Glutamate chemical exchange saturation transfer imaging reveals cerebellar glutamatergic alterations in Parkinson's disease subtypes.

Glutamate accumulation linked to Parkinson's disease (PD) pathogenesis. While glutamate chemical exchange saturation transfer (GluCEST) imaging has been applied in various CNS disorders, its utility in PD remains underexplored. This study investigated the clinical relevance of dentate nucleus and cerebellar hemisphere glutamate levels across PD motor subtypes. We enrolled 36 resting-tremor predominant PD (PDRT), 33 akinetic-rigid predominant PD (PDAR), and 40 healthy controls (HCs). GluCEST data were quantified via magnetization-transfer-ratio asymmetry (MTRasym) analysis, with four regions of interest (ROIs) manually delineated. Cerebellar volumetry was derived using the SUIT atlas. Results demonstrated significantly elevated MTRasym values in the dentate nucleus and cerebellar hemisphere of PDRT patients (*p*<0.05), indicative of increased glutamate concentrations. Concurrently, PDRT exhibited reduced cerebellar volumes compared to HCs, whereas PDAR showed no significant volumetric differences. These findings establish GluCEST as a sensitive, non-invasive biomarker for cerebellar glutamatergic pathology in PD. The subtype-specific metabolic disturbances imply distinct etiological mechanisms underlying tremor-dominant and akinetic-rigid phenotypes.