Optical-resolution photoacoustic microscopy (OR-PAM) can visualize cellular-level wavelength-dependent optical absorption with high resolution and sensitivity. However, the imaging speed of OR-PAM has been limited by the laser repetition rate due to the point-by-point scanning of a focused laser beam. To overcome this limitation, we propose multifocal optical-resolution photoacoustic microscopy (MOR-PAM) with a single-element ultrasonic transducer, leveraging the diffractive optical element (DOE) and a custom-designed encoding acoustic mask. The DOE generates 8 focal spots of $3~\mu $ m diameter. The acoustic mask was designed to encode photoacoustic signals from different focal spots. MOR-PAM achieved an 8-fold increase in imaging speed compared to conventional OR-PAM with the same laser repetition rate. We demonstrated the MOR-PAM using a 266 nm laser at 10 KHz, providing solutions for rapid OR-PAM beyond the laser repetition rate in a cost-effective way. The proposed method can be applied to versatile OR-PAM configurations and enable new applications where high-speed imaging is critical.

Photoacoustic tomography holds tremendous potential for neuroimaging due to its functional magnetic resonance imaging (fMRI)-like functional contrast and greater specificity, richer contrast, portability, open platform, faster imaging, magnet-free and quieter operation, and lower cost. However, accounting for the skull-induced acoustic distortion remains a long-standing challenge due to the problem size. This is aggravated in functional imaging, where high accuracy is needed to detect minuscule functional changes. Here, we develop an acoustic solver based on the boundary-element method (BEM) to model the skull and de-aberrate the images. BEM uses boundary meshes and compression for superior computational efficiency compared to volumetric discretization-based methods. We demonstrate BEM's higher accuracy and favorable scalability relative to the widely used pseudo-spectral time-domain method (PSTD). In imaging through an ex-vivo adult human skull, BEM outperforms PSTD in several metrics. Our work establishes BEM as a valuable and naturally suited technique in photoacoustic tomography and lays the foundation for BEM-based de-aberration methods.

Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression.

Thermoacoustic tomography (TAT) is an emerging imaging technique with great potential for a wide range of biomedical imaging applications. In this paper, we propose and investigate reconstruction approaches for TAT that are based on the half-time reflectivity tomography paradigm. We reveal that half-time reconstruction approaches permit for the explicit control of statistically complementary information that can result in the optimal reduction of image variances. We also show that half-time reconstruction approaches can mitigate image artifacts due to heterogeneous acoustic properties of an object. Reconstructed images and numerical results produced from simulated and experimental TAT measurement data are employed to demonstrate these effects.

Scanning thermoacoustic tomography based on microwave-induced thermoacoustic waves studied. Two-dimensional images of /spl sim/50 mm thick biological tissue samples were obtained. The thermoacoustic signals were also simulated theoretically. The image resolution was significantly improved compared with purely microwave imaging.