First activation radiation is provided to a sample that includes phototransformable optical labels ("PTOLs") to activate a first subset of the PTOLs. Deactivation radiation is provided to the sample to transform activated PTOLs to an unactivated state. The deactivation radiation has a spatially-structured radiation field including intensity minima, such that a second subset of PTOLs located substantially at the intensity minima remain activated, while activated PTOLs exposed to the deactivation radiation outside the minima are transformed into an unactivated form. Excitation radiation is provided to the sample to excite activated PTOLs in the sample located substantially at the intensity minima of the deactivation radiation. Radiation emitted from the activated and excited PTOLs is detected with imaging optics.