Essential tremor (ET) is the most common movement disorder with an estimated prevalence of about 0.3% and 5.55% and increases with age. Both RF and deep brain stimulation techniques have proven to be effective in treating ET. Recent advances in focused ultrasound technology with MR guidance make it possible to target regions in the brain with great accuracy. Recently concluded Pivotal Study for thalamotomy treatment of medication refractory essential tremor subjects demonstrated remarkable reduction in tremors and improved quality of life for the patients immediately following treatment that persisted up to one year. In the context of the remarkable improvement in quality of life at one year after the MRgFUS thalamotomy procedure, we performed preliminary examination of the pre- and post-imaging data including an assessment of the accuracy of MRgFUS targeting of the VIM nuclei.In the multi-center trial, Seventy-six patients from multiple centers with severe, medication-refractory essential tremor were randomized 3:1 to receive a unilateral MR-guided focused ultrasound thalamotomy or a sham procedure. Combined data from the multi-center trial revealed that contralateral hand tremor, the primary endpoint, improved 49% at 3 months (p<0.001) with the treatment (18.09 +4.81 to 9.55 + 5.06) compared to no change in sham procedures (16.00 + 4.42 to 15.75 + 4.90), and the effect was maintained at one year (10.89+4.86). Similarly, functional measures of disability and quality of life reported by the patients were statistically improved compared to sham cohort. In the Maryland subset of patients (n=9) we examined the pre- and post imaging data to asses targeting accuracy with respect to stereotactic location of VIM and lesion evolution over 12 months. MRImages were obtained on a 3T system before the HIFU treatment (V1), post-treatment (within 24hr) (V2) and at 12 months (V3) using a 12-channel head coil. 3D T1-weighted-MPRAGE (TE = 2.91ms, TR = 2300ms, TI = 900ms, flip angle = 9⁰) and 3D T2-weighted SPACE (TE = 222ms, TR = 3000ms, ETL = 133) were both acquired in the sagittal plane with an isotropic resolution of 1x1x1 mm3 (matrix size: 256x256x176) pre-procedure, one day post procedure and at 12 months. Accuracy of the HIFU ablation location was estimated by measuring the distance from individual lesion center to the atlas-based VIM target (marked at x=-14mm, y=-19mm, z=-2mm on a Montreal Neurological Institute.1 Both T1 and T2-weighted images from each time point were registered to the MNI template using SPM8. Lesion volume was measured on T2-weighted images by drawing a region of interest over the 3D-volume with hyperintensity. Center of the lesion for each patient was then identified from this volume and marked on the template space. In addition, we performed minimum intensity projection (MIP) on the T1-weighted images from V2 and V3 to measure the overall extent of the lesions. In the immediate post-operative period, thalamotomy lesions demonstrated restricted diffusion and a variable region of surrounding vasogenic edema on T2W images. The edema subsided completely and the T2W core lesions demonstrated regression in the volume at 1 year follow-up (Figure 1). The average lesion size at V2 was 82 ± 41mm3 (range: 37mm3 - 174mm3) which reduced dramatically to 13 ± 18mm3 (range: 0 - 48mm3). For two patients; there was a planned shift in the target during the treatment resulting in extended lesions but their overall lesion size was comparable to average lesion size.Lesions were close to the VIM target, with an average distance of 2.82±1.04mm (1.78±1.03mm more medial, and 1.28±1.54mm more superior) from the stereotactically defined VIM target. In addition, the lesions from each subjects were mapped onto Oxford thalamic connectivity atlas¹ (FMRIB), where 7 sub-thalamic regions were identified, each with anatomical connections to one of the 7 cortical zones, based on the probabilistic diffusion tractography from multiple subjects. HIFU lesions were centered mostly at the inferior end of the sub-region connected to the pre-motor cortex (PM). The lesions were shown to be connected to the primary motor cortex (M1) and/or the frontal pole region (FP) on probabilistic diffusion map (Figure 3).High intensity MR-guided focused ultrasound can be delivered through the intact skull to make precise ablations deep in the brain. MR guided focused ultrasound thalamotomy improves hand tremor in ET and was well tolerated. Lesions generated by this procedure are accurately placed, and match well with the known location of VIM nucleus based on anatomical atlases. The lesions appear to regress in size over a 12 month period but the therapeutic effect is maintained. Additional studies will be need to determine the long term durability of the treatment.