A system and method for optimized diffusion-weighted imaging is provided. In one aspect, the method includes providing a plurality of constraints for imaging a target at a selected diffusion weighting, and applying an optimization framework to generate an optimized diffusion encoding gradient waveform satisfying the plurality of constraints. The method also includes performing, using the MRI system, a pulse sequence comprising the optimized diffusion encoding gradient waveform to generate diffusion-weighted data, and generating at least one image of the target using the diffusion-weighted data.
