I'll be presenting some of the ongoing work at Penn on the use of tractography in surgical targeting, specifically for thalamic DBS for tremor control. In DBS for essential tremor, the primary target, the VIM nucleus, cannot be clearly visualized with structural imaging, even on a 7T scanner. As such, there has been much interest in the dentatorubothalamic tract for target localization, but evidence for DRTT as a putative stimulation target in tremor suppression is lacking. Hence, our objective in the study was to evaluate proximity of DRTT to the active contact in relation to DBS stimulation parameters. This was a retrospective analysis of 26 consecutive essential tremor patients who underwent VIM DBS at our institution using standard MER-based techniques. Overall, 20 patients had bilateral implants, and the remaining six had unilateral implants. Fiber tracking was performed on clinical-grade diffusion MR acquisitions using a published deterministic tracking methodology that was implemented under guidance of a neuroradiologist on FDA-approved MR analysis software. Our primary clinical outcome were DBS stimulation parameters at six months. Programming was conducted by movement disorder specialists who were agnostic to the tractography results. At an average follow-up of three months, tremor severity was reduced by 70%. Here we show the coordinates of implanted leads at the level of the anterior and posterior commissural line. At the group level, the DRTT were generally anterior and lateral to the lead by about two millimeters. The active contact was generally found to be three millimeters superior to the level of the ACPC line. At the level of the active contact, the nearest fibers of the DRTT were 2.5 millimeters lateral to the contact. The radius of the volume of tissue activated calculated from a published finite element model was slightly longer at three millimeters. Across all implanted leads, DBS stimulation therefore influenced the DRTT in the majority of active contacts. To provide statistical evidence that stimulation of DRTT is clinically relevant, we calculated the distance from the active contact to the DRTT. We found a significant correlation with stimulation voltage in which a greater DRTT to active contact distance predicted higher voltage requirements. As a control, we performed the same analysis with distance to ATLAS-based VIN coordinates, which did not demonstrate a significant correlation. In summary, our data provides correlative evidence for DRTT as an effective stimulation target for thermal control. Importantly, tractography was performed on clinical-grade MRI acquisitions with deterministic tracking implemented on widely used surgical planning software, suggesting that tractography-based targeting for thalamic DBS is a feasible approach with the current technology available to most clinical centers. We emphasize that prior studies have been unable to find statistical evidence to validate DRTT for surgical targeting, which may be due in part to smaller sample sizes ranging between 5 to 11 patients in these previous studies. Key issues for future work in this domain include variability across studies in the choice of seed regions and termination regions for fiber tracking, which has been shown to significantly affect tractography results. Second, there is ambiguity about where along the extent of the tract stimulation should be provided for maximal clinical efficacy, with our results suggesting slightly above the level of the intercommercial line. Finally, as more advanced MRI acquisitions, as well as more advanced processing techniques, become progressively more available to clinicians, it is important to keep in mind that such improvements incur increased scan time, increased computational load, and additional technical expertise, and therefore should be justified for the specific clinical setting prior to implementation. Thank you for your attention.

tractography

deep brain stimulation

tremors

dentatorubothalamic tract

stimulation target