Enhanced visibility through microbubble-induced photoacoustic fluctuation imaging.

A photoacoustic contrast mechanism is presented based on the photoacoustic fluctuations induced by microbubbles flowing inside a micro-vessel filled with a continuous absorber. It is demonstrated that the standard deviation of a homogeneous absorber mixed with microbubbles increases non-linearly as the microbubble concentration and microbubble size is increased. This effect is then utilized to perform photoacoustic fluctuation imaging with increased visibility and contrast of a blood flow phantom.

Photoacoustic Impulse Response of Lipid-Coated Ultrasound Contrast Agents.

The utility of ultrasound imaging and therapy with microbubbles may be greatly enhanced by determining their impulse-response dynamics as a function of size and composition. Prior methods for microbubble characterization utilizing high-speed cameras, acoustic transducers and laser-based techniques typically scan a limited frequency range. Here, we report on the use of a novel photoacoustic technique to measure the impulse response of single microbubbles. Individual microbubbles are driven with a broadband photoacoustic wave generated by a nanosecond-pulse laser illuminating an optical absorber. The resulting microbubble oscillations were detected by following transmission of a second laser as it passes twice through the microbubble. The system could even resolve oscillations resulting from a single-shot. As a proof-of-concept study, the size-dependent, linear impulse response of lipid-coated microbubbles was characterized using this technique. This unique method of microbubble characterization with exceptional spatiotemporal resolution opens new avenues for capturing and analyzing microbubble system dynamics.

Hydrophobically Modified Silica-Coated Gold Nanorods for Generating Nonlinear Photoacoustic Signals.

In this work, we report that gold nanorods coated with hydrophobically-modified mesoporous silica shells not only enhance photoacoustic (PA) signal over unmodified mesoporous silica coated gold nanorods, but that the relationship between PA amplitude and input laser fluence is strongly nonlinear. Mesoporous silica shells of ~14 nm thickness and with ~3 nm pores were grown on gold nanorods showing near infrared absorption. The silica was rendered hydrophobic with addition of dodecyltrichlorosilane, then re-suspended in aqueous media with a lipid monolayer. Analysis of the PA signal revealed not only an enhancement of PA signal compared to mesoporous silica coated gold nanorods at lower laser fluences, but also a nonlinear relationship between PA signal and laser fluence. We attribute each effect to the entrapment of solvent vapor in the mesopores: the vapor has both a larger expansion coefficient and thermal resistance than silica that enhances conversion to acoustic energy, and the hydrophobic porous surface is able to promote phase transition at the surface, leading to a nonlinear PA response even at fluences as low as 5 mJ cm-2. At 21 mJ cm-2, the highest laser fluence tested, the PA enhancement was >12-fold over mesoporous silica coated gold nanorods.

Sub-acoustic resolution optical focusing through scattering using photoacoustic fluctuation guided wavefront shaping.

Focusing light through turbid media using wavefront shaping generally requires a noninvasive guide star to provide feedback on the focusing process. Here we report a photoacoustic guide star mechanism suitable for wavefront shaping through a scattering wall that is based on the fluctuations in the photoacoustic signals generated in a micro-vessel filled with flowing absorbers. The standard deviation of photoacoustic signals generated from random distributions of particles is dependent on the illumination volume and increases nonlinearly as the illumination volume is decreased. We harness this effect to guide wavefront shaping using the standard deviation of the photoacoustic response as the feedback signal. We further demonstrate sub-acoustic resolution optical focusing through a diffuser with a genetic algorithm optimization routine.