Flow versus permeability weighting in estimating the forward volumetric transfer constant (K) obtained by DCE-MRI with contrast agents of differing molecular sizes.

PURPOSE

To quantify the differential plasma flow- (F-) and permeability surface area product per unit mass of tissue- (PS-) weighting in forward volumetric transfer constant (K) estimates by using a low molecular (Gd-DTPA) versus high molecular (Gadomer) weight contrast agent in dynamic contrast enhanced (DCE) MRI.

MATERIALS AND METHODS

DCE MRI was performed using a 7T animal scanner in 14 C57BL/6J mice syngeneic for TRAMP tumors, by administering Gd-DTPA (0.9kD) in eight mice and Gadomer (35kD) in the remainder. The acquisition time was 10min with a sampling rate of one image every 2s. Pharmacokinetic modeling was performed to obtain K by using Extended Tofts model (ETM). In addition, the adiabatic approximation to the tissue homogeneity (AATH) model was employed to obtain the relative contributions of F and PS.

RESULTS

The K values derived from DCE-MRI with Gd-DTPA showed significant correlations with both PS (r=0.64, p=0.009) and F (r=0.57, p=0.016), whereas those with Gadomer were found only significantly correlated with PS (r=0.96, p=0.0003) but not with F (r=0.34, p=0.111). A voxel-based analysis showed that K approximated PS (<30% difference) in 78.3% of perfused tumor volume for Gadomer, but only 37.3% for Gd-DTPA.

CONCLUSIONS

The differential contributions of F and PS in estimating K values vary with the molecular weight of the contrast agent used. The macromolecular contrast agent resulted in K values that were much less dependent on flow. These findings support the use of macromolecular contrast agents for estimating tumor vessel permeability with DCE-MRI.