Abstract. This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo-or acoustic-mediated delivery is also possible.

A microbubble-based imaging/therapeutic agent is introduced. Specifically, gold nanoparticles (AuNRs) are encapsulated in microbubbles (MBs) for both ultrasound (US) imaging and laser-induced thermotherapy (LIT). In addition, this agent, AuNR-MB, takes albumin microbubble as a carrier and includes the AuNRs that maintain the original absorption peak at around 760nm. AuNR-MBs in different sizes are synthesized. Imaging is first performed to evaluate its feasibility. The enhanced PA and US signals in polyacrylamide gel for in vitro study are measured. The PA spectroscopy is then performed and the results generally agree with the measured optical absorption although its peak is slightly broadened and shifted possibly due to mixing. In phantoms, the contrast is 1.531, 2.447, 2.085, 1.994, 0.768, and 0.573 at wavelength of 720, 760, 800, 860, 900, and 940 nm respectively. Finally, the application of the new agent to LIT is presented. A continuous wave laser at 800 nm is used to heat the samples with the power at 1W. The photoacoustic (PA) intensity in the region of interest (ROI) is increased by an average of 5.2dB. The increased signal level implies that the temperature in the ROI can be increased to 44.3 o C in aqueous filled setup. Furthermore, the dualmodality agent has the potential to be used in HIFU therapy, drug delivery and loading of DNA for gene transfer.