{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:13:07Z","timestamp":1791231187672,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001865","name":"Latvian Academy of Sciences\n\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/02vxngq63","doi-asserted-by":"publisher","award":["lzp-2022\/1-0100"],"award-info":[{"award-number":["lzp-2022\/1-0100"]}],"id":[{"id":"10.13039\/501100001865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Parkinson\u2019s 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\u2013based substantia nigra volumetry in PD. Methods: In this prospective case\u2013control 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\u2019s Disease Rating Scale (UPDRS) Part III and Hoehn and Yahr (H&amp;Y) staging. Group comparisons, receiver operating characteristic (ROC) analysis, and reliability testing using intraclass correlation coefficients (ICC) were performed. Results: Corrected substantia nigra volume was significantly reduced in PD patients compared with controls (18% reduction; p = 0.039, Mann\u2013Whitney 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&amp;Y stage. Conclusions: Semi-automated NM-MRI volumetry detects biologically meaningful substantia nigra volume loss in early-stage Parkinson\u2019s 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.<\/jats:p>","DOI":"10.3390\/diagnostics16071046","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:53Z","timestamp":1774878113000},"page":"1046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Semi-Automated Neuromelanin-Sensitive MRI Reveals Substantia Nigra Volume Reduction in Early Parkinson\u2019s Disease with Moderate Diagnostic Performance"],"prefix":"10.3390","volume":"16","author":[{"given":"Arturs","family":"Silovs","sequence":"first","affiliation":[{"name":"Department of Radiology, Riga East University Hospital, Hipokrata Street 2, LV-1038 Riga, Latvia"},{"name":"Department of Radiology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"},{"name":"Latvian Maritime Medicine Centre, Patversmes Street 29, LV-1005 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0793-1286","authenticated-orcid":false,"given":"Gvido Karlis","family":"Skuburs","sequence":"additional","affiliation":[{"name":"Department of Radiology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8255-7392","authenticated-orcid":false,"given":"Nauris","family":"Zdanovskis","sequence":"additional","affiliation":[{"name":"Department of Radiology, Riga East University Hospital, Hipokrata Street 2, LV-1038 Riga, Latvia"},{"name":"Department of Radiology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksejs","family":"Sevcenko","sequence":"additional","affiliation":[{"name":"Department of Neurology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-0916","authenticated-orcid":false,"given":"Janis","family":"Mednieks","sequence":"additional","affiliation":[{"name":"Department of Neurology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgars","family":"Naudins","sequence":"additional","affiliation":[{"name":"Department of Radiology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-3334","authenticated-orcid":false,"given":"Santa","family":"Bartusevica","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solvita","family":"Umbrasko","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liga","family":"Zarina","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Zelge","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese Anna","family":"Pastare","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Steinberga","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-970X","authenticated-orcid":false,"given":"Jurgis","family":"Skilters","sequence":"additional","affiliation":[{"name":"Laboratory for Perceptual and Cognitive Systems, University of Latvia, Rai\u0146a Bulv\u0101ris 19, LV-1586 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baingio","family":"Pinna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardis","family":"Platkajis","sequence":"additional","affiliation":[{"name":"Department of Radiology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"},{"name":"Latvian Maritime Medicine Centre, Patversmes Street 29, LV-1005 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"862","DOI":"10.12688\/f1000research.25634.1","article-title":"Recent developments in the treatment of Parkinson\u2019s Disease","volume":"9","author":"Stoker","year":"2020","journal-title":"F1000Research"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/mds.26431","article-title":"MDS research criteria for prodromal Parkinson\u2019s disease","volume":"30","author":"Berg","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/mds.27802","article-title":"Update of the MDS research criteria for prodromal Parkinson\u2019s disease","volume":"34","author":"Heinzel","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41531-018-0047-3","article-title":"Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson\u2019s disease","volume":"4","author":"Sulzer","year":"2018","journal-title":"NPJ Park. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nrn1537","article-title":"Iron, brain ageing and neurodegenerative disorders","volume":"5","author":"Zecca","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/mds.26417","article-title":"Quantitative Susceptibility Mapping of the Midbrain in Parkinson\u2019s Disease","volume":"31","author":"Du","year":"2016","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1002\/hbm.23192","article-title":"Diffusion tensor imaging of the substantia nigra in Parkinson\u2019s disease revisited","volume":"37","author":"Langley","year":"2016","journal-title":"Hum. Brain Mapp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1002\/mds.23722","article-title":"T1-Weighted MRI shows stage-dependent substantia nigra signal loss in Parkinson\u2019s disease","volume":"26","author":"Schwarz","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1002\/mrm.26584","article-title":"Contrast mechanisms associated with neuromelanin-MRI","volume":"78","author":"Trujillo","year":"2017","journal-title":"Magn. Reson. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.parkreldis.2014.04.005","article-title":"Differentiation of early-stage parkinsonisms using neuromelanin-sensitive magnetic resonance imaging","volume":"20","author":"Ohtsuka","year":"2014","journal-title":"Park. Relat. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1002\/hbm.22928","article-title":"Region-specific disturbed iron distribution in early idiopathic Parkinson\u2019s disease measured by quantitative susceptibility mapping","volume":"36","author":"He","year":"2015","journal-title":"Hum. Brain Mapp."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1097\/01.wnr.0000227984.84927.a7","article-title":"Neuromelanin magnetic resonance imaging of locus ceruleus and substantia nigra in Parkinson\u2019s disease","volume":"17","author":"Sasaki","year":"2006","journal-title":"Neuroreport"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.pneurobio.2015.09.012","article-title":"Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson\u2019s disease","volume":"155","author":"Zucca","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1111\/j.1471-4159.2008.05541.x","article-title":"Neuromelanin can protect against iron-mediated oxidative damage in system modeling iron overload of brain aging and Parkinson\u2019s disease","volume":"106","author":"Zecca","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-7091-0643-3_8","article-title":"The neuromelanin of human substantia nigra: Structure, synthesis and molecular behaviour","volume":"65","author":"Zecca","year":"2003","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Moreno-Garc\u00eda, A., Kun, A., Calero, M., and Calero, O. (2021). The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration. Antioxidants, 10.","DOI":"10.3390\/antiox10010124"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12640-013-9435-y","article-title":"Neuromelanin of the Human Substantia Nigra: An Update","volume":"25","author":"Zucca","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1002\/mds.28531","article-title":"Longitudinal Changes in Neuromelanin MRI Signal in Parkinson\u2019s Disease: A Progression Marker","volume":"36","author":"Gaurav","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1148\/radiol.2020191235","article-title":"Substantia Nigra Volumetry with 3-T MRI in De Novo and Advanced Parkinson Disease","volume":"296","author":"Vitali","year":"2020","journal-title":"Radiology"},{"key":"ref_21","unstructured":"(2026, March 20). MDS Clinical Diagnostic Criteria for Parkinson\u2019s Disease\u2014Postuma\u20142015\u2014Movement Disorders\u2014Wiley Online Library. Available online: https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.26424."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/nimg.1998.0395","article-title":"Cortical surface-based analysis. I. Segmentation and surface reconstruction","volume":"9","author":"Dale","year":"1999","journal-title":"NeuroImage"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"NeuroImage"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1162\/jocn.1993.5.2.162","article-title":"Improved Localizadon of Cortical Activity by Combining EEG and MEG with MRI Cortical Surface Reconstruction: A Linear Approach","volume":"5","author":"Dale","year":"1993","journal-title":"J. Cogn. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.neuroimage.2004.06.018","article-title":"A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: Reliability and validation against manual measurement of total intracranial volume","volume":"23","author":"Buckner","year":"2004","journal-title":"NeuroImage"},{"key":"ref_27","first-page":"540","article-title":"Substantia nigra neuromelanin magnetic resonance imaging in de novo Parkinson\u2019s disease patients","volume":"22","author":"Lobo","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1093\/brain\/awaa216","article-title":"Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson\u2019s disease","volume":"143","author":"Biondetti","year":"2020","journal-title":"Brain"},{"key":"ref_29","first-page":"2479","article-title":"The diagnostic value of SNpc using NM-MRI in Parkinson\u2019s disease: Meta-analysis","volume":"40","author":"Wang","year":"2019","journal-title":"Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1007\/s00330-020-07240-7","article-title":"Diagnostic performance of neuromelanin-sensitive magnetic resonance imaging for patients with Parkinson\u2019s disease and factor analysis for its heterogeneity: A systematic review and meta-analysis","volume":"31","author":"Cho","year":"2021","journal-title":"Eur. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41531-018-0050-8","article-title":"Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson\u2019s disease","volume":"4","author":"Zucca","year":"2018","journal-title":"NPJ Park. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.neuroimage.2017.11.035","article-title":"Specific visualization of neuromelanin-iron complex and ferric iron in the human post-mortem substantia nigra using MR relaxometry at 7T","volume":"172","author":"Lee","year":"2017","journal-title":"NeuroImage"},{"key":"ref_33","first-page":"1460","article-title":"Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease","volume":"39","author":"Pyatigorskaya","year":"2018","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neulet.2016.09.011","article-title":"A longitudinal study of neuromelanin-sensitive magnetic resonance imaging in Parkinson\u2019s disease","volume":"633","author":"Matsuura","year":"2016","journal-title":"Neurosci. Lett."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/7\/1046\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:49:56Z","timestamp":1774878596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/7\/1046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["diagnostics16071046"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16071046","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]}}}