Susceptibility and diffusion MRI biomarkers predict development of Parkinsonism in iRBD

Quantitative MRI techniques, including quantitative susceptibility mapping (QSM) and diffusion tensor imaging (DTI), may detect early neurodegenerative changes in ɑ-synucleinopathies, especially within the midbrain. This study evaluated their potential to predict phenoconversion to overt synucleinopathy in 79 patients with isolated REM sleep behavior disorder (iRBD) followed annually over 5.6 ± 3.0 years. Phenoconversion, defined by emergence of parkinsonism or dementia, occurred in 21 patients. Baseline QSM and DTI data were analyzed to identify regional brain differences, revealing increased magnetic susceptibility and fractional anisotropy (FA) in the bilateral cerebral peduncle of phenoconverters. Increased magnetic susceptibility and FA within this region were associated with higher phenoconversion risk (FA: hazard ratio (HR) = 1.84, susceptibility: HR = 1.67). Their combined score predicted phenoconversion with accuracy similar to dopamine-transporter imaging (HR 2.58 vs 2.85). Findings suggest that increased susceptibility and FA in the cerebral peduncle may serve as biomarkers of early phenoconversion, potentially reflecting compensatory neuroplastic changes in subthalamo-pallidal pathways.