在早期阿尔茨海默病的[F-18]MK6240 PET 扫描中评估脑外脱靶结合的影响

Andrew K McVea, A. DiFilippo, Max McLachlan, Matthew D. Zammit, B. Bendlin, Sterling C. Johnson, T. Betthauser, Bradley T. Christian
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摘要

摘要 [F-18]MK6240是一种正电子发射断层扫描(PET)放射性配体,具有良好的成像特性,可用于测量阿尔茨海默病(AD)中的tau聚集。在本研究中,我们研究了[F-18]MK6240 PET 扫描中出现的脑膜和窦的脑外脱靶结合(ECB)对量化临床前 AD 中 tau 负担的影响。根据威斯康星大学麦迪逊分校获得的 433 次 [F-18]MK6240 扫描的大量队列数据,通过改变 ECB 曲线和输入放射性示踪剂浓度曲线来检查 ECB 对 AD 早期 tau 累积区域的影响范围。成像队列中ECB的范围和模式在参与者之间有很大的变异性;然而,35%的ECB显示出中等到较高的脑膜信号,这可能会影响量化。部分容积效应会导致相邻区域的 PET 信号影响相邻相关区域的信号,模拟图像对这种效应进行了研究。模拟结果表明,来自静脉窦的信号会增加邻近内侧皮质区域(ERC)的信号,而从脑膜检测到的活动同样会影响小脑下部灰质参考区域。在我们的队列中,窦的ECB效应最为普遍,具有平均ECB特征的模拟的ERC摄取量(SUV)比没有ECB的模拟高23%。窦的溢入效应会增加颞叶内侧和腹侧皮层的标准化摄取值比(SUVR),而脑膜溢入小脑参考区域则会导致总体 SUVR 降低,这两种效应的作用方向相反,从而使[F-18]MK6240 图像的 SUVR 解释变得复杂。这些模拟结果量化了[F-18]MK6240扫描中ECB的影响,并引入了校正因子以尽量减少SUVR测量的偏差。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluating the effect of extra-cerebral off-target binding in [F-18]MK6240 PET scans in early-stage Alzheimer’s disease
Abstract [F-18]MK6240 is a Positron Emission Tomography (PET) radioligand with favorable imaging characteristics for measuring tau aggregation in Alzheimer’s disease (AD). In this study, we investigated the impact of extra-cerebral off-target binding (ECB) in the meninges and sinus present in [F-18]MK6240 PET scans on quantifying tau burden in preclinical AD. Based on large cohort data from 433 [F-18]MK6240 scans acquired at the University of Wisconsin-Madison, simulations were conducted to examine the range of effects of ECB by varying the ECB profile and input radiotracer concentration curves on areas of early tau accumulation in AD. The range and patterning of ECB in the imaging cohort had high variability between participants; however, 35% revealed moderate to high meningeal signal that could influence quantification. Partial volume effects, which can lead to measured PET signal from neighboring regions influencing signal in adjacent areas of interest, were examined in the simulated images. The simulations demonstrate that signal from the sinus increases the neighboring entorhinal cortex region (ERC) signal and activity detected from the meninges can similarly influence the inferior cerebellar grey matter reference region. ECB effects from the sinus were the most prevalent in our cohort, and simulations with the average ECB profile had ERC uptake (SUV) 23% higher than simulations with no ECB. Spill-in effects from the sinus, which increases the medial and ventral temporal cortex standardized uptake value ratio (SUVR), and spill-in from the meninges into the cerebellar reference region, which leads to a reduction in global SUVR, act in opposite directions, complicating the interpretation of the derived SUVR of [F-18]MK6240 images. These simulation results quantify the effects of ECB in [F-18]MK6240 scans and introduce correction factors to minimize bias of the SUVR measure.
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