We optimized and tested a two-compartment water exchange model for fractional myocardial blood volume (fMBV) quantification. Nine healthy swine and one swine model with single-vessel coronary stenosis underwent MOLLI T1 imaging at 3.0 T following multiple individual ferumoxytol infusions. Healthy normal swine showed a mean mid-ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s-1. In one swine model with artificially‑induced single-vessel coronary stenosis, quantitative pixel-wise fMBV showed regional differences in hypoperfused relative to perfused regions. This study demonstrates the feasibility of fMBV estimation using multi-dose ferumoxytol‑enhanced MRI with a two-compartment water exchange model.