Department of Radiology, Mayo Clinic, Rochester, Minnesota
Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
J Nucl Med. 2018 Oct;59(10):1583-1589. doi: 10.2967/jnumed.117.204271. Epub 2018 Apr 19.
Amyloid-β (Aβ) deposition as seen on PET using an Aβ-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. To investigate the suitability of WM as a reference region and the factors affecting WM C-Pittsburgh compound B (C-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants ( = 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a cross-sectional study of single-scan PET imaging in CU subjects ( = 1,349). In the longitudinal study, annual changes in WM C-PiB uptake were assessed, and in the cross-sectional study, WM C-PiB uptake was assessed relative to subject age. Overall, we found that WM C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM C-PiB uptake changes were seen with different gray matter (GM) C-PiB baseline uptake levels. WM binding increases with age and varies with GM C-PiB. These correlations should be considered when using WM for normalization in C-PiB PET studies. The cerebellar crus1+crus2 showed no increase with age and cerebellar GM+WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM C-PiB uptake may relate to disease progression, warranting examination of the causes of WM C-PiB uptake.
淀粉样蛋白-β（Aβ）在正电子发射断层扫描（PET）中与 Aβ 结合剂结合的沉积是阿尔茨海默病（AD）的一个关键诊断生物标志物。一些报告表明，使用脑白质（WM）作为定量分析淀粉样蛋白 PET 研究的参考区域；然而，在痴呆或认知正常（CU）的人群中，淀粉样蛋白 PET 中的非特异性 WM 保留已被广泛报道，但知之甚少。为了研究 WM 作为参考区域的适宜性以及影响 WM C-Pittsburgh 化合物 B（C-PiB）摄取变异性的因素，我们对 2 个大型数据集进行了回顾性研究：一个是参与者的纵向研究（=577），他们是 CU，有轻度认知障碍，或有痴呆症，可能是 AD；另一个是 CU 受试者单扫描 PET 成像的横断面研究（=1349）。在纵向研究中，评估了 WM C-PiB 摄取的年度变化，在横断面研究中，评估了 WM C-PiB 摄取与受试者年龄的关系。总的来说，我们发现 WM C-PiB 摄取随年龄增长而增加，这与所选 WM 区域有关。此外，还发现不同的灰质（GM）C-PiB 基线摄取水平下 WM C-PiB 摄取的年变化存在差异。WM 结合物随年龄增长而增加，与 GM C-PiB 有关。在使用 WM 进行 C-PiB PET 研究的归一化时，应考虑这些相关性。小脑 crus1+crus2 与年龄无关，小脑 GM+WM 增加最小，支持将其用作比较宽年龄跨度的横断面研究的参考区域。在纵向研究中，短期内 WM 摄取的增加可能很小，因此在这些研究中使用 WM 作为参考区域似乎是合理的。然而，随着参与者年龄的增长，WM 摄取的变化可能会受到影响。WM C-PiB 摄取的变化可能与疾病进展有关，有必要检查 WM C-PiB 摄取的原因。
