Normal Childhood Brain Growth and a Universal Sex and Anthropomorphic Relationship to Cerebrospinal Fluid

ObjectThe study of brain size and growth has a long and contentious history, yet normal brain volume development has yet to be fully described. In particular, the normal brain growth and cerebrospinal fluid (CSF) accumulation relationship is critical to characterize because it is impacted in numerous conditions of early childhood where brain growth and fluid accumulation are affected such as infection, hemorrhage, hydrocephalus, and a broad range of congenital disorders. This study aims to describe normal brain volume growth, particularly in the setting of cerebrospinal fluid accumulation.MethodsWe analyzed 1067 magnetic resonance imaging (MRI) scans from 505 healthy pediatric subjects from birth to age 18 to quantify component and regional brain volumes. The volume trajectories were compared between the sexes and hemispheres using Smoothing Spline ANOVA. Population growth curves were developed using Generalized Additive Models for Location, Scale, and Shape.ResultsBrain volume peaked at 10-12 years of age. Males exhibited larger age-adjusted total brain volumes than females, and body size normalization procedures did not eliminate this difference. The ratio of brain to CSF volume, however, revealed a universal age-dependent relationship independent of sex or body size.ConclusionsThese findings enable the application of normative growth curves in managing a broad range of childhood disease where cognitive development, brain growth, and fluid accumulation are interrelated.