Methods of imaging described herein comprises disposing a first and second ultrasound-switchable fluorophore in an environment; exposing the environment to an ultrasound beam to create an activation region; disposing the first and/or second fluorophore within the activation region to switch the first and/or second fluorophore from an off state to an on state; exposing the environment to a beam of electromagnetic radiation; detecting a first photoluminescence signal at a first location within the environment, the photoluminescence signal comprising at least one of a first ultrasound fluorescence signal emitted by the first fluorophore, a first fluorescence signal emitted by the second fluorophore, and a background signal; correlating the first photoluminescence signal with a first reference signal to generate a correlation coefficient for the first location; and multiplying the first photoluminescence signal by the first correlation coefficient for the first location to generate a first modified photoluminescence signal for the first location.