Simultaneous Increase of Mean Susceptibility and Mean Kurtosis in the Substantia Nigra as an MRI Neuroimaging Biomarker for Early-Stage Parkinson's Disease: A Systematic Review and Meta-Analysis

Background Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early detection is crucial for treatment and slowing disease progression. Hypothesis Simultaneous alterations in mean susceptibility (MS) from quantitative susceptibility mapping (QSM) and mean kurtosis (MK) from diffusion kurtosis imaging (DKI) can serve as reliable neuroimaging biomarkers for early-stage PD (ESPD) in the basal ganglia nuclei, including the substantia nigra (SN), putamen (PUT), globus pallidus (GP), and caudate nucleus (CN). Study Type Systematic review and meta-analysis. Population One hundred eleven patients diagnosed with ESPD and 81 healthy controls (HCs) were included from four studies that utilized both QSM and DKI in both subject groups. Field Strength/Sequence Three-dimensional multi-echo gradient echo sequence for QSM and spin echo planar imaging sequence for DKI at 3 Tesla. Assessment A systematic review and meta-analysis using PRISMA guidelines searched PubMed, Web of Science, and Scopus. Statistical Tests Random-effects model, standardized mean difference (SMD) to compare MS and MK between ESPD patients and HCs, I2 statistic for heterogeneity, Newcastle-Ottawa Scale (NOS) for risk of bias, and Egger's test for publication bias. A P-value <0.05 was considered significant. Results MS values were significantly higher in SN (SMD 0.72, 95% CI 0.31 to 1.12), PUT (SMD 0.68, 95% CI 0.29 to 1.07), and GP (SMD 0.53, 95% CI 0.19 to 0.87) in ESPD patients compared to HCs. CN did not show a significant difference in MS values (P = 0.15). MK values were significantly higher only in SN (SMD = 0.72, 95% CI 0.16 to 1.27). MK values were not significantly different in PUT (P = 1.00), GP (P = 0.97), and CN (P = 0.59). Studies had high quality (NOS 7-8) and no publication bias (P = 0.967). Data Conclusion Simultaneous use of MS and MK may be useful as an early neuroimaging biomarker for ESPD detection and its differentiation from HCs, with significant differences observed in the SN. Evidence Level2 Technical Efficacy Stage 2