Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.
ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France.
Brain. 2020 Sep 1;143(9):2757-2770. doi: 10.1093/brain/awaa216.
This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson's disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson's disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson's disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson's disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra's morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson's disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.
本研究旨在探究早期或进展期帕金森病患者、无帕金森病体征的特发性快速眼动睡眠行为障碍(iRBD)患者与健康对照组患者黑质内神经黑色素敏感 MRI 信号的时空变化及其与疾病严重程度临床评分的关系。本研究纳入了 iRBD 患者、早期或进展期帕金森病患者和健康对照组,对其进行了纵向 T1 加权解剖和神经黑色素敏感 MRI 检查。通过使用特定于研究的大脑解剖模板对黑质进行对齐分段,为不同严重程度的疾病患者和对照组计算了每个体素属于黑质的概率参数图。对于黑质中的每个体素,计算 iRBD 和帕金森病患者的神经黑色素敏感 MRI 的信噪比与运动障碍、认知和情绪/行为临床评分之间的相关性。结果显示,与健康对照组相比,患者的黑质体积随着疾病严重程度的增加而逐渐减小。神经黑色素信号的变化似乎首先出现在黑质的后外侧运动区域,然后逐渐发展到该区域的更内侧区域。帕金森病患者的黑质体积与对照组的比值最适合用单指数衰减拟合。基于该模型,疾病的无症状期在疾病诊断前 5.3 年开始,诊断时黑质体积丢失 23.1%,这与使用人类黑质的尸检组织学和人类纹状体的放射性示踪研究的先前发现一致。神经黑色素敏感 MRI 信噪比与运动、认知和情绪/行为临床评分之间的相关性的体素模式定位于黑质的不同区域。这种定位反映了非人类灵长类动物的组织学和电生理学研究中观察到的黑质纹状体系统的功能组织(运动、认知和情绪/行为领域)。总之,神经黑色素敏感 MRI 使我们能够在人类中评估黑质形态的体素变化,包括健康对照组、iRBD 患者和帕金森病患者,并确定其与所有运动、认知和行为领域的黑质功能的相关性。这种深入了解可能有助于评估疾病修饰药物试验中的疾病进展。