Boccalini Cecilia, Peretti Debora Elisa, Ribaldi Federica, Scheffler Max, Stampacchia Sara, Tomczyk Szymon, Rodriguez Cristelle, Montandon Marie Louise, Haller Sven, Giannakopoulos Panteleimon, Frisoni Giovanni Battista, Perani Daniela, Garibotto Valentina
Vita-Salute San Raffaele University, Italy.
University of Geneva, Switzerland.
J Nucl Med. 2022 Jul 21;64(2):266-73. doi: 10.2967/jnumed.122.264256.
Alzheimer's disease (AD) neuropathologic changes are β-amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual-phase amyloid-PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early-phase amyloid-PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late frames depict amyloid distribution. Our study aims to assess the comparability between early-phase amyloid-PET scans and F-fluorodeoxyglucose (F-FDG)-PET brain topography at the individual level, and their ability to discriminate patients. 166 subjects evaluated at the Geneva Memory Center, ranging from cognitively unimpaired to Mild Cognitive Impairment (MCI) and dementia, underwent early-phase amyloid-PET - using either F-florbetapir (eFBP) ( = 94) or F-flutemetamol (eFMM) ( = 72) - and F-FDG-PET. Aβ status was assessed. Standardized uptake value ratios (SUVR) were extracted to evaluate the correlation of eFBP/eFMM and their respective F-FDG-PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by Dice coefficient. Receiver operating characteristic analyses were performed to compare the discriminative power of eFBP/eFMM, and F-FDG-PET SUVR in AD-related metaROI between Aβ-negative healthy controls and cases in the AD continuum. Positive correlations were found between eFBP/eFMM and F-FDG-PET SUVR independently of Aβ status and Aβ radiotracer (R>0.72, p<0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabolism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and F-FDG-PET SUVR significantly discriminated AD patients from controls in the AD-related metaROIs (AUCFB = 0.888; AUCFMM=0.801), with F-FDG-PET performing slightly better, however not significantly (all p-value higher than 0.05), than others (AUCFDG=0.915 and 0.832 for subjects evaluated with F-FBP and F-FMM, respectively). The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP/eFMM imaging can replace F-FDG-PET imaging, as they reveal typical neurodegenerative patterns, or allow to exclude the presence of neurodegeneration. The finding shows cost-saving capacities of amyloid-PET and supports the routine use of the modality for individual classification in clinical practice.
阿尔茨海默病(AD)的神经病理变化包括β-淀粉样蛋白(Aβ)沉积、病理性tau蛋白和神经退行性变。双相淀粉样蛋白正电子发射断层扫描(PET)或许能够通过单次注射示踪剂来评估Aβ沉积和神经退行性变。早期淀粉样蛋白PET扫描可提供脑灌注的替代指标,该指标已显示出与通过代谢消耗测量的神经功能障碍具有良好的相关性,而晚期图像则描绘淀粉样蛋白的分布。我们的研究旨在评估个体水平上早期淀粉样蛋白PET扫描与F-氟脱氧葡萄糖(F-FDG)PET脑图谱之间的可比性,以及它们区分患者的能力。166名在日内瓦记忆中心接受评估的受试者,范围从认知未受损到轻度认知障碍(MCI)和痴呆,接受了早期淀粉样蛋白PET检查——使用F-氟贝他哌(eFBP)(n = 94)或F-氟替美莫(eFMM)(n = 72)——以及F-FDG-PET检查。评估了Aβ状态。提取标准化摄取值比率(SUVR)以评估eFBP/eFMM及其各自的F-FDG-PET扫描之间的相关性。采用单受试者程序通过Dice系数研究代谢减低和灌注减低图谱及其空间重叠情况。进行受试者工作特征分析,以比较eFBP/eFMM和F-FDG-PET SUVR在Aβ阴性健康对照与AD连续体病例中AD相关元感兴趣区(metaROI)的鉴别能力。发现eFBP/eFMM与F-FDG-PET SUVR之间存在正相关,与Aβ状态和Aβ放射性示踪剂无关(R>0.72,p<0.001)。eFBP/eFMM单受试者分析显示,存在与代谢减低图谱具有良好对应关系的显著灌注减低簇,与潜在的神经退行性模式无关。在AD相关的metaROI中,eFBP/eFMM和F-FDG-PET SUVR均能显著区分AD患者与对照(AUC FBP = 0.888;AUC FMM = 0.801),F-FDG-PET的表现略好,但与其他指标相比无显著差异(所有p值均高于0.05)(使用F-FBP和F-FMM评估的受试者的AUC FDG分别为0.915和0.832)。通过参数分析,在单受试者水平上,灌注分布与代谢分布具有可比性,尤其是在存在高神经退行性变负担的情况下。我们的研究结果表明,eFBP/eFMM成像可以替代F-FDG-PET成像,因为它们能揭示典型的神经退行性模式,或有助于排除神经退行性变的存在。这一发现显示了淀粉样蛋白PET的成本节约能力,并支持在临床实践中常规使用该方法进行个体分类。