SANDI: A compartment-based model for non-invasive apparent soma and neurite imaging by diffusion MRI

TLDR

Current diffusion‑MRI microstructure models treat white‑matter water as restricted diffusion in neurites and gray‑matter water as a mixture of extra‑cellular and soma water, accurately describing data up to b≈3,000 s/mm² but failing at higher b‑values. This study proposes SANDI, a compartment‑based model that explicitly includes soma of all brain cell types to explain the high‑b failure. Using numerical simulations and high‑b DW‑MRI data from mice (bmax = 40,000 s/mm²) and humans (bmax = 10,000 s/mm²), the authors evaluate how soma size and density influence the direction‑averaged signal. SANDI yields new contrasts that map soma and neurite fractions, closely matching histological cyto‑ and myelo‑architecture in 25 healthy subjects and offering promising biomarkers for biomedical and neuroscience research.

Abstract

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.