Estimation of Cellular-interstitial Water Exchange in Dynamic Contrast Enhanced MRI Using Two Flip Angles

Purpose: To investigate the feasibility of using multiple flip angles in dynamic contrast enhanced (DCE) MRI to reduce the uncertainty in estimation of intracellular water lifetime (τ ).

Methods: Numerical simulation studies were conducted to assess the uncertainty in estimation of τ using dynamic contrast enhanced MRI with one or two flip angles. In vivo experiments with a murine brain tumor model were conducted at 7T using two flip angles. The in vivo data were used to compare τ estimation using the single-flip-angle (SFA) protocol with that using the double-flip-angle (DFA) protocol. Data analysis was conducted using the two-compartment exchange model combined with the three-site-two-exchange model for water exchange.

Results: In the numerical simulation studies with a range of contrast kinetic parameters and signal-to-noise ratio = 20, the median bias of τ estimation decreased from 72 ms with SFA to 65 ms with DFA, and the corresponding median inter-quartile range reduced from 523 ms to 156 ms. In the in vivo studies, τ estimation with SFA was not successful in most voxels in the tumors, as the estimated τ values reached the upper limit of the parameter range (2 s). In contrast, the estimated τ values with DFA were mostly between 0.2 and 1.5 s and homogeneously distributed spatially across the tumor. The τ estimation with DFA was less sensitive to arterial input function scaling but more sensitive to pre-contrast T than the other contrast kinetic parameters.

Conclusion: This study results demonstrate the feasibility of using multiple flip angles to encode the post-contrast time-intensity curve with different weighting of water exchange effect to reduce the uncertainty in τ estimation.