Longitudinal Changes in Brain Connectivity and Structure after MRgFUS VIM Thalamotomy for Essential Tremor

Essential Tremor (ET) is the most common movement disorder. Magnetic Resonance-guided Focused Ultrasound (MRgFUS), an incisionless surgery involving thermal ablation of targeted brain regions, like the Ventral Intermediate Nucleus of the Thalamus (VIM) and surrounding white matter tracts, is an effective treatment option. Fractional Anisotropy (FA), a metric of diffusion tensor imaging, can be used to determine white matter structural integrity and their changes following MRgFUS. This study investigates white matter and morphological brain remodeling after MRgFUS VIM thalamotomy and its association with tremor improvement, assessed by the Clinical Rating Scale for Tremor (CRST), over the first postoperative year. We retrospectively analyzed 56 ET patients who underwent unilateral MRgFUS VIM thalamotomy. Subjects' CRST scores, T1-weighted MRI scans, and diffusion-weighted imaging (DWI) scans were acquired pre-operatively and at three and twelve months post-operatively. FA maps were generated and registered to a standard space. Voxel clusters that exhibited significant change in FA over time were identified using FSL's cluster tool (p<0.001) and their change in FA value over time was Spearman correlated with relative change in CRST score. Deformation-Based Morphometry of T1-weighted images evaluated changes in structural volume, and a linear mixed-effects model was applied. We permuted these values 1000 times randomly to isolate significant (p<0.01) clusters related to the interaction between time and outcome and Spearman correlated them with relative improvement in CRST. Four main FA clusters demonstrated strong associations between CRST score and time. The insula produced consistent positive correlations at three (R=0.32, p=0.04) and twelve months (R=0.29, p=0.11). Yet, the visual cortex exhibited no significant association at three months (R=0.11, p=0.46), but did at twelve months (R=0.35, p=0.05), suggesting malleable white matter remodeling. Our morphometry analysis revealed two primary clusters located in the pre-supplementary motor area (pre-SMA) and visual cortex. The pre-SMA exhibited the strongest correlations at three months (three months: R=0.34, p=0.03, twelve months: R=0.17, p=0.36), while the visual cortex displayed a similar strength throughout (three months: R=0.20, p=0.18, twelve months: R=-0.22, p=0.23). These findings suggest that MRgFUS VIM thalamotomy is associated with broad structural tract and volumetric changes that extend beyond motor networks. Both analyses demonstrated post-treatment volume growth and increased tract structure in visual and cognitive regions. Correlation with tremor improvement indicates many of these changes may contribute to individual outcomes during the first post-operative year.