A Multi-sequence MRI Study in Parkinson's Disease: Association Between Rigidity and Myelin

Background The pathophysiology of rigidity in Parkinson's disease (PD) is poorly understood. Multi-sequence functional and structural brain MRI may further clarify the origin of this clinical characteristic. Purpose To examine both joint and unique relationships of MRI-based functional and structural imaging modalities to rigidity and other clinical features of PD. Study Type Retrospective cross-sectional study. Population 31 PD subjects (aged 68.0 +/- 5.9 years, 21 males) with average disease duration 9.3 +/- 5.4 years. Field Strength/Sequence Multi-echo GRASE, diffusion-weighted echo planar imaging (EPI), and blood oxygen level dependent contrast EPI T2*-weighted sequences on a 3T scanner. Assessment Myelin water fraction (MWF) and fractional anisotropy (FA) of 20 white-matter regions of interest (ROIs), and functional connectivity derived from resting-state fMRI among 56 ROIs were assessed. The Unified Parkinson's Disease Rating Scale-Part III, Montreal Cognitive Assessment, Beck Depression Index, and Apathy Rating Scales were used to assess motor and non-motor symptoms. Statistical Tests Multiset canonical correlation analysis (MCCA) and canonical correlation analysis (CCA) were utilized to examine the joint and unique relationships of multiple imaging measures with clinical symptoms of PD. A permutation test was used to determine statistical significance (P < 0.05). Results MCCA revealed a single significant component jointly linking MWF, FA, and functional connectivity to age, bradykinesia, and leg agility, non-motor symptoms of cognition, depression, and apathy, but not rigidity (P = 0.77), tremor (P = 0.50 and 0.67 on the left and right side), or sex (P = 0.54). After controlling for this joint component, CCA found a unique significant association between MWF and rigidity, but no other associations were detected, including with FA (P = 0.87). Data Conclusion MWF, FA, and functional connectivity can serve as multi-sequence imaging markers to characterize many PD symptoms. However, rigidity in PD is additionally associated with widespread myelin changes. Evidence Level 4 Technical Efficacy Stage 3