Deep diffusion MRI template (DDTemplate): A novel deep learning groupwise diffusion MRI registration method for brain template creation.

Diffusion MRI (dMRI) is an advanced imaging technique that enables in-vivo tracking of white matter fiber tracts and estimates the underlying cellular microstructure of brain tissues. Groupwise registration of dMRI data from multiple individuals is an important task for brain template creation and investigation of inter-subject brain variability. However, groupwise registration is a challenging task due to the uniqueness of dMRI data that include multi-dimensional, orientation-dependent signals that describe not only the strength but also the orientation of water diffusion in brain tissues. Deep learning approaches have shown successful performance in standard subject-to-subject dMRI registration. However, no deep learning methods have yet been proposed for groupwise dMRI registration. . In this work, we propose Deep Diffusion MRI Template (DDTemplate), which is a novel deep-learning-based method building upon the popular VoxelMorph framework to take into account dMRI fiber tract information. DDTemplate enables joint usage of whole-brain tissue microstructure and tract-specific fiber orientation information to ensure alignment of white matter fiber tracts and whole brain anatomical structures. We propose a novel deep learning framework that simultaneously trains a groupwise dMRI registration network and generates a population brain template. During inference, the trained model can be applied to register unseen subjects to the learned template. We compare DDTemplate with several state-of-the-art registration methods and demonstrate superior performance on dMRI data from multiple cohorts (adolescents, young adults, and elderly adults) acquired from different scanners. Furthermore, as a testbed task, we perform a between-population analysis to investigate sex differences in the brain, using the popular Tract-Based Spatial Statistics (TBSS) method that relies on groupwise dMRI registration. We find that using DDTemplate can increase the sensitivity in population difference detection, showing the potential of our method's utility in real neuroscientific applications.