Costoya-Sánchez Alejandro, Moscoso Alexis, Sobrino Tomás, Ruibal Álvaro, Grothe Michel J, Schöll Michael, Silva-Rodríguez Jesús, Aguiar Pablo
Molecular Imaging Group. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Av. Barcelona SN, 15782, Santiago de Compostela, Galicia, Spain; Nuclear Medicine Department and Molecular Imaging Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Psychiatry and Neurochemistry, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden.
Neuroimage. 2024 Apr 1;289:120537. doi: 10.1016/j.neuroimage.2024.120537. Epub 2024 Feb 15.
[F]flortaucipir (FTP) tau PET quantification is known to be affected by non-specific binding in off-target regions. Although partial volume correction (PVC) techniques partially account for this effect, their inclusion may also introduce noise and variability into the quantification process. While the impact of these effects has been studied in cross-sectional designs, the benefits and drawbacks of PVC on longitudinal FTP studies is still under scrutiny. The aim of this work was to study the performance of the most common PVC techniques for longitudinal FTP imaging.
A cohort of 247 individuals from the Alzheimer's Disease Neuroimaging Initiative with concurrent baseline FTP-PET, amyloid-beta (Aβ) PET and structural MRI, as well as with follow-up FTP-PET and MRI were included in the study. FTP-PET scans were corrected for partial volume effects using Meltzer's, a simple and popular analytical PVC, and both the region-based voxel-wise (RBV) and the iterative Yang (iY) corrections. FTP SUVR values and their longitudinal rates of change were calculated for regions of interest (ROI) corresponding to Braak Areas I-VI, for a temporal meta-ROI and for regions typically displaying off-target FTP binding (caudate, putamen, pallidum, thalamus, choroid plexus, hemispheric white matter, cerebellar white matter, and cerebrospinal fluid). The longitudinal correlation between binding in off-target and target ROIs was analysed for the different PVCs. Additionally, group differences in longitudinal FTP SUVR rates of change between Aβ-negative (A-) and Aβ-positive (A+), and between cognitively unimpaired (CU) and cognitively impaired (CI) individuals, were studied. Finally, we compared the ability of different partial-volume-corrected baseline FTP SUVRs to predict longitudinal brain atrophy and cognitive decline.
Among off-target ROIs, hemispheric white matter showed the highest correlation with longitudinal FTP SUVR rates from cortical target ROIs (R=0.28-0.82), with CSF coming in second (R=0.28-0.42). Application of voxel-wise PVC techniques minimized this correlation, with RBV performing best (R=0.00-0.07 for hemispheric white matter). PVC also increased group differences between CU and CI individuals in FTP SUVR rates of change across all target regions, with RBV again performing best (No PVC: Cohen's d = 0.26-0.66; RBV: Cohen's d = 0.43-0.74). These improvements were not observed for differentiating A- from A+ groups. Additionally, voxel-wise PVC techniques strengthened the correlation between baseline FTP SUVR and longitudinal grey matter atrophy and cognitive decline.
Quantification of longitudinal FTP SUVR rates of change is affected by signal from off-target regions, especially the hemispheric white matter and the CSF. Voxel-wise PVC techniques significantly reduce this effect. PVC provided a significant but modest benefit for tasks involving the measurement of group-level longitudinal differences. These findings are particularly relevant for the estimations of sample sizes and analysis methodologies of longitudinal group studies.
氟替卡匹（FTP）tau正电子发射断层扫描（PET）定量分析已知会受到非靶区域非特异性结合的影响。尽管部分容积校正（PVC）技术部分抵消了这种影响，但采用这些技术也可能在定量过程中引入噪声和变异性。虽然在横断面研究设计中已经对这些影响进行了研究，但PVC在纵向FTP研究中的利弊仍在审视之中。这项工作的目的是研究纵向FTP成像中最常用的PVC技术的性能。
该研究纳入了来自阿尔茨海默病神经影像学倡议组织的247名个体，他们同时进行了基线FTP-PET、淀粉样β蛋白（Aβ）PET和结构磁共振成像（MRI）检查，以及后续的FTP-PET和MRI检查。使用梅尔策方法（一种简单且常用的分析性PVC方法）、基于区域的体素级（RBV）校正和迭代杨（iY）校正对FTP-PET扫描进行部分容积效应校正。计算了与Braak区域I-VI、一个颞部元感兴趣区域（meta-ROI）以及通常显示非靶FTP结合的区域（尾状核、壳核、苍白球、丘脑、脉络丛、半球白质、小脑白质和脑脊液）相对应的感兴趣区域（ROI）的FTP标准化摄取值（SUVR）及其纵向变化率。分析了不同PVC情况下非靶和靶ROI中结合的纵向相关性。此外，研究了Aβ阴性（A-）和Aβ阳性（A+）个体之间以及认知未受损（CU）和认知受损（CI）个体之间纵向FTP SUVR变化率的组间差异。最后，我们比较了不同部分容积校正的基线FTP SUVR预测纵向脑萎缩和认知衰退的能力。
在非靶ROI中，半球白质与皮质靶ROI的纵向FTP SUVR变化率相关性最高（R=0.28-0.82），脑脊液次之（R=0.28-0.42）。应用体素级PVC技术使这种相关性最小化，其中RBV表现最佳（半球白质的R=0.00-0.07）。PVC还增加了CU和CI个体在所有靶区域FTP SUVR变化率方面的组间差异，RBV同样表现最佳（无PVC：科恩d值=0.26-0.66；RBV：科恩d值=0.43-0.74）。在区分A-和A+组时未观察到这些改善。此外，体素级PVC技术增强了基线FTP SUVR与纵向灰质萎缩和认知衰退之间的相关性。
纵向FTP SUVR变化率的定量分析受非靶区域信号的影响，尤其是半球白质和脑脊液。体素级PVC技术显著降低了这种影响。PVC在涉及测量组水平纵向差异的任务中提供了显著但适度的益处。这些发现对于纵向组研究的样本量估计和分析方法尤其重要。
