Neuromelanin-sensitive MRI has been proposed as a biomarker of Parkinson's disease pathology. However, the biological and physical origins of this contrast are debated. A recent rodent model of controlled neuromelanin accumulation in the substantia nigra has been developed and recapitulates several features of Parkinson's disease. In this work, we first combined neuromelanin-sensitive-MRI and histology to study neuromelanin accumulation and neurodegeneration in a humanized rat model of Parkinson's disease. Neuromelanin-sensitive-MRI signal changes were biphasic with an initial increase due to the accumulation of neuromelanin in dopaminergic neurons, followed signal decrease due to neurodegeneration. In healthy subjects and patients with isolated rapid eye movement sleep behaviour disorder, neuromelanin-sensitive-MRI signal increased initially and then decreased similarly as in rodents after reaching a similar maximum signal intensity in both groups. In early Parkinson's disease and converted isolated rapid eye movement sleep behaviour disorder patients, neuromelanin-sensitive-MRI signal drop was greater than in healthy individuals. Results in animals and humans show that neuromelanin-sensitive-MRI is a marker of the intracellular neuromelanin accumulation and then of neuronal degeneration and originates mainly from T₁ reduction effect of neuromelanin.

Keywords: Parkinson’s disease.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.

神经黑素敏感性MRI被提议作为帕金森病病理学的生物标志物。然而，这种对比的生物学和物理起源仍存在争议。最近开发了一种受控神经黑素积累的小鼠模型，并且该模型再现了帕金森病的一些特征。在这项研究中，我们首先结合使用了神经黑素敏感性MRI和组织学技术来研究人类化大鼠帕金森病模型中的神经黑素积累和神经退行性疾病。神经黑素敏感性MRI信号变化呈双相模式，在早期由于多巴胺能神经元中神经黑素的累积导致信号增加，随后因神经退变而出现信号减少。在健康受试者及具有孤立快速眼动睡眠行为障碍的患者中，神经黑素敏感性MRI信号最初会增加然后和啮齿动物模型类似地降低，在两组达到峰值强度相似后情况一致。早期帕金森病患者以及转为孤立快速眼动睡眠行为障碍患者的神经黑素敏感性MRI信号下降幅度大于健康个体。实验结果表明，神经黑素敏感性MRI是细胞内神经黑素累积及随后的神经元退变的重要标志，并且主要来源于神经黑素对T1减少效应的影响。

关键词：帕金森病

© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.