Background Diffusion Tensor Imaging provides indirect information about the quality of the microstructural organisation of tissues. In this longitudinal study, cross-sectional as well as time-related changes of diffusion measures were assessed in (premanifest) Huntington’s disease using automated histogram analysis.

Methods Twenty-two premanifest (preHD), 10 manifest Huntington’s disease (HD) and 24 healthy control subjects completed scans at baseline and two year follow-up. Stratification of preHD into a far (preHD-A) and near (preHD-B) to predicted disease onset group was performed. Age-corrected histograms of whole brain white matter (WM), grey matter (GM) and striatal diffusion measures were computed and normalised by the number of voxels in each subject’s data set.

Results Higher cross-sectional mean, axial and radial diffusivities were found in both WM and GM in HD compared to preHD and controls (p ≤ 0.001). In preHD, WM axial diffusivity was higher than in controls and lower than in HD (p ≤ 0.01). This finding remained valid only in preHD-B (p ≤ 0.001). Axial diffusivity was also found to be higher in the striatum of preHD-B compared to controls and preHD-A (p ≤ 0.01). No longitudinal differences in diffusivity measures between the groups were found.

Conclusions Alterations in cross-sectional diffusion profiles between HD subjects and controls were evident, both in whole brain and striatum. In preHD, only axial diffusivity alterations were found, a finding that applied only to preHD-B upon group stratification. This suggests that axial diffusivity is a sensitive marker for early change in HD prior to disease manifestation. The individual eigenvalues were superior to fractional anisotropy in revealing pathologic microstructural brain alterations. No longitudinal differences were found in any of the diffusivity measures between the groups.