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.

中文翻译：

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帕金森氏病中黑质神经黑色素含量的时空变化。

这项研究的目的是调查早期或进行性帕金森氏病和特发性快速眼动睡眠行为障碍（iRBD）豁免的黑质黑质中神经黑色素敏感MRI信号的时空变化及其与疾病严重程度临床评分的关系与健康对照组相比，帕金森症的体征更高。纵向T ₁在两个队列中进行了加权加权解剖和神经黑色素敏感的MRI，包括iRBD患者，帕金森氏病早期或进展的患者以及对照组。基于使用研究特定的脑解剖模板的对齐的黑质黑质分割，针对具有不同程度的疾病严重程度和对照的患者，计算了属于黑质的体素概率的参数图。对于黑质中的每个体素，计算了对照的概率图，iRBD和帕金森氏病患者神经黑色素敏感MRI的信噪比之间的相关性以及运动障碍，认知和情绪/行为的临床评分。我们的结果表明，与健康对照组相比，患者中，随着疾病严重程度的增加，黑质的体积逐渐减少。神经黑色素信号的变化似乎始于黑质的后外侧运动区域，然后发展到该区域的更多内侧区域。帕金森氏病患者黑质相对于对照组的体积比最好通过单指数衰减来拟合。基于该模型，疾病的症状前期始于疾病诊断前5.3年，在诊断时损失了23.1％的黑质体积，这与先前使用尸体的尸体组织学检查结果相符。人类黑质和人类纹状体的放射性示踪剂研究。神经黑色素敏感MRI信噪比与运动之间的体素相关模式 认知和情绪/行为临床评分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使我们能够评估黑质形态的体素修饰包括健康对照，iRBD患者和帕金森氏病患者在内的人类体内，并在所有运动，认知和行为领域确定其与黑色素功能的相关性。这种见解可以帮助评估疾病改良药物试验中的疾病进展。