Methods and systems for determining fractional regional ventilation are disclosed. A method includes obtaining first and second lung image data indicative of a first phase and a second phase of a respiratory cycle, respectively, determining an apparent mass ratio k based on the first lung image data and the second lung image data, determining first and second spatially matched lung image data, each including N voxels, based on the first lung image data and the second lung image data, and determining at least one fractional regional ventilation value (FRV value), in accordance with a first equation FRV(n)=(k·ρ2_n−ρ1_n)/ρ1_n. The value of n is a voxel index, ρ1_n is indicative of a density of a voxel n of the first spatially matched lung image data, and ρ2_n is indicative of a density of a voxel n of the second spatially matched lung image data.
