Triple diffusion encoding MRI predicts intra-axonal and extra-axonal diffusion tensors in white matter

Purpose: To demonstrate how triple diffusion encoding (TDE) MRI can be applied to separately estimate the intra-axonal and extra-axonal diffusion tensors in white matter (WM). Methods: Using a TDE pulse sequence with an axially symmetric b-matrix, diffusion MRI data were acquired at 3T for 3 healthy adults with an axial b-value of 4000 s/mm², a radial b-value of 307 s/mm², and 64 diffusion encoding directions. This acquisition was then repeated with the radial b-value set to 0. A previously proposed theory was applied to these data in order to estimate the intra-axonal diffusivity and axonal water fraction for each WM voxel. Conventional single diffusion encoding data were also obtained with b-values of 1000 and 2000 s/mm², which provided additional information sufficient for determining both the intra-axonal and extra-axonal diffusion tensors. Results: From the TDE data, the average intra-axonal diffusivity in WM was found to be 2.24 ± 0.18 µm²/ms, and the average axonal water fraction was found to be 0.60 ± 0.11. From the 2 diffusion tensors, average WM values were estimated for several compartment-specific diffusion parameters. In particular, the extra-axonal mean diffusivity was 1.09 ± 0.19 µm²/ms, the intra-axonal fractional anisotropy was 0.50 ± 0.14, and the extra-axonal fractional anisotropy was 0.23 ± 0.13. Conclusion: By using a simple TDE pulse sequence with an axially symmetric b-matrix, the diffusion tensors for the intra-axonal and extra-axonal spaces can be separately estimated in adult WM. This allows one to determine compartment-specific diffusion properties for these 2 water pools.