In Vivo Photoacoustic Tomography of Chemicals: High-Resolution Functional and Molecular Optical Imaging at New Depths

High-resolution volumetric optical imaging modalities, such as confocal microscopy, two-photon microscopy, and optical coherence tomography, have become increasingly important in the biomedical imaging field. However, due to strong light scattering, the penetration depths of these imaging modalities are limited to the optical transport mean free path in biological tissues, for example, ∼1 mm in the skin. Photoacoustic tomography (PAT), an emerging hybrid imaging modality that can provide strong endogenous and exogenous optical absorption contrasts with high ultrasonic spatial resolution using the photoacoustic (PA) effect, has overcome the fundamental depth limitation. The image resolution is scalable with the ultrasonic frequency. The imaging depth is limited to the reach of photons and up to a few centimeters deep in biological tissues. This Review will focus on the following aspects of PAT described in works published from 2003 to 2009: (1) multiscale PAT systems, (2) morphological and functional PAT using intrinsic contrasts (hemoglobin or melanin), and (3) functional and molecular PAT using exogenous contrast agents (organic dyes, nanoparticles, reporter genes, or fluorescence proteins)