Linking spherical mean diffusion weighted signal with intra-axonal volume fraction.

Diffusion MRI has been widely used to assess brain tissue microstructure. However, the conventional diffusion tensor imaging (DTI) is inadequate for characterizing fiber direction or fiber density in voxels with crossing fibers in brain white matter. The constrained spherical deconvolution (CSD) technique has been proposed to measure the complex fiber orientation distribution (FOD) using a single high b-value (b ≥ 3000 s/mm2) to derive the intra-axonal volume fraction (Vin) from the calculated FOD. Recently, the spherical mean technique (SMT) was developed to fit Vin directly from a multi-compartment model with multi-shell b-values. Although different numbers of b-values are needed in the two techniques, both methods have been suggested to be related to the spherical mean diffusion weighted signal (S¯). The current study compared the two techniques on the same high-quality Human Connectome Project diffusion data and investigated the relation between S¯ and Vin systematically. At high b-values (b ≥ 3000 s/mm2), S¯ is linearly related to Vin, and S¯ provides similar contrast with Vin in white matter. At low b-values (b ~ 1000 s/mm2), the linear relation between S¯ and Vin is sensitive to the variations of intrinsic diffusivity. These results demonstrate that S¯ measured with the typical b-value of 1000 s/mm2 is not an indicator of Vin, and previous DTI studies acquired with b = 1000 s/mm2 cannot be re-analyzed to provide Vin-weighted contrast.