A new method for structural volume analysis of longitudinal brain MRI data and its application in studying the growth trajectories of anatomical brain structures in childhood.

Cross-sectional analysis of longitudinal anatomical magnetic resonance imaging (MRI) data may be suboptimal as each dataset is analyzed independently. In this study, we evaluate how much variability can be reduced by analyzing structural volume changes in longitudinal data using longitudinal analysis. We propose a two-part pipeline that consists of longitudinal registration and longitudinal classification. The longitudinal registration step includes the creation of subject-specific linear and nonlinear templates that are then registered to a population template. The longitudinal classification step comprises a four-dimensional expectation-maximization algorithm, using a priori classes computed by averaging the tissue classes of all time points obtained cross-sectionally. To study the impact of these two steps, we apply the framework completely ("LL method": Longitudinal registration and Longitudinal classification) and partially ("LC method": Longitudinal registration and Cross-sectional classification) and compare these with a standard cross-sectional framework ("CC method": Cross-sectional registration and Cross-sectional classification). The three methods are applied to (1) a scan-rescan database to analyze reliability and (2) the NIH pediatric population to compare gray matter growth trajectories evaluated with a linear mixed model. The LL method, and the LC method to a lesser extent, significantly reduced the variability in the measurements in the scan-rescan study and gave the best-fitted gray matter growth model with the NIH pediatric MRI database. The results confirm that both steps of the longitudinal framework reduce variability and improve accuracy in comparison with the cross-sectional framework, with longitudinal classification yielding the greatest impact. Using the improved method to analyze longitudinal data, we study the growth trajectories of anatomical brain structures in childhood using the NIH pediatric MRI database. We report age- and gender-related growth trajectories of specific regions of the brain during childhood that could be used as a reference in studying the impact of neurological disorders on brain development.