Fractional Anisotropy and Mean Diffusion as Measures of Dopaminergic Function in Parkinson's Disease: Challenging Results.

BACKGROUND: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson's disease.

OBJECTIVE: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT.

METHODS: One-hundred and eleven patients with Parkinson's disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13). Four equipment combinations of MRI scanners/SPECT gamma cameras were used during the study. Data from each combination were analyzed separately. Regions-of-interest were outlined in the substantia nigra (three subareas, DTI only) and in the striatum (putamen and caudate). Side differences and bilateral averages were correlated using linear regression. The significance threshold was set at P < 0.001 and 0.001 < P< 0.05 was defined as a trend towards significance.

RESULTS: For side differences, no significant correlations were observed, but in patients, there was a trend towards a negative correlation between MD in the middle nigra and putaminal DAT uptake in two combinations (P = 0.04 and P = 0.03). For averages, in patients, striatal MD correlated negatively with striatal DAT uptake in one combination (P = 0.0005) and trended towards negative correlations with striatal D2R uptake (one combination, P = 0.03) and with the sum of striatal DAT and D2R uptake (two combinations P = 0.002 and P = 0.03). FA showed no correlations in patients, and no correlations were found in controls.

CONCLUSIONS: The poor correlations between MD and dopamine activity -and absent correlations for FA - imply that additional diffusion measures must be developed to reliably assess the dopaminergic degeneration in Parkinson's disease.