Spatiotemporal 3D image registration for mesoscale studies of brain development.

Comparison of brain samples representing different developmental stages often necessitates registering the samples to common coordinates. Although the available software tools are successful in registering 3D images of adult brains, registration of perinatal brains remains challenging due to rapid growth-dependent morphological changes and variations in developmental pace between animals. To address these challenges, we propose a multi-step algorithm for the registration of perinatal brains. First, we optimized image preprocessing to increase the algorithm9s sensitivity to mismatches in registered images. Second, we developed an attention-gated simulated annealing (Monte Carlo) procedure capable of focusing on the differences between perinatal brains. Third, we applied classical multidimensional scaling (CMDS) to align (synchronize) brain samples in time, accounting for individual development paces. We tested this multi-step algorithm on 28 samples of whole-mounted perinatal mouse brains (P0 - P9) and observed accurate registration results. Our computational pipeline offers a runtime of several minutes per brain on a personal computer and automates brain registration tasks including mapping brain data to atlases, comparison of averaged experimental groups, and monitoring brain development dynamics.