Accurate and fast quantification of myocardial blood flow (MBF) with MR first-pass perfusion imaging techniques on a pixel-by-pixel basis remains difficult due to relatively long calculation times and noise-sensitive algorithms. In this study, Zierler's central volume principle was used to develop an algorithm for the calculation of MBF with few assumptions on the shapes of residue curves. Simulation was performed to evaluate the accuracy of this algorithm in the determination of MBF. To examine our algorithm in vivo, studies were performed in nine normal dogs. Two first-pass perfusion imaging sessions were performed with the administration of the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Radiolabeled microspheres were injected to measure MBF at the same time. MBF measurements in dogs using MR methods correlated well with the microsphere measurements (R2 = 0.96, slope = 0.9), demonstrating a fair accuracy in the perfusion measurements at rest and during the vasodilation stress. In addition to its accuracy, this method can also be optimized to run relatively fast, providing potential for fast and accurate myocardial perfusion mapping in a clinical setting.