Importance Imaging biomarkers in Parkinson disease (PD) are increasingly important for monitoring progression in clinical trials and also have the potential to improve clinical care and management. This Review addresses a critical need to make clear the temporal relevance for diagnostic and progression imaging biomarkers to be used by clinicians and researchers over the clinical course of PD. Magnetic resonance imaging (diffusion imaging, neuromelanin-sensitive imaging, iron-sensitive imaging, T1-weighted imaging), positron emission tomography/single-photon emission computed tomography dopaminergic, serotonergic, and cholinergic imaging as well as metabolic and cerebral blood flow network neuroimaging biomarkers in the preclinical, prodromal, early, and moderate to late stages are characterized. Observations If a clinical trial is being carried out in the preclinical and prodromal stages, potentially useful disease-state biomarkers include dopaminergic imaging of the striatum; metabolic imaging; free-water, neuromelanin-sensitive, and iron-sensitive imaging in the substantia nigra; and T1-weighted structural magnetic resonance imaging. Disease-state biomarkers that can distinguish atypical parkinsonisms are metabolic imaging, free-water imaging, and T1-weighted imaging; dopaminergic imaging and other molecular imaging track progression in prodromal patients, whereas other established progression biomarkers need to be evaluated in prodromal cohorts. Progression in early-stage PD can be monitored using dopaminergic imaging in the striatum, metabolic imaging, and free-water and neuromelanin-sensitive imaging in the posterior substantia nigra. Progression in patients with moderate to late-stage PD can be monitored using free-water imaging in the anterior substantia nigra, R2* of substantia nigra, and metabolic imaging. Cortical thickness and gyrification might also be useful markers or predictors of progression. Dopaminergic imaging and free-water imaging detect progression over 1 year, whereas other modalities detect progression over 18 months or longer. The reliability of progression biomarkers varies with disease stage, whereas disease-state biomarkers are relatively consistent in individuals with preclinical, prodromal, early, and moderate to late-stage PD. Conclusions and Relevance Imaging biomarkers for various stages of PD are readily available to be used as outcome measures in clinical trials and are potentially useful in multimodal combination with routine clinical assessment. This Review provides a critically important template for considering disease stage when implementing diagnostic and progression biomarkers in both clinical trials and clinical care settings.

中文翻译：

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帕金森病跨疾病阶段的新兴神经影像生物标志物：综述。


重要性 帕金森病 (PD) 的成像生物标志物对于监测临床试验的进展越来越重要，并且还有可能改善临床护理和管理。本综述解决了明确临床医生和研究人员在 PD 临床过程中使用的诊断和进展成像生物标志物的时间相关性的迫切需要。磁共振成像（扩散成像、神经黑色素敏感成像、铁敏感成像、T1加权成像）、正电子发射断层扫描/单光子发射计算机断层扫描多巴胺能、血清素能和胆碱能成像以及代谢和脑血流网络神经成像对临床前、前驱、早期和中晚期阶段的生物标志物进行了表征。观察如果在临床前和前驱阶段进行临床试验，潜在有用的疾病状态生物标志物包括纹状体的多巴胺能成像；代谢成像；黑质中的游离水、神经黑色素敏感和铁敏感成像；和 T1 加权结构磁共振成像。能够区分非典型帕金森病的疾病状态生物标志物有代谢成像、自由水成像和T1加权成像；多巴胺能成像和其他分子成像追踪前驱患者的进展，而其他已建立的进展生物标志物需要在前驱队列中进行评估。可以使用纹状体中的多巴胺能成像、代谢成像以及黑质后部的游离水和神经黑色素敏感成像来监测早期 PD 的进展。 中度至晚期 PD 患者的进展可以使用黑质前部自由水成像、黑质 R2* 和代谢成像来监测。皮质厚度和回旋也可能是有用的进展标记或预测因子。多巴胺能成像和自由水成像可检测 1 年以上的进展，而其他方式可检测 18 个月或更长时间的进展。进展生物标志物的可靠性随疾病阶段的不同而变化，而临床前、前驱、早期和中晚期 PD 个体的疾病状态生物标志物相对一致。结论和相关性 PD 各个阶段的成像生物标志物很容易用作临床试验中的结果测量，并且在与常规临床评估的多模式组合中可能有用。本综述为在临床试验和临床护理环境中实施诊断和进展生物标志物时考虑疾病阶段提供了一个至关重要的模板。