Simulating the effect of input errors on the accuracy of Tofts' pharmacokinetic model parameters

Pharmacokinetic modeling in Dynamic Contrast Enhanced (DCE)-MRI is an elegant and useful method that provides valuable insight into angiogenesis in cancer and inflammatory diseases. Despite its widespread use, the reliability of the model results is still questioned, as many factors hamper the calculation of the model's parameters, resulting in the poor reproducibility and accuracy of the method. Pharmacokinetic modeling relies on the knowledge of inputs such as the Arterial Input Function (AIF) and of the tissue contrast agent concentration, both of which are difficult to accurately measure. Any errors in the measurement of either of the inputs propagate into the calculated pharmacokinetic model parameters (PMPs), and the significance of the effect depends on the source of the measurement error. In this work we systematically investigate the effect of the incorrect estimation of the parameters describing the inputs of the model on the calculated PMPs when using Tofts' model. Furthermore, we analyze the dependence of these errors on the native values of the PMPs. We show that errors on the measurement of the native T1 as well as errors on the parameters describing the initial peak of the AIF have the largest impact on the calculated PMPs. The parameter whose error has the least effect is the one describing the slow decay of the AIF. The effect of input parameter (IP) errors on the calculated PMPs is found to be dependent on the native set of PMPs: this is particularly true for the errors in the flip angle, and for the errors in parameters describing the initial AIF peak. Conversely the effect of T1 and AIF scaling errors on the calculated PMPs is only slightly dependent on the native PMPs.