Parkinson’s disease (PD) is a neurodegenerative synucleinopathy characterized by the degeneration of neuromelanin (NM)-containing dopaminergic neurons and deposition of iron in the substantia nigra (SN). How regional NM loss and iron accumulation within specific areas of SN relate to nigro-striatal dysfunction needs to be clarified. We measured dopaminergic function in pre- and postcommissural putamen by [¹⁸F]DOPA PET in 23 Parkinson’s disease patients and 23 healthy control (HC) participants in whom NM content and iron load were assessed in medial and lateral SN, respectively, by NM-sensitive and quantitative R2* MRI. Data analysis consisted of voxelwise regressions testing the group effect and its interaction with NM or iron signals. In PD patients, R2* was selectively increased in left lateral SN as compared to healthy participants, suggesting a local accumulation of iron in Parkinson’s disease. By contrast, NM signal differed between PD and HC, without specific regional specificity within SN. Dopaminergic function in posterior putamen decreased as R2* increased in lateral SN, indicating that dopaminergic function impairment progresses with iron accumulation in the SN. Dopaminergic function was also positively correlated with NM signal in lateral SN, indicating that dopaminergic function impairment progresses with depigmentation in the SN. A complex relationship was detected between R2* in the lateral SN and NM signal in the medial SN. In conclusion, multimodal imaging reveals regionally specific relationships between iron accumulation and depigmentation within the SN of Parkinson’s disease and provides in vivo insights in its neuropathology.

帕金森病 (PD) 是一种神经退行性突触核蛋白病，其特征是含有神经黑色素 (NM) 的多巴胺能神经元退化和铁在黑质 (SN) 中沉积。需要澄清 SN 特定区域内的区域 NM 损失和铁积累与黑质纹状体功能障碍的关系。我们通过 [ ^18]测量了连合前和连合后壳核的多巴胺能功能F]DOPA PET 在 23 名帕金森病患者和 23 名健康对照 (HC) 参与者中，分别通过 NM 敏感和定量 R2* MRI 在内侧和外侧 SN 中评估了 NM 含量和铁负荷。数据分析包括体素回归测试组效应及其与 NM 或铁信号的相互作用。在 PD 患者中，与健康参与者相比，左侧 SN 中的 R2* 有选择地增加，表明帕金森病中铁的局部积累。相比之下，NM 信号在 PD 和 HC 之间不同，在 SN 内没有特定的区域特异性。随着外侧 SN 中 R2* 的增加，后壳核的多巴胺能功能降低，表明多巴胺能功能受损随着 SN 中铁的积累而进展。多巴胺能功能也与外侧 SN 中的 NM 信号呈正相关，表明多巴胺能功能损害随着 SN 中的色素脱失而进展。在外侧 SN 中的 R2* 和内侧 SN 中的 NM 信号之间检测到复杂的关系。总之，多模态成像揭示了帕金森氏病 SN 内铁积累和脱色之间的区域特异性关系，并提供了对其神经病理学的体内见解。