Changes in the Cerebello-Thalamo-Cortical Network After Magnetic Resonance-Guided Focused Ultrasound Thalamotomy

Abstract

Objective: In recent years, transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor (ET). So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in ET patients treated with tcMRgFUS thalamotomy. Methods: Eleven patients diagnosed with ET were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3 Tesla magnetic resonance imaging (3T MRI) including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed before the procedure as well as 1 year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus, and the corticospinal tract in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results: The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p < 0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r = -0.54, p = 0.04; MD: r = 0.57, p = 0.04); RD: r = 0.67, p = 0.036). Further, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r = 0.58; p = 0.062; MD: r = -0.52, p = 0.64; RD: r = -0.61 p = 0.090). Conclusions: Microstructural changes were detected within the CTCT after tcMRgFUS, and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism, and ultimately to improve targeting prospectively. Impact statement The results of this study demonstrate microstructural changes within the cerebello-thalamo-cortical pathways 1 year after MR-guided focused ultrasound thalamotomy. Even more, microstructural changes within the cerebello-thalamo-cortical pathways correlated significantly with clinical outcome. These findings do not only highly emphasize the need of new targeting strategies for MR-guided focused ultrasound thalamotomy but also help to elucidate the treatment mechanism of it.

Keywords: MR-guided focused ultrasound; diffusion tensor imaging; essential tremor; microstructural change; structural connectivity; tractography.

FIG. 1.

Example of ROI placement and tractography results in a representative patient. (A) The CTCT (blue), CST (red), and ML (green) overlaid on T1w images (affinely co-registered to T2w images using the reg_aladin function from the NiftyReg software with the default parameters) in sagittal, coronal, and axial views. Examples of seed, target, and waypoints for the (B) CTCT, (C) CST, and (D) ML. CST, corticospinal tract; CTCT, cerebello-thalamo-cortical tract; ML, medial lemniscus; ROI, region of interest; T2w, T₂-weighted.

FIG. 2.

Lesion location in relation to tract location within the thalamus. CTCT (blue), CST (red), ML (green), and tcMRgFUS lesion (yellow) overlaid on post-treatment T2w images of all patients (S1–S11). tcMRgFUS, transcranial magnetic resonance-guided focused ultrasound.

FIG. 3.

Correlation between changes of DTI metrics within the CTCT and the clinical outcome as well as the tract-lesion overlap. The correlation between changes of DTI metrics and clinical outcome was performed on only data from 10 subjects since the post-treatment clinical scores were not available for one subject (S3) due to personal reasons. Δ implicates the percent changes between the pre-treatment and post-treatment DTI metrics and CRST scores. The p-values reported in the panels are adjusted to account for multiple comparisons using the Benjamini-Hochberg method. (A–C) Correlation between changes of DTI metrics within the CTCT and clinical improvement. (D–F) Correlation between changes of DTI metrics within the CTCT and weighted lesion overlap. CRST, Clinical Rating Scale for Tremor; DTI, diffusion tensor imaging.