Abstract

During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggests that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a new method to estimate local growth from sequential cortical reconstructions. Using anatomically-constrained Multimodal Surface Matching (aMSM), we obtain accurate, physically-guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned 2-4 times during the period of rapid cortical expansion (28 to 38 weeks postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with patterns of active folding. Furthermore, these growth patterns shift over the course of development, with non-injured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully-automated surface analysis, based on tools freely available to the brain mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.\n\nSignificance StatementThe human brain exhibits complex folding patterns that emerge during the third trimester of fetal development. Minor folds are quasi-randomly shaped and distributed. Major folds, in contrast, are more conserved and form important landmarks. Disruption of cortical folding is associated with devastating disorders of cognition and emotion. Despite decades of study, the processes that produce normal and abnormal folding remain unresolved, although the relatively rapid tangential expansion of the cortex has emerged as a driving factor. Accurate and precise measurement of cortical growth patterns during the period of folding has remained elusive. Here, we illuminate the spatiotemporal dynamics of cortical expansion by analyzing MRI-derived surfaces of preterm infant brains, using a novel strain energy minimization approach.