Diagnostic performance and methodological heterogeneity of neuromelanin-sensitive MRI in Parkinson's disease: A systematic review and meta-analysis
- 1Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland
- 2Roche Products Ltd, Welwyn Garden City, UK
- 3University of Exeter Medical School, London, UK
Abstract
Background: Parkinson's disease (PD) diagnosis remains primarily clinical and is often delayed until substantial neurodegeneration has occurred. Neuromelanin-sensitive MRI (NM-MRI) assesses the integrity of neuromelanin-rich nuclei affected in PD, the substantia nigra pars compacta (SNpc) and locus coeruleus (LC), but its diagnostic performance, technical determinants, and translational applicability remain unclear amid heterogeneity. We aimed to quantify diagnostic accuracy, determine whether performance varies across methodological approaches, and contextualise evidence from clinically relevant settings.
Methods: We systematically reviewed NM-MRI diagnostic studies through December 2025. QUADAS-2 assessed risk of bias. Sensitivity and specificity were jointly pooled using a bivariate model, and AUC using random-effects meta-analysis. Subgroup analyses and exploratory meta-regressions assessed methodological heterogeneity; broader clinical evidence was synthesised qualitatively.
Results: Thirty-nine studies were included. Across 20 PD-versus-healthy-control (HC) studies (878 PD; 690 HCs), pooled sensitivity was 89.03% (95% CI 86.01–91.45%), specificity 87.02% (95% CI 82.76–90.34%), PLR 6.86, NLR 0.126, and DOR 54.37. Across 32 studies (1411 PD; 1086 HCs), pooled AUC was 0.909 (95% CI 0.884–0.929; I2 = 64.6%). No significant unadjusted differences emerged by sequence, dimensionality, segmentation, or measurement type. NM-MRI abnormalities were detectable across prodromal, early- and advanced-stage PD, although global measures showed limited discrimination between disease stages. Subregional measures captured phenotypic variation, genotype discrimination was limited, and PD-versus-ET/APS performance was promising but variable, within small, heterogeneous evidence bases.
Conclusion: NM-MRI is a promising non-invasive imaging biomarker for PD, with strong discrimination across diverse methodological approaches. Harmonised acquisition and analysis, externally validated diagnostic thresholds, and prospective multicentre studies in clinically representative populations are needed to support future clinical implementation.
Related
- From underdiagnosis to scalable screening: Applications of artificial intelligence for vertebral compression fracture detection – a systematic review and meta-analysis of diagnostic performance
- Biomarkers in Acute Mesenteric Ischemia: A Systematic Review of Diagnostic Performance and Injury-Related Signals
- Performance of Large Language Models Across Diagnostic Tasks in Oral and Maxillofacial Pathology: A Systematic Review
- Diagnostic Performance of Deep Learning Using Retinal Images for Detection of Chronic Kidney Disease: A Systematic Review and Meta-Analysis
- Diagnostic Performance of cfDNA-Based Liquid Biopsy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
BibTeX
@article{akande2026diagnostic,
title = {{Diagnostic performance and methodological heterogeneity of neuromelanin-sensitive MRI in Parkinson's disease: A systematic review and meta-analysis}},
author = {Rayo Akande and Thomas Kustermann and Štefan Holiga and Judith Anzures-Cabrera and Gennaro Pagano},
journal = {NeuroImage: Clinical},
year = {2026},
month = oct,
doi = {10.1016/j.nicl.2026.104082},
url = {https://doi.org/10.1016/j.nicl.2026.104082},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Diagnostic performance and methodological heterogeneity of neuromelanin-sensitive MRI in Parkinson's disease: A systematic review and meta-analysis
AU - Rayo Akande
AU - Thomas Kustermann
AU - Štefan Holiga
AU - Judith Anzures-Cabrera
AU - Gennaro Pagano
PY - 2026
DA - 2026/10/21
JO - NeuroImage: Clinical
DO - 10.1016/j.nicl.2026.104082
UR - https://doi.org/10.1016/j.nicl.2026.104082
AB - Background: Parkinson's disease (PD) diagnosis remains primarily clinical and is often delayed until substantial neurodegeneration has occurred. Neuromelanin-sensitive MRI (NM-MRI) assesses the integrity of neuromelanin-rich nuclei affected in PD, the substantia nigra pars compacta (SNpc) and locus coeruleus (LC), but its diagnostic performance, technical determinants, and translational applicability remain unclear amid heterogeneity. We aimed to quantify diagnostic accuracy, determine whether performance varies across methodological approaches, and contextualise evidence from clinically relevant settings. Methods: We systematically reviewed NM-MRI diagnostic studies through December 2025. QUADAS-2 assessed risk of bias. Sensitivity and specificity were jointly pooled using a bivariate model, and AUC using random-effects meta-analysis. Subgroup analyses and exploratory meta-regressions assessed methodological heterogeneity; broader clinical evidence was synthesised qualitatively. Results: Thirty-nine studies were included. Across 20 PD-versus-healthy-control (HC) studies (878 PD; 690 HCs), pooled sensitivity was 89.03% (95% CI 86.01–91.45%), specificity 87.02% (95% CI 82.76–90.34%), PLR 6.86, NLR 0.126, and DOR 54.37. Across 32 studies (1411 PD; 1086 HCs), pooled AUC was 0.909 (95% CI 0.884–0.929; I2 = 64.6%). No significant unadjusted differences emerged by sequence, dimensionality, segmentation, or measurement type. NM-MRI abnormalities were detectable across prodromal, early- and advanced-stage PD, although global measures showed limited discrimination between disease stages. Subregional measures captured phenotypic variation, genotype discrimination was limited, and PD-versus-ET/APS performance was promising but variable, within small, heterogeneous evidence bases. Conclusion: NM-MRI is a promising non-invasive imaging biomarker for PD, with strong discrimination across diverse methodological approaches. Harmonised acquisition and analysis, externally validated diagnostic thresholds, and prospective multicentre studies in clinically representative populations are needed to support future clinical implementation.
SN - 2213-1582
ER -