Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease
Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease
复制标题
DOI：
10.1093/brain/awaa216
复制
发表时间：
2020-09-01
期刊：
影响因子：
14.5
通讯作者：
Lehericy, Stephane
中科院分区：
文献类型：
--
作者：
Biondetti, Emma;Gaurav, Rahul;Lehericy, Stephane
本研究旨在研究与健康对照受试者相比，早期或进展性帕金森病患者和无帕金森症状的特发性快速眼动睡眠行为障碍（iRBD）患者黑质神经黑素敏感MRI信号的时空变化及其与疾病严重程度临床评分的关系。在两个队列中进行纵向T-1加权解剖和神经黑色素敏感MRI，包括iRBD患者，早期或进展性帕金森病患者和对照受试者。基于使用研究特定的脑解剖模板对齐的黑质分割，计算具有不同疾病严重程度的患者和对照的体素属于黑质的概率的参数图。对于黑质中的每个体素，计算对照的概率图、iRBD和帕金森病患者的神经黑素敏感MRI上的信噪比与运动障碍、认知和情绪/行为的临床评分之间的相关性。我们的研究结果表明，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少。神经黑色素信号变化似乎开始于黑质的后外侧运动区，然后进展到该区域的更内侧区域。帕金森病患者黑质体积与对照组的比值最适合单指数衰减。基于该模型，疾病的症状前阶段开始于疾病诊断前5.3年，诊断时黑质体积损失23.1%，这与先前使用人类黑质死后组织学和人类纹状体放射性示踪剂研究的结果一致。神经黑素敏感的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。这种定位反映了在非人类灵长类动物（运动，认知和情绪/行为领域）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。总之，神经黑色素敏感的MRI使我们能够评估人体内黑质形态的体素修饰，包括健康对照，iRBD患者和帕金森病患者，并确定它们与所有运动，认知和行为领域的黑质功能的相关性。这种见解可以帮助评估疾病改善药物试验中的疾病进展。
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 T-1-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.