Data_Sheet_1_Iron Imaging as a Diagnostic Tool for Parkinson's Disease: A Systematic Review and Meta-Analysis.doc

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra (SN). There is also an increase in iron content in the SN in postmortem and imaging studies using iron-sensitive MRI techniques. However, MRI results are variable across studies.Objectives: We performed a systematic meta-analysis of SN iron imaging studies in PD to better understand the role of iron-sensitive MRI quantification to distinguish patients from healthy controls. We also studied the factors that may influence iron quantification and analyzed the correlations between demographic and clinical data and iron load.Methods: We searched PubMed and ScienceDirect databases (from January 1994 to December 2019) for studies that analyzed iron load in the SN of PD patients using T2*, R2*, susceptibility weighting imaging (SWI), or quantitative susceptibility mapping (QSM) and compared the values with healthy controls. Details for each study regarding participants, imaging methods, and results were extracted. The effect size and confidence interval (CI) of 95% were calculated for each study as well as the pooled weighted effect size for each marker over studies. Hence, the correlations between technical and clinical metrics with iron load were analyzed.Results: Forty-six articles fulfilled the inclusion criteria including 27 for T2*/R2* measures, 10 for SWI, and 17 for QSM (3,135 patients and 1,675 controls). Eight of the articles analyzed both R2* and QSM. A notable effect size was found in the SN in PD for R2* increase (effect size: 0.84, 95% CI: 0.60 to 1.08), for SWI measurements (1.14, 95% CI: 0.54 to 1.73), and for QSM increase (1.13, 95% CI: 0.86 to 1.39). Correlations between imaging measures and Unified Parkinson's Disease Rating Scale (UPDRS) scores were mostly observed for QSM.Conclusions: The consistent increase in MRI measures of iron content in PD across the literature using R2*, SWI, or QSM techniques confirmed that these measurements provided reliable markers of iron content in PD. Several of these measurements correlated with the severity of motor symptoms. Lastly, QSM appeared more robust and reproducible than R2* and more suited to multicenter studies.

背景：帕金森病（PD）是一种进行性的神经退行性疾病，其主要病理特征为黑质（SN）多巴胺能神经元的丧失。在尸检和采用铁敏感性磁共振成像技术进行的成像研究中，发现黑质中铁含量增加。然而，不同研究中的MRI结果存在差异。目标：我们对帕金森病中黑质铁成像研究进行了系统性的荟萃分析，以更好地理解铁敏感性磁共振量化在区分患者与健康对照者中的作用。我们还研究了可能影响铁量化的因素，并分析了人口统计学和临床数据与铁负荷之间的相关性。方法：我们检索了PubMed和ScienceDirect数据库（从1994年1月到2019年12月）中分析帕金森病患者黑质铁负荷的研究，这些研究使用了T2*、R2*、磁化率加权成像（SWI）或定量磁化率映射（QSM），并将结果与健康对照者进行了比较。提取了每项研究关于参与者、成像方法和结果的相关细节。对每项研究计算了效应量及95%置信区间（CI），以及每个标记的加权效应量。因此，分析了技术指标和临床指标与铁负荷之间的相关性。结果：共有46篇文章符合纳入标准，包括27篇关于T2*/R2*测量，10篇关于SWI，以及17篇关于QSM（包括3135名患者和1675名对照者）。其中8篇文章分析了R2*和QSM。在PD患者的黑质中，我们发现R2*增加（效应量：0.84，95%CI：0.60至1.08）、SWI测量（1.14，95%CI：0.54至1.73）和QSM增加（1.13，95%CI：0.86至1.39）均有显著效应量。成像指标与统一帕金森病评分量表（UPDRS）评分之间的相关性主要在QSM中观察到。结论：使用R2*、SWI或QSM技术在文献中关于PD铁含量MRI指标的持续增加，证实了这些测量提供了PD中铁含量的可靠指标。其中一些测量与运动症状的严重程度相关。最后，QSM相较于R2*更为稳健和可重复，更适合多中心研究。