Every new imaging technology has an aura of magic about it because it suddenly reveals what had been concealed, and makes visible what had been invisible. So, too, with photoacoustic tomography, which is allowing scientists to virtually peel away the top several inches of flesh to see what lies beneath. The technique achieves this depth vision by an elegant marriage between light and sound, combining the high contrast due to light absorption by colored molecules such as hemoglobin or melanin with the spatial resolution of ultrasound. Lihong V. Wang, PhD, the Gene K. Beare Distinguished Professor of Biomedical Engineering in the School of Engineering & Applied Science at Washington University in St. Louis, summarizes the state of the art in photoacoustic imaging in Science. He is already working with physicians at the Washington University School of Medicine to move four applications of photoacoustic tomography into clinical trials. One is to visualize the sentinel lymph nodes that are important in breast cancer staging; a second to monitor early response to chemotherapy; a third to image melanomas; and the fourth to image the gastrointestinal tract. Among the most exciting advances is the ability of photoacoustic tomography to reveal the use of oxygen by tissues, because excessive oxygen-burning (called hypermetabolism) is a hallmark of cancer. In the early stages of cancer, there isn\'t much else to go on, Wang says, and so an early warning diagnostic test that does not require a contrast agent is potentially a game changer. How photoacoustic tomography works Although we\'ve all come to accept the grayness of X-ray images, where structure appears as lights and shadows, they are a poor substitute for \"photographs\" of our insides. No such photographs exist because light photons can penetrate soft tissue only to the depth of about a millimeter before they\'re so scattered it isn\'t possible to unsnarl their paths and create an image. But scattering doesn\'t destroy the photons, which can reach a depth of about 7 centimeters (about 3 inches). The trick of photoacoustic tomography is to convert light absorbed at depth to sound waves, which scatter a thousand times less than light, for transmission back to the surface. The tissue to be imaged is irradiated by a nanosecond-pulsed laser at an optical wavelength. Absorption by light by molecules beneath the surface creates a thermally induced pressure jump that launches sound waves that are measured by ultrasound receivers at the surface and reassembled to create what is, in effect, a photograph. Light, unlike X-rays, which also penetrate deeply, poses no health hazard. Moreover, photoacoustic images have much higher contrast than X-ray images because there are many highly colored molecules in the body that serve as \"endogenous\" contrast agents. These include hemoglobin, which changes color as it gains or loses oxygen, but also melanin, the pigment that makes moles dark, and DNA, which in its \"condensed\" form in the cell nucleus is \"darker\" than the cell cytoplasm.