Longitudinal evolution of diffusion metrices within the Cerebello-Thalamo-cortical tract after MRgFUS thalamotomy for essential tremor

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) targets ventral intermediate nucleus hub region within cerebello-thalamo-cortical tract (CTCT). Understanding the microstructural changes in CTCT over time and their link to tremor improvement is crucial from a tremor-network perspective. We retrospectively analyzed tremor scores, lesion characteristics, and diffusion MRI-derived CTCT microstructural measures in 27 ET patient's pre-treatment (T0), at 1 month (T2), and 6 months (T3) post-MRgFUS. Using probabilistic tractography, we created an average CTCT mask at T0 for assessing fractional anisotropy (FA), axial (AD), mean (MD), and radial diffusivity (RD) measures across time points. Significant tremor reduction was observed at T2 and T3. The Linear mixed effect analyses showed significant time effects for FA, MD, and AD. Relative to baseline, post-hoc comparisons showed a significant decrease of FA and AD at lesion site only for T2. Instead, there was a significant increase in AD and MD at T3 compared to T2 at lesion site, and remotely near the motor cortex. Lesion size and FA changes in the CTCT at T2 showed only trend-level correlations with tremor outcome. Stronger associations were observed for the thalamic lesion-tract overlap at T2, which were even more robust at T3. Dynamic microstructural changes suggest early axonal disruption at the lesion site and subsequent reorganization, with remote CTCT changes potentially indicating chronic degeneration. Meanwhile, microstructural measures show limited predictive value for tremor outcome at 6 months compared with macroanatomical lesion-CTCT overlap. Yet, advanced diffusion imaging protocol could increase the sensitivity to predict MRgFUS clinical outcome.