Free water and iron content in the substantia nigra at different stages of Parkinson's disease

Abnormalities in free water (FW) and susceptibility values exist in the substantia nigra (SN) of patients with Parkinson's disease (PD), but their role in characterizing the disease processes remains uncertain. This study investigated these values at various SN locations and stages of PD, and their relationship with clinical symptoms.FW and quantitative susceptibility mapping (QSM) values were evaluated in the anterior and posterior SN, along with swallow-tail-sign (STS) ratings, in patients with PD (early-stage: n = 39; middle-to-advanced-stage: n = 97) and healthy controls (n = 82). The correlation between these indices and motor and non-motor symptoms, and their capability to distinguish PD from healthy controls, were also examined.Increased FW in the anterior and posterior SN and increased QSM values in the posterior SN were observed in both early-stage and middle-to-advanced-stage PD patients (p < 0.05). However, there was no significant difference in FW, QSM values, or STS ratings among patients at different stages. FW and QSM values correlated with motor symptoms in middle-to-advanced-stage patients (p < 0.05), while STS ratings were associated with non-motor symptoms (p < 0.05). Additionally, combining FW and QSM values in the posterior SN with STS ratings in logistic regression showed better performance in distinguishing PD (area under curve = 0.931) compared to using STS ratings alone (area under curve = 0.880).Findings suggest elevated FW and iron content in PD at different stages, with dissociation in SN location between the two indices. Elevated signals are related to the motor symptom severity in middle-to-advanced-stage patients, and may have the potential for PD diagnosis and symptom assessment.