Objective: To quantify associations between neuromelanin-sensitive MRI (NM-MRI) metrics and clinical severity and cumulative disease burden markers in Parkinson’s disease (PD).

Background: NM-MRI visualises neuromelanin-containing catecholaminergic nuclei that degenerate in PD, namely the substantia nigra (SN) and locus coeruleus (LC), providing a biologically grounded structural index of dopaminergic and noradrenergic integrity. However, associations with clinical severity and disease burden have not been systematically quantified.

Method: A PRISMA-compliant systematic review and meta-analysis of PD studies reporting NM-MRI associations with clinical outcomes was performed. Random-effects models pooled correlations with motor severity (UPDRS-III/MDS-UPDRS-III), disease duration, Hoehn and Yahr (H&Y) stage, and levodopa equivalent daily dose (LEDD). Sensitivity analyses imputing r=0 for unreported null effects evaluated robustness. Studies also contributed to qualitative synthesis exploring anatomical specificity, domain-specific motor and non-motor patterns, longitudinal change, and multimodal integration.

Results: Thirty-nine studies (N=3,382; PD=2,009) were included. The motor meta-analysis showed a moderate inverse association between nigral NM integrity and motor severity (r=−0.399), stronger for UPDRS-III (r=−0.453) than MDS-UPDRS-III (r=−0.272). NM-MRI correlated inversely with disease duration (r=−0.414), H&Y stage (r=−0.336), and LEDD (r=−0.367) (all p<0.001), with sensitivity analyses confirming directionally consistent findings. SN metrics most consistently tracked motor severity, with hemispheric and subregional patterns reflecting laterality and phenotype. LC measures showed weaker motor but consistent non-motor associations. Longitudinal studies demonstrated annual NM decline (~5–19%). Multimodal evidence indicated complementary value when integrated with dopaminergic, iron-sensitive, or diffusion imaging.

Conclusion: NM-MRI is an in vivo marker of structural neurodegeneration closely aligned with disease pathophysiology. SN metrics primarily reflect motor system degeneration and disease stage, whereas LC measures delineate non-motor domains, supporting functional dissociation within catecholaminergic systems. Collectively, these findings position NM-MRI as a clinically relevant biomarker, with translational advancement dependent on harmonised acquisition and longitudinal validation.

NM Integrity and Clinical Measures Overview

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuromelanin-sensitive-mri-as-a-marker-of-clinical-severity-and-disease-burden-in-parkinsons-disease/