Light focusing plays a central role in biomedical imaging, manipulation, and therapy. In scattering media, direct light focusing becomes infeasible beyond one transport mean free path. All previous methods1–3 to overcome this diffusion limit lack a practical internal “guide star.”4 Here we proposed and experimentally validated a novel concept, called Time-Reversed Ultrasonically Encoded (TRUE) optical focusing, to deliver light into any dynamically defined location inside a scattering medium. First, diffused coherent light is encoded by a focused ultrasonic wave to provide a virtual internal “guide star”; then, only the encoded light is time-reversed and transmitted back to the ultrasonic focus. The TRUE optical focus–defined by the ultrasonic wave–is unaffected by multiple scattering of light. Such focusing is especially desirable in biological tissue where ultrasonic scattering is ~1000 times weaker than optical scattering. Various fields including biomedical and colloidal optics can benefit from TRUE optical focusing.

The expression of retinoic acid receptor-beta mRNA is selectively lost in premalignant oral lesions and can be restored by treatment with isotretinoin. Restoration of the expression of retinoic acid receptor-beta mRNA is associated with a clinical response. Retinoic acid receptor-beta may have a role in mediating the response to retinoids and may be a useful intermediate biologic marker in trials of these agents for the prevention of oral carcinogenesis.

Focusing light deep inside living tissue has not been achieved despite its promise to play a central role in biomedical imaging, optical manipulation and therapy. To address this challenge, internal-guide-star-based wavefront engineering techniques—for example, time-reversed ultrasonically encoded (TRUE) optical focusing—were developed. The speeds of these techniques, however, were limited to no greater than 1 Hz, preventing them from in vivo applications. Here we improve the speed of optical focusing deep inside scattering media by two orders of magnitude, and focus diffuse light inside a dynamic scattering medium having a speckle correlation time as short as 5.6 ms, typical of living tissue. By imaging a target, we demonstrate the first focusing of diffuse light inside a dynamic scattering medium containing living tissue. Since the achieved focusing speed approaches the tissue decorrelation rate, this work is an important step towards in vivo deep tissue noninvasive optical imaging, optogenetics and photodynamic therapy.