Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

We report on experimental demonstration of photoacoustic tomography for reconstructing the optical absorption coefficient images of heterogeneous media. Photoacoustic images are obtained from a series of tissuelike phantom experiments using a finite element-based reconstruction algorithm coupled with a scanning photoacoustic imaging system. The experimental results show that optical absorption images can be quantitatively reconstructed when the photon diffusion model is coupled with the Helmholtz photoacoustic wave equation.

Photoacoustic tomography (PAT) offers three-dimensional (3D) structural and functional imaging of living biological tissue with label-free, optical absorption contrast. These attributes lend PAT imaging to a wide variety of applications in clinical medicine and preclinical research. Despite advances in live animal imaging with PAT, there is still a need for 3D imaging at centimeter depths in real-time. We report the development of four dimensional (4D) PAT, which integrates time resolutions with 3D spatial resolution, obtained using spherical arrays of ultrasonic detectors. The 4D PAT technique generates motion pictures of imaged tissue, enabling real time tracking of dynamic physiological and pathological processes at hundred micrometer-millisecond resolutions. The 4D PAT technique is used here to image needle-based drug delivery and pharmacokinetics. We also use this technique to monitor 1) fast hemodynamic changes during inter-ictal epileptic seizures and 2) temperature variations during tumor thermal therapy.

A finite-element reconstruction algorithm for simultaneous reconstruction of both optical and acoustic properties of heterogeneous media is presented. The algorithm is based on the Helmholtz-like photoacoustic wave equation in the frequency domain. A dual meshing scheme is described and an adjoint sensitivity method is adopted for efficient inverse computation. The algorithm is implemented with the second-order absorbing boundary conditions and with a multireceiving and multifrequency strategy. The algorithm is evaluated using simulated data under various practical cases including different noise levels, varied range of receiving frequency, different contrast levels between the heterogeneity and background region, and multiple targets. The effect of acoustic heterogeneity on conventional pure optical absorption reconstruction is also studied.

The use of photoacoustic effect is a promising approach for biomedical imaging in living tissues. Photoacoustic tomography (PAT) has been demonstrated to image breast cancer, brain vasculature, arthritis and seizure focus owing to its rich optical contrast and high resolution in a single imaging modality. Here we report a microelectromechanical systems (MEMS)-based intraoperative PAT (iPAT) technique, and demonstrate its ability to accurately map tumors in three-dimension and to inspect the completeness of tumor resection during surgery in a tumor-bearing mouse model. The MEMS imaging probe is small and has the potential to be conveniently used to guide surgical resection of tumors in the breast.