Nanoparticle-targeted photoacoustic cavitation for deep tissue optical imaging.

Abstract

Photoacoustic tomography is a non-invasive imaging technique based on broadband acoustic emissions from light absorption in tissue. Light-absorbing gold nanoparticles can be introduced and targeted to specific cell populations, thereby promoting both contrast and the ability to delineate tissue types. For sufficiently high laser fluence, a transient vapor cavity is formed and undergoes inertial collapse, generating enhanced emission and additional contrast. However, the fluence required to achieve this effect usually exceeds the maximum permissible exposure for tissue. By combining ultrasonic and optical pulses, the light and sound thresholds required to repeatedly generate inertial cavitation were reduced to 5 mJ/cm2 and 1 MPa, respectively. Experiments employed a transparent arylimide gel possessing a small (<600 μm) region doped with 80nm diameter gold nanoparticles and simultaneously exposed to pulsed laser light (532 nm) and pulsed ultrasound (1.1 MHz). The amplitude of broadband emissions induced by both light and sound exceeded that produced by light alone by almost two orders of magnitude, thereby facilitating imaging a deeper depth within tissue. Two-dimensional images of doped regions generated from conventional photoacoustic and ultrasound-enhanced emissions are presented and compared. Implications for imaging and HIFU therapy are discussed. [Work is supported by a Boston University Dean’s Catalyst Award.]