Bubbles (118-122) are utilized in some embodiments as part of a photoacoustic contrast agent (162) and, in some embodiments, to localize one or more locations (126-38) of a source of acoustic energy. The bubbles, such as microbubbles, can be used in proximity of nanoparticles of a first photoacoustic contrast agent, thereby affording a second photoacoustic contrast agent. The bubbles can intercept and re-radiate acoustic energy emitted by light-based activation of the first photoacoustic contrast agent in the immediate vicinity of the bubbles. As a further option, if the nanoparticles permeate further to tissue structures but remain in close enough proximity, their positions can be triangulated by the nearby bubbles, based on direction (144-148) and time delays (150-160) of ultrasound received by a transducer array.
