Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
Gordon Center for Medical Imaging, NMMI, Radiology Department, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts.
J Nucl Med. 2018 Jan;59(1):107-114. doi: 10.2967/jnumed.116.178335. Epub 2017 Aug 17.
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 C-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 () 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, SUVR, and SUVR 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 Additional voxelwise SUVR group analyses were performed. We observed no significant group differences in pseudoreference or SUV, excepting whole-brain , which was higher in cLBP patients than controls. Target elevations in patients ( = 0.028 and 0.051 in cLBP and ALS, respectively) were similarly detected by SUVR and SUVR, and by refDVR and blDVR (less reliably by SUVR). In voxelwise analyses, SUVR, but not SUVR, identified regional group differences initially observed with SUVR, 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 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 C-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.
转位蛋白（TSPO）是一种常用于研究神经炎症的成像靶点。尽管 TSPO 成像显示出巨大的应用前景，但它的信号存在很大的个体间变异性，需要对其进行解释以揭示真正反映神经免疫激活的组间效应。最近的证据表明，使用伪参照方法计算的相对指标可以最小化组内变异性并提高检测具有生理意义的组间差异的敏感性。在这里，我们评估了 TSPO 成像的各种比率方法，并将其与标准动力学建模技术进行了比较，分析了 2 个不同的疾病队列。患有慢性下腰痛（cLBP）或肌萎缩侧索硬化症（ALS）的患者和匹配的健康对照者接受了 C-PBR28 PET 扫描。通过测试在使用动脉输入函数估计的 SUV 和分布容积（）中是否存在组间差异，首先将枕叶皮层、小脑和全脑评估为候选伪参照区域。使用候选伪参照区域（即枕叶皮层、小脑和全脑）对目标区域（cLBP 研究，丘脑；ALS 研究，中央前回）的 SUV 进行归一化，以获得 SUVR、SUV 和 SUV 。使用各种 SUVR 方法比较了检测目标区域组间差异的敏感性，还比较了使用（blDVR）或不使用动脉输入函数（refDVR）估计的分布容积比（DVR）以及额外的体素水平 SUVR 组分析。我们观察到除全脑外，候选物的 SUV 和分布容积均无显著组间差异，而全脑的分布容积则高于对照组。患者的靶标升高（cLBP 和 ALS 分别为 0.028 和 0.051），同样可以通过 SUVR 和 SUVR 以及 refDVR 和 blDVR 检测到（通过 SUVR 检测到的可靠性较低）。在体素水平分析中，SUVR 而非 SUVR 识别了最初通过 SUVR 观察到的区域性组间差异，并在被检查的病理中怀疑受到影响的其他区域中识别了这些差异。所有比率指标都高度相关，但与总体分布容积无显著相关性。虽然在使用相对指标时需要注意一些重要的注意事项，但比率分析似乎与经典动力学建模技术一样，能够检测到 C-PBR28 信号中与病理相关的组间差异。在等待更大队列进一步验证的情况下，枕叶皮层可能是一种合适的伪参照区域，至少对于评估的人群是如此。
