Creatine-weighted imaging in patients with Parkinson’s disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder featured impaired bioenergetics and mitochondrial dysfunction. Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted treatment strategy; however, clinical outcomes remain inconsistent despite encouraging preclinical findings. The lack of methods to measure Cr distribution in the human brain may hinder the investigation. This study utilized a novel neuroimaging technique, guanidino chemical exchange saturation transfer (GuanCEST) MRI, to assess regional Cr levels in patients with PD (PwPD) and healthy controls (HCs). Twenty-five patients with PD and 24 age- and sex-matched HCs were enrolled. GuanCEST values in the caudate nucleus were significantly lower in PwPD (1.67 ± 0.26%) than HCs (1.82 ± 0.16%), p = 0.023. Moreover, GuanCEST signal reductions correlated with increasing PD severity, particularly in thalamic subregions. Kendall's correlation revealed a significant negative correlation between GuanCEST values in the internal medullary lamina and MDS-UPDRS-III scores (r = -0.44, p = 0.03). Regional ANCOVA further indicated that GuanCEST values in this region decreased by approximately 0.01% per unit increase in MDS-UPDRS-III (p = 0.007), adjusted for age and sex. These findings highlight GuanCEST MRI's potential as a noninvasive biomarker of Cr metabolism in PD, offering insights into disease mechanisms, therapeutic optimization, and clinical trial designs.