Evaluation of reference tissue models for the analysis of [11C](R)-PK11195 studies
Evaluation of reference tissue models for the analysis of [11C](R)-PK11195 studies
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DOI：
10.1038/sj.jcbfm.9600289
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发表时间：
2006-11-01
影响因子：
6.3
通讯作者：
Lammertsma, Adriaan A.
中科院分区：
文献类型：
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作者：
Kropholler, Marc A.;Boellaard, Ronald;Lammertsma, Adriaan A.
[C-11]（R）-PK 11195是活化的小胶质细胞的标志物，可用于测量神经系统疾病中的炎症。本研究的目的是根据与经验证的血浆输入模型的比较，并使用临床研究和Monte Carlo模拟来定义最佳参考组织模型。参考组织模型的准确性和再现性使用Monte Carlo模拟进行了评价。评价了噪声和特异性结合、非特异性结合和血容量变化的影响。对13名受试者进行动态正电子发射断层扫描，并在线监测动脉血中的放射性。此外，采集血样以生成代谢物校正的血浆输入函数。将K-1/k（2）固定于整个皮质的（经验证的）两组织可逆房室模型和各种参考组织模型拟合到数据。最后，研究了使用血浆输入数据（SRTMpl-corr）校正非特异性结合的简化参考组织模型（SRTM）。计算参考组织模型（包括SRTMpl-corr）和血浆输入模型之间的相关性。Monte Carlo模拟表明，低特异性结合导致准确性和重现性降低。在这方面，SRTM和SRTMpl-corr表现相对较好。不同的血容量对性能没有影响。在临床评价中，SRTMpl-corr和SRTM与血浆输入模型的相关性最高（R-2分别= 0.82和0.78）。当动脉血浆输入曲线可用时，SRTMpl-corr是最佳的。当没有血浆输入时，简化的参考组织模型是最好的选择。
[C-11](R)-PK11195 is a marker of activated microglia, which can be used to measure inflammation in neurologic disorders. The purpose of the present study was to define the optimal reference tissue model based on a comparison with a validated plasma input model and using clinical studies and Monte Carlo simulations. Accuracy and reproducibility of reference tissue models were evaluated using Monte Carlo simulations. The effects of noise and variation in specific binding, nonspecific binding and blood volume were evaluated. Dynamic positron emission tomography scans were performed on 13 subjects, and radioactivity in arterial blood was monitored online. In addition, blood samples were taken to generate a metabolite corrected plasma input function. Both a (validated) two-tissue reversible compartment model with K-1/k(2) fixed to whole cortex and various reference tissue models were fitted to the data. Finally, a simplified reference tissue model (SRTM) corrected for nonspecific binding using plasma input data (SRTMpl-corr) was investigated. Correlations between reference tissue models (including SRTMpl-corr) and the plasma input model were calculated. Monte Carlo simulations indicated that low-specific binding results in decreased accuracy and reproducibility. In this respect, the SRTM and SRTMpl-corr performed relatively well. Varying blood volume had no effect on performance. In the clinical evaluation, SRTMpl-corr and SRTM had the highest correlations with the plasma input model (R-2 = 0.82 and 0.78, respectively). SRTMpl-corr is optimal when an arterial plasma input curve is available. Simplified reference tissue model is the best alternative when no plasma input is available.