Diffusion MRI is an excellent method for detecting subtle changes of brain microstructure, but rarely gives unambiguous information about whether the observations originate from variations in cell density, size, shape, orientation, or any combination thereof. Capitalizing on our recent pulse sequences with data acquisition as a function of both the spherical and the conventional linear components of the diffusion encoding tensor b, we here introduce and demonstrate a method to quantify the composition of a heterogeneous voxel as a multidimensional distribution of diffusion tensors where the information about size, shape, and orientation is cleanly separated in the respective dimensions of the distribution. When transferred to a neuroimaging context, our method will allow for unconstrained estimation of fiber bundle orientation distributions and radial and axial diffusivities, as well as fractions of extracellular water and cerebrospinal fluid.
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