| Summary: | This work introduces a compartment-based model for apparent cell body (namely soma) and neurite density imaging (SANDI) using non-invasive diffusion-weighted MRI (DW-MRI). The existing conjecture in brain microstructure imaging through DW-MRI presents water diffusion in white (WM) and gray (GM) matter as restricted diffusion in neurites, modelled by infinite cylinders of null radius embedded in the hindered extra-neurite water. The extra-neurite pool in WM corresponds to water in the extra-axonal space, but in GM it combines water in the extra-cellular space with water in soma. While several studies showed that this microstructure model successfully describe DW-MRI data in WM and GM at b ≤ 3,000 s/mm2 (or 3 ms/μm2), it has been also shown to fail in GM at high b values (b≫3,000 s/mm2 or 3 ms/μm2). Here we hypothesise that the unmodelled soma compartment (i.e. cell body of any brain cell type: from neuroglia to neurons) may be responsible for this failure and propose SANDI as a new model of brain microstructure where soma of any brain cell type is explicitly included. We assess the effects of size and density of soma on the direction-averaged DW-MRI signal at high b values and the regime of validity of the model using numerical simulations and comparison with experimental data from mouse (bmax = 40,000 s/mm2, or 40 ms/μm2) and human (bmax = 10,000 s/mm2, or 10 ms/μm2) brain. We show that SANDI defines new contrasts representing complementary information on the brain cyto- and myelo-architecture. Indeed, we show maps from 25 healthy human subjects of MR soma and neurite signal fractions, that remarkably mirror contrasts of histological images of brain cyto- and myelo-architecture. Although still under validation, SANDI might provide new insight into tissue architecture by introducing a new set of biomarkers of potential great value for biomedical applications and pure neuroscience.
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