Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
J Nucl Med. 2021 Feb;62(2):247-252. doi: 10.2967/jnumed.120.245209. Epub 2020 Jul 31.
Amyloid-β deposition into plaques is a pathologic hallmark of Alzheimer disease appearing years before the onset of symptoms. Although cerebral amyloid-β deposition occurs on a continuum, dichotomization into positive and negative groups has advantages for diagnosis, clinical management, and population enrichment for clinical trials. F-AZD4694 (also known as F-NAV4694) is an amyloid-β imaging ligand with high affinity for amyloid-β plaques. Despite being used in multiple academic centers, no studies have assessed a quantitative cutoff for amyloid-β positivity using F-AZD4694 PET. We assessed 176 individuals [young adults ( = 22), cognitively unimpaired elderly ( = 89), and cognitively impaired ( = 65)] who underwent amyloid-β PET with F-AZD4694, lumbar puncture, structural MRI, and genotyping for F-AZD4694 values were normalized using the cerebellar gray matter as a reference region. We compared 5 methods for deriving a quantitative threshold for F-AZD4694 PET positivity: comparison with young-control SUV ratios (SUVRs), receiver-operating-characteristic (ROC) curves based on clinical classification of cognitively unimpaired elderly versus Alzheimer disease dementia, ROC curves based on visual Aβ-positive/Aβ-negative classification, gaussian mixture modeling, and comparison with cerebrospinal fluid measures of amyloid-β, specifically the Aβ/Aβ ratio. We observed good convergence among the 4 methods: ROC curves based on visual classification (optimal cut point, 1.55 SUVR), ROC curves based on clinical classification (optimal cut point, 1.56 SUVR) gaussian mixture modeling (optimal cut point, 1.55 SUVR), and comparison with cerebrospinal fluid measures of amyloid-β (optimal cut point, 1.51 SUVR). Means and 2 SDs from young controls resulted in a lower threshold (1.33 SUVR) that did not agree with the other methods and labeled most elderly individuals as Aβ-positive. Good convergence was obtained among several methods for determining an optimal cutoff for F-AZD4694 PET positivity. Despite conceptual and analytic idiosyncrasies linked with dichotomization of continuous variables, an F-AZD4694 threshold of 1.55 SUVR had reliable discriminative accuracy. Although clinical use of amyloid PET is currently by visual inspection of scans, quantitative thresholds may be helpful to arbitrate disagreement among raters or in borderline cases.
淀粉样蛋白-β在斑块中的沉积是阿尔茨海默病的病理标志，早在症状出现前多年就出现了。尽管脑淀粉样蛋白-β沉积是连续的，但将其分为阳性和阴性组有利于诊断、临床管理和临床试验人群的富集。F-AZD4694（也称为 F-NAV4694）是一种淀粉样蛋白-β成像配体，对淀粉样蛋白-β斑块具有高亲和力。尽管已在多个学术中心使用，但尚无研究使用 F-AZD4694 PET 评估淀粉样蛋白-β阳性的定量截止值。我们评估了 176 名个体[年轻人（ = 22）、认知正常的老年人（ = 89）和认知受损的老年人（ = 65）]，他们接受了 F-AZD4694 淀粉样蛋白-β PET、腰椎穿刺、结构 MRI 检查，并对 F-AZD4694 值进行了基因分型，使用小脑灰质作为参考区域对 F-AZD4694 PET 阳性的定量阈值进行了归一化。我们比较了 5 种用于确定 F-AZD4694 PET 阳性定量阈值的方法：与年轻对照组 SUV 比（SUVR）比较、基于认知正常老年人与阿尔茨海默病痴呆临床分类的受试者工作特征（ROC）曲线、基于视觉 Aβ-阳性/Aβ-阴性分类的 ROC 曲线、高斯混合建模以及与脑脊液中淀粉样蛋白-β的比较，特别是 Aβ/Aβ 比值。我们观察到 4 种方法之间有很好的一致性：基于视觉分类的 ROC 曲线（最佳截断点，1.55 SUVR）、基于临床分类的 ROC 曲线（最佳截断点，1.56 SUVR）、高斯混合建模（最佳截断点，1.55 SUVR），以及与脑脊液中淀粉样蛋白-β的比较（最佳截断点，1.51 SUVR）。来自年轻对照组的平均值和 2 SD 导致较低的阈值（1.33 SUVR），该阈值与其他方法不一致，并导致大多数老年人被标记为 Aβ 阳性。对于确定 F-AZD4694 PET 阳性的最佳截断值，几种方法之间获得了很好的一致性。尽管与连续变量的二分法相关联的概念和分析上的特殊性，但 F-AZD4694 阈值为 1.55 SUVR 具有可靠的判别准确性。尽管淀粉样蛋白 PET 的临床应用目前是通过扫描的视觉检查，但定量阈值可能有助于在评分者之间或在边界情况下做出裁决。
