最近的研究表明,使用血浆输入或小脑参考组织输入的标准隔室模型通常对于量化阿尔茨海默病的动态18F-flortaucipirPET研究中的tau负担并不可靠。到目前为止,估计18F-flortaucipir递送和特异性tau结合的最佳参考区域尚未确定。该研究的目的是使用具有双重参考组织的空间约束动力学模型来改善18F-flortaucipir脑tauPET定量。
根据临床评估,参与者被分为认知正常(CN)或认知障碍(CI)。对每个参与者进行T1加权结构MRI和105分钟动态18F-flortaucipirPET扫描。使用简化的参考组织模型(SRTM2)和洛根图,以小脑灰质或半卵中心(CS)白质作为参考组织,我们估计了基于感兴趣区域(ROI)和基于体素分析的分布体积比(DVR)和相对传输速率常数R1.然后评估具有空间约束(LRSC)参数成像算法的常规线性回归(LR)和LR。将参数图像中的噪声引起的偏差与基于ROI时间活动曲线的动力学建模的估计进行比较。我们最终评估了早期的标准化摄取值比率(SUVREP,0.7-2.9分钟)和后期(SUVRLP,80-105分钟)接近R1和DVR,分别。
使用空间约束建模的SRTM2的R1和DVR估计值的变异系数百分比与Logan图和SUVR的百分比相当。使用具有LRSC的CS参考组织的SRTM2将LR生成的DVR图像中的噪声引起的低估降低到可忽略的水平(<1%)。SUVRLP中DVR的不一致高估仅使用小脑参考基于组织的测量发生。CS参考基于组织的DVR和SUVRLP,基于小脑的SUVREP和R1提供了更高的Cohen效应大小d,以检测CI个体中tau沉积的增加和相对示踪剂转运率的降低。
使用具有双参考组织的空间约束动力学模型显著改善了相对灌注和tau结合的定量。小脑和CS是估计R1和DVR的建议参考组织,分别,用于动态18F-flortaucipirPET研究。基于小脑的SUVREP和基于CS的SUVRLP可用于简化18F-flortaucipirPET研究。
Recent studies have shown that standard compartmental models using plasma input or the cerebellum reference tissue input are generally not reliable for quantifying tau burden in dynamic 18F-flortaucipir PET studies of Alzheimer disease. So far, the optimal reference region for estimating 18F-flortaucipir delivery and specific tau binding has yet to be determined. The objective of the study is to improve 18F-flortaucipir brain tau PET quantification using a spatially constrained kinetic model with dual reference tissues.
Participants were classified as either cognitively normal (CN) or cognitively impaired (CI) based on clinical assessment. T1-weighted structural MRI and 105-min dynamic 18F-flortaucipir PET scans were acquired for each participant. Using both a simplified reference tissue model (SRTM2) and Logan plot with either cerebellum gray matter or centrum semiovale (CS) white matter as the reference tissue, we estimated distribution volume ratios (DVRs) and the relative transport rate constant R1 for region of interest-based (ROI) and voxelwise-based analyses. Conventional linear regression (LR) and LR with spatially constrained (LRSC) parametric imaging algorithms were then evaluated. Noise-induced bias in the parametric images was compared to estimates from ROI time activity curve-based kinetic modeling. We finally evaluated standardized uptake value ratios at early phase (SUVREP, 0.7-2.9 min) and late phase (SUVRLP, 80-105 min) to approximate R1 and DVR, respectively.
The percent coefficients of variation of R1 and DVR estimates from SRTM2 with spatially constrained modeling were comparable to those from the Logan plot and SUVRs. The SRTM2 using CS reference tissue with LRSC reduced noise-induced underestimation in the LR generated DVR images to negligible levels (< 1%). Inconsistent overestimation of DVR in the SUVRLP only occurred using the cerebellum reference tissue-based measurements. The CS reference tissue-based DVR and SUVRLP, and cerebellum-based SUVREP and R1 provided higher Cohen\'s effect size d to detect increased tau deposition and reduced relative tracer transport rate in CI individuals.
Using a spatially constrained kinetic model with dual reference tissues significantly improved quantification of relative perfusion and tau binding. Cerebellum and CS are the suggested reference tissues to estimate R1 and DVR, respectively, for dynamic 18F-flortaucipir PET studies. Cerebellum-based SUVREP and CS-based SUVRLP may be used to simplify 18F-flortaucipir PET study.