Ventralis intermedius nucleus anatomical variability assessment by MRI structural connectivity

Abstract

The ventralis intermedius nucleus (Vim) is centrally placed in the dentato-thalamo-cortical pathway (DTCp) and is a key surgical target in the treatment of severe medically refractory tremor. It is not visible on conventional MRI sequences; consequently, stereotactic targeting currently relies on atlas-based coordinates. This fails to capture individual anatomical variability, which may lead to poor long-term clinical efficacy. Probabilistic tractography, combined with known anatomical connectivity, enables localisation of thalamic nuclei at an individual subject level. There are, however, a number of confounds associated with this technique that may influence results. Here we focused on an established method, using probabilistic tractography to reconstruct the DTCp, to identify the connectivity-defined Vim (cd-Vim) in vivo. Using 100 healthy individuals from the Human Connectome Project, our aim was to quantify cd-Vim variability across this population, measure the discrepancy with atlas-defined Vim (ad-Vim), and assess the influence of potential methodological confounds. We found no significant effect of any of the confounds. The mean cd-Vim coordinate was located within 1.88 mm (left) and 2.12 mm (right) of the average midpoint and 3.98 mm (left) and 5.41 mm (right) from the ad-Vim coordinates. cd-Vim location was more variable on the right, which reflects hemispheric asymmetries in the probabilistic DTC reconstructed. The method was reproducible, with no significant cd-Vim location differences in a separate test-retest cohort. The superior cerebellar peduncle was identified as a potential source of artificial variance. This work demonstrates significant individual anatomical variability of the cd-Vim that atlas-based coordinate targeting fails to capture. This variability was not related to any methodological confound tested. Lateralisation of cerebellar functions, such as speech, may contribute to the observed asymmetry. Tractography-based methods seem sensitive to individual anatomical variability that is missed by conventional neurosurgical targeting; these findings may form the basis for translational tools to improve efficacy and reduce side-effects of thalamic surgery for tremor.

Keywords: Connectivity; Functional neurosurgery; Individualized targeting; Probabilistic tractography; Tremor.

Fig. 1

A - Nissl-stained histological sagittal section of a human thalamus at +10.75 mm from the midline; B – Outline of VL (dotted line) and position of Vim within VL on this atlas (red dotted line); C. Highlight of surrounding structures (bold yellow = Vim; pale yellow – VL; blue = Ventrolateral anterior; red – Ventroposterior inferior; green - Ventroposterior medial); D - Diagrammatic representation of lateral view of the thalamus showing relationships between thalamic nuclei, colourised as per C. A-C adapted with permission from Ilinsky et al. (2018). D adapted with permission from Gross et al. (2004). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Right (blue) and left (green) group average DTCp windowed between PICo 0 –1. Values <0.05 were zeroed for visualisation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Principal directions of variance for tractography-defined Vim. The eigenvector corresponding to the first principal component is shown as solid line.

Fig. 4

Raincloud plots for tractography defined Vim data. The average tractography (solid line) and atlas (dashed line) defined coordinates are shown on the distributions above. The boxplots below show the original, tractography-defined centroid locations, and mark the average, interquartile range and two standard deviations for each axis (AP, ML and SI), in mm.

Fig. 5

DBS trajectory planning using atlas-based coordinates. View down bore of left (A) and right (B) thalamic electrode, with individual tract centroids and variance projected orthogonal to the electrode trajectories; Coronal (C) and Axial (D) views of DBS electrode trajectory showing thalamic renderings (top) and original planning MRI (bottom).

Fig. 6

Top row: NeuroSynth fMRI meta-analysis results of 944 studies obtained with search term “word”. Bottom row: left hemisphere M1 mask used for this study (arrow).