Photoacoustic imaging using endogenous chromophores as a contrast has been widely applied in biomedical studies owing to its functional imaging capability at the molecular level. Various exogenous contrast agents have also been investigated for use in contrast-enhanced imaging and functional analyses. This review focuses on contrast agents, particularly in the wavelength range, for use in photoacoustic imaging. The basic principles of photoacoustic imaging regarding light absorption and acoustic release are introduced, and the optical characteristics of tissues are summarized according to the wavelength region. Various types of contrast agents, including organic dyes, semiconducting polymeric nanoparticles, gold nanoparticles, and other inorganic nanoparticles, are explored in terms of their light absorption range in the near-infrared region. An overview of the contrast-enhancing capacity and other functional characteristics of each agent is provided to help researchers gain insights into the development of contrast agents in photoacoustic imaging.

Photoacoustic imaging has drawn a significant amount of attention due to its unique capacity for functional, metabolic, and molecular imaging, which is achieved by the combination of optical excitation and acoustic detection. With both strengths of light and ultrasound, photoacoustic images can provide strong optical contrast at high ultrasound resolution in deep tissue. As photoacoustic imaging can be used to visualize complementary information to ultrasound imaging using the same data acquisition process, several studies have been conducted on combining photoacoustic imaging with existing clinical ultrasound systems. This review highlights our development of a photoacoustic/ultrasound dual-modal imaging system, various features and functionalities implemented for clinical translation, and preclinical/clinical studies performed by using the systems.

Photoacoustic imaging can be used to extract functional information at the molecular level for imaging the whole body of small animals in vivo. However, the use of a mechanical scanner to image the whole body involves acquiring the data for a period of time which can lead to breathing-related artifacts. Thus, the acquired three-dimensional data cannot be analyzed and visualized using two-dimensional projection rendering techniques unless the respiratory distortions are minimized. In this study, an ultrasound-guided breath-compensation method for the three-dimensional data of photoacoustic macroscopy to facilitate visualization and analysis in the depth direction is presented. Photoacoustic and ultrasound data of the whole body of mice were acquired in vivo, then the distorted skin layers were compensated in ultrasound data. The extracted distortion parameters were then applied to the corresponding photoacoustic data to compensate for the motion. The compensation method was successfully applied to visualize three-dimensional hemoglobin oxygen saturation in the whole body of mice in vivo by using multispectral photoacoustic data. The resulting three-dimensional images show that the developed methodology can be used in various biomedical studies, including monitoring drug delivery, imaging of tumors, and analysis of vasculature networks.

In recent decades, photoacoustic imaging has been used widely in biomedical research, providing molecular and functional information from biological tissues in vivo. In addition to being used for research in small animals, photoacoustic imaging has also been utilized for in vivo human studies, achieving a multispectral photoacoustic response in deep tissue. There have been several clinical trials for screening cancer patients by analyzing multispectral responses, which in turn provide metabolomic information about the underlying biological tissues. This review summarizes the methods and results of clinical photoacoustic trials available in the literature to date to classify cancerous tissues, specifically of the thyroid and breast. From the review, we can conclude that a great potential exists for photoacoustic imaging to be used as a complementary modality to improve diagnostic accuracy for suspicious tumors, thus significantly benefitting patients’ healthcare.

Photoacoustic agents are widely used in various theranostic applications. By evaluating the biodistribution obtained from photoacoustic images, the effectiveness of theranostic agents in terms of their delivery efficiency and treatment responses can be analyzed. Through this study, we evaluate and summarize the recent advances in photoacoustic-guided phototherapy, particularly in photothermal and photodynamic therapy. This overview can guide the future directions for theranostic development. Because of the recent applications of photoacoustic imaging in clinical trials, theranostic agents with photoacoustic monitoring have the potential to be translated into the clinical world.