Combined ultrasound and photoacoustic imaging systems are being developed for biomedical and clinical applications. One common probe configuration is to use a linear transducer array with external light delivery to produce coregistered ultrasound and photoacoustic images. The diagnostic capability of these systems is dependent on the effectiveness of light delivery to the imaging target. We use Monte Carlo modeling to investigate the optimal design geometry of an integrated probe. Simulations are conducted with multiple tissue compositions and wavelengths. The effect of a skin layer with the thickness of a mouse or a human is also considered. The model was validated using a tissue-mimicking gelatin phantom and corresponding Monte Carlo simulations. The optimal illumination angle is shallower with human skin thickness, whereas intermediate angles are ideal with mouse skin thickness. The effect of skin thickness explains differences in the results of prior work. The simulations also indicate that even with identical hardware and imaging parameters, light delivery will be up to 3  ×   smaller in humans than in mice, due to the increased scattering from thicker skin. Our findings have clear implications for the many researchers using mice to test and develop imaging methods for clinical translation.

Utility of glycol-chitosan-coated gold nanoparticles (GC-AuNPs) as a photoacoustic contrast agent for cancer cell imaging was demonstrated. Through the synergistic effect of glycol chitosan and gold nanoparticles, GC-AuNPs showed cellular uptake in breast cancer cells and resulted in strong photoacoustic signals in tissue-mimicking cell phantoms. The performance of GC-AuNPs as contrast agents was established with photoacoustic imaging and confirmed with dark-field microscopy. The cell phantoms displayed strong photoacoustic signals if cells were incubated more than 3 h with GC-AuNPs, compared with PEG-AuNPs that showed no photoacoustic signal increase. The enhanced photoacoustic signals originated from the plasmon coupling effect of GC-AuNPs after the cellular uptake in cancer cells. Importantly, photoacoustic imaging of cancer cells was achieved with GC-AuNPs—contrast agents that did not require antibodies or complex surface modification. The endocytosis of GC-AuNPs was also confirmed with dark-field microscopy. The results show that GC-AuNPs have potential as a photoacoustic contrast agent for cellular imaging including tumor tissue imaging.