Simultaneously imaging protein aggregation and iron in patients with synucleinopathies using sub-voxel magnetic susceptibility imaging

Motivation: Synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA), are neurodegenerative disorders marked by the abnormal accumulation of α-synuclein protein and iron in the brain. Goal(s): This study investigates the simultaneous in vivo imaging of iron and proteins in deep brain matter (DGM). Approach: We employed the proposed sub-voxel QSM method to simultaneously quantify paramagnetic iron and diamagnetic α-synuclein in Synucleinopathies. Results: We confirmed the diamagnetism of α-synuclein and observed an increase in paramagnetic and diamagnetic concentration in DGMs, suggesting higher presence of α-synuclein and iron deposition in both PD and MSA than HCs, indicating consistent α-synuclein deposition in synucleinopathies. Impact: This study confirms that diamagnetic signals reconstructed through sub-voxel QSM can measure α-synuclein aggregation in the brains of synucleinopathy patients. Our preliminary findings indicate that sub-voxel QSM holds significant promise as an MRI technique for monitoring neurodegeneration in synucleinopathies.