Model-free parameters from dynamic contrast-enhanced-MRI: Sensitivity to EES volume fraction and bolus timing

Purpose: To quantify the unknown relative sensitivities of semiquantitative measures from dynamic contrast-enhanced (DCE) MRI to variations in the volume fraction V_e of the extravascular extracellular space (EES), and the duration of the contrast injection. Materials and Methods: Tissue-uptake curves were simulated across various values of F, PS, V_e, and bolus timings, with and without additive noise and at different image re-acquisition rates. From each, the peak of the first derivative (G_peak), the total uptake after the rapid first phase (CE), and the IAUC were calculated and plotted against F for each experimental condition. Relationships between each measure and the corresponding quantitative measure K^trans were also examined, particularly for linearity. Results: The highest sensitivity to flow was achieved for shorter bolus timings for G_peak, CE, and IAUC. G _peak and IAUC were most linearly related to K^trans. The sensitivity to V_e was lowest for G_peak, followed by IAUC and CE. Long sampling intervals resulted in severe underestimation of G _peak, while IAUC was unaffected provided that the limits of integration were properly applied. G_peak could not be properly calculated in the presence of noise without a prior smoothing of the acquired curves, while IAUC was again unaffected by noise. Conclusion: G_peak and IAUC are both useful model-free analogs of blood flow (i.e., K ^trans) for pre- and posttreatment comparisons. G_peak may be the better choice in cases where larger changes in V_e are likely, but only if sufficient noise reduction and fast image sampling are applied. If V_e is expected to remain stable, IAUC is superior to G_peak by virtue of its stability in the face of noise and more reliable estimation over a wider range of sampling rates.