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,1 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). Figure 1 illustrates the PA effect and its application to imaging. In general, a target is irradiated by a short-pulsed laser beam. A portion of the light is absorbed by the target’s constituents and then partially converted into heat, which generates a pressure rise through thermo-elastic expansion. This initial pressure rise, determined by the local optical energy deposition and other thermal and mechanical properties, is propagated as an acoustic wave in the biological tissue and detected by ultrasonic transducers. PA images are derived from the arrival times of the ultrasonic waves. PAT image contrast is determined by optical absorption in the PA excitation phase, whereas its resolution is derived from ultrasonic detection in the PA emission phase. The combination of these intrinsic properties enables PA imaging to break through the fundamental limitations of pure optical imaging2-5 (i.e., shallow imaging depth for high resolution or low spatial resolution beyond the transport mean free path) and pure ultrasonic imaging (i.e., weak contrast for early cancer detection and speckle artifacts). By scaling the ultrasonic detection frequency, the spatial resolution and imaging depth can be tuned accordingly to the imaging application. * To whom correspondence should be addressed. Tel.: (314) 935-6152. Fax: (314) 935-7448. E-mail: [email protected]. Chem. Rev. 2010, 110, 2756–2782 2756