Neurosurgeons, neurologists, neuroradiologists, and scientists with an interest in movement disorders and in MR-guided high-intensity focused ultrasoundTo describe the relationship between lesion size, location, and dose and clinical outcome after transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) ablation of the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) for the treatment of essential tremor.11 patients with essential tremor refractory to medical management were included in this study (female:male= 3(27%):8(73%), mean age 76±6years, dominant hand [right:left] 9(72%):2(18%)) of which 7 had undergone 1-year follow-up at the time of submission. Patients were assessed clinically by an experienced neurologist specializing in movement disorders at baseline (immediately before the treatment), and at 1, 3, 6, and 12 months after treatment, using the CRST score (range: 0 to 160, higher scores indicating worse tremor), hand, task and disability subscores (range: 0-32). Treatment was performed using the tcMRgFUS system (ExAblate 4000, InSightec), consisting of a 30-cm diameter hemispheric 1024-element phased-array transducer operating at 650 kHz, working inside a 3T MRI scanner. Sonications (mean number 20.1±7.9; range 12-35, mean number of sonication to symptom suppression 12.3±6.8, range 7-24) were started at low energies, and escalated progressively toward therapeutic temperature, under clinical surveillance and MR thermometry guidance (GRE TE/TR=12.7/27.6, α=-.00909ppm/°C). Patients were imaged immediately post treatment and at 1-year follow-up at 3T using a White-Matter-nulled MPRAGE2 (WMnMPRAGE) with the following parameters: TR 11.6ms, TE 4.9ms, inversion pulse repetition time 4.5s, inversion time 500ms, bandwidth 93 kHz/Pixel, flip angle 7°, voxel size 0.7x0.7x0.7 mm3, scan time 4min. The MNI152 brain template3 was coregistered to the WMnMPRAGE post treatment images of each patient in two steps using ANTS5: first, using an affine transformation (12 degrees of freedom) over the full brain, and second, employing a b-spline deformation and a normalized mutual information similarity metric on cropped images centered on the thalamus. An atlas of the thalamic nuclei4 in MNI space was subsequently warped to patient space using the resultant deformation field. Dose maps from individual sonication were compiled into a 3-dimensional dose volume, which was coregistered to the WMnMPRAGE post treatment images using anatomical landmarks from intraoperative T2-weighted images. Finally, the WMnMPRAGE images obtained at 1 year were automatically coregistered to the post treatment images using a 12 dimensional affine transformation. The post-treatment lesion and edema, as well as the 1-year follow-up lesion, were outlined on WMnMPRAGE images by an experienced neuroradiologist (Fig. 1). Lesion (±edema) size and lesion (±edema) size inside the VLpv were correlated to the clinical score at 1 month and 1 year using Pearson’s correlation coefficient. Statistical significance was assessed comparing each follow-up time point to baseline, using Wilcoxon two-tailed rank test. Significance level was set to α < 0.05. After treatment, we observed a significant decrease in CRST hand tremor score on the treated side, from 6.4±2.2 at baseline to 1.4±1.6 (p=0.0001) at 1 month, which only slightly increased to 2±1.1 (p=0.0006) at 1 year (Fig. 2). Total tremor decreased significantly as well, from 21.1±2.0 at baseline, to 7.8±4.6 (p=0.0002) at 1 month, to 9.4±5.4 (p=0.0006) at 1 year. Significant decreases were found in CRST task and disability scores at every time point after treatment (Fig. 2). No significant differences were found in the non-treated, contralateral side. Lesion location and size can be found in Table 1. Correlation between lesion (±edema) volumes post treatment and clinical outcomes were better at 1 year compared to 1 month (Fig. 3). The association between lesion volume and outcome at 1 year was good (r = 0.73) (Fig. 4 Top). Interestingly, the lesion size inside the VLpv at 1 year correlated less well with clinical outcome, r = 0.53. Correlation between dose in VLpv and clinical outcome was better at 1 year (r=0.65) compared to 1 month (r=0.48) (Fig. 4 Bottom). In our initial group of 11 patients, essential tremor improved after treatment with tcMRgFUS. Clinical outcome correlated best with lesion size visible at 1 year. Clinical outcome at 1 year correlated as well with thermal dose measured in the VLpv. Interestingly, correlation with clinical outcome decreased when the lesion size inside the VLpv was considered, compared to total lesion size. Various limiting factors of the method might explain this finding, such as underestimation of the size of the VLpv by the atlas, variability of the size of the VLpv in the various patients, and errors in coregistration. Alternatively, lesions in adjacent structures might also be beneficial.