Diffusion MRI is a powerful tool for non-invasive probing of brain tissue microstructure. Recent multi-center efforts in the acquisition and analysis of diffusion MRI data significantly increase sample sizes and hence improve sensitivity and reliability in detecting subtle changes associated with development, aging, and diseases. However, discrepancies resulting from different scanner vendors, acquisition protocols, and image reconstruction algorithms can cause data incompatibility across imaging centers. In this paper, we introduce a model-free method that is based on the method of moments for the direct harmonization of diffusion MRI data to reduce site-specific variations. Our method directly harmonizes diffusion-attenuated signal without the need to fit any diffusion model. Moreover, our method allows the explicit definition of well-behaved mapping functions with properties such as invertibility, smoothness, and injectivity. We show that our method is effective in lowering the variations of diffusion scalars of traveling human phantoms scanned at different sites from 1%–3% to less than 0.9% for fractional anisotropy (FA) and mean diffusivity and from 1%–2.5% to 0.3%–1.2% for generalized FA. We also demonstrate its ability in preserving individual differences and in increasing across-site consistency in tractography and white matter connectivity.

Brain atlases are spatial references for integrating, processing, and analyzing brain features gathered from different individuals, sources, and scales. Here we introduce a collection of joint surface–volume atlases that chart postnatal development of the human brain in a spatiotemporally dense manner from two weeks to two years of age. Our month-specific atlases chart normative patterns and capture key traits of early brain development and are therefore conducive to identifying aberrations from normal developmental trajectories. These atlases will enhance our understanding of early structural and functional development by facilitating the mapping of diverse features of the infant brain to a common reference frame for precise multifaceted quantification of cortical and subcortical changes.

During the first years of life, the human brain undergoes dynamic spatially-heterogeneous changes, involving differentiation of neuronal types, dendritic arborization, axonal ingrowth, outgrowth and retraction, synaptogenesis, and myelination. To better quantify these changes, this article presents a method for probing tissue microarchitecture by characterizing water diffusion in a spectrum of length scales, factoring out the effects of intra-voxel orientation heterogeneity. Our method is based on the spherical means of the diffusion signal, computed over gradient directions for a set of diffusion weightings (i.e., b-values). We decompose the spherical mean profile at each voxel into a spherical mean spectrum (SMS), which essentially encodes the fractions of spin packets undergoing fine-to coarse-scale diffusion processes, characterizing restricted and hindered diffusion stemming respectively from intra-and extra-cellular water compartments. From the SMS, multiple orientation distribution invariant indices can be computed, allowing for example the quantification of neurite density, microscopic fractional anisotropy (μFA), per-axon axial/radial diffusivity, and free/restricted isotropic diffusivity. We show that these indices can be computed for the developing brain for greater sensitivity and specificity to development related changes in tissue microstructure. Also, we demonstrate that our method, called spherical mean spectrum imaging (SMSI), is fast, accurate, and can overcome the biases associated with other state-of-the-art microstructure models.