Nonlinear photoacoustic contrast enhancement with gold nanospheres coated emulsion beads

A new technique using a composite contrast agent is proposed to increase specific contrast in photoacoustic (PA) molecular imaging. The composite particle has an emulsion bead core with a surface-assembled monolayer of gold nanospheres (GNSs), which efficiently absorbs optical energy under laser irradiation and promotes a phase transition of the emulsion bead to form a transient bubble. Much stronger PA signals are generated by the phase transition process than those from thermal expansion, the most common mechanism of laser-sound conversion. By applying a differential scheme of images, recorded at a series of variable fluences, assuming a linear relation between laser fluence and the PA signal amplitude, a nearly perfect suppression of a linear agent can be obtained, while large residues for the nonlinear emulsion beads remain. This result clearly indicates enhanced PA sensitivity and specificity. Localized bubble generation activated by a short laser pulse was also demonstrated using a microscope coupled with a high-speed camera. With simultaneous ultrasound/laser probing, i.e., delivering a probe ultrasound beam after bubble formation, the nonlinear agent shows great potential for ultrasound contrast-enhanced imaging and harmonic imaging.