Thie Joseph A
University of Tennessee, 12334 Bluff Shore Dr., Knoxville, TN 37922, USA.
Mol Imaging Biol. 2007 Nov-Dec;9(6):348-56. doi: 10.1007/s11307-007-0111-6.
A region's early and late tracer uptake activities, QE and QL, within a dual-time scan (i.e. using two frames) or in serial scans (as for monitoring therapeutic response), are popular quantitative diagnostic aids, especially in oncology. In this paper, maximum performance is sought from their joint use.
QL/QnE is introduced as a tumor marker with an empirical n. This generalizes traditional data weighting having n=1 for QL/QE, the retention index (RI), with its associated % difference. Using patient data, iterative guessing finds an optimal n that maximizes a measure of diagnostic performance: D=(difference of normal and abnormal marker means)/(their combined SD), which may be computed from values of QL/QnE, as well as of QL, QE, and RI each used alone. For 2-deoxy-2-[F-18]fluoro-D-glucose(FDG)-positron emission tomography (PET) dual-time protocols, another approach to optimization-selection of scan times-is investigated by simulations using the Sokolov model.
A meta-analysis of 12 PET and single photon emission computed tomography (SPECT) studies with various tracers, cancers, and scan classes (dual-time or serial) finds ns from 0.5 to 1.1. The optimal D necessarily exceeds the best (or any) computed using QE, QL, or RI: negligibly to by as much as 0.6 (or 1.5). The increases in optimal receiver operating curve area (Az) over the best (or any) traditional marker range from negligible to 0.07 (or 0.4). QE alone usually has the lowest D and Az. Statistically significant performance improvement of QL/QnE over QE and QL is shown for most studies. Contrasting with an optimal n, another value n0 can also be found where D=0. Occasionally, n0 can be close to 1, and RI then will have a small D and poor performance. Simulation with kinetic modeling of FDG dual-time scans for liver and liver metastases demonstrates worst and best scan times. Indicated for these imaging protocols are QE at very early cellular transport associated times and QL rather late when phosphorylation/dephosphorylation dominate. Benefits from choosing optimal times in dual-time protocols, especially in combination with choosing optimal ns, can be significant.
A protocol-dependent optimizing parameter n in an improved classification marker can easily be identified in a learning set of scans having normals and abnormals. Finding this parameter below 1.0 in most all studies suggests that a popularly used QL/QE may often overweight early activities. Additionally, QL/QE may sometimes be a poor marker choice and underestimate a protocol's diagnostic capability. Subsequent use of the proposed QL/QnE in settings similar to that of the learning set gives improved diagnostic performance over traditional approaches, although by widely varying amounts. Additionally, a method of seeking optimal scan times is demonstrated and suggests significant gains in dual-time protocol performances are possible.
在双时相扫描(即使用两个时相)或系列扫描(如监测治疗反应)中,一个区域的早期和晚期示踪剂摄取活性,即QE和QL,是常用的定量诊断辅助指标,尤其在肿瘤学领域。本文旨在寻求联合使用它们时的最佳性能。
引入QL/QnE作为具有经验值n的肿瘤标志物。这推广了传统的数据加权,对于QL/QE(保留指数,RI),传统数据加权时n = 1及其相关的百分比差异。利用患者数据,通过迭代猜测找到使诊断性能指标D最大化的最佳n值:D =(正常和异常标志物均值之差)/(它们的合并标准差),该指标可根据QL/QnE以及单独使用的QL、QE和RI的值来计算。对于2-脱氧-2-[F-18]氟-D-葡萄糖(FDG)-正电子发射断层扫描(PET)双时相方案,通过使用索科洛夫模型进行模拟研究了另一种优化方法——扫描时间的选择。
对12项PET和单光子发射计算机断层扫描(SPECT)研究进行的荟萃分析,这些研究涉及各种示踪剂、癌症和扫描类型(双时相或系列),得出n值在0.5至1.1之间。最佳的D必然超过使用QE、QL或RI计算出的最佳(或任何)值:从可忽略不计到高达0.6(或1.5)。最佳受试者工作特征曲线面积(Az)相对于最佳(或任何)传统标志物的增加幅度从可忽略不计到0.07(或0.4)。单独使用QE时通常D和Az最低。大多数研究表明,QL/QnE在统计学上比QE和QL有显著的性能提升。与最佳n值形成对比的是,还能找到另一个n0值,此时D = 0。偶尔,n0可能接近1,此时RI的D值较小但性能较差。对肝脏和肝转移灶的FDG双时相扫描进行动力学建模模拟,显示了最差和最佳扫描时间。这些成像方案表明,在细胞转运非常早期的相关时间点选择QE,而在磷酸化/去磷酸化占主导的较晚时间点选择QL。在双时相方案中选择最佳时间,尤其是结合选择最佳n值,可能会带来显著益处。
在包含正常和异常情况的扫描学习集中,可以轻松识别改进的分类标志物中依赖于方案的优化参数n。在大多数研究中发现该参数低于1.0,这表明常用的QL/QE可能经常过度加权早期活性。此外,QL/QE有时可能是较差的标志物选择,并且会低估方案的诊断能力。在与学习集类似的环境中随后使用所提出的QL/QnE,与传统方法相比,诊断性能有所提高,尽管提高幅度差异很大。此外,展示了一种寻求最佳扫描时间的方法,表明双时相方案性能可能会有显著提升。