion size of ~100 CEM43 (best for T2w MRI) and ~200 CEM43 (best for T1w MRI).
Duration of biological effect 1 year
Safety-related matter Intraoperative pain from cranial heating prevented raising the focal temperature above 54°C in 19 patients; no other adverse events or safety issues are reported in the provided text.

Brain Region

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency Multiple

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