Molecular Imaging Group, Department of Radiology, Faculty of Medicine and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Galicia, Spain; Molecular Imaging Unit (UIM), Centro de Investigaciones Médico-Sanitarias (CIMES), General Foundation of the University of Málaga (Fguma), Málaga, Spain.
Molecular Imaging Group, Department of Radiology, Faculty of Medicine and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Galicia, Spain; Nuclear Medicine Department and Molecular Imaging Group, University Hospital CHUS-IDIS, Travesía da Choupana s/n, Santiago de Compostela, 15706, Spain.
Neuroimage. 2022 Oct 1;259:119396. doi: 10.1016/j.neuroimage.2022.119396. Epub 2022 Jun 24.
[F]Flortaucipir (FTP) PET quantification is usually hindered by spill-in counts from off-target binding (OFF) regions. The present work aims to provide an in-depth analysis of the impact of OFF in FTP PET quantification, as well as to identify optimal partial volume correction (PVC) strategies to minimize this problem.
309 amyloid-beta (Aβ) negative cognitively normal subjects were included in the study. Additionally, 510 realistic FTP images with different levels of OFF were generated using Monte Carlo simulation (MC). Images were corrected for PVC using both a simple two-compartment and a multi-region method including OFF regions. FTP standardized uptake value ratio (SUVR) was quantified in Braak Areas (BA), the hippocampus (which was not included in Braak I/II) and different OFF regions (caudate, putamen, pallidum, thalamus, choroid plexus (ChPlex), cerebellar white matter (cerebWM), hemispheric white matter (hemisWM) and cerebrospinal fluid (CSF)) using the lower portion of the cerebellum as a reference region. The correlations between OFF and cortical SUVRs were studied both in real and in simulated PET images, with and without PVC.
In-vivo, we found correlations between all OFF and target regions, especially strong for the hemisWM (slope>0.63, R>0.4). All the correlations were attenuated but remained significant after applying PVC, except for the ChPlex. In MC simulations, the hemisWM and CSF were the main contributors to PVE in all BA (slopes 0.15-0.26 and 0.13-0.21 respectively). The hemisWM (slope=0.2), as well as the ChPlex (slope=0.02), influenced SUVRs in the hippocampus. The CerebWM was negatively correlated with all target regions (slope<-0.02, R>0.8). While no other correlations between OFF and target regions were found, hemisWM was correlated with all OFF regions but the cerebWM (slopes 0.06-0.33). HemisWM correlations attenuated (slopes<0.06) when applying two-compartment PVC, but the hippocampus-ChPlex and the cerebWM correlations required more complex PVC with dedicated compartments for these regions. In-vivo, PVC removed a notably higher fraction of the correlation between OFF regions found to be affected by PVE in the simulation studies and BA (≈50%) than for OFF regions not affected by PVE (16%).
HemisWM is the main driver of spill-in effects in FTP PET, affecting both target regions and the rest of OFF regions. PVC successfully reduces PVE, even when using a simple two-compartment method. Despite PVC, non-zero correlations were still observed between target and OFF regions in vivo, which suggests the existence of biological or tracer-related contributions to these correlations.
[F]Flortaucipir（FTP）PET 定量通常受到来自非靶区结合（OFF）区域的溢出计数的阻碍。本研究旨在深入分析 OFF 对 FTP PET 定量的影响，并确定最佳的部分容积校正（PVC）策略以最小化此问题。
本研究纳入了 309 名无淀粉样蛋白-β（Aβ）认知正常的受试者。此外，使用蒙特卡罗模拟（MC）生成了 510 张具有不同 OFF 水平的逼真的 FTP 图像。使用简单的两室模型和包括 OFF 区域的多区域方法对图像进行 PVC 校正。在 Braak 区域（BA）、海马体（未包括在 Braak I/II 中）和不同的 OFF 区域（尾状核、壳核、苍白球、丘脑、脉络丛（ChPlex）、小脑白质（cerebWM）、半脑白质（hemisWM）和脑脊液（CSF））中定量 FTP 标准化摄取值比值（SUVR），使用小脑下部作为参考区域。研究了真实和模拟 PET 图像中 OFF 与皮质 SUVRs 之间的相关性，包括有无 PVC。
在体内，我们发现所有 OFF 与靶区之间均存在相关性，尤其是与 hemisWM 的相关性较强（斜率>0.63，R>0.4）。在应用 PVC 后，除了 ChPlex 外，所有相关性均减弱但仍具有统计学意义。在 MC 模拟中，hemisWM 和 CSF 是所有 BA 中 PVE 的主要贡献者（斜率分别为 0.15-0.26 和 0.13-0.21）。hemisWM（斜率=0.2）和 ChPlex（斜率=0.02）影响海马体的 SUVRs。CerebWM 与所有靶区呈负相关（斜率<-0.02，R>0.8）。虽然未发现 OFF 与靶区之间的其他相关性，但 hemisWM 与所有 OFF 区域但与 cerebWM 相关（斜率 0.06-0.33）。当应用两室 PVC 时，hemisWM 的相关性减弱（斜率<0.06），但需要更复杂的 PVC 来校正 hippocampus-ChPlex 和 cerebWM 相关性，为这些区域分配专门的容量。在体内，PVC 去除了模拟研究中发现的受 PVE 影响的 OFF 区域与 BA 之间相关性中明显更高的部分（≈50%），而去除不受 PVE 影响的 OFF 区域的相关性（16%）。
hemisWM 是 FTP PET 溢出效应的主要驱动因素，影响靶区和其他 OFF 区域。即使使用简单的两室方法，PVC 也能成功地减少 PVE。尽管进行了 PVC，但在体内仍观察到靶区和 OFF 区域之间存在非零相关性，这表明这些相关性存在生物学或示踪剂相关的贡献。
