The translocator protein (TSPO) is a commonly used imaging target to investigate neuroinflammation. Although TSPO imaging demonstrates great promise, its signal exhibits substantial interindividual variability, which needs to be accounted for to uncover group effects that are truly reflective of neuroimmune activation. Recent evidence suggests that relative metrics computed using pseudoreference approaches can minimize within-group variability and increase sensitivity to detect physiologically meaningful group differences. Here, we evaluated various ratio approaches for TSPO imaging and compared them with standard kinetic modeling techniques, analyzing 2 different disease cohorts. Patients with chronic low back pain (cLBP) or amyotrophic lateral sclerosis (ALS) and matching healthy controls received ¹¹C-PBR28 PET scans. The occipital cortex, cerebellum and whole brain were first evaluated as candidate pseudoreference regions by testing for the absence of group differences in SUV and distribution volume (V_T) estimated with an arterial input function. The SUV from target regions (cLBP study, thalamus; ALS study, precentral gyrus) was normalized with the SUV from candidate pseudoreference regions (i.e., occipital cortex, cerebellum, and whole brain) to obtain SUVR_occip, SUVR_cereb, and SUVR_WB. The sensitivity to detect group differences in target regions was compared using various SUVR approaches, as well as distribution volume ratio (DVR) estimated with (blDVR) or without arterial input function (refDVR), and V_T. Additional voxelwise SUVR group analyses were performed. We observed no significant group differences in pseudoreference V_T or SUV, excepting whole-brain V_T, which was higher in cLBP patients than controls. Target V_T elevations in patients (P = 0.028 and 0.051 in cLBP and ALS, respectively) were similarly detected by SUVR_occip and SUVR_WB, and by refDVR and blDVR (less reliably by SUVR_cereb). In voxelwise analyses, SUVR_occip, but not SUVR_cereb, identified regional group differences initially observed with SUVR_WB, and in additional areas suspected to be affected in the pathology examined. All ratio metrics were highly cross-correlated, but generally were not associated with V_T. Although important caveats need to be considered when using relative metrics, ratio analyses appear to be similarly sensitive to detect pathology-related group differences in ¹¹C-PBR28 signal as classic kinetic modeling techniques. The occipital cortex may be a suitable pseudoreference region, at least for the populations evaluated, pending further validation in larger cohorts.

易位蛋白（TSPO）是研究神经炎症的常用成像靶点。尽管 TSPO 成像显示出巨大的前景，但其信号表现出巨大的个体间差异，需要考虑到这一点才能揭示真正反映神经免疫激活的群体效应。最近的证据表明，使用伪参考方法计算的相对指标可以最大限度地减少组内变异性，并提高检测具有生理意义的组差异的灵敏度。在这里，我们评估了 TSPO 成像的各种比率方法，并将它们与标准动力学建模技术进行比较，分析了 2 个不同的疾病队列。患有慢性腰痛 (cLBP) 或肌萎缩侧索硬化症 (ALS) 的患者以及匹配的健康对照者接受了^{11 次}C-PBR28 PET 扫描。首先通过测试用动脉输入函数估计的 SUV 和分布容积 ( VT ) 是否存在组间差异_，将枕叶皮层、小脑和全脑评估为候选伪参考区域。将目标区域（cLBP 研究、丘脑；ALS 研究、中央前回）的 SUV 用候选伪参考区域（即枕叶皮质、小脑和全脑）的 SUV 标准化，以获得 SUVR _occip 、SUVR _cereb和 SUVR _WB 。使用各种 SUVR 方法以及使用 (blDVR) 或不使用动脉输入功能 (refDVR) 估计的分布容积比 (DVR) 和V _T来比较检测目标区域中群体差异的敏感性。进行了额外的体素 SUVR 组分析。 我们观察到伪参考V _T或 SUV 没有显着的组间差异，但全脑V _T除外，cLBP 患者的全脑 V T 高于对照组。患者的目标V _T升高（cLBP 和 ALS 中分别P = 0.028 和 0.051）通过 SUVR _occip和 SUVR _WB以及 refDVR 和 blDVR（SUVR _cereb不太可靠）检测到。在体素分析中，SUVR _occip而非 SUVR _cereb确定了最初在 SUVR _WB中观察到的区域组差异，以及在所检查的病理学中怀疑受到影响的其他区域。所有比率指标均高度互相关，但通常与V _T无关。尽管在使用相对指标时需要考虑重要注意事项，但比率分析似乎对于检测¹¹ C-PBR28 信号中病理相关的组差异同样敏感作为经典的动力学建模技术。枕叶皮层可能是一个合适的伪参考区域，至少对于所评估的人群来说是这样，有待在更大的队列中进一步验证。