Dept. of Nuclear Medicine, University of Munich, Germany.
MNI, New Haven, USA.
Neuroimage. 2015 Mar;108:450-9. doi: 10.1016/j.neuroimage.2014.11.055. Epub 2014 Dec 4.
Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET. We analyzed [(18)F]-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal [(18)F]-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time. Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (-18%) and MCI (-10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0.907) or with brainstem scaling for the contrast between HC/MCI (0.658). Longitudinal increases were greatest in all diagnosis groups with application of PVEC, and inter-subject variability was lowest for the white matter reference. Thus, discriminatory power of [(18)F]-AV45-PET was improved by use of a VOI-based PVEC and white matter or brainstem rather than cerebellum reference region. Detection of longitudinal amyloid increases was optimized with PVEC and white matter reference tissue.
淀粉样蛋白正电子发射断层扫描（PET）为研究阿尔茨海默病（AD）提供了重要的研究和诊断工具。大多数淀粉样蛋白 PET 研究都使用小脑作为参考区域，而临床研究并未考虑基于萎缩的部分容积效应（PVE）。使用小脑作为参考组织的纵向研究仅显示出淀粉样蛋白结合的平均小幅度增加和受试者间的高度变异性。我们旨在测试不同参考区域和 PVE 校正（PVEC）对淀粉样蛋白 PET 的鉴别能力和纵向性能的影响。我们分析了 962 名受试者在基线时的 [(18)F]-AV45 PET 和 T1 加权 MRI 数据，以及 258 名受试者在两年时的随访数据。使用全脑图谱 VOI、灰质分割 VOI 或基于 VOI 的 PVEC 后的灰质分割 VOI 生成示踪剂摄取的皮质复合 VOI（COMP）值。通过将 COMP 值缩放到小脑（SUVRCBL）、脑桥（SUVRBST）或白质（SUVRCBL）中的摄取量来计算标准摄取比值（SUVR）。在基线时，比较了诊断组健康对照组（HC；N=316）、轻度认知障碍（MCI；N=483）和 AD（N=163）之间的平均 SUV、SUV 和 PVEC 后的变化。计算了用于区分 HC、MCI 和 AD 的接收者操作特征（ROC），并表示为曲线下面积（AUC）。最后，使用纵向 [(18)F]-AV45-PET 数据来分析定量程序对随时间变化的淀粉样蛋白负荷的表观变化的影响。对于白质，参考区域 SUV 在诊断组之间最为稳定。PVEC 导致 HC（-18%）和 MCI（-10%）的 COMP-SUV 减少，但 AD（+7%）增加。当使用基于白质的 SUV 进行对比时，HC/AD（0.907）或基于脑桥的 SUV 进行对比时，HC/MCI（0.658）时，发现最高的 AUC。在应用 PVEC 的所有诊断组中，纵向增加最大，并且白质参考的受试者间变异性最低。因此，使用基于 VOI 的 PVEC 和白质或脑桥而不是小脑参考区域可提高 [(18)F]-AV45-PET 的鉴别能力。使用 PVEC 和白质参考组织优化了纵向淀粉样蛋白增加的检测。
