The field of photoacoustic tomography (PAT) has grown a great deal in the past few years. PAT is cross-sectional or three-dimensional imaging based on the photoacoustic effect. Alexander Graham Bell first reported on the photoacoustic effect in 1880. Only recently, however, was PAT developed as an imaging technology.1–29
PAT combines high ultrasonic resolution and strong optical contrast in a single modality, capable of providing high-resolution structural, functional,19
and molecular30, 31
imaging in vivo in optically scattering biological tissue at new depths.
In biological tissues, light transfer is dominated by scattering. The mean free path is on the order of 0.1 mm, and the transport mean free path is on the order of 1 mm. While the former measures the frequency of predominantly anisotropic scattering, the latter assesses the frequency of equivalent isotropic scattering. As a result of scattering, photon propagation transitions from the ballistic regime into the diffusive regime around one transport mean free path.4
Two important depth limits exist for optical imaging. One is near the optical transport mean free path, representing the depth of the quasi-ballistic regime in biological tissue. Ballistic light intensity attenuates exponentially with a decay constant equal to the mean free path. To reach one transport mean free path deep, photons must undergo significant scattering, making focusing ineffective.32
We refer to this barrier as the soft depth limit for high-resolution optical imaging. Another depth limit is around 50–70 mm, which equals roughly 10 times the 1/e
optical penetration depth. To reach this depth, light must experience 43 dB or 20,000 times one-way decay in intensity. Beyond this limit, even diffuse photons are too few for practical purposes. We refer to this limit as the hard depth limit for optical imaging. Nevertheless, if the tissue is illuminated from opposite sides, a thickness greater than 10 cm can be potentially covered, which is adequate for many biomedical applications such as breast imaging.
High-resolution optical imaging beyond the soft depth limit remained a void until filled by PAT. None of the commercially available optical ballistic imaging modalities—including confocal microscopy, two-photon microscopy and optical coherence tomography—can penetrate into scattering biological tissue beyond the soft depth limit. By contrast, diffuse optical tomography—based on multiple-scattered photons—can provide rapid functional and molecular imaging beyond the soft depth limit; however, it has poor spatial resolution. The motivation driving the development of PAT is to overcome the poor spatial resolution of diffuse optical tomography or the soft depth limit of existing high-resolution optical imaging.
An approach to overcoming the optical hard depth limit is to adopt radiofrequency (RF) or microwaves for photoacoustic excitation.6, 7
In this case, the technology is referred to as radiofrequency- or microwave-induced acoustic tomography or thermoacoustic tomography (TAT). For simplicity here, RF refers to microwaves as well. In TAT, an RF generator instead of a laser is used. The RF generator transmits RF pulses into the tissue to be imaged. RF absorption produces heat and subsequent ultrasonic waves. The ultrasound detection and image formation are similar to those in PAT.
Both PAT and TAT are designed to overcome the poor spatial resolution of pure optical or RF imaging yet to retain the high electromagnetic contrasts. In terms of spatial resolution, pure optical imaging beyond the soft depth limit suffers from strong diffusion due to tissue scattering, whereas pure RF imaging suffers from strong diffraction due to the long wavelength. Ultrasonic scattering coefficient in tissue is 2–3 orders of magnitude less than the optical counterpart, and the acoustic diffraction (or wavelength) is 2–3 orders of magnitude weaker (or shorter) than the RF counterpart. As a result, PAT and TAT can provide high spatial resolution by detecting the induced ultrasonic waves. Unlike ultrasonography or optical coherence tomography, PAT and TAT produce speckle-free images.
The subsequent sections are organized as follows. First, the basic principle of PAT is reviewed. Then, the future prospects of PAT and TAT are envisioned on twelve specific topics. Finally, a summary is provided.