Diffusion MRI (Fig 2) reflects the random diffusion of water molecules, which is affected by the microscopic structure of tissue14, enabling us to infer the local density of cellular compartments in tissue (e.g. neurites). Additionally, axon bundles in white matter create an orientation dependence of water movement due to hindrance of diffusion perpendicular to the long axis of white matter tracts, an effect that can be tracked from voxel to voxel (“tractography”) to derive long-range white matter pathways. Three complementary diffusion models were fit to the signal in each voxel: (i) the diffusion tensor model15, describing the signal phenomenologically as resulting from a 3D ellipsoid profile of water displacement; (ii) the neurite orientation dispersion and density imaging (NODDI) model16, estimating microstructural properties (e.g., neurites vs. extracellular space); and (iii) the ball & sticks model17, estimating the orientation of multiple fiber populations within a voxel for tractography. 675 IDPs were extracted, by averaging parameters estimated by the first two models over 75 different white-matter tract regions based both on subject-specific tractography18 and from population-average white matter masks19.
