Ayers Gregory D, Cohen Allison S, Bae Seong-Woo, Wen Xiaoxia, Pollard Alyssa, Sharma Shilpa, Claus Trey, Payne Adria, Geng Ling, Zhao Ping, Tantawy Mohammed Noor, Gammon Seth T, Manning H Charles
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States of America.
PLoS One. 2025 Jan 9;20(1):e0313123. doi: 10.1371/journal.pone.0313123. eCollection 2025.
Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.
Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 MBq of 18F-Gln and imaged in an Inveon microPET. Three individuals analyzed the tumor uptake of 18F-Gln using the same set of images, the same image analysis software, and the same analysis method. Scans were randomly re-ordered for a second repeatability measurement 6 months later. Statistical analyses were performed using the methods of Bland and Altman (B&A), Gauge Reproducibility and Repeatability (Gauge R&R), and Lin's Concordance Correlation Coefficient. A comprehensive equivalency test, designed to reject a null hypothesis of non-equivalence, was also conducted.
In a two-way random effects Gauge R&R model, variance among mice and their measurement variance were 0.5717 and 0.024. Reproducibility and repeatability accounted for 31% and 69% of the total measurement error, respectively. B&A repeatability coefficients for analysts 1, 2, and 3 were 0.16, 0.35, and 0.49. One-half B&A agreement limits between analysts 1 and 2, 1 and 3, and 2 and 3 were 0.27, 0.47, and 0.47, respectively. The mean square deviation and total deviation index were lowest for analysts 1 and 2, while coverage probabilities and coefficients of the individual agreement were highest. Finally, the definitive agreement inference hypothesis test for equivalency demonstrated that all three confidence intervals for the average difference of means from repeated measures lie within our a priori limits of equivalence (i.e. ± 0.5%ID/g).
Our data indicate high individual analyst and laboratory-level reproducibility and repeatability. The assessment of R&R using the appropriate methods is critical and should be adopted by the broader imaging community.
测量重复性和再现性（R&R）对于充分发挥正电子发射断层扫描（PET）的潜力至关重要。多项研究评估了使用18F-FDG（肿瘤学中最常用的PET示踪剂）的PET的再现性，但使用其他PET示踪剂的类似研究却很少。更少的研究使用专门为此任务设计的统计方法来评估一致性和R&R。18F-(2S,4R)-4-氟谷氨酰胺（18F-Gln）是一种用于成像谷氨酰胺摄取和代谢的PET示踪剂。本研究表明18F-Gln在体内研究中具有高再现性和重复性。
给20只携带结直肠癌细胞系异种移植瘤的小鼠注射约9 MBq的18F-Gln，并在Inveon微型PET中成像。三名研究人员使用同一组图像、相同的图像分析软件和相同的分析方法分析18F-Gln的肿瘤摄取情况。6个月后对扫描结果进行随机重新排序以进行第二次重复性测量。使用布兰德-奥特曼（B&A）方法、量具再现性和重复性（量具R&R）以及林氏一致性相关系数进行统计分析。还进行了一项旨在拒绝非等效性零假设的综合等效性检验。
在双向随机效应量具R&R模型中，小鼠之间的方差及其测量方差分别为0.5717和0.024。再现性和重复性分别占总测量误差的31%和69%。研究人员1、2和3的B&A重复性系数分别为0.16、0.35和0.49。研究人员1与2、1与3以及2与3之间的B&A一致性界限的一半分别为0.27、0.47和0.47。研究人员1和2的均方差和总偏差指数最低，而个体一致性的覆盖概率和系数最高。最后，等效性的确定性一致性推断假设检验表明，重复测量均值差异的所有三个置信区间均在我们预先设定的等效性界限内（即±0.5%ID/g）。
我们的数据表明个体研究人员和实验室水平具有高再现性和重复性。使用适当方法评估R&R至关重要，更广泛的成像领域应采用这种方法。
