Subregional neuromelanin-sensitive MRI of the substantia nigra is associated with striatal dopaminergic function in early-stage Parkinson's disease

Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) enables radiation-free assessment of nigral dopaminergic integrity in Parkinson's disease (PD), but its quantitative relationship with striatal dopaminergic function has not been well established. We therefore investigated whether NM-MRI-derived volumes of the substantia nigra pars compacta (SNpc) are associated with striatal dopamine transporter availability measured by 18 F-FP-CIT positron emission tomography (PET) in early-stage PD. In this retrospective study, consecutive patients with early-stage PD who underwent both NM-MRI and 18 F-FP-CIT PET between October 2021 and May 2023 were identified, and those with an inter-scan interval exceeding 90 days were excluded. NM-MRI-derived volumes of the associative, limbic, and sensorimotor SNpc subregions were quantified, and striatal dopaminergic function was assessed as specific binding ratios (SBRs) of the ventral and dorsal striatum, striatal mean standardized uptake value, striatal volume, and total dopamine transporter activity. Univariate and multivariable linear regression models incorporating subregion volume, age, and sex were used to relate SNpc subregion volumes to PET measures. Among 136 patients (mean age, 67.5 ± 9.0 years; 81 men [59.6%]), the limbic subregion showed the strongest associations with all 18 F-FP-CIT PET measures, with the greatest explanatory power for ventral striatal SBR ( R 2 = 0.276, p < 0.001) and dorsal striatal SBR ( R 2 = 0.225, p < 0.001). Multivariable models incorporating limbic subregion volume, age, and sex yielded adjusted R 2 values of 0.472 and 0.318 for ventral and dorsal striatal SBRs, respectively, with limbic subregion volume remaining independently associated with both models ( p < 0.001). In repeated 5-fold cross-validation, these models yielded cross-validated R 2 values of 0.449 and 0.287, respectively, and were higher than those of corresponding models based on whole-SNpc volume. These findings suggest that limbic SNpc subregion volume on NM-MRI is associated with striatal dopaminergic function in early-stage PD, supporting NM-MRI as a radiation-free complement to dopamine transporter PET.