Early joint cranial and brain development from fetal and pediatric imaging

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PROJECT SUMMARY The devastating impacts of early-childhood cranial and skull deformities affect nearly 25% of infants from single pregnancies and 50% of those from multiple pregnancies. If not diagnosed early and treated effectively, these abnormalities can impact brain development, leading to cognitive impairment, elevated intracranial pressure, and motor disabilities. Clinicians’ capacity to effectively diagnose and treat these disorders is hindered by two things: first, a limited understanding of how the cranium and brain normally grow and co- develop; and, second, a dearth of imaging techniques that are sensitive enough to analyze joint cranial and brain development in both healthy and abnormal instances. To address these limitations, a strong, interdisciplinary, collaborative team from Children’s National Hospital, Children’s Hospital Los Angeles, Brown University, University of Colorado and Arizona State University proposes the current R01 aimed at developing the first normative joint model of brain and cranium development before and after birth. This work is f ueled by the team’s robust prior efforts, in which they independently collected large, normative datasets of computed tomography (CT) and magnetic resonance (MR) images of infants and fetuses, and implemented preliminary tools to analyze them as a starting point for new methods to be developed as part of this project . The team’s hypothesis is that the development of regional cortical and cranial morphologies will be strongly associated. It will be tested using the following aims: (1) Develop quantitative imaging tools to model healthy cranial development in infants; (2) Determine the joint development of cranial and cortical shape and thickness in infants; (3) Develop a preliminary model of fetal brain and cranial growth across gestation; and (4) Build and disseminate a user-friendly toolbox for clinicians and researchers. This project will be the first systematic in-vivo study of joint healthy cranial and brain development before and after birth. As such, it will determine typical variations of the cranial shape and their correlations with brain parameters, adjusted for age and sex. The normative models generated here will serve as clinical resources for matched comparisons in individual children with suspected disorders that involve abnormal cranial shapes. Additionally, precise in-vivo quantitative imaging methods for assessing joint cranial and brain shape in inf ants will be developed in this project and will serve as invaluable tools for physicians to better assess, diagnose, and plan treatment for infant cranial deformities in the future.