T1- and T2*-dominant extravasation correction in DSC-MRI: part I--theoretical considerations and implications for assessment of tumor hemodynamic properties.

We present a novel contrast agent (CA) extravasation-correction method based on analysis of the tissue residue function for assessment of multiple hemodynamic parameters. The method enables semiquantitative determination of the transfer constant and can be used to distinguish between T(1)- and T(2)(*)-dominant extravasation effects, while being insensitive to variations in tissue mean transit time (MTT). Results in 101 patients with confirmed glioma suggest that leakage-corrected absolute cerebral blood volume (CBV) values obtained with the proposed method provide improved overall survival prediction compared with normalized CBV values combined with an established leakage-correction method. Using a standard gradient-echo echo-planar imaging sequence, ∼60% and 10% of tumors with detectable CA extravasation mainly exhibited T(1)- and T(2)(*)-dominant leakage effects, respectively. The remaining 30% of leaky tumors had mixed T(1)- and T(2)(*)-dominant effects. Using an MTT-sensitive correction method, our results show that CBV is underestimated when tumor MTT is significantly longer than MTT in the reference tissue. Furthermore, results from our simulations suggest that the relative contribution of T(1)- versus T(2)(*)-dominant extravasation effects is strongly dependent on the effective transverse relaxivity in the extravascular space and may thus be a potential marker for cellular integrity and tissue structure.