Quantitative comparison of femurs in apolipoprotein E mouse models using high-resolution photon-counting micro-CT

Apolipoprotein E (APOE) genotype and nitric oxide synthase 2 (NOS2) expression are key genetic factors that influence bone health. While prior studies explored differences in bones by APOE genotype, the role of sex and NOS2 require further investigation. In this study, we acquired micro-CT scans of femurs and analyzed their characteristics in a cohort of mice with variation in age, sex, APOE genotype, and humanized NOS2 (HN) expression. Femurs were extracted from 57 mice and scanned using photon-counting micro-CT with two energy thresholds. Scan data was iteratively reconstructed and decomposed into water and calcium material maps. Trabecular and cortical femur features were computed from calcium maps of femurs using ImageJ’s BoneJ plugin. Statistical analyses of femur features were applied on the entire cohort of mice and on subgroups stratified by sex, APOE genotype, and HN status. Our image quality assessment found that the calcium map has higher contrast to noise ratio than both energy channels of the iterative reconstruction. Differences in bone volume fraction by APOE genotype were found in the whole group, but this result was not reproduced in subgroups stratified by sex or HN status. Analyses in the whole group and in stratified subgroups revealed that the interaction between sex and HN status was a significant predictor of femur features and that HN females tend to have low trabecular bone content. This study illustrates the benefits of photon-counting CT for femur imaging and shows meaningful effects of age, APOE genotype, sex, HN, and their interactions on bone health.