A method of characterizing an imaging system includes generating a plurality of point spread function (“PSF”) samples using the imaging system, each PSF sample representing a response of an imaging system to a point illumination source, each PSF sample comprising one or more pixel values. The method also includes co-registering the pixel values contained in each of the plurality of PSF samples to form an oversampled point spread function (“PSF”) population; resampling the oversampled PSF population to uniform spacing to form a PSF image; slicing the PSF image in an evaluation direction to form a slice of the PSF image; and evaluating the slice to determine a value of a resolution metric of the imaging system that is specific to the evaluation direction.