School of Medicine, Mental Health & Clinical Neurosciences, Nottingham, United Kingdom.
Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
Mov Disord. 2022 May;37(5):1028-1039. doi: 10.1002/mds.28934. Epub 2022 Feb 15.
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.
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.
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.
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.
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.
由于缺乏既定的生物标志物，帕金森病（PD）的临床诊断和监测仍然具有挑战性。神经黑色素磁共振成像（NM-MRI）是一种新兴的黑质脱色素生物标志物，可用于评估黑色素神经元的丢失，但在多中心环境中，其前瞻性诊断和跟踪性能尚不清楚。
旨在研究 NM-MRI 在多协议设置中对早期 PD 的诊断准确性，并确定和比较 PD 和对照组的 NM-MRI 系列变化。
在这项纵向病例对照 3T MRI 研究中，来自六个英国临床中心的 148 名患者和 97 名对照者被纳入研究，其中 140 名患者在 1.5 至 3 年后接受了第二次扫描。应用基于模板的自动分析方法进行亚区黑质 NM-MRI 对比和体积评估。计算了预诊断脱色素期的点估计值。
所有 NM 指标在区分患者和对照组方面表现良好，接受者操作特征曲线显示腹侧 NM 对比的准确率为 85%，体积的准确率为 83%。使用先验体积截止值的可推广性较好（准确率为 79%）。与对照组相比，患者的 MRI 显示 NM 丢失加速。腹侧 NM 对比损失估计在临床诊断前 5 至 6 年开始。受影响最严重的一侧、更严重的病例的黑质脱色素更为严重，并且黑质 NM 体积变化与运动严重程度的变化相关。
我们证明 NM-MRI 在早期 PD 中跨方案、平台和地点提供了有临床意义的诊断信息。它提供了方法和估计的脱色素率，这突出了检测临床前 PD 和为基于生物标志物的临床试验跟踪进展的潜力。
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