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

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.

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 reacquisition 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.

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.

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.