RATIONALE In Parkinson's disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP). METHODS The PDRPNL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRPIT was identified in 20 controls and 20 "de-novo" PD patients from an Italian cohort. A further 24 controls and 18 "de-novo" Italian patients were used for validation. The PDRPSP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy. RESULTS A PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in "de-novo" PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRPIT, PDRPNL, and PDRPSP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA. CONCLUSION The PDRP is a reproducible disease characteristic across PD populations and scanning platforms globally. Further study is needed to identify the topography of specific PD subtypes, and to identify and correct for center-specific effects.

中文翻译：

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帕金森氏病中脑葡萄糖代谢的异常模式：在三个欧洲队列中的复制。

理由对于帕金森氏病（PD），对18F-FDG PET数据的空间协方差分析始终显示出与PD相关的特征性大脑模式（PDRP）。通过逐个扫描地定量PDRP表达，该技术可以客观评估单个受试者的疾病活动。通过对来自荷兰（NL），意大利（IT）和西班牙（SP）的PD队列应用空间协方差分析，我们对PDRP进行了进一步的验证。方法先前已鉴定出PDRPNL（17个对照，19个PD），并在19个健康对照和20个来自荷兰的PD患者中确定了其表达。在来自意大利队列的20名对照和20名“新” PD患者中鉴定出PDRPIT。另有24名对照和18名“创新”意大利患者用于验证。在西班牙队列晚期PD的19例对照和19例PD患者中鉴定出PDRPSP。30名西班牙PD患者用于验证。目视比较三个中心的模式，然后进行交叉验证。此外，在8名多系统萎缩患者中确定了PDRP表达。结果可以在每个队列中确定PDRP。每种PDRP的特征都是丘脑，壳壳/苍白球，脑桥，小脑和运动皮层的相对过度代谢。这些变化与后顶叶，枕叶和额叶皮质的低代谢程度不同。在“ de-novo” PD受试者中，额叶代谢不足的程度较轻（意大利队列）。晚期PD受试者（西班牙队列）的枕骨代谢不足更为明显。PDRPIT，PDRPNL，在同一中心的验证队列中，PD患者中PD和PDRPSP的表达明显高于对照组（P <0.0001），并在交叉验证中保持显着性（P <0.005）。MSA中不存在PDRP表达。结论PDRP是跨PD人群和全球扫描平台的可再现疾病特征。需要进一步的研究来确定特定PD亚型的形貌，并确定和纠正中心特异的影响。