Adoption of quantitative clinical DCE-MRI remains limited given the challenges in accurate and precise estimation of kinetic parameters. Simulations are being increasingly used to guide protocol optimization1, but the relative effects of altering protocol variables are seldom considered. We used a modified K-CNR metric to quantify tumor Ktrans estimation. K-CNR provided a simple way to compare how input variables affect Ktrans output. The extended Toft’s model was shown to be robust for tumor relevant Ktrans. Lengthening baseline time can improve Ktrans estimation. Care must be taken when using nested model analysis; wrong model convergence can occur with non-optimized acquisition variables.