Automatic analysis of skull thickness, scalp-to-cortex distance and association with age and sex in cognitively normal elderly

Personalized neurostimulation has been a potential treatment for many brain diseases, which requires insights into brain/skull geometry. Here, we developed an open source efficient pipeline BrainCalculator for automatically computing the skull thickness map, scalp-to-cortex distance (SCD), and brain volume based on T(1)-weighted magnetic resonance imaging (MRI) data. We examined the influence of age and sex cross-sectionally in 407 cognitively normal older adults (71.9±8.0 years, 60.2% female) from the ADNI. We demonstrated the compatibility of our pipeline with commonly used preprocessing packages and found that BrainSuite Skullfinder was better suited for such automatic analysis compared to FSL Brain Extraction Tool 2 and SPM12-based unified segmentation using ground truth. We found that the sphenoid bone and temporal bone were thinnest among the skull regions in both females and males. There was no increase in regional minimum skull thickness with age except in the female sphenoid bone. No sex difference in minimum skull thickness or SCD was observed. Positive correlations between age and SCD were observed, faster in females (0.307%/y) than males (0.216%/y) in temporal SCD. A negative correlation was observed between age and whole brain volume computed based on brain surface (females −1.031%/y, males −0.998%/y). In conclusion, we developed an automatic pipeline for MR-based skull thickness map, SCD, and brain volume analysis and demonstrated the sex-dependent association between minimum regional skull thickness, SCD and brain volume with age. This pipeline might be useful for personalized neurostimulation planning.