The main objective of this project was to develop and implement techniques for high-resolution quantitative imaging of ventilation in lungs using hyperpolarized gas magnetic resonance imaging (MRI). Pulmonary ventilation is an important aspect of lung function and is frequently compromised through several different mechanisms and at varying degrees in presence of certain lung conditions, such as chronic obstructive pulmonary diseases. The primary focus of this development is on large mammalian species as a steppingstone towards translation to human subjects. The key deliverables of this project are a device for real-time mixing and delivery of hyperpolarized gases such as 3He and 129Xe in combination with O2, an MRI acquisition scheme for practical imaging of ventilation signal build-up in the lungs, and a robust mathematical model for estimation of regional fractional ventilation values at a high resolution. A theoretical framework for fractional gas replacement in the lungs is presented to describe MRI signal dynamics during continuous breathing of a mixture of hyperpolarized gases in presence of several depolarization mechanisms. A hybrid ventilation and imaging acquisition scheme is proposed to acquire a series of images during short end-inspiratory breath-holds over several breaths. The sensitivity of the estimation algorithm is assessed with respect to noise, model uncertainty and acquisition parameters, and subsequently an optimal set of acquisition parameters is proposed to minimize the fractional ventilation estimation error. This framework is then augmented by an undersampled parallel MRI scheme to accelerate image acquisition to enable fractional ventilation imaging over the entire lung volume in a single pass. The image undersampling was also leveraged to minimize the coupling associated with signal buildup in the airways and the irreversible effect of RF pulses. The proposed technique was successfully implemented in pigs under mechanical ventilation, and preliminary measurements were performed in an adult human subject under voluntary breathing.