Woodcock Eric A, Schain Martin, Cosgrove Kelly P, Hillmer Ansel T
Department of Pscyhiatry, Yale School of Medicine, 300 George St., New Haven, CT, USA.
Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark.
EJNMMI Res. 2020 Mar 12;10(1):19. doi: 10.1186/s13550-020-0605-7.
Lipopolysaccharide (LPS) is a classic immune stimulus. LPS combined with positron emission tomography (PET) 18 kDa translocator protein (TSPO) brain imaging provides a robust human laboratory model to study neuroimmune signaling. To evaluate optimal analysis of these data, this work compared the sensitivity of six quantification approaches.
[C]PBR28 data from healthy volunteers (N = 8) were collected before and 3 h after LPS challenge (1.0 ng/kg IV). Quantification approaches included total volume of distribution estimated with two tissue, and two tissue plus irreversible uptake in whole blood, compartment models (2TCM and 2TCM-1k, respectively) and multilinear analysis-1 (MA-1); binding potential estimated with simultaneous estimation (SIME); standardized uptake values (SUV); and SUV ratio (SUVR).
The 2TCM, 2TCM-1k, MA-1, and SIME approaches each yielded substantive effect sizes for LPS effects (partial η = 0.56-0.89, ps <. 05), whereas SUV and SUVR did not.
These findings highlight the importance of incorporating AIF measurements to quantify LPS-TSPO studies.
脂多糖(LPS)是一种经典的免疫刺激物。LPS与正电子发射断层扫描(PET)18 kDa转位蛋白(TSPO)脑成像相结合,为研究神经免疫信号提供了一个强大的人体实验室模型。为了评估这些数据的最佳分析方法,本研究比较了六种定量方法的敏感性。
收集8名健康志愿者在静脉注射LPS(1.0 ng/kg)前和注射后3小时的[C]PBR28数据。定量方法包括用两种组织、两种组织加全血不可逆摄取的分布总体积估计的房室模型(分别为2TCM和2TCM-1k)以及多线性分析-1(MA-1);用同时估计法(SIME)估计的结合潜能;标准化摄取值(SUV);以及SUV比值(SUVR)。
2TCM、2TCM-1k、MA-1和SIME方法对LPS效应均产生了显著的效应量(偏η=0.56-0.89,p<0.05),而SUV和SUVR则没有。
这些发现突出了纳入动脉输入函数(AIF)测量以量化LPS-TSPO研究的重要性。