Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes
Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes
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DOI：
10.1001/jamaneurol.2015.1633
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发表时间：
2015-10-01
期刊：
影响因子：
29
通讯作者：
Jagust, William J.
中科院分区：
文献类型：
--
作者：
Schreiber, Stefanie;Landau, Susan M.;Jagust, William J.
重要性 β-淀粉样肽 (Aβ) 正电子发射断层扫描 (PET) 作为临床环境中的生物标志物以帮助选择临床前和前驱阿尔茨海默病 (AD) 个体的适用性将取决于 PET 图像分析的实用性。在这种情况下，基于视觉的 Aβ PET 评估似乎是最可行的方法。 目的 确定视觉和定量 Aβ PET 分析之间的一致性，并评估两种技术预测从轻度认知障碍 (MCI) 转变为 AD 的能力。 设计、设置和参与者 在美国和加拿大的阿尔茨海默病神经影像计划 (ADNI) 站点中进行了一项纵向研究，平均随访期为 1.6 年。该研究于2010年9月21日至2014年8月11日进行；数据分析于2014年9月21日至2015年5月26日进行。参与者包括401名在专科诊所接受护理的MCI患者（219名[54.6%]男性；平均[SD]年龄，71.6[7.5]岁；16.2[2.7]年教育）。所有参与者均接受了氟贝吡 F 18 [F-18] PET 研究。标准化摄取值比 (SUVR) 阳性阈值为 1.11，一位读者对所有图像进行评分，其中 125 个扫描的子集由另一位读者评分。 主要结果和测量 阳性和阴性 [F-18] 氟贝丕 PET 分类的敏感性和特异性，以脑脊液 A beta 1-42 作为参考标准进行估计。使用 Cox 比例风险回归模型评估转化为 AD 的风险。 结果 Aβ 阳性频率为 48.9%（196 名患者；视觉分析）、55.1%（221 名患者；SUVR）和 64.8%（166 名患者；脑脊液），视觉和 SUVR 数据之间（kappa = 0.74）以及所有方法之间（Fleiss kappa = 0.71）。在 401 名视觉和 SUVR 数据不一致的参与者中，大约有 10% 的参与者间可靠性中等（kappa = 0.44），但如果视觉和定量结果一致，则该可靠性非常高（kappa = 0.92）。与SUVR相比，视觉分析的敏感性较低（79% vs 85%），但特异性较高（96% vs 90%）。平均 1.6 年内的转化率为 15.2%，[F-18] 氟倍吡基线扫描阳性与 AD 转化风险增加 6.91 倍（SUVR）或 11.38 倍（视觉）相关，在对载脂蛋白 epsilon 4 进行协变量调整、同时进行氟脱氧葡萄糖 F 18 PET 扫描和基线认知状态后，这种风险仅略有变化。相关性 视觉和 SUVR A beta PET 分析可等效用于确定参与临床试验的 MCI 个体的 A beta 状态，并且这两种方法都为临床病程预测增加了重要价值。
IMPORTANCE The applicability of beta-amyloid peptide (A beta) positron emission tomography (PET) as a biomarker in clinical settings to aid in selection of individuals at preclinical and prodromal Alzheimer disease (AD) will depend on the practicality of PET image analysis. In this context, visual-based A beta PET assessment seems to be the most feasible approach.OBJECTIVES To determine the agreement between visual and quantitative A beta PET analysis and to assess the ability of both techniques to predict conversion from mild cognitive impairment (MCI) to AD.DESIGN, SETTING, AND PARTICIPANTS A longitudinal study was conducted among the Alzheimer's Disease Neuroimaging Initiative (ADNI) sites in the United States and Canada during a 1.6-year mean follow-up period. The study was performed from September 21, 2010, to August 11, 2014; data analysis was conducted from September 21, 2014, to May 26, 2015. Participants included 401 individuals with MCI receiving care at a specialty clinic (219 [54.6%] men; mean [SD] age, 71.6 [7.5] years; 16.2 [2.7] years of education). All participants were studied with florbetapir F 18 [F-18] PET. The standardized uptake value ratio (SUVR) positivity threshold was 1.11, and one reader rated all images, with a subset of 125 scans rated by a second reader.MAIN OUTCOMES AND MEASURES Sensitivity and specificity of positive and negative [F-18] florbetapir PET categorization, which was estimated with cerebrospinal fluid A beta 1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models.RESULTS The frequency of A beta positivity was 48.9%(196 patients; visual analysis), 55.1%(221 patients; SUVR), and 64.8%(166 patients; cerebrospinal fluid), yielding substantial agreement between visual and SUVR data (kappa = 0.74) and between all methods (Fleiss kappa = 0.71). For approximately 10% of the 401 participants in whom visual and SUVR data disagreed, interrater reliability was moderate (kappa = 0.44), but it was very high if visual and quantitative results agreed (kappa = 0.92). Visual analysis had a lower sensitivity (79% vs 85%) but higher specificity (96% vs 90%), respectively, compared with SUVR. The conversion rate was 15.2% within a mean of 1.6 years, and a positive [F-18] florbetapir baseline scan was associated with a 6.91-fold (SUVR) or 11.38-fold (visual) greater hazard for AD conversion, which changed only modestly after covariate adjustment for apolipoprotein epsilon 4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status.CONCLUSIONS AND RELEVANCE Visual and SUVR A beta PET analysis may be equivalently used to determine A beta status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication.