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

Xing, Y. and Sapuan, A.H. and Martín-Bastida, A. and Naidu, S. and Tench, C. and Evans, J. and Sare, G. and Schwarz, S.T. and Al-bachari, S. and Parkes, L.M. and Kanavou, S. and Raw, J. and Silverdale, M. and Bajaj, N. and Pavese, N. and Burn, D. and Piccini, P. and Grosset, D.G. and 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. ISSN 0885-3185

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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.

Item Type:
Journal Article
Journal or Publication Title:
Movement Disorders
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2808
Subjects:
ID Code:
166578
Deposited By:
Deposited On:
24 Feb 2022 11:55
Refereed?:
Yes
Published?:
Published
Last Modified:
04 May 2022 02:45