Quantitative iron-neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification

Septian Hartono; Robert Chun Chen; Thomas Welton; An Sen Tan; Weiling Lee; Peik Yen Teh; Celeste Chen; Wenlu Hou; Wei Ping Tham; Ee Wei Lim; Kumar M Prakash; Yao-Chia Shih; Kuan Jin Lee; Louis C S Tan; Eng King Tan; Ling Ling Chan

doi:10.3389/fnagi.2023.1287917

Quantitative iron-neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification

Front Aging Neurosci. 2023 Nov 27:15:1287917. doi: 10.3389/fnagi.2023.1287917. eCollection 2023.

Authors

Septian Hartono^{1

2}, Robert Chun Chen^{2

3}, Thomas Welton^{1

2}, An Sen Tan³, Weiling Lee³, Peik Yen Teh³, Celeste Chen¹, Wenlu Hou³, Wei Ping Tham³, Ee Wei Lim¹, Kumar M Prakash¹, Yao-Chia Shih^{3

4}, Kuan Jin Lee⁵, Louis C S Tan^{1

2}, Eng King Tan^{1

2}, Ling Ling Chan^{2

3}

Affiliations

¹ Department of Neurology, National Neuroscience Institute, Singapore, Singapore.
² Duke-NUS Graduate Medical School, Singapore, Singapore.
³ Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore.
⁴ Yuan Ze University, Taoyuan, Taiwan.
⁵ Singapore BioImaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

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.

Keywords: MRI; Parkinson's disease; classification; comparative study; correlation analysis; iron; neuromelanin; substantia nigra.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Singapore National Medical Research Council (NMRC/CSA/INV2017 and NMRC/CSASI/20nov-0008).