Small-Animal Whole-Body Photoacoustic Tomography: A Review
Small animals, especially mice, are widely used in biomedical research for studying and modeling the progression of human diseases and the response to potential therapies. During the past thirty years, there has been an exponential increase in the number of scientific publications on small-animal models. Compared with slicing and staining numerous sacrificed animals at multiple time points, in vivo whole-body imaging allows researchers to follow biological processes and disease progression more accurately. Photoacoustic tomography (PAT) embodied for whole-body imaging has shown great potential for preclinical research. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous tissue chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents, such as organic dyes, nanoparticles, and fluorescent proteins. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Using near-infrared light, which has relatively low blood absorption, PAT can image through the whole body of small animals with acoustically defined spatial resolution. Anatomical and vascular structures are imaged with endogenous hemoglobin contrast, while functional and molecular images are enabled by the wide choice of exogenous optical contrasts. In addition, functional and molecular images are naturally co-registered with anatomical and vascular images, allowing precise localization of the biological process. Several small-animal whole-body PAT systems, employing different light illumination and detection schemes, have been developed. In this paper, we review these techniques and highlight selected studies done in the past decade.