Research Team for Neuroimaging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage, Chiba, 263-8555, Japan.
Ann Nucl Med. 2022 Oct;36(10):865-875. doi: 10.1007/s12149-022-01769-x. Epub 2022 Jul 11.
Although beta-amyloid (Aβ) positron emission tomography (PET) images are interpreted visually as positive or negative, approximately 10% are judged as equivocal in Alzheimer's disease. Therefore, we aimed to develop an automated semi-quantitative analysis technique using F-flutemetamol PET images without anatomical images.
Overall, 136 cases of patients administered F-flutemetamol were enrolled. Of 136 cases, five PET images each with the highest and lowest values of standardized uptake value ratio (SUVr) of cerebral cortex-to-pons were used to create positive and negative templates. Using these templates, PET images of the remaining 126 cases were standardized, and SUVr images were produced with the pons as a reference region. The mean of SUVr values in the volume of interest delineated on the cerebral cortex was compared to those in the CortexID Suite (GE Healthcare). Furthermore, centiloid (CL) values were calculated for the 126 cases using data from the Centiloid Project ( http://www.gaain.org/centiloid-project ) and both templates. F-flutemetamol-PET was interpreted visually as positive/negative based on Aβ deposition in the cortex. However, the criterion "equivocal" was added for cases with focal or mild Aβ accumulation that were difficult to categorize. Optimal cutoff values of SUVr and CL maximizing sensitivity and specificity for Aβ detection were determined by receiver operating characteristic (ROC) analysis using the visual evaluation as a standard of truth.
SUVr calculated by our method and CortexID were highly correlated (R = 0.9657). The 126 PET images comprised 84 negative and 42 positive cases of Aβ deposition by visual evaluation, of which 11 and 10 were classified as equivocal, respectively. ROC analyses determined the optimal cutoff values, sensitivity, and specificity for SUVr as 0.544, 89.3%, and 92.9%, respectively, and for CL as 12.400, 94.0%, and 92.9%, respectively. Both semi-quantitative analyses showed that 12 and 9 of the 21 equivocal cases were negative and positive, respectively, under the optimal cutoff values.
This semi-quantitative analysis technique using F-flutemetamol-PET calculated SUVr and CL automatically without anatomical images. Moreover, it objectively and homogeneously interpreted positive or negative Aβ burden in the brain as a supplemental tool for the visual reading of equivocal cases in routine clinical practice.
尽管β-淀粉样蛋白(Aβ)正电子发射断层扫描(PET)图像的解读结果为阳性或阴性,但在阿尔茨海默病中,约有 10%的结果被判断为不确定。因此,我们旨在开发一种无需解剖图像的使用 F-氟替美莫 PET 图像的自动半定量分析技术。
共纳入 136 例接受 F-氟替美莫 PET 检查的患者。在这 136 例患者中,每例各选取皮质与脑桥标准化摄取值比值(SUVr)最高和最低的 5 个 PET 图像,以创建阳性和阴性模板。使用这些模板,对其余 126 例患者的 PET 图像进行标准化,并以脑桥为参考区域生成 SUVr 图像。比较皮质感兴趣容积内 SUVr 值的平均值与 CortexID 套件(GE Healthcare)的结果。此外,使用 Centiloid 项目(http://www.gaain.org/centiloid-project)的数据,为 126 例患者计算了 centiloid(CL)值,并使用这两种模板。根据皮质 Aβ 沉积情况,F-氟替美莫 PET 图像通过视觉评估解读为阳性/阴性。然而,对于难以分类的局灶性或轻度 Aβ 积聚病例,添加了“不确定”标准。使用受试者工作特征(ROC)分析,以视觉评估为标准,确定了用于 Aβ 检测的 SUVr 和 CL 的最佳截断值,以最大化灵敏度和特异性。
本研究方法计算的 SUVr 与 CortexID 高度相关(R=0.9657)。126 例 PET 图像根据视觉评估结果,包括 84 例 Aβ 沉积阴性和 42 例 Aβ 沉积阳性,其中 11 例和 10 例分别被归类为不确定。ROC 分析确定 SUVr 的最佳截断值、灵敏度和特异性分别为 0.544、89.3%和 92.9%,CL 为 12.400、94.0%和 92.9%。两种半定量分析结果均显示,21 例不确定病例中,12 例和 9 例分别在最佳截断值下为阴性和阳性。
本研究使用 F-氟替美莫 PET 自动计算 SUVr 和 CL,无需使用解剖图像。此外,该技术还可作为常规临床实践中视觉解读不确定病例的补充工具,客观、均匀地解读大脑中 Aβ 负担的阳性或阴性。