Variability and Landmark Quality in Anatomical Co-Registration in Neuronavigation for Brain Stimulation

Accurate neuronavigation depends not only on the technical performance of the tracking system but also on the reproducibility with which anatomical landmarks are physically localized. We quantified operator- and landmark-specific variability in repeated facial and cranial landmark localization in 19,630 measurements from 16 participants, four operators, and 13 landmarks under marked and unmarked conditions. Within-operator precision, inter-operator agreement, and marked–unmarked displacement were analyzed separately. Median within-operator precision was 1.60 mm and median inter-operator distance was 2.91 mm, with substantial differences across both operators and landmarks. The left medial canthus showed the greatest within-operator precision (1.43 mm), whereas the pronasale showed the closest inter-operator agreement (2.05 mm). Marking the positions before the procedure did not significantly improve within-operator precision overall but reduced inter-operator distances by 29.2%, which indicates convergence on a shared spatial reference rather than improved intrinsic repeatability. Between-operator differences also contained systematic directional components; signed offsets approached 1.5 mm. Exploratory analyses did not suggest general left--right difference in precision, although the approach side produced systematic spatial shifts for midline landmarks despite comparable repeatability. These findings demonstrate that anatomical landmark localization is both operator- and landmark-specific. Standardized landmark definitions, operator calibration, consistent pointer approach, and the use of multiple well-defined registration features should therefore be considered integral components of neuronavigation quality control.