Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising tool for evaluating tumor vascularity, as it can provide vasculature-derived, functional, and quantitative parameters. To implement DCE-MRI parameters as biomarkers for monitoring the effect of antiangiogenic or vascular-disrupting treatment, two crucial elements of surrogate endpoint, ie, validation and qualification, should be satisfied. Although early studies have shown the accuracy and reliability of DCE-MRI parameters for evaluating treatment-driven vascular alterations, there have been an increasing number of studies demonstrating the limitations of DCE-MRI parameters as surrogate endpoints. Therefore, in order to improve the application of DCE-MRI parameters in drug development, it is necessary to establish a standardized evaluation method and to determine the correct therapeutics-oriented meaning of individual DCE-MRI parameter. In this regard, this article describes the biophysical background and data acquisition/analysis techniques of DCE-MRI while focusing on the validation and qualification issues. Specifically, the causes of disagreement and confusion encountered in the preclinical and clinical trials using DCE-MRI are presented in detail. Finally, considering these limitations, we present potential strategies to optimize implementation of DCE-MRI. J. Magn. Reson. Imaging 2016;44:251-264.

Objective: To evaluate the diagnostic accuracy of four-dimensional MR angiography (4D-MRA) at 3.0 T for detecting residual arteriovenous malformations (AVMs) after Gamma Knife j (Elekta Instrument AB, Stockholm, Sweden) radiosurgery (GKRS). Methods: We assessed 36 angiographically confirmed AVMs in 36 patients who had been treated with GKRS. 4D-MRA was performed after GKRS and the time intervals were 39.4¡26.0 months [mean ¡ standard deviation (SD)]. 4D-MRA was obtained at 3.0 T after contrast injection, with a measured voxel size of 16161 mm and a temporal resolution of 1.1 s (13 patients) or a voxel size of 16162 mm and a temporal resolution of 0.98 s (23 patients). X-ray angiography was performed as the standard reference within 53¡47 days (mean ¡ SD) after MRA. To determine a residual AVM, the 4D-MRA results were independently reviewed by two readers blinded to the X-ray angiography results. We evaluated diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 4D-MRA for detection of a residual AVM. Results: A residual AVM was identified in 13 patients (13/36, 36%) on X-ray angiography. According to Readers 1 and 2, 4D-MRA had a sensitivity of 79.6% and 64.3%, a specificity of 90.9% and 100%, a PPV of 84.6% and 100% and an NPV of 90% and 81.5%, respectively, and a diagnostic accuracy of 86.1% for Readers 1 and 2, for detecting residual AVMs after GKRS. Conclusion: The diagnostic accuracy of 4D-MRA at 3.0 T seems high, but there is still the possibility of further improving the spatiotemporal resolution of this technique.