Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville.
Paris Brain Institute, Centre de NeuroImagerie de Recherche, INSERM 1127, CNRS 7225, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
JAMA Neurol. 2021 Oct 1;78(10):1262-1272. doi: 10.1001/jamaneurol.2021.1312.
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.
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.
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.
成像生物标志物在帕金森病（PD）中越来越重要，可用于监测临床试验中的进展，也有可能改善临床护理和管理。本综述旨在明确诊断和进展成像生物标志物在 PD 临床病程中的时间相关性，这是临床医生和研究人员的迫切需求。本文介绍了在临床前、前驱期、早期和中晚期，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、5-羟色胺能和胆碱能成像以及代谢和脑血流网络神经影像学生物标志物在疾病早期阶段的特点。
如果临床试验在临床前和前驱期进行，潜在的有用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；黑质中的自由水、神经黑色素敏感和铁敏感成像；以及 T1 加权结构磁共振成像。可区分非典型帕金森病的疾病状态生物标志物包括代谢成像、自由水成像和 T1 加权成像；多巴胺能成像和其他分子成像可在前驱期患者中追踪进展，而其他已建立的进展生物标志物则需要在前驱期队列中进行评估。在早期 PD 患者中，可以使用纹状体的多巴胺能成像、代谢成像以及后黑质的自由水和神经黑色素敏感成像来监测进展。在中晚期 PD 患者中，可以使用前黑质的自由水成像、黑质的 R2*和代谢成像来监测进展。皮质厚度和脑回可能也是进展的有用标志物或预测指标。多巴胺能成像和自由水成像可在 1 年内检测到进展，而其他模式则可在 18 个月或更长时间内检测到进展。进展生物标志物的可靠性因疾病阶段而异，而疾病状态生物标志物在临床前、前驱期、早期和中晚期 PD 患者中相对一致。
PD 各个阶段的成像生物标志物可用于临床试验中的结局测量，并且与常规临床评估相结合具有潜在的应用价值。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非常重要的模板。
