Microstructural changes of the dentato-rubro-thalamic tract after transcranial MR guided focused ultrasound ablation of the posteroventral VIM in essential tremor

Abstract

Essential tremor is the most common movement disorder in adults. In patients who are not responsive to medical treatment, functional neurosurgery and, more recently, transcranial MR-guided focused ultrasound thalamotomy are considered effective therapeutic approaches. However, the structural brain changes following a thalamotomy that mediates the clinical improvement are still unclear. In here diffusion weighted images were acquired in a cohort of 24 essential tremor patients before and 3 months after unilateral transcranial MR-guided focused ultrasound thalamotomy targeting at the posteroventral part of the VIM. Microstructural changes along the DRTT were quantified by means of probabilistic tractography, and later related to the clinical improvement of the patients at 3-months and at 1-year after the intervention. In addition the changes along two neighboring tracts, that is, the corticospinal tract and the medial lemniscus, were assessed, as well as the relation between these changes and the presence of side effects. Thalamic lesions produced local and distant alterations along the trajectory of the DRTT, and each correlated with clinical improvement. Regarding side effects, gait imbalance after thalamotomy was associated with greater impact on the DRTT, whereas the presence of paresthesias was significantly related to a higher overlap between the lesion and the medial lemniscus. This work represents the largest series describing the microstructural changes following transcranial MR-guided focused ultrasound thalamotomy in essential tremor. These results suggest that clinical benefits are specific for the impact on the cerebello-thalamo-cortical pathway, thus reaffirming the potential of tractography to aid thalamotomy targeting.

Keywords: MR guided focused ultrasound; essential tremor; tractography.

Figure 1

(a) Sample images showing tissue lesions. The first row shows the lesion 1‐day postintervention and the second row shows the 3‐months postintervention. Lesions at different contrasts are outlined in red; (b) Probabilistic lesion map and anatomical projections. Axial slice on MNI space showing the average lesion (1‐day post‐treatment) and the reconstruction of the anatomical pathways traveling in the vicinity of the lesion, that is, dentato‐rubro‐thalamic tract (DRTT), corticospinal tract (CST), and medial lemniscus (ML); (c) Probabilistic lesion map and topography of the lesions across subjects. It represents in what percentage of the patients a voxel was identified as lesioned tissue. VIM: ventral intermediate nucleus; VLa: ventral lateral anterior nucleus; VPL: ventral posterior lateral nucleus; VPM: ventral posterior medial nucleus; STh: subthalamic nucleus [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Bar plots representing average values and standard deviations across subjects in DTI scores within the lesion borders. Light red/blue colors indicate values computed within the 1‐day lesion borders at baseline and 3‐months post‐treatment DTI. Dark colors represent the same values within the 3‐months lesion borders. Statistical significance was compared pairwise using parametric paired t‐tests (*p < 0.05; **p < 0.01; ***p < 0.001) [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Microstructural changes along the anatomical pathways in the target hemisphere. (a) Tractography maps of the three reconstructed pathways in MNI space. From left to right: the dentato‐rubro‐thalamic tract in green, the cortico‐spinal tract in orange, and the medial lemniscus in blue. (b–d) Representation of the differences in the DTI metrics (FA, MD, RD, AD) and AFD between baseline and 3 months post‐treatment for the dentato‐rubro‐thalamic tract (b), the cortico‐spinal tract (c) and the medial lemniscus (d). The x‐axis represent the 100 orthogonal ROIs to the pathways' trajectories, being ROI = 1 the most ventral, and ROI = 100 the most dorsal, that is, in the white matter below the motor cortex. Dark lines represent average differences across subjects, and shaded regions represent the standard errors. Above the axes there are red‐blue (increase–decrease) colorbars that indicate the statistical power of the differences thresholded at p < 0.01 [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Microstructural changes along the anatomical pathways in the nontarget hemisphere. (a) Tractography maps of the three reconstructed pathways in MNI space. From left to right: the dentato‐rubro‐thalamic tract in green, the cortico‐spinal tract in orange, and the medial lemniscus in blue. (b–d). Representation of the differences in the DTI metrics (FA, MD, RD, AD) and AFD between baseline and 3 months post‐treatment for the dentato‐rubro‐thalamic tract (B), the cortico‐spinal tract (C) and the medial lemniscus (D). The x‐axis represents the 100 orthogonal ROIs to the pathways' trajectories, ROI = 1 being the most ventral, and ROI = 100 the most dorsal, that is, in the white matter below the motor cortex. Dark lines represent average differences across subjects, and shaded regions represent the standard errors. Above the axes there are red‐blue (increase–decrease) colorbars that indicate the statistical power of the differences thresholded at p < 0.01 [Color figure can be viewed at http://wileyonlinelibrary.com]