Teipel Stefan J, Dyrba Martin, Vergallo Andrea, Lista Simone, Habert Marie Odile, Potier Marie-Claude, Lamari Foudil, Dubois Bruno, Hampel Harald, Grothe Michel J
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.
Front Aging Neurosci. 2021 Dec 22;13:748198. doi: 10.3389/fnagi.2021.748198. eCollection 2021.
To test whether correcting for unspecific signal from the cerebral white matter increases the sensitivity of amyloid-PET for early stages of cerebral amyloidosis. We analyzed 18F-Florbetapir-PET and cerebrospinal fluid (CSF) Aβ42 data from 600 older individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), including people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia. We determined whether three compartmental partial volume correction (PVC-3), explicitly modeling signal spill-in from white matter, significantly improved the association of CSF Aβ42 levels with global 18F-Florbetapir-PET values compared with standard processing without PVC (non-PVC) and a widely used two-compartmental PVC method (PVC-2). In additional voxel-wise analyses, we determined the sensitivity of PVC-3 compared with non-PVC and PVC-2 for detecting early regional amyloid build-up as modeled by decreasing CSF Aβ42 levels. For replication, we included an independent sample of 43 older individuals with subjective memory complaints from the INveStIGation of AlzHeimer's PredicTors cohort (INSIGHT-preAD study). In the ADNI sample, PVC-3 18F-Florbetapir-PET values normalized to whole cerebellum signal showed significantly stronger associations with CSF Aβ42 levels than non-PVC or PVC-2, particularly in the lower range of amyloid levels. These effects were replicated in the INSIGHT-preAD sample. PVC-3 18F-Florbetapir-PET data detected regional amyloid build-up already at higher (less abnormal) CSF Aβ42 levels than non-PVC or PVC-2 data. A PVC approach that explicitly models unspecific white matter binding improves the sensitivity of amyloid-PET for identifying the earliest stages of cerebral amyloid pathology which has implications for future primary prevention trials.
为了测试校正来自脑白质的非特异性信号是否会提高淀粉样蛋白PET对脑淀粉样变性早期阶段的敏感性。我们分析了来自阿尔茨海默病神经影像学倡议（ADNI）的600名老年人的18F-氟代贝他吡PET和脑脊液（CSF）Aβ42数据，包括认知正常、轻度认知障碍（MCI）和阿尔茨海默病（AD）痴呆患者。我们确定，与未进行部分容积校正（非PVC）的标准处理和广泛使用的两室部分容积校正方法（PVC-2）相比，明确模拟白质信号溢出的三室部分容积校正（PVC-3）是否能显著改善CSF Aβ42水平与整体18F-氟代贝他吡PET值之间的相关性。在额外的体素级分析中，我们确定了PVC-3与非PVC和PVC-2相比，在检测由CSF Aβ42水平降低所模拟的早期区域淀粉样蛋白积聚方面的敏感性。为了进行重复验证，我们纳入了来自阿尔茨海默病预测指标队列（INSIGHT-preAD研究）的43名有主观记忆主诉的老年人的独立样本。在ADNI样本中，归一化为全小脑信号的PVC-3 18F-氟代贝他吡PET值与CSF Aβ42水平的相关性显著强于非PVC或PVC-2，特别是在较低的淀粉样蛋白水平范围内。这些效应在INSIGHT-preAD样本中得到了重复验证。与非PVC或PVC-2数据相比，PVC-3 18F-氟代贝他吡PET数据在CSF Aβ42水平较高（异常程度较轻）时就能检测到区域淀粉样蛋白积聚。一种明确模拟非特异性白质结合的部分容积校正方法提高了淀粉样蛋白PET识别脑淀粉样病变最早阶段的敏感性，这对未来的一级预防试验具有重要意义。
