A$^3$PreCore: Robust Rigid Registration for Native FLAIR-Space Brain-Mask Transfer

Abstract: Reliable brain-mask transfer into native fluid-attenuated inversion recovery (FLAIR) space can fail when T1-to-FLAIR rigid registration is unstable. We developed A$<sup>3$PreCore, a six-degree-of-freedom rigid-registration strategy that aligns the full bias-corrected T1-weighted image to native FLAIR using normalized mutual information while preserving the established T1-space anatomical mask. We also introduced extended quantitative quality control (E-QC), which characterizes mask extent, field-of-view-relative position, FLAIR intensity support, boundary support, inferior morphology, and pairwise geometric disagreement. In 78 participants with paired T1-weighted and FLAIR imaging, A$<sup>3$PreCore was compared with fsl_anat and the Brain Extraction Tool (BET). Gross rigid-body misregistration occurred in 21/78 fsl_anat outputs (26.9%) and 0/78 A$<sup>3$PreCore outputs (exact two-sided McNemar p=9.54 x 10^-7). Among 57 participants without gross fsl_anat misregistration, A$<sup>3$PreCore preserved close agreement (median Dice=0.993; median paired Delta NMI=-0.00007, p=0.429). A$<sup>3$PreCore remained broadly concordant with BET (median Dice=0.955), with less inferior and extracranial extension in representative comparisons. Method-blinded neuroscientists ranked A$<sup>3$PreCore first in 35/40 participants (87.5%). E-QC additionally exposed severe orientation-related disagreement not evident from global descriptors or centroid displacement alone. These findings support A$<sup>3$PreCore as a robust native-FLAIR brain-mask transfer strategy and E-QC as a complementary framework for multidimensional mask characterization and participant-specific geometric quality control.