Magnetic resonance imaging (MRI) with hyperpolarized 3-helium gas (HP 3He) offers the possibility of studying functional lung parameters such as the alveolar oxygen concentration and oxygen depletion rate. Until now, a double-acquisition technique has been utilized to extract these parameters. A complicated single-acquisition technique was previously developed to avoid the necessity of performing two identical breathing maneuvers. The results obtained with this technique were significantly less accurate than the results obtained with the double-acquisition method. In this work, a novel, easily implemented single-acquisition sequence is presented that provides results comparable to those obtained with the established double-acquisition method. This method is demonstrated in a phantom and a pig model on a 1.5 T scanner using a 2D fast low-angle shot (FLASH) gradient-echo sequence. Numerical simulations of the time evolution of the oxygen concentration were performed. Simulation results are presented to support the experimental data. Various parameter regimes were experimentally and numerically investigated.