Human/nonhuman primate AC-PC ratio--considerations for translational brain measurements

Abstract

This comparative magnetic resonance imaging (MRI) analysis evaluated the ratio of AC-PC (anterior commissure to posterior commissure) distance measures in selected groups of humans and nonhuman primates (NHPs). An understanding of the basis of this ratio between primate species may allow more accurate translation of NHP stereotactic targeting measurements to upcoming human trials. MRI datasets of adult humans [n=21], and juvenile and adult NHPs (Macaca fascicularis [n=40], and Macaca mulatta [n=32]), were evaluated in a mid-sagittal plane to obtain the AC-PC distance measure for each examined subject. Two trained evaluators, blinded to each other's results, carried out three separate measurements of the AC-PC length for each subject. Each observer carried out measurements of the entire dataset [n=93] before repeating the measurements two additional times. Previous dataset measures were not available for review at the time of subsequent measures. Inter- and intra-observer variabilities were not statistically significant. Minimal intraspecies variation was found in the AC-PC measurement of our human and NHP groups. We found significant interspecies differences, however, more between humans and NHPs, and less between the NHP groups. Regression analysis confirms the strong linear relationship of AC-PC distance based primarily on species in our study groups. Human/NHP AC-PC ratios varied between 2.1 and 2.3 based on the compared NHP species groups. We conclude that the scale differences in brain measurements between NHPs and humans described in this study allows improved translation of stereotactic targeting coordinates in future human clinical trials, which may lead to improved efficacy and safety.