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 remain 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 (STN) 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 (STN) had AFREs that spatially covaried, suggesting consistent spatial patterns of misregistration to stereotactic space. These identified spatial patterns account for 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). The AFIDs framework provides millimetric estimates of registration accuracy in DBS, while allowing the 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.