Optimized pharmacokinetic modeling for the detection of perfusion differences in skeletal muscle with DCE-MRI: Effect of contrast agent size

Purpose: The goal of this study was to optimize dynamic contrast-enhanced (DCE)-MRI analysis for differently sized contrast agents and to evaluate the sensitivity for microvascular differences in skeletal muscle. Methods: In rabbits, pathophysiological perfusion differences between hind limbs were induced by unilateral femoral artery ligation. On days 14 and 21, DCE-MRI was performed using a medium-sized contrast agent (MCA) (Gadomer) or a small contrast agent (SCA) (Gd-DTPA). Acquisition protocols were adapted to the pharmacokinetic properties of the contrast agent. Model-based data analysis was optimized by selecting the optimal model, considering fit error, estimation uncertainty, and parameter interdependency from three two-compartment pharmacokinetic models (normal and extended generalized kinetic models and Patlak model). Model-based parameters were compared to the model-free parameter area-under-curve (AUC). Finally, the sensitivity of transfer constant K-trans and AUC for physiological and pathophysiological microvascular differences was evaluated. Results: For the MCA, the optimal model included K-trans and plasma fraction upsilon(p). For the SCA, K-trans and interstitial fraction upsilon(e) should be incorporated. For the MCA, K-trans were (4.8 +/- 0.2) X 10(-3) min(-1) (mean +/- standard error) and (3.6 +/- 0.1) X 10(-3) min(-1) for the red soleus and white tibialis muscle, respectively, p <0.01. With the SCA, K-trans were (81 +/- 5) X 10(-3) min(-1) (soleus) and (66 +/- 5) X 10(-3) min(-1) (tibialis) p <0.01. In the ischemic limb, K-trans was significantly decreased relative to the control limb (soleus: 15%-20%; tibialis: 5%-10%). Similar differences in AUC were found for both contrast agents. Conclusions: For optimal estimation of microvascular parameters, both model-based and model-free analysis should be adapted to the pharmacokinetic properties of the contrast agent. The detection of microvascular differences based on both K-trans and AUC was most sensitive when the analysis strategy was tailored to the contrast agent used. The MCA was equally sensitive for microvascular differences as the SCA, with the advantage of improved spatial resolution.