Altered Nigral Amide Proton Transfer Imaging Signal Concordant With Motor Asymmetry in Parkinson's Disease: A Multipool CEST MRI Study

Asymmetry is a natural characteristic of Parkinson's disease (PD), which can be used to distinguish PD from atypical parkinsonism. Chemical exchange saturation transfer (CEST) has demonstrated value in reflecting the subtle changes related to neuron loss and abnormal protein accumulation in PD but has not been used to investigate asymmetry in PD. This study aimed to examine asymmetrical changes in the mesencephalic nucleus of PD patients with motor asymmetry using four-pool CEST analysis and to explore the relationship between imaging asymmetry and motor asymmetry. Forty-six PD cases with motor asymmetry (PD_MA) and 23 normal controls (NC) were included. The patients were divided into three subgroups based on their conditions: PD with mild motor asymmetry (PD_MMA), PD with severe motor asymmetry (PD_SMA), and hemiparkinsonism (PD_Hemi). Differences among the more affected and less affected sides of cases in various PD subgroups and the NC group were analyzed. Motor laterality and imaging laterality were determined to evaluate the concordance. Motor asymmetry and imaging asymmetry indexes were calculated to evaluate the correlation. Compared with NC, amide proton transfer (APT) was significantly decreased in the more affected sides of substantia nigra (SN) and red nucleus in the PD_MA, PD_SMA, and PD_Hemi groups. In the PD-SMA group, the APT signal in the SN was significantly reduced in the more affected side compared with the less affected side. The imaging asymmetry index in APT for the SN was positively associated with the motor asymmetry index in the PD_SMA group (β = 0.431, p = 0.014). The imaging laterality in APT for the SN had a significant consistency with motor laterality in the PD_SMA group (κ = 0.566, p = 0.001). These findings suggest inherent asymmetry of APT signal in the SN in PD patients with severe asymmetry, with nigral APT potentially serving as a noninvasive biomarker of lateralization in PD.