Asymmetrical Cerebral Mitochondrial Dysfunction Correlates With Motor Laterality in Parkinson's Disease: A ³¹ Phosphorus Magnetic Resonance Spectroscopy Study

Background 31 P magnetic resonance spectroscopy ( 31 P‐MRS) allows non‐invasive assessment of mitochondrial function by quantifying metabolites of energy and phospholipid metabolism, but the association between these metabolic alterations and motor laterality in Parkinson's disease (PD) remains unknown. Purpose To investigate the association between mitochondrial dysfunction and motor symptom lateralization in PD using 31 P‐MRS. Study Type Retrospective. Population 34 PD patients with left‐sided predominance (LPD; 20 M/14 F), 35 PD patients with right‐sided predominance (RPD; 16 M/19 F), and 43 healthy controls (HCs; 20 M/23 F). Fieldstrength/Sequence 3T; 3D T1‐weighted gradient‐echo and 2D FID‐based chemical shift imaging sequences. Assessment 31 P‐MRS spectra from bilateral putamen, frontal, and temporoparietal cortices were quantified for adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and phosphodiesters (PDE). Metabolite levels were corrected for cerebrospinal fluid (CSF) partial volume effects. Metabolic ratios and laterality indices (LIs) were calculated and correlated with motor symptom LIs. Statistical Tests General linear models, spearman's rank correlation, and receiver operating characteristic (ROC) analysis. p < 0.05 was considered statistically significant. Results RPD patients exhibited significantly elevated ATP (0.181 ± 0.005) and reduced PCr / ATP (0.979 ± 0.033) in the left putamen compared to HCs (0.164 ± 0.004; 1.098 ± 0.030); they also showed a significantly lower frontal PDE LI (−0.069 ± 0.022), higher temporoparietal Pi LI (0.086 ± 0.039), and reduced PCr /Pi LI (−0.106 ± 0.041) relative to LPD patients (−0.019 ± 0.022; −0.075 ± 0.040; 0.047 ± 0.042). In the temporoparietal cortex, the LIs of PCr /Pi ( r = 0.260), PME / PDE ( r = 0.323), and Pi ( r = −0.315) were significantly correlated with the LIs of UPDRS ‐ III scores. The Pi LI in the temporoparietal cortex showed a promising ability to distinguish LPD from RPD patients ( AUC = 0.709). Data Conclusion Asymmetrical mitochondrial dysfunction, detected by 31 P‐MRS, correlates with motor symptom laterality in PD. These metabolic asymmetries may serve as the underlying basis for symptom lateralization. Evidence Level 3. Technical Efficacy Stage 1.