Jacobs Igor, Strijkers Gustav J, Keizer Henk M, Janssen Henk M, Nicolay Klaas, Schabel Matthias C
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Magn Reson Med. 2016 Mar;75(3):1142-53. doi: 10.1002/mrm.25704. Epub 2015 Apr 4.
To develop a novel tracer-kinetic modeling approach for multi-agent dynamic contrast-enhanced MRI (DCE-MRI) that facilitates separate estimation of parameters characterizing blood flow and microvascular permeability within one individual.
Monte Carlo simulations were performed to investigate the performance of the constrained multi-agent model. Subsequently, multi-agent DCE-MRI was performed on tumor-bearing mice (n = 5) on a 7T Bruker scanner on three measurement days, in which two dendrimer-based contrast agents having high and intermediate molecular weight, respectively, along with gadoterate meglumine, were sequentially injected within one imaging session. Multi-agent data were simultaneously fit with the gamma capillary transit time model. Blood flow, mean capillary transit time, and bolus arrival time were constrained to be identical between the boluses, while extraction fractions and washout rate constants were separately determined for each agent.
Simulations showed that constrained multi-agent model regressions led to less uncertainty and bias in estimated tracer-kinetic parameters compared with single-bolus modeling. The approach was successfully applied in vivo, and significant differences in the extraction fraction and washout rate constant between the agents, dependent on their molecular weight, were consistently observed.
A novel multi-agent tracer-kinetic modeling approach that enforces self-consistency of model parameters and can robustly characterize tumor vascular status was demonstrated.
开发一种用于多剂动态对比增强磁共振成像（DCE-MRI）的新型示踪剂动力学建模方法，以促进在个体内分别估计表征血流和微血管通透性的参数。
进行蒙特卡罗模拟以研究约束多剂模型的性能。随后，在7T布鲁克扫描仪上对荷瘤小鼠（n = 5）在三个测量日进行多剂DCE-MRI，在一次成像过程中依次注射两种分别具有高分子量和中等分子量的基于树枝状大分子的造影剂以及钆喷酸葡胺。多剂数据与γ毛细血管通过时间模型同时拟合。血流、平均毛细血管通过时间和团注到达时间在各团注之间被约束为相同，而每种造影剂的提取分数和洗脱速率常数则分别确定。
模拟表明，与单团注建模相比，约束多剂模型回归在估计示踪剂动力学参数时导致的不确定性和偏差更小。该方法在体内成功应用，并且始终观察到各造影剂之间提取分数和洗脱速率常数的显著差异，这取决于它们的分子量。
证明了一种新型的多剂示踪剂动力学建模方法，该方法可强制模型参数的自一致性，并能稳健地表征肿瘤血管状态。
