MRI biomarkers to assess substantia nigra damage in idiopathic REM sleep behavior disorder.

Abstract Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in iRBD patients. We aimed to quantify SN damage in iRBD patients using multimodal MRI and to determine biomarker efficacy in preclinical Parkinsonism. Nineteen patients with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging and T2* mapping. Regions of interest in the SN area were drawn in NM-sensitive and T2-weighted images. The volume and normalized signal intensity in NM-sensitive images, R2* and diffusion tensor measures were quantified in the SN. Additionally, 2 raters performed visual analysis of the SN using the NM-sensitive images. Patients with iRBD showed a reduction in the NM-sensitive volume and signal intensity and a decrease in fractional anisotropy (FA) versus controls but showed no differences in axial, radial or mean diffusivity or in R2*. For NM-sensitive volume and signal intensity, the ROC analysis discriminated between iRBD patients and controls with a diagnostic accuracy of 0.86 and 0.79, respectively, whereas the accuracy was 0.77 for FA. The 3 biomarkers had a combined accuracy of 0.92. The fraction of subjects correctly characterized by visual assessment was 0.81. NM-sensitive imaging and FA allowed for the detection of SN damage in iRBD patients with good diagnostic accuracy. These measures may represent valuable biomarkers for prodromal Parkinsonism.