Optimization of two-compartment-exchange-model analysis for dynamic contrast-enhanced mri incorporating bolus arrival time

Purpose: To optimize the analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) under the two-compartment-exchange-model (2CXM) and to incorporate voxelwise bolus-arrival-time (BAT). Materials and Methods: The accuracy of the pharmacokinetic (PK) parameters, extracted from 3T DCE-MRI using 2CXM, was tested under several conditions: eight algorithms for data estimation; correction for BAT; using model selection; different temporal resolution and scan duration. Comparisons were performed on simulated data. The best algorithm was applied to seven patients with brain tumors or following stroke. The extracted perfusion parameters were compared to those of dynamic susceptibility contrast MRI (DSC-MRI). Results: ACoPeD (AIF-corrected-perfusion-DCE-MRI), an analysis using a 2^nd derivative regularized-spline and incorporating BAT, achieved the most accurate estimation in simulated data, mean-relative-error: F_p, F, v_p, v_e: 24.8%, 41.7%, 26.4%, 27.2% vs. 76.5%, 190.8%, 78.8%, 82.39% of the direct four parameters estimation (one-sided two-sample t-test, P < 0.001). Correction for BAT increased the estimation accuracy of the PK parameters by more than 30% and provided a supertemporal resolution estimation of the BAT (higher than the acquired resolution, mean-absolute-error 0.2 sec). High temporal resolution (∼2 sec) is required to avoid biased estimation of PK parameters, and long scan duration (∼20 min) is important for reliable permeability but not for perfusion estimations, mean-error-reduction: E: ∼12%, v_e: ∼6%. Using ACoPeD, PK values from normal-appearing white matter, gray matter, and lesion were extracted from patients. Preliminary results showed significant voxelwise correlations to DSC-MRI, between flow values in a patient following stroke (r = 0.49, P < 0.001), and blood volume in a patient with a brain tumor (r = 0.62, P < 0.001). Conclusion: This study proposes an optimized analysis method, ACoPeD, for tissue perfusion and permeability estimation using DCE-MRI, to be used in clinical settings. Level of Evidence: 1. J. Magn. Reson. Imaging 2017;45:237–249.