PURPOSE: Patients with CO intoxication were demonstrated to exhibit white matter (WM) injuries, changes in substantia nigra, dopamine transporter dysfunctions of striatum and Parkinsonism symptoms. We aimed to investigate the relationship between WM injuries of dopaminergic pathways and dopamine transporter dysfunctions of the striatum in patients with acute CO intoxication using both diffusion kurtosis imaging (DKI) and single photon-emission computed tomography (SPECT). MATERIALS AND METHODS: Seventeen patients with acute CO intoxication and 19 age- and gender-matched healthy subjects were enrolled. DKI data were acquired from all participants and Tc-99m-TRODAT-1 SPECT scan was performed on each patient. DKI datasets were fitted to obtain axial, radial and mean diffusivity, fractional anisotropy, axial, radial and mean kurtosis for voxel-based comparison. In addition, the TRODAT-1 binding ratio of the striatum was calculated using the occipital cortices as a reference. In significant regions, correlational analysis was performed to understand the relationship between DKI indices and TRODAT-1 binding ratio. RESULTS: The results showed that DKI indices were significantly altered in multiple WM regions broadly involving the basal ganglia-thalamocortical circuit and nigrostriatal pathway. The correlation analysis further revealed significant correlations between DKI indices and the TRODAT-1 binding ratio in the nigrostriatal pathway (absolute correlation coefficients ranged from 0.5992 to 0.6950, p<0.05), suggesting that CO-induced early WM injuries were associated with dopamine transporter dysfunctions of striatum. CONCLUSION: We concluded that DKI and Tc-99m-TRODAT-1 SPECT scans were helpful in early detection of global WM injuries associated with dysfunctions of dopamine transporter in patients with acute CO intoxication. KEY POINTS: • Voxel-based diffusion kurtosis imaging analysis was helpful in globally detecting early white matter injuries in patients with acute CO intoxication. • CO-induced early white matter injuries were broadly located in basal ganglia-thalamocortical circuit and nigrostriatal pathway. • Early white matter injuries in dopaminergic pathways were significantly correlated with dopamine transporter dysfunctions of the striatum.