Kim S M, Cho Y B, Haider M A, Milosevic M, Yeung I W T
Radiation Medicine Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Med Phys. 2008 Dec;35(12):5921-33. doi: 10.1118/1.3021138.
Contrast injection protocol is known to affect the estimation of kinetic parameters in functional CT. A novel method is proposed to maximize the precision of parameter estimates by modulating the contrast injection scheme. The method models the intravenous contrast bolus to be dispersed by a "patient function" to give rise to the arterial input function, which, in turn, carries the contrast agent to tissue leading to contrast enhancement. The covariance matrix analysis was applied to calculate the uncertainty of parameter estimates as the coefficients of variation (CV) in the adiabatic tissue homogeneity (ATH), two-compartment, and the modified Kety model in which tumor pathophysiology is modeled. An optimization scheme was used to determine the optimal injection protocol which would minimize the CV of a particular kinetic parameter. For clinical utility, a recommended injection protocol was suggested from a statistical analysis with the optimal injection protocols obtained from the first group of 12 patients with cervix cancer. The efficacy of the recommended injection protocol was tested with a second group of 12 patients. In addition, the robustness of the recommended injection protocol to longitudinal study has been investigated in the presence of variations in arterial input function and tumor pathophysiology. Based on the data of the second group of patients, and using the ATH model, the recommended biphasic injection of two boluses improves the precision in the estimation of blood flow and mean transit time (MTT), by 36.9% and 38.4%, respectively, compared to the standard uniphasic injection protocol in the CV. However, measurement of the permeability surface area product and extravascular extracellular space volume favors a single fast bolus of the same contrast amount. The two-compartment model and the modified Kety model also benefited from the single fast bolus. The effect of variation in the arterial input function and tumor pathophysiology on the applicability of the recommended injection was also investigated. Based on computer simulation for a range of variations in the arterial input function and pathophysiology, the recommended biphasic injection was found to improve the precision in blood flow and MTT estimates by 31.4% and 36.5% on average, respectively, compared to the uniphasic injection.
已知对比剂注射方案会影响功能CT中动力学参数的估计。本文提出了一种新方法，通过调整对比剂注射方案来最大化参数估计的精度。该方法将静脉注射对比剂团注建模为由“患者函数”分散，从而产生动脉输入函数，进而将对比剂输送到组织导致对比增强。应用协方差矩阵分析来计算参数估计的不确定性，以绝热组织均匀性（ATH）、双室模型和模拟肿瘤病理生理学的改良凯蒂模型中的变异系数（CV）表示。采用优化方案来确定最佳注射方案，该方案可使特定动力学参数的CV最小化。为了临床应用，通过对第一组12例宫颈癌患者获得的最佳注射方案进行统计分析，提出了一种推荐注射方案。用第二组12例患者测试了推荐注射方案的疗效。此外，还研究了在动脉输入函数和肿瘤病理生理学存在变异的情况下，推荐注射方案对纵向研究的稳健性。基于第二组患者的数据，并使用ATH模型，与标准单相注射方案相比，推荐的双相注射两剂团注在估计血流和平均通过时间（MTT）时，CV分别提高了约36.9%和38.4%。然而，对于通透表面积乘积和血管外细胞外间隙体积的测量，相同对比剂用量的单次快速团注更有利。双室模型和改良凯蒂模型也受益于单次快速团注。还研究了动脉输入函数和肿瘤病理生理学变异对推荐注射适用性的影响。基于对一系列动脉输入函数和病理生理学变异的计算机模拟，发现与单相注射相比，推荐的双相注射平均分别将血流和MTT估计的精度提高了31.4%和36.5%。
