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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

Lookup NU author(s): Laura Parkes, Professor Nicola PaveseORCiD, Professor David Burn

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. 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.


Publication metadata

Author(s): Xing Y, Sapuan AH, Martin-Bastida A, Naidu S, Tench C, Evans J, Sare G, Schwarz ST, Al-bachari S, Parkes LM, Kanavou S, Raw J, Silverdale M, Bajaj N, Pavese N, Burn D, Piccini P, Grosset DG, Auer DP

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2022

Volume: 37

Issue: 5

Pages: 1028-1039

Print publication date: 19/05/2022

Online publication date: 15/02/2022

Acceptance date: 09/01/2022

Date deposited: 17/03/2022

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/mds.28934

DOI: 10.1002/mds.28934

PubMed id: 35165920


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Funding

Funder referenceFunder name
11473
J-1204
UB190188

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