What question did this study set out to answer?

This study aims to assess the feasibility and reliability of semi-automated NM-MRI for measuring substantia nigra volume in early Parkinson's disease.

April 1, 2026Open Access

Semi-Automated Neuromelanin-Sensitive MRI Reveals Substantia Nigra Volume Reduction in Early Parkinson’s Disease with Moderate Diagnostic Performance

Key Points

This study aims to assess the feasibility and reliability of semi-automated NM-MRI for measuring substantia nigra volume in early Parkinson's disease.
Conducted a prospective case-control study involving 50 participants (25 PD patients and 25 healthy controls).
Utilized 3T neuromelanin-sensitive MRI with a T1-weighted spin-echo sequence for imaging.
Performed semi-automated segmentation of the substantia nigra using Mango software and normalized for intracranial volume.
Used statistical analyses including ROC analysis and intraclass correlation coefficients to assess reliability.
Significantly reduced corrected substantia nigra volume in PD patients (18% reduction, p = 0.039).
High agreement observed between semi-automated and manual segmentation (ICC = 0.945).
Moderate discriminative performance found for corrected volume with AUC = 0.700 (sensitivity 68.4%, specificity 74.1%).
No significant correlation found between volume and motor scores, but a trend noted toward lower volumes with advanced H&Y stages.

Abstract

Background: Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, accompanied by neuromelanin loss. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) enables in vivo visualization of these changes; however, its diagnostic and clinical utility remains incompletely defined. This study evaluated the feasibility, reliability, and biological sensitivity of semi-automated NM-MRI–based substantia nigra volumetry in PD. Methods: In this prospective case–control study, 50 participants (25 PD patients and 25 healthy controls) underwent 3T NM-sensitive MRI using a high-resolution T1-weighted spin-echo sequence. Semi-automated segmentation of hyperintense substantia nigra regions was performed using Mango v3.5.1, with intracranial volume normalization derived from FreeSurfer v7.3. Four participants were excluded due to motion artifacts, yielding a final cohort of 46 subjects. Clinical assessment included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III and Hoehn and Yahr (H p = 0.039, Mann–Whitney U test). Semi-automated measurements demonstrated excellent agreement with manual segmentation (ICC = 0.945). ROC analysis showed moderate discriminative performance for corrected volume (AUC = 0.700; sensitivity 68.4%, specificity 74.1%). No significant correlation was observed between corrected substantia nigra volume and UPDRS-III motor scores, while a trend toward lower SNc volume was observed with advancing H&Y stage. Conclusions: Semi-automated NM-MRI volumetry detects biologically meaningful substantia nigra volume loss in early-stage Parkinson’s disease with high measurement reliability. However, diagnostic performance was moderate and insufficient for standalone clinical diagnosis or motor severity prediction. These findings support the role of NM-MRI as a complementary imaging marker within multimodal diagnostic and research frameworks rather than as an independent diagnostic tool.

Semi-Automated Neuromelanin-Sensitive MRI Reveals Substantia Nigra Volume Reduction in Early Parkinson’s Disease with Moderate Diagnostic Performance

Key Points

Abstract

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