Contrast and stability of the axon diameter index from microstructure imaging with diffusion MRI

The ActiveAx technique fits the minimal model of white matter diffusion to diffusion MRI data acquired using optimized protocols that provide orientationally invariant indices of axon diameter and density. We investigated how limitations of the available maximal gradient strength (G(max)) on a scanner influence the sensitivity to a range of axon diameters. Multishell high-angular-diffusion-imaging (HARDI) protocols for G(max) of 60, 140, 200, and 300 mT/m were optimized for the pulsed-gradient-spin-echo (PGSE) sequence. Data were acquired on a fixed monkey brain and Monte-Carlo simulations supported the results. Increasing G(max) reduces within-voxel variation of the axon diameter index and improves contrast beyond what is achievable with higher signal-to-noise ratio. Simulations reveal an upper bound on the axon diameter (∼10 μm) that pulsed-gradient-spin-echo measurements are sensitive to, due to a trade-off between short T(2) and the long diffusion time needed to probe larger axon diameters. A lower bound (∼2.5 μm) slightly dependent on G(max) was evident, below which axon diameters are identifiable as small, but impossible to differentiate. These results emphasize the key-role of G(max) for enhancing contrast between axon diameter distributions and are, therefore, relevant in general for microstructure imaging methods and highlight the need for increased G(max) on future commercial systems.