The impact of localization and registration accuracy on estimates of deep brain stimulation electrode position in stereotactic space

Effects of deep brain stimulation (DBS) depend on millimetric accuracy and are commonly studied across populations by registering patient scans to a stereotactic space. Multiple factors contribute to estimates of electrode position, but the millimetric contributions of these factors remains poorly quantified. We previously validated 32 anatomical fiducials (AFIDs) to measure AFID registration error (AFRE), which can capture focal misregistration not observed using volume-based methods. To this end, we used the AFIDs framework to examine the effects of misregistration on electrode position in stereotactic space, leveraging a retrospective series of patients who underwent subthalamic nucleus DBS. Raters independently localized DBS electrodes and AFIDs on patient scans, which were non-linearly registered to a common stereotactic (MNI) space. AFIDs provided intuitive measures of registration accuracy, with AFREs ranging from 1.49 mm to 6.85 mm across brain regions. Subcortical AFIDs in proximity to the DBS target had AFREs that spatially covaried, suggesting consistent spatial patterns of misregistration to stereotactic space. These identified spatial patterns explained 28% of the variance in electrode position along the axis of maximum variance, corresponding to a median of 0.64 mm (range of 0.05 to 2.05 mm). To our knowledge, these represent the first millimetric estimates of registration accuracy in DBS, allowing uncoupling of registration-related factors from other sources of variance in electrode position. Furthermore, they can be employed for estimating registration-related variance in population studies, for quality control, and to provide a basis for comparison as well as optimization of registration parameters and software. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement M.A. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Scholarship, Ontario Graduate Scholarship and the Clinician Investigator Program Stipend at Western University. J.L. was supported by research start-up funding from the Department of Clinical Neurological Sciences at Western University and an NSERC Discovery Grant (RGPIN-2023-05562). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human Subject Research Ethics Board of Lawson Health Research Institute gave ethical approval for this work (REB# 109045). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data and scripts used are available online at: https://github.com/afids/afids-dbs