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Neuromelanin imaging outperforms free water imaging in diagnosing early Parkinson’s disease: a comparative MRI study

Jan. 2026

Background and Objectives:

Early and accurate diagnosis of Parkinson's disease (PD) remains challenging due to reliance on clinical assessment of motor symptoms, which underscores the need for accurate and objective diagnostic methods ; in this context, neuromelanin (NM)-sensitive MRI serves as a crucial diagnostic pillar by non-invasively assessing the loss of dopaminergic neurons in the substantia nigra , and therefore, this study aimed to provide a harmonized head-to-head comparison of NM-MRI and free water (FW) imaging to evaluate their relative diagnostic utility in the earliest clinically recognizable phase of PD.


Methods:

This retrospective study compared the diagnostic performance of NM-sensitive MRI and free water (FW) imaging in 247 patients with early PD and 78 controls, utilizing a fully automated subregional analysis of the substantia nigra.


Results:

This study demonstrated that NM-MRI significantly outperformed FW imaging in diagnosing early PD with an AUC of 0.833, particularly through the combined NM model based on SNpc subregions ; notably, this superior performance was maintained in patients with a disease duration of ≤24 months, suggesting that imaging biomarkers (reflecting dopaminergic neuron loss) may react earlier than observable clinical symptoms, whereas FW values showed no significant group differences in these early stages.


Discussion: These findings highlight the clinical utility of NM-MRI for early diagnostic assessment and serve as evidence supporting the clinical and product validity of NM-MRI (Sandwich NM) as a reliable early PD biomarker , facilitating its potential integration into emerging multimodal biomarker frameworks for improved clinical management.

  • Link

    https://www.nature.com/articles/s41531-026-01286-y
  • Author

    Yun Hwa Roh, Jinyoung Youn, Sang-Young Kim, Hwan Heo, Soohwa Song, Jeongwon Jo, Eung Yeop Kim, Yangsean Choi, Sun Ju Chung, Sungyang Jo & Beomseok Sohn
  • Keywords

    PD, Parkinson's disease, Neuromelanin-sensitive MRI, Free water imaging, Substantia nigra, Biomarker, Early diagnosis, SNpc subregions, AUC, Dopaminergic neurons, Automated analysis
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