Histogram analysis of DTI-derived indices reveals pontocerebellar degeneration and its progression in SCA2

To assess the potential of histogram metrics of diffusion-tensor imaging (DTI)-derived indices in revealing neurodegeneration and its progression in spinocerebellar ataxia type 2 (SCA2).

Nine SCA2 patients and 16 age-matched healthy controls, were examined twice (SCA2 patients 3.6±0.7 years and controls 3.3±1.0 years apart) on the same 1.5T scanner by acquiring T1-weighted and diffusion-weighted (b-value = 1000 s/mm2) images. Cerebrum and brainstem-cerebellum regions were segmented using FreeSurfer suite. Histogram analysis of DTI-derived indices, including mean diffusivity (MD), fractional anisotropy (FA), axial (AD) / radial (RD) diffusivity and mode of anisotropy (MO), was performed.

At baseline, significant differences between SCA2 patients and controls were confined to brainstem-cerebellum. Median values of MD/AD/RD and FA/MO were significantly (p<0.001) higher and lower, respectively, in SCA2 patients (1.11/1.30/1.03×10(-3) mm2/s and 0.14/0.19) than in controls (0.80/1.00/0.70×10(-3) mm2/s and 0.20/0.41). Also, peak location values of MD/AD/RD and FA were significantly (p<0.001) higher and lower, respectively, in SCA2 patients (0.91/1.11/0.81×10(-3) mm2/s and 0.12) than in controls (0.71/0.91/0.63×10(-3) mm2/s and 0.18). Peak height values of FA and MD/AD/RD/MO were significantly (p<0.001) higher and lower, respectively, in SCA2 patients (0.20 and 0.07/0.06/0.07×10(-3) mm2/s/year /0.07) than in controls (0.15 and 0.14/0.11/0.12/×10(-3) mm2/s/year /0.09). The rate of change of MD median values was significantly (p<0.001) higher (i.e., increased) in SCA2 patients (0.010×10(-3) mm2/s/year) than in controls (-0.003×10(-3) mm2/s/year) in the brainstem-cerebellum, whereas no significant difference was found for other indices and in the cerebrum.

Histogram analysis of DTI-derived indices is a relatively straightforward approach which reveals microstructural changes associated with pontocerebellar degeneration in SCA2 and the median value of MD is capable to track its progression.