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The accuracy of DSC-MR imaging CBV maps in glioblastoma depends on acquisition and analysis protocols. The authors sought to compare the accuracy of routinely used protocols using a digital reference object that consisted of 10,000 simulated voxels recapitulating typical signal heterogeneity encountered in vivo. The influence of acquisition and postprocessing methods on CBV reliability was evaluated across 6912 parameter combinations, including contrast agent dosing schemes, pulse sequence parameters, field strengths, and postprocessing methods. Across all parameter space, the optimal protocol included full-dose contrast agent preload and bolus, intermediate (60°) flip angle, 30-ms TE, and postprocessing with a leakage-correction algorithm.