Estimation of cellular-interstitial water exchange in dynamic contrast enhanced MRI using two flip angles

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_i ).

Numerical simulation studies were conducted to assess the uncertainty in estimation of τ_i 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_i 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.

In the numerical simulation studies with a range of contrast kinetic parameters and signal-to-noise ratio = 20, the median bias of τ_i 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_i estimation with SFA was not successful in most voxels in the tumors, as the estimated τ_i values reached the upper limit of the parameter range (2 s). In contrast, the estimated τ_i values with DFA were mostly between 0.2 and 1.5 s and homogeneously distributed spatially across the tumor. The τ_i estimation with DFA was less sensitive to arterial input function scaling but more sensitive to pre-contrast T₁ than the other contrast kinetic parameters.

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_i estimation.