Described here are systems and methods for estimating phase measurements obtained using a magnetic resonance imaging (MRI) system such that phase ambiguities in the measurements are significantly mitigated. Echo time spacings are determined by optimizing phase ambiguity functions associated with the echo time spacings. Data is then acquired using a multi-echo pulse sequence that utilizes the determined echo spacings. Phase measurements are then estimated and images are reconstructed using a reconstruction technique that disambiguates the phase ambiguities in the phase measurements.