This study applies multiparametric MRI (R1, R2*, proton density, MTsat) to identify cortical microstructural differences in Parkinson's patients versus controls and links regional imaging changes to motor severity, levodopa dose, and cognitive impairment.

Although it does not identify therapeutic mechanisms, the paper establishes MPM as a sensitive, biologically informed noninvasive biomarker for cortical pathology and disease progression that can aid patient stratification and outcome measurement in PD therapeutic development.

Parkinson's disease (PD) is a progressive neurodegenerative disease caused by the loss of dopaminergic neurons; however, growing evidence indicates the widespread involvement of cortical regions underlying motor and non-motor symptoms. In this study, we evaluated multiparametric mapping (MPM) as a non-invasive imaging technique for the detection of microstructural brain alterations in PD. We assessed 31 patients with idiopathic PD (PwPD) and 68 healthy controls (HCs) utilizing MPM-derived longitudinal relaxation rate (R1), effective transverse relaxation rate (R2*), proton density, and magnetic transfer saturation (MTsat). We performed a whole-brain voxel-based quantification (VBQ) and multiple linear regression analysis to assess group differences and associations with the clinical phenotype. Lower MTsat within the left superior frontal gyrus (SFG) predicted motor symptom severity in PwPD, while higher R2* values in the right SFG were associated with higher levodopa-equivalent daily dose. Higher R2* values in the posterior cingulate gyrus and lower proton density in the left superior parietal lobule were associated with a stronger cognitive impairment in PwPD. Additionally, numerous clusters presented with group differences across multiple MPM modalities, including the supplementary motor area and cingulate cortex. Overall, we successfully replicated previously documented cortical microstructural changes in PwPD, presenting MPM as a sensitive tool for the detection of disease-specific alterations. This study further underscores the utility of MPM for monitoring disease progression through biologically informed measures, opening avenues for further research.