Several studies have demonstrated strong agreement between routine clinical visual assessment and quantification, suggesting that quantification approaches could support assessment by less experienced readers or in challenging cases. However, all studies to date have implemented a retrospective case collection, and challenging cases were generally underrepresented. Methods: We included all participants (n = 741) from the AMYPAD diagnostic and patient management study with available baseline amyloid PET quantification. Quantification was done with the PET-only AmyPype pipeline, providing global Centiloid and regional z scores. Visual assessment was performed by local readers for the entire cohort. From the total cohort, we selected a subsample of 85 cases for which the amyloid status based on the local reader’s visual assessment and the Centiloid classification (cutoff = 21) was discordant or that were assessed with low confidence (i.e., ≤3 on a 5-point scale) by the local reader. In addition, concordant negative (n = 8) and positive (n = 8) scans across tracers were selected. In this sample (n = 101 cases; [¹⁸F]flutemetamol, n = 48; [¹⁸F]florbetaben, n = 53), the visual assessments and corresponding confidence by 5 certified independent central readers were captured before and after disclosure of the quantification results. Results: For the whole AMYPAD diagnostic and patient management study cohort, overall assessment by local readers highly agreed with Centiloid status ( = 0.85, 92.3% agreement). This was consistently observed within disease stages (subjective cognitive decline–plus, = 0.82, 92.3% agreement; mild cognitive impairment, = 0.80, 89.8% agreement; dementia, = 0.87, 94.6% agreement). Across all central reader assessments in the challenging subsample, quantification of global Centiloid and regional z scores was considered supportive of visual reads in 70.3% and 49.3% of assessments, respectively. After disclosure of the quantitative results, we observed improvement in concordance across the 5 readers (baseline = 0.65, 65.3% agreement; after disclosure = 0.74, 73.3% agreement) and a significant increase in reader confidence (baseline mean (M) = 4.0 vs. M after disclosure = 4.34, Wilcoxon statistic (W) = 101,056, P < 0.001). Conclusion: In this clinical study enriched for challenging amyloid PET cases, we demonstrate the value of quantification to support visual assessment. After disclosure, both interreader agreement and confidence showed significant improvement. These results are important considering the arrival of antiamyloid therapies, which used the Centiloid metric for trial inclusion and target engagement. Moreover, quantification could support determination of amyloid-β status with high certainty, an important factor for treatment initiation.

几项研究表明，常规临床视觉评估和量化之间有很强的一致性，这表明量化方法可以支持经验不足的读者或具有挑战性的病例进行评估。然而，迄今为止的所有研究都实施了回顾性病例收集，具有挑战性的病例通常代表性不足。方法：我们纳入了来自 AMYPAD 诊断和患者管理研究的所有参与者 （n = 741），并提供了可用的基线淀粉样蛋白 PET 定量。使用仅 PET 的 AmyPype 管道进行定量，提供全球 Centiloid 和区域 z 评分。由本地读者对整个队列进行视觉评估。从总队列中，我们选择了 85 例病例的子样本，这些病例的淀粉样蛋白状态基于当地读者的视觉评估和 Centiloid 分类 （临界值 = 21） 不一致或以低置信度评估 （即，≤3 分制） 由当地读者。此外，还选择了跨示踪剂的一致阴性 （n = 8） 和阳性 （n = 8） 扫描。在这个样本中 （n = 101 个案例;[¹⁸F]flutemetamol， n = 48;[¹⁸F]florbetaben， n = 53），在量化结果披露之前和之后捕获 5 名经过认证的独立中央读者的视觉评估和相应的置信度。结果：对于整个 AMYPAD 诊断和患者管理研究队列，当地读者的总体评估与 Centiloid 状态高度一致 （ = 0.85,92.3% 一致性）。这在疾病阶段中一致观察到 （主观认知能力下降 – plus，= 0.82,92.3% 一致性;轻度认知障碍，= 0.80,89。8% 协议;痴呆，= 0.87,94.6% 一致性）。在具有挑战性的子样本中的所有中央读者评估中，全球 Centiloid 和区域 z 分数的量化分别在 70.3% 和 49.3% 的评估中被认为支持视觉阅读。披露定量结果后，我们观察到 5 名读者的一致性有所提高（基线 = 0.65,65.3% 一致性;披露后 = 0.74,73.3% 一致性）和读者信心显着增加（基线平均值 （M） = 4.0 vs. 披露后 M = 4.34，Wilcoxon 统计量 （W） = 101,056，P < 0.001）。 结论：在这项针对具有挑战性的淀粉样蛋白 PET 病例的丰富临床研究中，我们证明了定量对支持视觉评估的价值。披露后，读者的一致性和信心均显示出显着改善。考虑到抗淀粉样蛋白疗法的到来，这些结果很重要，这些疗法使用 Centiloid 指标进行试验纳入和靶点参与。此外，定量可以支持高质量地确定淀粉样蛋白β状态，这是治疗开始的一个重要因素。