帕金森病中渐进性铁沉积和广泛的神经功能障碍：一项多模态MRI研究

摘要(中文译文)

帕金森病（PD）是一种以运动症状和非运动症状为特征的进行性神经退行性疾病，然而其阶段依赖性神经生物学机制仍未完全阐明。多模态磁共振成像（MRI）为研究不同疾病阶段的功能和结构改变提供了一种无创方法。因此，本研究旨在利用多模态MRI表征帕金森病中阶段依赖的功能性和铁相关脑改变，并探讨其与运动严重程度的关系。我们纳入了104例帕金森病患者，根据Hoehn和Yahr（H&Y）评分分为早期组（n=49）和晚期组（n=55），同时纳入53名年龄和性别匹配的健康对照。定量磁化率成像（QSM）定量测量黑质（SN）和苍白球（GP）的铁沉积，静息态功能磁共振成像（rs-fMRI）用于评估功能改变，采用局部一致性（ReHo）和低频波动分数幅值（fALFF）。组间比较采用单因素方差分析（ANOVA）及事后检验，体素水平分析采用簇水平错误发现率（FDR，P<0.05）校正。进行相关性分析以评估影像学指标与统一帕金森病评定量表第三部分（UPDRS-III）运动评分之间的关系。与健康对照相比，早期和晚期帕金森病患者均显示双侧黑质和苍白球铁沉积显著增加（均P<0.05），且晚期帕金森病患者的QSM值高于早期帕金森病患者（均P<0.01）。这些区域的铁沉积与UPDRS-III评分评估的运动严重程度呈正相关（均P<0.001）。早期帕金森病主要表现为视觉相关区域的fALFF和ReHo异常，而晚期帕金森病则表现出更广泛的基底节-丘脑皮质运动环路、额顶叶区域和边缘结构的受累。运动相关区域的功能改变与UPDRS-III评分显著相关（均P<0.001），而边缘区域ReHo变化与认知表现（简易精神状态检查，MMSE；P<0.001）相关。基于帕金森病涉及黑质和苍白球进行性铁沉积及广泛神经网络功能障碍的已有证据，我们的多模态MRI研究结果表明，整合ReHo、fALFF和QSM为表征阶段特异性病理生理变化提供了框架，并支持其作为早期诊断、疾病分期和治疗开发生物标志物的潜力。

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, yet its stage-dependent neurobiological mechanisms remain incompletely understood. Multimodal magnetic resonance imaging (MRI) offers a noninvasive approach to investigate both functional and structural alterations across disease stages. Therefore, this study aimed to characterize stage-dependent functional and iron-related brain alterations in PD using multimodal MRI and to explore their associations with motor severity. We enrolled 104 PD patients, stratified into early-stage (n=49) and advanced-stage (n=55) based on Hoehn and Yahr (H&Y) score, along with 53 age- and sex- matched healthy controls. Quantitative susceptibility mapping (QSM) quantified iron deposition in the substantia nigra (SN) and globus pallidus (GP), while resting-state functional magnetic resonance imaging (rs-fMRI) was used to assess functional alterations using regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). Group comparisons were conducted using one-way analysis of variance (ANOVA) with post-hoc tests, and voxel-wise analyses were corrected using cluster-level false discovery rate (FDR, P<0.05). Correlation analyses were performed to evaluate associations between imaging metrics and Unified Parkinson's Disease Rating Scale part III (UPDRS-III) motor scores. Compared with healthy controls, both early and advanced-stage PD patients showed significantly increased iron deposition in the bilateral SN and GP (all P<0.05), with higher QSM values in advanced-stage PD than in early-stage PD (all P<0.01). Iron deposition in these regions was positively correlated with motor severity assessed by UPDRS-III scores (all P<0.001). Early-stage PD primarily exhibited abnormal fALFF and ReHo in visual-related regions, whereas advanced-stage PD showed more widespread involvement of the basal ganglia-thalamocortical motor circuit, frontoparietal regions, and limbic structures. Functional alterations in motor-related regions were significantly associated with UPDRS-III scores (all P<0.001), while ReHo changes in limbic regions were correlated with cognitive performance (Mini-Mental State Examination, MMSE; P<0.001). Building on established evidence that PD involves progressive iron deposition in the SN and GP and widespread neural network dysfunction, our multimodal MRI findings demonstrate that integrating ReHo, fALFF, and QSM provides a framework for characterizing stage-specific pathophysiological changes and support their potential as biomarkers for early diagnosis, disease staging, and therapeutic development.

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