Hahn Andreas, Schain Martin, Erlandsson Maria, Sjölin Petter, James Gregory M, Strandberg Olof T, Hägerström Douglas, Lanzenberger Rupert, Jögi Jonas, Olsson Tomas G, Smith Ruben, Hansson Oskar
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
J Nucl Med. 2017 Apr;58(4):623-631. doi: 10.2967/jnumed.116.174508. Epub 2016 Oct 20.
Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer disease (AD). In vivo imaging with PET may offer important insights into pathophysiologic mechanisms, diagnosis, and disease progression. We describe different strategies for quantification of F-AV-1451 (T807) tau binding, including models with blood sampling and noninvasive alternatives. Fifteen subjects (4 controls, 6 AD, 3 progressive supranuclear palsy, 2 cortico basal syndrome) underwent 180-min PET with F-AV-1451 and arterial blood sampling. Modeling with arterial input functions included 1-, 2-, and 3-tissue-compartment models and the Logan plot. Using the cerebellum as reference region, we applied the simplified reference tissue model 2 and Logan reference plot. Finally, simplified outcome measures were calculated as ratio, with reference to cerebellar concentrations (SUV ratio [SUVR]) and SUVs. Tissue compartment models were not able to describe the kinetics of F-AV-1451, with poor fits in 33%-53% of cortical regions and 80% in subcortical areas. In contrast, the Logan plot showed excellent fits and parameter variance (total volume of distribution SE < 5%). Compared with the 180-min arterial-based Logan model, strong agreement was obtained for the Logan reference plot also for a reduced scan time of 100 min ( = 0.91) and SUVR 100-120 min ( = 0.94), with 80-100 min already representing a reasonable compromise between duration and accuracy ( = 0.93). Time-activity curves and kinetic parameters were equal for cortical regions and the cerebellum in control subjects but different in the putamen. Cerebellar total volumes of distribution were higher in controls than patients. For these methods, increased cortical binding was observed for AD patients and to some extent for cortico basal syndrome, but not progressive supranuclear palsy. The Logan plot provided the best estimate of tau binding using arterial input functions. Assuming that the cerebellum is a valid reference region, simplified methods seem to provide robust alternatives for quantification, such as the Logan reference plot with 100-min scan time. Furthermore, SUVRs between target and cerebellar activities obtained from an 80- to 100-min static scan offer promising potential for clinical routine application.
过度磷酸化tau蛋白的聚集是包括阿尔茨海默病（AD）在内的许多神经退行性疾病的主要标志。正电子发射断层扫描（PET）的体内成像可能为病理生理机制、诊断和疾病进展提供重要见解。我们描述了定量F-AV-1451（T807）tau蛋白结合的不同策略，包括有血样采集的模型和非侵入性替代方法。15名受试者（4名对照者、6名AD患者、3名进行性核上性麻痹患者、2名皮质基底节综合征患者）接受了180分钟的F-AV-1451 PET检查及动脉血样采集。使用动脉输入函数进行建模包括单组织室模型、双组织室模型和三组织室模型以及洛根图。以小脑作为参考区域，我们应用了简化参考组织模型2和洛根参考图。最后，计算简化的结果测量值作为比值，参照小脑浓度（标准化摄取值比值[SUVR]）和标准化摄取值。组织室模型无法描述F-AV-1451的动力学，在33%-53%的皮质区域拟合不佳，在皮质下区域拟合不佳率达80%。相比之下，洛根图显示拟合良好且参数方差较小（分布总体积标准误<5%）。与基于180分钟动脉血样的洛根模型相比，对于扫描时间缩短至100分钟的洛根参考图也获得了高度一致性（r = 0.91），以及100 - 120分钟时的SUVR（r = 0.94），80 - 100分钟已经代表了在时长和准确性之间的合理折衷（r = 0.93）。在对照受试者中，皮质区域和小脑的时间-活性曲线及动力学参数相同，但在壳核中不同。对照者的小脑分布总体积高于患者。对于这些方法，在AD患者中观察到皮质结合增加，在某种程度上皮质基底节综合征患者也有增加，但进行性核上性麻痹患者没有。洛根图使用动脉输入函数提供了对tau蛋白结合的最佳估计。假设小脑是一个有效的参考区域，简化方法似乎为定量提供了可靠的替代方法，例如扫描时间为100分钟的洛根参考图。此外，从80至100分钟静态扫描获得的目标与小脑活性之间的SUVR在临床常规应用中具有良好的潜力。
