Use of probabilistic tractography to provide reliable distinction of the motor and sensory thalamus for prospective targeting during asleep deep brain stimulation
Authors: Muller Jennifer , Alizadeh Mahdi , Matias Caio M. , Thalheimer Sara , Romo Victor , Martello Justin , Liang Tsao-Wei , Mohamed Feroze B. , Wu Chengyuan 
Published: October 2021

OBJECTIVE
Accurate electrode placement is key to effective deep brain stimulation (DBS). The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for the treatment of essential tremor (ET). Retrospective tractography-based analysis of electrode placement has associated successful outcomes with modulation of motor input to VIM, but no study has yet evaluated the feasibility and efficacy of prospective presurgical tractography-based targeting alone. Therefore, the authors sought to demonstrate the safety and efficacy of probabilistic tractography–based VIM targeting in ET patients and to perform a systematic comparison of probabilistic and deterministic tractography.

METHODS
Fourteen patients with ET underwent preoperative diffusion imaging. Probabilistic tractography was applied for preoperative targeting, and deterministic tractography was performed as a comparison between methods. Tractography was performed using the motor and sensory areas as initiation seeds, the ipsilateral thalamus as an inclusion mask, and the contralateral dentate nucleus as a termination mask. Tract-density maps consisted of voxels with 10% or less of the maximum intensity and were superimposed onto anatomical images for presurgical planning. Target planning was based on probabilistic tract-density images and indirect target coordinates. Patients underwent robotic image-guided, image-verified implantation of directional DBS systems. Postoperative tremor scores with and without DBS were recorded. The center of gravity and Dice similarity coefficients were calculated and compared between tracking methods.

RESULTS
Prospective probabilistic targeting of VIM was successful in all 14 patients. All patients experienced significant tremor reduction. Formal postoperative tremor scores were available for 9 patients, who demonstrated a mean 68.0% tremor reduction. Large differences between tracking methods were observed across patients. Probabilistic tractography–identified VIM fibers were more anterior, lateral, and superior than deterministic tractography–identified fibers, whereas probabilistic tractography–identified ventralis caudalis fibers were more posterior, lateral, and superior than deterministic tractography–identified fibers. Deterministic methods were unable to clearly distinguish between motor and sensory fibers in the majority of patients, but probabilistic methods produced distinct separation.

CONCLUSIONS
Probabilistic tractography–based VIM targeting is safe and effective for the treatment of ET. Probabilistic tractography is more precise than deterministic tractography for the delineation of VIM and the ventralis caudalis nucleus of the thalamus. Deterministic algorithms tended to underestimate separation between motor and sensory fibers, which may have been due to its limitations with crossing fibers. Larger studies across multiple centers are necessary to further validate this method.