Data-driven Normative Reference of Pediatric Cranial Bone Development

Background: Available normative references of cranial bone development and suture fusion are incomplete or based on simplified assumptions due to the lack of large datasets. We present a fully data-driven normative model that represents the age- and sex-specific variability of bone shape, thickness, and density between birth and 10 years of age at every location of the calvaria. Methods: The model was built using a cross-sectional and multi-institutional pediatric computed tomography image dataset with 2068 subjects without cranial pathology (age 0-10 years). We combined principal component analysis and temporal regression to build a statistical model of cranial bone development at every location of the calvaria. We studied the influences of sex on cranial bone growth, and our bone density model allowed quantifying for the first time suture fusion as a continuous temporal process. We evaluated the predictive accuracy of our model using an independent longitudinal image dataset of 51 subjects. Results: Our model achieved temporal predictive errors of 2.98 +/- 0.69 mm, 0.27 +/- 0.29 mm, and 76.72 +/- 91.50 HU in cranial bone shape, thickness, and mineral density changes, respectively. Significant sex differences were found in intracranial volume and bone surface areas (P < 0.01). No significant differences were found in cephalic index, bone thickness, mineral density, or suture fusion. Conclusions: We presented the first pediatric age- and sex-specific statistical reference for local cranial bone shape, thickness, and mineral density changes. We showed its predictive accuracy using an independent longitudinal dataset, we studied developmental differences associated with sex, and we quantified suture fusion as a continuous process.