Matsuda Hiroshi, Ito Kengo, Ishii Kazunari, Shimosegawa Eku, Okazawa Hidehiko, Mishina Masahiro, Mizumura Sunao, Ishii Kenji, Okita Kyoji, Shigemoto Yoko, Kato Takashi, Takenaka Akinori, Kaida Hayato, Hanaoka Kohei, Matsunaga Keiko, Hatazawa Jun, Ikawa Masamichi, Tsujikawa Tetsuya, Morooka Miyako, Ishibashi Kenji, Kameyama Masashi, Yamao Tensho, Miwa Kenta, Ogawa Masayo, Sato Noriko
Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira, Japan.
Department of Radiology, National Center of Neurology and Psychiatry, Kodaira, Japan.
Front Neurol. 2021 Jan 13;11:578753. doi: 10.3389/fneur.2020.578753. eCollection 2020.
In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development. We aimed to determine cutoffs for positivity in quantitative analysis of F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321). Ninety-three patients suspected of having AD underwent F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area. Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ = 51.3, < 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%. Quantitative analysis of amyloid PET using F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.
在临床实践中，在视觉判读淀粉样蛋白正电子发射断层扫描（PET）结果是阳性还是阴性时，模棱两可的结果不可避免。因此，有必要建立一种更客观的定量评估方法，以确定目前正在研发的疾病修饰药物的适用症。我们旨在确定认知障碍和疑似阿尔茨海默病（AD）患者中F-氟代甲硫氨酸PET定量分析的阳性临界值。我们还评估了淀粉样蛋白PET在AD诊断中的临床疗效。本研究已在日本临床试验注册中心（jRCTs，031180321）注册。93例疑似AD患者在7家机构接受了F-氟代甲硫氨酸PET检查。由两名获得董事会认证的核医学医师对每位患者的PET图像进行视觉评估，并将其分为淀粉样蛋白阳性或淀粉样蛋白阴性。如果两位阅片者得出不同的解读结果，则重新进行视觉评级，直至达成共识。使用标准化摄取值比率（SUVR）和标准化Centiloid（CL）量表，并以整个小脑作为参考区域，对PET图像进行定量分析。视觉判读得出61例PET扫描结果为阳性，32例为阴性。受试者操作特征分析确定，PET扫描定量评估与视觉判读的最佳一致性在SUVR为1.13、CL为16时曲线下面积为0.982。使用这些临界值，两种方法之间具有高度一致性（kappa = 0.88）。5例不一致的病例中，SUVR和CL值分别为1.00至1.22和1至26。在这些不一致的病例中，皮质活动的弥漫性或轻度局灶性升高使视觉判读产生混淆。淀粉样蛋白PET结果显著改变了AD的诊断（χ = 51.3，< 0.0001）。PET成像将极高度可能性类别所占比例从20.4%提高到46.2%，将极低可能性类别所占比例从0提高到22.6%。使用F-氟代甲硫氨酸对淀粉样蛋白PET进行定量分析，可以使用确定的SUVR和CL临界值客观地评估淀粉样蛋白阳性情况。此外，对于认知障碍和疑似AD的痴呆患者，淀粉样蛋白PET可能比标准诊断检查具有更高的价值。
