Real-time photoacoustic (PA) imaging involves beamforming methods using an assumed fixed sound speed, typically 1540 m/s in soft tissue. This leads to degradation of PA image quality because the true sound speed changes as PA signal propagates through different types of soft tissues: the range from 1450 m/s to 1600 m/s. This paper proposes a new method for estimating an optimal sound speed to enhance the cross-sectional PA image quality. The optimal sound speed is determined when coherent factor with the sound speed is maximized. The proposed method was validated through simulation and ex vivo experiments with microcalcification-contained breast cancer specimen. The experimental results demonstrated that the best lateral resolution of PA images of microcalcifications can be achieved when the optimal sound speed is utilized.

We present a new melanin-like nanoparticle (MelNP) and its performance evaluation results. This particle is proposed as an exogenous contrast agent for photoacoustic (PA) imaging. Conventional PA contrast agents are based on non-biological materials. In contrast, the MelNPs are organic nanoparticles inspired by natural melanin. Melanin is an endogenous chromophore that has the ability to produce a PA signal in vivo. The developed MelNPs are capable of aggregating with one another under mildly acidic conditions after introducing hydrolysis-susceptible citraconic amide on the surface of bare MelNPs. We ascertained that the physical aggregation of the MelNPs resulted in an increased PA signal strength in the near-infrared window of biological tissue (i.e., 700 nm) without absorption tuning. This phenomenon is likely because of the overlapping thermal fields of the developed MelNPs. The PA signal produced from the developed MelNPs, after exposure to mildly acidic conditions (i.e., pH 6), is 8.1 times stronger than under neutral conditions. This unique characteristic found in this study can be utilized in a practical strategy for highly sensitive in vivo cancer target imaging in response to its acidic microenvironment. This approach to amplify the PA response of MelNPs in clusters could accelerate the use of MelNPs as an alternative to non-biological nanoprobes, so that MelNPs may be applicable in PA imaging and functional PA imaging such as stimuli sensitive, multimodal, and theranostic imaging.