AUTHOR=Hartono Septian , Chen Robert Chun , Welton Thomas , Tan An Sen , Lee Weiling , Teh Peik Yen , Chen Celeste , Hou Wenlu , Tham Wei Ping , Lim Ee Wei , Prakash Kumar M. , Shih Yao-Chia , Lee Kuan Jin , Tan Louis C. S. , Tan Eng King , Chan Ling Ling TITLE=Quantitative iron–neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification JOURNAL=Frontiers in Aging Neuroscience VOLUME=15 YEAR=2023 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1287917 DOI=10.3389/fnagi.2023.1287917 ISSN=1663-4365 ABSTRACT=Background

Neuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case–control PD cohort, we evaluated the diagnostic accuracy of quantitative iron–neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association.

Methods

PD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin–iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity.

Results

In total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p < 0.0001) and smaller sizes after thresholding for low susceptibility (p < 0.0001) on QSM and (b) lower contrast range (p < 0.0001) and smaller sizes after thresholding for high-signal voxels (p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r | <0.6, p < 0.0001), respectively. A composite quantitative neuromelanin–iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI.

Conclusion

Quantitative neuromelanin–iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.