Contrast enhancement by simultaneous ultrasound/laser pulse probing of gold nanosphere encapsulated emulsion beads

A new technique using pulsed laser heating of a nanocomposite contrast agent resulting in local bubble formation and concomitant harmonic generation in a scattered probe ultrasound (US) beam is proposed to increase specific contrast in both US imaging and laser-induced photoacoustic (PA) imaging. The composite combines an emulsion bead core with amphiphilic gold nanospheres (GNSs) assembled at the interface. Clustered GNSs result in a broadened absorption spectrum in the near infrared range (700-1000 nm) compared to the typical 520 nm peak of distributed GNSs, enabling their use at depth in tissue. Illuminating the composite with a pulsed laser with appropriately chosen parameters heats the composite through optical absorption by the GNSs and results in a phase transition of the emulsion bead to form a transient bubble. By delivering a probe US pulse simultaneously, or immediately after the laser pulse is delivered, harmonic signals are produced in the scattered US beam. The results show that a residual signal created by subtracting a US signal from the simultaneous US/laser probing signal of the emulsion bead sample is 1.7 dB higher than the laser alone generated PA signal and 20 dB higher than the PA signal of a control homogeneous GNSs dispersion with the same optical absorption, indicating the nonlinear contrast enhancement from bubble dynamics. The proposed technique of local activation of this designed contrast agent can be used to dramatically enhance both the specificity and sensitivity of integrated US/PA molecular imaging.