Creatine-weighted imaging in patients with Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder involving impaired bioenergetics and mitochondrial dysfunction. Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted therapy, yet human studies have yielded heterogeneous results. This study employs guanidino chemical exchange saturation transfer (GuanCEST) magnetic resonance imaging (MRI), a novel Cr-weighted imaging technique, to evaluate Cr level changes in patients with PD (PwPD) compared to healthy controls (HCs).

25 PwPD and 24 age- and sex-matched HCs underwent standardized clinical assessments and GuanCEST MRI. Region-of-interest (ROI) and voxel-wise analyses were conducted to assess group differences. Kendall's correlation and ANCOVA were used to explore associations between GuanCEST signals, disease presence, and clinical severity.

GuanCEST signals in the caudate nucleus were significantly lower in PwPD (1.67 ± 0.26%) than in HCs (1.82 ± 0.16%; p = 0.023). Signal reduction correlated with increasing PD severity, particularly in thalamic subregions. In the internal medullary lamina, GuanCEST values negatively correlated with MDS-UPDRS-III scores (r = -0.44, p = 0.03) and a trend was also seen in the lateral thalamic nuclei (r = -0.39, p = 0.06). ANCOVA indicated GuanCEST values in the internal medullary lamina decreased by ∼0.01% per point increase in MDS-UPDRS-III (p = 0.007), adjusted for age and sex.

GuanCEST MRI shows promise as a non-invasive tool for detecting Cr alterations in PD. This technique may enhance our understanding of Cr metabolism in PD and support the development of targeted therapeutic strategies.