A framework for spatial normalization and voxelwise analysis of diffusion propagators in multiple MAP-MRI data sets

We describe a pipeline for constructing a study-specific template of diffusion propagators measured with mean apparent propagator (MAP) MRI that supports direct voxelwise analysis of differences between propagators across multiple data sets. The pipeline leverages the fact that MAP-MRI is a generalization of diffusion tensor imaging (DTI) and combines simple and robust processing steps from existing tensor-based image registration methods. First, we compute a DTI study template which provides the reference frame and scaling parameters needed to construct a standardized set of MAP-MRI basis functions at each voxel in template space. Next, we transform each subjects diffusion data, including diffusion weighted images (DWIs) and gradient directions, from native to template space using the corresponding tensor-based deformation fields. Finally, we fit MAP coefficients in template space to the transformed DWIs of each subject using the standardized template of MAP basis functions. The consistency of MAP basis functions across all data sets in template space allows us to: 1. compute a template of propagators by directly averaging MAP coefficients and 2. quantify voxelwise differences between co-registered propagators using the angular dissimilarity, or a probability distance metric, such as the Jensen-Shannon Divergence. We illustrate the application of this method by generating a template of MAP propagators for a cohort of healthy volunteers and show a proof-of-principle example of how this pipeline may be used to detect subtle differences between propagators in a single-subject longitudinal clinical data set. The ability to standardize and analyze multiple clinical MAP-MRI data sets could improve assessments in cross-sectional and single-subject longitudinal clinical studies seeking to detect subtle microstructural changes, such as those occurring in mild traumatic brain injury (mTBI), or during the early stages of neurodegenerative diseases, or cancer.