R2* relaxometry analysis for mapping of white matter alteration in Parkinson's disease with mild cognitive impairment

Background: R2* relaxometry analysis combined with quantitative susceptibility mapping (QSM), which has high sensitivity to iron deposition, can distinguish microstructural changes of the white matter (WM) and iron deposition, thereby providing a sensitive and biologically specific measure of the WM owing to the changes in myelin and its surrounding environment. This study aimed to explore the microstructural WM alterations associated with cognitive impairment in patients with Parkinson's disease (PD) using R2* relaxometry analysis combined with QSM. Materials and methods: We enrolled 24 patients with PD and mild cognitive impairment (PD-MCI), 22 patients with PD and normal cognition (PD-CN), and 19 age- and sex-matched healthy controls (HC). All participants underwent Montreal Cognitive Assessment (MoCA) and brain magnetic resonance imaging, including structural three-dimensional T1-weighted images and multiple spoiled gradient echo sequence (mGRE). The R2* and susceptibility maps were estimated from the multiple magnitude images of mGRE. The susceptibility maps were used for verifying iron deposition in the WM. The voxel-based R2* of the entire WM and its correlation with cognitive performance were analyzed. Results: In the voxel-based group comparisons, the R2* in the PD-MCI group was lower in some WM regions, including the corpus callosum, than R2* in the PD-CN and HC groups. The mean susceptibility values in almost all brain regions were negative and close-to-zero values, indicating no detectable paramagnetic iron deposition in the WM of all subjects. There was a significant positive correlation between R2* and MoCA in some regions of the WM, mainly the corpus callosum and left hemisphere. Conclusion: R2* relaxometry analysis for WM microstructural changes provided further biologic insights on demyelination and changes in the surrounding environment, supported by the QSM results demonstrating no iron existence. This analysis highlighted the potential for the early evaluation of cognitive decline in patients with PD.