Evidence-based optimization of treatment timing in the craniofacial complex - Growth standards for the cranium and face have not kept pace with advances in imaging technology. Craniofacial growth models currently used in clinical practice rely on two-dimensional (2D) views of a three- dimensional (3D) structure, the craniofacial complex. While this approach has served the discipline well for the better part of a century, recent advances in 3D imaging mean that significant progress in treatment can only be expected once growth standards advance to incorporate growth in three dimensions. The proposed study accelerates the science behind clinical treatments by developing growth models using state-of-the-art cone- beam computed tomography (CBCT). Models will be rooted in dense longitudinal data from the investigators’ prior NIH-funded projects to ensure a robust and rigorous approach that clinicians can rely on. New technologies beget new approaches and analytical methodologies to propel the field forward. The potential for inclusion of a detailed assessment of craniofacial growth in clinical treatment has reached a watershed moment. While CBCT imaging technology has been available for two decades, the ability for clinicians to easily collect data from those images has lagged. Software allowing for autolandmarking of cephalometric points and measures are in development and will soon be available in commercial packages (e.g., InVivo, Dolphin). Through three innovative aims, the proposed work will collect and utilize 40,000 CBCT (3D craniofacial) images of children and young adults to create new growth standards based on the three-dimensional nature of the craniofacial complex and consider age, sex, race, ethnicity, facial type, and dental maturation. Assessment of growth, growth milestones, and prediction of future growth will be included in models for clinical and research use. In Aim 1, a large and racially/ethnically diverse database of clinically-relevant craniofacial phenotypes, will serve as the foundation of analyses in the proposed work. Resulting growth models will also be available to the craniofacial community via web interfaces such as FaceBase and the AAOF Legacy Collection website to maximize adoption in clinical practice. Through Aim 2 we will use shape-based approaches to capture global differences and analyze variation and covariation in anatomical regions across ages, sexes, and races. In so doing, we will also test shape groupings against clinically established facial types. Improvements in diagnostic abilities and treatment strategies will directly result from those analyses. To integrate these new approaches to assessment and prediction of growth, Specific Aim 3 will determine the degree to which dysmorphic growth and growth variation resemble that of normal growth, and whether divergence in growth trajectory provides added clinical utility. The overall impact of the proposed research will be a shift in clinical management of pediatric craniofacial patients toward more evidence-based treatment planning, utilizing references and predictions based on a large, racially diverse sample of modern U.S. children.