Beyond Parkinson's Disease: A Narrative Review of Neuromelanin MRI in Neurodegenerative Diseases.

BACKGROUND AND PURPOSE: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is an emerging noninvasive biomarker of catecholaminergic neurons. It assesses neuromelanin-rich regions such as the substantia nigra pars compacta (SNc) and locus coeruleus (LC). Although initially developed for Parkinson's disease (PD), evidence supports broader utility. This narrative review highlights the diagnostic and prognostic applications of NM-MRI in PD, atypical parkinsonian syndromes, spinocerebellar ataxias (SCA), and Alzheimer's disease (AD), while evaluating methodological heterogeneity, diagnostic performance across diseases, and directions for clinical implementation.

RESULTS

In PD, reduced SNc volume and contrast-to-noise ratio (CNR) correlate with motor symptom severity. Early-stage PD shows lateral SNc signal attenuation progressing ventromedially with disease advancement. NM-MRI sensitivity and specificity range from 70%-92% to 65%-89%, respectively, with higher accuracy at 7T. In progressive supranuclear palsy (PSP), SNc degeneration is more pronounced medially; LC contrast ratio (CR) is elevated compared to PD. In multiple system atrophy (MSA), LC signal attenuation is particularly marked in the parkinsonian subtype (MSA-P). NM-MRI findings in SCA (notably SCA2 and SCA7) vary by genotype; AD is characterized by reduction in the middle and caudal segments of LC, reflecting early tau pathology. NM-MRI LC signal reduction variably correlates with cognitive scores and Braak staging, suggesting potential as a preclinical biomarker.

CONCLUSION

NM-MRI holds promise for early diagnosis and monitoring of neurodegenerative diseases. While its role in PD is well established, emerging data in PSP, MSA, SCA, and AD suggest wider applicability. Standardization, multimodal imaging integration, and machine learning are critical for clinical translation.