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Neuromelanin-MRI to Quantify and Track Nigral Depigmentation in Parkinson's Disease: A Multicenter Longitudinal Study Using Template-Based Standardized Analysis

Xing, Yue; Sapuan, Abdul Halim; Martín-Bastida, Antonio; Naidu, Saadnah; Tench, Christopher; Evans, Jonathan; Sare, Gillian; Schwarz, Stefan T.; Al-bachari, Sarah; Parkes, Laura M.; Kanavou, Sofia; Raw, Jason; Silverdale, Monty; Bajaj, Nin; Pavese, Nicola; Burn, David; Piccini, Paola; Grosset, Donald G.; Auer, Dorothee P.

Neuromelanin-MRI to Quantify and Track Nigral Depigmentation in Parkinson's Disease: A Multicenter Longitudinal Study Using Template-Based Standardized Analysis Thumbnail


Authors

YUE XING YUE.XING@NOTTINGHAM.AC.UK
Research Fellow

Abdul Halim Sapuan

Antonio Martín-Bastida

Saadnah Naidu

Jonathan Evans

Gillian Sare

Stefan T. Schwarz

Sarah Al-bachari

Laura M. Parkes

Sofia Kanavou

Jason Raw

Monty Silverdale

Nin Bajaj

Nicola Pavese

David Burn

Paola Piccini

Donald G. Grosset

DOROTHEE AUER dorothee.auer@nottingham.ac.uk
Professor of Neuroimaging



Abstract

Background: Clinical diagnosis and monitoring of Parkinson's disease (PD) remain challenging because of the lack of an established biomarker. Neuromelanin-magnetic resonance imaging (NM-MRI) is an emerging biomarker of nigral depigmentation indexing the loss of melanized neurons but has unknown prospective diagnostic and tracking performance in multicenter settings. Objectives: The aim was to investigate the diagnostic accuracy of NM-MRI in early PD in a multiprotocol setting and to determine and compare serial NM-MRI changes in PD and controls. Methods: In this longitudinal case–control 3 T MRI study, 148 patients and 97 controls were included from six UK clinical centers, of whom 140 underwent a second scan after 1.5 to 3 years. An automated template-based analysis was applied for subregional substantia nigra NM-MRI contrast and volume assessment. A point estimate of the period of prediagnostic depigmentation was computed. Results: All NM metrics performed well to discriminate patients from controls, with receiver operating characteristic showing 85% accuracy for ventral NM contrast and 83% for volume. Generalizability using a priori volume cutoff was good (79% accuracy). Serial MRI demonstrated accelerated NM loss in patients compared to controls. Ventral NM contrast loss was point estimated to start 5 to 6 years before clinical diagnosis. Ventral nigral depigmentation was greater in the most affected side, more severe cases, and nigral NM volume change correlated with change in motor severity. Conclusions: We demonstrate that NM-MRI provides clinically useful diagnostic information in early PD across protocols, platforms, and sites. It provides methods and estimated depigmentation rates that highlight the potential to detect preclinical PD and track progression for biomarker-enabled clinical trials. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Citation

Xing, Y., Sapuan, A. H., Martín-Bastida, A., Naidu, S., Tench, C., Evans, J., …Auer, D. P. (2022). Neuromelanin-MRI to Quantify and Track Nigral Depigmentation in Parkinson's Disease: A Multicenter Longitudinal Study Using Template-Based Standardized Analysis. Movement Disorders, 37(5), 1028-1039. https://doi.org/10.1002/mds.28934

Journal Article Type Article
Acceptance Date Jan 13, 2022
Online Publication Date Feb 15, 2022
Publication Date 2022-05
Deposit Date Jan 28, 2022
Publicly Available Date Mar 28, 2024
Journal Movement Disorders
Print ISSN 0885-3185
Electronic ISSN 1531-8257
Peer Reviewed Peer Reviewed
Volume 37
Issue 5
Pages 1028-1039
DOI https://doi.org/10.1002/mds.28934
Public URL https://nottingham-repository.worktribe.com/output/7344014
Publisher URL https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.28934

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