Photoacoustic tomography: Ultrasonically breaking through the optical diffusion limit

Abstract

Photoacoustic tomography (PAT), combining optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale non-ionizing functional and molecular imaging. Light offers rich tissue contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to depths within the optical diffusion limit (~1 mm in the skin). In PAT, pulsed laser light penetrates the tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, ~1000 times less scattering than optical waves in tissue, are then detected to form high-resolution images at depths up to 7 cm, breaking through the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs with consistent contrast. Such a technology has the potential to enable multiscale systems biology and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to the earliest detection of cancer by in vivo label-free quantification of hypermetabolism, the quintessential hallmark of cancer. The technology is commercialized by several companies.